InterPro Protein Classification

  • Jennifer McDowall
  • Sarah Hunter
Part of the Methods in Molecular Biology book series (MIMB, volume 694)


Improvements in nucleotide sequencing technology have resulted in an ever increasing number of nucleotide and protein sequences being deposited in databases. Unfortunately, the ability to manually classify and annotate these sequences cannot keep pace with their rapid generation, resulting in an increased bias toward unannotated sequence. Automatic annotation tools can help redress the balance. There are a number of different groups working to produce protein signatures that describe protein families, functional domains or conserved sites within related groups of proteins. Protein signature databases include CATH-Gene3D, HAMAP, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY, and TIGRFAMs. Their approaches range from characterising small conserved motifs that can identify members of a family or subfamily, to the use of hidden Markov models that describe the conservation of residues over entire domains or whole proteins. To increase their value as protein classification tools, protein signatures from these 11 databases have been combined into one, powerful annotation tool: the InterPro database ( (Hunter et al., Nucleic Acids Res 37:D211–D215, 2009). InterPro is an open-source protein resource used for the automatic annotation of proteins, and is scalable to the analysis of entire new genomes through the use of a downloadable version of InterProScan, which can be incorporated into an existing local pipeline. InterPro provides structural information from PDB (Kouranov et al., Nucleic Acids Res 34:D302–D305, 2006), its classification in CATH (Cuff et al., Nucleic Acids Res 37:D310–D314, 2009) and SCOP (Andreeva et al., Nucleic Acids Res 36:D419–D425, 2008), as well as homology models from ModBase (Pieper et al., Nucleic Acids Res 37:D347–D354, 2009) and SwissModel (Kiefer et al., Nucleic Acids Res 37:D387–D392, 2009), allowing a direct comparison of the protein signatures with the available structural information. This chapter reviews the signature methods found in the InterPro database, and provides an overview of the InterPro resource itself.

Key words

Protein family Domain Signature Functional classification Homology Hidden Markov model Profile Clustering Regular expression 


  1. 1.
    Hunter S, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bork P, Das U, Daugherty L, Duquenne L, Finn RD, Gough J, Haft D, Hulo N, Kahn D, Kelly E, Laugraud A, Letunic I, Lonsdale D, Lopez R, Madera M, Maslen J, McAnulla C, McDowall J, Mistry J, Mitchell A, Mulder N, Natale D, Orengo C, Quinn AF, Selengut JD, Sigrist CJ, Thimma M, Thomas PD, Valentin F, Wilson D, Wu CH, Yeats C. (2009) InterPro: the integrative protein signature database. Nucleic Acids Res. 37, D211–D215.PubMedCrossRefGoogle Scholar
  2. 2.
    Kouranov A, Xie L, de la Cruz J, Chen L, Westbrook J, Bourne PE, Berman HM. (2006) The RCSB PDB information portal for structural genomics. Nucleic Acids Res. 34, D302–D305.PubMedCrossRefGoogle Scholar
  3. 3.
    Cuff AL, Sillitoe I, Lewis T, Redfern OC, Garratt R, Thornton J, Orengo CA. (2009) The CATH classification revisited--architectures reviewed and new ways to characterize structural divergence in superfamilies. Nucleic Acids Res. 37, D310–D314.PubMedCrossRefGoogle Scholar
  4. 4.
    Andreeva A, Howorth D, Chandonia JM, Brenner SE, Hubbard TJ, Chothia C, Murzin AG. (2008) Data growth and its impact on the SCOP database: new developments. Nucleic Acids Res. 36, D419–D425.PubMedCrossRefGoogle Scholar
  5. 5.
    Pieper U, Eswar N, Webb BM, Eramian D, Kelly L, Barkan DT, Carter H, Mankoo P, Karchin R, Marti-Renom MA, Davis FP, Sali A. (2009) MODBASE, a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res. 37, D347–D354.PubMedCrossRefGoogle Scholar
  6. 6.
    Kiefer F, Arnold K, Künzli M, Bordoli L, Schwede T. (2009) The SWISS-MODEL Repository and associated resources. Nucleic Acids Res. 37, D387–D392.PubMedCrossRefGoogle Scholar
  7. 7.
    Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. (1990) Basic local alignment search tool. J Mol Biol. 215, 403–410.PubMedGoogle Scholar
  8. 8.
    Pearson WR. (1990) Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol. 183, 63–98.PubMedCrossRefGoogle Scholar
  9. 9.
    UniProt Consortium. (2009) The Universal Protein Resource (UniProt) 2009. Nucleic Acids Res. 37, D169–D174.CrossRefGoogle Scholar
  10. 10.
    Servant F, Bru C, Carrère S, Courcelle E, Gouzy J, Peyruc D, Kahn D. (2002) ProDom: automated clustering of homologous domains. Brief Bioinform. 3(3), 246–251.PubMedCrossRefGoogle Scholar
  11. 11.
    Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25(17), 3389–3402.PubMedCrossRefGoogle Scholar
  12. 12.
    Sigrist CJA, Cerutti L, Hulo N, Gattiker A, Falquet L, Pagni M, Bairoch A, Bucher P. (2002) PROSITE: a documented database using patterns and profiles as motif descriptors. Brief Bioinform. 3, 265–274.PubMedCrossRefGoogle Scholar
  13. 13.
    Gribskov M, Lüthy R, Eisenberg D. (1990) Profile analysis. Methods Enzymol. 183, 146–159.PubMedCrossRefGoogle Scholar
  14. 14.
    Lima T, Auchincloss AH, Coudert E, Keller G, Michoud K, Rivoire C, Bulliard V, de Castro E, Lachaize C, Baratin D, Phan I, Bougueleret L, Bairoch A. (2009) HAMAP: a database of completely sequenced microbial proteome sets and manually curated microbial protein families in UniProtKB/Swiss-Prot. Nucleic Acids Res. 37, D471–D478.PubMedCrossRefGoogle Scholar
  15. 15.
    Attwood TK. (2002) The PRINTS database: a resource for identification of protein families. Brief Bioinform. 3(3), 252–263.PubMedCrossRefGoogle Scholar
  16. 16.
    Krogh A, Brown M, Mian IS, Sjölander K, Haussler D. (1994) Hidden Markov models in computational biology. Applications to protein modeling. J Mol Biol. 235(5), 1501–1531.PubMedCrossRefGoogle Scholar
  17. 17.
    Finn RD, Tate J, Mistry J, Coggill PC, Sammut SJ, Hotz HR, Ceric G, Forslund K, Eddy SR, Sonnhammer EL, Bateman A. (2008) The Pfam protein families database. Nucleic Acids Res. 36, D281–D288.PubMedCrossRefGoogle Scholar
  18. 18.
    Heger A, Wilton CA, Sivakumar A, Holm L. (2005) ADDA: a domain database with global coverage of the protein universe. Nucleic Acids Res. 33, D188–D191.PubMedCrossRefGoogle Scholar
  19. 19.
    Letunic I, Doerks T, Bork P. (2009) SMART 6: recent updates and new developments. Nucleic Acids Res. 37, D229–D232.PubMedCrossRefGoogle Scholar
  20. 20.
    Haft DH, Selengut JD, White O. (2003) The TIGRFAMs database of protein families. Nucleic Acids Res. 31(1), 371–373.PubMedCrossRefGoogle Scholar
  21. 21.
    Wu CH, Nikolskaya A, Huang H, Yeh LS, Natale DA, Vinayaka CR, Hu ZZ, Mazumder R, Kumar S, Kourtesis P, Ledley RS, Suzek BE, Arminski L, Chen Y, Zhang J, Cardenas JL, Chung S, Castro-Alvear J, Dinkov G, Barker WC. (2004) PIRSF: family classification system at the Protein Information Resource. Nucleic Acids Res. 32, D112–D114.PubMedCrossRefGoogle Scholar
  22. 22.
    Mi H, Lazareva-Ulitsky B, Loo R, Kejariwal A, Vandergriff J, Rabkin S, Guo N, Muruganujan A, Doremieux O, Campbell MJ, Kitano H, Thomas PD. (2005) The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic Acids Res. 33, D284–D288.PubMedCrossRefGoogle Scholar
  23. 23.
    Wilson D, Pethica R, Zhou Y, Talbot C, Vogel C, Madera M, Chothia C, Gough J. (2009) SUPERFAMILY – sophisticated comparative genomics, data mining, visualization and phylogeny. Nucleic Acids Res. 37, D380–D386.PubMedCrossRefGoogle Scholar
  24. 24.
    Yeats C, Lees J, Reid A, Kellam P, Martin N, Liu X, Orengo C. (2008) Gene3D: comprehensive structural and functional annotation of genomes. Nucleic Acids Res. 36, D414–D418.PubMedCrossRefGoogle Scholar
  25. 25.
    Quevillon E, Silventoinen V, Pillai S, Harte N, Mulder N, Apweiler R, Lopez R. (2005) InterProScan: protein domains identifier. Nucleic Acids Res. 33, W116–W120.PubMedCrossRefGoogle Scholar
  26. 26.
    Haider S, Ballester B, Smedley D, Zhang J, Rice P, Kasprzyk A. (2009) BioMart Central Portal – unified access to biological data. Nucleic Acids Res. 37, W23–W27.PubMedCrossRefGoogle Scholar
  27. 27.
    Jones P, Côté RG, Cho SY, Klie S, Martens L, Quinn AF, Thorneycroft D, Hermjakob H. (2008) PRIDE: new developments and new datasets. Nucleic Acids Res. 36, D878–D883.PubMedCrossRefGoogle Scholar
  28. 28.
    Joshi-Tope G, Gillespie M, Vastrik I, D’Eustachio P, Schmidt E, de Bono B, Jassal B, Gopinath GR, Wu GR, Matthews L, Lewis S, Birney E, Stein L. (2005) Reactome: a knowledgebase of biological pathways. Nucleic Acids Res. 33, D428–D432.PubMedCrossRefGoogle Scholar
  29. 29.
    Reference Genome Group of the Gene Ontology Consortium. (2009) The Gene Ontology’s Reference Genome Project: a unified framework for functional annotation across species. PLoS Comput Biol. 5(7), e1000431.CrossRefGoogle Scholar
  30. 30.
    Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, Dimmer E, Feuermann M, Friedrichsen A, Huntley R, Kohler C, Khadake J, Leroy C, Liban A, Lieftink C, Montecchi-Palazzi L, Orchard S, Risse J, Robbe K, Roechert B, Thorneycroft D, Zhang Y, Apweiler R, Hermjakob H. (2007) IntAct – open source resource for molecular interaction data. Nucleic Acids Res. 35, D561–D565.PubMedCrossRefGoogle Scholar
  31. 31.
    Fleischmann A, Darsow M, Degtyarenko K, Fleischmann W, Boyce S, Axelsen KB, Bairoch A, Schomburg D, Tipton KF, Apweiler R. (2004) IntEnz, the integrated relational enzyme database. Nucleic Acids Res. 32, D434–D437.PubMedCrossRefGoogle Scholar
  32. 32.
    Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B. (2009) The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 37, D233–D238.PubMedCrossRefGoogle Scholar
  33. 33.
    Harmar AJ, Hills RA, Rosser EM, Jones M, Buneman OP, Dunbar DR, Greenhill SD, Hale VA, Sharman JL, Bonner TI, Catterall WA, Davenport AP, Delagrange P, Dollery CT, Foord SM, Gutman GA, Laudet V, Neubig RR, Ohlstein EH, Olsen RW, Peters J, Pin JP, Ruffolo RR, Searls DB, Wright MW, Spedding M. (2009) IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res. 37, D680–D685.PubMedCrossRefGoogle Scholar
  34. 34.
    Degtyarenko K, Contrino S. (2004) COMe: the ontology of bioinorganic proteins. BMC Struct Biol. 4, 3.PubMedCrossRefGoogle Scholar
  35. 35.
    Rawlings ND, Morton FR, Kok CY, Kong J, Barrett AJ. (2008) MEROPS: the peptidase database. Nucleic Acids Res. 36, D320–D325.PubMedCrossRefGoogle Scholar
  36. 36.
    Whelan S, de Bakker PI, Quevillon E, Rodriguez N, Goldman N. (2006) PANDIT: an evolution-centric database of protein and associated nucleotide domains with inferred trees. Nucleic Acids Res. 34, D327–D331.PubMedCrossRefGoogle Scholar
  37. 37.
    Golovin A, Henrick K. (2008) MSDmotif: exploring protein sites and motifs. BMC Bioinformatics. 9, 312.PubMedCrossRefGoogle Scholar
  38. 38.
    Petryszak R, Kretschmann E, Wieser D, Apweiler R. (2005) The predictive power of the CluSTr database. Bioinformatics. 21(18), 3604–3609.PubMedCrossRefGoogle Scholar
  39. 39.
    Haft DH, Selengut JD, Brinkac LM, Zafar N, White O. (2005) Genome Properties: a system for the investigation of prokaryotic genetic content for microbiology, genome annotation and comparative genomics. Bioinformatics. 21(3), 293–306.PubMedCrossRefGoogle Scholar
  40. 40.
    Jimenez RC, Quinn AF, Garcia A, Labarga A, O’Neill K, Martinez F, Salazar GA, Hermjakob H. (2008) Dasty2, an Ajax protein DAS client. Bioinformatics. 21(14), 3198–3199.Google Scholar
  41. 41.
    Prlić A, Down TA, Hubbard TJ. (2005) Adding some SPICE to DAS. Bioinformatics. 21(Suppl 2), ii40–ii41.PubMedCrossRefGoogle Scholar
  42. 42.
    Hartshorn MJ. (2002) AstexViewer: a visualisation aid for structure-based drug design. J Comput Aided Mol Des. 16(12), 871–881.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jennifer McDowall
    • 1
  • Sarah Hunter
    • 1
  1. 1.EMBL OutstationEuropean Bioinformatics Institute (EBI)CambridgeUK

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