InterPro

InterPro is a database of

InterPro's intention is to provide a one-stop-shop for protein classification, where all the signatures produced by the different member databases are placed into entries within the InterPro database. Signatures which represent equivalent domains, sites or families are put into the same entry and entries can also be related to one another. Additional information 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

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 homeomorphic family, whose 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:

InterPro entry types

InterPro entries can be further broken down into five types:

• Homologous Superfamily: A group of proteins that share a common evolutionary origin as seen in 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.

• Protein family
• Domain of unknown function
• Sequence motif

References