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Protein

Dipeptidyl peptidase 4

Gene

Dpp4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity

Catalytic activityi

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

Enzyme regulationi

Inhibited by GPC3 and diprotin A.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei631Charge relay systemPROSITE-ProRule annotation1
Active sitei709Charge relay systemPROSITE-ProRule annotation1
Active sitei741Charge relay systemPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • cell adhesion Source: UniProtKB-KW
  • endothelial cell migration Source: UniProtKB
  • establishment of localization Source: RGD
  • negative regulation of extracellular matrix disassembly Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • proteolysis Source: RGD
  • regulation of T cell mediated immunity Source: RGD
  • T cell costimulation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Protease, Serine protease

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

BRENDAi3.4.14.5. 5301.

Protein family/group databases

ESTHERiratno-dpp4. DPP4N_Peptidase_S9.
MEROPSiS09.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Dipeptidyl peptidase 4 (EC:3.4.14.5By similarity)
Alternative name(s):
Bile canaliculus domain-specific membrane glycoprotein
Dipeptidyl peptidase IV
Short name:
DPP IV
GP110 glycoprotein
T-cell activation antigen CD26
CD_antigen: CD26
Cleaved into the following 3 chains:
Alternative name(s):
Dipeptidyl peptidase IV membrane form
Alternative name(s):
Dipeptidyl peptidase IV soluble form
Alternative name(s):
Dipeptidyl peptidase IV 60 kDa soluble form
Gene namesi
Name:Dpp4
Synonyms:Cd26
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2515. Dpp4.

Subcellular locationi

Dipeptidyl peptidase 4 soluble form :
  • Secreted

  • Note: Detected in the serum and the seminal fluid.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6CytoplasmicSequence analysis6
Transmembranei7 – 28Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini29 – 767ExtracellularSequence analysisAdd BLAST739

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • cell junction Source: UniProtKB-SubCell
  • cell surface Source: UniProtKB
  • endocytic vesicle Source: UniProtKB
  • endoplasmic reticulum Source: RGD
  • extracellular region Source: UniProtKB-SubCell
  • Golgi apparatus Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • invadopodium membrane Source: UniProtKB
  • lamellipodium Source: UniProtKB
  • lamellipodium membrane Source: UniProtKB-SubCell
  • membrane raft Source: UniProtKB-SubCell
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi629G → A: Reduced activity. 1 Publication1
Mutagenesisi629G → R: Reduced activity. 1 Publication1
Mutagenesisi630W → E: No effect on activity. 1 Publication1
Mutagenesisi631S → A: Reduced activity. 1 Publication1
Mutagenesisi632Y → F: No effect on activity. 1 Publication1
Mutagenesisi632Y → G: Reduced activity. 1 Publication1
Mutagenesisi632Y → L: Reduced activity. 1 Publication1
Mutagenesisi633G → A: Reduced activity. 1 Publication1
Mutagenesisi633G → S: Reduced activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000272191 – 767Dipeptidyl peptidase 4 membrane formAdd BLAST767
ChainiPRO_000002722037 – 767Dipeptidyl peptidase 4 soluble formAdd BLAST731
ChainiPRO_0000027221281 – 767Dipeptidyl peptidase 4 60 kDa soluble formAdd BLAST487

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi83N-linked (GlcNAc...)1 Publication1
Glycosylationi90N-linked (GlcNAc...)1 Publication1
Glycosylationi148N-linked (GlcNAc...)By similarity1
Glycosylationi217N-linked (GlcNAc...)By similarity1
Glycosylationi227N-linked (GlcNAc...)1 Publication1
Glycosylationi319N-linked (GlcNAc...)1 Publication1
Disulfide bondi326 ↔ 3371 Publication
Disulfide bondi383 ↔ 3951 Publication
Disulfide bondi445 ↔ 4481 Publication
Disulfide bondi455 ↔ 4731 Publication
Glycosylationi521N-linked (GlcNAc...)1 Publication1
Disulfide bondi650 ↔ 7631 Publication
Glycosylationi686N-linked (GlcNAc...)By similarity1

Post-translational modificationi

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.By similarity
N- and O-Glycosylated.By similarity
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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP14740.
PRIDEiP14740.

PTM databases

iPTMnetiP14740.
PhosphoSitePlusiP14740.
SwissPalmiP14740.

Expressioni

Tissue specificityi

Expressed in bile ducts and other epithelial brush borders (small intestine, kidney, colon, pancreatic duct); acinar structures in salivary glands; endothelial structures and T cell areas in thymus, spleen and lymph node.1 Publication

Interactioni

Subunit structurei

Monomer. Homodimer. 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 (via 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.By similarity

GO - Molecular functioni

  • collagen binding Source: RGD
  • protease binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

IntActiP14740. 1 interactor.
MINTiMINT-4655516.
STRINGi10116.ENSRNOP00000045536.

Chemistry databases

BindingDBiP14740.

Structurei

Secondary structure

1767
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi43 – 48Combined sources6
Beta strandi58 – 60Combined sources3
Beta strandi62 – 72Combined sources11
Beta strandi74 – 82Combined sources9
Beta strandi84 – 88Combined sources5
Helixi90 – 93Combined sources4
Helixi97 – 99Combined sources3
Beta strandi100 – 105Combined sources6
Beta strandi109 – 120Combined sources12
Beta strandi122 – 124Combined sources3
Beta strandi126 – 134Combined sources9
Turni135 – 138Combined sources4
Beta strandi139 – 141Combined sources3
Beta strandi148 – 150Combined sources3
Beta strandi152 – 155Combined sources4
Beta strandi157 – 160Combined sources4
Beta strandi162 – 166Combined sources5
Beta strandi169 – 175Combined sources7
Turni189 – 191Combined sources3
Beta strandi192 – 196Combined sources5
Helixi199 – 204Combined sources6
Beta strandi207 – 210Combined sources4
Beta strandi212 – 214Combined sources3
Beta strandi216 – 227Combined sources12
Beta strandi233 – 238Combined sources6
Beta strandi248 – 253Combined sources6
Beta strandi263 – 271Combined sources9
Helixi273 – 276Combined sources4
Beta strandi283 – 285Combined sources3
Turni289 – 293Combined sources5
Beta strandi296 – 305Combined sources10
Beta strandi308 – 329Combined sources22
Turni330 – 333Combined sources4
Beta strandi334 – 336Combined sources3
Helixi339 – 341Combined sources3
Beta strandi342 – 346Combined sources5
Beta strandi348 – 350Combined sources3
Beta strandi352 – 356Combined sources5
Beta strandi366 – 374Combined sources9
Beta strandi376 – 378Combined sources3
Beta strandi380 – 388Combined sources9
Turni391 – 393Combined sources3
Beta strandi396 – 398Combined sources3
Beta strandi401 – 403Combined sources3
Beta strandi405 – 411Combined sources7
Beta strandi413 – 421Combined sources9
Helixi423 – 425Combined sources3
Beta strandi430 – 438Combined sources9
Beta strandi443 – 450Combined sources8
Turni452 – 454Combined sources3
Beta strandi455 – 462Combined sources8
Beta strandi466 – 473Combined sources8
Beta strandi475 – 478Combined sources4
Beta strandi480 – 488Combined sources9
Beta strandi491 – 496Combined sources6
Helixi499 – 504Combined sources6
Helixi505 – 507Combined sources3
Beta strandi512 – 520Combined sources9
Beta strandi523 – 531Combined sources9
Beta strandi541 – 547Combined sources7
Helixi564 – 570Combined sources7
Beta strandi575 – 579Combined sources5
Beta strandi585 – 587Combined sources3
Helixi589 – 592Combined sources4
Helixi593 – 595Combined sources3
Turni599 – 601Combined sources3
Helixi602 – 616Combined sources15
Beta strandi620 – 630Combined sources11
Helixi632 – 641Combined sources10
Turni642 – 644Combined sources3
Beta strandi649 – 655Combined sources7
Helixi660 – 662Combined sources3
Helixi665 – 672Combined sources8
Turni677 – 680Combined sources4
Helixi681 – 686Combined sources6
Helixi690 – 698Combined sources9
Beta strandi699 – 706Combined sources8
Beta strandi710 – 712Combined sources3
Helixi714 – 726Combined sources13
Beta strandi732 – 736Combined sources5
Helixi746 – 764Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GBCX-ray2.80A/B38-767[»]
2GBFX-ray3.10A/B38-767[»]
2GBGX-ray3.00A/B38-767[»]
2GBIX-ray3.30A/B38-767[»]
2I3ZX-ray2.90A/B38-767[»]
2OAEX-ray3.00A/B38-767[»]
4FFVX-ray2.40A/B38-767[»]
4FFWX-ray2.90A/B38-767[»]
ProteinModelPortaliP14740.
SMRiP14740.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14740.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase S9B family. DPPIV subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2100. Eukaryota.
COG1506. LUCA.
HOGENOMiHOG000231875.
HOVERGENiHBG005527.
InParanoidiP14740.
KOiK01278.
PhylomeDBiP14740.

Family and domain databases

Gene3Di2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B_N.
[Graphical view]
PfamiPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14740-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTPWKVLLG LLGVAALVTI ITVPVVLLNK DEAAADSRRT YTLADYLKNT
60 70 80 90 100
FRVKSYSLRW VSDSEYLYKQ ENNILLFNAE HGNSSIFLEN STFEIFGDSI
110 120 130 140 150
SDYSVSPDRL FVLLEYNYVK QWRHSYTASY SIYDLNKRQL ITEEKIPNNT
160 170 180 190 200
QWITWSQEGH KLAYVWKNDI YVKIEPHLPS HRITSTGKEN VIFNGINDWV
210 220 230 240 250
YEEEIFGAYS ALWWSPNGTF LAYAQFNDTG VPLIEYSFYS DESLQYPKTV
260 270 280 290 300
WIPYPKAGAV NPTVKFFIVN TDSLSSTTTT IPMQITAPAS VTTGDHYLCD
310 320 330 340 350
VAWVSEDRIS LQWLRRIQNY SVMAICDYDK TTLVWNCPTT QEHIETSATG
360 370 380 390 400
WCGRFRPAEP HFTSDGSSFY KIVSDKDGYK HICQFQKDRK PEQVCTFITK
410 420 430 440 450
GAWEVISIEA LTSDYLYYIS NEYKEMPGGR NLYKIQLTDH TNKKCLSCDL
460 470 480 490 500
NPERCQYYSV SLSKEAKYYQ LGCRGPGLPL YTLHRSTDQK ELRVLEDNSA
510 520 530 540 550
LDKMLQDVQM PSKKLDFIVL NETRFWYQMI LPPHFDKSKK YPLLIDVYAG
560 570 580 590 600
PCSQKADAAF RLNWATYLAS TENIIVASFD GRGSGYQGDK IMHAINKRLG
610 620 630 640 650
TLEVEDQIEA ARQFLKMGFV DSKRVAIWGW SYGGYVTSMV LGSGSGVFKC
660 670 680 690 700
GIAVAPVSRW EYYDSVYTER YMGLPTPEDN LDHYRNSTVM SRAENFKQVE
710 720 730 740 750
YLLIHGTADD NVHFQQSAQI SKALVDAGVD FQAMWYTDED HGIASSTAHQ
760
HIYSHMSHFL QQCFSLR
Length:767
Mass (Da):88,089
Last modified:December 7, 2004 - v2
Checksum:iED947174F1F3E440
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti38R → A in AAA41096 (PubMed:2563382).Curated1
Sequence conflicti54Missing AA sequence (PubMed:1970322).Curated1
Sequence conflicti183I → T in AAA41272 (PubMed:3479775).Curated1
Sequence conflicti332T → N in AAA41272 (PubMed:3479775).Curated1
Sequence conflicti352C → V in AAA41272 (PubMed:3479775).Curated1
Sequence conflicti394V → D in AAA41272 (PubMed:3479775).Curated1
Sequence conflicti562L → F in AAA41272 (PubMed:3479775).Curated1
Sequence conflicti624R → Q in AAA41272 (PubMed:3479775).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04591 mRNA. Translation: AAA41096.1.
J02997 mRNA. Translation: AAA41272.1.
PIRiA39914.
RefSeqiNP_036921.1. NM_012789.1.
UniGeneiRn.91364.

Genome annotation databases

GeneIDi25253.
KEGGirno:25253.
UCSCiRGD:2515. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04591 mRNA. Translation: AAA41096.1.
J02997 mRNA. Translation: AAA41272.1.
PIRiA39914.
RefSeqiNP_036921.1. NM_012789.1.
UniGeneiRn.91364.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GBCX-ray2.80A/B38-767[»]
2GBFX-ray3.10A/B38-767[»]
2GBGX-ray3.00A/B38-767[»]
2GBIX-ray3.30A/B38-767[»]
2I3ZX-ray2.90A/B38-767[»]
2OAEX-ray3.00A/B38-767[»]
4FFVX-ray2.40A/B38-767[»]
4FFWX-ray2.90A/B38-767[»]
ProteinModelPortaliP14740.
SMRiP14740.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP14740. 1 interactor.
MINTiMINT-4655516.
STRINGi10116.ENSRNOP00000045536.

Chemistry databases

BindingDBiP14740.
ChEMBLiCHEMBL4653.

Protein family/group databases

ESTHERiratno-dpp4. DPP4N_Peptidase_S9.
MEROPSiS09.003.

PTM databases

iPTMnetiP14740.
PhosphoSitePlusiP14740.
SwissPalmiP14740.

Proteomic databases

PaxDbiP14740.
PRIDEiP14740.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25253.
KEGGirno:25253.
UCSCiRGD:2515. rat.

Organism-specific databases

CTDi1803.
RGDi2515. Dpp4.

Phylogenomic databases

eggNOGiKOG2100. Eukaryota.
COG1506. LUCA.
HOGENOMiHOG000231875.
HOVERGENiHBG005527.
InParanoidiP14740.
KOiK01278.
PhylomeDBiP14740.

Enzyme and pathway databases

BRENDAi3.4.14.5. 5301.

Miscellaneous databases

EvolutionaryTraceiP14740.
PROiP14740.

Family and domain databases

Gene3Di2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B_N.
[Graphical view]
PfamiPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDPP4_RAT
AccessioniPrimary (citable) accession number: P14740
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: December 7, 2004
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.