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Identification
HMDB Protein ID HMDBP01651
Secondary Accession Numbers
  • 6981
Name Dipeptidyl peptidase 4
Synonyms
  1. ADABP
  2. ADCP-2
  3. Adenosine deaminase complexing protein 2
  4. CD26 antigen
  5. DPP IV
  6. Dipeptidyl peptidase 4 membrane form
  7. Dipeptidyl peptidase 4 soluble form
  8. Dipeptidyl peptidase IV
  9. Dipeptidyl peptidase IV membrane form
  10. Dipeptidyl peptidase IV soluble form
  11. T-cell activation antigen CD26
  12. TP103
Gene Name DPP4
Protein Type Enzyme
Biological Properties
General Function Involved in serine-type endopeptidase activity
Specific Function Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF- kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
endopeptidase activity
serine hydrolase activity
serine-type peptidase activity
serine-type endopeptidase activity
catalytic activity
hydrolase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Cell membrane
  2. Single-pass type II membrane protein
  3. Single-pass type II membrane protein
  4. Single-pass type II membrane protein
  5. Single-pass type II membrane protein
  6. Apical cell membrane
  7. Cell junction
  8. Cell projection
  9. Cell projection
  10. Membrane raft
  11. invadopodium membrane
  12. lamellipodium membrane
Gene Properties
Chromosome Location Chromosome:2
Locus 2q24.3
SNPs DPP4
Gene Sequence
>2301 bp
ATGAAGACACCGTGGAAGATTCTTCTGGGACTGCTGGGTGCTGCTGCGCTTGTCACCATC
ATCACCGTGCCCGTGGTTCTGCTGAACAAAGGCACAGATGATGCTACAGCTGACAGTCGC
AAAACTTACACTCTAACTGATTACTTAAAAAATACTTATAGACTGAAGTTATACTCCTTA
AGATGGATTTCAGATCATGAATATCTCTACAAACAAGAAAATAATATCTTGGTATTCAAT
GCTGAATATGGAAACAGCTCAGTTTTCTTGGAGAACAGTACATTTGATGAGTTTGGACAT
TCTATCAATGATTATTCAATATCTCCTGATGGGCAGTTTATTCTCTTAGAATACAACTAC
GTGAAGCAATGGAGGCATTCCTACACAGCTTCATATGACATTTATGATTTAAATAAAAGG
CAGCTGATTACAGAAGAGAGGATTCCAAACAACACACAGTGGGTCACATGGTCACCAGTG
GGTCATAAATTGGCATATGTTTGGAACAATGACATTTATGTTAAAATTGAACCAAATTTA
CCAAGTTACAGAATCACATGGACGGGGAAAGAAGATATAATATATAATGGAATAACTGAC
TGGGTTTATGAAGAGGAAGTCTTCAGTGCCTACTCTGCTCTGTGGTGGTCTCCAAACGGC
ACTTTTTTAGCATATGCCCAATTTAACGACACAGAAGTCCCACTTATTGAATACTCCTTC
TACTCTGATGAGTCACTGCAGTACCCAAAGACTGTACGGGTTCCATATCCAAAGGCAGGA
GCTGTGAATCCAACTGTAAAGTTCTTTGTTGTAAATACAGACTCTCTCAGCTCAGTCACC
AATGCAACTTCCATACAAATCACTGCTCCTGCTTCTATGTTGATAGGGGATCACTACTTG
TGTGATGTGACATGGGCAACACAAGAAAGAATTTCTTTGCAGTGGCTCAGGAGGATTCAG
AACTATTCGGTCATGGATATTTGTGACTATGATGAATCCAGTGGAAGATGGAACTGCTTA
GTGGCACGGCAACACATTGAAATGAGTACTACTGGCTGGGTTGGAAGATTTAGGCCTTCA
GAACCTCATTTTACCCTTGATGGTAATAGCTTCTACAAGATCATCAGCAATGAAGAAGGT
TACAGACACATTTGCTATTTCCAAATAGATAAAAAAGACTGCACATTTATTACAAAAGGC
ACCTGGGAAGTCATCGGGATAGAAGCTCTAACCAGTGATTATCTATACTACATTAGTAAT
GAATATAAAGGAATGCCAGGAGGAAGGAATCTTTATAAAATCCAACTTATTGACTATACA
AAAGTGACATGCCTCAGTTGTGAGCTGAATCCGGAAAGGTGTCAGTACTATTCTGTGTCA
TTCAGTAAAGAGGCGAAGTATTATCAGCTGAGATGTTCCGGTCCTGGTCTGCCCCTCTAT
ACTCTACACAGCAGCGTGAATGATAAAGGGCTGAGAGTCCTGGAAGACAATTCAGCTTTG
GATAAAATGCTGCAGAATGTCCAGATGCCCTCCAAAAAACTGGACTTCATTATTTTGAAT
GAAACAAAATTTTGGTATCAGATGATCTTGCCTCCTCATTTTGATAAATCCAAGAAATAT
CCTCTACTATTAGATGTGTATGCAGGCCCATGTAGTCAAAAAGCAGACACTGTCTTCAGA
CTGAACTGGGCCACTTACCTTGCAAGCACAGAAAACATTATAGTAGCTAGCTTTGATGGC
AGAGGAAGTGGTTACCAAGGAGATAAGATCATGCATGCAATCAACAGAAGACTGGGAACA
TTTGAAGTTGAAGATCAAATTGAAGCAGCCAGACAATTTTCAAAAATGGGATTTGTGGAC
AACAAACGAATTGCAATTTGGGGCTGGTCATATGGAGGGTACGTAACCTCAATGGTCCTG
GGATCGGGAAGTGGCGTGTTCAAGTGTGGAATAGCCGTGGCGCCTGTATCCCGGTGGGAG
TACTATGACTCAGTGTACACAGAACGTTACATGGGTCTCCCAACTCCAGAAGACAACCTT
GACCATTACAGAAATTCAACAGTCATGAGCAGAGCTGAAAATTTTAAACAAGTTGAGTAC
CTCCTTATTCATGGAACAGCAGATGATAACGTTCACTTTCAGCAGTCAGCTCAGATCTCC
AAAGCCCTGGTCGATGTTGGAGTGGATTTCCAGGCAATGTGGTATACTGATGAAGACCAT
GGAATAGCTAGCAGCACAGCACACCAACATATATATACCCACATGAGCCACTTCATAAAA
CAATGTTTCTCTTTACCTTAG
Protein Properties
Number of Residues 766
Molecular Weight 88277.9
Theoretical pI 5.92
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 7-28
Protein Sequence
>Dipeptidyl peptidase 4
MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSL
RWISDHEYLYKQENNILVFNAEYGNSSVFLENSTFDEFGHSINDYSISPDGQFILLEYNY
VKQWRHSYTASYDIYDLNKRQLITEERIPNNTQWVTWSPVGHKLAYVWNNDIYVKIEPNL
PSYRITWTGKEDIIYNGITDWVYEEEVFSAYSALWWSPNGTFLAYAQFNDTEVPLIEYSF
YSDESLQYPKTVRVPYPKAGAVNPTVKFFVVNTDSLSSVTNATSIQITAPASMLIGDHYL
CDVTWATQERISLQWLRRIQNYSVMDICDYDESSGRWNCLVARQHIEMSTTGWVGRFRPS
EPHFTLDGNSFYKIISNEEGYRHICYFQIDKKDCTFITKGTWEVIGIEALTSDYLYYISN
EYKGMPGGRNLYKIQLSDYTKVTCLSCELNPERCQYYSVSFSKEAKYYQLRCSGPGLPLY
TLHSSVNDKGLRVLEDNSALDKMLQNVQMPSKKLDFIILNETKFWYQMILPPHFDKSKKY
PLLLDVYAGPCSQKADTVFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINRRLGT
FEVEDQIEAARQFSKMGFVDNKRIAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWE
YYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQIS
KALVDVGVDFQAMWYTDEDHGIASSTAHQHIYTHMSHFIKQCFSLP
GenBank ID Protein 35336
UniProtKB/Swiss-Prot ID P27487
UniProtKB/Swiss-Prot Entry Name DPP4_HUMAN
PDB IDs
GenBank Gene ID X60708
GeneCard ID DPP4
GenAtlas ID DPP4
HGNC ID HGNC:3009
References
General References
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  4. Gorvel JP, Ferrero A, Chambraud L, Rigal A, Bonicel J, Maroux S: Expression of sucrase-isomaltase and dipeptidylpeptidase IV in human small intestine and colon. Gastroenterology. 1991 Sep;101(3):618-25. [PubMed:1677636 ]
  5. Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C: Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993 Jul 23;261(5120):466-9. [PubMed:8101391 ]
  6. De Meester I, Vanham G, Kestens L, Vanhoof G, Bosmans E, Gigase P, Scharpe S: Binding of adenosine deaminase to the lymphocyte surface via CD26. Eur J Immunol. 1994 Mar;24(3):566-70. [PubMed:7907293 ]
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  8. Gines S, Marino M, Mallol J, Canela EI, Morimoto C, Callebaut C, Hovanessian A, Casado V, Lluis C, Franco R: Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. Biochem J. 2002 Jan 15;361(Pt 2):203-9. [PubMed:11772392 ]
  9. Aertgeerts K, Ye S, Shi L, Prasad SG, Witmer D, Chi E, Sang BC, Wijnands RA, Webb DR, Swanson RV: N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding. Protein Sci. 2004 Jan;13(1):145-54. [PubMed:14691230 ]
  10. Ohnuma K, Uchiyama M, Yamochi T, Nishibashi K, Hosono O, Takahashi N, Kina S, Tanaka H, Lin X, Dang NH, Morimoto C: Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem. 2007 Mar 30;282(13):10117-31. Epub 2007 Feb 6. [PubMed:17287217 ]
  11. Misumi Y, Hayashi Y, Arakawa F, Ikehara Y: Molecular cloning and sequence analysis of human dipeptidyl peptidase IV, a serine proteinase on the cell surface. Biochim Biophys Acta. 1992 Jul 15;1131(3):333-6. [PubMed:1352704 ]
  12. Darmoul D, Lacasa M, Baricault L, Marguet D, Sapin C, Trotot P, Barbat A, Trugnan G: Dipeptidyl peptidase IV (CD 26) gene expression in enterocyte-like colon cancer cell lines HT-29 and Caco-2. Cloning of the complete human coding sequence and changes of dipeptidyl peptidase IV mRNA levels during cell differentiation. J Biol Chem. 1992 Mar 5;267(7):4824-33. [PubMed:1347043 ]
  13. Tanaka T, Camerini D, Seed B, Torimoto Y, Dang NH, Kameoka J, Dahlberg HN, Schlossman SF, Morimoto C: Cloning and functional expression of the T cell activation antigen CD26. J Immunol. 1992 Jul 15;149(2):481-6. [PubMed:1352530 ]
  14. Tanaka T: Cloning and functional expression of the T cell activation antigen CD26. J Immunol. 1993 Mar 1;150(5):2090. [PubMed:8094732 ]
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  16. Darmoul D, Lacasa M, Chantret I, Swallow DM, Trugnan G: Isolation of a cDNA probe for the human intestinal dipeptidylpeptidase IV and assignment of the gene locus DPP4 to chromosome 2. Ann Hum Genet. 1990 Jul;54(Pt 3):191-7. [PubMed:1977364 ]
  17. Bohm SK, Gum JR Jr, Erickson RH, Hicks JW, Kim YS: Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter. Biochem J. 1995 Nov 1;311 ( Pt 3):835-43. [PubMed:7487939 ]
  18. Davoodi J, Kelly J, Gendron NH, MacKenzie AE: The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26. Proteomics. 2007 Jun;7(13):2300-10. [PubMed:17549790 ]
  19. Morrison ME, Vijayasaradhi S, Engelstein D, Albino AP, Houghton AN: A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. J Exp Med. 1993 Apr 1;177(4):1135-43. [PubMed:8096237 ]
  20. Loster K, Zeilinger K, Schuppan D, Reutter W: The cysteine-rich region of dipeptidyl peptidase IV (CD 26) is the collagen-binding site. Biochem Biophys Res Commun. 1995 Dec 5;217(1):341-8. [PubMed:8526932 ]
  21. Cordero OJ, Salgado FJ, Vinuela JE, Nogueira M: Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes. Immunobiology. 1997 Nov;197(5):522-33. [PubMed:9413751 ]
  22. Abbott CA, McCaughan GW, Gorrell MD: Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity. FEBS Lett. 1999 Sep 24;458(3):278-84. [PubMed:10570924 ]
  23. Cordero OJ, Ayude D, Nogueira M, Rodriguez-Berrocal FJ, de la Cadena MP: Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer. Br J Cancer. 2000 Nov;83(9):1139-46. [PubMed:11027426 ]
  24. Salgado FJ, Vela E, Martin M, Franco R, Nogueira M, Cordero OJ: Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human activated lymphocytes. Cytokine. 2000 Jul;12(7):1136-41. [PubMed:10880264 ]
  25. Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C: Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8439-44. [PubMed:10900005 ]
  26. Alfalah M, Jacob R, Naim HY: Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans as well as association with lipid microdomains. J Biol Chem. 2002 Mar 22;277(12):10683-90. Epub 2001 Dec 28. [PubMed:11773049 ]
  27. Salgado FJ, Lojo J, Alonso-Lebrero JL, Lluis C, Franco R, Cordero OJ, Nogueira M: A role for interleukin-12 in the regulation of T cell plasma membrane compartmentation. J Biol Chem. 2003 Jul 4;278(27):24849-57. Epub 2003 Apr 3. [PubMed:12676959 ]
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  30. Shin JW, Jurisic G, Detmar M: Lymphatic-specific expression of dipeptidyl peptidase IV and its dual role in lymphatic endothelial function. Exp Cell Res. 2008 Oct 1;314(16):3048-56. doi: 10.1016/j.yexcr.2008.07.024. Epub 2008 Aug 3. [PubMed:18708048 ]
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  35. Thoma R, Loffler B, Stihle M, Huber W, Ruf A, Hennig M: Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV. Structure. 2003 Aug;11(8):947-59. [PubMed:12906826 ]