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The Concise Guide To Pharmacology 201920 Transport

THE_CONCISE_GUIDE_TO PHARMACOLOGY

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88 views97 pages

The Concise Guide To Pharmacology 201920 Transport

THE_CONCISE_GUIDE_TO PHARMACOLOGY

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S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters.

British Journal of Pharmacology (2019) 176, S397–S493

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters

Stephen PH Alexander1 , Eamonn Kelly2 , Alistair Mathie3 , John A Peters4 , Emma L Veale3 ,
Jane F Armstrong5 , Elena Faccenda5 , Simon D Harding5 , Adam J Pawson5 , Joanna L Sharman5 ,
Christopher Southan5 , Jamie A Davies5 and CGTP Collaborators
1 School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK
2 School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK
3 Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue,
Chatham Maritime, Chatham, Kent, ME4 4TB, UK
4 Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
5 Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK

Abstract
The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human
drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org),
which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared
to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at
http://onlinelibrary.wiley.com/doi/10.1111/bph.14753. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled re-
ceptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological
tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to
mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International
Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human
drug targets, where appropriate.

Conﬂict of interest
The authors state that there are no conﬂicts of interest to disclose.

© 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Overview: The majority of biological solutes are charged organic teins, which transport (primarily) inorganic cations. The second, 400 members. Many of these overlap in terms of the solutes that
or inorganic molecules. Cellular membranes are hydrophobic F-type or V-type ATPases, are proton-coupled motors, which can they carry. For example, amino acids accumulation is mediated
and, therefore, effective barriers to separate them allowing the for- function either as transporters or as motors. Last, are ATP-binding by members of the SLC1, SLC3/7, SLC6, SLC15, SLC16, SLC17,
mation of gradients, which can be exploited, for example, in the cassette transporters, heavily involved in drug disposition as well SLC32, SLC36, SLC38 and SLC43 families. Further members of
generation of energy. Membrane transporters carry solutes across as transporting endogenous solutes. the SLC superfamily regulate ion ﬂuxes at the plasma membrane,
cell membranes, which would otherwise be impermeable to them. The second largest family of membrane proteins in the human or solute transport into and out of cellular organelles. Some SLC
The energy required for active transport processes is obtained from genome, after the G protein-coupled receptors, are the SLC so- family members remain orphan transporters, in as much as a phys-
ATP turnover or by exploiting ion gradients. lute carrier family. Within the solute carrier family, there are a iological function has yet to be dtermined. Within the SLC super-
ATP-driven transporters can be divided into three major classes: P- great variety of solutes transported, from simple inorganic ions to family, there is an abundance in diversity of structure. Two fami-
type ATPases; F-type or V-type ATPases and ATP-binding cassette amino acids and sugars to relatively complex organic molecules lies (SLC3 and SLC7) only generate functional transporters as het-
transporters. The ﬁrst of these, P-type ATPases, are multimeric pro- like haem. The solute carrier family includes 65 families of almost eromeric partners, where one partner is a single TM domain pro-

Searchable database: http://www.guidetopharmacology.org/index.jsp Transporters S397

Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

tein. Membrane topology predictions for other families suggest direction. Symports allow concentration gradients of one solute to dients. A more complex family of transporters, the SLC27 fatty
3,4,6,7,8,9,10,11,12,13 or 14 TM domains. The SLC transporters allow co-transport of a second solute across a membrane. A third, acid transporters also express enzymatic function. Many of the
include members which function as antiports, where solute move- relatively small group are equilibrative transporters, which allow transporters also express electrogenic properties of ion channels.
ment in one direction is balanced by a solute moving in the reverse solutes to travel across membranes down their concentration gra-

Family structure

S399 ATP-binding cassette transporter family S428 SLC8 family of sodium/calcium exchangers S457 SLC27 family of fatty acid transporters
S399 ABCA subfamily S429 SLC9 family of sodium/hydrogen exchangers S458 SLC28 and SLC29 families of nucleoside transporters
S401 ABCB subfamily S429 SLC10 family of sodium-bile acid co-transporters S458 SLC28 family
S403 ABCC subfamily S431 SLC11 family of proton-coupled metal ion transporters S459 SLC29 family
S404 ABCD subfamily of peroxisomal ABC transporters S431 SLC12 family of cation-coupled chloride transporters S461 SLC30 zinc transporter family
S405 ABCG subfamily S433 SLC13 family of sodium-dependent sulphate/carboxylate S461 SLC31 family of copper transporters
S406 F-type and V-type ATPases transporters S462 SLC32 vesicular inhibitory amino acid transporter
S406 F-type ATPase S434 SLC14 family of facilitative urea transporters S463 SLC33 acetylCoA transporter
S407 V-type ATPase S435 SLC15 family of peptide transporters S464 SLC34 family of sodium phosphate co-transporters
S407 P-type ATPases S437 SLC16 family of monocarboxylate transporters S465 SLC35 family of nucleotide sugar transporters
S407 Na+ /K+ -ATPases S438 SLC17 phosphate and organic anion transporter family S466 SLC36 family of proton-coupled amino acid transporters
S408 Ca2+ -ATPases S438 Type I sodium-phosphate co-transporters S468 SLC37 family of phosphosugar/phosphate exchangers
S408 H+ /K+ -ATPases S439 Sialic acid transporter S468 SLC38 family of sodium-dependent neutral
S408 Cu+ -ATPases S439 Vesicular glutamate transporters (VGLUTs) amino acid transporters
S409 Phospholipid-transporting ATPases S440 Vesicular nucleotide transporter S469 System A-like transporters
S409 SLC superfamily of solute carriers S440 SLC18 family of vesicular amine transporters S469 System N-like transporters
S410 SLC1 family of amino acid transporters S442 SLC19 family of vitamin transporters S470 Orphan SLC38 transporters
S410 Glutamate transporter subfamily S443 SLC20 family of sodium-dependent phosphate S470 SLC39 family of metal ion transporters
S412 Alanine/serine/cysteine transporter subfamily transporters S471 SLC40 iron transporter
S413 SLC2 family of hexose and sugar alcohol transporters S443 SLC22 family of organic cation and anion transporters S472 SLC41 family of divalent cation transporters
S413 Class I transporters S444 Organic cation transporters (OCT) S473 SLC42 family of Rhesus glycoprotein ammonium
S414 Class II transporters S445 Organic zwitterions/cation transporters (OCTN) transporters
S415 Proton-coupled inositol transporter S446 Organic anion transporters (OATs) S473 SLC43 family of large neutral amino acid transporters
S415 SLC3 and SLC7 families of heteromeric amino acid S446 Urate transporter S474 SLC44 choline transporter-like family
transporters (HATs) – Orphan or poorly characterized S475 SLC45 family of putative sugar transporters
S415 SLC3 family SLC22 family members S475 SLC46 family of folate transporters
S416 SLC7 family S447 Atypical SLC22B subfamily S477 SLC47 family of multidrug and toxin extrusion
S417 SLC4 family of bicarbonate transporters S448 SLC23 family of ascorbic acid transporters transporters
S417 Anion exchangers S449 SLC24 family of sodium/potassium/calcium exchangers S477 SLC48 heme transporter
S418 Sodium-dependent HCO3 - transporters S450 SLC25 family of mitochondrial transporters S478 SLC49 family of FLVCR-related heme transporters
S418 SLC5 family of sodium-dependent glucose transporters S450 Mitochondrial di- and tri-carboxylic acid S479 SLC50 sugar transporter
S419 Hexose transporter family transporter subfamily S479 SLC51 family of steroid-derived molecule transporters
S420 Choline transporter S451 Mitochondrial amino acid transporter subfamily S480 SLC52 family of riboﬂavin transporters
S421 Sodium iodide symporter, sodium-dependent S452 Mitochondrial phosphate transporters S481 SLC53 Phosphate carriers
multivitamin transporter and sodium-coupled S452 Mitochondrial nucleotide transporter subfamily S481 SLC54 Mitochondrial pyruvate carriers
monocarboxylate transporters S453 Mitochondrial uncoupling proteins S482 SLC55 Mitochondrial cation/proton exchangers
S422 Sodium myo-inositol cotransporter transporters S454 Miscellaneous SLC25 mitochondrial transporters S482 SLC56 Sideroﬂexins
S423 SLC6 neurotransmitter transporter family S454 SLC26 family of anion exchangers S483 SLC57 NiPA-like magnesium transporter family
S423 Monoamine transporter subfamily S454 Selective sulphate transporters S483 SLC58 MagT-like magnesium transporter family
S424 GABA transporter subfamily S455 Chloride/bicarbonate exchangers S484 SLC59 Sodium-dependent lysophosphatidylcholine
S425 Glycine transporter subfamily S455 Anion channels symporter family
S427 Neutral amino acid transporter subfamily S456 Other SLC26 anion exchangers S484 SLC60 Glucose transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp Transporters S398

S485 SLC61 Molybdate transporter family S486 SLC64 Golgi Ca2+ /H+ exchangers
S485 SLC62 Pyrophosphate transporters S487 SLC65 NPC-type cholesterol transporters
S486 SLC63 Sphingosine-phosphate transporters S488 SLCO family of organic anion transporting polypeptides

ATP-binding cassette transporter family

Transporters → ATP-binding cassette transporter family

Overview: ATP-binding cassette transporters are ubiquitous (NBD). The majority of eukaryotic ABC transporters are ‘full’ trans- convey substrates from the cytoplasm, either out of the cell or into
membrane proteins characterized by active ATP-dependent move- porters incorporating both TM and NBD entities. Some ABCs, no- intracellular organelles. Their role in the efﬂux of exogenous com-
ment of a range of substrates, including ions, lipids, peptides, tably the ABCD and ABCG families are half-transporters with only pounds, notably chemotherapeutic agents, has led to considerable
steroids. Individual subunits are typically made up of two groups a single membrane spanning domain and one NBD, and are only interest.
of 6TM-spanning domains, with two nucleotide-binding domains functional as homo- or heterodimers. Eukaryotic ABC transporters

ABCA subfamily
Transporters → ATP-binding cassette transporter family → ABCA subfamily
Overview: To date, 12 members of the human ABCA subfamily are identified. They share a high degree of sequence conservation and have been mostly related with lipid trafficking in a wide range
of body locations. Mutations in some of these genes have been described to cause severe hereditary diseases related with lipid transport, such as fatal surfactant deficiency or harlequin ichthyosis. In
addition, most of them are hypothesized to participate in the subcellular sequestration of drugs, thereby being responsible for the resistance of several carcinoma cell lines against drug treatment [8].

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCA subfamily S399

Nomenclature ABCA1 ABCA3 ABCA4

Common abbreviation ABC1, CERP ABC3, ABCC ABCR
HGNC, UniProt ABCA1, O95477 ABCA3, Q99758 ABCA4, P78363
Selective ligands bihelical apoA-I mimetic peptide 5A (Binding) [567] – –
Selective inhibitors probucol [195, 676] – –
Comments – Loss-of-function mutations are associated with pulmonary Retinal-speciﬁc transporter of N-retinylPE; loss-of-function
surfactant deﬁciency mutations are associated with childhood-onset Stargardt
disease, a juvenile onset macular degenerative disease. The
earlier onset disease is often associated with the more severe
and deleterious ABCA4 variants [216].
ABCA4 facilitates the clearance of all-trans-retinal from
photoreceptor disc membranes following photoexcitation.
ABCA4 can also transport
N-11-cis-retinylidene-phosphatidylethanolamine, the
Schiff-base adduct of 11-cis-retinal; loss of function mutation
cause a buildup of lipofuscin, atrophy of the central retina,
and severe progressive loss in vision [512].

Nomenclature ABCA5 ABCA6 ABCA7 ABCA12

HGNC, UniProt ABCA5, Q8WWZ7 ABCA6, Q8N139 ABCA7, Q8IZY2 ABCA12, Q86UK0
Comments ABCA5 is a lysosomal protein whose loss of A recent genome wide association study Genome wide association studies identify Reported to play a role in skin ceramide
function compromises integrity of lysosomes identified an ABCA6 variant associated with ABCA7 variants as associated with Alzheimer’s formation [727]. A recent study shows that
and leads to intra-endolysosomal cholesterol levels [636]. Disease [294]. ABCA12 expression also impacts cholesterol
accumulation of cholesterol. It has recently efflux from macrophages. ABCA12 is
been associated with Congenital Generalized postulated to associate with ABCA1 and LXR
Hypertrichosis Terminalis (CGHT), a hair beta, and stabilize expression of ABCA1.
overgrowth syndrome, in a patient with a ABCA12 deficiency causes decreased
mutation in ABCA5 that significantly decreased expression of Abca1, Abcg1 and Nr1h2 [215].
its expression [147].

Comments: A number of structural analogues are not found in man: Abca14 (ENSMUSG00000062017); Abca15 (ENSMUSG00000054746); Abca16 (ENSMUSG00000051900) and Abca17
(ENSMUSG00000035435).

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCA subfamily S400

ABCB subfamily
Transporters → ATP-binding cassette transporter family → ABCB subfamily
Overview: The ABCB subfamily is composed of four full transporters and two half transporters. This is the only human subfamily to have both half and full types of transporters. ABCB1 was discovered
as a protein overexpressed in certain drug resistant tumor cells. It is expressed primarily in the blood brain barrier and liver and is thought to be involved in protecting cells from toxins. Cells that
overexpress this protein exhibit multi-drug resistance [142].

Nomenclature ABCB1 ABCB2 ABCB3

Common abbreviation MDR1, PGP1 TAP1 TAP2
HGNC, UniProt ABCB1, P08183 TAP1, Q03518 TAP2, Q03519
Comments Responsible for the cellular export of many therapeutic drugs. The mouse and rat have two Endoplasmic reticulum peptide transporter is a hetero-dimer composed of the two
Abcb1 genes (gene names; Abcb1a and Abcb1b) while the human has only the one gene, half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). The transporter shuttles peptides into
ABCB1. the endoplasmic reticulum where they are loaded onto major histocompatibility complex
class I (MHCI) molecules via the macromoldecular peptide-loading complex and are
eventually presented at the cell surface, attributing to TAP an important role in the adaptive
immune response [568].

Nomenclature ABCB4 ABCB5 ABCB6

Common abbreviation PGY3 – MTABC3
HGNC, UniProt ABCB4, P21439 ABCB5, Q2M3G0 ABCB6, Q9NP58
Comments Transports phosphatidylcholine from intracellular to A drug efflux transporter that has been shown to identify Putative mitochondrial porphyrin transporter [374]; other
extracellular face of the hepatocyte canalicular membrane cancer stem-like cells in diverse human malignancies, and is subcellular localizations are possible, such as the plasma
[484]. Heterozygous ABCB4 variants contribute to mild also identified as a limbal stem cell that is required for membrane, as a specific determinant of the Langereis blood
cholestatic phenotypes, while homozygous deficiency leads corneal development and repair [377, 670]. group system [285]. Loss of Abcb6 expression in mice leads
to Progressive Intrahepatic Familial Cholestasis (PFIC) Type to decreased expression and activity of CYP450 [103].
3, and increased risk of cholesterol gallstones [291].

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCB subfamily S401

Nomenclature ABCB7 ABCB8 ABCB9

Common abbreviation ABC7 MABC1 TAPL
HGNC, UniProt ABCB7, O75027 ABCB8, Q9NUT2 ABCB9, Q9NP78
Comments Mitochondrial; reportedly essential for haematopoiesis Mitochondrial; suggested to play a role in chemoresistance A homodimeric transport complex that translocates cytosolic
[501]. Deletion studies in mice demonstrate that Abcb7 is of melanoma [177]. Cardiac speciﬁc deletion of Abcb8 leads peptides into the lumen of lysosome for degradation [145].
essential in mammals and substantiate a role for to cardiomyopathy and accumulation of mitochondrial iron,
mitochondria in cytosolic Fe-S cluster assembly [502]. and is thus thought to modulate mitochondrial iron export
[305].

Nomenclature ABCB10 ABCB11

Common abbreviation MTABC2 ABC16
HGNC, UniProt ABCB10, Q9NRK6 ABCB11, O95342
Ligands – glycochenodeoxycholic acid (Binding) (pKi 5.2) [89]
Comments Mitochondrial location; the first human ABC transporter to have a crystal structure reported Loss-of-function mutations are associated with progressive familial intrahepatic cholestasis
[575]. ABCB10 is important in early steps of heme synthesis in the heart and is required for type 2 [590]. ATP-dependent transport of bile acids into the confines of the canalicular
normal red blood cell development [45, 606]. space by ABCB11 (BSEP) generates an osmotic gradient and thereby, bile flow. Mutations in
BSEP that decrease its function or expression cause Progressive Familial Cholestasis Type 2
(PFIC2), which in severe cases, can be fatal in the absence of a liver transplant. Drugs that
inhibit BSEP function with IC50 values less than 25 μM [450] or decrease its expression
[228] can cause Drug-Induced Liver Injury (DILI) in the form of cholestatic liver injury.

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCB subfamily S402

ABCC subfamily
Transporters → ATP-binding cassette transporter family → ABCC subfamily
Overview: Subfamily ABCC contains thirteen members and nine of these transporters are referred to as Multidrug Resistance Proteins (MRPs). MRP proteins are found throughout nature and mediate
many important functions. They are known to be involved in ion transport, toxin secretion, and signal transduction [142].

Nomenclature ABCC1 ABCC2 ABCC3

Common abbreviation MRP1 MRP2, cMOAT MRP3
HGNC, UniProt ABCC1, P33527 ABCC2, Q92887 ABCC3, O15438
Inhibitors WP814 (pKi 7.2) [507] PAK-104P (pKi 5.4) [111] –
Comments Exhibits a broad substrate speciﬁcity [37], including LTC4 Loss-of-function mutations are associated with Transports conjugates of glutathione, sulfate or glucuronide
(Km 97 nM [394]) and estradiol-17β-glucuronide [595]. Dubin-Johnson syndrome, in which plasma levels of [67]
conjugated bilirubin are elevated (OMIM: 237500).

Nomenclature ABCC4 ABCC5 ABCC6

Common abbreviation MRP4 MRP5 MRP6
HGNC, UniProt ABCC4, O15439 ABCC5, O15440 ABCC6, O95255
Inhibitors estradiol disulfate (pIC50 6.7) [702] compound 2 (pKi 7.2) [541], sildenaﬁl (pKi 5.9) [541] –
Comments Although reported to facilitate cellular cyclic nucleotide Although reported to facilitate cellular cyclic nucleotide Loss-of-function mutations in ABCC6 are associated with
export, this role has been questioned [67]; reported to export, this role has been questioned [67] pseudoxanthoma elasticum (OMIM: 264800).
export prostaglandins in a manner sensitive to NSAIDS [523]

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCC subfamily S403

Nomenclature ATP-binding cassette, sub-family C (CFTR/MRP), member 8 ABCC9 ABCC11

Systematic nomenclature ABCC8 – –
Common abbreviation SUR1 SUR2 MRP8
HGNC, UniProt ABCC8, Q09428 ABCC9, O60706 ABCC11, Q96J66
Selective inhibitors repaglinide (pIC50 7) [680] – –
Comments The sulfonyurea drugs (acetohexamide, tolbutamide and Associated with familial atrial fibrillation, Cantu syndrome Single nucleotide polymorphisms distinguish wet vs. dry
glibenclamide) appear to bind sulfonylurea receptors and it and familial isolated dilated cardiomyopathy. earwax (OMIM: 117800); an association between earwax
has been shown experimentally that tritiated glibenclamide allele and breast cancer risk is reported in Japanese but not
can be used to pull out a 140 kDa protein identified as European populations.
SUR1 (now known as ABCC8) [522]. SUR2 (ABCC9) has
also been identified [307]. However, this is not the full
mechanism of action and the functional channel has been
characterised as a hetero-octamer formed by four SUR and
four Kir 6.2 subunits, with the Kir 6.2 subunits forming the
core ion pore and the SUR subunits providing the
regulatory properties [440]. Co-expression of Kir 6.2 with
SUR1, reconstitutes the ATP-dependent K+ conductivity
inhibited by the sulfonyureas [307].

Comments: ABCC7 (also known as CFTR, a 12TM ABC tion of the Guide. ABCC8 (ENSG00000006071, also known as lar K+ channels (Kir6.1-6.2), conferring nucleotide sensitivity to
transporter-type protein, is a cAMP-regulated epithelial cell mem- SUR1, sulfonylurea receptor 1) and ABCC9 (ENSG00000069431, these channels to generate the canonical KATP channels. ABCC13
brane Cl- channel involved in normal ﬂuid transport across var- also known as SUR2, sulfonylurea receptor 2) are unusual in that (ENSG00000155288) is a possible pseudogene.
ious epithelia and can be viewed in the Chloride channels sec- they lack transport capacity but regulate the activity of particu-

ABCD subfamily of peroxisomal ABC transporters

Transporters → ATP-binding cassette transporter family → ABCD subfamily of peroxisomal ABC transporters
Overview: Peroxisomes are indispensable organelles in higher eukaryotes. They are essential for the oxidation of a wide variety of metabolites, which include: saturated, monounsaturated and
polyunsaturated fatty acids, branched-chain fatty acids, bile acids and dicarboxylic acids [348]. However, the peroxisomal membrane forms an impermeable barrier to these metabolites. The mammalian
peroxisomal membrane harbours three ATP-binding cassette (ABC) half-transporters, which act as homo- and/or heterodimers to transport these metabolites across the peroxisomal membrane.

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCD subfamily of peroxisomal ABC transporters S404

Nomenclature ABCD1 ABCD2 ABCD3

Common abbreviation ALDP ALDR PMP70
HGNC, UniProt ABCD1, P33897 ABCD2, Q9UBJ2 ABCD3, P28288
Comments Transports coenzyme A esters of very long chain fatty acids In vitro experiments indicate that ABCD2 has overlapping Transports long-chain dicarboxylic acids, branched-chain
[637, 638]. Loss-of-function mutations in ABCD1 (mutation substrate specificity with ABCD1 towards saturated and fatty acids and C27 bile acids DHC-CoA and THC-CoA [198].
registry held by the Adrenoleukodystrophy database; monounsaturated very long-chain fatty acids, albeit at much In mitochondrial fatty acid deficient cells and mice, ABCD3
https://adrenoleukodystrophy.info/) result in lower specificity. ABCD2 has affinity for the polyunsaturated accepts medium and long-chain fatty acids
adrenoleukodystrophy (OMIM: 300100) [347]. fatty acids C22:6-CoA and C24:6-CoA. However, in vivo
proof for its true function is still lacking. No disease has yet
been linked to a deficiency of ABCD2.

Comments: ABCD4 (ENSG00000119688, also known as PMP69, PXMP1-L or P70R) is located at the lysosome and is involved in the transport of vitamin B12 (cobalamin) from lysosomes into the
cytosol [122].

ABCG subfamily
Transporters → ATP-binding cassette transporter family → ABCG subfamily
Overview: This family of ’half-transporters’ act as homo- or heterodimers; particularly ABCG5 and ABCG8 are thought to be obligate heterodimers. The ABCG5/ABCG heterodimer sterol transporter
structure has been determined [389], suggesting an extensive intracellular nucleotide binding domain linked to the transmembrane domains by a fold in the primary sequence. The functional ABCG2
transporter appears to be a homodimer with structural similarities to the ABCG5/ABCG8 heterodimer [609].

Nomenclature ABCG1 ABCG2 ABCG4 ABCG5 ABCG8

Common abbreviation ABC8 ABCP – – –
HGNC, UniProt ABCG1, P45844 ABCG2, Q9UNQ0 ABCG4, Q9H172 ABCG5, Q9H222 ABCG8, Q9H221
Inhibitors – cyclosporin A (pKi 6.3) [486] – – –
Comments Transports sterols and choline Exhibits a broad substrate Putative functional dependence on The ABCG5/ABCG8 heterodimer The ABCG5/ABCG8 heterodimer
phospholipids [351] speciﬁcity, including urate and ABCG1 transports phytosterols and transports phytosterols and
haem, as well as multiple synthetic cholesterol [389]. Loss-of-function cholesterol [389]. Loss-of-function
compounds [351]. mutations in ABCG5 or ABCG8 are mutations in ABCG5 or ABCG8 are
associated with sitosterolemia associated with sitosterolemia
(OMIM: 210250). (OMIM: 210250).

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCG subfamily S405

Comments on ATP-binding cassette transporter family: to be functional transporters, but appear to have a role in protein as ABC50 or TNF-α-stimulated ABC protein); ABCF2 (Q9UG63,
A further group of ABC transporter-like proteins have been iden- translation [110, 490]: ABCE1 (P61221, also known as OABP or 2’- also known as iron-inhibited ABC transporter 2) and ABCF3
tiﬁed to lack membrane spanning regions and are not believed 5’ oligoadenylate-binding protein); ABCF1 (Q8NE71, also known (Q9NUQ8).

F-type and V-type ATPases

Transporters → F-type and V-type ATPases

Overview: The F-type (ATP synthase) and the V-type (vacuolar complex (termed F1 or V1 ) and a membrane complex (Fo or Vo ). type and V-type ATPases have been assigned enzyme commission
or vesicular proton pump) ATPases, although having distinct sub- Within each ATPase complex, the two individual sectors appear to number E.C. 3.6.3.14
cellular locations and roles, exhibit marked similarities in subunit function as connected opposing rotary motors, coupling catalysis
structure and mechanism. They are both composed of a ‘soluble’ of ATP synthesis or hydrolysis to proton transport. Both the F-

F-type ATPase
Transporters → F-type and V-type ATPases → F-type ATPase

Overview: The F-type ATPase, also known as ATP synthase although it is also possible for the enzyme to function as an AT- The F0 motor, responsible for ion translocation, is complex in
or ATP phosphohydrolase (H+ -transporting), is a mitochondrial Pase. The ATP5O subunit (oligomycin sensitivity-conferring pro- mammals, with probably nine subunits centring on A, B, and C
membrane-associated multimeric complex consisting of two do- tein, OSCP, (P48047)), acts as a connector between F1 and F0 mo- subunits in the membrane, together with D, E, F2, F6, G2 and 8
mains, an F0 channel domain in the membrane and an F1 do- tors. subunits. Multiple pseudogenes for the F0 motor proteins have
main extending into the lumen. Proton transport across the in- The F1 motor, responsible for ATP turnover, has the subunit com- been deﬁned in the human genome.
ner mitochondrial membrane is used to drive the synthesis of ATP, position α3β3γδ.

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp F-type ATPase S406

V-type ATPase
Transporters → F-type and V-type ATPases → V-type ATPase
Overview: The V-type ATPase is most prominently associated with lysosomes in mammals, but also appears to be expressed on the plasma membrane and neuronal synaptic vesicles.
The V1 motor, responsible for ATP turnover, has eight subunits with a composition of A-H.
TheV0 motor, responsible for ion translocation, has six subunits (a-e).

Information on members of this family may be found in the online database.

Comments: Na+ /K+ -ATPases are inhibited by ouabain and cardiac glycosides, such as digoxin, as well as potentially endogenous cardiotonic steroids [34].

Searchable database: http://www.guidetopharmacology.org/index.jsp Na+/K+-ATPases S407

Ca2+-ATPases
Transporters → P-type ATPases → Ca2+ -ATPases

Overview: The sarcoplasmic/endoplasmic reticulum Ca2+ - The plasma membrane Ca2+ -ATPase (PMCA) is a cell-surface pump loops.
ATPase (SERCA) is an intracellular membrane-associated pump for extruding calcium from the cytosol, usually associated with the Secretory pathway Ca2+ -ATPases (SPCA) allow accumulation of
for sequestering calcium from the cytosol into intracellular or- recovery phase following excitation of cells. The active pump is calcium and manganese in the Golgi apparatus.
ganelles, usually associated with the recovery phase following ex- a homodimer, each subunit of which is made up of ten TM seg-
citation of muscle and nerves. ments, with cytosolic C- and N-termini and two large intracellular

Information on members of this family may be found in the online database.

Comments: The fungal toxin ochratoxin A has been described to activate SERCA in kidney microsomes [116]. Cyclopiazonic acid [564], thapsigargin [414] and BHQ are widely employed to block SERCA.
Thapsigargin has also been described to block the TRPV1 vanilloid receptor [629].
The stoichiometry of ﬂux through the PMCA differs from SERCA, with the PMCA transporting 1 Ca2+ while SERCA transports 2 Ca2+ .
Loss-of-function mutations in SPCA1 appear to underlie Hailey-Hailey disease [299].

H+/K+-ATPases
Transporters → P-type ATPases → H+ /K+ -ATPases
Overview: The H+ /K+ ATPase is a heterodimeric protein, made up of α and β subunits. The α subunit has 10 TM domains and exhibits catalytic and pore functions, while the β subunit has a single
TM domain, which appears to be required for intracellular trafﬁcking and stabilising the α subunit. The ATP4A and ATP4B subunits are expressed together, while the ATP12A subunit is suggested to be
expressed with the β1 (ATP1B1) subunit of the Na+ /K+ -ATPase [495].

Information on members of this family may be found in the online database.

Comments: The gastric H+ /K+ -ATPase is inhibited by proton pump inhibitors used for treating excessive gastric acid secretion, including dexlansoprazole and a metabolite of esomeprazole.

Cu+-ATPases
Transporters → P-type ATPases → Cu+ -ATPases
Overview: Copper-transporting ATPases convey copper ions across cell-surface and intracellular membranes. They consist of eight TM domains and associate with multiple copper chaperone proteins
(e.g. ATOX1, O00244).

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp Cu+ -ATPases S408

Phospholipid-transporting ATPases
Transporters → P-type ATPases → Phospholipid-transporting ATPases
Overview: These transporters are thought to translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine from one side of the phospholipid bilayer to the other to generate
asymmetric membranes. They are also proposed to be involved in the generation of vesicles from intracellular and cell-surface membranes.

Information on members of this family may be found in the online database.

Comments: Loss-of-function mutations in ATP8B1 are associated A further series of structurally-related proteins have been iden- including ATP13A1 (Q9HD20), ATP13A2 (Q9NQ11), ATP13A3
with type I familial intrahepatic cholestasis. tiﬁed in the human genome, with as yet undeﬁned function, (Q9H7F0), ATP13A4 (Q4VNC1) and ATP13A5 (Q4VNC0).

SLC superfamily of solute carriers

Transporters → SLC superfamily of solute carriers

Overview: The SLC superfamily of solute carriers is the second SLC1, SLC3/7, SLC6, SLC15, SLC16, SLC17, SLC32, SLC36, SLC38 Functionally, members may be divided into those dependent on
largest family of membrane proteins after G protein-coupled re- and SLC43. Further members of the SLC superfamily regulate ion gradients of ions (particularly sodium, chloride or protons), ex-
ceptors, but with a great deal fewer therapeutic drugs that exploit fluxes at the plasma membrane, or solute transport into and out change of solutes or simple equilibrative gating. For many mem-
them. As with the ABC transporters, however, they play a major of cellular organelles. bers, the stoichiometry of transport is not yet established. Fur-
role in drug disposition and so can be hugely influential in deter- Within the SLC superfamily, there is an abundance in diversity of thermore, one family of transporters also possess enzymatic activ-
mining the clinical efficacy of particular drugs. structure. Two families (SLC3 and SLC7) only generate functional ity (SLC27), while many members function as ion channels (e.g.
48 families are identified on the basis of sequence similarities, but transporters as heteromeric partners, where one partner is a sin- SLC1A7/EAAT5), which increases the complexity of function of
many of them overlap in terms of the solutes that they carry. For gle TM domain protein. Membrane topology predictions for other the SLC superfamily.
example, amino acid accumulation is mediated by members of the families suggest 3, 4 6, 7, 8, 9, 10, 11, 12, 13, or 14 TM domains.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC superfamily of solute carriers S409

SLC1 family of amino acid transporters

Transporters → SLC superfamily of solute carriers → SLC1 family of amino acid transporters
Overview: The SLC1 family of sodium dependent transporters includes the plasma membrane located glutamate transporters and the neutral amino acid transporters ASCT1 and ASCT2 [11, 46, 338,
339, 487].

Glutamate transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC1 family of amino acid transporters → Glutamate transporter subfamily

Overview: Glutamate transporters present the unusual structural low ambient extracellular concentrations of glutamate (protecting moter activation [226, 390, 536] reviewed by [353]). PPARγ acti-
motif of 8TM segments and 2 re-entrant loops [262]. The crystal against excitotoxicity) and provide glutamate for metabolism in- vation (e.g. by rosiglitazone) also leads to enhanced expression
structure of a glutamate transporter homologue (GltPh) from Py- cluding the glutamate-glutamine cycle. The Na+ /K+ -ATPase that of EAAT though promoter activation [532]. In addition, several
rococcus horikoshii supports this topology and indicates that the maintains the ion gradients that drive transport has been demon- translational activators of EAAT2 have recently been described
transporter assembles as a trimer, where each monomer is a func- strated to co-assemble with EAAT1 and EAAT2 [533]. Recent ev- [125] along with treatments that increase the surface expression of
tional unit capable of substrate permeation [68, 526, 696] re- idence supports altered glutamate transport and novel roles in EAAT2 (e.g. [384, 726]), or prevent its down-regulation (e.g. [248]).
viewed by [329]). This structural data is in agreement with the pro- brain for splice variants of EAAT1 and EAAT2 [231, 386]. Three pa-
A thermodynamically uncoupled Cl- flux, activated by Na+ and
posed quaternary structure for EAAT2 [232] and several functional tients with dicarboxylic aminoaciduria (DA) were recently found
studies that propose the monomer is the functional unit [257, 366, to have loss-of-function mutations in EAAT3 [35]. DA is charac- glutamate [259, 339, 419] (Na+ and aspartate in the case of GltPh
385, 539]. Recent evidence suggests that EAAT3 and EAAT4 may terized by excessive excretion of the acidic amino acids glutamate [538]), is sufficiently large, in the instances of EAAT4 and EAAT5,
assemble as heterotrimers [467]. The activity of glutamate trans- and aspartate and EAAT3 is the predominant glutamate/aspartate to influence neuronal excitability [621, 648]. Indeed, it has re-
porters located upon both neurones (predominantly EAAT3, 4 and transporter in the kidney. Enhanced expression of EAAT2 result- cently been suggested that the primary function of EAAT5 is as a
5) and glia (predominantly EAAT 1 and 2) serves, dependent upon ing from administration of β-lactam antibiotics (e.g. ceftriaxone) is slow anion channel gated by glutamate, rather than a glutamate
their location, to regulate excitatory neurotransmission, maintain neuroprotective and occurs through NF-κB-mediated EAAT2 pro- transporter [220].

Searchable database: http://www.guidetopharmacology.org/index.jsp Glutamate transporter subfamily S410

Nomenclature Excitatory amino acid transporter 1 Excitatory amino acid transporter 2 Excitatory amino acid transporter 3 Excitatory amino acid transporter 4 Excitatory amino acid transporter 5
Systematic nomenclature SLC1A3 SLC1A2 SLC1A1 SLC1A6 SLC1A7
Common abbreviation EAAT1 EAAT2 EAAT3 EAAT4 EAAT5
HGNC, UniProt SLC1A3, P43003 SLC1A2, P43004 SLC1A1, P43005 SLC1A6, P48664 SLC1A7, O00341
Substrates DL-threo-β-hydroxyaspartate (Ki D-aspartic acid, L-trans-2,4-pyrolidine D-aspartic acid, D-aspartic acid,
5.8×10−5 M) [571], D-aspartic acid, DL-threo-β-hydroxyaspartate, dicarboxylate, DL-threo-β-hydroxyaspartate, L-trans-2,4-pyrolidine
L-trans-2,4-pyrolidine L-trans-2,4-pyrolidine DL-threo-β-hydroxyaspartate, L-trans-2,4-pyrolidine dicarboxylate,
dicarboxylate dicarboxylate [367] D-aspartic acid dicarboxylate DL-threo-β-hydroxyaspartate
Endogenous substrates L-aspartic acid, L-glutamic acid L-glutamic acid, L-aspartic acid L-aspartic acid, L-cysteine [706], L-glutamic acid, L-aspartic acid L-aspartic acid, L-glutamic acid
L-glutamic acid
Stoichiometry Probably 3 Na+ : 1 H+ : 1 3 Na+ : 1 H+ : 1 glutamate (in): 1 3 Na+ : 1 H+ : 1 glutamate (in): 1 Probably 3 Na+ : 1 H+ : 1 Probably 3 Na+ : 1 H+ : 1
glutamate (in): 1 K+ (out) K+ (out) [396] K+ (out) [705] glutamate (in): 1 K+ (out) glutamate (in): 1 K+ (out)
Inhibitors UCPH-101 (membrane potential WAY-213613 (pIC50 7.1) [167], NBI-59159 (pIC50 7.1) [165], DL-TBOA (pKi 5.4) [570], DL-TBOA (pKi 5.5) [570]
assay) (pIC50 6.9) [326], DL-TBOA DL-TBOA (pKB 6.9) [571], L-β-BA ([3 H]D-aspartate uptake threo-3-methylglutamate (pKi 4.3)
(pKB 5) [571] SYM2081 (pKB 5.5) [640], assay) (pKi 6.1) [186], DL-TBOA [176]
dihydrokainate (pKB 5), (pIC50 5.1) [573]
threo-3-methylglutamate (pKB
4.7) [640]
Labelled ligands [3 H]ETB-TBOA (Binding) (pKd 7.8) [3 H]ETB-TBOA (Binding) (pKd 7.8) [3 H]ETB-TBOA (Binding) (pKd 6.5) [3 H]ETB-TBOA (Binding) (pKd 7.9) [3 H]ETB-TBOA (Binding) (pKd 7.6)
[572] – Rat, [3 H]D-aspartic acid, [572] – Rat, [3 H]D-aspartic acid, [572] – Rat, [3 H]D-aspartic acid, [572] – Rat, [3 H]D-aspartic acid, [572] – Rat, [3 H]D-aspartic acid,
[3 H]L-aspartic acid, [3 H]SYM2081 [3 H]L-aspartic acid, [3 H]SYM2081 [3 H]L-aspartic acid [3 H]L-aspartic acid [3 H]L-aspartic acid

Comments: The KB (or Ki ) values reported, unless indicated oth- ence for EAAT2 over EAAT3 and EAAT1 [166, 167]. NBI-59159 substrate-like currents at EAAT4, but does not elicit heteroex-
erwise, are derived from transporter currents mediated by EAATs is a non-substrate inhibitor with modest selectivity for EAAT3 change of [3 H]-aspartate in synaptosome preparations, inconsis-
expressed in voltage-clamped Xenopus laevis oocytes [176, 570, over EAAT1 (>10-fold) and EAAT2 (5-fold) [126, 164]. Analo- tent with the behaviour of a substrate inhibitor [176]. Parawixin 1,
571, 640]. KB (or Ki ) values derived in uptake assays are generally gously, L-β-threo-benzyl-aspartate (L-β-BA) is a competitive non- a compound isolated from the venom from the spider Parawixia
higher (e.g. [571]). In addition to acting as a poorly transportable substrate inhibitor that preferentially blocks EAAT3 versus EAAT1, bistriata is a selective enhancer of the glutamate uptake through
inhibitor of EAAT2, (2S,4R)-4-methylglutamate, also known as or EAAT2 [186]. [3 H]SYM2081 demonstrates low afﬁnity binding EAAT2 but not through EAAT1 or EAAT3 [207, 208]. In addition
SYM2081, is a competitive substrate for EAAT1 (KM = 54μM; [300, (KD ∼= 6.0 μM) to EAAT1 and EAAT2 in rat brain homogenates to the agents listed in the table, DL-threo-β-hydroxyaspartate and
640]) and additionally is a potent kainate receptor agonist [715] [25] and EAAT1 in murine astrocyte membranes [23], whereas L-trans-2,4-pyrolidine dicarboxylate act as non-selective compet-
which renders the compound unsuitable for autoradiographic lo- [3 H]ETB-TBOA binds with high afﬁnity to all EAATs other than itive substrate inhibitors of all EAATs. Zn2+ and arachidonic acid
calisation of EAATs [24]. Similarly, at concentrations that inhibit EAAT3 [572]. The novel isoxazole derivative (-)-HIP-A may in- are putative endogenous modulators of EAATs with actions that
EAAT2, dihydrokainate binds to kainate receptors [571]. WAY-855 teract at the same site as TBOA and preferentially inhibit reverse differ across transporter subtypes (reviewed by [639]).
and WAY-213613 are both non-substrate inhibitors with a prefer- transport of glutamate [124]. Threo-3-methylglutamate induces

Searchable database: http://www.guidetopharmacology.org/index.jsp Glutamate transporter subfamily S411

Alanine/serine/cysteine transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC1 family of amino acid transporters → Alanine/serine/cysteine transporter subfamily
Overview: ASC transporters mediate Na+ -dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr and their structure is predicted to be similar to that of the glutamate transporters
[27, 634]. ASCT1 and ASCT2 also exhibit thermodynamically uncoupled chloride channel activity associated with substrate transport [79, 704]. Whereas EAATs counter-transport K+ (see above) ASCTs
do not and their function is independent of the intracellular concentration of K+ [704].

Nomenclature Alanine/serine/cysteine transporter 1 Alanine/serine/cysteine transporter 2

Systematic nomenclature SLC1A4 SLC1A5
Common abbreviation ASCT1 ASCT2
HGNC, UniProt SLC1A4, P43007 SLC1A5, Q15758
Endogenous substrates L-cysteine > L-alanine = L-serine > L-threonine L-alanine = L-serine = L-cysteine (low Vmax) = L-threonine = L-glutamine = L-asparagine
L-methionine ∼ = glycine ∼
= L-leucine > L-valine > L-glutamic acid (enhanced at low pH)
Stoichiometry 1 Na+ : 1 amino acid (in): 1 Na+ : 1 amino acid (out); (homo-, or hetero-exchange; [705]) 1 Na+ : 1 amino acid (in): 1 Na+ : 1 amino acid (out); (homo-, or hetero-exchange; [77])
Inhibitors – p-nitrophenyl glutamyl anilide (pKi 4.3) [187] – Rat, benzylcysteine (pKi 3.1) [258],
benzylserine (pKi 3) [258]

Comments: The substrate speciﬁcity of ASCT1 may extend to L-proline and trans-4-hydroxy-proline [499]. At low pH (5.5) both ASCT1 and ASCT2 are able to exchange acidic amino acids such as
L-cysteate and glutamate [605, 634]. In addition to the inhibitors tabulated above, HgCl2 , methylmercury and mersalyl, at low micromolar concentrations, non-competitively inhibit ASCT2 by covalent
modiﬁciation of cysteine residues [480].

Searchable database: http://www.guidetopharmacology.org/index.jsp Alanine/serine/cysteine transporter subfamily S412

SLC2 family of hexose and sugar alcohol transporters

Transporters → SLC superfamily of solute carriers → SLC2 family of hexose and sugar alcohol transporters
Overview: The SLC2 family transports D-glucose, D-fructose, inositol (e.g. myo-inositol) and related hexoses. Three classes of glucose transporter can be identiﬁed, separating GLUT1-4 and 14, GLUT6,
8, 10 and 12; and GLUT5, 7, 9 and 11. Modelling suggests a 12 TM membrane topology, with intracellular termini, with functional transporters acting as homodimers or homotetramers.

Class I transporters
Transporters → SLC superfamily of solute carriers → SLC2 family of hexose and sugar alcohol transporters → Class I transporters
Overview: Class I transporters are able to transport D-glucose, but not D-fructose, in the direction of the concentration gradient and may be inhibited non-selectively by phloretin and cytochalasin B.
GLUT1 is the major glucose transporter in brain, placenta and erythrocytes, GLUT2 is found in the pancreas, liver and kidneys, GLUT3 is neuronal and placental, while GLUT4 is the insulin-responsive
transporter found in skeletal muscle, heart and adipose tissue. GLUT14 appears to result from gene duplication of GLUT3 and is expressed in the testes [678].

Nomenclature Glucose transporter 1 Glucose transporter 2 Glucose transporter 3 Glucose transporter 4 Glucose transporter 14
Systematic nomenclature SLC2A1 SLC2A2 SLC2A3 SLC2A4 SLC2A14
Common abbreviation GLUT1 GLUT2 GLUT3 GLUT4 GLUT14
HGNC, UniProt SLC2A1, P11166 SLC2A2, P11168 SLC2A3, P11169 SLC2A4, P14672 SLC2A14, Q8TDB8
Substrates D-glucosamine (D-glucose = D-glucosamine (D-glucosamine > D-glucose D-glucosamine (D-glucosamine ≥ –
D-glucosamine) [631], D-glucose) [631], D-glucose D-glucose) [631], D-glucose
dehydroascorbic acid [55], D-glucose (D-glucosamine > D-glucose) [631] (D-glucosamine ≥ D-glucose) [631]
(D-glucose = D-glucosamine) [631]
Labelled ligands [3 H]2-deoxyglucose [3 H]2-deoxyglucose [3 H]2-deoxyglucose [3 H]2-deoxyglucose –
Comments GLUT1 is a class I facilitative sugar – – – –
transporter. GLUT1 functions to
maintain basal glucose import which
is required for cellular respiration.

Searchable database: http://www.guidetopharmacology.org/index.jsp Class I transporters S413

Class II transporters
Transporters → SLC superfamily of solute carriers → SLC2 family of hexose and sugar alcohol transporters → Class II transporters
Overview: Class II transporters transport D-fructose and appear to be insensitive to cytochalasin B. Class II transporters appear to be predominantly intracellularly located.

Nomenclature Glucose transporter 5 Glucose transporter 7 Glucose transporter 9

Systematic nomenclature SLC2A5 SLC2A7 SLC2A9
Common abbreviation GLUT5 GLUT7 GLUT9
HGNC, UniProt SLC2A5, P22732 SLC2A7, Q6PXP3 SLC2A9, Q9NRM0
Substrates D-fructose (D-fructose > D-glucose) [83], D-glucose (D-fructose > D-glucose) [83] D-fructose [104], D-glucose [104] D-fructose [94], uric acid [94]

Nomenclature Glucose transporter 11 Glucose transporter 6 Glucose transporter 8 Glucose transporter 10 Glucose transporter 12
Systematic nomenclature SLC2A11 SLC2A6 SLC2A8 SLC2A10 SLC2A12
Common abbreviation GLUT11 GLUT6 GLUT8 GLUT10 GLUT12
HGNC, UniProt SLC2A11, Q9BYW1 SLC2A6, Q9UGQ3 SLC2A8, Q9NY64 SLC2A10, O95528 SLC2A12, Q8TD20
Substrates D-fructose [426], D-glucose [156] – D-glucose [303] dehydroascorbic acid [392], D-glucose [530]
D-glucose [392]

Searchable database: http://www.guidetopharmacology.org/index.jsp Class II transporters S414

Proton-coupled inositol transporter

Transporters → SLC superfamily of solute carriers → SLC2 family of hexose and sugar alcohol transporters → Proton-coupled inositol transporter
Overview: Proton-coupled inositol transporters are expressed predominantly in the brain and can be inhibited by phloretin and cytochalasin B [631].

Nomenclature Proton myo-inositol cotransporter

Systematic nomenclature SLC2A13
Common abbreviation HMIT
HGNC, UniProt SLC2A13, Q96QE2
Substrates D-chiro-inositol [631], myo-inositol [631], scyllo-inositol [631], muco-inositol [631]
Stoichiometry 1 H+ : 1 inositol (in) [150]

SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

Transporters → SLC superfamily of solute carriers → SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)
Overview: The SLC3 and SLC7 families combine to generate functional transporters, where the subunit composition is a disulphide-linked combination of a heavy chain (SLC3 family) with a light chain
(SLC7 family).

SLC3 family
Transporters → SLC superfamily of solute carriers → SLC3 and SLC7 families of heteromeric amino acid transporters (HATs) → SLC3 family
Overview: SLC3 family members are single TM proteins with extensive glycosylation of the exterior C-terminus, which heterodimerize with SLC7 family members in the endoplasmic reticulum and
assist in the plasma membrane localization of the transporter.

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC3 family S415

SLC7 family
Transporters → SLC superfamily of solute carriers → SLC3 and SLC7 families of heteromeric amino acid transporters (HATs) → SLC7 family
Overview: SLC7 family members may be divided into two major groups: cationic amino acid transporters (CATs) and glycoprotein-associated amino acid transporters (gpaATs).
Cationic amino acid transporters are 14 TM proteins, which mediate pH- and sodium-independent transport of cationic amino acids (system y+ ), apparently as an exchange mechanism. These transporters
are sensitive to inhibition by N-ethylmaleimide.

Nomenclature High afﬁnity cationic amino acid Low afﬁnity cationic amino acid Cationic amino acid transporter 3 L-type amino acid transporter 1 L-type amino acid transporter 2
transporter 1 transporter 2
Systematic nomenclature SLC7A1 SLC7A2 SLC7A3 SLC7A5 SLC7A8
Common abbreviation CAT1 CAT2 CAT3 LAT1 LAT2
HGNC, UniProt SLC7A1, P30825 SLC7A2, P52569 SLC7A3, Q8WY07 SLC7A5, Q01650 SLC7A8, Q9UHI5
Substrates L-ornithine, L-arginine, L-lysine, L-ornithine, L-arginine, L-lysine, L-ornithine, L-arginine, L-lysine – –
L-histidine L-histidine
Selective inhibitors – – – KYT-0353 [476] –

Nomenclature y+L amino acid transporter 1 y+L amino acid transporter 2 b0,+ -type amino acid Asc-type amino acid Cystine/glutamate transporter AGT1
transporter 1 transporter 1
Systematic nomenclature SLC7A7 SLC7A6 SLC7A9 SLC7A10 SLC7A11 SLC7A13
Common abbreviation y+LAT1 y+LAT2 b0,+ AT Asc-1 xCT –
HGNC, UniProt SLC7A7, Q9UM01 SLC7A6, Q92536 SLC7A9, P82251 SLC7A10, Q9NS82 SLC7A11, Q9UPY5 SLC7A13, Q8TCU3
Inhibitors – – – – quisqualate (pIC50 5.3) [188] –

Comments: CAT4 appears to be non-functional in heterologous Heterodimers between 4F2hc and y+ LAT1 or y+ LAT2 generate Asc-1 appears to heterodimerize with 4F2hc to allow the trans-
expression [672], while SLC7A14 has yet to be characterized. transporters similar to the system y+ L , which transport cationic port of small neutral amino acids (such as L-alanine, L-serine,
Glycoprotein-associated amino acid transporters are 12 TM pro- (L-arginine, L-lysine, L-ornithine) amino acids independent L-threonine, L-glutamine and glycine), as well as D-serine, in a
teins, which heterodimerize with members of the SLC3 family to of sodium and neutral (L-leucine, L-isoleucine, L-methionine, sodium-independent manner.
act as cell-surface amino acid exchangers. L-glutamine) amino acids in a partially sodium-dependent man- xCT generates a heterodimer with 4F2hc for a system x- e-c
Heterodimers between 4F2hc and LAT1 or LAT2 generate sodium- ner. These transporters are N-ethylmaleimide-insensitive. Het- transporter that mediates the sodium-independent exchange of
independent system L transporters. LAT1 transports large neutral erodimers between rBAT and b0,+ AT appear to mediate sodium- L-cystine and L-glutamic acid.
amino acids including branched-chain and aromatic amino acids independent system b0,+ transport of most of the neutral AGT has been conjugated with SLC3 members as fusion proteins
as well as miglustat, whereas LAT2 transports most of the neutral amino acids and cationic amino acids (L-arginine, L-lysine and to generate functional transporters, but the identity of a native
amino acids. L-ornithine). heterodimer has yet to be ascertained.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC7 family S416

Further reading on SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

Bhutia YD et al. (2015) Amino Acid transporters in cancer and their relevance to "glutamine addic- Palacín M et al. (2005) The genetics of heteromeric amino acid transporters. Physiology (Bethesda) 20:
tion": novel targets for the design of a new class of anticancer drugs. Cancer Res. 75: 1782-8 112-24 [PMID:15772300]
[PMID:25855379] Verrey F et al. (2004) CATs and HATs: the SLC7 family of amino acid transporters. Pﬂugers Arch. 447:
Fotiadis D et al. (2013) The SLC3 and SLC7 families of amino acid transporters. Mol. Aspects Med. 532-42 [PMID:14770310]
34: 139-58 [PMID:23506863]
Palacín M et al. (2004) The ancillary proteins of HATs: SLC3 family of amino acid transporters.
Pﬂugers Arch. 447: 490-4 [PMID:14770309]

SLC4 family of bicarbonate transporters

Transporters → SLC superfamily of solute carriers → SLC4 family of bicarbonate transporters

Overview: Together with the SLC26 family, the SLC4 family of Within the family, subgroups of transporters are identiﬁable: the gests a dimeric or tetrameric arrangement, with subunits made up
transporters subserve anion exchange, principally of chloride and electroneutral sodium-independent Cl- /HCO3 - transporters (AE1, of 13 TM domains and re-entrant loops at TM9/10 and TM11/12.
bicarbonate (HCO3 - ), but also carbonate and hydrogen sulphate AE2 and AE3), the electrogenic sodium-dependent HCO3 - trans- The N terminus exhibits sites for interaction with multiple pro-
(HSO4 - ). SLC4 family members regulate bicarbonate ﬂuxes as part porters (NBCe1 and NBCe2) and the electroneutral HCO3 - trans- teins, including glycolytic enzymes, haemoglobin and cytoskele-
of carbon dioxide movement, chyme neutralization and reabsorp- porters (NBCn1 and NBCn2). Topographical information derives tal elements.
tion in the kidney. mainly from study of AE1, abundant in erythrocytes, which sug-

Anion exchangers
Transporters → SLC superfamily of solute carriers → SLC4 family of bicarbonate transporters → Anion exchangers

Nomenclature Anion exchange protein 1 Anion exchange protein 2 Anion exchange protein 3 Anion exchange protein 4
Systematic nomenclature SLC4A1 SLC4A2 SLC4A3 SLC4A9
Common abbreviation AE1 AE2 AE3 AE4
HGNC, UniProt SLC4A1, P02730 SLC4A2, P04920 SLC4A3, P48751 SLC4A9, Q96Q91
Endogenous substrates HCO3 -, Cl- Cl- , HCO3 - Cl- , HCO3 - –
Stoichiometry 1 Cl- (in) : 1 HCO3 - (out) 1 Cl- (in) : 1 HCO3 - (out) 1 Cl- (in) : 1 HCO3 - (out) –

Searchable database: http://www.guidetopharmacology.org/index.jsp Anion exchangers S417

Sodium-dependent HCO3- transporters

Transporters → SLC superfamily of solute carriers → SLC4 family of bicarbonate transporters → Sodium-dependent HCO3 - transporters

Nomenclature Electrogenic sodium Electrogenic sodium Electroneutral sodium Electroneutral sodium NBCBE NaBC1
bicarbonate cotransporter 1 bicarbonate cotransporter 4 bicarbonate cotransporter 1 bicarbonate cotransporter 2
Systematic nomenclature SLC4A4 SLC4A5 SLC4A7 SLC4A10 SLC4A8 SLC4A11
Common abbreviation NBCe1 NBCe2 NBCn1 NBCn2 NDCBE BTR1
HGNC, UniProt SLC4A4, Q9Y6R1 SLC4A5, Q9BY07 SLC4A7, Q9Y6M7 SLC4A10, Q6U841 SLC4A8, Q2Y0W8 SLC4A11, Q8NBS3
Endogenous substrates NaHCO3 - NaHCO3 - NaHCO3 - NaHCO3 - NaHCO3 - , Cl- Cl- , NaHCO3 -
Stoichiometry 1 Na+ : 2/3 HCO3 - (out) or 1 1 Na+ : 2/3 HCO3 - (out) or 1 1 Na+ : 1 HCO3 - (out) or 1 1Na+ -
: 1 HCO3 (out) or 1 Na 1 Na+ -
: 2HCO3 (in) : 1 Cl- –
Na+ : CO3 2* Na+ : CO3 2* Na+ : CO3 2* : CO3 2* (out)

SLC5 family of sodium-dependent glucose transporters

Transporters → SLC superfamily of solute carriers → SLC5 family of sodium-dependent glucose transporters
Overview: The SLC5 family of sodium-dependent glucose transporters includes, in mammals, the Na+ /substrate co-transporters for glucose (e.g. choline), D-glucose, monocarboxylates, myo-inositol and
I- [200, 224, 674, 675]. Members of the SLC5 and SLC6 families, along with other unrelated Na+ cotransporters (i.e. Mhp1 and BetP), share a common structural core that contains an inverted repeat of
5TM α-helical domains [2].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC5 family of sodium-dependent glucose transporters S418

Hexose transporter family

Transporters → SLC superfamily of solute carriers → SLC5 family of sodium-dependent glucose transporters → Hexose transporter family

Overview: Detailed characterisation of members of the hexose pressed in the small intestine, mediating the absorption of glucose reabsorption of glucose. SGLT3 is not a transporter but instead
transporter family is limited to SGLT1, 2 and 3, which are all in- (e.g. D-glucose), but also occurs in the brain, heart and in the late acts as a glucosensor generating an inwardly directed ﬂux of Na+
hibited in a competitive manner by phlorizin, a natural dihydro- proximal straight tubule of the kidney. The expression of SGLT2 that causes membrane depolarization [153].
choline glucoside, that exhibits modest selectivity towards SGLT2 is almost exclusively restricted to the early proximal convoluted
(see [674] for an extensive review). SGLT1 is predominantly ex- tubule of the kidney, where it is largely responsible for the renal

Nomenclature Sodium/glucose cotransporter 1 Sodium/glucose cotransporter 2 Low affinity sodium-glucose Sodium/glucose cotransporter 4 Sodium/glucose cotransporter 5
cotransporter
Systematic nomenclature SLC5A1 SLC5A2 SLC5A4 SLC5A9 SLC5A10
Common abbreviation SGLT1 SGLT2 SGLT3 SGLT4 SGLT5
HGNC, UniProt SLC5A1, P13866 SLC5A2, P31639 SLC5A4, Q9NY91 SLC5A9, Q2M3M2 SLC5A10, A0PJK1
Substrates D-galactose [650], α-MDG [650], α-MDG, D-glucose D-glucose [650], D-glucose, D-mannose, α-MDG D-galactose, D-glucose
D-glucose [650] 1-deoxynojirimycin-1-sulfonic acid
[650], N-ethyl-1-deoxynojirimycin
[650], miglustat [650], miglitol
[650], 1-deoxynojirimycin [650]
Stoichiometry 2 Na+ : 1 glucose [340] 1 Na+ : 1 glucose [301] – – –
Selective inhibitors mizagliflozin (pKi 7.6) [311] dapagliflozin (pIC50 9.3) [343] – – –
Comments – – SGLT3 acts as a glucosensor. – –

Comments: Recognition and transport of substrate by SGLTs re- and C3, is tolerated (see [674] for a detailed quantification). Al- iological conditions [301]. Selective blockers of SGLT2, and thus
quires that the sugar is a pyranose. De-oxyglucose derivatives have though SGLT1 and SGLT2 have been described as high- and low- blocking 50% of renal glucose reabsorption, are in development
reduced affinity for SGLT1, but the replacement of the sugar equa- affinity sodium glucose co-transporters, respectively, recent work for the treatment of diabetes (e.g. [100]).
torial hydroxyl group by fluorine at some positions, excepting C2 suggests that they have a similar affinity for glucose under phys-

Searchable database: http://www.guidetopharmacology.org/index.jsp Hexose transporter family S419

Choline transporter
Transporters → SLC superfamily of solute carriers → SLC5 family of sodium-dependent glucose transporters → Choline transporter

Overview: The high affinity, hemicholinium-3-sensitive, choline hydrolysis of ACh by acetylcholinesterase, CHT serves to maintain remains to be identified at the molecular level may involve multi-
transporter (CHT) is expressed mainly in cholinergic neurones on acetylcholine synthesis within the presynaptic terminal [200]. Ho- ple transporters. In addition, a family of choline transporter-like
nerve cell terminals and synaptic vesicles (keratinocytes being an mozygous mice engineered to lack CHT die within one hour of (CTL) proteins, (which are members of the SLC44 family) with
additional location). In autonomic neurones, expression of CHT birth as a result of hypoxia arising from failure of transmission at weak Na+ dependence have been described [622].
requires an activity-dependent retrograde signal from postsynap- the neuromuscular junction of the skeletal muscles that support
tic neurones [375]. Through recapture of choline generated by the respiration [199]. A low affinity choline uptake mechanism that

Nomenclature CHT
Systematic nomenclature SLC5A7
HGNC, UniProt SLC5A7, Q9GZV3
Substrates triethylcholine
Endogenous substrates choline
Stoichiometry Na+ : choline (variable stoichimetry); modulated by extracellular Cl- [322]
Selective inhibitors hemicholinium-3 (pKi 7–8) [478]
Labelled ligands [3 H]hemicholinium-3 (pKd 8.2–8.4)

Comments: Ki and KD values for hemicholinium-3 listed in the table are for human CHT expressed in Xenopus laevis oocytes [479], or COS-7 cells [22]. Hemicholinium mustard is a substrate for CHT
that causes covalent modiﬁcation and irreversible inactivation of the transporter. Several exogenous substances (e.g. triethylcholine) that are substrates for CHT act as precursors to cholinergic false
transmitters.

Searchable database: http://www.guidetopharmacology.org/index.jsp Choline transporter S420

Sodium iodide symporter, sodium-dependent multivitamin

transporter and sodium-coupled monocarboxylate transporters
Transporters → SLC superfamily of solute carriers → SLC5 family of sodium-dependent glucose transporters → Sodium iodide symporter, sodium-dependent multivitamin transporter and
sodium-coupled monocarboxylate transporters

Overview: The sodium-iodide symporter (NIS) is an iodide trans- (SLC5A8), which transports a wide range of monocarboxylates, is the kidney, SMCT2 is responsible for the bulk absorption of lactate
porter found principally in the thyroid gland where it mediates expressed in the apical membrane of epithelia of the small in- because of its low-affinity/high-capacity nature. Absence of both
the accumulation of I- within thyrocytes. Transport of I- by NIS testine, colon, kidney, brain neurones and the retinal pigment transporters in the kidney leads to massive excretion of lactate in
from the blood across the basolateral membrane followed by api- epithelium [224]. SMCT2 (SLC5A12) also localises to the apical urine and consequently drastic decrease in the circulating levels
cal efflux into the colloidal lumen, mediated at least in part by membrane of kidney, intestine, and colon, but in the brain and of lactate in blood [615]. SMCT1 also functions as a tumour sup-
pendrin (SLC22A4), and most likely not SMCT1 (SLC5A8) as once retina is restricted to astrocytes and Müller cells, respectively [224]. pressor in the colon as well as in various other non-colonic tissues
thought, provides the I- required for the synthesis of the thyroid SMCT1 is a high-affinity transporter whereas SMCT2 is a low- [225]. The tumour-suppressive function of SMCT1 is based on its
hormones triiodothyronine (triiodothyronine) and thyroxine (T4 ) affinity transporter. The physiological substrates for SMCT1 and ability to transport pyruvic acid, an inhibitor of histone deacety-
[59]. NIS is also expressed in the salivary glands, gastric mucosa, SMCT2 are lactate (L-lactic acid and D-lactic acid), pyruvic acid, lases, into cells in non-colonic tissues [616]; in the colon, the abil-
intestinal enterocytes and lactating breast. NIS mediates I- ab- propanoic acid, and nicotinic acid in non-colonic tissues such as ity of SMCT1 to transport butyric acid and propanoic acid, also in-
sorption in the intestine and I- secretion into the milk. SMVT is the kidney. SMCT1 is also likely to be the principal transporter for hibitors of histone deacetylases, underlies the tumour-suppressive
expressed on the apical membrane of intestinal enterocytes and the absorption of nicotinic acid (vitamin B3 ) in the intestine and function of this transporter [224, 225, 271]. The ability of SMCT1
colonocytes and is the main system responsible for biotin (vi- kidney [246]. In the small intestine and colon, the physiological to promote histone acetylase inhibition through accumulation of
tamin H) and pantothenic acid (vitamin B5 ) uptake in humans substrates for these transporters are nicotinic acid and the short- butyric acid and propanoic acid in immune cells is also respon-
[544]. SMVT located in kidney proximal tubule epithelial cells chain fatty acids acetic acid, propanoic acid, and butyric acid that sible for suppression of dendritic cell development in the colon
mediates the reabsorption of biotin and pantothenic acid. SMCT1 are produced by bacterial fermentation of dietary fiber [447]. In [579].

Nomenclature NIS SMVT SMCT1 SMCT2

Systematic nomenclature SLC5A5 SLC5A6 SLC5A8 SLC5A12
HGNC, UniProt SLC5A5, Q92911 SLC5A6, Q9Y289 SLC5A8, Q8N695 SLC5A12, Q1EHB4
Substrates ClO4 - , SCN- , I- , NO3 - , pertechnetate lipoic acid [139], pantothenic acid propanoic acid, 3-bromopyruvate, pyroglutamic acid, pyruvic acid, L-lactic acid, nicotinic acid
[139], I- [139], biotin [139] nicotinic acid, D-lactic acid, β-D-hydroxybutyric acid,
L-lactic acid, salicylic acid, dichloroacetate, butyric acid,
α-ketoisocaproate, pyruvic acid, acetoacetic acid,
benzoate, γ-hydroxybutyric acid,
2-oxothiazolidine-4-carboxylate, acetic acid,
β-L-hydroxybutyric acid, 5-aminosalicylate
Stoichiometry 2Na+ : 1 I- [185]; 1Na+ : 1 ClO4 - [157] 2Na+ : 1 biotin (or pantothenic acid) 2Na+ : 1 monocarboxylate [120] –
[506]
Inhibitors – – fenoprofen (pIC50 4.6) [319], ibuprofen (pIC50 4.2) –
[319], ketoprofen (pIC50 3.9) [319]

Comments: I- , ClO4 - , thiocyanate and NO3 - are competitive substrate inhibitors of NIS [157]. Lipoic acid appears to act as a competitive substrate inhibitor of SMVT [654] and the anticonvulsant drugs
primidone and carbamazepine competitively block the transport of biotin by brush border vesicles prepared from human intestine [545].

Searchable database: http://www.guidetopharmacology.org/index.jsp Sodium ionide symporter, sodium-dependent multivitamin S421

Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full transporter and sodium-coupled monocarboxylate transporters
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

Sodium myo-inositol cotransporter transporters

Transporters → SLC superfamily of solute carriers → SLC5 family of sodium-dependent glucose transporters → Sodium myo-inositol cotransporter transporters

Overview: Three different mammalian myo-inositol cotrans- Darby canine kidney cell line, they segregate to the basolateral from the ﬁltrate. In some species (e.g. rat, but not rabbit) apically
porters are currently known; two are the Na+ -coupled SMIT1 and and apical membranes, respectively [58]. In the nephron, SMIT1 located SMIT2 is responsible for the uptake of myo-inositol from
SMIT2 tabulated below and the third is proton-coupled HMIT mediates myo-inositol uptake as a ‘compatible osmolyte’ when in- the intestinal lumen [21].
(SLC2A13). SMIT1 and SMIT2 have a widespread and overlap- ner medullary tubules are exposed to increases in extracellular os-
ping tissue location but in polarized cells, such as the Madin- molality, whilst SMIT2 mediates the reabsorption of myo-inositol

Nomenclature SMIT SGLT6

Systematic nomenclature SLC5A3 SLC5A11
Common abbreviation SMIT1 SMIT2
HGNC, UniProt SLC5A3, P53794 SLC5A11, Q8WWX8
Substrates myo-inositol, scyllo-inositol > L-fucose > L-xylose > L-glucose, D-glucose, α-MDG > myo-inositol = D-chiro-inositol> D-glucose > D-xylose > L-xylose [121]
D-galactose, D-fucose > D-xylose [273]
Stoichiometry 2 Na+ :1 myo-inositol [273] 2 Na+ :1 myo-inositol [70]
Inhibitors phlorizin [121] phlorizin (pKi 4.1) [121]

Comments: The data tabulated are those for dog SMIT1 and rabbit SMIT2. SMIT2 transports D-chiro-inositol, but SMIT1 does not. In addition, whereas SMIT1 transports both D-xylose and L-xylose
and D-fucose and L-fucose, SMIT2 transports only the D-isomers of these sugars [121, 273]. Thus the substrate speciﬁcities of SMIT1 (for L-fucose) and SMIT2 (for D-chiro-inositol) allow discrimination
between the two SMITs. Human SMIT2 appears not to transport glucose [402].

Searchable database: http://www.guidetopharmacology.org/index.jsp Sodium myo-inositol cotransporter transporters S422

SLC6 neurotransmitter transporter family

Transporters → SLC superfamily of solute carriers → SLC6 neurotransmitter transporter family

Overview: Members of the solute carrier family 6 (SLC6) of monoamines, GABA, glycine and neutral amino acids, plus the LeuTAa , a Na+ -dependent amino acid transporter from Aquiﬂex ae-
sodium- and (sometimes chloride-) dependent neurotransmitter related bacterial NSS transporters [546]. The members of this su- olicus [687] and in several other transporter families structurally
transporters [80, 106, 376] are primarily plasma membrane lo- perfamily share a structural motif of 10 TM segments that has related to LeuT [209].
cated and may be divided into four subfamilies that transport been observed in crystal structures of the NSS bacterial homolog

Monoamine transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC6 neurotransmitter transporter family → Monoamine transporter subfamily
Overview: Monoamine neurotransmission is limited by perisynaptic transporters. Presynaptic monoamine transporters allow recycling of synaptically released noradrenaline, dopamine and 5-hydroxytryptamine.

Nomenclature NET DAT SERT

Systematic nomenclature SLC6A2 SLC6A3 SLC6A4
HGNC, UniProt SLC6A2, P23975 SLC6A3, Q01959 SLC6A4, P31645
Substrates MPP+ , methamphetamine, amphetamine MPP+ , methamphetamine, amphetamine MDMA, p-chloroamphetamine
Endogenous substrates dopamine, (-)-adrenaline, (-)-noradrenaline dopamine, (-)-adrenaline, (-)-noradrenaline 5-hydroxytryptamine
Stoichiometry 1 noradrenaline: 1 Na+ :1 Cl- [266] 1 dopamine: 1˘2 Na+ : 1 Cl- [265] 1 5-HT:1 Na+ :1 Cl- (in), + 1 K+ (out) [603]
Inhibitors H05 (pKi 8.2) [682] – Rat – H05 (pKi 8.3) [682] – Rat
Sub/family-selective inhibitors sibutramine (pKi 5.2) [31] sibutramine (pKi 6.3) [31] sibutramine (pKi 6) [31]
Selective inhibitors mazindol (pKi 8.9), protriptyline (pIC50 8.8) [449], mazindol (pKi 8), WIN35428 (pKi 7.9) [524], GBR12935 clomipramine (pKi 9.7) [608], paroxetine (pKi 9.6) [608],
nisoxetine (pKi 8.4), protriptyline (pKi 8.2) [404], (pKi 7.6), dexmethylphenidate (pKi 7.6) [381], clomipramine (pKd 9.6) [608], sertraline (pKi 9.1),
nomifensine (pKi 8.1), reboxetine (pKi 8) [673] methylphenidate (pIC50 7.1) [214] escitalopram (pIC50 9) [535], dapoxetine (pIC50 8.9)
[233], ﬂuvoxamine (pKd 8.7) [608], ﬂuoxetine (pKi 8.5)
[608], citalopram (pKi 8.4) [49]
Labelled ligands [3 H]mazindol (Inhibitor) (pKd 9.3) [514] – Rat, [3 H]GBR12935 (Inhibitor) (pKd 8.5) [508], [3 H]paroxetine (Inhibitor) (pKd 9.7), [3 H]citalopram
[3 H]nisoxetine (Inhibitor) (pKd 8.4) [3 H]WIN35428 (Inhibitor) (pKd 8) [508] (Inhibitor) (pKd 8.3)

Comments: [125 I]RTI55 labels all three monoamine transporters (NET, DAT and SERT) with afﬁnities between 0.5 and 5 nM. Cocaine is an inhibitor of all three transporters with pKi values between 6.5
and 7.2. Potential alternative splicing sites in non-coding regions of SERT and NET have been identiﬁed. A bacterial homologue of SERT shows allosteric modulation by selected anti-depressants [580].

Searchable database: http://www.guidetopharmacology.org/index.jsp Monoamine transporter subfamily S423

GABA transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC6 neurotransmitter transporter family → GABA transporter subfamily

Overview: The activity of GABA-transporters located predomi- [566]. GAT1 is the predominant GABA transporter in the brain and is a high affinity taurine transporter involved in osmotic balance
nantly upon neurones (GAT-1), glia (GAT-3) or both (GAT-2, BGT- occurs primarily upon the terminals of presynaptic neurones and that occurs in the brain and non-neuronal tissues, such as the kid-
1) serves to terminate phasic GABA-ergic transmission, maintain to a much lesser extent upon distal astocytic processes that are in ney, brush border membrane of the intestine and blood brain bar-
low ambient extracellular concentrations of GABA, and recycle proximity to axons terminals. GAT3 resides predominantly on dis- rier [106, 279]. CT1, which transports creatine, has a ubiquitous
GABA for reuse by neurones. Nonetheless, ambient concentra- tal astrocytic terminals that are close to the GABAergic synapse. By expression pattern, often co-localizing with creatine kinase [106].
tions of GABA are sufficient to sustain tonic inhibition mediated contrast, BGT1 occupies an extrasynaptic location possibly along
by high affinity GABAA receptors in certain neuronal populations with GAT2 which has limited expression in the brain [422]. TauT

Nomenclature GAT1 GAT2 GAT3 BGT1 TauT CT1

Systematic nomenclature SLC6A1 SLC6A13 SLC6A11 SLC6A12 SLC6A6 SLC6A8
HGNC, UniProt SLC6A1, P30531 SLC6A13, Q9NSD5 SLC6A11, P48066 SLC6A12, P48065 SLC6A6, P31641 SLC6A8, P48029
Substrates nipecotic acid, guvacine nipecotic acid, guvacine guvacine, nipecotic acid – – –
Endogenous substrates GABA β-alanine, GABA β-alanine, GABA GABA, betaine β-alanine, taurine, GABA creatine
[15]
Stoichiometry 2Na+ : 1Cl- : 1GABA 2Na+ : 1Cl- :1GABA ≥ 2Na+ : 2 Cl- : 1GABA 3Na+ : 1 (or 2) Cl- : 1GABA 2Na+ : 1Cl- : 1 taurine Probably 2Na+ : 1Cl- : 1
creatine
Selective inhibitors NNC-711 (pIC50 7.4) [66], SNAP-5114 (pIC50 4.7) [65] SNAP-5114 (pIC50 5.2) [65] NNC052090 (pKi 5.9) [618] – –
tiagabine (pIC50 7.2) [66], – Rat – Mouse, (R/S) EF-1500
SKF89976A (pIC50 6.9) (pIC50 4.9), (R)-EF-1520
[149], CI-966 (pIC50 6.6) (pIC50 3.7–4.7), (S)-EF-1520
[66], (R/S) EF-1500 (pIC50 (pIC50 3.6–4.5), LU32-176B
4.9–5.7), (R)-EF-1520 (pIC50 (pIC50 4) [667] – Mouse
5.1–5.4), LU32-176B (pIC50
5.4) [667] – Mouse,
(S)-EF-1520 (pIC50 3.6–3.9)
Labelled ligands [3 H]tiagabine (Inhibitor) – – – – –

Comments: The IC50 values for GAT1-4 reported in the table re- [218]. In addition to the inhibitors listed, deramciclane is a take of GABA [see [119, 561] for reviews]. GAT3 is inhibited by
flect the range reported in the literature from studies of both hu- moderately potent, though non-selective, inhibitor of all cloned physiologically relevant concentrations of Zn2+ [123]. Taut trans-
man and mouse transporters. There is a tendency towards lower GABA transporters (IC50 = 26-46 μM; [148]). Diaryloxime and ports GABA, but with low affinity, but CT1 does not, although
IC50 values for the human orthologue [380]. SNAP-5114 is only diarylvinyl ether derivatives of nipecotic acid and guvacine that it can be engineered to do so by mutagenesis guided by LeuT
weakly selective for GAT 2 and GAT3, with IC50 values in the
potently inhibit the uptake of [3 H]GABA into rat synaptosomes as a structural template [155]. Although inhibitors of creatine
range 22 to >30 μM at GAT1 and BGT1, whereas NNC052090
has at least an order of magnitude selectivity for BGT1 [see have been described [359]. Several derivatives of exo-THPO (e.g. transport by CT1 (e.g. β-guanidinopropionic acid, cyclocreatine,
[119, 562] for reviews]. Compound (R)-4d is a recently described N-methyl-exo-THPO and N-acetyloxyethyl-exo-THPO) demon- guanidinoethane sulfonic acid) are known (e.g. [131]) they insuf-
compound that displays 20-fold selectivity for GAT3 over GAT1 strate selectivity as blockers of astroglial, versus neuronal, up- ficiently characterized to be included in the table.

Searchable database: http://www.guidetopharmacology.org/index.jsp GABA transporter subfamily S424

Glycine transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC6 neurotransmitter transporter family → Glycine transporter subfamily

Overview: Two gene products, GlyT1 and GlyT2, are known that gous mice engineered to totally lack GlyT1 exhibit severe respi- second postnatal week [244] and mutations in the human gene
give rise to transporters that are predominantly located on glia and ratory and motor deficiencies due to hyperactive glycinergic sig- encoding GlyT2 (SLC6A5) have been identified in patients with
neurones, respectively. Five variants of GlyT1 (a,b,c,d & e) differ- nalling and die within the first postnatal day [243, 624]. Dis- hyperekplexia (reviewed by [281]). ATB0+ (SLC6A14) is a trans-
ing in their N- and C-termini are generated by alternative pro- ruption of GlyT1 restricted to forebrain neurones is associated porter for numerous dipolar and cationic amino acids and thus
moter usage and splicing, and three splice variants of GlyT2 (a,b with enhancement of EPSCs mediated by NMDA receptors and
has a much broader substrate specificity than the glycine trans-
& c) have also been identified (see [51, 189, 242, 594] for reviews). behaviours that are suggestive of a promnesic action [695]. GlyT2
porters alongside which it is grouped on the basis of structural
GlyT1 transporter isoforms expressed in glia surrounding gluta- transporters localised on the axons and boutons of glycinergic
matergic synapses regulate synaptic glycine concentrations in- neurones appear crucial for efficient transmitter loading of synap- similarity [106]. ATB0+ is expressed in various peripheral tissues
fluencing NMDA receptor-mediated neurotransmission [50, 219], tic vesicles but may not be essential for the termination of in- [106]. By contrast PROT (SLC6A7), which is expressed only in
but also are important, in early neonatal life, for regulating glycine hibitory neurotransmission [244, 537]. Mice in which GlyT2 has brain in association with a subset of excitatory nerve terminals,
concentrations at inhibitory glycinergic synapses [243]. Homozy- been deleted develop a fatal hyperekplexia phenotype during the shows specificity for the transport of L-proline.

Searchable database: http://www.guidetopharmacology.org/index.jsp Glycine transporter subfamily S425

Nomenclature GlyT1 GlyT2 ATB0,+ PROT

Systematic nomenclature SLC6A9 SLC6A5 SLC6A14 SLC6A7
HGNC, UniProt SLC6A9, P48067 SLC6A5, Q9Y345 SLC6A14, Q9UN76 SLC6A7, Q99884
Substrates – – BCH, zwitterionic or cationic NOS inhibitors –
[284], 1-methyltryptophan [345],
valganciclovir [632]
Endogenous substrates sarcosine, glycine glycine β-alanine [13, 15] L-proline
L-isoleucine > L-leucine, L-methionine >
L-phenylalanine > L-tryptophan > L-valine
> L-serine [581]
Stoichiometry 2 Na+ : 1 Cl- : 1 glycine 3 Na+ : 1 Cl- : 1 glycine 2-3 Na+ : 1 Cl- : 1 amino acid [581] Probably 2 Na+ : 1 Cl- : 1 L-proline
Inhibitors PF-03463275 (pKi 7.9) [411] bitopertin (pEC50 <4.5) [498] – –
Selective inhibitors (R)-NFPS (pIC50 8.5–9.1), SSR-103800 Org 25543 (pIC50 7.8) [95], ALX 1393, α-methyl-D,L-tryptophan (pIC50 3.6) [345] compound 58 (pIC50 7.7) [724], LP-403812
(pIC50 8.7) [69], N-methyl-SSR504734 ALX 1405 (pIC50 7) [698]
(pIC50 8.6), LY2365109 (pIC50 7.8),
GSK931145 (pIC50 7.6), bitopertin (pEC50
7.5) [498]
Labelled ligands [3 H](R)-NPTS (Binding) (pKd 9) [410], – – –
[3 H]GSK931145 (Binding) (pKd 8.8) [287],
[35 S]ACPPB (Binding) (pKd 8.7) [703],
[3 H]SB-733993 (Binding) (pKd 8.7) [287],
[3 H]N-methyl-SSR504734 (pKd 8.1–8.5),
[3 H]NFPS (pKd 7.7–8.2)
Comments – N-Oleoyl-L-carnitine (0.3μM, [91]) and and – –
N-arachidonoylglycine (IC50 5-8 μM, [668])
have been described as potential
endogenous selective GlyT2 inhibitors

Comments: Sarcosine is a selective transportable inhibitor of vary, most likely due to differences in assay conditions [74, 424]. and N-arachidonyl-D-alanine have been described as endogenous
GlyT1 and also a weak agonist at the glycine binding site of the The tricyclic antidepressant amoxapine weakly inhibits GlyT2 non-competitive inhibitors of GlyT2a, but not GlyT1b [170, 327,
NMDA receptor [707], but has no effect on GlyT2. This differ- (IC50 92 μM) with approximately 10-fold selectivity over GlyT1 668]. Protons [30] and Zn2+ [332] act as non-competitive in-
ence has been attributed to a single glycine residue in TM6 (ser- [473]. The endogenous lipids arachidonic acid and anandamide hibitors of GlyT1b, with IC50 values of 100 nM and 10 μM respec-
ine residue in GlyT2) [641]. Inhibition of GLYT1 by the sarco- exert opposing effects upon GlyT1a, inhibiting (IC50 2 μM) tively, but neither ion affects GlyT2 (reviewed by [639]). Glycine
sine derivatives NFPS, NPTS and Org 24598 is non-competitive and potentiating (EC50 13 μM) transport currents, respectively transport by GLYT1 is inhibited by Li+ , whereas GLYT2 transport
[424, 436]. IC50 values for Org 24598 reported in the literature [491]. N-arachidonyl-glycine, N-arachidonyl-γ-aminobutyric acid is stimulated (both in the presence of Na+ ) [509].

Searchable database: http://www.guidetopharmacology.org/index.jsp Glycine transporter subfamily S426

Neutral amino acid transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC6 neurotransmitter transporter family → Neutral amino acid transporter subfamily
Overview: Certain members of neutral amino acid transport family are expressed upon the apical surface of epithelial cells and are important for the absorption of amino acids from the duodenum,
jejunum and ileum and their reabsorption within the proximal tubule of the nephron (i.e. B0 AT1 (SLC6A19), SLC6A18, SLC6A20). Others may function as transporters for neurotransmitters or their
precursors (i.e. B0 AT2, SLC6A17) [81]. B0 AT1 has been proposed as a drug target to treat phenylketonuria [47].

Nomenclature B0 AT1 B0 AT2 B0 AT3 NTT5 NTT4 SIT1

Systematic nomenclature SLC6A19 SLC6A15 SLC6A18 SLC6A16 SLC6A17 SLC6A20
HGNC, UniProt SLC6A19, Q695T7 SLC6A15, Q9H2J7 SLC6A18, Q96N87 SLC6A16, Q9GZN6 SLC6A17, Q9H1V8 SLC6A20, Q9NP91
Endogenous substrates L-leucine, L-methionine, L-proline > L-alanine, L-alanine, glycine > – L-leucine, L-methionine, L-proline
L-isoleucine, L-valine > L-valine, L-methionine, L-methionine, L-proline > L-cysteine,
L-asparagine, L-leucine > L-isoleucine, L-phenylalanine, L-leucine, L-alanine, L-glutamine,
L-phenylalanine, L-alanine, L-threonine, L-asparagine, L-histidine, L-glutamine L-serine > L-histidine,
L-serine > L-threonine, L-serine, L-phenylalanine > [643] glycine [700]
glycine, L-proline [80] glycine [80]
Stoichiometry 1 Na+ : 1 amino acid [90] 1 Na+ : 1 amino acid [78] Na+ - and Cl- -dependent – Na+ -dependent, 2 Na+ : 1 Cl- : 1 imino acid
transport [578] Cl- -independent transport [76]
[700]
Inhibitors cinromide (pIC50 6.4) [134], – – – – –
nimesulide (pIC50 4.6) [500]
– Rat, benzatropine (pIC50
4.4) [112]
Selective inhibitors – loratadine (pIC50 5.4) [130] – – – –
Comments Mutations in B0 AT1 are – SLC6A18 is a functional – – –
associated with Hartnup transporter in mouse, but
disorder not in humans.

Searchable database: http://www.guidetopharmacology.org/index.jsp Neutral amino acid transporter subfamily S427

SLC8 family of sodium/calcium exchangers

Transporters → SLC superfamily of solute carriers → SLC8 family of sodium/calcium exchangers

Overview: The sodium/calcium exchangers (NCX) use the extra- ATPase (SERCA), as well as the sodium/potassium/calcium ex- tion to allow calcium influx and sodium efflux, as an electrogenic
changers (NKCX, SLC24 family), NCX allow recovery of intracel- mechanism. Structural modelling suggests the presence of 9 TM
cellular sodium concentration to facilitate the extrusion of cal-
lular calcium back to basal levels after cellular stimulation. When segments, with a large intracellular loop between the fifth and
cium out of the cell. Alongside the plasma membrane Ca2+ - intracellular sodium ion levels rise, for example, following de- sixth TM segments.
ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum Ca2+ - polarisation, these transporters can operate in the reverse direc-

Nomenclature Sodium/calcium exchanger 1 Sodium/calcium exchanger 2 Sodium/calcium exchanger 3

Systematic nomenclature SLC8A1 SLC8A2 SLC8A3
Common abbreviation NCX1 NCX2 NCX3
HGNC, UniProt SLC8A1, P32418 SLC8A2, Q9UPR5 SLC8A3, P57103
Stoichiometry 3 Na+ (in) : 1 Ca2+ (out) or 4 Na+ (in) : 1 Ca2+ (out) [158]; – –
Reverse mode 1 Ca2+ (in): 1 Na+ (out)
Selective inhibitors – – YM-244769 (pIC50 7.7) [323]

Comments: Although subtype-selective inhibitors of NCX function are not widely available, 3,4-dichlorobenzamil and CBDMB act as non-selective NCX inhibitors, while SEA0400, KB-R7943, SN6, and
ORM-10103 [331] act to inhibit NCX function with varying degrees of selectivity. BED is a selective NCX3 inhibitor [563] and and YM-244769 inhibits NCX3 preferentially over other isoforms [323, 688].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC8 family of sodium/calcium exchangers S428

SLC9 family of sodium/hydrogen exchangers

Transporters → SLC superfamily of solute carriers → SLC9 family of sodium/hydrogen exchangers

Overview: Sodium/hydrogen exchangers or sodium/proton an- NHE9 appear to locate on intracellular membranes [448, 457, 472]. NHE1 is considered to be a ubiquitously-expressed ‘housekeeping’
tiports are a family of transporters that maintain cellular pH by Li+ and NH4 + , but not K+ , ions may also be transported by some transporter. NHE3 is highly expressed in the intestine and kid-
utilising the sodium gradient across the plasma membrane to ex- isoforms. Modelling of the topology of these transporters indi- neys and regulate sodium movements in those tissues. NHE10 is
trude protons produced by metabolism, in a stoichiometry of 1 cates 12 TM regions with an extended intracellular C-terminus present in sperm [653] and osteoclasts [391]; gene disruption re-
Na+ (in) : 1 H+ (out). Several isoforms, NHE6, NHE7, NHE8 and containing multiple regulatory sites. sults in infertile male mice [653].

Information on members of this family may be found in the online database.

Comments: Analogues of the non-selective cation transport inhibitor amiloride appear to inhibit NHE function through competitive inhibition of the extracellular Na+ binding site. The more selective
amiloride analogues MPA and ethylisopropylamiloride exhibit a rank order of afﬁnity of inhibition of NHE1 > NHE2 > NHE3 [127, 625, 626].

SLC10 family of sodium-bile acid co-transporters

Transporters → SLC superfamily of solute carriers → SLC10 family of sodium-bile acid co-transporters

Overview: The SLC10 family transport bile acids, sulphated maintain the enterohepatic circulation of bile acids [138, 357]. tity of their endogenous substrates remain unknown [201, 236,
solutes, and other xenobiotics in a sodium-dependent manner. SLC10A6 (SOAT) functions as a sodium-dependent transporter 241, 649]. Members of the SLC10 family are predicted to have
The founding members, SLC10A1 (NTCP) and SLC10A2 (ASBT) of sulphated solutes including sulfphated steroids and bile acids seven transmembrane domains with an extracellular N-terminus
function, along with members of the ABC transporter family [234, 236]. Transport function has not yet been demonstrated and cytoplasmic C-terminus [42, 274].
(MDR1/ABCB1, BSEP/ABCB11 and MRP2/ABCC2) and the organic for the 4 remaining members of the SLC10 family, SLC10A3 (P3),
solute transporter obligate heterodimer OSTα:OSTβ (SLC51), to SLC10A4 (P4), SLC10A5 (P5), and SLC10A7 (P7), and the iden-

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC10 family of sodium-bile acid co-transporters S429

Nomenclature Sodium/bile acid and sulphated solute cotransporter 1 Sodium/bile acid and sulphated solute cotransporter 2 Sodium/bile acid and sulphated solute cotransporter 6
Systematic nomenclature SLC10A1 SLC10A2 SLC10A6
Common abbreviation NTCP ASBT SOAT
HGNC, UniProt SLC10A1, Q14973 SLC10A2, Q12908 SLC10A6, Q3KNW5
Substrates – glycodeoxycholic acid > glycoursodeoxycholic acid, pregnenolone sulphate [234], estrone-3-sulphate,
glycochenodeoxycholic acid > taurocholic acid > dehydroepiandrosterone sulphate [236],
cholic acid [129] taurolithocholic acid-3-sulphate
Endogenous substrates dehydroepiandrosterone sulphate [129, 201, 430], – –
estrone-3-sulphate, iodothyronine sulphates [649]
tauroursodeoxycholic acid, taurocholic acid,
taurochenodeoxycholic acid > glycocholic acid >
cholic acid [430]
Stoichiometry 2 Na+ : 1 bile acid [42, 234] >1 Na+ : 1 bile acid [129, 662] –
Inhibitors (-)-propranolol (pIC50 8.2) [355], cyclosporin A (pIC50 6) elobixibat (pIC50 8.9) [237], SC-435 (pIC50 8.8) [54], –
[355], (+)-propranolol (pIC50 5.3) [355], cyclosporin A (pKi 264W94 (pIC50 7.3) [620, 679]
5.1) [159], irbesartan (pKi 4.9) [159]
Labelled ligands – [3 H]taurocholic acid [129] –
Comments – Chenodeoxycholyl-N -nitrobenzoxadiazol-lysine is a –
ﬂuorescent bile acid analogue used as a probe [662].

Comments: Heterologously expressed SLC10A4 [235] or SLC10A7 [241] failed to exhibit signiﬁcant transport of taurocholic acid, pregnenolone sulphate, dehydroepiandrosterone sulphate or choline.
SLC10A4 has recently been suggested to associate with neuronal vesicles [84].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC10 family of sodium-bile acid co-transporters S430

SLC11 family of proton-coupled metal ion transporters

Transporters → SLC superfamily of solute carriers → SLC11 family of proton-coupled metal ion transporters

Overview: The family of proton-coupled metal ion trans- dent on proton transport. Both proteins appear to have 12 TM re- the pathogen. Alternatively, export of divalent cations from the
porters are responsible for movements of divalent cations, par- gions and cytoplasmic N- and C- termini. NRAMP1 is involved in phagosome may deprive the pathogen of essential enzyme cofac-
ticularly ferrous and manganese ions, across the cell membrane antimicrobial action in macrophages, although its precise mech- tors. SLC11A2/DMT1 is more widely expressed and appears to
(SLC11A2/DMT1) and across endosomal (SLC11A2/DMT1) or anism is undeﬁned. Facilitated diffusion of divalent cations into assist in divalent cation assimilation from the diet, as well as in
lysosomal/phagosomal membranes (SLC11A1/NRAMP1), depen- phagosomes may increase intravesicular free radicals to damage phagocytotic cells.

Nomenclature NRAMP1 DMT1

Systematic nomenclature SLC11A1 SLC11A2
HGNC, UniProt SLC11A1, P49279 SLC11A2, P49281
Endogenous substrates Fe2+ , Mn2+ Cu2+ , Co2+ , Cd2+ , Fe2+ , Mn2+
Stoichiometry 1 H+ :1 Fe2+ (out) or 1 Fe2+ (in) : 1 H+ (out) 1 H+ : 1 Fe2+ (out) [269]
Inhibitors – compound 6b (pIC50 7.1) [710]

Comments: Loss-of-function mutations in NRAMP1 are associated with increased susceptibility to microbial infection (OMIM: 607948). Loss-of-function mutations in DMT1 are associated with microcytic
anemia (OMIM: 206100).

SLC12 family of cation-coupled chloride transporters

Transporters → SLC superfamily of solute carriers → SLC12 family of cation-coupled chloride transporters

Overview: The SLC12 family of chloride transporters contribute thiazide diuretics. These 12 TM proteins exhibit cytoplasmic ter- tended extracellular loop at TM 5/6. CCC6 exhibits structural sim-
to ion fluxes across a variety of tissues, particularly in the kidney mini and an extended extracellular loop at TM7/8 and are kidney- ilarities with the K-Cl co-transporters, while CCC9 is divergent,
and choroid plexus of the brain. Within this family, further sub- specific (NKCC2 and NCC) or show a more widespread distribu- with 11 TM domains and a cytoplasmic N-terminus and extracel-
families are identifiable: NKCC1, NKCC2 and NCC constitute a tion (NKCC1). A second family, the K-Cl co-transporters are also lular C-terminus.
group of therapeutically-relevant transporters, targets for loop and 12 TM domain proteins with cytoplasmic termini, but with an ex-

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC12 family of cation-coupled chloride transporters S431

Nomenclature Kidney-speciﬁc Na-K-Cl symporter Basolateral Na-K-Cl symporter Na-Cl symporter K-Cl cotransporter 1 K-Cl cotransporter 2
Systematic nomenclature SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5
Common abbreviation NKCC2 NKCC1 NCC KCC1 KCC2
HGNC, UniProt SLC12A1, Q13621 SLC12A2, P55011 SLC12A3, P55017 SLC12A4, Q9UP95 SLC12A5, Q9H2X9
Stoichiometry 1 Na+ : 1 K+ : 2 Cl- (in) 1 Na+ : 1 K+ : 2 Cl- (in) 1 Na+ : 1 Cl- (in) 1 K+ : 1 Cl- (out) 1 K+ : 1 Cl- (out)
Inhibitors bumetanide (pIC50 6.5) [280], piretanide (pIC50 5.6) [280], chlorothiazide, cyclothiazide, DIOA VU0240551 (pIC50 6.2) [143],
piretanide (pIC50 6) [280], bumetanide (pIC50 5.6) [280], hydrochlorothiazide, metolazone DIOA
furosemide (pIC50 5.2) [280] furosemide (pIC50 5.1) [280]

Nomenclature K-Cl cotransporter 3 K-Cl cotransporter 4 Cation-chloride cotransporter 9

Systematic nomenclature SLC12A6 SLC12A7 SLC12A8
Common abbreviation KCC3 KCC4 CCC9
HGNC, UniProt SLC12A6, Q9UHW9 SLC12A7, Q9Y666 SLC12A8, A0AV02
Substrates – – L-glutamic acid, spermine, L-aspartic acid, spermidine
Stoichiometry 1 K+ : 1 Cl- (out) 1 K+ : 1 Cl- (out) Unknown
Inhibitors DIOA DIOA –
Comments – – In mouse studies Slc12a8 has been shown to transport the nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide
mononucleotide (NMN) in to cells, and administration of NMN produces anti-ageing effects in vivo [261].

Comments: DIOA is able to differentiate KCC isoforms from NKCC and NCC transporters, but also inhibits CFTR [321].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC12 family of cation-coupled chloride transporters S432

SLC13 family of sodium-dependent sulphate/carboxylate transporters

Transporters → SLC superfamily of solute carriers → SLC13 family of sodium-dependent sulphate/carboxylate transporters
Overview: Within the SLC13 family, two groups of transporters may be differentiated on the basis of the substrates transported: NaS1 and NaS2 convey sulphate, while NaC1-3 transport carboxylates.
NaS1 and NaS2 transporters are made up of 13 TM domains, with an intracellular N terminus and are electrogenic with physiological roles in the intestine, kidney and placenta. NaC1, NaC2 and NaC3
are made up of 11 TM domains with an intracellular N terminus and are electrogenic, with physiological roles in the kidney and liver.

Nomenclature Na+ /sulfate cotransporter Na+ /dicarboxylate cotransporter 1 Na+ /dicarboxylate cotransporter 3 Na+ /sulfate cotransporter Na+ /citrate cotransporter
Systematic nomenclature SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5
Common abbreviation NaS1 NaC1 NaC3 NaS2 NaC2
HGNC, UniProt SLC13A1, Q9BZW2 SLC13A2, Q13183 SLC13A3, Q8WWT9 SLC13A4, Q9UKG4 SLC13A5, Q86YT5
Endogenous substrates SeO4 2- , SO4 2- , S2 O3 2- citric acid, succinic acid citric acid, succinic acid SO4 2- citric acid, pyruvic acid
Stoichiometry 3 Na+ : 1 SO4 2- (in) 3 Na+ : 1 dicarboxylate2- (in) Unknown 3 Na+ : SO4 2- (in) Unknown

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC13 family of sodium-dependent sulphate/ S433

Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full carboxylate transporters
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

SLC14 family of facilitative urea transporters

Transporters → SLC superfamily of solute carriers → SLC14 family of facilitative urea transporters

Overview: As a product of protein catabolism, urea is moved its concentration gradient. Multiple splice variants of these trans- mains, with a glycosylated extracellular loop at TM5/6, and intra-
around the body and through the kidneys for excretion. Although porters have been identified; for UT-A transporters, in particular, cellular C- and N-termini. The UT-A1 splice variant, exceptionally,
there is experimental evidence for concentrative urea transporters, there is evidence for cell-specific expression of these variants with has 20 TM domains, equivalent to a combination of the UT-A2 and
these have not been defined at the molecular level. The SLC14 functional impact [589]. Topographical modelling suggests that UT-A3 splice variants.
family are facilitative transporters, allowing urea movement down the majority of the variants of SLC14 transporters have 10 TM do-

Nomenclature Erythrocyte urea transporter Kidney urea transporter

Systematic nomenclature SLC14A1 SLC14A2
Common abbreviation UT-B UT-A
HGNC, UniProt SLC14A1, Q13336 SLC14A2, Q15849
Substrates acetamide [711], acrylamide [711], methylurea [711] –
Endogenous substrates ammonium carbonate [711], urea [711], formamide [711] urea [420]
Stoichiometry Equilibrative Equilibrative
Inhibitors compound 1a (pIC50 ∼8) [406], compound 1a (pIC50 7.6) [406] – Mouse –

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC14 family of facilitative urea transporters S434

SLC15 family of peptide transporters

Transporters → SLC superfamily of solute carriers → SLC15 family of peptide transporters

Overview: The Solute Carrier 15 (SLC15) family of peptide digestion, SLC15A2 (PEPT2) mainly allows renal tubular reup- transporters variably interacts with a very large number of pep-
transporters, alias H+ -coupled oligopeptide cotransporter family, take of di/tripeptides from ultrafiltration and brain-to-blood ef- tidomimetics and peptide-like drugs. It is conceivable, based on
is a group of membrane transporters known for their key role flux of di/tripeptides in the choroid plexus, SLC15A3 (PHT2) and the currently acknowledged structural and functional differences,
in the cellular uptake of di- and tripeptides (di/tripeptides). Of SLC15A4 (PHT1) interact with both di/tripeptides and histidine, to divide the SLC15 family of peptide transporters into two sub-
its members, SLC15A1 (PEPT1) chiefly mediates intestinal ab- e.g. in certain immune cells, and SLC15A5 has unknown phys- families.
sorption of luminal di/tripeptides from overall dietary protein iological function. In addition, the SLC15 family of peptide

Nomenclature Peptide transporter 1 Peptide transporter 2

Systematic nomenclature SLC15A1 SLC15A2
Common abbreviation PEPT1 PEPT2
HGNC, UniProt SLC15A1, P46059 SLC15A2, Q16348
Substrates fMet-Leu-Phe [88, 102, 432, 433, 677], His-Leu-lopinavir [425], D-Ala-Lys-AMCA [245, muramyl dipeptide [297, 592], β-Ala-Lys-AMCA [3, 152, 372, 531, 540, 592, 722, 723],
260, 372, 599], β-Ala-Lys-AMCA [3, 324, 372], alafosfalin [462], muramyl dipeptide [318, D-Ala-Lys-AMCA [372, 599, 663], γ-iE-DAP [592, 597], alafosfalin [462]
645]
Endogenous substrates protons, dipeptides [169], 5-aminolevulinic acid [16, 53, 169, 312, 461, 549], tripeptides dipeptides, protons, tripeptides, 5-aminolevulinic acid [169, 312, 681]
[169]
Stoichiometry Transport is electrogenic and involves a variable proton-to-substrate stoichiometry for Transport is electrogenic and involves a variable proton-to-substrate stoichiometry for
uptake of neutral and mono- or polyvalently charged peptides, as well as 5-aminolevulic uptake of neutral and mono- or polyvalently charged peptides, as well as 5-aminolevulic
acid. acid.
Inhibitors Lys[Z(NO2 )]-Val (pKi 5.7) [360], 4-AMBA (pKi 5.5) [135, 431], Lys[Z(NO2 )]-Pro (pKi Lys[Z(NO2 )]-Lys[Z(NO2 )] (pKi 8) [57, 617], Lys[Z(NO2 )]-Pro
5–5.3) [362]
Labelled ligands [11 C]GlySar [444], [14 C]GlySar [6, 40, 56, 221, 222, 223, 312, 361, 362, 363, 413, 425, [11 C]GlySar [453], [14 C]GlySar [217, 221, 222, 223, 298, 312, 361, 363, 405, 413, 556,
556, 604, 612, 613, 614], [3 H]GlySar [12, 87, 118, 128, 278, 325, 399, 483, 549, 599] 612, 614], [3 H]GlySar [399, 412, 483, 550, 583, 599]
Comments A variety of dipeptides and drugs interact with PEPT1, including carnosine [288], D-Phe-Ala Other high-afﬁnity (non-transported) inhibitors: Lys[Z(NO2 )]-Val (Ki 2 μM) [360, 362],
[169, 362], D-Phe-Gln [16], 5-aminolevulinic acid [461, 475, 529], nateglinide [614], Lys[Z(NO2 )]-Pro (Ki 3-7 μM) [360, 362]; other low-afﬁnity, (non-transported) inhibitors:
glibenclamide [556], valacyclovir [39, 40, 53, 270], cefadroxil [664], cephalexin [221] and 4-AMBA (Ki 3 mM) [16, 135, 431]. Like PEPT1, PEPT2 interact with dipeptides and drugs
penicillin G (benzylpenicillin) [53], as detected using [3 H] and [14 C] radio-labelled probes. including carnosine [681], D-Phe-Ala [169, 617], 5-aminolevulinic acid [169, 312, 461,
475, 529], nateglinide [614], glibenclamide [556], cefadroxil [475], cephalexin [221] and
penicillin G (benzylpenicillin) [475].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC15 family of peptide transporters S435

Nomenclature Peptide transporter 3 Peptide transporter 4

Systematic nomenclature SLC15A3 SLC15A4
Common abbreviation PHT2 PHT1
HGNC, UniProt SLC15A3, Q8IY34 SLC15A4, Q8N697
Substrates MDP-rhodamine [456], muramyl dipeptide [456, 660], Tri-DAP [660] His-Leu-lopinavir [425], Tri-DAP [388, 554, 584], C12-iE-DAP [388], glycyl-sarcosine [52,
298, 584, 599], muramyl dipeptide [456, 584], valacyclovir [52], MDP-rhodamine [297,
456]
Endogenous substrates L-histidine [548], dipeptides, tripeptides, protons L-histidine [52, 365, 425, 658, 689], carnosine [52, 689]
Stoichiometry PHT2 has not been analyzed systematically with respect to driving force, mode of PHT1 has not been analyzed systematically with respect to driving force, mode of
transport, and substrate speciﬁcity. The pH dependence observed for transport of histidine transport, and substrate speciﬁcity. The pH dependence observed for transport of histidine
[548] and the model peptides used, i.e., carnosine [548] and histidyl-leucine [548], [52, 365, 425, 658, 689] and the model peptide used, i.e., carnosine [52, 689], suggest a
suggest a similar mode of operation as PEPT1 and PEPT2 proteins. similar mode of operation as PEPT1 and PEPT2 proteins.
Labelled ligands [14 C]histidine [548] [14 C]histidine (Binding) [658, 659, 689], [3 H]histidine [52, 425, 599, 658]
Comments PHT2 interacts with [3 H]carnosine [548]. Other PHT1 ligands include [3 H]histidine [52, 425, 599, 658], d3-L-histidine [584],
[3 H]carnosine [52, 689] [14 C]GlySar [298], [3 H]GlySar [52, 599] and [3 H]valacyclovir [52].

Comments: The members of the SLC15 family of peptide with the SLC15 family transporters. Known substrates include of Gly-Sar by SLC15A1 and/or SLC15A2 [483].
transporters are particularly promiscuous in the transport of cefadroxil, valacyclovir, 5-aminolevulinic acid, L-Dopa prodrugs, There is evidence to suggest the existence of a ﬁfth member of
di/tripeptides, and D-amino acid containing peptides are also gemcitabine prodrugs, ﬂoxuridine prodrugs, Maillard reaction this transporter family, SLC15A5 (A6NIM6; ENSG00000188991),
transported. While SLC15A3 and SLC15A4 transport histi- products, JBP485, zanamivir, oseltamivir prodrugs, doxorubicin but to date there is no established biological function or reported
dine, none of them transport tetrapeptides. In addition, many prodrugs, polymyxins, and didanosine prodrugs. Frequently used pharmacology for this protein [585].
molecules, among which beta-lactam antibiotics, angiotensin- pharmaceutical excipients such as Tween® 20, Tween® 80, Solu-
converting enzyme inhibitors and sartans, variably interact tol® HS 15 and Cremophor EL® strongly inhibit cellular uptake

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC15 family of peptide transporters S436

SLC16 family of monocarboxylate transporters

Transporters → SLC superfamily of solute carriers → SLC16 family of monocarboxylate transporters
Overview: Members of the SLC16 family may be divided into subfamilies on the basis of substrate selectivities, particularly lactate (e.g. L-lactic acid), pyruvic acid and ketone bodies, as well as aromatic
amino acids. Topology modelling suggests 12 TM domains, with intracellular termini and an extended loop at TM 6/7.
The proton-coupled monocarboxylate transporters (monocarboxylate transporters 1, 4, 2 and 3) allow transport of the products of cellular metabolism, principally lactate (e.g. L-lactic acid) and pyruvic acid.

Nomenclature Monocarboxylate Monocarboxylate Monocarboxylate Monocarboxylate Monocarboxylate Monocarboxylate Monocarboxylate

transporter 1 transporter 2 transporter 3 transporter 4 transporter 6 transporter 8 transporter 10
Systematic nomenclature SLC16A1 SLC16A7 SLC16A8 SLC16A3 SLC16A5 SLC16A2 SLC16A10
Common abbreviation MCT1 MCT2 MCT3 MCT4 MCT6 MCT8 TAT1
HGNC, UniProt SLC16A1, P53985 SLC16A7, O60669 SLC16A8, O95907 SLC16A3, O15427 SLC16A5, O15375 SLC16A2, P36021 SLC16A10, Q8TF71
Substrates γ-hydroxybutyric acid – – – – – –
[657]
Endogenous substrates pyruvic acid, pyruvic acid, L-lactic acid pyruvic acid, – triiodothyronine [213], L-tryptophan,
L-lactic acid, L-lactic acid L-lactic acid T4 [213] L-phenylalanine,
β-D-hydroxybutyric acid levodopa, L-tyrosine
Stoichiometry 1 H+ : 1 1 H+ : 1 1 H+ : 1 1 H+ : 1 Unknown Unknown Unknown
monocarboxylate- (out) monocarboxylate- (out) monocarboxylate- (out) monocarboxylate- (out)
Inhibitors compound 30 7ACC2 (pIC50 8) [162] – – – – –
(Compound 30 is a
channel blocker.) (pKi
8.3) [268]
Comments – – – – MCT6 has been – –
reported to transport
bumetanide, but not
short chain fatty acids
[451].

Comments: MCT1 and MCT2, but not MCT3 and MCT4, are inhibited by CHC, which also inhibits members of the mitochondrial transporter family, SLC25.
MCT5-MCT7, MCT9 and MCT11-14 are regarded as orphan transporters.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC16 family of monocarboxylate transporters S437

SLC17 phosphate and organic anion transporter family

Transporters → SLC superfamily of solute carriers → SLC17 phosphate and organic anion transporter family
Overview: The SLC17 family are sometimes referred to as Type I sodium-phosphate co-transporters, alongside Type II (SLC34 family) and Type III (SLC20 family) transporters. Within the SLC17 family,
however, further subgroups of organic anion transporters may be deﬁned, allowing the accumulation of sialic acid in the endoplasmic reticulum and glutamate (e.g. L-glutamic acid) or nucleotides in
synaptic and secretory vesicles. Topology modelling suggests 12 TM domains.

Type I sodium-phosphate co-transporters

Transporters → SLC superfamily of solute carriers → SLC17 phosphate and organic anion transporter family → Type I sodium-phosphate co-transporters
Overview: Type I sodium-phosphate co-transporters are expressed in the kidney and intestine.

Nomenclature Sodium/phosphate cotransporter 1 Sodium/phosphate cotransporter 3 Sodium/phosphate cotransporter 4 Sodium/phosphate cotransporter homolog
Systematic nomenclature SLC17A1 SLC17A2 SLC17A3 SLC17A4
Common abbreviation NPT1 NPT3 NPT4 –
HGNC, UniProt SLC17A1, Q14916 SLC17A2, O00624 SLC17A3, O00476 SLC17A4, Q9Y2C5
Substrates probenecid [86], penicillin G [86], Cl- [306], – – –
organic acids [306], uric acid [306],
phosphate [306]
Stoichiometry Unknown Unknown Unknown Unknown

Searchable database: http://www.guidetopharmacology.org/index.jsp Type I sodium-phosphate co-transporters S438

Sialic acid transporter

Transporters → SLC superfamily of solute carriers → SLC17 phosphate and organic anion transporter family → Sialic acid transporter
Overview: The sialic acid transporter is expressed on both lysosomes and synaptic vesicles, where it appears to allow export of sialic acid and accumulation of acidic amino acids, respectively [446],
driven by proton gradients. In lysosomes, degradation of glycoproteins generates amino acids and sugar residues, which are metabolized further following export from the lysosome.

Nomenclature Sialin
Systematic nomenclature SLC17A5
Common abbreviation AST
HGNC, UniProt SLC17A5, Q9NRA2
Endogenous substrates L-lactic acid, gluconate (out), L-glutamic acid (in) [446], glucuronic acid, L-aspartic acid [446], sialic acid
Stoichiometry 1 H+ : 1 sialic acid (out)

Comments: Loss-of-function mutations in sialin are associated with Salla disease (OMIM: 604369), an autosomal recessive neurodegenerative disorder associated with sialic acid storage disease [647].

Vesicular glutamate transporters (VGLUTs)

Transporters → SLC superfamily of solute carriers → SLC17 phosphate and organic anion transporter family → Vesicular glutamate transporters (VGLUTs)
Overview: Vesicular glutamate transporters (VGLUTs) allow accumulation of glutamate into synaptic vesicles, as well as secretory vesicles in endocrine tissues. The roles of VGLUTs in kidney and liver
are unclear. These transporters appear to utilize the proton gradient and also express a chloride conductance [48].

Nomenclature Vesicular glutamate transporter 1 Vesicular glutamate transporter 2 Vesicular glutamate transporter 3
Systematic nomenclature SLC17A7 SLC17A6 SLC17A8
Common abbreviation VGLUT1 VGLUT2 VGLUT3
HGNC, UniProt SLC17A7, Q9P2U7 SLC17A6, Q9P2U8 SLC17A8, Q8NDX2
Endogenous substrates L-glutamic acid > D-glutamic acid L-glutamic acid > D-glutamic acid L-glutamic acid > D-glutamic acid
Stoichiometry Unknown Unknown Unknown

Comments: Endogenous ketoacids produced during fasting have been proposed to regulate VGLUT function through blocking chloride ion-mediated allosteric enhancement of transporter function
[333].

Searchable database: http://www.guidetopharmacology.org/index.jsp Vesicular glutamate transporters (VGLUTs) S439

Vesicular nucleotide transporter

Transporters → SLC superfamily of solute carriers → SLC17 phosphate and organic anion transporter family → Vesicular nucleotide transporter
Overview: The vesicular nucleotide transporter is the most recent member of the SLC17 family to have an assigned function. Uptake of ATP was independent of pH, but dependent on chloride ions and
membrane potential [555].

Nomenclature Vesicular nucleotide transporter

Systematic nomenclature SLC17A9
Common abbreviation VNUT
HGNC, UniProt SLC17A9, Q9BYT1
Endogenous substrates guanosine 5’-diphosphate [555], guanosine-5’-triphosphate [555], ATP [555]
Stoichiometry Unknown
Selective inhibitors clodronic acid (pIC50 7.8) [346]

Comments: VGLUTs and VNUT can be inhibited by DIDS and evans blue dye.

SLC18 family of vesicular amine transporters

Transporters → SLC superfamily of solute carriers → SLC18 family of vesicular amine transporters

Overview: The vesicular amine transporters (VATs) are puta- multi-subunit vacuolar ATPase that acidiﬁes secretory vesicles (re- [183] distributes between both central and peripheral sympathetic
tive 12 TM domain proteins that function to transport singly viewed by [174]). The vesicular acetylcholine transporter (VAChT; monoaminergic neurones [175]. The vescular polyamine trans-
positively charged amine neurotransmitters and hormones from [184]) localizes to cholinergic neurons, but non-neuronal expres- porter (VPAT) is highly expressed in the lungs and placenta, with
the cytoplasm and concentrate them within secretory vesicles. sion has also been claimed [558]. Vesicular monoamine trans- moderate expression in brain and testis, and with low expression
They function as amine/proton antiporters driven by secondary porter 1 (VMAT1, [182]) is mainly expressed in peripheral neu- in heart and skeletal muscle [290]. VPAT mediates vesicular accu-
active transport utilizing the proton gradient established by a roendocrine cells, but most likely not in the CNS, whereas VMAT2 mulation of polyamines in mast cells [602].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC18 family of vesicular amine transporters S440

Nomenclature Vesicular monoamine transporter 1 Vesicular monoamine transporter 2 Vesicular acetylcholine transporter
Systematic nomenclature SLC18A1 SLC18A2 SLC18A3
Common abbreviation VMAT1 VMAT2 VAChT
HGNC, UniProt SLC18A1, P54219 SLC18A2, Q05940 SLC18A3, Q16572
Substrates dexamfetamine (Ki 4.7×10−5 M) [183], β-phenylethylamine β-phenylethylamine (Ki 3.7×10−6 M) [183], dexamfetamine TPP+ [71], ethidium [71], N-methyl-pyridinium-2-aldoxime
(Ki 3.4×10−5 M) [183], fenﬂuramine (Ki 3.1×10−6 M) [183], (Ki 2.1×10−6 M) [183], fenﬂuramine (Ki 5.1×10−6 M) [183], [71],
MPP+ (Ki 6.9×10−5 M) [183], MDMA (Ki 1.9×10−5 M) [183] MPP+ (Ki 8.9×10−6 M) [183], MDMA (Ki 6.9×10−6 M) [183] N-(4’-pentanonyl)-4-(4”-dimethylamino-styryl)pyridinium
[71]
Endogenous substrates histamine (Ki 4.6×10−3 M) [183], 5-hydroxytryptamine (Ki histamine (Ki 1.4×10−4 M) [183], dopamine (Ki acetylcholine (Ki 7.9×10−4 M) [72, 352], choline (Ki
1.4×10−6 M) [183], dopamine (Ki 3.8×10−6 M) [183], 1.4×10−6 M) [183], 5-hydroxytryptamine (Ki 9×10−7 M) 5×10−3 M) [72, 352]
(-)-noradrenaline (Ki 1.3×10−5 M) [183], (-)-adrenaline (Ki [183], (-)-noradrenaline (Ki 3.4×10−6 M) [183],
5.5×10−6 M) [183] (-)-adrenaline (Ki 1.9×10−6 M) [183]
Stoichiometry 1 amine (in): 2H+ (out) 1 amine (in): 2H+ (out) 1 amine (in): 2H+ (out)
Inhibitors reserpine (pKi 7.5) [183], ketanserin (pKi 5.8) [183], reserpine (pKi 7.9) [183], tetrabenazine (pKi 7) [183], aminobenzovesamicol (pKi 10.9) [173], vesamicol (pKi 8.7)
tetrabenazine (pKi 4.7) [183] ketanserin (pKi 6.3) [183] [173]
Labelled ligands – [3 H]TBZOH (Inhibitor) (pKd 8.2) [644], [125 I]iodovinyl-TBZ [3 H]vesamicol (pKd 8.4) [644], [123 I]iodobenzovesamicol
(Inhibitor) (pKd 8.1) [378], [11 C]DTBZ (Inhibitor),
[125 I]7-azido-8-iodoketanserine (Inhibitor) [577]

Comments: pKi values for endogenous and synthetic substrate inhibitors of human VMAT1 and VMAT2 are for inhibition of [3 H]5-HT uptake in transfected and permeabilised CV-1 cells as detailed
by [183]. In addition to the monoamines listed in the table, the trace amines tyramine and β-phenylethylamine are probable substrates for VMAT2 [175]. Probes listed in the table are those currently
employed; additional agents have been synthesized (e.g. [720]).

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC18 family of vesicular amine transporters S441

SLC19 family of vitamin transporters

Transporters → SLC superfamily of solute carriers → SLC19 family of vitamin transporters
Overview: The B vitamins folic acid and thiamine are transported across the cell membrane, particularly in the intestine, kidneys and placenta, using pH differences as driving forces. Topological
modelling suggests the transporters have 12 TM domains.

Nomenclature Reduced folate transporter 1 Thiamine transporter 1 Thiamine transporter 2

Systematic nomenclature SLC19A1 SLC19A2 SLC19A3
Common abbreviation FOLT ThTr1 ThTr2
HGNC, UniProt SLC19A1, P41440 SLC19A2, O60779 SLC19A3, Q9BZV2
Substrates N5 -formyltetrahydrofolate, folinic acid, methotrexate, – –
folic acid [505]
Endogenous substrates Other tetrahydrofolate-cofactors, Organic phosphates; in thiamine thiamine
particular, adenine nucleotides, tetrahydrofolic acid [505],
N5 -methylfolate [505], thiamine monophosphate [712]
Stoichiometry Folate (in) : organic phosphate (out), precise stoichiometry A facilitative carrier not known to be coupled to an A facilitative carrier not known to be coupled to an
unknown inorganic or organic ion gradient inorganic or organic ion gradient
Inhibitors compound 9 (pKi 6.6) [534], methotrexate (pKi 5.3) [534] – –
Labelled ligands [3 H]folic acid [29], [3 H]methotrexate [29] [3 H]thiamine [168] [3 H]thiamine [518]

Comments: Loss-of-function mutations in ThTr1 underlie thiamine-responsive megaloblastic anemia syndrome [151].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC19 family of vitamin transporters S442

SLC20 family of sodium-dependent phosphate transporters

Transporters → SLC superfamily of solute carriers → SLC20 family of sodium-dependent phosphate transporters
Overview: The SLC20 family is looked upon not only as ion transporters, but also as retroviral receptors. As ion transporters, they are sometimes referred to as Type III sodium-phosphate co-transporters,
alongside Type I (SLC17 family) and Type II (SLC34 family). PiTs are cell-surface transporters, composed of ten TM domains with extracellular C- and N-termini. PiT1 is a focus for dietary phosphate and
vitamin D regulation of parathyroid hormone secretion from the parathyroid gland. PiT2 appears to be involved in intestinal absorption of dietary phosphate.

Nomenclature Sodium-dependent phosphate transporter 1 Sodium-dependent phosphate transporter 2

Systematic nomenclature SLC20A1 SLC20A2
Common abbreviation PiT1 PiT2
HGNC, UniProt SLC20A1, Q8WUM9 SLC20A2, Q08357
Substrates AsO4 3- [519], phosphate [519] phosphate [519]
Stoichiometry >1 Na+ : 1 HPO4 2- (in) >1 Na+ : 1 HPO4 2- (in)

SLC22 family of organic cation and anion transporters

Transporters → SLC superfamily of solute carriers → SLC22 family of organic cation and anion transporters
Overview: The SLC22 family of transporters is mostly composed of non-selective transporters, which are expressed highly in liver, kidney and intestine, playing a major role in drug disposition. The
family may be divided into three subfamilies based on the nature of the substrate transported: organic cations (OCTs), organic anions (OATs) and organic zwiterrion/cations (OCTN). Membrane topology
is predicted to contain 12 TM domains with intracellular termini, and an extended extracellular loop at TM 1/2.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC22 family of organic cation and anion transporters S443
Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

Organic cation transporters (OCT)

Transporters → SLC superfamily of solute carriers → SLC22 family of organic cation and anion transporters → Organic cation transporters (OCT)
Overview: Organic cation transporters (OCT) are electrogenic, Na+ -independent and reversible.

Nomenclature Organic cation transporter 1 Organic cation transporter 2 Organic cation transporter 3
Systematic nomenclature SLC22A1 SLC22A2 SLC22A3
Common abbreviation OCT1 OCT2 OCT3
HGNC, UniProt SLC22A1, O15245 SLC22A2, O15244 SLC22A3, O75751
Substrates MPP+ , tetraethylammonium, desipramine, metformin MPP+ [247], pancuronium [247], tetraethylammonium MPP+ , tetraethylammonium, quinidine, metformin [368]
[576], aciclovir [247], tubocurarine [247], cisplatin [368], metformin [368]
Endogenous substrates PGF2α , choline, PGE2 , 5-hydroxytryptamine PGE2 [356], dopamine [263], histamine [263] (-)-noradrenaline [719], 5-hydroxytryptamine [719],
dopamine [719]
Stoichiometry Unknown Unknown Unknown
Inhibitors clonidine (pKi 6.3) [708] decynium 22 (pKi 7) [247] disprocynium24 (pKi 7.8) [264]

Comments: Corticosterone and quinine are able to inhibit all three organic cation transporters.

Searchable database: http://www.guidetopharmacology.org/index.jsp Organic cation transporters (OCT) S444

Organic zwitterions/cation transporters (OCTN)

Transporters → SLC superfamily of solute carriers → SLC22 family of organic cation and anion transporters → Organic zwitterions/cation transporters (OCTN)
Overview: Organic zwitterions/cation transporters (OCTN) function as organic cation uniporters, organic cation/proton exchangers or sodium/L-carnitine co-transporters.

Nomenclature Organic cation/carnitine transporter 1 Organic cation/carnitine transporter 2 Carnitine transporter 2

Systematic nomenclature SLC22A4 SLC22A5 SLC22A16
Common abbreviation OCTN1 OCTN2 CT2
HGNC, UniProt SLC22A4, Q9H015 SLC22A5, O76082 SLC22A16, Q86VW1
Substrates verapamil, mepyramine, tetraethylammonium, MPP+ verapamil, tetraethylammonium, MPP+ , mepyramine –
Endogenous substrates L-carnitine L-carnitine, acetyl-L-carnitine L-carnitine
Stoichiometry Unknown Unknown Unknown

Comments: Mutations in the SLC22A5 gene lead to primary carnitine deﬁciency [409].

Searchable database: http://www.guidetopharmacology.org/index.jsp Organic zwitterions/cation transporters (OCTN) S445

Organic anion transporters (OATs)

Transporters → SLC superfamily of solute carriers → SLC22 family of organic cation and anion transporters → Organic anion transporters (OATs)
Overview: Organic anion transporters (OATs) are non-selective transporters prominent in the kidney, placenta and blood-brain barrier.

Nomenclature Organic anion transporter 1 Organic anion transporter 2 Organic anion transporter 3 Organic anion transporter 4 Organic anion transporter 5 Organic anion transporter 7
Systematic nomenclature SLC22A6 SLC22A7 SLC22A8 SLC22A11 SLC22A10 SLC22A9
Common abbreviation OAT1 OAT2 OAT3 – OAT5 OAT4
HGNC, UniProt SLC22A6, Q4U2R8 SLC22A7, Q9Y694 SLC22A8, Q8TCC7 SLC22A11, Q9NSA0 SLC22A10, Q63ZE4 SLC22A9, Q8IVM8
Substrates aminohippuric acid, aminohippuric acid, PGE2 , uric acid [466], uric acid [466], ochratoxin A [697] –
non-steroidal non-steroidal estrone-3-sulphate [379], dehydroepiandrosterone sulphate
anti-inﬂammatory drugs anti-inﬂammatory drugs aminohippuric acid [379], [97], estrone-3-sulphate
cimetidine [379], [97], ochratoxin A [97]
ochratoxin A [379]
Stoichiometry Unknown Unknown Unknown Unknown Unknown Unknown
Inhibitors probenecid (Inhibition of – – – – –
urate transport by human
SCL22A6.) (pIC50 4.9) [304]

Searchable database: http://www.guidetopharmacology.org/index.jsp Urate transporter S446

Nomenclature Urate anion exchanger 1

Systematic nomenclature SLC22A12
Common abbreviation URAT1
HGNC, UniProt SLC22A12, Q96S37
Endogenous substrates uric acid [181], orotic acid [181]
Stoichiometry Unknown
Selective inhibitors suﬁnpyrazone (pIC50 4) [699]
Comments URAT1 is expressed in the proximal tubule of the kidney and regulates uric acid excretion from the body. Inhibitors of this transporter, such as losartan, ﬁnd clinical utility in managing
hyperuricemia in patients with gout [85, 275].

Atypical SLC22B subfamily

Transporters → SLC superfamily of solute carriers → SLC22 family of organic cation and anion transporters → Atypical SLC22B subfamily
Overview: This family of transporters has previously been classiﬁed as part of the atypical major facilitator superfamily (MSF) protein superfamily [489, 492, 493, 520]. The atypical SLCs share sequence
similarities and phylogenetic ancestry with other SLCs, and they have historically been classiﬁed in to subfamilies (also referred to as atypical MFS transporter families (AMTF1-15)) based on phylogenetic,
sequence and structural analyses [492].

Nomenclature synaptic vesicle glycoprotein 2A

Systematic nomenclature SLC22B1
HGNC, UniProt SV2A, Q7L0J3
Substrates Galactose [421]
Inhibitors brivaracetam (pIC50 7) [349] – Rat, levetiracetam (pKi 5.8) [470] – Rat

Comments: There are three human synaptic vesicle glycoprotein 2 family members, SV2A, SV2B and SV2C. They have transmembrane transporter activity and can be classiﬁed in to the SLC superfamily
of solute carriers in subfamily SLC22, as SCL22B1, B2 and B3 respectively. SV2A (SCL22B1) has been identiﬁed as the brain binding-site for the antiepileptic drugs levetiracetam [358, 415] and brivaracetam
[465].

Searchable database: http://www.guidetopharmacology.org/index.jsp Atypical SLC22B subfamily S447

SLC23 family of ascorbic acid transporters

Transporters → SLC superfamily of solute carriers → SLC23 family of ascorbic acid transporters
Overview: Predicted to be 12 TM segment proteins, members of this family transport the reduced form of ascorbic acid (while the oxidized form may be handled by members of the SLC2 family
(GLUT1/SLC2A1, GLUT3/SLC2A3 and GLUT4/SLC2A4). Phloretin is considered a non-selective inhibitor of these transporters, with an afﬁnity in the micromolar range.

Nomenclature Sodium-dependent vitamin C transporter 1 Sodium-dependent vitamin C transporter 2 Sodium-dependent vitamin C transporter 3
Systematic nomenclature SLC23A1 SLC23A2 SLC23A3
Common abbreviation SVCT1 SVCT2 SVCT3
HGNC, UniProt SLC23A1, Q9UHI7 SLC23A2, Q9UGH3 SLC23A3, Q6PIS1
Endogenous substrates L-ascorbic acid > D-ascorbic acid > dehydroascorbic acid L-ascorbic acid > D-ascorbic acid > dehydroascorbic acid –
[628] [628]
Stoichiometry 2 Na+ : 1 ascorbic acid (in) [628] 2 Na+ : 1 ascorbic acid (in) [628] –
Inhibitors phloretin (pKi 4.2) [628] – –
Labelled ligands [14 C]ascorbic acid (Binding) [417] [14 C]ascorbic acid –
Comments – – SLC23A3 does not transport ascorbic acid and remains an
orphan transporter.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC23 family of ascorbic acid transporters S448

Nomenclature Sodium-dependent nucleobase transporter

Systematic nomenclature SLC23A4
Common abbreviation SNBT1
HGNC, UniProt SLC23A4P, –
Substrates 5-ﬂuorouracil [685]
Endogenous substrates uracil > thymine > guanine, hypoxanthine > xanthine, uridine [685]
Stoichiometry 1 Na+ : 1 uracil (in) [685]
Comments SLC23A4/SNBT1 is found in rodents and non-human primates, but the sequence is truncated in the human genome and named as a pseudogene, SLC23A4P

SLC24 family of sodium/potassium/calcium exchangers

Transporters → SLC superfamily of solute carriers → SLC24 family of sodium/potassium/calcium exchangers
Overview: The sodium/potassium/calcium exchange family of transporters utilize the extracellular sodium gradient to drive calcium and potassium co-transport out of the cell. As is the case for NCX
transporters (SLC8A family), NKCX transporters are thought to be bidirectional, with the possibility of calcium inﬂux following depolarization of the plasma membrane. Topological modeling suggests
the presence of 10 TM domains, with a large intracellular loop between the ﬁfth and sixth TM regions.

Nomenclature Sodium/potassium/calcium exchanger 1 Sodium/potassium/calcium exchanger 6

Systematic nomenclature SLC24A1 SLC24A6
Common abbreviation NKCX1 NKCX6
HGNC, UniProt SLC24A1, O60721 SLC8B1, Q6J4K2
Stoichiometry 4Na+ :(1Ca2+ + 1K+ ) –

Comments: NKCX6 has been proposed to be the sole member of a CAX Na+ /Ca2+ exchanger family, which may be the mitochondrial transporter responsible for calcium accumulation from the cytosol
[565].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC24 family of sodium/potassium/calcium exchangers S449

SLC25 family of mitochondrial transporters

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters
Overview: Mitochondrial transporters are nuclear-encoded proteins, which convey solutes across the inner mitochondrial membrane. Topological modelling suggests homodimeric transporters, each
with six TM segments and termini in the cytosol.

Mitochondrial di- and tri-carboxylic acid transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters → Mitochondrial di- and tri-carboxylic acid transporter subfamily
Overview: Mitochondrial di- and tri-carboxylic acid transporters are grouped on the basis of commonality of substrates and include the citrate transporter which facilitates citric acid export from the
mitochondria to allow the generation of oxalacetic acid and acetyl CoA through the action of ATP:citrate lyase.

Nomenclature Mitochondrial citrate transporter Mitochondrial dicarboxylate transporter Mitochondrial oxoglutarate carrier Mitochondrial oxodicarboxylate carrier
Systematic nomenclature SLC25A1 SLC25A10 SLC25A11 SLC25A21
Common abbreviation CIC DIC OGC ODC
HGNC, UniProt SLC25A1, P53007 SLC25A10, Q9UBX3 SLC25A11, Q02978 SLC25A21, Q9BQT8
Substrates phosphoenolpyruvic acid, malic acid, 2- ,
SO4 phosphate, S2 O3 2- , succinic acid, α-ketoglutaric acid, malic acid α-ketoglutaric acid, α-oxoadipic acid
citric acid malic acid
Stoichiometry Malate2- (in) : H-citrate2- (out) PO3 4- (in) : malate2- (out) Malate2- (in) : oxoglutarate2- (out) Oxoadipate (in) : oxoglutarate (out)
Inhibitors 1,2,3-benzenetricarboxylic acid – – –

Searchable database: http://www.guidetopharmacology.org/index.jsp Mitochondrial di- and tri-carboxylic acid transporter subfamily S450
Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

Mitochondrial amino acid transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters → Mitochondrial amino acid transporter subfamily
Overview: Mitochondrial amino acid transporters can be subdivided on the basis of their substrates. Mitochondrial ornithine transporters play a role in the urea cycle by exchanging cytosolic ornithine
(L-ornithine and D-ornithine) for mitochondrial citrulline (L-citrulline and D-citrulline) in equimolar amounts. Further members of the family include transporters of S-adenosylmethionine and carnitine.

Nomenclature AGC1 AGC2 Mitochondrial Mitochondrial Mitochondrial ornithine Mitochondrial ornithine Carnitine/acylcarnitine
glutamate carrier 2 glutamate carrier 1 transporter 2 transporter 1 carrier
Systematic nomenclature SLC25A12 SLC25A13 SLC25A18 SLC25A22 SLC25A2 SLC25A15 SLC25A20
Common abbreviation – – GC2 GC1 ORC2 ORC1 CAC
HGNC, UniProt SLC25A12, O75746 SLC25A13, Q9UJS0 SLC25A18, Q9H1K4 SLC25A22, Q9H936 SLC25A2, Q9BXI2 SLC25A15, Q9Y619 SLC25A20, O43772
Substrates L-glutamic acid, 2-amino-3- L-glutamic acid L-glutamic acid L-citrulline [202], L-lysine [202], –
2-amino-3- sulﬁnopropanoic acid, L-arginine [202], L-ornithine [202],
sulﬁnopropanoic acid, L-glutamic acid, L-lysine [202], D-lysine L-citrulline [202],
L-aspartic acid L-aspartic acid [202], D-arginine [202], L-arginine [202]
D-citrulline [202],
D-ornithine [202],
L-ornithine [202],
D-histidine [202],
L-histidine [202]
Stoichiometry Aspartate : glutamate Aspartate : glutamate Glutamate : H+ Glutamate : H+ 1 Ornithine (in) :1 1 Ornithine (in) :1 –
H+ (bidirectional) H+ (bidirectional) (bidirectional) (bidirectional) citrulline : 1 H+ (out) citrulline : 1 H+ (out)
Comments – – – – – – Exchanges cytosolic
acylcarnitine for
mitochondrial carnitine

Comments: Both ornithine transporters are inhibited by the polyamine spermine [203]. Loss-of-function mutations in these genes are associated with hyperornithinemia-hyperammonemia-homocitrullinuria.

Searchable database: http://www.guidetopharmacology.org/index.jsp Mitochondrial amino acid transporter subfamily S451

Mitochondrial phosphate transporters

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters → Mitochondrial phosphate transporters
Overview: Mitochondrial phosphate transporters allow the import of inorganic phosphate for ATP production.

Nomenclature Mitochondrial phosphate carrier

Systematic nomenclature SLC25A3
Common abbreviation PHC
HGNC, UniProt SLC25A3, Q00325
Stoichiometry PO3 4- (in) : OH- (out) or PO3 4- : H+ (in)

Mitochondrial nucleotide transporter subfamily

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters → Mitochondrial nucleotide transporter subfamily
Overview: Mitochondrial nucleotide transporters, deﬁned by structural similarlities, include the adenine nucleotide translocator family (SLC25A4, SLC25A5, SLC25A6 and SLC25A31), which under
conditions of aerobic metabolism, allow coupling between mitochondrial oxidative phosphorylation and cytosolic energy consumption by exchanging cytosolic ADP for mitochondrial ATP. Further
members of the mitochondrial nucleotide transporter subfamily convey diverse substrates including CoA, although not all members have had substrates identiﬁed.

Nomenclature Mitochondrial Mitochondrial Mitochondrial Mitochondrial Graves disease carrier Peroxisomal membrane
adenine nucleotide adenine nucleotide adenine nucleotide adenine nucleotide protein
translocator 1 translocator 2 translocator 3 translocator 4
Systematic nomenclature SLC25A4 SLC25A5 SLC25A6 SLC25A31 SLC25A16 SLC25A17
Common abbreviation ANT1 ANT2 ANT3 ANT4 GDC PMP34
HGNC, UniProt SLC25A4, P12235 SLC25A5, P05141 SLC25A6, P12236 SLC25A31, Q9H0C2 SLC25A16, P16260 SLC25A17, O43808
Substrates – – – – CoA and congeners ADP, ATP,
adenosine 5’-monophosphate
Stoichiometry ADP3- (in) : ATP4- (out) ADP3- (in) : ATP4- (out) ADP3- (in) : ATP4- (out) ADP3- (in) : ATP4- (out) CoA (in) ATP (in)
Inhibitors bongkrek acid, – – – – –
carboxyatractyloside

Searchable database: http://www.guidetopharmacology.org/index.jsp Mitochondrial nucleotide transporter subfamily S452

Nomenclature Deoxynucleotide carrier 1 S-Adenosylmethionine carrier Mitochondrial phosphate carrier 1 Mitochondrial phosphate carrier 2 Mitochondrial phosphate carrier 3
Systematic nomenclature SLC25A19 SLC25A26 SLC25A24 SLC25A23 SLC25A25
Common abbreviation DNC SAMC1 APC1 APC2 APC3
HGNC, UniProt SLC25A19, Q9HC21 SLC25A26, Q70HW3 SLC25A24, Q6NUK1 SLC25A23, Q9BV35 SLC25A25, Q6KCM7
Substrates Nucleotide Diphosphates (NDPs), S-adenosyl methionine – – –
Deoxynucleotide Diphosphates
(dNDPs), Dideoxynucleotide
Triphosphates (ddNTPs),
Deoxynucleotide Triphosphates
(dNTPs)
Stoichiometry dNDP (in) : ATP (out) – – – –

Mitochondrial uncoupling proteins

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters → Mitochondrial uncoupling proteins
Overview: Mitochondrial uncoupling proteins allow dissipation of the mitochondrial proton gradient associated with thermogenesis and regulation of radical formation.

Nomenclature Uncoupling protein 1 Uncoupling protein 2 Uncoupling protein 3 Uncoupling protein 4 Uncoupling protein 5 KMCP1
Systematic nomenclature SLC25A7 SLC25A8 SLC25A9 SLC25A27 SLC25A14 SLC25A30
Common abbreviation UCP1 UCP2 UCP3 UCP4 UCP5 –
HGNC, UniProt UCP1, P25874 UCP2, P55851 UCP3, P55916 SLC25A27, O95847 SLC25A14, O95258 SLC25A30, Q5SVS4
Stoichiometry H+ (in) H+ (in) H+ (in) H+ (in) H+ (in) –

Searchable database: http://www.guidetopharmacology.org/index.jsp Mitochondrial uncoupling proteins S453

Miscellaneous SLC25 mitochondrial transporters

Transporters → SLC superfamily of solute carriers → SLC25 family of mitochondrial transporters → Miscellaneous SLC25 mitochondrial transporters
Overview: Many of the transporters identiﬁed below have yet to be assigned functions and are currently regarded as orphans.

Information on members of this family may be found in the online database.

SLC26 family of anion exchangers

Transporters → SLC superfamily of solute carriers → SLC26 family of anion exchangers
Overview: Along with the SLC4 family, the SLC26 family acts to allow movement of monovalent and divalent anions across cell membranes. The predicted topology is of 10-14 TM domains with
intracellular C- and N-termini, probably existing as dimers. Within the family, subgroups may be identiﬁed on the basis of functional differences, which appear to function as anion exchangers and anion
channels (SLC26A7 and SLC26A9).

Selective sulphate transporters

Transporters → SLC superfamily of solute carriers → SLC26 family of anion exchangers → Selective sulphate transporters

Nomenclature Sat-1 DTDST

Systematic nomenclature SLC26A1 SLC26A2
HGNC, UniProt SLC26A1, Q9H2B4 SLC26A2, P50443
Substrates SO4 2- , oxalate SO4 2-
Stoichiometry SO4 2- (in) : anion (out) 1 SO4 2- (in) : 2 Cl- (out)

Searchable database: http://www.guidetopharmacology.org/index.jsp Selective sulphate transporters S454

Chloride/bicarbonate exchangers
Transporters → SLC superfamily of solute carriers → SLC26 family of anion exchangers → Chloride/bicarbonate exchangers

Nomenclature DRA Pendrin PAT-1

Systematic nomenclature SLC26A3 SLC26A4 SLC26A6
HGNC, UniProt SLC26A3, P40879 SLC26A4, O43511 SLC26A6, Q9BXS9
Substrates Cl- formate, HCO3 - , OH- , I- , Cl- formate, oxalate, SO4 2- , OH- , Cl- , HCO3 - , I-
Stoichiometry 2 Cl- (in) : 1 HCO3 - (out) or 2 Cl- (in) : 1 OH- (out) Unknown 1 SO4 2- (in) : 2 HCO3 - (out) or 1 Cl- (in) : 2 HCO3 - (out)

Anion channels
Transporters → SLC superfamily of solute carriers → SLC26 family of anion exchangers → Anion channels

Nomenclature SLC26A7 SLC26A9

HGNC, UniProt SLC26A7, Q8TE54 SLC26A9, Q7LBE3
Substrates NO3 - Cl- = Br- = I- > SO4 2- = L-glutamic acid I- > Br- > NO3 - > Cl- > L-glutamic acid
Functional Characteristics Voltage- and time-independent current, linear I-V relationship [354] Voltage- and time-independent current, linear I-V relationship [161]
Comments – SLC26A9 has been suggested to operate in two additional modes as a Cl- -HCO3 -
exchanger and as a Na+ -anion cotransporter [99].

Searchable database: http://www.guidetopharmacology.org/index.jsp Anion channels S455

Other SLC26 anion exchangers

Transporters → SLC superfamily of solute carriers → SLC26 family of anion exchangers → Other SLC26 anion exchangers

Nomenclature Prestin
Systematic nomenclature SLC26A5
HGNC, UniProt SLC26A5, P58743
Substrates HCO3 - [443], Cl- [443]
Stoichiometry Unknown
Comments Prestin has been suggested to function as a molecular motor, rather than a transporter

Searchable database: http://www.guidetopharmacology.org/index.jsp Other SLC26 anion exchangers S456

SLC27 family of fatty acid transporters

Transporters → SLC superfamily of solute carriers → SLC27 family of fatty acid transporters

Overview: Fatty acid transporter proteins (FATPs) are a family brane associated domain, peripheral membrane associated do- chain acyl-CoA synthetase (EC 6.2.1.- , EC 6.2.1.7) enzyme activ-
(SLC27) of six transporters (FATP1-6). They have at least one, main, FATP signature, intracellular AMP binding motif, dimer- ity. Within the cell, these transporters may associate with plasma
and possibly six [397, 557], transmembrane segments, and are ization domain, lipocalin motif, and an ER localization domain and peroxisomal membranes. FATP1-4 and -6 transport long- and
predicted on the basis of structural similarities to form dimers. (identiﬁed in FATP4 only) [190, 441, 481]. These transporters very long-chain fatty acids, while FATP5 transports long-chain
SLC27 members have several structural domains: integral mem- are unusual in that they appear to express intrinsic very long- fatty acids as well as bile acids [439, 557].

Nomenclature Fatty acid transport protein 1 Fatty acid transport Fatty acid transport Fatty acid transport protein 4 Fatty acid transport Fatty acid transport
protein 2 protein 3 protein 5 protein 6
Systematic nomenclature SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6
Common abbreviation FATP1 FATP2 FATP3 FATP4 FATP5 FATP6
HGNC, UniProt SLC27A1, Q6PCB7 SLC27A2, O14975 SLC27A3, Q5K4L6 SLC27A4, Q6P1M0 SLC27A5, Q9Y2P5 SLC27A6, Q9Y2P4
Endogenous substrates palmitic acid > oleic acid > – – palmitic acid , oleic acid > γ-linolenic acid – palmitic acid >
γ-linolenic acid > octanoic acid [238] > octanoic acid [238] oleic acid >
arachidonic acid > palmitic acid > palmitic acid > oleic acid > butyric acid, γ-linolenic acid >
oleic acid > butyric acid [557] γ-linolenic acid > arachidonic acid [586] octanoic acid [238]
Inhibitors – – – compound 1l (pIC50 7.1) [60] – –
Comments – – – FATP4 is genetically linked to – –
restrictive dermopathy.

Comments: Although the stoichiometry of fatty acid transport [718], have been described; analysis of the mechanism of action of FATP2 has two variants: Variant 1 encodes the full-length protein,
is unclear, it has been proposed to be facilitated by the coupling some of these inhibitors suggests that transport may be selectively while Variant 2 encodes a shorter isoform missing an internal pro-
of fatty acid transport to conjugation with coenzyme A to form inhibited without altering enzymatic activity of the FATP. tein segment. FATP6 also has two variants: Variant 2 encodes the
fatty acyl CoA esters. Small molecule inhibitors of FATP2 [398, C1-BODIPY-C12 accumulation has been used as a non-selective same protein as Variant 1 but has an additional segment in the 5’
553] and FATP4 [60, 718], as well as bile acid inhibitors of FATP5 index of fatty acid transporter activity. UTR.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC27 family of fatty acid transporters S457

SLC28 and SLC29 families of nucleoside transporters

Transporters → SLC superfamily of solute carriers → SLC28 and SLC29 families of nucleoside transporters
Overview: Nucleoside transporters are divided into two families, the sodium-dependent, concentrative solute carrier family 28 (SLC28) and the equilibrative, solute carrier family 29 (SLC29). The
endogenous substrates are typically nucleosides, although some family members can also transport nucleobases and organic cations.

SLC28 family
Transporters → SLC superfamily of solute carriers → SLC28 and SLC29 families of nucleoside transporters → SLC28 family
Overview: SLC28 family membersappear to have 13 TM segments with cytoplasmic N-termini and extracellular C-termini, and function as concentrative nucleoside transporters.

Nomenclature Sodium/nucleoside cotransporter 1 Sodium/nucleoside cotransporter 2 Solute carrier family 28 member 3

Systematic nomenclature SLC28A1 SLC28A2 SLC28A3
Common abbreviation CNT1 CNT2 CNT3
HGNC, UniProt SLC28A1, O00337 SLC28A2, O43868 SLC28A3, Q9HAS3
Substrates ribavirin [115], gemcitabine [114], zalcitabine, zidovudine cladribine [485], didanosine, vidarabine, fludarabine [382], zalcitabine, formycin B, cladribine, 5-fluorouridine,
formycin B [382] floxuridine, didanosine, zidovudine, zebularine,
gemcitabine
Endogenous substrates adenosine, uridine, cytidine, thymidine adenosine, guanosine, inosine, thymidine adenosine, uridine, guanosine, thymidine, inosine, cytidine
Stoichiometry 1 Na+ : 1 nucleoside (in) 1 Na+ : 1 nucleoside (in) 2 Na+ /H+
Inhibitors – – compound 16 (pKi 5.5) [272]
Comments – – CNT3 forms cyclic homotrimers [588]. Genetic variants of
SLC28A3 are associated with increased risk of
anthracycline-induced cardiomyopathy [587].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC28 family S458

SLC29 family
Transporters → SLC superfamily of solute carriers → SLC28 and SLC29 families of nucleoside transporters → SLC29 family
Overview: SLC29 family members appear to be composed of 11 TM segments with cytoplasmic N-termini and extracellular C-termini. ENT1, ENT2 and ENT4 are cell-surface transporters, while ENT3 is
intracellular, possibly lysosomal [38]. ENT1-3 are described as broad-spectrum equilibrative nucleoside transporters, while ENT4 is primarily a polyspeciﬁc organic cation transporter at neutral pH [293].

Nomenclature Equilibrative nucleoside transporter 1 Equilibrative nucleoside transporter 2

Systematic nomenclature SLC29A1 SLC29A2
Common abbreviation ENT1 ENT2
HGNC, UniProt SLC29A1, Q99808 SLC29A2, Q14542
Endogenous substrates in order of increasing Km: adenosine < inosine < uridine < guanosine < cytidine < hypoxanthine < –
adenine < thymine
Substrates abacavir [96], atenolol [442], pentostatin, vidarabine, gemcitabine, formycin B, 2-chloroadenosine, cytarabine, tubercidin, cladribine,
2-chloroadenosine, cytarabine, zalcitabine, didanosine, tubercidin, formycin B, gemcitabine, vidarabine, zidovudine
cladribine, ribavirin [115], floxuridine
Endogenous substrates thymine [691], guanosine [691], hypoxanthine [691], uridine [691], inosine adenosine, guanine, thymine, uridine, guanosine, hypoxanthine, inosine,
[691], adenine [691], cytidine [691], thymidine [691], adenosine [691] thymidine, cytosine
Stoichiometry Equilibrative Equilibrative
Inhibitors nitrobenzylmercaptopurine ribonucleoside (pKi 9.7), draflazine (pKi 9.6) –
[276], KF24345 (pKi 9.4) [277], NBTGR (pKi 9.3), dilazep (pKi 9),
dipyridamole (pKi 8.8) [277], ticagrelor (pKi 7.3) [26]
Labelled ligands [3 H]nitrobenzylmercaptopurine ribonucleoside (pKd 9.3) –
Comments ENT1 has 100-1000-fold lower affinity for nucleobases as compared with –
nucleosides [691].
The affinities of draflazine, dilazep, KF24345 and dipyridamole at ENT1
transporters are species dependent, exhibiting lower affinity at rat transporters
than at human transporters [277, 593].
The loss of ENT1 activity in ENT1-null mice has been associated with a
hypermineralization disorder similar to human diffuse idiopathic skeletal
hyperostosis [661]. Lack of ENT1 also results in the Augustine-null blood type
[133].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC29 family S459

Nomenclature Equilibrative nucleoside transporter 3 Plasma membrane monoamine transporter

Systematic nomenclature SLC29A3 SLC29A4
Common abbreviation ENT3 PMAT
HGNC, UniProt SLC29A3, Q9BZD2 SLC29A4, Q7RTT9
Substrates zidovudine [38], zalcitabine [38], didanosine [38], fludarabine [38], cordycepin [38], tetraethylammonium [180, 655], MPP+ [180, 655], metformin [717], atenolol [442]
floxuridine [38], cladribine [38], tubercidin [38], zebularine [38]
Endogenous substrates adenosine [38], inosine [38], uridine [38], thymidine [38], guanosine [38], adenine [38] histamine [180, 655], tyramine [180, 655], adenosine [716], 5-hydroxytryptamine [180,
655], dopamine [180, 655]
Stoichiometry Equilibrative Equilibrative
Inhibitors – decynium 22 (pKi 7) [180, 655], rhodamine123 (pKi 6) [180, 655], dipyridamole (pKi
5.9) [652], verapamil (pKi 4.7) [180, 655], fluoxetine (pKi 4.6) [180, 655], quinidine (pKi
4.6) [180, 655], quinine (pKi 4.6) [180, 655], desipramine (pKi 4.5) [180, 655],
cimetidine (pKi <3.3) [180, 655]
Comments Defects in SLC29A3 have been implicated in histiocytosis-lymphadenopathy plus syndrome Uptake of substrates by PMAT is pH dependent, with greater uptake observed at acidic
(OMIM:602782) and lysosomal storage diseases [296, 342]. extracellular pH [43, 717].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC29 family S460

SLC30 zinc transporter family

Transporters → SLC superfamily of solute carriers → SLC30 zinc transporter family

Overview: Along with the SLC39 family, SLC30 transporters reg- membrane extruding zinc, while ZnT3 is associated with synap- lent linking has been suggested as a mechanism for dimerisation,
ulate the movement of zinc ions around the cell. In particular, tic vesicles and ZnT4 and ZnT5 are linked with secretory granules. particularly for ZnT3 [551]. The mechanism for zinc transport is
these transporters remove zinc ions from the cytosol, allowing ac- Membrane topology predictions suggest a multimeric assembly, unknown.
cumulation into intracellular compartments or efﬂux through the potentially heteromultimeric [596], with subunits having six TM
plasma membrane. ZnT1 is thought to be placed on the plasma domains, and both termini being cytoplasmic. Dityrosine cova-

Information on members of this family may be found in the online database.

Comments: ZnT8/SLC30A8 is described as a type 1 diabetes susceptibility gene.

Zinc ﬂuxes may be monitored through the use of radioisotopic Zn-65 or the ﬂuorescent dye FluoZin 3.

SLC31 family of copper transporters

Transporters → SLC superfamily of solute carriers → SLC31 family of copper transporters
Overview: SLC31 family members, alongside the Cu-ATPases are involved in the regulation of cellular copper levels. The CTR1 transporter is a cell-surface transporter to allow monovalent copper
accumulation into cells, while CTR2 appears to be a vacuolar/vesicular transporter [521]. Functional copper transporters appear to be trimeric with each subunit having three TM regions and an
extracellular N-terminus. CTR1 is considered to be a higher afﬁnity copper transporter compared to CTR2. The stoichiometry of copper accumulation is unclear, but appears to be energy-independent
[387].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC31 family of copper transporters S461

Nomenclature Copper transporter 1 Copper transporter 2

Systematic nomenclature SLC31A1 SLC31A2
Common abbreviation CTR1 CTR2
HGNC, UniProt SLC31A1, O15431 SLC31A2, O15432
Substrates cisplatin [317] cisplatin [61]
Endogenous substrates copper [387] copper
Stoichiometry Unknown Unknown

Comments: Copper accumulation through CTR1 is sensitive to silver ions, but not divalent cations [387].

SLC32 vesicular inhibitory amino acid transporter

Transporters → SLC superfamily of solute carriers → SLC32 vesicular inhibitory amino acid transporter

Overview: The vesicular inhibitory amino acid transporter, termini [429]. However, an alternative 9TM structure with the N that VIAAT is instead a Cl- /GABA co-transporter. VIAAT co-exists
VIAAT (also termed the vesicular GABA transporter VGAT), terminus facing the cytoplasm and the C terminus residing in the with VGLUT1 (SLC17A7), or VGLUT2 (SLC17A6), in the synaptic
which is the sole representative of the SLC32 family, trans- synaptic vesicle lumen has subsequently been reported [427]. VI- vesicles of selected nerve terminals [194, 701]. VIAAT knock out
ports GABA, or glycine, into synaptic vesicles [229, 230], and AAT acts as an antiporter for inhibitory amino acids and protons. mice die between embryonic day 18.5 and birth [671]. In cultures
is a member of the structurally-deﬁned amino acid-polyamine- The accumulation of GABA and glycine within vesicles is driven by of spinal cord neurones established from earlier embryos, the co-
organocation/APC clan composed of SLC32, SLC36 and SLC38 both the chemical (pH) and electrical (ψ) components of the release of of GABA and glycine from synaptic vesicles is drastically
transporter families (see [559]). VIAAT was originally suggested proton electrochemical gradient (μH +) established by a vacuolar reduced, providing direct evidence for the role of VIAAT in the se-
to be composed of 10 TM segments with cytoplasmic N- and C- H+ -ATPase [429]. However, one study, [334], presented evidence questration of both transmitters [547, 671].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC32 vesicular inhibitory amino acid transporter S462
Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

Nomenclature Vesicular inhibitory amino acid transporter

Systematic nomenclature SLC32A1
Common abbreviation VIAAT
HGNC, UniProt SLC32A1, Q9H598
Endogenous substrates β-alanine, γ-hydroxybutyric acid, GABA (Km 5×10−3 M) [429], glycine
Stoichiometry 1 amino acid (in): 1 H+ (out) [229] or 1 amino acid: 2Cl- (in) [334]
Inhibitors vigabatrin (pIC50 2.1) [429]

SLC33 acetylCoA transporter

Transporters → SLC superfamily of solute carriers → SLC33 acetylCoA transporter
Overview: Acetylation of proteins is a post-translational modiﬁcation mediated by speciﬁc acetyltransferases, using the donor acetyl CoA. SLC33A1/AT1 is a putative 11 TM transporter present on the
endoplasmic reticulum, expressed in all tissues, but particularly abundant in the pancreas [341], which imports cytosolic acetyl CoA into these intracellular organelles.

Nomenclature AcetylCoA transporter

Systematic nomenclature SLC33A1
Common abbreviation ACATN1
HGNC, UniProt SLC33A1, O00400
Endogenous substrates acetyl CoA
Stoichiometry Unknown
Labelled ligands [14 C]acetylCoA (Binding)

Comments: In heterologous expression studies, acetyl CoA transport through AT1 was inhibited by coenzyme A, but not acetic acid, ATP or UDP-galactose [330]. A loss-of-function mutation in
ACATN1/SLC33A1 has been associated with spastic paraplegia (SPG42, [401]), although this observation could not be replicated in a subsequent study [560].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC33 acetylCoA transporter S463

SLC34 family of sodium phosphate co-transporters

Transporters → SLC superfamily of solute carriers → SLC34 family of sodium phosphate co-transporters
Overview: The SLC34 family are sometimes referred to as Type II sodium-phosphate co-transporters, alongside Type I (SLC17 family) and Type III (SLC20 family) transporters. Topological modelling
suggests eight TM domains with C- and N- termini in the cytoplasm, and a re-entrant loop at TM7/8. SLC34 family members are expressed on the apical surfaces of epithelia in the intestine and kidneys
to regulate body phosphate levels, principally NaPi-IIa and NaPi-IIb, respectively. NaPi-IIa and NaPi-IIb are electrogenic, while NaPiIIc is electroneutral [18].

Nomenclature Sodium phosphate 1 Sodium phosphate 2 Sodium phosphate 3

Systematic nomenclature SLC34A1 SLC34A2 SLC34A3
Common abbreviation NaPi-IIa NaPi-IIb NaPi-IIc
HGNC, UniProt SLC34A1, Q06495 SLC34A2, O95436 SLC34A3, Q8N130
Stoichiometry 3 Na+ : 1 HPO4 2- (in) [210] 3 Na+ : 1 HPO4 2- (in) [18] 2 Na+ : 1 HPO4 2- (in) [18]
Antibodies – lifastuzumab vedotin (Binding) [146] –

Comments: These transporters can be inhibited by foscarnet, in contrast to type III sodium-phosphate cotransporters, the SLC20 family.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC34 family of sodium phosphate co-transporters S464

SLC35 family of nucleotide sugar transporters

Transporters → SLC superfamily of solute carriers → SLC35 family of nucleotide sugar transporters
Overview: Glycoprotein formation in the Golgi and endoplasmic reticulum relies on the accumulation of nucleotide-conjugated sugars via the SLC35 family of transporters. These transporters have a
predicted topology of 10 TM domains, with cytoplasmic termini, and function as exchangers, swopping nucleoside monophosphates for the corresponding nucleoside diphosphate conjugated sugar. Five
subfamilies of transporters have been identiﬁed on the basis of sequence similarity, namely SLC35A1, SLC35A2, SLC35A3, SLC35A4 and SLC35A5; SLC35B1, SLC35B2, SLC35B3 and SLC35B4; SLC35C1
and SLC35C2; SLC35D1, SL35D1, SLC35D2 and SLC35D3, and the subfamily of orphan SLC35 transporters, SLC35E1-4 and SLC35F1-5.

Nomenclature CMP-sialic acid transporter UDP-galactose transporter UDP-N-acetylglucosamine PAPS transporter 1 PAPS transporter 2
transporter
Systematic nomenclature SLC35A1 SLC35A2 SLC35A3 SLC35B2 SLC35B3
HGNC, UniProt SLC35A1, P78382 SLC35A2, P78381 SLC35A3, Q9Y2D2 SLC35B2, Q8TB61 SLC35B3, Q9H1N7
Substrates CMP-sialic acid [313] UDP-galactose [315, 445], UDP N-acetyl-glucosamine [316] A3P5PS [336] A3P5PS [335]
UDP N-acetyl-glucosamine [315,
445]

Nomenclature YEA GDP-Fucose transporter UDP-glucuronic HFRC1

acid/UDP-N-acetylgalactosamine dual
transporter
Systematic nomenclature SLC35B4 SLC35C1 SLC35D1 SLC35D2
HGNC, UniProt SLC35B4, Q969S0 SLC35C1, Q96A29 SLC35D1, Q9NTN3 SLC35D2, Q76EJ3
Substrates UDP-xylose [28], UDP N-acetyl-glucosamine GDP-fucose [416] UDP-N-acetylgalactosamine [452], UDP-N-acetylgalactosamine [314]
[28] UDP-glucuronic acid [452]

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC35 family of nucleotide sugar transporters S465

SLC36 family of proton-coupled amino acid transporters

Transporters → SLC superfamily of solute carriers → SLC36 family of proton-coupled amino acid transporters

Overview: Members of the SLC36 family of proton-coupled expressed at the luminal surface of the small intestine and absorbs brown/beige adipocytes [633]. PAT1 and PAT4 are involved in reg-
amino acid transporters are involved in membrane transport of amino acids and derivatives [3]. In lysosomes, PAT1 functions as ulation of the mTORC1 pathway [191]. More comprehensive lists
amino acids and derivatives. The four transporters show variable an efﬂux mechanism for amino acids produced during intralysoso- of substrates can be found within the reviews under Further Read-
tissue expression patterns and are expressed in various cell types mal proteolysis [5, 542]. PAT2 is expressed at the apical membrane ing and in the references.
at the plasma-membrane and in intracellular organelles. PAT1 is of the renal proximal tubule [82] and at the plasma-membrane in

Nomenclature Proton-coupled Amino acid Transporter 1 Proton-coupled Amino acid Transporter 2

Systematic nomenclature SLC36A1 SLC36A2
Common abbreviation PAT1 PAT2
HGNC, UniProt SLC36A1, Q7Z2H8 SLC36A2, Q495M3
Substrates muscimol [619], arecaidine [619], betaine [619], L-cycloserine [619], 5-aminolevulinic acid MeAIB [109], D-cycloserine, L-cycloserine, L-azetidine-2-carboxylate [350]
[619], gaboxadol [383, 619], β-guanidinopropionic acid [619], D-cycloserine [619],
MeAIB [619], vigabatrin [1, 619], L-azetidine-2-carboxylate [619], THPO [619]
Endogenous substrates GABA [619], L-alanine [619], β-alanine [619], taurine [619], D-serine [619], D-proline sarcosine, L-proline, glycine, L-alanine, trans-4-hydroxy-proline
[619], trans-4-hydroxy-proline [619], sarcosine [619], D-cysteine [619], glycine [619],
D-alanine [619]
Stoichiometry 1 H+ : 1 amino acid (symport) 1 H+ : 1 amino acid (symport)
Inhibitors 5-hydroxy-L-tryptophan (pKi 3) [434], L-tryptophan (pKi 2.3) [434], 5-hydroxy-L-tryptophan (pIC50 2.8) [171], α-methyl-D,L-tryptophan (pIC50 2.5) [171]
indole-3-propionic acid (pKi 2.3) [434], 5-hydroxytryptamine (pKi 2.2) [434]
Comments [3 H] or [14 C] labelled substrates as listed above are used as probes. PAT1 can also function [3 H] or [14 C] labelled substrates as listed above are used as probes. Loss-of-function
as an electroneutral transport system for protons and fatty acids including acetic acid, mutations in PAT2 lead to iminoglycinuria and hyperglycinuria in man [82]. PAT2 can also
propanoic acid and butyric acid [206]. In addition, forskolin, phosphodiesterase inhibitors, function as an electroneutral transport system for protons and fatty acids including acetic
amiloride analogues and SLC9A3 (NHE3) selective inhibitors all reduce PAT1 activity acid, propanoic acid and butyric acid [206]. Replacement of a Phe residue in
indirectly (in intact mammalian intestinal epithelia such as human intestinal Caco-2 cells) transmembrane domain 3 with Cys (that has a smaller side-chain) broadens substrate
by inhibiting the Na+ /H+ exchanger NHE3 which is required to maintain the speciﬁcity to include larger substrates (e.g. methionine, leucine) [172].
H+ -electrochemical gradient driving force for H+ /amino acid cotransport [14, 17, 619].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC36 family of proton-coupled amino acid transporters S466
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Nomenclature Proton-coupled Amino acid Transporter 3 Proton-coupled Amino acid Transporter 4

Systematic nomenclature SLC36A3 SLC36A4
Common abbreviation PAT3 PAT4
HGNC, UniProt SLC36A3, Q495N2 SLC36A4, Q6YBV0
Endogenous substrates – L-tryptophan [497], L-proline [497]
Stoichiometry Unknown Unknown
Comments The function of the testes-speciﬁc PAT3 remains unknown. PAT4 is not proton-coupled and functions by facilitated diffusion in an electroneutral,
Na+ -independent, manner [497]. PAT4 is expressed ubiquitously and is predominantly
associated with the Golgi [192].. High PAT4 expression is associated with reduced
relapse-free survival after colorectal cancer surgery [192].

SLC37 family of phosphosugar/phosphate exchangers

Transporters → SLC superfamily of solute carriers → SLC37 family of phosphosugar/phosphate exchangers
Overview: The family of sugar-phosphate exchangers pass particular phosphorylated sugars across intracellular membranes, exchanging for inorganic phosphate. Of the family of sugar phosphate
transporters, most information is available on SPX4, the glucose-6-phosphate transporter. This is a 10 TM domain protein with cytoplasmic termini and is associated with the endoplasmic reticulum,
with tissue-speciﬁc splice variation.

Nomenclature Glycerol-3-phosphate transporter Sugar phosphate exchanger 2 Glucose-6-phosphate transporter

Systematic nomenclature SLC37A1 SLC37A2 SLC37A4
Common abbreviation SPX1 SPX2 SPX4
HGNC, UniProt SLC37A1, P57057 SLC37A2, Q8TED4 SLC37A4, O43826
Endogenous substrates glycerol 3-phosphate, glucose 6-phosphate glucose 6-phosphate glucose 6-phosphate
Stoichiometry Glucose 6-phosphate (in): phosphate (out) [488]. Glucose 6-phosphate (in): phosphate (out) [488]. Glucose 6-phosphate (in): phosphate (out) [107].
Inhibitors – – S-4048 (pIC50 8.7) [101] – Rat
Comments – – Multiple polymorphisms have been described for the
SLC37A4 gene, some of which associate with a glycogen
storage disease [9].

SLC38 family of sodium-dependent neutral amino acid transporters

Transporters → SLC superfamily of solute carriers → SLC38 family of sodium-dependent neutral amino acid transporters
Overview: The SLC38 family of transporters appears to be responsible for the functionally-defined system A and system N mechanisms of amino acid transport and are mostly expressed in the CNS. Two
distinct subfamilies are identifiable within the SLC38 transporters. SNAT1, SNAT2 and SNAT4 appear to resemble system A transporters in accumulating neutral amino acids under the influence of the
sodium gradient. SNAT3 and SNAT5 appear to resemble system N transporters in utilizing proton co-transport to accumulate amino acids. The predicted membrane topology is of 11 TM domains with
an extracellular C-terminus and intracellular N-terminus [559].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC38 family of sodium-dependent neutral amino acid transporters S468
Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full
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System A-like transporters

Transporters → SLC superfamily of solute carriers → SLC38 family of sodium-dependent neutral amino acid transporters → System A-like transporters

Nomenclature sodium-coupled neutral amino acid transporter 1 sodium-coupled neutral amino acid transporter 2 sodium-coupled neutral amino acid transporter 4
Systematic nomenclature SLC38A1 SLC38A2 SLC38A4
Common abbreviation SNAT1 SNAT2 SNAT4
HGNC, UniProt SLC38A1, Q9H2H9 SLC38A2, Q96QD8 SLC38A4, Q969I6
Substrates MeAIB MeAIB MeAIB
L-alanine > L-serine, L-glutamine, L-asparagine, L-histidine, L-alanine, L-methionine > L-asparagine, L-glutamine, L-histidine > L-arginine, L-alanine, L-asparagine, L-lysine >
L-cysteine, L-methionine > glycine, L-threonine, L-proline, L-serine, L-proline, glycine > L-threonine, L-leucine, glycine, L-glutamine, L-serine, L-proline, L-leucine,
L-tyrosine, L-valine [7] L-phenylalanine [283] L-phenylalanine [282]
Stoichiometry 1 Na+ : 1 amino acid (in) [7] 1 Na+ : 1 amino acid (in) [283] 1 Na+ : 1 neutral amino acid (in) [282]
Labelled ligands [14 C]alanine, [3 H]alanine [14 C]alanine, [3 H]alanine [14 C]alanine, [14 C]glycine, [3 H]alanine, [3 H]glycine
Comments – – Transport of cationic amino acids by SNAT4 was
sodium-independent [282].

System N-like transporters

Transporters → SLC superfamily of solute carriers → SLC38 family of sodium-dependent neutral amino acid transporters → System N-like transporters

Nomenclature Sodium-coupled neutral amino acid transporter 3 Sodium-coupled neutral amino acid transporter 5
Systematic nomenclature SLC38A3 SLC38A5
Common abbreviation SNAT3 SNAT5
HGNC, UniProt SLC38A3, Q99624 SLC38A5, Q8WUX1
Substrates MeAIB MeAIB
L-histidine , L-glutamine > L-asparagine, L-alanine > L-glutamic acid [197] L-asparagine, L-serine, L-histidine, L-glutamine > glycine, L-alanine [459]
Stoichiometry 1 Na+ : 1 amino acid (in) : 1 H+ (out) [75] 1 Na+ : 1 amino acid (in) : 1 H+ (out) [459]
Labelled ligands [14 C]glutamine, [3 H]glutamine [14 C]histidine, [3 H]histidine

Searchable database: http://www.guidetopharmacology.org/index.jsp System N-like transporters S469

Orphan SLC38 transporters

Transporters → SLC superfamily of solute carriers → SLC38 family of sodium-dependent neutral amino acid transporters → Orphan SLC38 transporters

Nomenclature Putative sodium-coupled neutral amino acid transporter 7

Systematic nomenclature SLC38A7
Common abbreviation SNAT7
HGNC, UniProt SLC38A7, Q9NVC3
Comments SNAT7/SLC38A7 has been described to be a system N-like transporter allowing preferential accumulation of glutamine (e.g. L-glutamine), histidine (e.g. L-histidine) and asparagine
(e.g. L-asparagine) [302].

SLC39 family of metal ion transporters

Transporters → SLC superfamily of solute carriers → SLC39 family of metal ion transporters
Overview: Along with the SLC30 family, SLC39 family members regulate zinc movement in cells. SLC39 metal ion transporters accumulate zinc into the cytosol. Membrane topology modelling suggests
the presence of eight TM regions with both termini extracellular or in the lumen of intracellular organelles. The mechanism for zinc transport for many members is unknown but appears to involve
co-transport of bicarbonate ions [240, 407].

Nomenclature Zinc transporter 8 Zinc transporter 14

Systematic nomenclature SLC39A8 SLC39A14
Common abbreviation ZIP8 ZIP14
HGNC, UniProt SLC39A8, Q9C0K1 SLC39A14, Q15043
Substrates Cd2+ [132, 407] Cd2+ [240], Mn2+ [240], Fe2+ [408]
Stoichiometry 1 Zn2+ -
(in) : 2 HCO3 (in) [407] –

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC39 family of metal ion transporters S470

Comments: Zinc ﬂuxes may be monitored through the use of radioisotopic Zn-65 or the ﬂuorescent dye FluoZin 3.
The bicarbonate transport inhibitor DIDS has been reported to inhibit cation accumulation through ZIP14 [240].

SLC40 iron transporter

Transporters → SLC superfamily of solute carriers → SLC40 iron transporter

Overview: Alongside the SLC11 family of proton-coupled metal [4, 140]. Ferroportin is essential for iron homeostasis [160]. Ferro- and degradation, lowering the levels of iron export to the blood.
transporters, ferroportin allows the accumulation of iron from the portin is expressed on the surface of cells that store and transport Novel therapeutic agents which stabilise ferroportin or protect it
diet. Whilst SLC11A2 functions on the apical membrane, ferro- iron, such as duodenal enterocytes, hepatocytes, adipocytes and from hepcidin-induced degradation are being developed as anti-
portin acts on the basolateral side of the enterocyte, as well as reticuloendothelial macrophages. Levels of ferroportin are regu- anemia agents. Anti-ferroportin monoclonal antibodies are such
regulating macrophage and placental iron levels. The predicted lated by its association with (binding to) hepcidin, a 25 amino an agent.
topology is of 12 TM domains, with intracellular termini [527], acid hormone responsive to circulating iron levels (amongst other
with the functional transporter potentially a dimeric arrangement signals). Hepcidin binding targets ferroportin for internalisation

Nomenclature Ferroportin
Systematic nomenclature SLC40A1
Common abbreviation IREG1
HGNC, UniProt SLC40A1, Q9NP59
Endogenous substrates Fe2+
Stoichiometry Unknown
Antibodies LY2928057 (Binding) [395]

Comments: Hepcidin (HAMP, P81172), cleaved into hepcidin-25 (HAMP, P81172) and hepcidin-20 (HAMP, P81172), is a small protein that increases upon inﬂammation, binds to ferroportin to regulate
its cellular distribution and degradation. Gene disruption in mice results in embryonic lethality [160], while loss-of-function mutations in man are associated with haemochromatosis [141].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC40 iron transporter S471

SLC41 family of divalent cation transporters

Transporters → SLC superfamily of solute carriers → SLC41 family of divalent cation transporters
Overview: By analogy with bacterial orthologues, this family is probably magnesium transporters. The prokaryote orthologue, MgtE, is responsible for uptake of divalent cations, while the heterologous
expression studies of mammalian proteins suggest Mg2+ efﬂux [369], possibly as a result of co-expression of particular protein partners (see [543]). Topological modelling suggests 10 TM domains with
cytoplasmic C- and N- termini.

Nomenclature Solute carrier family 41 member 1 Solute carrier family 41 member 2

Systematic nomenclature SLC41A1 SLC41A2
Common abbreviation MgtE –
HGNC, UniProt SLC41A1, Q8IVJ1 SLC41A2, Q96JW4
Substrates Co2+ [252], Cu2+ [252], Ba2+ [252], Cd2+ [252], Zn2+ [252], Mg2+ [252], Sr2+ [252], Fe2+ [252] Ba2+ [253], Mg2+ [253], Co2+ [253], Ni2+ [253], Mn2+ [253], Fe2+ [253]
Stoichiometry Unknown Unknown

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC41 family of divalent cation transporters S472

SLC42 family of Rhesus glycoprotein ammonium transporters

Transporters → SLC superfamily of solute carriers → SLC42 family of Rhesus glycoprotein ammonium transporters

Overview: Rhesus is commonly deﬁned as a ‘factor’ that de- associates with these antigens and functions as an ammonium yeast, plants and bacteria. More recent evidence points to family
termines, in part, blood type, and whether neonates suffer from transporter. RhBG and RhBG are non-erythroid related sequences members being permeable to carbon dioxide, leading to the term
haemolytic disease of the newborn. These glycoprotein antigens associated with epithelia. Topological modelling suggests the pres- gas channels.
derive from two genes, RHCE (P18577) and RHD (Q02161), ex- ence of 12TM with cytoplasmic N- and C- termini. The majority
pressed on the surface of erythrocytes. On erythrocytes, RhAG of information on these transporters derives from orthologues in

Nomenclature Ammonium transporter Rh type A Ammonium transporter Rh type B Ammonium transporter Rh type C
Systematic nomenclature SLC42A1 SLC42A2 SLC42A3
Common abbreviation RhAG RhBG RhCG
HGNC, UniProt RHAG, Q02094 RHBG, Q9H310 RHCG, Q9UBD6
Substrates NH4 + [665], NH3 [528], CO2 [179] – NH3 [721]
Stoichiometry Unknown Unknown Unknown
Labelled ligands [14 C]methylamine (Binding) [286] – [14 C]methylamine (Binding) [423] – Mouse

SLC43 family of large neutral amino acid transporters

Transporters → SLC superfamily of solute carriers → SLC43 family of large neutral amino acid transporters

Overview: LAT3 (SLC43A1) and LAT4 (SLC43A2) are transporters put.ative TM domains with both N and C termini located intra- in the pancreas, liver, skeletal muscle and fetal liver [33] whereas
with system L amino acid transporter activity, along with the cellularly. They transport neutral amino acids in a manner inde- LAT4/SLC43A2 is primarily expressed in the placenta, kidney and
structurally and functionally distinct transporters LAT1 and LAT2 pendent of Na+ and Cl- and with two kinetic components [33, peripheral blood leukocytes [64]. SLC43A3 is expressed in vascular
that are members of the SLC7 family. LAT3 and LAT4 contain 12 64]. LAT3/SLC43A1 is expressed in human tissues at high levels endothelial cells [651] but remains to be characterised.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC43 family of large neutral amino acid transporters S473
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Nomenclature L-type amino acid transporter 3 L-type amino acid transporter 4

Systematic nomenclature SLC43A1 SLC43A2
Common abbreviation LAT3 LAT4
HGNC, UniProt SLC43A1, O75387 SLC43A2, Q8N370
Substrates L-isoleucine [33], L-valinol [33], L-leucinol [33], L-phenylalaninol [33], L-leucine [33], L-isoleucine, L-valinol, L-leucinol, L-leucine, L-phenylalanine, L-valine, L-methionine
L-phenylalanine [33], L-valine [33], L-methionine [33]
Stoichiometry Operates by facilitative diffusion Operates by facilitative diffusion

Comments: Covalent modiﬁcation of LAT3 by N-ethylmaleimide inhibits its function [33] and at LAT4 inhibits the low-, but not high-afﬁnity component of transport [64].

SLC44 choline transporter-like family

Transporters → SLC superfamily of solute carriers → SLC44 choline transporter-like family

Overview: Members of the choline transporter-like family are en- with an affinity that is intermediate to that of the high affinity membranes [437]. Transport of choline by CTL2, which in rodents
coded by five genes (CTL1-CTL5) with further diversity occurring choline transporter CHT1 (SLC5A7) and the low affinity organic- is expressed as two isoforms (CTL2P1 and CLTP2; [370]) in lung,
through alternative splicing of CTL1, 4 and 5 [622]. CTL fam- cation transporters [OCT1 (SLC22A1) and OCT2 (SLC22A2)] [438]. colon, inner ear and spleen and to a lesser extent in brain, tongue,
ily members are putative 10TM domain proteins with extracel- CLT1 is expressed almost ubiquitously in human tissues [669] and liver, and kidney, has only recently been demonstrated [370, 458].
lular termini that mediate Na+ -independent transport of choline mediates choline transport across the plasma and mitochondrial CTL3-5 remain to be characterized functionally.

Nomenclature Choline transporter-like 1

Systematic nomenclature SLC44A1
Common abbreviation CTL1
HGNC, UniProt SLC44A1, Q8WWI5
Substrates choline
Stoichiometry Unknown: uptake enhanced in the absence of extracellular Na+ , reduced by membrane depolarization, extracellular acidiﬁcation and collapse of plasma membrane H+ electrochemical
gradient
Inhibitors hemicholinium-3 (pKi 3.5–4.5)

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC44 choline transporter-like family S474

Comments: Data tabulated are features observed for CLT1 endogenous to: rat astrocytes [308]; rat renal tubule epithelial cells [683]; human colon carcinoma cells [373]; human keratinocytes [630] and
human neuroblastoma cells [684]. Choline uptake by CLT1 is inhibited by numerous organic cations (e.g. [308, 683, 684]). In the guinea-pig, CTL2 is a target for antibody-induced hearing loss [454] and
in man, a polymorphism in CTL2 constitutes the human neutrophil alloantigen-3a (HNA-3a; [256]).

SLC45 family of putative sugar transporters

Transporters → SLC superfamily of solute carriers → SLC45 family of putative sugar transporters
Overview: Members of the SLC45 family remain to be fully characterised. SLC45A1 was initially identiﬁed in the rat brain, particularly predominant in the hindbrain, as a proton-associated sugar
transport, induced by hypercapnia [574]. The protein is predicted to have 12TM domains, with intracellular termini. The SLC45A2 gene is thought to encode a transporter protein that mediates melanin
synthesis. Mutations in SLC45A2 are a cause of oculocutaneous albinism type 4 (e.g. [463]), and polymorphisms in this gene are associated with variations in skin and hair color (e.g. [254]).

Nomenclature Proton-associated sugar transporter A

Systematic nomenclature SLC45A1
HGNC, UniProt SLC45A1, Q9Y2W3
Substrates L-glucose [574], Galactose [574]
Stoichiometry Unknown; increased at acid pH [574].

SLC46 family of folate transporters

Transporters → SLC superfamily of solute carriers → SLC46 family of folate transporters
Overview: Based on the proptypical member of this family, PCFT, this family includes proton-driven transporters with 11 TM segments. SLC46A1 has been described to act as an intestinal proton-coupled
high-affinity folic acid transporter [510], with lower affinity for heme. Folic acid accumulation is independent of Na+ or K+ ion concentrations, but driven by extracellular protons with an as yet undefined
stoichiometry.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC46 family of folate transporters S475

Nomenclature Proton-coupled folate transporter

Systematic nomenclature SLC46A1
Common abbreviation PCFT
HGNC, UniProt SLC46A1, Q96NT5
Substrates pemetrexed, N-formyltetrahydrofolate, methotrexate [510] folic acid (1.3μM) > heme (>100 μM) [455]
Endogenous substrates N5 -methyltetrafolate [510]
Labelled ligands [3 H]N5 -methylfolate (Binding), [3 H]folic acid, [3 H]folinic acid (Binding), [3 H]methotrexate, [3 H]pemetrexed (Binding)
Comments Loss-of-function mutations in PCFT (SLC46A1) are the molecular basis for hereditary folate maladsorption [552].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC46 family of folate transporters S476

SLC47 family of multidrug and toxin extrusion transporters

Transporters → SLC superfamily of solute carriers → SLC47 family of multidrug and toxin extrusion transporters
Overview: These proton:organic cation exchangers are predicted to have 13 TM segments [709] and are suggested to be responsible for excretion of many drugs in the liver and kidneys.

Nomenclature Multidrug and toxin extrusion MATE2

Systematic nomenclature SLC47A1 SLC47A2
Common abbreviation MATE1 MATE2-K
HGNC, UniProt SLC47A1, Q96FL8 SLC47A2, Q86VL8
Substrates quinidine [607], cephradine [607], metformin (Km 7.8×10−4 M) [607], cephalexin guanidine [607], procainamide [428], metformin (Km 1.9×10−3 M) [428, 607], aciclovir
[607], cimetidine (Km 1.7×10−4 M) [477, 607], paraquat [108] [607], MPP+ [428], cimetidine (Km 1.2×10−4 M) [428, 607], N1 -methylnicotinamide
[428]
Endogenous substrates thiamine [607], creatine [607] creatine [607], thiamine [607]
Sub/family-selective inhibitors pyrimethamine (pKi 7.1) [320], cimetidine (pKi 6) [627] pyrimethamine (pKi 6.3) [320] – Mouse, cimetidine (pKi 5.1) [627]
Labelled ligands [14 C]TEA [482, 611], [14 C]metformin [607, 611] [14 C]TEA [607], [14 C]metformin [607]

Comments: DAPI has been used to allow quantiﬁcation of MATE1 and MATE2-mediated transport activity [693]. MATE2 and MATE2-B are inactive splice variants of MATE2-K [428].

SLC48 heme transporter

Transporters → SLC superfamily of solute carriers → SLC48 heme transporter
Overview: HRG1 has been identiﬁed as a cell surface and lysosomal heme transporter [517]. In addition, evidence suggests this 4TM-containing protein associates with the V-ATPase in lysosomes [474].
Recent studies conﬁrm its lysosomal location and demonstrate that it has an important physiological function in macrophages ingesting senescent red blood cells (erythrophagocytosis), recycling heme
(released from the red cell hemoglobin) from the phagolysosome into the cytosol, where the heme is subsequently catabolized to recycle the iron [666].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC48 heme transporter S477

Nomenclature Heme transporter

Systematic nomenclature SLC48A1
Common abbreviation HRG1
HGNC, UniProt SLC48A1, Q6P1K1

SLC49 family of FLVCR-related heme transporters

Transporters → SLC superfamily of solute carriers → SLC49 family of FLVCR-related heme transporters

Overview: FLVCR1 was initially identified as a cell-surface at- poiesis. Flvcr1 gene mutations have been identified as the cause Fowler’s syndrome, is associated with a loss-of-function mutation
tachment site for feline leukemia virus subgroup C [601], and of PCARP (posterior column ataxia with retinitis pigmentosa in FLVCR2 [435].
later identified as a cell surface accumulation which exports heme (PCARP) [516].There are three paralogs of FLVCR1 in the human
from the cytosol [513]. A recent study indicates that an isoform of genome.
FLVCR1 is located in the mitochondria, the site of the final steps FLVCR2, most similar to FLVCR1 [403], has been reported to func- The functions of the other two members of the SLC49 family,
of heme synthesis, and appears to transport heme into the cytosol tion as a heme importer [163]. In addition, a congenital syndrome MFSD7 and DIRC2, are unknown, although DIRC2 has been im-
[113]. FLVCR-mediated heme transport is essential for erythro- of proliferative vasculopathy and hydranencephaly, also known as plicated in hereditary renal carcinomas [63].

Nomenclature Feline leukemia virus subgroup C cellular receptor family, member 1 Feline leukemia virus subgroup C cellular receptor family, member 2
Systematic nomenclature SLC49A1 SLC49A2
Common abbreviation FLVCR1 FLVCR2
HGNC, UniProt FLVCR1, Q9Y5Y0 FLVCR2, Q9UPI3
Substrates heme [513] heme [163]
Stoichiometry Unknown Unknown

Comments: Non-functional splice alternatives of FLVCR1 have been implicated as a cause of a congenital red cell aplasia, Diamond Blackfan anemia [525].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC49 family of FLVCR-related heme transporters S478

SLC50 sugar transporter

Transporters → SLC superfamily of solute carriers → SLC50 sugar transporter
Overview: A mouse stromal cell cDNA library was used to clone C2.3 [598], later termed Rag1-activating protein 1, with a sequence homology predictive of a 4TM topology. The plant orthologues,
termed SWEETs, appear to be 7 TM proteins, with extracellular N-termini, and the capacity for bidirectional ﬂux of D-glucose [105]. Expression of mouse SWEET in the mammary gland was suggestive of
a role in Golgi lactose synthesis [105].

Nomenclature SLC50 sugar exporter

Systematic nomenclature SLC50A1
Common abbreviation RAG1AP1
HGNC, UniProt SLC50A1, Q9BRV3

SLC51 family of steroid-derived molecule transporters

Transporters → SLC superfamily of solute carriers → SLC51 family of steroid-derived molecule transporters

Overview: The SLC51 organic solute transporter family of trans- pendent of sodium, potassium, chloride ions or protons [41, tein, while OSTβ is a single TM ’ancillary’ protein, both of which
porters is a pair of heterodimeric proteins which regulate bile 137]. OSTα/OSTβ heterodimers have been shown to trans- are thought to have intracellular C-termini [400]. Both pro-
salt movements in the small intestine, bile duct, and liver, as port [3 H]taurocholic acid, [3 H]dehydroepiandrosterone sulphate, teins function in solute transport and bimolecular ﬂuorescence
part of the enterohepatic circulation [41, 137]. OSTα/OSTβ is [3 H]estrone-3-sulphate, [3 H]pregnenolone sulphate and complementation studies suggest the possibility of OSTα homo-
also expressed in steroidogenic cells of the brain and adrenal 3
[ H]dehydroepiandrosterone sulphate [41, 137, 193]. oligomers, as well as OSTα/OSTβ hetero-oligomers [117, 400]. An
gland, where it may contribute to steroid movement [193]. OSTα/OSTβ-mediated transport of bile salts is inhibited by inherited mutation in OSTβ is associated with congenital diarrhea
Bile acid transport is suggested to be facilitative and inde- clofazimine [635]. OSTα is suggested to be a seven TM pro- in children [591].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC51 family of steroid-derived molecule transporters S479

Nomenclature Organic solute transporter subunit α Organic solute transporter subunit β

Systematic nomenclature SLC51A1 SLC51B
Common abbreviation OSTα OSTβ
HGNC, UniProt SLC51A, Q86UW1 SLC51B, Q86UW2

SLC52 family of riboﬂavin transporters

Transporters → SLC superfamily of solute carriers → SLC52 family of riboflavin transporters
Overview: Riboflavin, also known as vitamin B2, is a precursor of the enzyme cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Riboflavin transporters are predicted to
possess 10 or 11 TM segments.

Nomenclature solute carrier family 52 member 1 solute carrier family 52 member 2 solute carrier family 52 member 3
Systematic nomenclature SLC52A1 SLC52A2 SLC52A3
Common abbreviation RFVT1 RFVT2 RFVT3
HGNC, UniProt SLC52A1, Q9NWF4 SLC52A2, Q9HAB3 SLC52A3, Q9NQ40
Endogenous substrates riboflavin (Km 1.3×10−3 M) [692] riboflavin (Km 9.8×10−4 M) [692] riboflavin (Km 3.3×10−4 M) [692]
Stoichiometry Unknown Unknown H+ -dependent

Comments: Although expressed elsewhere, RFVT3 is found on the luminal surface of intestinal epithelium and is thought to mediate uptake of dietary riboﬂavin, while RFVT1 and RFVT2 are thought
to allow movement from the epithelium into the blood.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC52 family of riboﬂavin transporters S480

SLC53 Phosphate carriers

Transporters → SLC superfamily of solute carriers → SLC53 Phosphate carriers

Nomenclature xenotropic and polytropic retrovirus receptor 1

Systematic nomenclature SLC53A1
HGNC, UniProt XPR1, Q9UBH6
Substrates Phosphate [239]
Comments XPR1/SLC53A1 is a phosphate carrier which appears to play a role in bone and tooth mineralization. It is ubiquitously expressed [44, 600]. The pathological consequences of defective
SLC53A1 expression in the brain [393] and kidney [20] have been reported.

SLC54 Mitochondrial pyruvate carriers

Transporters → SLC superfamily of solute carriers → SLC54 Mitochondrial pyruvate carriers

Nomenclature mitochondrial pyruvate carrier 1 mitochondrial pyruvate carrier 2 mitochondrial pyruvate carrier 1 like
Systematic nomenclature SLC54A1 SLC54A2 SLC54A3
HGNC, UniProt MPC1, Q9Y5U8 MPC2, O95563 MPC1L, P0DKB6
Substrates Pyruvate [73, 289] Pyruvate [73] Pyruvate [642]
Comments SLC54A1 is ubiquitously expressed [642]. SLC54A2 is ubiquitously expressed [642]. SLC54A3 is expressed in testis, postmeiotic spermatids and
sperm cells [642].

Comments: SLC54 family transporters appear to function as mechanisms for accumulating pyruvate into mitochondria to link glycolysis with oxidative phosphorylation.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC54 Mitochondrial pyruvate carriers S481

SLC55 Mitochondrial cation/proton exchangers

Transporters → SLC superfamily of solute carriers → SLC55 Mitochondrial cation/proton exchangers

Nomenclature leucine zipper and EF-hand containing transmembrane leucine zipper and EF-hand containing transmembrane LETM1 domain containing 1
protein 1 protein 2
Systematic nomenclature SLC55A1 SLC55A2 SLC55A3
HGNC, UniProt LETM1, O95202 LETM2, Q2VYF4 LETMD1, Q6P1Q0
Transport type Exchanger / Ca2+ :H+ [328, 569] – –
Exchanger / K+ :H+ [154, 468]
Substrates Ca2+ , K+ , H+ [154, 468, 469, 725] – –
Comments SLC55A1 is ubiquitously expressed [178]. Arguments – –
against SLC55A1’s role as a Ca2+ transporter are outlined
by Zotova et al. (2010) [725].

Comments: The family of SLC55 mitochondrial transporters appear to regulate ion ﬂuxes and to maintain tubular networks.

SLC56 Sideroﬂexins
Transporters → SLC superfamily of solute carriers → SLC56 Sideroﬂexins

Nomenclature sideroflexin 1 sideroflexin 2 sideroflexin 3 sideroflexin 4 sideroflexin 5

Systematic nomenclature SLC56A1 SLC56A2 SLC56A3 SLC56A4 SLC56A5
HGNC, UniProt SFXN1, Q9H9B4 SFXN2, Q96NB2 SFXN3, Q9BWM7 – SFXN5, Q8TD22
Comments Sideroflexin 1 (SFXN1/SLC56A1) was probably In mice sideroflexin 2 Sideroflexin 3 is ubiquitously Sideroflexin 4 is expressed in Sideroflexin 5 is expressed in
falsely identified as a tricarboxylate carrier in the expression is mainly detected expressed in mouse tissues mouse kidney, brain and heart mouse brain and liver [205].
1993 article by Azzi et al. [32], as discussed several in adult kidney and liver [205]. [205]. [205]. The SFXN4a isoform is
years later in [205]. SFXN1 likely transports In human tissues it is detected most highly expressed in
pyridoxin or another heme precursor or the at highest levels in kidney, liver human kidney and pancreas,
5’-aminolevulinate synthase 2 (ALAS2; P22557) and pancreas [694]. and the SFXN4b isoform is
cofactor [205, 694]. SFXN1 has recently been barely detectable in brain
suggested to be a mitochondrial serine transporter [713].
[371]. It is mainly expressed in adult kidney and
liver (mouse) [205].

Comments: These are a family of incompletely-characterised mitochondrial transporters.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC56 Sideroﬂexins S482

SLC57 NiPA-like magnesium transporter family

Transporters → SLC superfamily of solute carriers → SLC57 NiPA-like magnesium transporter family

Nomenclature NIPA magnesium transporter 1 NIPA magnesium transporter 2 NIPA like domain containing 1 NIPA like domain containing 3
Systematic nomenclature SLC57A1 SLC57A2 SLC57A3 SLC57A5
HGNC, UniProt NIPA1, Q7RTP0 NIPA2, Q8N8Q9 NIPAL1, Q6NVV3 NIPAL3, Q6P499
Substrates Sr2+ , Fe2+ and Co2+ to a lesser extent [250], Mg2+ [250] Mg2+ , Sr2+ , Ba2+ , Fe2+ , Cu2+ [250] –
Mg2+ [249]
Comments Human tissue expression: Constitutively – – –
expressed at low levels, with signiﬁcant
enrichment in the brain [515].
Mouse tissue expression: Widely expressed,
including in the heart, kidney, liver, colon,
less in the brain, and not in the small
intestine [249].

SLC58 MagT-like magnesium transporter family

Transporters → SLC superfamily of solute carriers → SLC58 MagT-like magnesium transporter family

Nomenclature magnesium transporter 1 tumor suppressor candidate 3

Systematic nomenclature SLC58A1 SLC58A2
HGNC, UniProt MAGT1, Q9H0U3 TUSC3, Q13454
Transport type Channel-like [511] –
Substrates Mg2+ [251] Mg2+ , Fe2+ , Cu2+ , Mn2+ [250, 511]
Comments Expressed in kidney, colon, heart and liver (the latter only at the mRNA level) [251]; Expressed in placenta, pancreas, testis, ovary, heart, and prostate [418].
universally expressed [714].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC58 MagT-like magnesium transporter family S483

SLC59 Sodium-dependent lysophosphatidylcholine symporter family

Transporters → SLC superfamily of solute carriers → SLC59 Sodium-dependent lysophosphatidylcholine symporter family

Nomenclature major facilitator superfamily domain containing 2A major facilitator superfamily domain containing 2B
Systematic nomenclature SLC59A1 SLC59A2
HGNC, UniProt MFSD2A, Q8NA29 MFSD2B, A6NFX1
Transport type Co-transporter: LPC:Na+ , uptake –
Substrates LPC (lysophosphatidylcholine) form of DHA (docosahexaenoic acid) [464] –
Comments MFSD2B/SLC59A has been suggested to be a sphingosine 1-phosphate transporter in Expressed in the spleen, lung, testis and subcellularly in the ER [19].
erythropoietic cells [364]. It is expressed in brain, intestine, kidney, liver, lung, mammary
gland, and prostate [19]; relatively low expression in BAT (brown adipose tissue), but
upregulated during cold-induced thermogenesis [19]. Subcellular locations: plasma
membrane [656] and ER [19].

SLC60 Glucose transporters

Transporters → SLC superfamily of solute carriers → SLC60 Glucose transporters

Nomenclature major facilitator superfamily domain containing 4A major facilitator superfamily domain containing 4B
Systematic nomenclature SLC60A1 SLC60A2
HGNC, UniProt MFSD4A, Q8N468 MFSD4B, Q5TF39
Transport type – Co-transporter / Na+ (1:1) uptake (Rat) [295]
Substrates – α-Me-glucose, D-glucose [295]
Inhibitors – phloretin [295] – Rat, phlorizin [295] – Rat, urea [460] – Rat
Comments – Expressed in rat kidney (cortex and medulla), brain, liver and lung [295].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC60 Glucose transporters S484

SLC61 Molybdate transporter family

Transporters → SLC superfamily of solute carriers → SLC61 Molybdate transporter family

Nomenclature major facilitator superfamily domain containing 5

Systematic nomenclature SLC61A1
HGNC, UniProt MFSD5, Q6N075
Substrates molybdate [610]
Comments MFSD5/SLC61 is a putative 12TM cell-surface protein which appears to allow the accumulation of molybdate, and where the neural expression appears to respond to changes in the
diet. It is expressed in cervix, stomach, nerve and skin [610]; ubiquitous but higher in skeletal muscle, olfactory bulb [212]; blood, cortex, hypothalamus, cerebellum and spinal cord
(mouse) [494].

SLC62 Pyrophosphate transporters

Transporters → SLC superfamily of solute carriers → SLC62 Pyrophosphate transporters

Nomenclature ANKH inorganic pyrophosphate transport regulator

Systematic nomenclature SLC62A1
HGNC, UniProt ANKH, Q9HCJ1
Substrates Pyrophosphate [292]
Comments ANKH/SLC62 is a putative 8TM membrane protein, also known as progressive ankylosis protein homolog. Mutations in this protein are associated with bone and joint abnormalities. It
is expressed in kidney and bone [92].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC62 Pyrophosphate transporters S485

SLC63 Sphingosine-phosphate transporters

Transporters → SLC superfamily of solute carriers → SLC63 Sphingosine-phosphate transporters
Overview: The SLC63 family of transporters has roles inside the cell (SLC63A1/SPNS1) or on the cell surface (SLC63A2/SPNS2) in sphingolipid transport.

Nomenclature sphingolipid transporter 1 (putative)

Systematic nomenclature SLC63A1
HGNC, UniProt SPNS1, Q9H2V7
Comments Expressed in mitochondria [690].

SLC64 Golgi Ca2+/H+ exchangers

Transporters → SLC superfamily of solute carriers → SLC64 Golgi Ca2+ /H+ exchangers

Nomenclature transmembrane protein 165

Systematic nomenclature SLC64A1
HGNC, UniProt TMEM165, Q9HC07
Transport type Exchanger/ Ca2+ :H+
Substrates Mn2+ [503, 504], Ca2+ , H+ [144]
Comments TMEM165/SLC64 is a putative 6TM intracellular membrane protein. Mutations in the protein are associated with congenital disorder of glycosylation. It has been suggested to be
essential for milk production in the mammary gland [582]. TMEM165 deﬁciency (via siRNA knockdown) causes Golgi glycosylation defects in transfected HEK cells [211].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC64 Golgi Ca2+ /H+ exchangers S486

SLC65 NPC-type cholesterol transporters

Transporters → SLC superfamily of solute carriers → SLC65 NPC-type cholesterol transporters
Overview: The SLC65 family of intracellular cholesterol transporters are 13TM membrane proteins. NPC1/SLC65A1 is an intracellular cholesterol transporter, which together with NPC2 (Uniprot ID
P61916), allows the accumulation into the cytosol of cholesterol acquired from low density lipoproteins.

Nomenclature NPC intracellular cholesterol transporter 1 NPC1 like intracellular cholesterol transporter 1
Systematic nomenclature SLC65A1 SLC65A2
HGNC, UniProt NPC1, O15118 NPC1L1, Q9UHC9
Substrates Cholesterol [309, 310, 496] Cholesterol [10]
Selective antagonists – ezetimibe (Inhibition) (pKd 6.7) [227]
Comments Expression is ubiquitous [10], with highest levels detected in liver, lung, and pancreas Expressed in small intestine, gallbladder, liver, testis and stomach [10].
[136]. NPC1 plays a critical role in the regulation of intracellular cholesterol trafﬁcking
[93]. Mutations in the NPC1 gene have been identiﬁed in patients with the lipid storage
disorder Niemann-Pick disease type C1 [62, 93, 255, 686].

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC65 NPC-type cholesterol transporters S487

SLCO family of organic anion transporting polypeptides

Transporters → SLC superfamily of solute carriers → SLCO family of organic anion transporting polypeptides

Overview: The SLCO superfamily is comprised of the organic an- cells throughout the body. They have 12 TM domains and intra- the multispeciﬁcity of these proteins, this guide lists classes of sub-
ion transporting polypeptides (OATPs). The 11 human OATPs are cellular termini, with multiple putative glycosylation sites. OATPs strates and inhibitors for each family member. More comprehen-
divided into 6 families and ten subfamilies based on amino acid mediate the sodium-independent uptake of a wide range of am- sive lists of substrates, inhibitors, and their relative afﬁnities may
identity. These proteins are located on the plasma membrane of phiphilic substrates, including many drugs and toxins. Due to be found in the review articles listed below.

Nomenclature OATP1A2 OATP1B1 OATP1B3 OATP1C1

Systematic nomenclature SLCO1A2 SLCO1B1 SLCO1B3 SLCO1C1
HGNC, UniProt SLCO1A2, P46721 SLCO1B1, Q9Y6L6 SLCO1B3, Q9NPD5 SLCO1C1, Q9NYB5
Substrates fluoroquinolones, beta blockers, deltorphin II, statins, opioids, β-lactam antibiotics, bile rifampicin, opioids, sartans, statins, statins, bromsulphthalein
rosuvastatin, fexofenadine, bromsulphthalein, acid derivatives and conjugates, digoxin, anticancer drugs,
anticancer drugs, antibiotics, HIV protease inhibitors, bromsulphthalein, anticancer drugs, HIV bromsulphthalein, bile acid derivatives
talinolol, ouabain, microcystin-LR [204] protease inhibitors, fexofenadine, and conjugates, β-lactam antibiotics,
antifungals, ACE inhibitors, rifampicin, ouabain, amanitin, saquinavir,
endothelin receptor antagonists, sartans fexofenadine, erythromycin, phalloidin
Endogenous substrates bile acids, thyroid hormones, steroid conjugates, leukotrienes, steroid conjugates, thyroid steroid conjugates, thyroid hormones, thyroid hormones, steroid conjugates
bilirubin, PGE2 hormones, bile acids, bilirubin bile acids, CCK-8 (CCK, P06307),
bilirubin, LTC4
Ligands – pravastatin (Binding) – –
Inhibitors rifamycin SV (pKi 5) [646], rifampicin (pKi 4.3) [646], cyclosporin A (pKi 7.3) [196, 344], cyclosporin A (pIC50 6.1) [344, 623], DPDPE, probenecid, taurocholic acid
naringin [36] estrone-3-sulphate (pIC50 7.2) [267], sildenafil (pIC50 6.1) [623], rifampicin
rifampicin (pKi 6) [344], rifamycin SV (pIC50 5.8) [344, 623], gemfibrozil,
(pKi 5.7) [646], gemfibrozil [471], glycyrrhizin, rifamycin SV
glycyrrhizin, indocyanine green
Labelled ligands [3 H]BSP, [3 H]DPDPE, [3 H]estrone-3-sulphate [3 H]estradiol-17β-glucuronide, [3 H]BSP, [125 I]thyroxine, [3 H]BSP,
[3 H]estrone-3-sulphate [3 H]CCK-8 (human, mouse, rat), [3 H]estrone-3-sulphate
[3 H]estradiol-17β-glucuronide
Comments Although rat and mouse OATP1A4 are considered the Other inhibitors include, fibrates, Other inhibitors include, HIV protease –
orthologs of human OATP1A2 we do not cross-link to flavonoids, glitazones and macrolide inhibitors, glitazones and macrolide
gene or protein databases for these since in reality antibiotics. Estrone-3-sulphate or the antibiotics. CCK-8 is used as an
there are five genes in rodents that arose through gene drug substrates atorvastatin, pravastatin OATP1B3-selective probe.
duplication in this family and it is not clear which one and rosuvastatin are used as a probe.
of these is the "true" ortholog.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLCO family of organic anion transporting polypeptides S488
Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14753/full
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493

Nomenclature OATP2A1 OATP2B1 OATP3A1 OATP4A1 OATP4C1

Systematic nomenclature SLCO2A1 SLCO2B1 SLCO3A1 SLCO4A1 SLCO4C1
HGNC, UniProt SLCO2A1, Q92959 SLCO2B1, O94956 SLCO3A1, Q9UIG8 SLCO4A1, Q96BD0 SLCO4C1, Q6ZQN7
Substrates synthetic prostaglandin derivatives amiodarone, bromsulphthalein, – penicillin G dipeptidyl peptidase-4
statins, glibenclamide, aliskiren, inhibitors, anticancer drugs,
fexofenadine, talinolol, cardiac glycosides
bosentan, telmisartan
Endogenous substrates prostaglandins, eicosanoids estrone-3-sulphate, BQ123, vasopressin (AVP, thyroid hormones, thyroid hormones, cyclic AMP,
dehydroepiandrosterone P01185), thyroid hormones, prostaglandins, bile acids, steroid conjugates
sulphate, T4 prostaglandins steroid conjugates
Inhibitors bromocresol green (Inhibition of PGF2α erlotinib (pKi 6.3) [344], – – –
uptake in PGT-expressing HeLa cells) (pKi 5.4) verlukast (pKi 5.6) [344],
[337] – Rat, bromsulphthalein (Inhibition of gemﬁbrozil, glibenclamide,
PGF2α uptake in PGT-expressing HeLa cells) rifamycin SV, sildenaﬁl [623]
(pKi 5.2) [337] – Rat
Labelled ligands [3 H]PGE2 (Binding) [98] [3 H]BSP, [3 H]estrone-3-sulphate [3 H]PGE2 , [3 H]estrone-3-sulphate [3 H]digoxin
[3 H]estrone-3-sulphate
Comments Other inhibitors include NSAIDs Other inhibitors include – – –
glitazones and citrus juices

Searchable database: http://www.guidetopharmacology.org/index.jsp References S490

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The Concise Guide To Pharmacology 201920 Transport

Uploaded by

The Concise Guide To Pharmacology 201920 Transport

Uploaded by

S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters.

British Journal of Pharmacology (2019) 176, S397–S493

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp Transporters S397

Searchable database: http://www.guidetopharmacology.org/index.jsp Transporters S398

ATP-binding cassette transporter family

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCA subfamily S399

Nomenclature ABCA1 ABCA3 ABCA4

Nomenclature ABCA5 ABCA6 ABCA7 ABCA12

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCA subfamily S400

Nomenclature ABCB1 ABCB2 ABCB3

Nomenclature ABCB4 ABCB5 ABCB6

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCB subfamily S401

Nomenclature ABCB7 ABCB8 ABCB9

Nomenclature ABCB10 ABCB11

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCB subfamily S402

Nomenclature ABCC1 ABCC2 ABCC3

Nomenclature ABCC4 ABCC5 ABCC6

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCC subfamily S403

Nomenclature ATP-binding cassette, sub-family C (CFTR/MRP), member 8 ABCC9 ABCC11

ABCD subfamily of peroxisomal ABC transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCD subfamily of peroxisomal ABC transporters S404

Nomenclature ABCD1 ABCD2 ABCD3

Nomenclature ABCG1 ABCG2 ABCG4 ABCG5 ABCG8

Searchable database: http://www.guidetopharmacology.org/index.jsp ABCG subfamily S405

Further reading on ATP-binding cassette transporter family

F-type and V-type ATPases

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp F-type ATPase S406

Information on members of this family may be found in the online database.

Further reading on F-type and V-type ATPases

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp Na+/K+-ATPases S407

Information on members of this family may be found in the online database.

Information on members of this family may be found in the online database.

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp Cu+ -ATPases S408

Information on members of this family may be found in the online database.

Further reading on P-type ATPases

SLC superfamily of solute carriers

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC superfamily of solute carriers S409

SLC1 family of amino acid transporters

Glutamate transporter subfamily

Searchable database: http://www.guidetopharmacology.org/index.jsp Glutamate transporter subfamily S410

Searchable database: http://www.guidetopharmacology.org/index.jsp Glutamate transporter subfamily S411

Alanine/serine/cysteine transporter subfamily

Nomenclature Alanine/serine/cysteine transporter 1 Alanine/serine/cysteine transporter 2

Further reading on SLC1 family of amino acid transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp Alanine/serine/cysteine transporter subfamily S412

SLC2 family of hexose and sugar alcohol transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp Class I transporters S413

Nomenclature Glucose transporter 5 Glucose transporter 7 Glucose transporter 9

Searchable database: http://www.guidetopharmacology.org/index.jsp Class II transporters S414

Proton-coupled inositol transporter

Nomenclature Proton myo-inositol cotransporter

Further reading on SLC2 family of hexose and sugar alcohol transporters

SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

Information on members of this family may be found in the online database.

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC3 family S415

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC7 family S416

SLC4 family of bicarbonate transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp Anion exchangers S417

Sodium-dependent HCO3- transporters

Further reading on SLC4 family of bicarbonate transporters

SLC5 family of sodium-dependent glucose transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp SLC5 family of sodium-dependent glucose transporters S418

Hexose transporter family

Searchable database: http://www.guidetopharmacology.org/index.jsp Hexose transporter family S419

Searchable database: http://www.guidetopharmacology.org/index.jsp Choline transporter S420

Sodium iodide symporter, sodium-dependent multivitamin

Nomenclature NIS SMVT SMCT1 SMCT2

Searchable database: http://www.guidetopharmacology.org/index.jsp Sodium ionide symporter, sodium-dependent multivitamin S421

Sodium myo-inositol cotransporter transporters

Nomenclature SMIT SGLT6

Further reading on SLC5 family of sodium-dependent glucose transporters

Searchable database: http://www.guidetopharmacology.org/index.jsp Sodium myo-inositol cotransporter transporters S422