{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P27487","secondaryAccessions":["Q53TN1"],"uniProtkbId":"DPP4_HUMAN","entryAudit":{"firstPublicDate":"1992-08-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-02-01","entryVersion":251,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Dipeptidyl peptidase 4"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10593948"}],"value":"3.4.14.5"}]},"alternativeNames":[{"fullName":{"value":"ADABP"}},{"fullName":{"value":"Adenosine deaminase complexing protein 2"},"shortNames":[{"value":"ADCP-2"}]},{"fullName":{"value":"Dipeptidyl peptidase IV"},"shortNames":[{"value":"DPP IV"}]},{"fullName":{"value":"T-cell activation antigen CD26"}},{"fullName":{"value":"TP103"}}],"cdAntigenNames":[{"value":"CD26"}],"contains":[{"recommendedName":{"fullName":{"value":"Dipeptidyl peptidase 4 membrane form"}},"alternativeNames":[{"fullName":{"value":"Dipeptidyl peptidase IV membrane form"}}]},{"recommendedName":{"fullName":{"value":"Dipeptidyl peptidase 4 soluble form"}},"alternativeNames":[{"fullName":{"value":"Dipeptidyl peptidase IV soluble form"}}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:3009"}],"value":"DPP4"},"synonyms":[{"value":"ADCP2"},{"value":"CD26"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10570924"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10593948"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10900005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10951221"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11772392"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14691230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16254193"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16651416"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17287217"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17549790"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18708048"}],"value":"Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:17287217). Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:14691230). Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). 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 (PubMed:10593948, PubMed:16651416). May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation (PubMed:18708048). When overexpressed, enhanced cell proliferation, a process inhibited by GPC3 (PubMed:17549790). Also acts 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 such as brain natriuretic peptide 32 (PubMed:10570924, PubMed:16254193). Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline (PubMed:10593948)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23835475"}],"value":"(Microbial infection) Acts as a receptor for human coronavirus MERS-CoV-2"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.","ecNumber":"3.4.14.5","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10593948"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17549790"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18708048"}],"value":"Inhibited by GPC3 and diprotin A"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10900005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10951221"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12483204"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12646248"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12676959"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12832764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12906826"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14691230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15016824"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448155"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16651416"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17287217"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17549790"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23486063"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7907293"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8101391"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8526932"}],"value":"Monomer. Homodimer (PubMed:12483204, PubMed:12646248, PubMed:12832764, PubMed:12906826, PubMed:15448155, PubMed:17287217). Heterodimer with Seprase (FAP) (PubMed:16651416). Requires homodimerization for optimal dipeptidyl peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217). Associates with collagen (PubMed:8526932). Interacts with PTPRC; the interaction is enhanced in an interleukin-12-dependent manner in activated lymphocytes (PubMed:12676959). Interacts (via extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity (PubMed:10951221, PubMed:14691230, PubMed:15016824, PubMed:7907293, PubMed:8101391). Interacts with CAV1 (via the N-terminus); the interaction is direct (PubMed:17287217). Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11 (PubMed:17287217). Interacts with IGF2R; the interaction is direct (PubMed:10900005). Interacts with GPC3 (PubMed:17549790). Interacts with human coronavirus-EMC spike protein and acts as a receptor for this virus (PubMed:23486063)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23835475"}],"value":"(Microbial infection) Interacts with MERS coronavirus/MERS-CoV spike protein"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P51671","geneName":"CCL11","intActId":"EBI-727357"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P02778","geneName":"CXCL10","intActId":"EBI-7815386"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"O14625","geneName":"CXCL11","intActId":"EBI-2871971"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P19875","geneName":"CXCL2","intActId":"EBI-2114901"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"Q07325","geneName":"CXCL9","intActId":"EBI-3911467"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P27487","geneName":"DPP4","intActId":"EBI-2871277"},"numberOfExperiments":12,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P01275","geneName":"GCG","intActId":"EBI-7629173"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"Q14416","geneName":"GRM2","intActId":"EBI-10232876"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P01282","geneName":"VIP","intActId":"EBI-751454"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"P56658","geneName":"ADA","intActId":"EBI-7475530"},"numberOfExperiments":5,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"A0A2R4KP93","geneName":"S","intActId":"EBI-25589622"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"K0BRG7","geneName":"S","intActId":"EBI-16040613"},"numberOfExperiments":5,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"K9N5Q8","geneName":"S","intActId":"EBI-25474996"},"numberOfExperiments":7,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P27487","intActId":"EBI-2871277"},"interactantTwo":{"uniProtKBAccession":"R9UQ53","geneName":"S","intActId":"EBI-25645424"},"numberOfExperiments":3,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Dipeptidyl peptidase 4 soluble form","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10951221"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16254193"}],"value":"Detected in the serum and the seminal fluid"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10951221"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16254193"}],"value":"Secreted","id":"SL-0243"}}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10900005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11772392"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11773049"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12676959"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16651416"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17287217"}],"value":"Translocated to the apical membrane through the concerted action of N- and O-Glycans and its association with lipid microdomains containing cholesterol and sphingolipids (PubMed:11773049). Redistributed to membrane rafts in T-cell in an interleukin-12-dependent activation (PubMed:12676959). Its interaction with CAV1 is necessary for its translocation to membrane rafts (PubMed:17287217). Colocalized with PTPRC in membrane rafts (PubMed:12676959). Colocalized with FAP in invadopodia and lamellipodia of migratory activated endothelial cells in collagenous matrix. Colocalized with FAP on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma (PubMed:16651416). Colocalized with ADA at the cell junction in lymphocyte-epithelial cell adhesion (PubMed:11772392). Colocalized with IGF2R in internalized cytoplasmic vesicles adjacent to the cell surface (PubMed:10900005)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10900005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11772392"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"8101391"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"value":"Single-pass type II membrane protein","id":"SL-9906"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11773049"}],"value":"Apical cell membrane","id":"SL-0015"},"topology":{"value":"Single-pass type II membrane protein","id":"SL-9906"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16651416"}],"value":"Cell projection, invadopodium membrane","id":"SL-0290"},"topology":{"value":"Single-pass type II membrane protein","id":"SL-9906"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16651416"}],"value":"Cell projection, lamellipodium membrane","id":"SL-0292"},"topology":{"value":"Single-pass type II membrane protein","id":"SL-9906"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11772392"}],"value":"Cell junction","id":"SL-0038"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17287217"}],"value":"Membrane raft","id":"SL-0370"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1677636"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18708048"}],"value":"Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney, uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10880264"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12676959"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16651416"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16670267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9413751"}],"value":"Up-regulated by IL12/interleukin-12 on activated T-cells. IL12-activated cells expressed enhanced levels of DPP4 but not mRNAs. Down-regulated by TNF. Up-regulated in migratory endothelial cells and in the invasive endothelial cells in tumors. Induced by hypoxia (PubMed:16670267)"}],"commentType":"INDUCTION"},{"texts":[{"value":"The extracellular cysteine-rich region is necessary for association with collagen, dimer formation and optimal dipeptidyl peptidase activity"}],"commentType":"DOMAIN"},{"texts":[{"value":"The soluble form (Dipeptidyl peptidase 4 soluble form also named SDPP) derives from the membrane form (Dipeptidyl peptidase 4 membrane form also named MDPP) by proteolytic processing"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10900005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11773049"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12483204"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12646248"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12906826"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16335952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19159218"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20684603"}],"value":"N- and O-Glycosylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10900005"}],"value":"Phosphorylated. Mannose 6-phosphate residues in the carbohydrate moiety are necessary for interaction with IGF2R in activated T-cells. Mannose 6-phosphorylation is induced during T-cell activation"}],"commentType":"PTM"},{"texts":[{"value":"Level of plasma concentrations of the soluble form (SDPP) can be managed as a colon carcinoma diagnostic and prognostic marker"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the peptidase S9B family. DPPIV subfamily"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/Dipeptidyl_peptidase-4","ftp":false,"note":"Dipeptidyl peptidase-4 entry"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/40360/DPP4","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":766,"modifier":"EXACT"}},"description":"Dipeptidyl peptidase 4 membrane form","featureId":"PRO_0000027213"},{"type":"Chain","location":{"start":{"value":39,"modifier":"EXACT"},"end":{"value":766,"modifier":"EXACT"}},"description":"Dipeptidyl peptidase 4 soluble form","featureId":"PRO_0000027214"},{"type":"Topological 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