P27487 (DPP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	766 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.13 Ref.14 Ref.16 Ref.17 Ref.23 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.35 Ref.36 Ref.37 Ref.38
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 projection › invadopodium membrane; Single-pass type II membrane protein. Cell projection › lamellipodium 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.29 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 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 process	Cell adhesion
Cellular component	Cell junction Cell membrane Cell projection Membrane Secreted
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Aminopeptidase Hydrolase Protease Receptor Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	T cell activation Inferred from direct assay. 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 proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell-cell adhesion mediated by integrin Inferred from direct assay Ref.24. Source: UniProtKB response to hypoxia Inferred from direct assay. Source: UniProtKB
Cellular component	apical plasma membrane Inferred from direct assay. Source: UniProtKB cell surface Inferred from direct assay Ref.23Ref.24Ref.16. Source: UniProtKB endocytic vesicle Inferred from direct assay Ref.23. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW invadopodium membrane Inferred from direct assay Ref.30. Source: UniProtKB lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aminopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW dipeptidyl-peptidase activity Inferred from direct assay Ref.30Ref.14. Source: UniProtKB protease binding Inferred from physical interaction Ref.30. Source: UniProtKB protein homodimerization activity Inferred from physical interaction Ref.27. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW receptor binding Inferred from physical interaction Ref.23. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 766

766

Dipeptidyl peptidase 4 membrane form

PRO_0000027213

Chain

39 – 766

728

Dipeptidyl peptidase 4 soluble form

PRO_0000027214

Regions

Topological domain

1 – 6

6

Cytoplasmic Potential

Transmembrane

7 – 28

22

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

29 – 766

738

Extracellular Potential

Sites

Active site

630

1

Charge relay system By similarity

Active site

708

1

Charge relay system By similarity

Active site

740

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

85

1

N-linked (GlcNAc...) Ref.36 Ref.37 Ref.38 Ref.39

Glycosylation

92

1

N-linked (GlcNAc...) Ref.34 Ref.39

Glycosylation

150

1

N-linked (GlcNAc...) Ref.34 Ref.37 Ref.38 Ref.39

Glycosylation

219

1

N-linked (GlcNAc...) Ref.36 Ref.37 Ref.39

Glycosylation

229

1

N-linked (GlcNAc...) Ref.36 Ref.37 Ref.38 Ref.39

Glycosylation

281

1

N-linked (GlcNAc...) Ref.36 Ref.37 Ref.38

Glycosylation

321

1

N-linked (GlcNAc...) Ref.36 Ref.37

Glycosylation

520

1

N-linked (GlcNAc...) Ref.29 Ref.34 Ref.37 Ref.39

Glycosylation

685

1

N-linked (GlcNAc...) Ref.29 Ref.34

Disulfide bond

328 ↔ 339

Ref.36 Ref.37 Ref.38

Disulfide bond

385 ↔ 394

Ref.36 Ref.37 Ref.38

Disulfide bond

444 ↔ 447

Ref.36 Ref.37 Ref.38

Disulfide bond

454 ↔ 472

Ref.36 Ref.37 Ref.38

Disulfide bond

649 ↔ 762

Ref.36 Ref.37 Ref.38

Experimental info

Mutagenesis

85

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

92

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

150

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

205

1

E → K: Inhibits dipeptidyl peptidase activity. Ref.20

Mutagenesis

206

1

E → L: Inhibits dipeptidyl peptidase activity. Ref.20

Mutagenesis

219

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

229

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

281

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

321

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

520

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

685

1

N → A: Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation. Ref.28

Mutagenesis

750

1

H → A: Inhibits weakly homodimerization and dipeptidyl peptidase activity. Ref.27 Ref.31

Mutagenesis

750

1

H → E: Inhibits strongly homodimerization, dipeptidyl peptidase activity, interaction with CARD11 and T-cell costimulation activity. Ref.27 Ref.31

Sequence conflict

6

1

K → R in AAA52308. Ref.2

Sequence conflict

7

1

V → I in CAA43118. Ref.1

Sequence conflict

437

1

S → I in CAA43118. Ref.1

Sequence conflict

557

1

T → I in AAA52308. Ref.2

Sequence conflict

663

1

D → E in AAA52308. Ref.2

Secondary structure

1

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766

Helix Strand Turn

Details...

Helix

45 – 50

6

Beta strand

64 – 72

9

Beta strand

75 – 80

6

Turn

81 – 83

3

Beta strand

86 – 90

5

Turn

92 – 95

4

Helix

96 – 98

3

Beta strand

102 – 107

6

Beta strand

111 – 122

12

Beta strand

124 – 126

3

Beta strand

128 – 136

9

Turn

137 – 140

4

Beta strand

154 – 157

4

Beta strand

159 – 162

4

Beta strand

164 – 168

5

Beta strand

171 – 177

7

Turn

191 – 193

3

Beta strand

194 – 198

5

Helix

201 – 205

5

Beta strand

208 – 212

5

Beta strand

214 – 216

3

Beta strand

220 – 229

10

Beta strand

235 – 240

6

Beta strand

250 – 255

6

Beta strand

265 – 272

8

Beta strand

278 – 280

3

Beta strand

284 – 287

4

Helix

291 – 294

4

Beta strand

298 – 307

10

Beta strand

310 – 319

10

Beta strand

322 – 330

9

Turn

332 – 334

3

Beta strand

337 – 339

3

Turn

341 – 343

3

Beta strand

345 – 348

4

Beta strand

350 – 352

3

Beta strand

354 – 358

5

Beta strand

368 – 376

9

Beta strand

382 – 388

7

Beta strand

391 – 393

3

Beta strand

395 – 397

3

Beta strand

400 – 402

3

Beta strand

404 – 410

7

Beta strand

412 – 420

9

Helix

422 – 424

3

Beta strand

429 – 435

7

Beta strand

442 – 446

5

Turn

451 – 453

3

Beta strand

456 – 461

6

Helix

463 – 465

3

Beta strand

466 – 472

7

Beta strand

475 – 477

3

Beta strand

479 – 484

6

Turn

485 – 488

4

Beta strand

489 – 495

7

Helix

498 – 505

8

Beta strand

511 – 530

20

Beta strand

540 – 546

7

Helix

563 – 569

7

Beta strand

574 – 578

5

Beta strand

584 – 586

3

Helix

588 – 591

4

Helix

592 – 594

3

Helix

601 – 615

15

Beta strand

619 – 629

11

Helix

631 – 640

10

Turn

641 – 643

3

Beta strand

648 – 654

7

Helix

659 – 661

3

Helix

664 – 671

8

Turn

676 – 679

4

Helix

680 – 685

6

Helix

689 – 697

9

Beta strand

698 – 705

8

Beta strand

709 – 711

3

Helix

713 – 725

13

Beta strand

731 – 735

5

Helix

745 – 762

18

Sequences

	Sequence		Length	Mass (Da)
	P27487 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 5FB4A2C6662D6117	FASTA	766	88,279
	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

References

	« Hide 'large scale' referencesShow '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: 1352704] [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: 1347043] [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: 1352530] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Peripheral blood.
[4]	Erratum Tanaka T. J. Immunol. 150:2090-2090(1993) [PubMed: 8094732] [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: 7927537] [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. , 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: 19054851] [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. , 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: 15815621] [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. , 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: 15489334] [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: 1977364] [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: 7487939] [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: 1677636] [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: 10951221] [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: 17549790] [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: 8096237] [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: 8101391] [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: 7907293] [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: 8526932] [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: 9413751] [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: 10570924] [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: 11027426] [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: 10880264] [Abstract] Cited for: INDUCTION.
[23]	"Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptr 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: 10900005] [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: 11772392] [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: 11773049] [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: 12676959] [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: 15448155] [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: 14691230] [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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-520 AND ASN-685, MASS SPECTROMETRY. 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: 16651416] [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: 17287217] [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: 18708048] [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: 19557413] [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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-92; ASN-150; ASN-520 AND ASN-685, MASS SPECTROMETRY. Tissue: Liver.
[35]	"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: 12832764] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 38-766 IN COMPLEX WITH INHIBITOR, HOMODIMERIZATION.
[36]	"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: 12646248] [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.
[37]	"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: 12483204] [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.
[38]	"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: 12906826] [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.
[39]	"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: 20684603] [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.

Web resources

Wikipedia

Dipeptidyl peptidase-4 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X60708 mRNA. Translation: CAA43118.1.
M80536 mRNA. Translation: AAA52308.1.
M74777 mRNA. Translation: AAA51943.1.
U13735 , 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.

IPI

IPI00018953.

PIR

CDHU26. S24313.

RefSeq

NP_001926.2. NM_001935.3.

UniGene

Hs.368912.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J2E	X-ray	2.60	A/B	33-766	[»]
1N1M	X-ray	2.50	A/B	39-766	[»]
1NU6	X-ray	2.10	A/B	39-766	[»]
1NU8	X-ray	2.50	A/B	39-766	[»]
1PFQ	X-ray	1.90	A/B	36-766	[»]
1R9M	X-ray	2.10	A/B/C/D	39-766	[»]
1R9N	X-ray	2.30	A/B/C/D	39-766	[»]
1RWQ	X-ray	2.20	A/B	39-766	[»]
1TK3	X-ray	2.00	A/B	39-766	[»]
1TKR	X-ray	2.70	A/B	39-766	[»]
1U8E	X-ray	2.20	A/B	39-766	[»]
1W1I	X-ray	3.03	A/B/C/D	39-766	[»]
1WCY	X-ray	2.20	A/B	33-766	[»]
1X70	X-ray	2.10	A/B	40-766	[»]
2AJL	X-ray	2.50	I/J	39-766	[»]
2BGN	X-ray	3.15	A/B/C/D	39-766	[»]
2BGR	X-ray	2.00	A/B	29-766	[»]
2BUB	X-ray	2.66	A/B	39-766	[»]
2FJP	X-ray	2.40	A/B	40-766	[»]
2G5P	X-ray	2.40	A/B	39-764	[»]
2G5T	X-ray	2.30	A/B	39-764	[»]
2G63	X-ray	2.00	A/B/C/D	39-764	[»]
2HHA	X-ray	2.35	A/B	40-766	[»]
2I03	X-ray	2.40	A/B/C/D	39-764	[»]
2I78	X-ray	2.50	A/B/C/D	39-764	[»]
2IIT	X-ray	2.35	A/B	40-766	[»]
2IIV	X-ray	2.15	A/B	40-766	[»]
2JID	X-ray	2.80	A/B	31-766	[»]
2OAG	X-ray	2.30	A/B/C/D	39-764	[»]
2OGZ	X-ray	2.10	A/B	39-766	[»]
2OLE	X-ray	2.40	A/B	39-766	[»]
2ONC	X-ray	2.55	A/B/C/D	41-766	[»]
2OPH	X-ray	2.40	A/B	40-766	[»]
2OQI	X-ray	2.80	A/B/C/D	39-766	[»]
2OQV	X-ray	2.80	A/B	39-764	[»]
2P8S	X-ray	2.20	A/B	40-766	[»]
2QJR	X-ray	2.20	A/B	31-766	[»]
2QKY	X-ray	3.10	A/B/C/D	40-766	[»]
2QOE	X-ray	2.30	A/B	40-766	[»]
2QT9	X-ray	2.10	A/B	1-766	[»]
2QTB	X-ray	2.25	A/B	1-766	[»]
2RGU	X-ray	2.60	A/B	39-766	[»]
2RIP	X-ray	2.90	A	38-766	[»]
3BJM	X-ray	2.35	A/B	39-766	[»]
3C43	X-ray	2.30	A/B	40-766	[»]
3C45	X-ray	2.05	A/B	40-766	[»]
3CCB	X-ray	2.49	A/B/C/D	39-766	[»]
3CCC	X-ray	2.71	A/B/C/D	39-766	[»]
3D4L	X-ray	2.00	A/B	40-766	[»]
3EIO	X-ray	2.00	A/B	39-766	[»]
3F8S	X-ray	2.43	A/B	31-766	[»]
3G0B	X-ray	2.25	A/B/C/D	39-766	[»]
3G0C	X-ray	2.69	A/B/C/D	39-766	[»]
3G0D	X-ray	2.39	A/B/C/D	39-766	[»]
3G0G	X-ray	2.45	A/B/C/D	39-766	[»]
3H0C	X-ray	2.66	A/B	39-766	[»]
3HAB	X-ray	2.10	A/B	40-766	[»]
3HAC	X-ray	2.00	A/B	40-766	[»]
3KWF	X-ray	2.40	A/B	39-766	[»]
3KWJ	X-ray	2.80	A/B	39-766	[»]
3NOX	X-ray	2.34	A/B	39-766	[»]
3O95	X-ray	2.85	A/B/C/D	39-766	[»]
3O9V	X-ray	2.75	A/B/C/D	39-766	[»]
3OC0	X-ray	2.70	A/B	39-766	[»]
3OPM	X-ray	2.72	A/B/C/D	39-766	[»]
3Q8W	X-ray	3.64	A/B	39-764	[»]
3SWW	X-ray	2.00	A/B	39-766	[»]
3SX4	X-ray	2.60	A/B	39-766	[»]

ProteinModelPortal

P27487.

SMR

P27487. Positions 39-766.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-351N.

IntAct

P27487. 2 interactions.

MINT

MINT-4998658.

STRING

P27487.

Protein family/group databases

MEROPS

S09.003.

PTM databases

PhosphoSite

P27487.

Polymorphism databases

DMDM

1352311.

Proteomic databases

PeptideAtlas

P27487.

PRIDE

P27487.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360534; ENSP00000353731; ENSG00000197635.

GeneID

1803.

KEGG

hsa:1803.

UCSC

uc002ubz.1. human.

Organism-specific databases

CTD

1803.

GeneCards

GC02M162812.

H-InvDB

HIX0002546.

HGNC

HGNC:3009. DPP4.

MIM

102720. gene.

neXtProt

NX_P27487.

PharmGKB

PA27467.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05407.

GeneTree

ENSGT00530000062751.

HOGENOM

HBG351121.

HOVERGEN

HBG005527.

InParanoid

P27487.

OMA

YLASTEN.

OrthoDB

EOG4XSKPF.

PhylomeDB

P27487.

Enzyme and pathway databases

BRENDA

3.4.14.5. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P27487.

Bgee

P27487.

CleanEx

HS_DPP4.

Genevestigator

P27487.

GermOnline

ENSG00000197635. Homo sapiens.

Family and domain databases

InterPro

IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]

KO

K01278.

Pfam

PF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]

PROSITE

PS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01261. Sitagliptin.

NextBio

7345.

SOURCE

Search...

Entry information

Entry name

DPP4_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 141 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.