Fibroblast activation protein, alpha

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Fibroblast activation protein, alpha
Protein FAP PDB 1z68.png
PDB rendering based on 1z68.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FAP ; DPPIV; FAPA
External IDs OMIM600403 MGI109608 HomoloGene48282 ChEMBL: 4683 GeneCards: FAP Gene
EC number 3.4.21.-
RNA expression pattern
PBB GE FAP 209955 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2191 14089
Ensembl ENSG00000078098 ENSMUSG00000000392
UniProt Q12884 P97321
RefSeq (mRNA) NM_001291807 NM_007986
RefSeq (protein) NP_001278736 NP_032012
Location (UCSC) Chr 2:
163.03 – 163.1 Mb
Chr 2:
62.5 – 62.57 Mb
PubMed search [1] [2]

Fibroblast activation protein, alpha (FAP) also known as seprase or 170 kDa melanoma membrane-bound gelatinase is a protein that in humans is encoded by the FAP gene .[1]

Function[edit]

The protein encoded by this gene 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.[1]

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.[2] 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.

As of April 2013 The endogenous substrates of FAP have not yet been identified.[3]

Structure[edit]

Fibroblast activation protein is a homodimeric integral protein with dipeptidyl peptidase IV (DPPIV)-like fold, featuring an alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain.[4]

Clinical significance[edit]

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

It has been shown that targeting inhibits stromagenesis and growth of tumor in mice.

Talabostat is an inhibitor of FAP and related enzymes, for which clinical trials have been done, but further research is suspended.

Sibrotuzumab is a monoclonal antibody against FAP.

References[edit]

  1. ^ a b "Entrez Gene: fibroblast activation protein, alpha". 
  2. ^ "Merops: the peptidase database". 
  3. ^ The Tumor Microenvironment as a Drug Target: Chasing Slippery Targets
  4. ^ PDB 1Z68; Aertgeerts K, Levin I, Shi L, Snell GP, Jennings A, Prasad GS, Zhang Y, Kraus ML, Salakian S, Sridhar V, Wijnands R, Tennant MG (May 2005). "Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha". J. Biol. Chem. 280 (20): 19441–4. doi:10.1074/jbc.C500092200. PMID 15809306. 


Further reading[edit]