DPP4_FELCA
ID DPP4_FELCA Reviewed; 765 AA.
AC Q9N2I7;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Dipeptidyl peptidase 4;
DE EC=3.4.14.5 {ECO:0000250|UniProtKB:P27487};
DE AltName: Full=Dipeptidyl peptidase IV;
DE Short=DPP IV;
DE AltName: Full=T-cell activation antigen CD26;
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 Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Peripheral blood;
RX PubMed=10630304; DOI=10.1007/s002510050616;
RA Nishimura Y., Miyazawa T., Ikeda Y., Izumiya Y., Nakamura K., Sato E.,
RA Mikami T., Takahashi E.;
RT "Molecular cloning and sequencing of a cDNA encoding the feline T-cell
RT activation antigen CD26 homologue.";
RL Immunogenetics 50:366-368(1999).
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 (extracellular domain) with
CC ADA; does not inhibit its dipeptidyl peptidase activity. Interacts with
CC CAV1 (via the N-terminus); the interaction is direct. Interacts (via
CC cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is
CC necessary for interaction with CARD11. Interacts with IGF2R; the
CC 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 -!- 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; AB023952; BAA92344.1; -; mRNA.
DR RefSeq; NP_001009838.1; NM_001009838.1.
DR AlphaFoldDB; Q9N2I7; -.
DR SMR; Q9N2I7; -.
DR STRING; 9685.ENSFCAP00000004117; -.
DR ESTHER; felca-CD26; DPP4N_Peptidase_S9.
DR MEROPS; S09.003; -.
DR PRIDE; Q9N2I7; -.
DR GeneID; 493787; -.
DR KEGG; fca:493787; -.
DR CTD; 1803; -.
DR eggNOG; KOG2100; Eukaryota.
DR InParanoid; Q9N2I7; -.
DR OrthoDB; 269253at2759; -.
DR Proteomes; UP000011712; Unplaced.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 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 2: Evidence at transcript level;
KW Aminopeptidase; Cell adhesion; Cell junction; Cell membrane;
KW Cell projection; Disulfide bond; Glycoprotein; Hydrolase; Membrane;
KW Protease; Receptor; Reference proteome; Secreted; Serine protease;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..765
FT /note="Dipeptidyl peptidase 4 membrane form"
FT /id="PRO_0000027211"
FT CHAIN 38..765
FT /note="Dipeptidyl peptidase 4 soluble form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000027212"
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:0000250"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
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 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 519
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
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; 88213 MW; 3EFCE98A22B175D9 CRC64;
MKTPWKVLLG LLGLAALITI ITVPVVLLNK GNDAAADSRR TYTLTDYLKN TFRVKFYSLR
WVSDHDYLYK QDNNILLFNA EYGNSSIFLE NSTFDEFEHS INDYSVSPDG QFILLEYNYV
KQWRHSYTAS YDIYDLNKRQ LITEEKIPNN TQWITWSPEG HKLAYVWKND VYVKNEPNSS
SHRITWTGEE NAIYNGIADW VYEEEIFSAY SALWWSPKGT FLAYAQFNDT QVPLIEYSFY
SDESLQYPMT MRIPYPKAGA ANPTVKLFVI KTDNLNPNTN ATSVEITPPA AMLTGDYYLC
DVTWANEERI SLQWLRRIQN YSVMDIRDYN NSTGKWISSA AQEHIEMSTT GWVGRFRPAE
PHFTSDGRNF YKIISNEDGY KHICRFQIDK KDCTFITKGA WEVIGIEALT TDYLYYISNE
YKGMPGGRNL YKIQLNDYTK VACLSCELKP ERCQYYSVSF SKEAKYYQLR CSGPGLPLYT
LHRSSNDEEL RVLEDNSALD KMLQEVQMPS KKLDFIILNE TKFWYQMILP PHFDTSKKYP
LLIDVYAGPC SQKADAIFRL NWATYLASTE NIIVASFDGR GSGYQGDKIM HAVNRRLGTF
EVEDQIEAAR QFSKMGFVDD KRIAIWGWSY GGYVTSMVLG AGSGVFKCGI AVAPVSRWEY
YDSVYTERYM GLPTPQDNLD YYKNSTVMSR AENFKQVEYL LIHGTADDNV HFQQSAQISK
ALVDAGVDFQ AMWYTDEDHG IASGPAHQHI YTHMSHFIKQ CFSLP
