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Protein

Dipeptidyl peptidase 4

Gene

Dpp4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity regulationi

Inhibited by GPC3 and diprotin A.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei624Charge relay systemPROSITE-ProRule annotation1
Active sitei702Charge relay systemPROSITE-ProRule annotation1
Active sitei734Charge relay systemPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAminopeptidase, Hydrolase, Protease, Receptor, Serine protease
Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-MMU-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-MMU-400511 Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)

Protein family/group databases

ESTHERimouse-dpp4 DPP4N_Peptidase_S9
MEROPSiS09.003

Names & Taxonomyi

Protein namesi
Recommended name:
Dipeptidyl peptidase 4 (EC:3.4.14.5By similarity)
Alternative name(s):
Dipeptidyl peptidase IV
Short name:
DPP IV
T-cell activation antigen CD26
Thymocyte-activating molecule
Short name:
THAM
CD_antigen: CD26
Cleaved into the following 2 chains:
Alternative name(s):
Dipeptidyl peptidase IV membrane form
Alternative name(s):
Dipeptidyl peptidase IV soluble form
Gene namesi
Name:Dpp4
Synonyms:Cd26
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:94919 Dpp4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6CytoplasmicSequence analysis6
Transmembranei7 – 28Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini29 – 760ExtracellularSequence analysisAdd BLAST732

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3883

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000272151 – 760Dipeptidyl peptidase 4 membrane formAdd BLAST760
ChainiPRO_000002721637 – 760Dipeptidyl peptidase 4 soluble formBy similarityAdd BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi83N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi90N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi144N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi223N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi315N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi322 ↔ 333By similarity
Glycosylationi328N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi379 ↔ 388By similarity
Disulfide bondi438 ↔ 441By similarity
Disulfide bondi448 ↔ 466By similarity
Glycosylationi514N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi643 ↔ 756By similarity
Glycosylationi679N-linked (GlcNAc...) asparagineBy 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

EPDiP28843
MaxQBiP28843
PaxDbiP28843
PeptideAtlasiP28843
PRIDEiP28843

PTM databases

iPTMnetiP28843
PhosphoSitePlusiP28843
SwissPalmiP28843

Expressioni

Gene expression databases

BgeeiENSMUSG00000035000 Expressed in 185 organ(s), highest expression level in intestinal villus
CleanExiMM_DPP4
GenevisibleiP28843 MM

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

Protein-protein interaction databases

BioGridi199300, 1 interactor
IntActiP28843, 5 interactors
MINTiP28843
STRINGi10090.ENSMUSP00000044050

Chemistry databases

BindingDBiP28843

Structurei

3D structure databases

ProteinModelPortaliP28843
SMRiP28843
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi295 – 466Cys-richAdd BLAST172

Sequence similaritiesi

Belongs to the peptidase S9B family. DPPIV subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2100 Eukaryota
COG1506 LUCA
GeneTreeiENSGT00760000119233
HOGENOMiHOG000231875
HOVERGENiHBG005527
InParanoidiP28843
KOiK01278
OMAiAYVWKND
OrthoDBiEOG091G0BU5
PhylomeDBiP28843
TreeFamiTF313309

Family and domain databases

Gene3Di2.140.10.30, 1 hit
3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002471 Pept_S9_AS
IPR001375 Peptidase_S9
IPR002469 Peptidase_S9B_N
IPR038554 Peptidase_S9B_N_sf
PfamiView protein in Pfam
PF00930 DPPIV_N, 1 hit
PF00326 Peptidase_S9, 1 hit
SUPFAMiSSF53474 SSF53474, 1 hit
PROSITEiView protein in PROSITE
PS00708 PRO_ENDOPEP_SER, 1 hit

Sequencei

Sequence statusi: Complete.

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

P28843-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKTPWKVLLG LLGVAALVTI ITVPIVLLSK DEAAADSRRT YSLADYLKST
60 70 80 90 100
FRVKSYSLWW VSDFEYLYKQ ENNILLLNAE HGNSSIFLEN STFESFGYHS
110 120 130 140 150
VSPDRLFVLL EYNYVKQWRH SYTASYNIYD VNKRQLITEE KIPNNTQWIT
160 170 180 190 200
WSPEGHKLAY VWKNDIYVKV EPHLPSHRIT STGEENVIYN GITDWVYEEE
210 220 230 240 250
VFGAYSALWW SPNNTFLAYA QFNDTGVPLI EYSFYSDESL QYPKTVWIPY
260 270 280 290 300
PKAGAVNPTV KFFIVNIDSL SSSSSAAPIQ IPAPASVARG DHYLCDVVWA
310 320 330 340 350
TEERISLQWL RRIQNYSVMA ICDYDKINLT WNCPSEQQHV EMSTTGWVGR
360 370 380 390 400
FRPAEPHFTS DGSSFYKIIS DKDGYKHICH FPKDKKDCTF ITKGAWEVIS
410 420 430 440 450
IEALTSDYLY YISNQYKEMP GGRNLYKIQL TDHTNVKCLS CDLNPERCQY
460 470 480 490 500
YAVSFSKEAK YYQLGCWGPG LPLYTLHRST DHKELRVLED NSALDRMLQD
510 520 530 540 550
VQMPSKKLDF IVLNETRFWY QMILPPHFDK SKKYPLLLDV YAGPCSQKAD
560 570 580 590 600
ASFRLNWATY LASTENIIVA SFDGRGSGYQ GDKIMHAINR RLGTLEVEDQ
610 620 630 640 650
IEAARQFVKM GFVDSKRVAI WGWSYGGYVT SMVLGSGSGV FKCGIAVAPV
660 670 680 690 700
SRWEYYDSVY TERYMGLPIP EDNLDHYRNS TVMSRAEHFK QVEYLLIHGT
710 720 730 740 750
ADDNVHFQQS AQISKALVDA GVDFQAMWYT DEDHGIASST AHQHIYSHMS
760
HFLQQCFSLH
Length:760
Mass (Da):87,437
Last modified:February 1, 1996 - v3
Checksum:iA5F644B46E4A3DF8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58384 mRNA Translation: CAA41274.1
U12620
, U12599, U12600, U12601, U12602, U12603, U12604, U12605, U12606, U12607, U12608, U12609, U12610, U12611, U12612, U12613, U12614, U12615, U12616, U12617, U12618, U12619 Genomic DNA Translation: AAA82213.1
AK085370 mRNA Translation: BAC39434.1
AK153939 mRNA Translation: BAE32266.1
BC022183 mRNA Translation: AAH22183.1
CCDSiCCDS16065.1
PIRiS23752
RefSeqiNP_001153015.1, NM_001159543.1
NP_034204.1, NM_010074.3
UniGeneiMm.1151

Genome annotation databases

EnsembliENSMUST00000047812; ENSMUSP00000044050; ENSMUSG00000035000
GeneIDi13482
KEGGimmu:13482
UCSCiuc008jvg.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58384 mRNA Translation: CAA41274.1
U12620
, U12599, U12600, U12601, U12602, U12603, U12604, U12605, U12606, U12607, U12608, U12609, U12610, U12611, U12612, U12613, U12614, U12615, U12616, U12617, U12618, U12619 Genomic DNA Translation: AAA82213.1
AK085370 mRNA Translation: BAC39434.1
AK153939 mRNA Translation: BAE32266.1
BC022183 mRNA Translation: AAH22183.1
CCDSiCCDS16065.1
PIRiS23752
RefSeqiNP_001153015.1, NM_001159543.1
NP_034204.1, NM_010074.3
UniGeneiMm.1151

3D structure databases

ProteinModelPortaliP28843
SMRiP28843
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199300, 1 interactor
IntActiP28843, 5 interactors
MINTiP28843
STRINGi10090.ENSMUSP00000044050

Chemistry databases

BindingDBiP28843
ChEMBLiCHEMBL3883

Protein family/group databases

ESTHERimouse-dpp4 DPP4N_Peptidase_S9
MEROPSiS09.003

PTM databases

iPTMnetiP28843
PhosphoSitePlusiP28843
SwissPalmiP28843

Proteomic databases

EPDiP28843
MaxQBiP28843
PaxDbiP28843
PeptideAtlasiP28843
PRIDEiP28843

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047812; ENSMUSP00000044050; ENSMUSG00000035000
GeneIDi13482
KEGGimmu:13482
UCSCiuc008jvg.2 mouse

Organism-specific databases

CTDi1803
MGIiMGI:94919 Dpp4

Phylogenomic databases

eggNOGiKOG2100 Eukaryota
COG1506 LUCA
GeneTreeiENSGT00760000119233
HOGENOMiHOG000231875
HOVERGENiHBG005527
InParanoidiP28843
KOiK01278
OMAiAYVWKND
OrthoDBiEOG091G0BU5
PhylomeDBiP28843
TreeFamiTF313309

Enzyme and pathway databases

ReactomeiR-MMU-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-MMU-400511 Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)

Miscellaneous databases

ChiTaRSiDpp4 mouse
PROiPR:P28843
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035000 Expressed in 185 organ(s), highest expression level in intestinal villus
CleanExiMM_DPP4
GenevisibleiP28843 MM

Family and domain databases

Gene3Di2.140.10.30, 1 hit
3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002471 Pept_S9_AS
IPR001375 Peptidase_S9
IPR002469 Peptidase_S9B_N
IPR038554 Peptidase_S9B_N_sf
PfamiView protein in Pfam
PF00930 DPPIV_N, 1 hit
PF00326 Peptidase_S9, 1 hit
SUPFAMiSSF53474 SSF53474, 1 hit
PROSITEiView protein in PROSITE
PS00708 PRO_ENDOPEP_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDPP4_MOUSE
AccessioniPrimary (citable) accession number: P28843
Secondary accession number(s): Q3U514
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: February 1, 1996
Last modified: November 7, 2018
This is version 169 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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