RefSeq

The Reference Sequence (RefSeq) database[1]

Refseq
is an open access, annotated and curated
collection of publicly available nucleotide
sequences (DNA, RNA) and their protein
products. RefSeq was first introduced in
2000.[2][3] This database is built by National
Center for Biotechnology Information (NCBI), Content
and, unlike GenBank, provides only a single Description curated non-redundant sequence
record for each natural biological molecule (i.e.
database of genomes.
DNA, RNA or protein) for major organisms
ranging from viruses to bacteria to eukaryotes. Contact
Research center National Center for Biotechnology
For each model organism, RefSeq aims to
Information
provide separate and linked records for the
[1]
genomic DNA, the gene transcripts, and the Primary citation Pruitt KD & al. (2005)
proteins arising from those transcripts. RefSeq Access
is limited to major organisms for which
Website https://www.ncbi.nlm.nih.gov/RefSeq
sufficient data are available (121,461 distinct
"named" organisms as of July 2022),[4] while
GenBank includes sequences for any organism submitted (approximately 504,000 formally described
species).[5]

RefSeq categories
RefSeq collection comprises different data types, with different origins, so it is necessary to establish
standard categories and identifiers to store each data type. The most important categories are:

RefSeq accession categories and molecule types

Category Description

NC Complete genomic molecules

NG Incomplete genomic region

NM mRNA

NR ncRNA
NP Protein

XM predicted mRNA model

XR predicted ncRNA model

XP predicted Protein model (eukaryotic sequences)

WP predicted Protein model (prokaryotic sequences)

For more details and more categories, see Table 1 (https://www.ncbi.nlm.nih.gov/books/NBK21091/table/c
h18.T.entrez_queries_to_retrieve_sets_o) in Chapter 18 of the book The Reference Sequence (RefSeq)
Database (https://www.ncbi.nlm.nih.gov/books/NBK21091).

RefSeq Projects
Several projects to improve RefSeq services are currently in development by the NCBI, often in
collaboration with research centers such as EMBL-EBI:

Consensus CDS (CCDS): This project aims to identify a core set of human and mouse
protein-coding regions and standardize sets of genes with high and consistent levels of
genomic annotation quality. This project was announced in 2009 and is still in
development.[6][7]
RefSeq Functional Elements (RefSeqFE): It is focused on describing non-genic functional
elements which are gene regulatory regions such as: enhancers, silencers, DNase I
hypersensitive regions, DNA replication origins etc.). The current scope of this project is
restricted to the human and mouse genomes.[8]
RefSeqGene: Its main goal is to define genomic sequences to be used as reference
standards for well-characterized genes. Previously described mRNA, protein and
chromosome sequences have the weaknesses of not providing explicit genomic coordinates
of gene flanking and intronic regions as well as showing awkwardly large coordinates that
change with every new genome assembly. The RefSeqGene project is designed to
eliminate these errors.[9]
Targeted Loci: This project records molecular markers, specially protein-coding and
ribosomal RNA loci that are used for phylogenetic and barcoding analysis. The scope of this
project includes sequences for Archaea, Bacteria and Fungi organisms, accessible via
Entrez and BLAST queries. It also includes GenBank sequences for Animals, Plants and
Protists, accessible via BLAST queries.[10]
Virus Variation (ViV): It is a specific resource of sequence data processing pipelines and
analysis tools for display and retrieval of sequences from several viral groups such as
influenza virus, ebolavirus, MERS coronavirus or Zika virus. New viruses, processing
pipelines, tools and other features are included regularly.[11]
RefSeq Select: This project aims to select datasets of RefSeq Select transcripts, as the
most representative for every protein-coding gene, based on multiple criteria: prior use in
clinical databases, transcript expression, evolutionary conservation of the coding region etc.
Since many genes are represented by multiple RefSeq transcripts/proteins due to the
biological process of alternative splicing, this complexity is problematic for studies such as
comparative genomics or exchange of clinical variant data.[12]
MANE (Matched Annotation from the NCBI and EMBL-EBI): It is a collaborative project
between NCBI and EMBL-EBI whose main goal is to define a set of transcripts and their
proteins for all the protein-coding genes in the human genome. By doing that, the differences
in transcripts annotation between RefSeq and Ensembl/GENCODE annotation systems are
reduced. A MANE Select transcripts set are created as a useful universal standard for
clinical reporting and comparative or evolutionary genomics. A second MANE Plus Clinical
set are also created with additional transcripts to report all Pathogenic (P) or Likely
Pathogenic (LP) clinical variants available in public resources.[13] This project was
announced in 2018 and is expected to finish in 2022.

Statistics
According to the RefSeq release 213 (July 2022), the number of species represented in the database by
counting distinct taxonomic IDs are as follows:[4]

Taxonomic ID Species

Archaea 1443
Bacteria 69122

Complete 121461

Fungi 16869
Invertebrate 5715

Mitochondrion 13648

Plant 9177
Plasmid 6073

Plastid 9430

Protozoa 746
Vertebrate (mammalian) 1509

Viral 11620

Vertebrate (other) 5237

Other 4

The counts of accession and basepairs per molecule type are:[4]

Molecule type Accessions Basepairs/residues

Genomics 40,758,769 2.923212393984 × 1012

RNA 45,781,716 1.22253022047 × 1011

Protein 234,520,053 9.129062394 × 1010

See also
GenBank
Sequence analysis
Sequence profiling tool
Sequence motif
UniProt
List of sequenced eukaryotic genomes
List of sequenced archaeal genomes

References
1. Pruitt KD, Tatusova T, Maglott DR (January 2005). "NCBI Reference Sequence (RefSeq): a
curated non-redundant sequence database of genomes, transcripts and proteins" (https://ww
w.ncbi.nlm.nih.gov/pmc/articles/PMC539979). Nucleic Acids Research. 33 (Database
issue): D501–D504. doi:10.1093/nar/gki025 (https://doi.org/10.1093%2Fnar%2Fgki025).
 PMC 539979 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539979). PMID 15608248 (http
s://pubmed.ncbi.nlm.nih.gov/15608248).
2. Maglott DR, Katz KS, Sicotte H, Pruitt KD (January 2000). "NCBI's LocusLink and RefSeq"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102393). Nucleic Acids Research. 28 (1):
126–128. doi:10.1093/nar/28.1.126 (https://doi.org/10.1093%2Fnar%2F28.1.126).
PMC 102393 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102393). PMID 10592200 (http
s://pubmed.ncbi.nlm.nih.gov/10592200).
3. Pruitt KD, Katz KS, Sicotte H, Maglott DR (January 2000). "Introducing RefSeq and
LocusLink: curated human genome resources at the NCBI". Trends in Genetics. 16 (1): 44–
47. doi:10.1016/s0168-9525(99)01882-x (https://doi.org/10.1016%2Fs0168-9525%2899%29
01882-x). PMID 10637631 (https://pubmed.ncbi.nlm.nih.gov/10637631).
4. RefSeq Release 213 Statistics (http://ftp.ncbi.nlm.nih.gov/refseq/release/release-notes/)
(Report). National Library of Medicine. 11 July 2022. Retrieved 20 July 2022.
5. Sayers EW, Cavanaugh M, Clark K, Pruitt KD, Schoch CL, Sherry ST, Karsch-Mizrachi I
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consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set
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9). Genome Research. 19 (7): 1316–1323. doi:10.1101/gr.080531.108 (https://doi.org/10.110
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"Consensus coding sequence (CCDS) database: a standardized set of human and mouse
protein-coding regions supported by expert curation" (https://www.ncbi.nlm.nih.gov/pmc/artic
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11. Hatcher EL, Zhdanov SA, Bao Y, Blinkova O, Nawrocki EP, Ostapchuck Y, et al. (January
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13. Morales J, Pujar S, Loveland JE, Astashyn A, Bennett R, Berry A, et al. (April 2022). "A joint
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Sources
 This article incorporates public domain material from NCBI Handbook (https://www.ncbi.nl
m.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=handbook.TOC&depth=2). National
Center for Biotechnology Information.

External links
RefSeq (https://www.ncbi.nlm.nih.gov/RefSeq)
GenBank, RefSeq, TPA and UniProt: What's in a Name? (https://www.ncbi.nlm.nih.gov/book
s/NBK21105/#ch1.Appendix_GenBank_RefSeq_TPA_and_UniP)

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