Names & Taxonomy
- Uniprot ID:
- Q12884
- Entry Name:
- SEPR_HUMAN
- Status:
- reviewed
- Protein Names:
- Prolyl endopeptidase FAP (EC 3.4.21.26) (170 kDa melanoma membrane-bound gelatinase) (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 Names:
- FAP
- Gene Names Primary:
- FAP
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 760
- Sequence:
- MKTWVKIVFGVATSAVLALLVMCIVLRPSRVHNSEENTMRALTLKDILNGTFSYKTFFPNWISGQEYLHQSADNNIVLYNIETGQSYTILSNRTMKSVNASNYGLSPDRQFVYLESDYSKLWRYSYTATYYIYDLSNGEFVRGNELPRPIQYLCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITFNGRENKIFNGIPDWVYEEEMLATKYALWWSPNGKFLAYAEFNDTDIPVIAYSYYGDEQYPRTINIPYPKAGAKNPVVRIFIIDTTYPAYVGPQEVPVPAMIASSDYYFSWLTWVTDERVCLQWLKRVQNVSVLSICDFREDWQTWDCPKTQEHIEESRTGWAGGFFVSTPVFSYDAISYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAINIFRVTQDSLFYSSNEFEEYPGRRNIYRISIGSYPPSKKCVTCHLRKERCQYYTASFSDYAKYYALVCYGPGIPISTLHDGRTDQEIKILEENKELENALKNIQLPKEEIKKLEVDEITLWYKMILPPQFDRSKKYPLLIQVYGGPCSQSVRSVFAVNWISYLASKEGMVIALVDGRGTAFQGDKLLYAVYRKLGVYEVEDQITAVRKFIEMGFIDEKRIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPVSSWEYYASVYTERFMGLPTKDDNLEHYKNSTVMARAEYFRNVDYLLIHGTADDNVHFQNSAQIAKALVNAQVDFQAMWYSDQNHGLSGLSTNHLYTHMTHFLKQCFSLSD
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Prolyl endopeptidase FAP: Cell surface
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 (PubMed:14751930, PubMed:16223769, PubMed:16480718, PubMed:16410248, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721). Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein (PubMed:9065413, PubMed:2172980, PubMed:7923219, PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711). Have also 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 (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16651416, PubMed:16410248, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288). Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB) (PubMed:21314817). 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.
- Catalytic Activity:
- Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.46 mM for Ala-Pro (Dipeptidyl peptidase activity)
- Enzyme Regulation:
- ENZYME 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.
- Active Site:
- ACT_SITE 624 624 Charge relay system.
- Gene Ontology Go:
- apical part of cell
basal part of cell
cell surface
cytoplasm
extracellular space
focal adhesion
integral component of membrane
invadopodium membrane
lamellipodium
lamellipodium membrane
plasma membrane
ruffle membrane
dipeptidyl-peptidase activity
endopeptidase activity
integrin binding
metalloendopeptidase activity
peptidase activity
protease binding
protein dimerization activity
protein homodimerization activity
serine-type endopeptidase activity
serine-type peptidase activity
angiogenesis
cell adhesion
endothelial cell migration
melanocyte apoptotic process
melanocyte proliferation
mitotic cell cycle arrest
negative regulation of cell proliferation involved in contact inhibition
negative regulation of extracellular matrix disassembly
negative regulation of extracellular matrix organization
positive regulation of cell cycle arrest
positive regulation of execution phase of apoptosis
proteolysis
proteolysis involved in cellular protein catabolic process
regulation of collagen catabolic process
regulation of fibrinolysis - Gene Ontology Biological Process:
- angiogenesis
cell adhesion
endothelial cell migration
melanocyte apoptotic process
melanocyte proliferation
mitotic cell cycle arrest
negative regulation of cell proliferation involved in contact inhibition
negative regulation of extracellular matrix disassembly
negative regulation of extracellular matrix organization
positive regulation of cell cycle arrest
positive regulation of execution phase of apoptosis
proteolysis
proteolysis involved in cellular protein catabolic process
regulation of collagen catabolic process
regulation of fibrinolysis - Gene Ontology Molecular Function:
- dipeptidyl-peptidase activity
endopeptidase activity
integrin binding
metalloendopeptidase activity
peptidase activity
protease binding
protein dimerization activity
protein homodimerization activity
serine-type endopeptidase activity
serine-type peptidase activity - Gene Ontology Cellular Component:
- apical part of cell
basal part of cell
cell surface
cytoplasm
extracellular space
focal adhesion
integral component of membrane
invadopodium membrane
lamellipodium
lamellipodium membrane
plasma membrane
ruffle membrane - Keywords:
- 3D-structure
Alternative splicing
Angiogenesis
Apoptosis
Cell adhesion
Cell junction
Cell membrane
Cell projection
Cleavage on pair of basic residues
Complete proteome
Cytoplasm
Direct protein sequencing
Disulfide bond
Glycoprotein
Hydrolase
Membrane
Polymorphism
Protease
Reference proteome
Secreted
Serine protease
Signal-anchor
Transmembrane
Transmembrane helix - Interacts With:
- P01275; P01282