seprase; 170 kD melanoma membrane-bound gelatinase; fibroblast activation protein alpha; integral membrane serine protease (FAP)
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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
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
Notes
major isoform