User Manual

What is InterPro?

InterPro is an integrated documentation resource for protein families, domains, regions and sites. InterPro combines a number of databases (referred to as member databases) that use different methodologies and a varying degree of biological information on well-characterised proteins to derive protein signatures. By uniting the member databases, InterPro capitalises on their individual strengths, producing a powerful integrated database and diagnostic tool (InterProScan).

The member databases use a number of approaches:

1. ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST.
2. PROSITE patterns: provider of simple regular expressions.
3. PROSITE and HAMAP profiles: provide sequence matrices.
4. PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs).
5. PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs).

Diagnostically, these resources have different areas of optimum application owing to the different underlying analysis methods. In terms of family coverage, the protein signature databases are similar in size but differ in content. While all of the methods share a common interest in protein sequence classification, some focus on divergent domains (e.g., Pfam), some focus on functional sites (e.g., PROSITE), and others focus on families, specialising in hierarchical definitions from superfamily down to subfamily levels in order to pin-point specific functions (e.g., PRINTS). TIGRFAMs focus on building HMMs for functionally equivalent proteins and PIRSF always produce HMMs over the full length of a protein and have protein length restrictions to gather family members. HAMAP profiles are manually created by expert curators they identify proteins that are part of well-conserved bacterial, archaeal and plastid-encoded proteins families or subfamilies. PANTHER build HMMs based on the divergence of function within families. SUPERFAMILY and Gene3D are based on structure using the SCOP and CATH superfamilies, respectively, as a basis for building HMMs.

Content

The content of the current release; statistics, lists of the entries by Type and matches to member database methods (both integrated and unintegrated) are provided in the Release Notes.

Previous releases are listed in the Documentation.

How is it useful?

Protein signature databases have become vital tools for identifying distant relationships in novel sequences and hence are used for the classification of protein sequences and for inferring their function. InterPro streamlines the analysis of newly determined sequences for the individual user and makes a significant contribution to the demanding task of automatic annotation of predicted proteins from genome sequencing projects.

InterPro provides internal consistency checks and deeper coverage, making it more efficient and reliable than using each of the pattern databases separately. This unified approach improves both the utility and the coverage of pattern databases, pin-pointing weaknesses and facilitating their further development.

Structure of an InterPro Entry

The information fields (or sections) in bold are the core fields, while those in italics are only displayed when applicable; all information field headers are linked to the relevant section in the User Manual. The fields in an entry are: Header: Accession number and Name, UniProtKB match count and match views, Accession: accession number and short name, Secondary accession number, Type, Signatures, Parent, Children, Found in, Contains, Gene Ontology Terms, Abstract, Structural Links, Database Links, IntAct Links, Taxonomy coverage, Overlapping InterPro entries, Example proteins, Publications and Additional Reading.

Display: Architectures

The InterPro Domain Architecture (IDA) Viewer is a graphical representation of protein domain architecture, where the domain architecture of a protein sequence is displayed as a series of non-overlapping domains. The domain architecture is derived from members database signatures that do not overlap on a protein sequence. They are depicted as coloured lozenges; the lozenge name derives from the InterPro entry short name and if repeated more than once, then the multiplication factor follows the short name e.g. - x2. In the example below there is one PAN domain, four Kringle domains followed by one Peptidase S1/S6 domain. In some instance the architectural domains can be nested, one inside the other, for example IDA1254 and IDA719 (1254[719]).

Entries are grouped by domain architecture. A count of the number of UniProtKB proteins with the same architecture is provided, an example and the IDA code for each group is also given in the left-hand column. The example is linked to the single-protein detailed view. The IDA code is linked to the compact view for all entries with this domain architecture. There is no relationship between the length of the architecture display and the actual protein length; neither is there any relationship between the length of the lozenge and the length of the member database signatures that they depict.

The key table near the bottom of the page identifies which architecture lozenge colours correspond to which InterPro entry.

Accession Number and Short Name

Every InterPro entry has an accession number of the form IPRXXXXXX, where X is a digit. The accession number provides a stable way of identifying InterPro entries. InterPro accession numbers are stable and therefore allow unambiguous citation of database entries.

The short name is a short, concise name unique to each InterPro entry.

Secondary

Accession numbers provide a stable way of identifying InterPro entries from release to release. When the signatures in an InterPro entry are split or merged to give new or modified entries, then the accession number of the original InterPro entry becomes the secondary accession number in the new or modified InterPro entry.

In a recent change accession numbers are now linked to methods so any accession number that has been associated with a method will become a secondary accession number in the entry in which the method currently appears. In this way it will be possible to trace movement of methods through splitting and merging of entries.

Type

Type defines the entry as a Family, Domain, Region, Repeat or Site. Sites are sub-classified into either Conserved Sites (includes Motifs), Active Sites, Binding Sites or PTMs (Post-translational Modifications).

InterPro has introduced a new Type, Region, and new entry classification rules that affect the typing of entries:

• Entries typed Repeat or Site remain the same.
• Entries typed Family or Domain follow stricter criteria to ensure they conform more closely to current biological concepts:
• Entries typed Family contain signatures that cover all domains in the matching proteins and span >80% of the protein length with no adjacent signatures of type Domain or Region
• Entries typed Domain identify biological units with defined boundaries, which includes structural and functional domains as well as defined sub-domains.
• Region is a new InterPro signature type. It defines signatures that cannot be typed as either Family or Domain.

• New relationship rules have been introduced that affect how different entries are related to one another. Parent/Child and Contains/Found in relationships will continue within InterPro with their existing definitions, but the following changes have been introduced:
• Entry types are no longer taken into consideration for relationships between entries. Instead, only the sequence covered by the signatures of an entry will be taken into consideration when forming relationships.
• Parent/Child relationships are permitted between entries of different types: Families, Domains and Regions.
• Parent/Child relationships are permitted for Repeats and for Sites but NOT to other entry types.
• All Contains/Found In relationships are displayed in the Relationships section of an entry (previously, only the most specific relationships were displayed).
• InterPro entries that contain signatures defining Repeats or Sites as their only signature(s) can only be Found In other InterPro entries.
• Repeats and Sites do NOT affect the typing or relationships of other InterPro entries.

Features of Sequences: Repeats and Sites

InterPro Repeat

A repeat is a region that is not expected to fold into a globular domain on its own. For example 6-8 copies of the WD40 repeat are needed to form a single globular domain. There are also many other short repeat motifs that probably do not form a globular fold.

InterPro Sites:

• A Conserved Site, otherwise known as 'Motif', is any short sequence pattern that may contain one or more unique residues and cannot be defined as a Active Site, Binding Site or Post-translational Modification (PTM).
• Active sites are best known as the catalytic pockets of enzymes where a substrate is bound and converted to a product, which is then released. Distant parts of a protein's primary structure may be involved in the formation of the catalytic pocket. Therefore, to describe an active site, one or more signatures will be needed to cover all the active site residues. To be classed as an Active Site the amino acids involved in the reaction must be described and mutational inactivation studies reported.
• Binding sites bind chemical compounds, which themselves are not substrates for a reaction. The compound, which is bound, may be a required co-factor for a chemical reaction, be involved in electron transport or be involved in protein structure modification. The binding is reversible and to be classed as a Binding Site the amino acids involved in the reaction must be described and mutational inactivation studies reported.
• A Post-translational Modification modifies the primary protein structure. This modification may be necessary for activation or de-activation of function. Examples include glycosylation, phosphorylation, sulphation and splicing etc. The process of modification may be permanent or reversible and the process may be required for functional activation or deactivation. To be recognised in InterPro the sequence signature must be described.

Lists of entry types:

Family; Domain; Region; Repeat; Conserved Site; Active Site; Binding Site; PTMs.

Signatures

The Signatures field lists the protein signature matches. For each protein signature the Member database, the signature ID, signature name and number of proteins it matches are given. The member database names are linked to their respective home page and the signature IDs are linked to the corresponding entry information page.

Relationships: PARENT/CHILD; CONTAINS/FOUND IN

The PARENT/CHILD relationship is used to indicate family/subfamily relationships defined by the member database methods in the entries. To be a CHILD, >75% of the protein set of the CHILD must be represented in the PARENT. If an InterPro PARENT has more than one InterPro CHILD a protein sequence should not be found in the match table of more than one of these children. If one InterPro entry is described as the child of another InterPro entry, this implies that the child entry is more specific than the parent, and that in all cases a protein sequence match to the child entry implies a match to the parent. Signatures for the parent and child entries must overlap by >50% of their sequence and there must be no adjacent signatures to the CHILD that are also covered by one or more of the PARENT signatures. A list of the PARENT/CHILD relationships by InterPro entry accession is available from the ftp site: ParentChildTreeFile.txt.

The CONTAINS/FOUND IN relationship is used to indicate features of the entry that are not defined by Parent/Child relationships, these include: Regions, Domains, Repeats and Sites. For a CONTAINS/FOUND IN relationship to be established, 40% or above of the proteins in the InterPro entry must contain the feature. Some features can be found in more than one type of protein or family of proteins, but is not children in the family sense. Features may be structural or functional and can be found in proteins with different domain organisations. The CONTAINS/FOUND IN relationship, is therefore useful in linking InterPro entries which are associated by composition but are not related hierarchically.

Gene Ontology Assignments

Functional classification of the entry is given by listing associated GO terms. The Gene Ontology project (GO) http://www.geneontology.org/ is a dynamic controlled vocabulary defined in three ontology's, molecular function, biological process and cellular component.

• Molecular function is the action characteristic of a gene product.
• Biological process describes a phenomenon marked by changes that lead to a particular result, mediated by one or more gene products.
• Cellular component is the part of a cell of which a gene product is a component; GO includes the extracellular environment of cells; a gene product may be a component of one or more parts of a cell.

For each associated term the name of the term and GO accession number is given. The assignment of GO terms to InterPro entries was done manually by reading the abstract of the entries and annotation of proteins in the protein match table for each entry. An appropriate GO term for an entry is one, which applies to the whole protein. The GO terms associated with an InterPro entry applies to all proteins with true hits to the signatures in that entry. The assignments are incomplete and are ongoing due to the dynamic nature of the GO project. Some entries could be mapped to very low level (specific) GO terms, while entries describing wider families or common domains were mapped to higher level terms or could not be mapped at all. The GO terms and mappings can be found using the EBI QuickGo browser.

It is important to remember these mappings provide useful predictions of GO assignments to the corresponding proteins however, biological exceptions like inactivated enzymes may occur. GO annotation is an ongoing process as new entries are incorporated and old entries are updated.

Abstract

The Abstract describes the signatures in the entry, the protein matches and provides references. Where possible a functional inference is made.

Structural Links

Links to CATH, SCOP and PDB are displayed when proteins in the entry have known structures. The PDB links are displayed within a pop-up box.

Structural links are generated automatically to the CATH and SCOP databases through residue-by-residue mappings with UniProtKB proteins. These databases describe the structural architecture of proteins, placing them within hierarchical classification schemes; InterPro entries are mapped to the 'Homologous Superfamily' level of CATH and to the 'Superfamily' level of SCOP. However, only those CATH- and SCOP-defined domains that are based on structural data describing single UniProtKB entries (as opposed to chimeric domains composed of multiple UniProtKB entries), and which overlap with InterPro signatures, are integrated into InterPro. Structural links are also provided to the Protein Databank in Europe (PDBe), via PDBe; PDB being the repository for crystallographic and NMR structures. These links are to all the PDBe entries for proteins that match the InterPro entry, provided they cover the signatures within the entry. It is important to stress that the structural links field contains curated mappings of SCOP and CATH domains to UniProtKB protein sequences. These, together with the PDBe data, are displayed as separate lines in the graphical view of protein matches, and should not be confused with the predictions of these domains as represented by the signatures.

Database Links

Database links include, cross-references to:

• The BLOCKS database; it contains multiple alignments of conserved regions in protein families
• The IntEnz database; EC numbers, systematic and common name, synonyms, function and links to other databases e.g. BRENDA, EXPASY, and KEGG. The link to Intenz is provided when >80% of the Swiss-Prot records map to a common EC class (the common stem is reported) or to a specific EC number. TrEMBL records are not considered, unlike PRIAM mapping (see below).
• The PRIAM database; a provider of enzyme-specific profiles for metabolic pathway prediction. A link is created when a PRIAM profile matchs >80% of the proteins in the InterPro entry.
• PROSITE documents; e.g. PDOC00020
• The Carbohydrate-Active EnZymes database; CAZy describes families of related catalytic and carbohydrate-binding modules of enzymes that act on glycosidic bonds
• The IUPHAR Receptor Database, the International Union of Pharmacology database of GPCR receptors.
• COMe database, a bioinorganic motif database
• MEROPS, a database of peptidases and peptidase inhibitors
• PANDIT, a database of multiple sequence alignments and phylogenetic trees based on Pfam signatures.
• PDBeMotif, is an integrated resource, which provides information about ligands, sequence and structure motifs, their relative position and the neighbour environment. The details are derived from the PDB together with a mapping to other motif and active-site sources. Search criteria combines sequence motifs, structure motifs, protein sequence, 3D properties, secondary structure elements, 3D associations of small motifs, protein side-chain and main-chain bonds and protein-ligand interactions.
• Pfam Clan, provides a pop-up display of the Pfam clan accession, clan name, clan description and a list of all the Pfam clan members with the corresponding InterPro entry and InterPro name. The Pfam clan accession is linked to the Pfam clan page and the InterPro entries link to the respective InterPro entry. These InterPro entries will not necessarily be related to each other through PARENT/CHILD or CONTAINS/FOUND IN relationships.
• Genome Properties, from TIGRFAMs. The GenProp ID's, when referenced, link to the Genome Properties system, which consists of a suite of Properties. These properties are carefully defined attributes of prokaryotic organisms whose status can be described by numerical values, or controlled vocabulary terms for complete sequenced genomes. The Genome Properties system has been designed to capture the widest possible range of attributes and currently encompasses taxonomic terms, genometric calculations, metabolic pathways, systems of interacting macromolecular components and quantitative and descriptive experimental observations (phenotypes) from the literature.

Interactions

Links from InterPro to IntAct are provided at the level of individual UniProtKB accessions only for manual curated protein:protein interactions. A limited set of 20 examples is provided. Each example links through to the IntAct page that describes the interaction: the UniProtKB accession numbers of the interacting proteins, the binding domains, experimental features and the InterPro entries of the interacting proteins.

Taxonomy Coverage

The Taxonomy Coverage aims to provide 'at a glance' view of the taxonomic range of the sequences associated with each InterPro entry and the number of sequences associated with each lineage. The taxonomic lineages are 'clickable' and provide a pop-up, which displays the tax-ID, the taxonomy and taxonomic subgroup(s)/species having matches to proteins, the protein match counts and a FASTA link. Clicking on the taxonomy or taxonomic subgroup(s)/species links to the protein overview matches for the selected taxonomy. Clicking on the FASTA box will download the complete set of FASTA sequences for the selected taxonomy of the entry.

The lineages were carefully selected to provide a view of the major groups of organisms. The circular display has the taxonomy-tree root as its centre. Selected model organisms populate the outer most circle. Nodes of the taxonomy-tree are placed on the inner circles. Radial lines lead to the description for each node. No significance is attached to the position of the node on a particular inner-circle, other than convenience, though some attempt has been made to group nodes. The nodes themselves are either true taxonomy nodes and have a NCBI taxonomy number or are artificial nodes created for this display; of which there are three: Unclassified, Other Eukaryotes (Non-Metazoa) and the Plastid Group.

Artificial Taxon: Unclassified contains the following NCBI taxon groups:

• Taxonomy:12884 Viroids
• Taxonomy:12908 unclassified sequences
• Taxonomy:28384 other sequences

The Eukaryota (TAXONOMY:2759) comprises 29 taxons, these have been grouped into two artificial taxons and one existing taxon:

Fungi/Metazoa (TAXONOMY:33154); Node Metazoa

Artificial Taxon; Plastid Group, this contains the following NCBI taxon groups:

• Taxonomy: 2763 Rhodophyta
• Taxonomy: 2830 Haptophyceae
• Taxonomy: 3027 Cryptophyta
• Taxonomy: 33090 Viridiplantae
• Taxonomy: 33630 Alveolata
• Taxonomy: 33634 stramenopiles
• Taxonomy: 33682 Euglenozoa
• Taxonomy: 38254 Glaucocystophyceae
• Taxonomy: 339960 Katablepharidophyta

Each taxonomic group within this artificial taxon contains organisms that have a plastid.

Artificial Taxon; Other Eukaryotes (Non-Metazoa), this comprises the following NCBI taxon groups:

• Taxonomy: 5719 Parabasalidea
• Taxonomy: 5752 Heterolobosea
• Taxonomy: 66288 Oxymonadida
• Taxonomy: 136087 Malawimonadidae
• Taxonomy: 154966 Nucleariidae
• Taxonomy: 193537 Centroheliozoa
• Taxonomy: 207245 Diplomonadida group
• Taxonomy: 543769 Rhizaria
• Taxonomy: 554296 Apusozoa
• Taxonomy: 554915 Amoebozoa
• Taxonomy: 556282 Jakobida

Each taxonomic group within this artificial taxon are the remaining taxonomic groups of the NCBI taxon:2759, which are not in the Plastid Group and are not Fungi/Metazoa (TAXONOMY:33154).

Overlapping InterPro Entries

This section displays entries that share more than 70% of their proteins. Such overlaps define PARENT/CHILD and CONTAINS/FOUND IN relationships between InterPro entries.

In the above example, InterPro entry IPR011969 contains proteins which are also found in IPR009007 as a result of the protein signatures of the two entries overlapping.

The two entries have been compared firstly by counting the number of proteins which are common to both, the results of which are displayed in the Venn diagram on the left, and secondly by calculating the average overlap of the protein signatures, in amino acids, with the results displayed in the bar diagram on the right.

Venn diagram display of the overlap of proteins common to both entries:

• The purple intersection contains the number of overlapping proteins common to both IPR009007 and IPR011969, which is 31 in this case.
• The pink section on the left is the number of proteins found in IPR009007 but not IPR011969, which is 35378.
• The blue section on the right is the number of proteins found in IPR011969 but not IPR009007, which is 0; i.e. all proteins associated with IPR011969 occur in IPR009007.

Bar diagram display of the average amino acid overlap between the protein signatures:

The average number of amino acids overlapping in the sequences of the 31 proteins common to both entries is then calculated, with the results displayed in the bar diagram on the right. The bar diagram display is only shown for 'Domain - Domain' relationships.

• The purple segment in the middle shows the average number of amino acids overlapping between IPR009007 and IPR011969 for the 31 proteins, in this case 104.
• The pink segment shows the average number of amino acids found in IPR009007, but not IPR011969, for the 31 proteins, which is 0.
• The blue segment shows the average number of amino acids found in IPR011969, but not IPR009007, for the 31 proteins, which is 15.

The results of these comparisons are used to calculate the percentage overlap score, with all scores greater than 70% displayed on the InterPro pages. In this example, since all proteins found in IPR011969 are also found in IPR009007, and all the amino acids from IPR009007 overlap with those from IPR011969, the percentage overlap score is 100%.

Examples

The protein entries in the examples illustrate as far as possible the diversity in taxonomy, structure and function of the proteins in the InterPro entry. For each example protein the accession number, UniProtKB name and a compact view of the matches is given.

Publications

The Publications field provides a list of references associated with each InterPro entry abstract. The list is originally derived from the reference lists of the member databases. Manual curation of abstracts often adds additional references.

PubMed Identifiers in the Publications and Additional Reading fields (below) now link to CiteXplore. The EBI's CiteXplore combines literature searching with text mining tools for biology. Search results are cross referenced to EBI applications based on publication identifiers. Links to full text versions are provided where available.

Additional Reading

The Additional Reading field provides a list of publications derived from the references provided by the member databases for the methods associated with each InterPro entry which are not referenced in the abstract. Additionally, a maximum of 5 references per entry are taken from the PDB where one or more of the proteins in the entry has had its structure determined.

Conventions Used in the Databank

Update Procedures

Member databases are released monthly or quarterly, while UniProtKB is updated every three weeks. As a result, the matches provided by the member databases may be outdated and incomplete since they would have used older versions of UniProtKB. Matches for new and changed protein sequences are calculated against member databases after each release of UniProtKB. Changed protein sequences are recognised by a change of the CRC64 (cyclic redundancy checksum), which provides a unique identifier for a given protein sequence.
Major updates to InterPro occur when member databases have new releases. In this case new methods are integrated into InterPro and run over all proteins in UniProtKB.
Annotation updates occur regularly and are ongoing. All changes in InterPro are made on the production database, and are publicly visible after the maximum of 3 months. We will produce a new, updated XML file at the same time to keep InterPro data in SRS, which is based on the XML file, in synch with the database.

InterPro cross-references in UniProtKB are shown in the DR lines of the flat files from entries in these databases. These are updated regularly in UniProtKB, so there may be a lag between the update of matches in InterPro and those in the UniProtKB flat files.

Appendix - PROSITE

PROSITE consists of documentation entries describing protein domains, families and functional sites, as well as associated patterns and profiles to identify them. Profiles and patterns are constructed from manually edited seed alignments. PROSITE is complemented by ProRule, a collection of rules based on profiles and patterns, which increases the discriminatory power of profiles and patterns by providing additional information about functionally and/or structurally critical amino acids.

Please cite:-

Hulo N, Bairoch A, Bulliard V, Cerutti L, Cuche BA, de Castro E, Lachaize C, Langendijk-Genevaux PS, Sigrist CJA. (2008)
The 20 years of PROSITE.
Nucleic Acids Res. 36, 245-249.

For more information see:- http://www.expasy.ch/prosite

Appendix - HAMAP

Members of HAMAP families are identified using PROSITE profile collections. HAMAP profiles are manually created by expert curators and they identify proteins that are part of well-conserved bacterial, archaeal and plastid-encoded proteins families or subfamilies. The aim of HAMAP is to propagate manually generated annotation to all members of a given protein family in an automated and controlled way using very strict criteria.

Please cite:-

Tania Lima, Andrea H. Auchincloss, Elisabeth Coudert, Guillaume Keller, Karine Michoud, Catherine Rivoire, Virginie Bulliard, Edouard de Castro, Corinne Lachaize, Delphine Baratin, Isabelle Phan, Lydie Bougueleret and Amos Bairoch (2009)
HAMAP: a database of completely sequenced microbial proteome sets and manually curated microbial protein families in UniProtKB/Swiss-Prot
Nucleic Acids Res. 37, Database issue D471-D478

Appendix - Pfam

Pfam is a collection of protein family alignments which were constructed semi-automatically using hidden Markov models (HMMs). Sequences that were not covered by Pfam were clustered and aligned automatically, and are released as Pfam-B. Pfam families have permanent accession numbers and contain functional annotation and cross-references to other databases, while Pfam-B families are re-generated at each release and are unannotated.

Please cite:-

Bateman, A., Birney, E., Cerruti, L., Durbin, R., Etwiller, L., Eddy, S.R., Griffiths-Jones, S., Howe, K.L., Marshall, M., Sonnhammer, E.L.L. (2002)
The Pfam Protein Families Database.
Nucleic Acids Res. 30, 276-280.

For more information see:-
http://pfam.sanger.ac.uk/

Appendix - 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 OWL. 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: the database thus provides a useful adjunct to PROSITE.

Please cite:-

Attwood, T.K., Bradley, P., Flower, D.R., Gaulton, A., Maudling, N., Mitchell, A.L., Moulton, G., Nordle, A., Paine, K., Taylor, P., Uddin, A., Zygouri, C. (2003)
PRINTS and its automatic supplement, prePRINTS.
Nucleic Acids Res. 31, 400-402.

For more information see:- http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/

Appendix - ProDom

The ProDom protein domain database consists of an automatic compilation of homologous domains. Current versions of ProDom are built using a novel procedure based on recursive PSI-BLAST searches. The ProDom database has been designed as a tool to help analyze domain arrangements of proteins and protein families. Strong emphasis has been put on the graphical user interface which allows for interactive analysis of protein homology relationships.

Please cite:-

Corpet F, Servant F, Gouzy J, Kahn D (2000)
ProDom and ProDom-CG: Tools for protein domain analysis and whole genome comparisons,
Nucleic Acids Res. 28:267-269.

For more information see:- http://www.toulouse.inra.fr/prodom.html

Appendix - SMART

SMART (a Simple Modular Architecture Research Tool) allows the identification and annotation of genetically mobile domains and the analysis of domain architectures. More than 500 domain families found in signalling, 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. Each domain found in a non-redundant protein database as well as search parameters and taxonomic information are stored in a relational database system. User interfaces to this database allow searches for proteins containing specific combinations of domains in defined taxa.

Please cite:-

Letunic, I., Goodstadt, L., Dickens, N.J., Doerks, T., Schultz, J., Mott, R., Ciccarelli, F., Copley, R.R., Ponting, C.P., Bork, P. (2002)
Recent improvements to the SMART domain-based sequence annotation resource.
Nucleic Acids Res. 30, 242-244.

For more information see:- http://smart.embl-heidelberg.de/

Appendix - 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.

Please cite:-

Haft, D.H., Selengut, J.D., White, O. (2003)
The TIGRFAMs database of protein families.
Nucleic Acids Res. 31, 371-373.

For more information see:- http://www.jcvi.org/cms/research/projects/tigrfams/overview/

Appendix - PIRSF

The 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).

Please cite:-

Wu CH, Yeh LL, Huang H, Arminski L, Castro-Alvear J, Chen Y, Hu Z, Ledley RS, Kourtesis P, Suzek BE, Vinayaka CR, Zhang J, Barker WC. (2003)
The Protein Information Resource.
Nucleic Acids Res. 31, 345-347.

For more information see:- http://pir.georgetown.edu/pirwww/dbinfo/pirsf.shtml

Appendix - 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. The results and analysis are available from the SUPERFAMILY website.

Please cite:-

Gough, J., Karplus, K., Hughey, R. and Chothia, C. (2001)
Assignment of Homology to Genome Sequences using a Library of Hidden Markov Models that Represent all Proteins of Known Structure.
J. Mol. Biol., 313, 903-919.

For more information see:- http://supfam.mrc-lmb.cam.ac.uk/SUPERFAMILY/

Appendix - Gene3D

Gene3D is a library of hidden Markov models that represent all proteins of known structure. The seed alignments for the models are derived from the proteins found within the homologous superfamily (H-level) classification level in CATH, which groups together domains that are thought to share a common ancestor. In CATH, similarities at H-level are identified first by sequence comparisons and subsequently by structure comparisons using SSAP. Gene3D has been used to carry out structural assignments to all completely sequenced genomes. The results and analysis are available from the Gene3D website.

With InterPro release 12.2 the Gene3D method accession number has changed to G3DSA: (note the colon). G3DSA is a specific subset of G3D data that is relevant to InterPro and permits direct links to the relevant pages in CATH.

Please cite:-

Frances Pearl, Annabel Todd, Ian Sillitoe, Mark Dibley, Oliver Redfern, Tony Lewis, Christopher Bennett, Russell Marsden, Alistair Grant, David Lee, Adrian Akpor, Michael Maibaum, Andrew Harrison, Timothy Dallman, Gabrielle Reeves, Ilhem Diboun, Sarah Addou, Stefano Lise, Caroline Johnston, Antonio Sillero, Janet Thornton, and Christine Orengo (2005)
The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis.
Nucleic Acids Res. 33, Database Issue:D247-D251.

For more information see:- http://www.cathdb.info

Appendix - PANTHER

PANTHER HMMs define protein families, and subfamilies modelled on the divergence of specific functions within the families; this permits more accurate association with function based on ontology terms and pathways, as well as inference of amino acids important for functional specificity.

Please cite:-

Huaiyu Mi, Betty Lazareva-Ulitsky, Rozina Loo, Anish Kejariwal, Jody Vandergriff, Steven Rabkin, Nan Guo, Anushya Muruganujan, Olivier Doremieux, Michael J. Campbell, Hiroaki Kitano, and Paul D. Thomas (2005)
The PANTHER database of protein families, subfamilies, functions and pathways.
Nucleic Acids Res. 33, Database Issue:D284-288.

For more information see:- http://www.pantherdb.org

Appendix - HLRN

A large proportion of HMMER-based calculations are performed on the IBMP690 Supercomputer at HLRN. We would like to thank Dr. Steffen Schulze-Kremer and the HLRN staff for their continued and valuable assistance.

Copyright Notice

InterPro - Integrated Resource Of Protein Families, Domains And Functional Sites Copyright (C) 2001 The InterPro Consortium. This manual and the accompanying database may be copied and redistributed freely, without advance permission, provided that this Copyright statement is reproduced with each copy.

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The InterPro member databases agreed that all data in InterPro and on the InterPro ftp server is freely distributable and no license agreements are required for use. For the databases that normally do require licenses for commercial use, all data from those databases that are distributed with the InterProScan package may be considered free and public and not subject to license agreements. These databases may have additional information not distributed by InterPro which is then subject to licensing.