InterPro

InterPro is a database of protein families,

protein domains and functional sites in which
InterPro
identifiable features found in known proteins
can be applied to new protein sequences[2] in
order to functionally characterise them.[3][4]

The contents of InterPro consist of diagnostic Content

signatures and the proteins that they Description InterPro functionally analyzes
significantly match. The signatures consist of protein sequences and classifies
models (simple types, such as regular them into protein families while
expressions or more complex ones, such as predicting the presence of domains
Hidden Markov models) which describe and functional sites.
protein families, domains or sites. Models are
built from the amino acid sequences of known Contact
families or domains and they are subsequently Research center EMBL
used to search unknown sequences (such as
Laboratory European Bioinformatics Institute
those arising from novel genome sequencing)
in order to classify them. Each of the member Primary citation The InterPro protein families and
databases of InterPro contributes towards a domains database: 20 years on[1]
different niche, from very high-level, structure- Release date 1999
based classifications (SUPERFAMILY and
CATH-Gene3D) through to quite specific sub- Access
family classifications (PRINTS and Website www.ebi.ac.uk/interpro/ (http://www.
PANTHER). ebi.ac.uk/interpro/)

InterPro's intention is to provide a one-stop- Download URL ftp.ebi.ac.uk/pub/databases/interpro/

shop for protein classification, where all the (http://ftp.ebi.ac.uk/pub/databases/in
signatures produced by the different member terpro/)
databases are placed into entries within the Miscellaneous
InterPro database. Signatures which represent
equivalent domains, sites or families are put Data release
8-weekly
into the same entry and entries can also be frequency
related to one another. Additional information Version 91.0 (13 October 2022)
such as a description, consistent names and
Gene Ontology (GO) terms are associated with each entry, where possible.

Data contained in InterPro

InterPro contains three main entities: proteins, signatures (also referred to as "methods" or "models") and
entries. The proteins in UniProtKB are also the central protein entities in InterPro. Information regarding
which signatures significantly match these proteins are calculated as the sequences are released by
UniProtKB and these results are made available to the public (see below). The matches of signatures to
proteins are what determine how signatures are integrated together into InterPro entries: comparative
overlap of matched protein sets and the location of the signatures' matches on the sequences are used as
indicators of relatedness. Only signatures deemed to be of sufficient quality are integrated into InterPro. As
of version 81.0 (released 21 August 2020) InterPro entries annotated 73.9% of residues found in
UniProtKB with another 9.2% annotated by signatures that are pending integration.[5]

The coverage of UniProtKB residues by InterPro entries as of InterPro version 81.0.[5]

InterPro also includes data for splice variants and the proteins contained in the UniParc and UniMES
databases.

InterPro consortium member databases

The signatures from InterPro come from 13 "member databases", which are listed below.

CATH-Gene3D
Describes protein families and domain architectures in complete genomes. Protein
families are formed using a Markov clustering algorithm, followed by multi-linkage
clustering according to sequence identity. Mapping of predicted structure and sequence
domains is undertaken using hidden Markov models libraries representing CATH and
Pfam domains. Functional annotation is provided to proteins from multiple resources.
Functional prediction and analysis of domain architectures is available from the Gene3D
website.
CDD
Conserved Domain Database is a protein annotation resource that consists of a collection
of annotated multiple sequence alignment models for ancient domains and full-length
proteins. These are available as position-specific score matrices (PSSMs) for fast
identification of conserved domains in protein sequences via RPS-BLAST.
HAMAP
Stands for High-quality Automated and Manual Annotation of microbial Proteomes.
HAMAP profiles are manually created by expert curators they identify proteins that are part
 of well-conserved bacterial, archaeal and plastid-encoded (i.e. chloroplasts, cyanelles,
apicoplasts, non-photosynthetic plastids) proteins families or subfamilies.
MobiDB
MobiDB is database annotating intrinsic disorder in proteins.
PANTHER
PANTHER is a large collection of protein families that have been subdivided into
functionally related subfamilies, using human expertise. These subfamilies model the
divergence of specific functions within protein families, allowing more accurate
association with function (human-curated molecular function and biological process
classifications and pathway diagrams), as well as inference of amino acids important for
functional specificity. Hidden Markov models (HMMs) are built for each family and
subfamily for classifying additional protein sequences.
Pfam
Is large collection of multiple sequence alignments and hidden Markov models covering
many common protein domains and families.
PIRSF
Protein
classification
system is a
network with
multiple levels of
sequence
diversity from
superfamilies to
subfamilies that
reflects the
evolutionary
relationship of
full-length
proteins and
domains. The
primary PIRSF
classification unit
is the
The 13 member databases of the InterPro consortium grouped by their signature
homeomorphic
family, whose
construction method and the biological entity they focus on.[6]
members are both
homologous
(evolved from a
common ancestor) and homeomorphic (sharing full-length sequence similarity and a
common domain architecture).
PRINTS
PRINTS is a compendium of protein fingerprints. A fingerprint is a group of conserved
motifs used to characterise a protein family; its diagnostic power is refined by iterative
scanning of UniProt. Usually the motifs do not overlap, but are separated along a
sequence, though they may be contiguous in 3D-space. Fingerprints can encode protein
folds and functionalities more flexibly and powerfully than can single motifs, their full
diagnostic potency deriving from the mutual context afforded by motif neighbours.
PROSITE
PROSITE is a database of protein families and domains. It consists of biologically
significant sites, patterns and profiles that help to reliably identify to which known protein
family (if any) a new sequence belongs.
SMART
Simple Modular Architecture Research Tool Allows the identification and annotation of
genetically mobile domains and the analysis of domain architectures. More than 800
 domain families found in signaling, extracellular and chromatin-associated proteins are
detectable. These domains are extensively annotated with respect to phyletic distributions,
functional class, tertiary structures and functionally important residues.
SUPERFAMILY
SUPERFAMILY is a library of profile hidden Markov models that represent all proteins of
known structure. The library is based on the SCOP classification of proteins: each model
corresponds to a SCOP domain and aims to represent the entire SCOP superfamily that
the domain belongs to. SUPERFAMILY has been used to carry out structural assignments
to all completely sequenced genomes.
SFLD
A hierarchical classification of enzymes that relates specific sequence-structure features to
specific chemical capabilities.
TIGRFAMs
TIGRFAMs is a collection of protein families, featuring curated multiple sequence
alignments, hidden Markov models (HMMs) and annotation, which provides a tool for
identifying functionally related proteins based on sequence homology. Those entries
which are "equivalogs" group homologous proteins which are conserved with respect to
function.

Data types

InterPro consists of seven types of data provided by different members of the consortium:

Data Types of InterPro

Contributing
Data Type Description
Databases

Structural and/or functional domains of proteins predicted using All 13 member

InterPro Entries
one or more signatures databases
Member Database Signatures from member databases. These include signatures All 13 member
signatures that are integrated into InterPro, and those that are not databases

UniProtKB (Swiss-Prot
Protein Protein sequences
and TrEMBL)

Proteome Collection of proteins that belong to a single organism UniProtKB

Structure 3-dimensional structures of proteins PDBe

Taxonomy Protein taxonomic information UniProtKB

Set Groups of evolutionary related families Pfam, CDD

InterPro entry types

InterPro entries can be further broken down into five types:

Icons that identify the five entry types found
Homologous Superfamily: A group of proteins in InterPro (Homologous Superfamily,
that share a common evolutionary origin as seen in Family, Domain, Repeat, or Site).[7]
their structural similarities, even if their sequences
are not highly similar. These entries are
specifically only provided by two member databases: CATH-Gene3D and SUPERFAMILY.
Family: A group of proteins that have a common evolutionary origin determined through
structural similarities, related functions, or sequence homology.
Domain: A distinct unit in a protein with a particular function, structure, or sequence.
 Repeat: A sequence of amino acids, usually no longer than 50 amino acids, that tend to
repeat many times in a protein.
Site: A short sequence of amino acids where at least one amino acid is conserved. These
include post-translation modification sites, conserved sites, binding sites, and active sites.

Access
The database is available for text- and sequence-based searches via a webserver, and for download via
anonymous FTP. Like other EBI databases, it is in the public domain, since its content can be used "by any
individual and for any purpose".[8] InterPro aims to release data to the public every 8 weeks, typically
within a day of the UniProtKB release of the same proteins.

InterPro application programming interface (API)

InterPro provides an API for programmatic access to all InterPro entries and their related entries in Json
format.[9] There are six main endpoints for the API corresponding to the different InterPro data types: entry,
protein, structure, taxonomy, proteome and set.

InterProScan
InterProScan is a software package that allows users to scan sequences against member database
signatures. Users can use this signature scanning software to functionally characterize novel nucleotide or
protein sequences.[10] InterProScan is frequently used in genome projects in order to obtain a "first-pass"
characterisation of the genome of interest.[11][12] As of December 2020, the public version of InterProScan
(v5.x) uses a Java-based architecture.[13] The software package is currently only supported on a 64-bit
Linux operating system.

InterProScan, along with many other EMBL-EBI bioinformatics tools, can also be accessed
programmatically using RESTful and SOAP Web Services APIs.[14]

See also
Protein family
Domain of unknown function
Sequence motif

References
1. Blum M, Chang HY, Chuguransky S, Grego T, Kandasaamy S, Mitchell A, et al. (November
2020). "The InterPro protein families and domains database: 20 years on" (https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC7778928). Nucleic Acids Research. 49 (D1): D344–D354.
doi:10.1093/nar/gkaa977 (https://doi.org/10.1093%2Fnar%2Fgkaa977). PMC 7778928 (http
s://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778928). PMID 33156333 (https://pubmed.ncbi.
nlm.nih.gov/33156333).
 2. Hunter S, Jones P, Mitchell A, Apweiler R, Attwood TK, Bateman A, et al. (January 2012).
"InterPro in 2011: new developments in the family and domain prediction database" (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC3245097). Nucleic Acids Research. 40 (Database
issue): D306-12. doi:10.1093/nar/gkr948 (https://doi.org/10.1093%2Fnar%2Fgkr948).
PMC 3245097 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245097). PMID 22096229
(https://pubmed.ncbi.nlm.nih.gov/22096229).
3. Apweiler R, Attwood TK, Bairoch A, Bateman A, Birney E, Biswas M, et al. (January 2001).
"The InterPro database, an integrated documentation resource for protein families, domains
and functional sites" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC29841). Nucleic Acids
Research. 29 (1): 37–40. doi:10.1093/nar/29.1.37 (https://doi.org/10.1093%2Fnar%2F29.1.3
7). PMC 29841 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC29841). PMID 11125043 (htt
ps://pubmed.ncbi.nlm.nih.gov/11125043).
4. Apweiler R, Attwood TK, Bairoch A, Bateman A, Birney E, Biswas M, et al. (December
2000). "InterPro--an integrated documentation resource for protein families, domains and
functional sites" (https://doi.org/10.1093%2Fbioinformatics%2F16.12.1145). Bioinformatics.
16 (12): 1145–50. doi:10.1093/bioinformatics/16.12.1145 (https://doi.org/10.1093%2Fbioinfo
rmatics%2F16.12.1145). PMID 11159333 (https://pubmed.ncbi.nlm.nih.gov/11159333).
5. Blum, Matthias; Chang, Hsin-Yu; Chuguransky, Sara; Grego, Tiago; Kandasaamy, Swaathi;
Mitchell, Alex; Nuka, Gift; Paysan-Lafosse, Typhaine; Qureshi, Matloob; Raj, Shriya;
Richardson, Lorna (2020-11-06). "The InterPro protein families and domains database: 20
years on" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778928). Nucleic Acids
Research. 49 (D1): D344–D354. doi:10.1093/nar/gkaa977 (https://doi.org/10.1093%2Fnar%
2Fgkaa977). ISSN 0305-1048 (https://www.worldcat.org/issn/0305-1048). PMC 7778928 (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778928). PMID 33156333 (https://pubmed.ncb
i.nlm.nih.gov/33156333).
6. EMBL-EBI. "Where does the data come from? | InterPro" (https://www.ebi.ac.uk/training-bet
a/online/courses/interpro-functional-and-structural-analysis/what-is-interpro/where-does-dat
a-come-from/). Retrieved 2020-12-04.
7. EMBL-EBI. "InterPro entry types | InterPro" (https://www.ebi.ac.uk/training-beta/online/course
s/interpro-functional-and-structural-analysis/what-is-an-interpro-entry/interpro-entry-types/).
Retrieved 2020-12-04.
8. "Terms of Use for EMBL-EBI Services | European Bioinformatics Institute" (http://www.ebi.ac.
uk/Information/termsofuse.html).
9. "How to download InterPro data? — InterPro Documentation" (https://interpro-documentatio
n.readthedocs.io/en/latest/download.html#interpro-application-programming-interface-api).
interpro-documentation.readthedocs.io. Retrieved 2020-12-04.
10. Quevillon E, Silventoinen V, Pillai S, Harte N, Mulder N, Apweiler R, Lopez R (July 2005).
"InterProScan: protein domains identifier" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11
60203) (Free full text). Nucleic Acids Research. 33 (Web Server issue): W116-20.
doi:10.1093/nar/gki442 (https://doi.org/10.1093%2Fnar%2Fgki442). PMC 1160203 (https://w
ww.ncbi.nlm.nih.gov/pmc/articles/PMC1160203). PMID 15980438 (https://pubmed.ncbi.nlm.
nih.gov/15980438).
11. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. (February 2001).
"Initial sequencing and analysis of the human genome" (https://deepblue.lib.umich.edu/bitstr
eam/2027.42/62798/1/409860a0.pdf) (PDF). Nature. 409 (6822): 860–921.
Bibcode:2001Natur.409..860L (https://ui.adsabs.harvard.edu/abs/2001Natur.409..860L).
doi:10.1038/35057062 (https://doi.org/10.1038%2F35057062). PMID 11237011 (https://pub
med.ncbi.nlm.nih.gov/11237011).
12. Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, et al. (October
2002). "The genome sequence of the malaria mosquito Anopheles gambiae". Science. 298
(5591): 129–49. Bibcode:2002Sci...298..129H (https://ui.adsabs.harvard.edu/abs/2002Sci...2
98..129H). CiteSeerX 10.1.1.149.9058 (https://citeseerx.ist.psu.edu/viewdoc/summary?doi=
10.1.1.149.9058). doi:10.1126/science.1076181 (https://doi.org/10.1126%2Fscience.107618
1). PMID 12364791 (https://pubmed.ncbi.nlm.nih.gov/12364791). S2CID 4512225 (https://ap
i.semanticscholar.org/CorpusID:4512225).
13. Jones P, Binns D, Chang HY, Fraser M, Li W, McAnulla C, et al. (May 2014). "InterProScan
5: genome-scale protein function classification" (https://www.ncbi.nlm.nih.gov/pmc/articles/P
MC3998142). Bioinformatics. 30 (9): 1236–40. doi:10.1093/bioinformatics/btu031 (https://doi.
org/10.1093%2Fbioinformatics%2Fbtu031). PMC 3998142 (https://www.ncbi.nlm.nih.gov/pm
c/articles/PMC3998142). PMID 24451626 (https://pubmed.ncbi.nlm.nih.gov/24451626).
14. Madeira F, Park YM, Lee J, Buso N, Gur T, Madhusoodanan N, et al. (July 2019). "The
EMBL-EBI search and sequence analysis tools APIs in 2019" (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC6602479). Nucleic Acids Research. 47 (W1): W636–W641.
doi:10.1093/nar/gkz268 (https://doi.org/10.1093%2Fnar%2Fgkz268). PMC 6602479 (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC6602479). PMID 30976793 (https://pubmed.ncbi.nl
m.nih.gov/30976793).

External links
Official website (http://www.ebi.ac.uk/interpro/) — webserver

Retrieved from "https://en.wikipedia.org/w/index.php?title=InterPro&oldid=1166578684"