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   24-JAN-2024, entry version 151.
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   GlyCosmos; P81425; 11 sites, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000020379; -.
DR   Ensembl; ENSBTAT00000056886.3; ENSBTAP00000049191.3; ENSBTAG00000048246.2.
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; DKYKATT; -.
DR   OrthoDB; 2876738at2759; -.
DR   Reactome; R-BTA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR   Reactome; R-BTA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR   PRO; PR:P81425; -.
DR   Proteomes; UP000009136; Chromosome 2.
DR   Bgee; ENSBTAG00000048246; Expressed in thymus and 97 other cell types or tissues.
DR   ExpressionAtlas; P81425; baseline and differential.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
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: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: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:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR   GO; GO:0010716; P:negative regulation of extracellular matrix disassembly; ISS:UniProtKB.
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:0031295; P:T cell costimulation; ISS:UniProtKB.
DR   Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR   Gene3D; 2.140.10.30; Dipeptidylpeptidase IV, N-terminal domain; 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   PANTHER; PTHR11731:SF128; DIPEPTIDYL PEPTIDASE 4; 1.
DR   PANTHER; PTHR11731; PROTEASE FAMILY S9B,C DIPEPTIDYL-PEPTIDASE IV-RELATED; 1.
DR   Pfam; PF00930; DPPIV_N; 1.
DR   Pfam; PF18811; DPPIV_rep; 1.
DR   Pfam; PF00326; Peptidase_S9; 1.
DR   SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR   SUPFAM; SSF82171; DPP6 N-terminal domain-like; 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
//