Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Dipeptidyl peptidase 4  

UniProtKB / Swiss-Prot ID :  DPP4_HUMAN

Gene Name (Synonyms) : 
DPP4, ADCP2, CD26  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Dipeptidyl peptidase 4 soluble form: Secreted. Note=Detected in the serum and the seminal fluid. Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein. Cell projection, invadopodium membrane; Sing 

Protein 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. 

Transmembrane Topology (topPTM) : DPP4_HUMAN 

Protein Sequence MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSLRWISDHEYLY...
Predicted Secondary Structure CCCCHHHHHHHHHHHHHHHHHHHHHHEEECCCCCCCCCCEEEEEEEEEECCCCCCCCCCCEECCCCCEEE...
Protein Variant -
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
44PhosphothreonineRKTYTLTDY
EEEEEEEEE
28.54Phosphositeplus
Link
52PhosphothreonineYLKNTYRLK
EECCCCCCC
14.39Phosphositeplus
Link
85N-linked (GlcNAc...).AEYGNSSVF
EEECCEEEE
30.15UniProtKB
Link
92N-linked (GlcNAc...).VFLENSTFD
EEECCCEEE
48.79UniProtKB
Link
150N-linked (Glc...)ERIPNNTQW
CCCCCCEEE
62.91HPRD
Link
150N-linked (GlcNAc...).ERIPNNTQW
CCCCCCEEE
62.91UniProtKB
Link
219N-linked (GlcNAc...).WWSPNGTFL
EECCCCCEE
57.53UniProtKB
Link
229N-linked (GlcNAc...).YAQFNDTEV
EEEECCCCC
43.12UniProtKB
Link
281N-linked (GlcNAc...).SSVTNATSI
CCCCCCCEE
38.78UniProtKB
Link
321N-linked (GlcNAc...).RRIQNYSVM
EECCCEEEE
28.77UniProtKB
Link
520N-linked (GlcNAc...).FIILNETKF
EEEECCEEE
44.47UniProtKB
Link
685N-linked (GlcNAc...).DHYRNSTVM
HHHHCCCHH
34.56UniProtKB
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
CD45_HUMANphysical interactionDIP:665EDIP1680916
ADA_HUMANin vitroHPRD:02187HPRD11772392
CXL10_HUMANin vitroHPRD:02187HPRD11390394
CD45_HUMANin vivoHPRD:02187HPRD1680916
DPP4_HUMANin vitroHPRD:02187HPRD11696365
SDF1_HUMANin vitroHPRD:02187HPRD11390394
CCL11_HUMANin vitroHPRD:02187HPRD11390394
CL3L1_HUMANin vitro
in vivo
HPRD:02187HPRD10961862
11390394
CXCL9_HUMANin vitroHPRD:02187HPRD11390394
CCL22_HUMANin vitro
in vivo
HPRD:02187HPRD9933589
11390394
CXL11_HUMANin vitroHPRD:02187HPRD11390394
CD4_HUMANin vitroHPRD:02187HPRD7539755
CCL5_HUMANin vitroHPRD:02187HPRD9516414
11390394
CXCR4_HUMANin vivoHPRD:02187HPRD11278278
CD4_HUMANENSP00000353731STRING
INS_HUMANENSP00000353731STRING
INS_HUMANENSP00000353731STRING
ITIH4_HUMANENSP00000353731STRING
CD45_HUMANENSP00000353731STRING
CCL5_HUMANENSP00000353731STRING
CAV1_HUMANENSP00000353731STRING
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Disease Reference
Kegg disease
H00032 Thyroid cancer
There are no disease associations of PTM sites.
Drug Reference
Kegg drug
D06553 Alogliptin benzoate (JAN/USAN)
D06578 Denagliptin tosylate (USAN)
D06645 Sitagliptin phosphate hydrate (JAN); Sitagliptin phosphate (USAN); Sitagliptin phosphate monohydrate
D07080 Vildagliptin (JAN/USAN/INN); Equa (TN); Galvus (TN)
D08516 Sitagliptin (Prop.INN)
D08616 Teneligliptin (INN)
D08631 Carmegliptin (USAN/INN)
D08996 Saxagliptin (INN)
D09326 Carmegliptin dihydrochloride (USAN)
D09333 Dutogliptin (USAN)
D09334 Dutogliptin tartrate (USAN)
D09566 Linagliptin (JAN/USAN/INN); Tradjenta (TN)
D09625 Gosogliptin (USAN/INN)
D09753 Saxagliptin hydrate (JAN/USAN); ONGLYZA (TN)
D09756 Teneligliptin hydrobromide hydrate (JAN)
D09780 Anagliptin (JAN/INN)
D10178 Trelagliptin (USAN)
D10179 Trelagliptin succinate (USAN)
D10262 Saxagliptin hydrochloride; Onglyza (TN)
D10317 Omarigliptin (USAN/INN)
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
N-linked Glycosylation
ReferencePubMed
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry.";
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.;
J. Proteome Res. 4:2070-2080(2005).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-520 AND ASN-685, AND MASSSPECTROMETRY.
"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry.";
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
J. Proteome Res. 8:651-661(2009).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-92; ASN-150; ASN-520 ANDASN-685, AND MASS SPECTROMETRY.
"The structure and function of human dipeptidyl peptidase IV,possessing a unique eight-bladed beta-propeller fold.";
Hiramatsu H., Kyono K., Higashiyama Y., Fukushima C., Shima H.,Sugiyama S., Inaka K., Yamamoto A., Shimizu R.;
Biochem. Biophys. Res. Commun. 302:849-854(2003).
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 35-771, HOMODIMERIZATION,GLYCOSYLATION AT ASN-85; ASN-219; ASN-229; ASN-281 AND ASN-321, ANDDISULFIDE BONDS.
"Crystal structure of human dipeptidyl peptidase IV/CD26 in complexwith a substrate analog.";
Rasmussen H.B., Branner S., Wiberg F.C., Wagtmann N.;
Nat. Struct. Biol. 10:19-25(2003).
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 39-766, HOMODIMERIZATION,GLYCOSYLATION AT ASN-85; ASN-150; ASN-219; ASN-229; ASN-281; ASN-321AND ASN-520, AND DISULFIDE BONDS.
"Structural basis of proline-specific exopeptidase activity asobserved in human dipeptidyl peptidase-IV.";
Thoma R., Loeffler B., Stihle M., Huber W., Ruf A., Hennig M.;
Structure 11:947-959(2003).
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 39-766, HOMODIMERIZATION,GLYCOSYLATION AT ASN-85; ASN-150; ASN-229 AND ASN-281, AND DISULFIDEBONDS.
"Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as potent, selectivedipeptidyl peptidase-4 (DPP4) inhibitors.";
Meng W., Brigance R.P., Chao H.J., Fura A., Harrity T.,Marcinkeviciene J., O'Connor S.P., Tamura J.K., Xie D., Zhang Y.,Klei H.E., Kish K., Weigelt C.A., Turdi H., Wang A., Zahler R.,Kirby M.S., Hamann L.G.;
J. Med. Chem. 53:5620-5628(2010).
Cited for: X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) OF 39-766, AND GLYCOSYLATION ATASN-85; ASN-92; ASN-150; ASN-219; ASN-229 AND ASN-520.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures