| IED ID | IndEnz0002010564 |
| Enzyme Type ID | protease010564 |
| Protein Name |
Prolyl endopeptidase FAP EC 3.4.21.26 Dipeptidyl peptidase FAP EC 3.4.14.5 Fibroblast activation protein alpha FAPalpha Gelatine degradation protease FAP EC 3.4.21.- Integral membrane serine protease Post-proline cleaving enzyme Serine integral membrane protease SIMP Surface-expressed protease Seprase Cleaved into: Antiplasmin-cleaving enzyme FAP, soluble form APCE EC 3.4.14.5 EC 3.4.21.- EC 3.4.21.26 |
| Gene Name | Fap |
| Organism | Mus musculus (Mouse) |
| 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 Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MKTWLKTVFGVTTLAALALVVICIVLRPSRVYKPEGNTKRALTLKDILNGTFSYKTYFPNWISEQEYLHQSEDDNIVFYNIETRESYIILSNSTMKSVNATDYGLSPDRQFVYLESDYSKLWRYSYTATYYIYDLQNGEFVRGYELPRPIQYLCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITYTGRENRIFNGIPDWVYEEEMLATKYALWWSPDGKFLAYVEFNDSDIPIIAYSYYGDGQYPRTINIPYPKAGAKNPVVRVFIVDTTYPHHVGPMEVPVPEMIASSDYYFSWLTWVSSERVCLQWLKRVQNVSVLSICDFREDWHAWECPKNQEHVEESRTGWAGGFFVSTPAFSQDATSYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAIYIFRVTQDSLFYSSNEFEGYPGRRNIYRISIGNSPPSKKCVTCHLRKERCQYYTASFSYKAKYYALVCYGPGLPISTLHDGRTDQEIQVLEENKELENSLRNIQLPKVEIKKLKDGGLTFWYKMILPPQFDRSKKYPLLIQVYGGPCSQSVKSVFAVNWITYLASKEGIVIALVDGRGTAFQGDKFLHAVYRKLGVYEVEDQLTAVRKFIEMGFIDEERIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPVSSWEYYASIYSERFMGLPTKDDNLEHYKNSTVMARAEYFRNVDYLLIHGTADDNVHFQNSAQIAKALVNAQVDFQAMWYSDQNHGISSGRSQNHLYTHMTHFLKQCFSLSD |
| Enzyme Length | 761 |
| Uniprot Accession Number | P97321 |
| Absorption | |
| Active Site | ACT_SITE 624; /note="Charge relay system"; /evidence="ECO:0000250|UniProtKB:Q12884, ECO:0000255|PROSITE-ProRule:PRU10084"; ACT_SITE 702; /note="Charge relay system"; /evidence="ECO:0000250|UniProtKB:Q12884"; ACT_SITE 734; /note="Charge relay system"; /evidence="ECO:0000250|UniProtKB:Q12884" |
| Activity Regulation | ACTIVITY REGULATION: Gelatinase activity is inhibited by serine-protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF). Dipeptidyl peptidase activity is inhibited by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP). Prolyl endopeptidase activity is inhibited by the boronic acid peptide Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-chloromethyl ketone. {ECO:0000250|UniProtKB:Q12884}. |
| Binding Site | BINDING 203; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q12884; BINDING 204; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q12884 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.; EC=3.4.21.26; Evidence={ECO:0000269|PubMed:24371721}; 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:0000255|PROSITE-ProRule:PRU10084, ECO:0000269|PubMed:10629066, ECO:0000269|PubMed:11330865, ECO:0000269|PubMed:15133496, ECO:0000269|PubMed:9688278}; |
| DNA Binding | |
| EC Number | 3.4.21.26; 3.4.14.5; 3.4.21.-; 3.4.14.5; 3.4.21.-; 3.4.21.26 |
| Enzyme Function | FUNCTION: Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2. Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein. Also has dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro. Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner. {ECO:0000269|PubMed:10629066, ECO:0000269|PubMed:11330865, ECO:0000269|PubMed:15133496, ECO:0000269|PubMed:21051638, ECO:0000269|PubMed:23710635, ECO:0000269|PubMed:24371721, ECO:0000269|PubMed:9688278}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Binding site (2); Chain (2); Disulfide bond (4); Glycosylation (6); Mutagenesis (1); Sequence conflict (1); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative splicing;Angiogenesis;Apoptosis;Cell adhesion;Cell junction;Cell membrane;Cell projection;Cleavage on pair of basic residues;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Protease;Reference proteome;Secreted;Serine protease;Signal-anchor;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Prolyl endopeptidase FAP]: Cell surface {ECO:0000269|PubMed:15133496}. Cell membrane {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein {ECO:0000255}. Cell projection, lamellipodium membrane {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein {ECO:0000255}. Cell projection, invadopodium membrane {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein {ECO:0000255}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein {ECO:0000255}. Note=Localized on cell surface with lamellipodia and invadopodia membranes and on shed vesicles. Colocalized with DPP4 at invadopodia and lamellipodia membranes of migratory activated endothelial cells in collagenous matrix. Colocalized with DPP4 on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma. Anchored and enriched preferentially by integrin alpha-3/beta-1 at invadopodia, plasma membrane protrusions that correspond to sites of cell invasion, in a collagen-dependent manner. Localized at plasma and ruffle membranes in a collagen-independent manner. Colocalized with PLAUR preferentially at the cell surface of invadopodia membranes in a cytoskeleton-, integrin- and vitronectin-dependent manner. Concentrated at invadopodia membranes, specialized protrusions of the ventral plasma membrane in a fibrobectin-dependent manner. Colocalizes with extracellular components (ECM), such as collagen fibers and fibronectin. {ECO:0000250|UniProtKB:Q12884}.; SUBCELLULAR LOCATION: [Antiplasmin-cleaving enzyme FAP, soluble form]: Secreted {ECO:0000269|PubMed:24371721}. Note=Found in blood plasma and serum. {ECO:0000269|PubMed:24371721}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q12884}.; PTM: The N-terminus may be blocked. {ECO:0000250|UniProtKB:Q12884}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11908948; 12466851; 15767544; 16141072; 18823010; 19463158; 19920354; 20225612; 20804499; 21267068; 21604185; 21668992; 21677750; 23704821; 23712428; 24038871; 24550112; 25994578; 26305550; 26663085; 26797127; 26962859; 27216177; 27545090; 27590504; 28004985; 28158223; 28302482; 28970566; 29361119; 29410133; 30054470; 30257879; 30726287; 31188013; 31324739; 31325484; 32084369; 32402085; 33053358; 33482262; 33667270; 34335962; |
| Motif | |
| Gene Encoded By | |
| Mass | 87,945 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.B28; |