FAP (gene)
Encyclopedia
Fibroblast activation protein, alpha (FAP) also known as seprase or 170 kDa melanoma membrane-bound gelatinase is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the FAP gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Function

The protein encoded by this gene is a homodimeric integral membrane gelatinase
Gelatinase
In biology and chemistry, gelatinase is a proteolytic enzyme that allows a living organism to hydrolyse gelatin into its sub-compounds that can cross the cell membrane and be used by the organism...

 belonging to the serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...

 family. It is selectively expressed in reactive stromal fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

s 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
DPP8
Dipeptidyl peptidase 8 is an enzyme that in humans is encoded by the DPP8 gene.-References:NotesFurther reading...

 and DPP9
DPP9
Dipeptidyl peptidase 9 is an enzyme that in humans is encoded by the DPP9 gene.-Further reading:...

. FAP is most closely related to DPPIV and they share about 50% of their amino acids.

FAP is catalytically active as a 170kD dimer and has dipeptidase and gelatinase activity. Its gelatinase activity requires a glycine in P2 position.

Clinical significance

FAP expression is seen on activated stromal fibroblasts of more than 90% of all human carcinomes. Stromal fibroblasts play an important role in the development, growth and metastasis of carcinomas.

Talabostat is a inhibitor of FAP and related enzymes, for which clinical trials have been done, but further research is suspended. Sibrotuzumab
Sibrotuzumab
Sibrotuzumab is a humanized monoclonal antibody intended for the treatment of cancer. It binds to FAP...

is a monoclonal antibody against FAP.
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