| IED ID | IndEnz0002003013 |
| Enzyme Type ID | protease003013 |
| Protein Name |
Dipeptidyl peptidase 4 EC 3.4.14.5 Bile canaliculus domain-specific membrane glycoprotein Dipeptidyl peptidase IV DPP IV GP110 glycoprotein T-cell activation antigen CD26 CD antigen CD26 Cleaved into: Dipeptidyl peptidase 4 membrane form Dipeptidyl peptidase IV membrane form ; Dipeptidyl peptidase 4 soluble form Dipeptidyl peptidase IV soluble form ; Dipeptidyl peptidase 4 60 kDa soluble form Dipeptidyl peptidase IV 60 kDa soluble form |
| Gene Name | Dpp4 Cd26 |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MKTPWKVLLGLLGVAALVTIITVPVVLLNKDEAAADSRRTYTLADYLKNTFRVKSYSLRWVSDSEYLYKQENNILLFNAEHGNSSIFLENSTFEIFGDSISDYSVSPDRLFVLLEYNYVKQWRHSYTASYSIYDLNKRQLITEEKIPNNTQWITWSQEGHKLAYVWKNDIYVKIEPHLPSHRITSTGKENVIFNGINDWVYEEEIFGAYSALWWSPNGTFLAYAQFNDTGVPLIEYSFYSDESLQYPKTVWIPYPKAGAVNPTVKFFIVNTDSLSSTTTTIPMQITAPASVTTGDHYLCDVAWVSEDRISLQWLRRIQNYSVMAICDYDKTTLVWNCPTTQEHIETSATGWCGRFRPAEPHFTSDGSSFYKIVSDKDGYKHICQFQKDRKPEQVCTFITKGAWEVISIEALTSDYLYYISNEYKEMPGGRNLYKIQLTDHTNKKCLSCDLNPERCQYYSVSLSKEAKYYQLGCRGPGLPLYTLHRSTDQKELRVLEDNSALDKMLQDVQMPSKKLDFIVLNETRFWYQMILPPHFDKSKKYPLLIDVYAGPCSQKADAAFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINKRLGTLEVEDQIEAARQFLKMGFVDSKRVAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWEYYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQISKALVDAGVDFQAMWYTDEDHGIASSTAHQHIYSHMSHFLQQCFSLR |
| Enzyme Length | 767 |
| Uniprot Accession Number | P14740 |
| Absorption | |
| Active Site | ACT_SITE 631; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU10084; ACT_SITE 709; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU10084; ACT_SITE 741; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU10084 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by GPC3 and diprotin A. {ECO:0000269|PubMed:16768443}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.; EC=3.4.14.5; Evidence={ECO:0000250|UniProtKB:P27487, ECO:0000255|PROSITE-ProRule:PRU10084}; |
| DNA Binding | |
| EC Number | 3.4.14.5 |
| Enzyme Function | FUNCTION: 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. {ECO:0000250|UniProtKB:P27487}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (53); Chain (3); Disulfide bond (5); Glycosylation (8); Helix (18); Mutagenesis (9); Sequence conflict (8); Topological domain (2); Transmembrane (1); Turn (10) |
| Keywords | 3D-structure;Aminopeptidase;Cell adhesion;Cell junction;Cell membrane;Cell projection;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Protease;Reference proteome;Secreted;Serine protease;Signal-anchor;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Dipeptidyl peptidase 4 soluble form]: Secreted. Note=Detected in the serum and the seminal fluid. {ECO:0000250}.; SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein. Apical cell membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}. Cell projection, invadopodium membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}. Cell projection, lamellipodium membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}. Cell junction {ECO:0000250}. Membrane raft {ECO:0000250}. Note=Translocated to the apical membrane through the concerted action of N- and O-Glycans and its association with lipid microdomains containing cholesterol and sphingolipids. Redistributed to membrane rafts in T-cell in an interleukin-12-dependent activation. Its interaction with CAV1 is necessary for its translocation to membrane rafts. Colocalized with PTPRC in membrane rafts. Colocalized with FAP in invadopodia and lamellipodia of migratory activated endothelial cells in collagenous matrix. Colocalized with FAP on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma. Colocalized with ADA at the cell junction in lymphocyte-epithelial cell adhesion. Colocalized with IGF2R in internalized cytoplasmic vesicles adjacent to the cell surface (By similarity). {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: 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. {ECO:0000250}.; PTM: N- and O-Glycosylated. {ECO:0000250}.; PTM: 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). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (9) |
| Cross Reference PDB | 2GBC; 2GBF; 2GBG; 2GBI; 2I3Z; 2OAE; 4FFV; 4FFW; 5VTA; |
| Mapped Pubmed ID | 10931192; 11901152; 12031691; 12675219; 12675233; 12705886; 12716896; 14568317; 15606609; 16478473; 16802131; 16962474; 17010607; 17175274; 17276063; 17415460; 17583752; 18047624; 18077600; 18538760; 18931022; 18940185; 18978811; 19327106; 19501934; 19540879; 19804410; 19876009; 20153005; 20560982; 20887754; 21139073; 21982785; 22373413; 22802229; 22918684; 23033273; 23035207; 23184393; 23359639; 23361237; 23408696; 23535306; 23832365; 23894014; 24357522; 24416433; 24874705; 25122001; 25635612; 25656369; 25936515; 26187356; 26259714; 26359413; 26399925; 27083282; 27238050; 27525674; 28372289; 28895067; 29472575; 29677638; 29765112; 30977110; 31089745; 32542696; 33162819; 8526932; |
| Motif | |
| Gene Encoded By | |
| Mass | 88,089 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.14.5; |