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P27487 (DPP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dipeptidyl peptidase 4

EC=3.4.14.5
Alternative name(s):
ADABP
Adenosine deaminase complexing protein 2
Short name=ADCP-2
Dipeptidyl peptidase IV
Short name=DPP IV
T-cell activation antigen CD26
TP103
CD_antigen=CD26

Cleaved into the following 2 chains:

  1. Dipeptidyl peptidase 4 membrane form
    Alternative name(s):
    Dipeptidyl peptidase IV membrane form
  2. Dipeptidyl peptidase 4 soluble form
    Alternative name(s):
    Dipeptidyl peptidase IV soluble form
Gene names
Name:DPP4
Synonyms:ADCP2, CD26
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length766 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.13 Ref.14 Ref.20 Ref.23 Ref.24 Ref.28 Ref.30 Ref.31 Ref.32

Catalytic activity

Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.

Enzyme regulation

Inhibited by GPC3 and diprotin A. Ref.14 Ref.32

Subunit structure

Monomer. Homodimer or heterodimer with Seprase (FAP). 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. Associates with collagen. Interacts with PTPRC; the interaction is enhanced in a interleukin-12-dependent manner in activated lymphocytes. Interacts (extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity. Interacts with CAV1 (via the N-terminus); the interaction is direct. Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11. Interacts with IGF2R; the interaction is direct. Interacts with GPC3. Interacts with human coronavirus-EMC spike protein and acts as a receptor for this virus. Ref.13 Ref.14 Ref.16 Ref.17 Ref.23 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40

Subcellular location

Dipeptidyl peptidase 4 soluble form: Secreted. Note: Detected in the serum and the seminal fluid. Ref.13 Ref.16 Ref.23 Ref.24 Ref.25 Ref.26 Ref.30 Ref.31

Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein. Cell projectioninvadopodium membrane; Single-pass type II membrane protein. Cell projectionlamellipodium membrane; Single-pass type II membrane protein. Cell junction. Membrane raft. Note: Translocated to the apical membrane through the concerted action of N- and O-Glycans and its association with lipid microdomains containing cholesterol and sphingolipids. Redistributed to membrane rafts in T-cell in a interleukin-12-dependent activation. Its interaction with CAV1 is necessary for its translocation to membrane rafts. Colocalized with PTPRC in membrane rafts. 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. Colocalized with ADA at the cell junction in lymphocyte-epithelial cell adhesion. Colocalized with IGF2R in internalized cytoplasmic vesicles adjacent to the cell surface. Ref.13 Ref.16 Ref.23 Ref.24 Ref.25 Ref.26 Ref.30 Ref.31

Tissue specificity

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. Ref.12 Ref.32

Induction

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. Ref.14 Ref.19 Ref.22 Ref.26 Ref.30 Ref.32

Domain

The extracellular cysteine-rich region is necessary for association with collagen, dimer formation and optimal dipeptidyl peptidase activity.

Post-translational modification

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.

N- and O-Glycosylated. Ref.23 Ref.25 Ref.38 Ref.39 Ref.40 Ref.41

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. Ref.23

Miscellaneous

Level of plasma concentrations of the soluble form (SDPP) can be managed as a colon carcinoma diagnostic and prognostic marker.

Sequence similarities

Belongs to the peptidase S9B family. DPPIV subfamily.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
Secreted
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionAminopeptidase
Hydrolase
Protease
Receptor
Serine protease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Inferred from direct assay PubMed 7594462. Source: UniProtKB

T cell costimulation

Inferred from direct assay Ref.23Ref.31. Source: UniProtKB

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

endothelial cell migration

Inferred from direct assay Ref.30. Source: UniProtKB

negative regulation of extracellular matrix disassembly

Inferred from direct assay Ref.30. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay Ref.14. Source: UniProtKB

regulation of cell-cell adhesion mediated by integrin

Inferred from direct assay Ref.24. Source: UniProtKB

response to hypoxia

Inferred from direct assay PubMed 16670267. Source: UniProtKB

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 15052268. Source: UniProtKB

cell surface

Inferred from direct assay Ref.23Ref.24PubMed 7594462Ref.16. Source: UniProtKB

endocytic vesicle

Inferred from direct assay Ref.23. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 21362503. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intercellular canaliculus

Inferred from electronic annotation. Source: Ensembl

invadopodium membrane

Inferred from direct assay Ref.30. Source: UniProtKB

lamellipodium

Inferred from direct assay Ref.30. Source: UniProtKB

lamellipodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 16670267. Source: UniProtKB

   Molecular_functionaminopeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

dipeptidyl-peptidase activity

Inferred from direct assay PubMed 14684150Ref.30Ref.14. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 22001206. Source: IntAct

protease binding

Inferred from physical interaction Ref.30. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 14684150Ref.31Ref.14PubMed 7594462Ref.16. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction PubMed 14684150Ref.27. Source: UniProtKB

receptor binding

Inferred from physical interaction Ref.23. Source: UniProtKB

serine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

serine-type peptidase activity

Inferred from direct assay PubMed 14684150. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 766766Dipeptidyl peptidase 4 membrane form
PRO_0000027213
Chain39 – 766728Dipeptidyl peptidase 4 soluble form
PRO_0000027214

Regions

Topological domain1 – 66Cytoplasmic Potential
Transmembrane7 – 2822Helical; Signal-anchor for type II membrane protein; Potential
Topological domain29 – 766738Extracellular Potential

Sites

Active site6301Charge relay system By similarity
Active site7081Charge relay system By similarity
Active site7401Charge relay system By similarity

Amino acid modifications

Glycosylation851N-linked (GlcNAc...) Ref.38 Ref.39 Ref.40 Ref.41
Glycosylation921N-linked (GlcNAc...) Ref.34 Ref.41
Glycosylation1501N-linked (GlcNAc...) Ref.34 Ref.39 Ref.40 Ref.41
Glycosylation2191N-linked (GlcNAc...) Ref.38 Ref.39 Ref.41
Glycosylation2291N-linked (GlcNAc...) Ref.38 Ref.39 Ref.40 Ref.41
Glycosylation2811N-linked (GlcNAc...) Ref.38 Ref.39 Ref.40
Glycosylation3211N-linked (GlcNAc...) Ref.38 Ref.39
Glycosylation5201N-linked (GlcNAc...) Ref.29 Ref.34 Ref.39 Ref.41
Glycosylation6851N-linked (GlcNAc...) Ref.29 Ref.34
Disulfide bond328 ↔ 339 Ref.38 Ref.39 Ref.40
Disulfide bond385 ↔ 394 Ref.38 Ref.39 Ref.40
Disulfide bond444 ↔ 447 Ref.38 Ref.39 Ref.40
Disulfide bond454 ↔ 472 Ref.38 Ref.39 Ref.40
Disulfide bond649 ↔ 762 Ref.38 Ref.39 Ref.40

Experimental info

Mutagenesis851N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis921N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis1501N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis2051E → K: Inhibits dipeptidyl peptidase activity. Ref.20
Mutagenesis2061E → L: Inhibits dipeptidyl peptidase activity. Ref.20
Mutagenesis2191N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis2291N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis2811N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis3211N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis5201N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis6851N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28
Mutagenesis7501H → A: Inhibits weakly homodimerization and dipeptidyl peptidase activity. Ref.27 Ref.31
Mutagenesis7501H → E: Inhibits strongly homodimerization, dipeptidyl peptidase activity, interaction with CARD11 and T-cell costimulation activity. Ref.27 Ref.31
Sequence conflict61K → R in AAA52308. Ref.2
Sequence conflict71V → I in CAA43118. Ref.1
Sequence conflict4371S → I in CAA43118. Ref.1
Sequence conflict5571T → I in AAA52308. Ref.2
Sequence conflict6631D → E in AAA52308. Ref.2

Secondary structure

.................................................................................................................................................................... 766
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P27487 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: 5FB4A2C6662D6117

FASTA76688,279
        10         20         30         40         50         60 
MKTPWKVLLG LLGAAALVTI ITVPVVLLNK GTDDATADSR KTYTLTDYLK NTYRLKLYSL 

        70         80         90        100        110        120 
RWISDHEYLY KQENNILVFN AEYGNSSVFL ENSTFDEFGH SINDYSISPD GQFILLEYNY 

       130        140        150        160        170        180 
VKQWRHSYTA SYDIYDLNKR QLITEERIPN NTQWVTWSPV GHKLAYVWNN DIYVKIEPNL 

       190        200        210        220        230        240 
PSYRITWTGK EDIIYNGITD WVYEEEVFSA YSALWWSPNG TFLAYAQFND TEVPLIEYSF 

       250        260        270        280        290        300 
YSDESLQYPK TVRVPYPKAG AVNPTVKFFV VNTDSLSSVT NATSIQITAP ASMLIGDHYL 

       310        320        330        340        350        360 
CDVTWATQER ISLQWLRRIQ NYSVMDICDY DESSGRWNCL VARQHIEMST TGWVGRFRPS 

       370        380        390        400        410        420 
EPHFTLDGNS FYKIISNEEG YRHICYFQID KKDCTFITKG TWEVIGIEAL TSDYLYYISN 

       430        440        450        460        470        480 
EYKGMPGGRN LYKIQLSDYT KVTCLSCELN PERCQYYSVS FSKEAKYYQL RCSGPGLPLY 

       490        500        510        520        530        540 
TLHSSVNDKG LRVLEDNSAL DKMLQNVQMP SKKLDFIILN ETKFWYQMIL PPHFDKSKKY 

       550        560        570        580        590        600 
PLLLDVYAGP CSQKADTVFR LNWATYLAST ENIIVASFDG RGSGYQGDKI MHAINRRLGT 

       610        620        630        640        650        660 
FEVEDQIEAA RQFSKMGFVD NKRIAIWGWS YGGYVTSMVL GSGSGVFKCG IAVAPVSRWE 

       670        680        690        700        710        720 
YYDSVYTERY MGLPTPEDNL DHYRNSTVMS RAENFKQVEY LLIHGTADDN VHFQQSAQIS 

       730        740        750        760 
KALVDVGVDF QAMWYTDEDH GIASSTAHQH IYTHMSHFIK QCFSLP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and sequence analysis of human dipeptidyl peptidase IV, a serine proteinase on the cell surface."
Misumi Y., Hayashi Y., Arakawa F., Ikehara Y.
Biochim. Biophys. Acta 1131:333-336(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"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."
Darmoul D., Lacasa M., Baricault L., Marguet D., Sapin C., Trotot P., Barbat A.
J. Biol. Chem. 267:4824-4833(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Colon.
[3]"Cloning and functional expression of the T cell activation antigen CD26."
Tanaka T., Camerini D., Seed B., Torimoto Y., Dang N.H., Kameoka J., Dahlberg H.N., Schlossman S.F., Morimoto C.
J. Immunol. 149:481-486(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Peripheral blood.
[4]Erratum
Tanaka T.
J. Immunol. 150:2090-2090(1993) [PubMed] [Europe PMC] [Abstract]
[5]"Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene."
Abbott C.A., Baker E., Sutherland G.R., McCaughan G.W.
Immunogenetics 40:331-338(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[6]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Prostate and Uterus.
[10]"Isolation of a cDNA probe for the human intestinal dipeptidylpeptidase IV and assignment of the gene locus DPP4 to chromosome 2."
Darmoul D., Lacasa M., Chantret I., Swallow D., Trugnan G.
Ann. Hum. Genet. 54:191-197(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 545-766.
Tissue: Colon.
[11]"Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter."
Boehm S.K., Gum J.R. Jr., Erickson R.H., Hicks J.W., Kim Y.S.
Biochem. J. 311:835-843(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
[12]"Expression of sucrase-isomaltase and dipeptidylpeptidase IV in human small intestine and colon."
Gorvel J.P., Ferrero A., Chambraud L., Rigal A., Bonicel J., Maroux S.
Gastroenterology 101:618-625(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-22, TISSUE SPECIFICITY.
[13]"Molecular characterization of dipeptidyl peptidase activity in serum: soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides."
Durinx C., Lambeir A.M., Bosmans E., Falmagne J.B., Berghmans R., Haemers A., Scharpe S., De Meester I.
Eur. J. Biochem. 267:5608-5613(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 29-34 AND 39-43, FUNCTION, INTERACTION WITH ADA, SUBCELLULAR LOCATION.
[14]"The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26."
Davoodi J., Kelly J., Gendron N.H., MacKenzie A.E.
Proteomics 7:2300-2310(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 659-669, FUNCTION, ENZYME REGULATION, INTERACTION WITH GPC3, IDENTIFICATION BY MASS SPECTROMETRY.
[15]"A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase."
Morrison M.E., Vijayasaradhi S., Engelstein D., Albino A.P., Houghton A.N.
J. Exp. Med. 177:1135-1143(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
Tissue: Kidney.
[16]"Direct association of adenosine deaminase with a T cell activation antigen, CD26."
Kameoka J., Tanaka T., Nojima Y., Schlossman S.F., Morimoto C.
Science 261:466-469(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADA, SUBCELLULAR LOCATION.
[17]"Binding of adenosine deaminase to the lymphocyte surface via CD26."
De Meester I., Vanham G., Kestens L., Vanhoof G., Bosmans E., Gigase P., Scharpe S.
Eur. J. Immunol. 24:566-570(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADA.
[18]"The cysteine-rich region of dipeptidyl peptidase IV (CD 26) is the collagen-binding site."
Loster K., Zeilinger K., Schuppan D., Reutter W.
Biochem. Biophys. Res. Commun. 217:341-348(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH COLLAGEN.
[19]"Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes."
Cordero O.J., Salgado F.J., Vinuela J.E., Nogueira M.
Immunobiology 197:522-533(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[20]"Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity."
Abbott C.A., McCaughan G.W., Gorrell M.D.
FEBS Lett. 458:278-284(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-205 AND GLU-206.
[21]"Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer."
Cordero O.J., Ayude D., Nogueira M., Rodriguez-Berrocal F.J., de la Cadena M.P.
Br. J. Cancer 83:1139-1146(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH CANCER.
[22]"Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human activated lymphocytes."
Salgado F.J., Vela E., Martin M., Franco R., Nogueira M., Cordero O.J.
Cytokine 12:1136-1141(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[23]"Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation."
Ikushima H., Munakata Y., Ishii T., Iwata S., Terashima M., Tanaka H., Schlossman S.F., Morimoto C.
Proc. Natl. Acad. Sci. U.S.A. 97:8439-8444(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IGF2R, GLYCOSYLATION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[24]"Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction."
Gines S., Marino M., Mallol J., Canela E.I., Morimoto C., Callebaut C., Hovanessian A., Casado V., Lluis C., Franco R.
Biochem. J. 361:203-209(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[25]"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."
Alfalah M., Jacob R., Naim H.Y.
J. Biol. Chem. 277:10683-10690(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, SUBCELLULAR LOCATION.
[26]"A role for interleukin-12 in the regulation of T cell plasma membrane compartmentation."
Salgado F.J., Lojo J., Alonso-Lebrero J.L., Lluis C., Franco R., Cordero O.J., Nogueira M.
J. Biol. Chem. 278:24849-24857(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPRC, INDUCTION, SUBCELLULAR LOCATION.
[27]"One site mutation disrupts dimer formation in human DPP-IV proteins."
Chien C.H., Huang L.H., Chou C.Y., Chen Y.S., Han Y.S., Chang G.G., Liang P.H., Chen X.
J. Biol. Chem. 279:52338-52345(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMODIMERIZATION, MUTAGENESIS OF HIS-750.
[28]"N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding."
Aertgeerts K., Ye S., Shi L., Prasad S.G., Witmer D., Chi E., Sang B.C., Wijnands R.A., Webb D.R., Swanson R.V.
Protein Sci. 13:145-154(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ADA, MUTAGENESIS OF ASN-85; ASN-92; ASN-150; ASN-219; ASN-229; ASN-281; ASN-321; ASN-520 AND ASN-685.
[29]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-520 AND ASN-685.
Tissue: Plasma.
[30]"The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices."
Ghersi G., Zhao Q., Salamone M., Yeh Y., Zucker S., Chen W.T.
Cancer Res. 66:4652-4661(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION, INDUCTION, SUBCELLULAR LOCATION.
[31]"Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1."
Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C.
J. Biol. Chem. 282:10117-10131(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, HOMODIMERIZATION, INTERACTION WITH CARD11 AND CAV1, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-750.
[32]"Lymphatic-specific expression of dipeptidyl peptidase IV and its dual role in lymphatic endothelial function."
Shin J.W., Jurisic G., Detmar M.
Exp. Cell Res. 314:3048-3056(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
[33]"On the origin of serum CD26 and its altered concentration in cancer patients."
Cordero O.J., Salgado F.J., Nogueira M.
Cancer Immunol. Immunother. 58:1723-1747(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[34]"Glycoproteomics analysis of human liver tissue by combination of multiple 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) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-92; ASN-150; ASN-520 AND ASN-685.
Tissue: Liver.
[35]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]"Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC."
Raj V.S., Mou H., Smits S.L., Dekkers D.H., Muller M.A., Dijkman R., Muth D., Demmers J.A., Zaki A., Fouchier R.A., Thiel V., Drosten C., Rottier P.J., Osterhaus A.D., Bosch B.J., Haagmans B.L.
Nature 495:251-254(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CORONAVIRUS-EMC SPIKE PROTEIN.
[37]"High-resolution structure of human apo dipeptidyl peptidase IV/CD26 and its complex with 1-[([2-[(5-iodopyridin-2-yl)amino]-ethyl]amino)-acetyl]-2-cyano-(S)-pyrrolidine."
Oefner C., D'Arcy A., Mac Sweeney A., Pierau S., Gardiner R., Dale G.E.
Acta Crystallogr. D 59:1206-1212(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 38-766 IN COMPLEX WITH INHIBITOR, HOMODIMERIZATION.
[38]"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) [PubMed] [Europe PMC] [Abstract]
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, DISULFIDE BONDS.
[39]"Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog."
Rasmussen H.B., Branner S., Wiberg F.C., Wagtmann N.
Nat. Struct. Biol. 10:19-25(2003) [PubMed] [Europe PMC] [Abstract]
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-321 AND ASN-520, DISULFIDE BONDS.
[40]"Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV."
Thoma R., Loeffler B., Stihle M., Huber W., Ruf A., Hennig M.
Structure 11:947-959(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 39-766, HOMODIMERIZATION, GLYCOSYLATION AT ASN-85; ASN-150; ASN-229 AND ASN-281, DISULFIDE BONDS.
[41]"Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as potent, selective dipeptidyl 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) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) OF 39-766, GLYCOSYLATION AT ASN-85; ASN-92; ASN-150; ASN-219; ASN-229 AND ASN-520.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X60708 mRNA. Translation: CAA43118.1.
M80536 mRNA. Translation: AAA52308.1.
M74777 mRNA. Translation: AAA51943.1.
U13735 expand/collapse EMBL AC list , U13710, U13711, U13712, U13713, U13714, U13715, U13716, U13717, U13718, U13719, U13720, U13721, U13722, U13723, U13724, U13725, U13726, U13727, U13728, U13729, U13730, U13731, U13732, U13733, U13734 Genomic DNA. Translation: AAB60646.1.
AB451339 mRNA. Translation: BAG70153.1.
AB451488 mRNA. Translation: BAG70302.1.
AC008063 Genomic DNA. Translation: AAX93179.1.
CH471058 Genomic DNA. Translation: EAX11361.1.
BC013329 mRNA. Translation: AAH13329.2.
BC065265 mRNA. Translation: AAH65265.1.
S79876 Genomic DNA. Translation: AAB35614.1.
CCDSCCDS2216.1.
PIRCDHU26. S24313.
RefSeqNP_001926.2. NM_001935.3.
UniGeneHs.368912.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1J2EX-ray2.60A/B33-766[»]
1N1MX-ray2.50A/B39-766[»]
1NU6X-ray2.10A/B39-766[»]
1NU8X-ray2.50A/B39-766[»]
1PFQX-ray1.90A/B36-766[»]
1R9MX-ray2.10A/B/C/D39-766[»]
1R9NX-ray2.30A/B/C/D39-766[»]
1RWQX-ray2.20A/B39-766[»]
1TK3X-ray2.00A/B39-766[»]
1TKRX-ray2.70A/B39-766[»]
1U8EX-ray2.20A/B39-766[»]
1W1IX-ray3.03A/B/C/D39-766[»]
1WCYX-ray2.20A/B33-766[»]
1X70X-ray2.10A/B39-766[»]
2AJLX-ray2.50I/J39-766[»]
2BGNX-ray3.15A/B/C/D39-766[»]
2BGRX-ray2.00A/B29-766[»]
2BUBX-ray2.66A/B39-766[»]
2FJPX-ray2.40A/B39-766[»]
2G5PX-ray2.40A/B39-764[»]
2G5TX-ray2.30A/B39-764[»]
2G63X-ray2.00A/B/C/D39-764[»]
2HHAX-ray2.35A/B40-766[»]
2I03X-ray2.40A/B/C/D39-764[»]
2I78X-ray2.50A/B/C/D39-764[»]
2IITX-ray2.35A/B39-766[»]
2IIVX-ray2.15A/B39-766[»]
2JIDX-ray2.80A/B31-766[»]
2OAGX-ray2.30A/B/C/D39-764[»]
2OGZX-ray2.10A/B39-766[»]
2OLEX-ray2.40A/B39-766[»]
2ONCX-ray2.55A/B/C/D41-766[»]
2OPHX-ray2.40A/B39-766[»]
2OQIX-ray2.80A/B/C/D39-766[»]
2OQVX-ray2.80A/B39-764[»]
2P8SX-ray2.20A/B40-766[»]
2QJRX-ray2.20A/B31-766[»]
2QKYX-ray3.10A/B/C/D40-766[»]
2QOEX-ray2.30A/B39-766[»]
2QT9X-ray2.10A/B1-766[»]
2QTBX-ray2.25A/B1-766[»]
2RGUX-ray2.60A/B39-766[»]
2RIPX-ray2.90A38-766[»]
3BJMX-ray2.35A/B39-766[»]
3C43X-ray2.30A/B39-766[»]
3C45X-ray2.05A/B39-766[»]
3CCBX-ray2.49A/B/C/D39-766[»]
3CCCX-ray2.71A/B/C/D39-766[»]
3D4LX-ray2.00A/B39-766[»]
3EIOX-ray2.00A/B39-766[»]
3F8SX-ray2.43A/B31-766[»]
3G0BX-ray2.25A/B/C/D39-766[»]
3G0CX-ray2.69A/B/C/D39-766[»]
3G0DX-ray2.39A/B/C/D39-766[»]
3G0GX-ray2.45A/B/C/D39-766[»]
3H0CX-ray2.66A/B39-766[»]
3HABX-ray2.10A/B39-766[»]
3HACX-ray2.00A/B39-766[»]
3KWFX-ray2.40A/B39-766[»]
3KWJX-ray2.80A/B39-766[»]
3NOXX-ray2.34A/B39-766[»]
3O95X-ray2.85A/B/C/D39-766[»]
3O9VX-ray2.75A/B/C/D39-766[»]
3OC0X-ray2.70A/B39-766[»]
3OPMX-ray2.72A/B/C/D39-766[»]
3Q0TX-ray2.40A/B39-766[»]
3Q8WX-ray3.64A/B39-764[»]
3QBJX-ray2.21A/B31-766[»]
3SWWX-ray2.00A/B39-766[»]
3SX4X-ray2.60A/B39-766[»]
3VJKX-ray2.49A/B33-766[»]
3VJLX-ray2.39A/B33-766[»]
3VJMX-ray2.10A/B33-766[»]
3W2TX-ray2.36A/B33-766[»]
4A5SX-ray1.62A/B39-766[»]
4DSAX-ray3.25A/B39-766[»]
4DSZX-ray3.20A/B39-766[»]
4DTCX-ray3.00A/B39-766[»]
4G1FX-ray2.90A/B/C/D39-766[»]
4J3JX-ray3.20A/B39-766[»]
4JH0X-ray2.35A/B39-766[»]
4KR0X-ray2.70A39-766[»]
4L72X-ray3.00A39-766[»]
4LKOX-ray2.43A/B39-766[»]
4N8DX-ray1.65A/B39-766[»]
4N8EX-ray2.30A/B39-766[»]
4PNZX-ray1.90A/B39-766[»]
ProteinModelPortalP27487.
SMRP27487. Positions 39-766.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108137. 5 interactions.
DIPDIP-351N.
IntActP27487. 21 interactions.
MINTMINT-4998658.
STRING9606.ENSP00000353731.

Chemistry

BindingDBP27487.
ChEMBLCHEMBL284.
DrugBankDB01261. Sitagliptin.
GuidetoPHARMACOLOGY1612.

Protein family/group databases

MEROPSS09.003.

PTM databases

PhosphoSiteP27487.

Polymorphism databases

DMDM1352311.

Proteomic databases

MaxQBP27487.
PaxDbP27487.
PeptideAtlasP27487.
PRIDEP27487.

Protocols and materials databases

DNASU1803.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360534; ENSP00000353731; ENSG00000197635.
GeneID1803.
KEGGhsa:1803.
UCSCuc002ubz.3. human.

Organism-specific databases

CTD1803.
GeneCardsGC02M162812.
HGNCHGNC:3009. DPP4.
HPACAB045970.
MIM102720. gene.
neXtProtNX_P27487.
PharmGKBPA27467.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1506.
HOGENOMHOG000231875.
HOVERGENHBG005527.
InParanoidP27487.
KOK01278.
OMAETKFWYQ.
OrthoDBEOG761BT2.
PhylomeDBP27487.
TreeFamTF313309.

Enzyme and pathway databases

BRENDA3.4.14.5. 2681.
ReactomeREACT_17015. Metabolism of proteins.
SABIO-RKP27487.

Gene expression databases

ArrayExpressP27487.
BgeeP27487.
CleanExHS_DPP4.
GenevestigatorP27487.

Family and domain databases

Gene3D2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProIPR029058. AB_hydrolase.
IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]
PfamPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMSSF53474. SSF53474. 1 hit.
PROSITEPS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDPP4. human.
EvolutionaryTraceP27487.
GeneWikiDipeptidyl_peptidase-4.
GenomeRNAi1803.
NextBio7345.
PROP27487.
SOURCESearch...

Entry information

Entry nameDPP4_HUMAN
AccessionPrimary (citable) accession number: P27487
Secondary accession number(s): Q53TN1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries