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seprase; 170 kD melanoma membrane-bound gelatinase; fibroblast activation protein alpha; integral membrane serine protease (FAP)
Function:
- in association with DPP4, involved in the pericellular proteolysis of extracellular matrix, the migration & invasion of endothelial cells into the extracellular matrix
- may have a role in tissue remodeling during development & wound healing
- degrades gelatin & heat-denatured type collagen type 1 & collagen type 4, but not native collagen type 1 or native collagen type 4
- does not cleave laminin, fibronectin, fibrin or casein
- homodimer, or heterodimer with DPP4
- the monomer is inactive
Structure:
- N-glycosylated
- the N-terminus may be blocked
- belongs to the peptidase S9B family
Compartment:
- cell membrane, cell projection, lamellipodium membrane
- single-pass type 2 membrane protein
- found in cell surface lamellipodia, & on shed vesicles
- colocalized with DPP4 in lamellipodia of migratory activated endothelial cells in collagenous matrix
Alternative splicing: named isoforms=2
Note: major isoform
Expression:
- in fibroblasts at times & sites of tissue remodeling during development, tissue repair, & carcinogenesis
- endothelial cells during angiogenesis ?
Pathology:
- may contribute to invasiveness in malignant cancers
- found in invadopodia, colocalized with DPP4
- colocalized with DPP4 on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma
General
glycoprotein
membrane protein
serine protease
Properties
SIZE: entity length = 760 aa
MW = 88 kD
COMPARTMENT: plasma membrane
MOTIF: transmembrane domain {5-25}
N-glycosylation site {N49}
N-glycosylation site {N92}
N-glycosylation site {N99}
binding site
SITE: 203-203
FOR-BINDING-OF: Substrate
binding site
SITE: 204-204
FOR-BINDING-OF: Substrate
N-glycosylation site {N227}
N-glycosylation site {N314}
cysteine residue {C321}
MODIFICATION: cysteine residue {C332}
cysteine residue {C332}
MODIFICATION: cysteine residue {C321}
cysteine residue {C438}
MODIFICATION: cysteine residue {C441}
cysteine residue {C441}
MODIFICATION: cysteine residue {C438}
cysteine residue {C448}
MODIFICATION: cysteine residue {C466}
cysteine residue {C466}
MODIFICATION: cysteine residue {C448}
serine residue {S624}
cysteine residue {C643}
MODIFICATION: cysteine residue {C755}
N-glycosylation site {N679}
aspartate residue {D702}
histidine residue {H734}
cysteine residue {C755}
MODIFICATION: cysteine residue {C643}
Database Correlations
OMIM 600403
UniProt Q12884
PFAM correlations
Entrez Gene 2191
Kegg hsa:2191
References
UniProt :accession Q12884