DPP4_BOVIN
ID DPP4_BOVIN Reviewed; 765 AA.
AC P81425; Q3ZCC2; Q8WMG8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 26-JUL-2002, sequence version 3.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Dipeptidyl peptidase 4;
DE EC=3.4.14.5 {ECO:0000250|UniProtKB:P27487};
DE AltName: Full=Activation molecule 3;
DE Short=ACT3;
DE AltName: Full=Adenosine deaminase complexing protein;
DE Short=ADCP-I;
DE AltName: Full=Dipeptidyl peptidase IV;
DE Short=DPP IV;
DE AltName: Full=T-cell activation antigen CD26;
DE AltName: Full=WC10;
DE AltName: CD_antigen=CD26;
DE Contains:
DE RecName: Full=Dipeptidyl peptidase 4 membrane form;
DE AltName: Full=Dipeptidyl peptidase IV membrane form;
DE Contains:
DE RecName: Full=Dipeptidyl peptidase 4 soluble form;
DE AltName: Full=Dipeptidyl peptidase IV soluble form;
GN Name=DPP4; Synonyms=CD26;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphocyte;
RX PubMed=12073152; DOI=10.1007/s00251-002-0456-6;
RA Lee S.-U., Park Y.-H., Davis W.C., Hamilton M.J., Naessens J., Bohach G.A.;
RT "Molecular characterization of bovine CD26 upregulated by a staphylococcal
RT superantigen.";
RL Immunogenetics 54:216-220(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-17.
RC TISSUE=Thymus;
RX PubMed=11981836;
RX DOI=10.1002/1521-4141(200205)32:5<1472::aid-immu1472>3.0.co;2-q;
RA Gliddon D.R., Howard C.J.;
RT "CD26 is expressed on a restricted subpopulation of dendritic cells in
RT vivo.";
RL Eur. J. Immunol. 32:1472-1481(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 1-24.
RC TISSUE=T-cell;
RX PubMed=11598101; DOI=10.1128/iai.69.11.7190-7193.2001;
RA Lee S.-U., Ferens W., Davis W.C., Hamilton M.J., Park Y.-H., Fox L.K.,
RA Naessens J., Bohach G.A.;
RT "Identity of activation molecule 3 on superantigen-stimulated bovine cells
RT is CD26.";
RL Infect. Immun. 69:7190-7193(2001).
RN [5]
RP PROTEIN SEQUENCE OF 537-546.
RC TISSUE=Kidney;
RX PubMed=9629661; DOI=10.1016/s0305-0491(97)00327-1;
RA Ben-Shooshan I., Parola A.H.;
RT "The CP-I subunit of adenosine deaminase complexing protein from calf
RT kidney is identical to human, mouse, and rat dipeptidyl peptidase IV.";
RL Comp. Biochem. Physiol. 119B:289-292(1998).
CC -!- FUNCTION: Cell surface glycoprotein receptor involved in the
CC costimulatory signal essential for T-cell receptor (TCR)-mediated T-
CC cell activation. Acts as a positive regulator of T-cell coactivation,
CC by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1
CC and CARD11 induces T-cell proliferation and NF-kappa-B activation in a
CC T-cell receptor/CD3-dependent manner. Its interaction with ADA also
CC regulates lymphocyte-epithelial cell adhesion. In association with FAP
CC is involved in the pericellular proteolysis of the extracellular matrix
CC (ECM), the migration and invasion of endothelial cells into the ECM.
CC May be involved in the promotion of lymphatic endothelial cells
CC adhesion, migration and tube formation. When overexpressed, enhanced
CC cell proliferation, a process inhibited by GPC3. Acts also as a serine
CC exopeptidase with a dipeptidyl peptidase activity that regulates
CC various physiological processes by cleaving peptides in the
CC circulation, including many chemokines, mitogenic growth factors,
CC neuropeptides and peptide hormones. Removes N-terminal dipeptides
CC sequentially from polypeptides having unsubstituted N-termini provided
CC that the penultimate residue is proline.
CC {ECO:0000250|UniProtKB:P27487}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a
CC polypeptide, preferentially when Yaa is Pro, provided Zaa is neither
CC Pro nor hydroxyproline.; EC=3.4.14.5;
CC Evidence={ECO:0000250|UniProtKB:P27487, ECO:0000255|PROSITE-
CC ProRule:PRU10084};
CC -!- ACTIVITY REGULATION: Inhibited by GPC3 and diprotin A. {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer. Heterodimer with Seprase (FAP). Requires
CC homodimerization for optimal dipeptidyl peptidase activity and T-cell
CC costimulation. Found in a membrane raft complex, at least composed of
CC BCL10, CARD11, DPP4 and IKBKB. Associates with collagen. Interacts with
CC PTPRC; the interaction is enhanced in an interleukin-12-dependent
CC manner in activated lymphocytes. Interacts (via extracellular domain)
CC with ADA; does not inhibit its dipeptidyl peptidase activity. Interacts
CC with CAV1 (via the N-terminus); the interaction is direct. Interacts
CC (via cytoplasmic tail) with CARD11 (via PDZ domain); its
CC homodimerization is necessary for interaction with CARD11. Interacts
CC with IGF2R; the interaction is direct. Interacts with GPC3.
CC {ECO:0000250|UniProtKB:P27487}.
CC -!- SUBCELLULAR LOCATION: [Dipeptidyl peptidase 4 soluble form]: Secreted.
CC Note=Detected in the serum and the seminal fluid. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC membrane protein {ECO:0000250}. Apical cell membrane {ECO:0000250};
CC Single-pass type II membrane protein {ECO:0000250}. Cell projection,
CC invadopodium membrane {ECO:0000250}; Single-pass type II membrane
CC protein {ECO:0000250}. Cell projection, lamellipodium membrane
CC {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}. Cell
CC junction {ECO:0000250}. Membrane raft {ECO:0000250}. Note=Translocated
CC to the apical membrane through the concerted action of N- and O-Glycans
CC and its association with lipid microdomains containing cholesterol and
CC sphingolipids. Redistributed to membrane rafts in T-cell in an
CC interleukin-12-dependent activation. Its interaction with CAV1 is
CC necessary for its translocation to membrane rafts. Colocalized with
CC PTPRC in membrane rafts. Colocalized with FAP in invadopodia and
CC lamellipodia of migratory activated endothelial cells in collagenous
CC matrix. Colocalized with FAP on endothelial cells of capillary-like
CC microvessels but not large vessels within invasive breast ductal
CC carcinoma. Colocalized with ADA at the cell junction in lymphocyte-
CC epithelial cell adhesion. Colocalized with IGF2R in internalized
CC cytoplasmic vesicles adjacent to the cell surface (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Intestinal epithelium, dendritic cells and several
CC immune system tissues.
CC -!- PTM: The soluble form (Dipeptidyl peptidase 4 soluble form also named
CC SDPP) derives from the membrane form (Dipeptidyl peptidase 4 membrane
CC form also named MDPP) by proteolytic processing. {ECO:0000250}.
CC -!- PTM: N- and O-Glycosylated. {ECO:0000250}.
CC -!- PTM: Phosphorylated. Mannose 6-phosphate residues in the carbohydrate
CC moiety are necessary for interaction with IGF2R in activated T-cells.
CC Mannose 6-phosphorylation is induced during T-cell activation (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S9B family. DPPIV subfamily.
CC {ECO:0000305}.
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DR EMBL; AF461806; AAL67836.1; -; mRNA.
DR EMBL; AY056834; AAL23628.1; -; mRNA.
DR EMBL; BC102523; AAI02524.1; -; mRNA.
DR RefSeq; NP_776464.1; NM_174039.2.
DR AlphaFoldDB; P81425; -.
DR SMR; P81425; -.
DR STRING; 9913.ENSBTAP00000049191; -.
DR BindingDB; P81425; -.
DR ChEMBL; CHEMBL2559; -.
DR ESTHER; bovin-dpp4; DPP4N_Peptidase_S9.
DR MEROPS; S09.003; -.
DR PaxDb; P81425; -.
DR PRIDE; P81425; -.
DR Ensembl; ENSBTAT00000056886; ENSBTAP00000049191; ENSBTAG00000048246.
DR GeneID; 281122; -.
DR KEGG; bta:281122; -.
DR CTD; 1803; -.
DR VEuPathDB; HostDB:ENSBTAG00000048246; -.
DR VGNC; VGNC:106715; DPP4.
DR eggNOG; KOG2100; Eukaryota.
DR GeneTree; ENSGT00940000161291; -.
DR InParanoid; P81425; -.
DR OMA; AYVWKND; -.
DR OrthoDB; 269253at2759; -.
DR PRO; PR:P81425; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000048246; Expressed in thymus and 97 other tissues.
DR ExpressionAtlas; P81425; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0045499; F:chemorepellent activity; IEA:Ensembl.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0010716; P:negative regulation of extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0090024; P:negative regulation of neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0036343; P:psychomotor behavior; IEA:Ensembl.
DR GO; GO:0033632; P:regulation of cell-cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0042110; P:T cell activation; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; ISS:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR040522; DPPIV_rep.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR001375; Peptidase_S9.
DR InterPro; IPR002469; Peptidase_S9B_N.
DR Pfam; PF00930; DPPIV_N; 1.
DR Pfam; PF18811; DPPIV_rep; 1.
DR Pfam; PF00326; Peptidase_S9; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00708; PRO_ENDOPEP_SER; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Cell adhesion; Cell junction; Cell membrane;
KW Cell projection; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Protease; Receptor; Reference proteome; Secreted;
KW Serine protease; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..765
FT /note="Dipeptidyl peptidase 4 membrane form"
FT /id="PRO_0000027209"
FT CHAIN 38..765
FT /note="Dipeptidyl peptidase 4 soluble form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000027210"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..765
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT ACT_SITE 629
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084"
FT ACT_SITE 707
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084"
FT ACT_SITE 739
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 684
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 384..393
FT /evidence="ECO:0000250"
FT DISULFID 443..446
FT /evidence="ECO:0000250"
FT DISULFID 453..471
FT /evidence="ECO:0000250"
FT DISULFID 648..761
FT /evidence="ECO:0000250"
SQ SEQUENCE 765 AA; 88369 MW; E32165421F43E116 CRC64;
MKTPWKVLLG LLAIAALVTV ITVPVVLLTK GNDASTDSRR TYTLADYLKN TFRMKFYNLR
WVSDHEYLYK QENNILLFNA EYGNSSIFLE NSTFDEFGHS INDYSVSPDR QYILFEYNYV
KQWRHSYTAS YDIYDLNKRQ LITEERIPNN TQWITWSSVG HKLAYVWNND IYVKNEPNSP
SQRITWTGKK DVIYNGITDW VYEEEVFSAY SALWWSPNST FLAYAQFNDT EVPLIEYSFY
SDESLQYPKT VKIPYPKAGA VNPTIKFFVV NISSLSPNIN ATSQQIVPPG SVLIGDHYLC
DVTWVTEERI SLQWLRRIQN YSIMDICDYD RSTGRWISSV GRQHIEISTT GWVGRFRPAE
PHFTSDGNSF YKIISNEEGY KHICHFQTDK RNCTFITKGA WEVIGIEALT SDYLYYISNE
YKGMPGARNL YKIQLNDYTK VTCLSCELNP DRCQYYSVSF SQEAKYYQLR CSGPGLPLYT
LHNSNNDKEL RVLENNSDLD QVLQDVQMPS KKLDFIHLHG TKFWYQMILP PHFDKSKKYP
LLLEVYAGPC SQKADAIFRL NWATYLASTE NIIVASFDGR GSGYQGDKIM HAINRRLGTF
EVEDQIEATR QFSKMGFVDD KRIAIWGWSY GGYVTSMVLG AGSGVFKCGI AVAPVSKWEY
YDSVYTERYM GLPTPEDNLD SYRNSTVMSR AENFKQVEYL LIHGTADDNV HFQQSAQISK
ALVDAGVDFQ SMWYTDEDHG IASSTAHQHI YTHMSHFLKQ CFSLL
