Fibroblast Activation Protein Alpha (FAPa)

APCE; SIMP; DPPIV; Seprase; 170 kDa melanoma membrane-bound gelatinase; Post-proline cleaving enzyme; Serine integral membrane protease; Surface-expressed protease

SPN	U379
HGNC	3590
MGI	109608
PubMed	11208014
RGD	621253
UniProt	Q12884
Wiki	FAPA

Fibroblast activation protein, alpha, also known as FAP, is a homodimeric integral membrane gelatinase belonging to the serine protease family. It is selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. This protein is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis. FAP, also known as seprase, belongs to the clan SC proteases and is a member of the S9B prolyl oligopeptidase subfamily. Other members of the S9B subfamily are DPPIV, DPP8 and DPP9. FAP is most closely related to DPPIV and they share about 50% of there amino acids.

Reference

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Proc. Natl. Acad. Sci. U.S.A. 91:5657-5661(1994) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning of seprase: a serine integral membrane protease from human melanoma."
Biochim. Biophys. Acta 1361:11-19(1997) [PubMed] [Europe PMC] [Abstract]

"Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease."
J. Biol. Chem. 272:7595-7601(1997) [PubMed] [Europe PMC] [Abstract]

"Identification of an alternatively spliced seprase mRNA that encodes a novel intracellular isoform."
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Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

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"A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion."
Blood 103:3783-3788(2004) [PubMed] [Europe PMC] [Abstract]

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"A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells."
Proc. Natl. Acad. Sci. U.S.A. 87:8296-8300(1990) [PubMed] [Europe PMC] [Abstract]

"A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells."
Cancer Res. 54:5702-5710(1994) [PubMed] [Europe PMC] [Abstract]

"Fibroblast activation protein: a cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis."
Hepatology 29:1768-1778(1999) [PubMed] [Europe PMC] [Abstract]

"Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts."
J. Biol. Chem. 274:36505-36512(1999) [PubMed] [Europe PMC] [Abstract]

"A novel protease-docking function of integrin at invadopodia."
J. Biol. Chem. 274:24947-24952(1999) [PubMed] [Europe PMC] [Abstract]

"Molecular proximity of seprase and the urokinase-type plasminogen activator receptor on malignant melanoma cell membranes: dependence on beta1 integrins and the cytoskeleton."
Carcinogenesis 23:1593-1601(2002) [PubMed] [Europe PMC] [Abstract]

"Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line."
Hepatology 42:935-945(2005) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
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"Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes."
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"Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein."
Blood 107:1397-1404(2006) [PubMed] [Europe PMC] [Abstract]

"The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices."
Cancer Res. 66:4652-4661(2006) [PubMed] [Europe PMC] [Abstract]

"Peptide substrate profiling defines fibroblast activation protein as an endopeptidase of strict Gly(2)-Pro(1)-cleaving specificity."
FEBS Lett. 580:1581-1586(2006) [PubMed] [Europe PMC] [Abstract]

"Selective inhibition of fibroblast activation protein protease based on dipeptide substrate specificity."
J. Biol. Chem. 281:7437-7444(2006) [PubMed] [Europe PMC] [Abstract]

"Ala657 and conserved active site residues promote fibroblast activation protein endopeptidase activity via distinct mechanisms of transition state stabilization."
Biochemistry 46:4598-4605(2007) [PubMed] [Europe PMC] [Abstract]

"Fibroblast activation protein peptide substrates identified from human collagen I derived gelatin cleavage sites."
Biochemistry 47:1076-1086(2008) [PubMed] [Europe PMC] [Abstract]

"Seprase: an overview of an important matrix serine protease."
Biochim. Biophys. Acta 1784:1130-1145(2008) [PubMed] [Europe PMC] [Abstract]

"Expression and role of the cell surface protease seprase/fibroblast activation protein-alpha (FAP-alpha) in astroglial tumors."
Biol. Chem. 392:199-207(2011) [PubMed] [Europe PMC] [Abstract]

"Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are novel substrates of fibroblast activation protein-alpha."
FEBS J. 278:1316-1332(2011) [PubMed] [Europe PMC] [Abstract]

"Cleavage-site specificity of prolyl endopeptidase FAP investigated with a full-length protein substrate."
J. Biochem. 149:685-692(2011) [PubMed] [Europe PMC] [Abstract]

"Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs."
FEBS Open Bio 4:43-54(2013) [PubMed] [Europe PMC] [Abstract]

"A rare variant in human fibroblast activation protein associated with ER stress, loss of enzymatic function and loss of cell surface localisation."
Biochim. Biophys. Acta 1844:1248-1259(2014) [PubMed] [Europe PMC] [Abstract]

"Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha."
J. Biol. Chem. 280:19441-19444(2005) [PubMed] [Europe PMC] [Abstract]