UniProt is a freely accessible database of

protein sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...

and functional information, many entries being derived from

genome sequencing project Genome projects are scientific endeavours that ultimately aim to determine the complete genome sequence of an organism (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist or a virus) and to annotate protein-coding genes and ot ...

s. It contains a large amount of information about the biological function of proteins derived from the research literature. It is maintained by the UniProt consortium, which consists of several European

bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

organisations and a foundation from

Washington, DC ) , image_skyline = , image_caption = Clockwise from top left: the Washington Monument and Lincoln Memorial on the National Mall, United States Capitol, Logan Circle, Jefferson Memorial, White House, Adams Morgan ...

, United States.

The UniProt consortium

The UniProt consortium comprises the

European Bioinformatics Institute The European Bioinformatics Institute (EMBL-EBI) is an Intergovernmental Organization (IGO) which, as part of the European Molecular Biology Laboratory (EMBL) family, focuses on research and services in bioinformatics. It is located on the Wel ...

(EBI), the Swiss Institute of Bioinformatics (SIB), and the

Protein Information Resource The Protein Information Resource (PIR), located at Georgetown University Medical Center, is an integrated public bioinformatics resource to support genomic and proteomic research, and scientific studies. It contains protein sequences databases H ...

(PIR). EBI, located at the

Wellcome Trust Genome Campus The Wellcome Genome Campus is a scientific research campus built in the grounds of Hinxton Hall, Hinxton in Cambridgeshire, England. Campus The Campus is home to some institutes and organisations in genomics and computational biology. The C ...

in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy (Expert Protein Analysis System) servers that are a central resource for proteomics tools and databases. PIR, hosted by the National Biomedical Research Foundation (NBRF) at the Georgetown University Medical Center in Washington, DC, US, is heir to the oldest protein sequence database,

Margaret Dayhoff Margaret Belle (Oakley) Dayhoff (March 11, 1925 – February 5, 1983) was an American physical chemist and a pioneer in the field of bioinformatics. Dayhoff was a professor at Georgetown University Medical Center and a noted research biochem ...

's Atlas of Protein Sequence and Structure, first published in 1965. In 2002, EBI, SIB, and PIR joined forces as the UniProt consortium.

The roots of the UniProt databases

Each consortium member is heavily involved in protein database maintenance and annotation. Until recently, EBI and SIB together produced the Swiss-Prot and TrEMBL databases, while PIR produced the Protein Sequence Database (PIR-PSD). These databases coexisted with differing

coverage and annotation priorities. Swiss-Prot was created in 1986 by

Amos Bairoch Amos Bairoch (born 22 November 1957) is a Swiss bioinformatician and Professor of Bioinformatics at the Department of Human Protein Sciences of the University of Geneva where he leads the CALIPHO group at the Swiss Institute of Bioinformatics (S ...

during his PhD and developed by the Swiss Institute of Bioinformatics and subsequently developed by

Rolf Apweiler Rolf Apweiler is a director of European Bioinformatics Institute (EBI) part of the European Molecular Biology Laboratory (EMBL) with Ewan Birney. Education Apweiler gained his PhD in biochemistry from Heidelberg University. Research Apweiler has ...

at the

. Swiss-Prot aimed to provide reliable protein sequences associated with a high level of annotation (such as the description of the function of a protein, its

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

structure,

post-translational modifications Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosom ...

, variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recognizing that sequence data were being generated at a pace exceeding Swiss-Prot's ability to keep up, TrEMBL (Translated EMBL Nucleotide Sequence Data Library) was created to provide automated annotations for those proteins not in Swiss-Prot. Meanwhile, PIR maintained the PIR-PSD and related databases, including iProClass, a database of protein sequences and curated families. The consortium members pooled their overlapping resources and expertise, and launched UniProt in December 2003.

Organization of the UniProt databases

UniProt provides four core databases: UniProtKB (with sub-parts Swiss-Prot and TrEMBL), UniParc, and UniRef.

UniProtKB

UniProt Knowledgebase (UniProtKB) is a protein database partially curated by experts, consisting of two sections: UniProtKB/Swiss-Prot (containing reviewed, manually annotated entries) and UniProtKB/TrEMBL (containing unreviewed, automatically annotated entries). , release "2014_03" of UniProtKB/Swiss-Prot contains 542,782 sequence entries (comprising 193,019,802 amino acids abstracted from 226,896 references) and release "2014_03" of UniProtKB/TrEMBL contains 54,247,468 sequence entries (comprising 17,207,833,179 amino acids).

UniProtKB/Swiss-Prot

UniProtKB/Swiss-Prot is a manually annotated, non-redundant protein sequence database. It combines information extracted from scientific literature and

biocurator Biocuration is the field of life sciences dedicated to organizing biomedical data, information and knowledge into structured formats, such as spreadsheets, tables and knowledge graphs. The biocuration of biomedical knowledge is made possible by th ...

-evaluated computational analysis. The aim of UniProtKB/Swiss-Prot is to provide all known relevant information about a particular protein. Annotation is regularly reviewed to keep up with current scientific findings. The manual annotation of an entry involves detailed analysis of the protein sequence and of the scientific literature. Sequences from the same

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

and the same

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

are merged into the same database entry. Differences between sequences are identified, and their cause documented (for example

alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...

, natural variation, incorrect

initiation Initiation is a rite of passage marking entrance or acceptance into a group or society. It could also be a formal admission to adulthood in a community or one of its formal components. In an extended sense, it can also signify a transformation ...

sites, incorrect

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

boundaries, frameshifts, unidentified conflicts). A range of sequence analysis tools is used in the annotation of UniProtKB/Swiss-Prot entries. Computer-predictions are manually evaluated, and relevant results selected for inclusion in the entry. These predictions include post-translational modifications,

transmembrane domain A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...

s and

topology In mathematics, topology (from the Greek language, Greek words , and ) is concerned with the properties of a mathematical object, geometric object that are preserved under Continuous function, continuous Deformation theory, deformations, such ...

, signal peptides, domain identification, and

protein family A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be c ...

classification. Relevant publications are identified by searching databases such as

PubMed PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain the ...

. The full text of each paper is read, and information is extracted and added to the entry. Annotation arising from the scientific literature includes, but is not limited to: *Protein and gene names *Function *

Enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

-specific information such as catalytic activity,

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...

and catalytic residues *

Subcellular location The cells of eukaryotic organisms are elaborately subdivided into functionally-distinct membrane-bound compartments. Some major constituents of eukaryotic cells are: extracellular space, plasma membrane, cytoplasm, nucleus, mitochondria, Golgi ...

* Protein-protein interactions *Pattern of expression *Locations and roles of significant domains and sites *

Ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

-, substrate- and cofactor-binding sites *Protein variant forms produced by natural genetic variation,

RNA editing RNA editing (also RNA modification) is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. It occurs in all living organism ...

, alternative splicing,

proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

processing, and post-translational modification Annotated entries undergo quality assurance before inclusion into UniProtKB/Swiss-Prot. When new data becomes available, entries are updated.

UniProtKB/TrEMBL

UniProtKB/TrEMBL contains high-quality computationally analyzed records, which are enriched with automatic annotation. It was introduced in response to increased dataflow resulting from genome projects, as the time- and labour-consuming manual annotation process of UniProtKB/Swiss-Prot could not be broadened to include all available protein sequences. The translations of annotated coding sequences in the EMBL-Bank/GenBank/DDBJ nucleotide sequence database are automatically processed and entered in UniProtKB/TrEMBL. UniProtKB/TrEMBL also contains sequences from PDB, and from gene prediction, including

Ensembl Ensembl genome database project is a scientific project at the European Bioinformatics Institute, which provides a centralized resource for geneticists, molecular biologists and other researchers studying the genomes of our own species and other v ...

RefSeq The Reference Sequence (RefSeq) database 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. This database is built by National ...

and CCDS. Since 22 July 2021 it also includes predicted with

AlphaFold AlphaFold is an artificial intelligence (AI) program developed by DeepMind, a subsidiary of Alphabet, which performs predictions of protein structure. The program is designed as a deep learning system. AlphaFold AI software has had two major ve ...

tertiary and Alphafold-multimer can even do quaternary structures.

UniParc

UniProt Archive (UniParc) is a comprehensive and non-redundant database, which contains all the protein sequences from the main, publicly available protein sequence databases. Proteins may exist in several different source databases, and in multiple copies in the same database. In order to avoid redundancy, UniParc stores each unique sequence only once. Identical sequences are merged, regardless of whether they are from the same or different species. Each sequence is given a stable and unique identifier (UPI), making it possible to identify the same protein from different source databases. UniParc contains only protein sequences, with no annotation. Database cross-references in UniParc entries allow further information about the protein to be retrieved from the source databases. When sequences in the source databases change, these changes are tracked by UniParc and history of all changes is archived.

Source databases

Currently UniParc contains protein sequences from the following publicly available databases: *

INSDC The International Nucleotide Sequence Database Collaboration (INSDC) consists of a joint effort to collect and disseminate databases containing DNA and RNA sequences. It involves the following computerized databases: DNA Data Bank of Japan (Japan ...

EMBL-Bank/

DDBJ The DNA Data Bank of Japan (DDBJ) is a biological database that collects DNA sequences. It is located at the National Institute of Genetics (NIG) in the Shizuoka prefecture of Japan. It is also a member of the International Nucleotide Sequence D ...

GenBank The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a part ...

nucleotide sequence databases *

European Patent Office The European Patent Office (EPO) is one of the two organs of the European Patent Organisation (EPOrg), the other being the Administrative Council. The EPO acts as executive body for the organisation

(EPO) * FlyBase: the primary repository of genetic and molecular data for the insect family Drosophilidae (FlyBase) * H-Invitational Database (H-Inv) * International Protein Index (IPI) *

Japan Patent Office The is a Japanese governmental agency in charge of industrial property right affairs, under the Ministry of Economy, Trade and Industry. The Japan Patent Office is located in Kasumigaseki, Chiyoda, Tokyo and is one of the world's largest pa ...

(JPO) *

(PIR-PSD) *

Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...

(PDB) * Protein Research Foundation (PRF) *

Saccharomyces Genome Database The ''Saccharomyces'' Genome Database (SGD) is a scientific database of the molecular biology and genetics of the yeast ''Saccharomyces cerevisiae'', which is commonly known as baker's or budding yeast. ''Saccharomyces'' Genome Database The SGD ...

(SGD) *

The Arabidopsis Information Resource The Arabidopsis Information Resource (TAIR) is a community resource and online model organism database of genetic and molecular biology data for the model plant ''Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress o ...

(TAIR) * TROMEftp://ftp.isrec.isb-sib.ch/pub/databases/trome *

US Patent Office The United States Patent and Trademark Office (USPTO) is an agency in the U.S. Department of Commerce that serves as the national patent office and trademark registration authority for the United States. The USPTO's headquarters are in Alexa ...

(USPTO) * UniProtKB/Swiss-Prot, UniProtKB/Swiss-Prot protein isoforms, UniProtKB/TrEMBL * Vertebrate and Genome Annotation Database (VEGA) * WormBase

UniRef

The UniProt Reference Clusters (UniRef) consist of three databases of clustered sets of protein sequences from UniProtKB and selected UniParc records. The UniRef100 database combines identical sequences and sequence fragments (from any

organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...

) into a single UniRef entry. The sequence of a representative protein, the accession numbers of all the merged entries and links to the corresponding UniProtKB and UniParc records are displayed. UniRef100 sequences are clustered using the CD-HIT

algorithm In mathematics and computer science, an algorithm () is a finite sequence of rigorous instructions, typically used to solve a class of specific Computational problem, problems or to perform a computation. Algorithms are used as specificat ...

to build UniRef90 and UniRef50. Each cluster is composed of sequences that have at least 90% or 50% sequence identity, respectively, to the longest sequence. Clustering sequences significantly reduces database size, enabling faster sequence searches. UniRef is available from th
UniProt FTP site

Funding

UniProt is funded by grants from the

National Human Genome Research Institute The National Human Genome Research Institute (NHGRI) is an institute of the National Institutes of Health, located in Bethesda, Maryland. NHGRI began as the Office of Human Genome Research in The Office of the Director in 1988. This Office transi ...

, the

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

(NIH), the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

, the Swiss Federal Government through the Federal Office of Education and Science, NCI-caBIG, and the US Department of Defense.

References

External links

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