Fibroblast Activation Protein

from Wikipedia, the free encyclopedia
Fibroblast Activation Protein alpha
Fibroblast Activation Protein alpha
according to PDB  1z68
other names
  • Seprase
  • 170 kDa melanoma membrane-bound gelatinase
Identifier
External IDs
Enzyme classification
EC, category 3.4.21.-

The fibroblast activation protein alpha (FAP), also known as fibroblast activation protein alpha , Seprase or 170 kDa melanoma membrane- bound gelatinase , is a protein that is encoded by the FAP gene in humans .

function

The protein encoded by this gene is a homodimeric integral membrane gelatinase that belongs to the serine protease family. It is particularly expressed in reactive stroma fibroblasts of epithelial tumors , granulation tissue of healing wounds and malignant cells of bone and soft tissue sarcomas . This protein is believed to be involved in controlling fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis . FAP belongs to the SC proteases and is a member of the S9B prolyloligopeptidase family. Other members of the subfamily S9B are DPPIV, DPP8, and DPP9. FAP is very closely related to DPPIV and shares about 50% of the amino acid sequence .

structure

Fibroblast activation protein is a homodimeric integral protein with dipeptidyl peptidase IV (DPP IV) - sheet structure , equipped with an alpha / beta hydrolase - domain and an eight-blade beta-propeller domain.

Medical relevance

FAP expression is observed on activated stromal fibroblasts in greater than 90% of all human carcinomas. Stromal fibroblasts play an important role in the development, growth and metastasis of carcinomas . Pharmaceutical blockade of FAP has been shown to inhibit stromagenesis and tumor growth in mice. For example, talabostat is an inhibitor of FAP and related enzymes. Sibrotuzumab is a monoclonal antibody against FAP.

Individual evidence

  1. ↑ http://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2191
  2. ↑ http://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2191
  3. ↑ http://merops.sanger.ac.uk/
  4. ↑ http://www.genengnews.com/insight-and-intelligence/the-tumor-microenvironment-as-a-drug-target-chasing-slippery-targets/77899808/
  5. ↑ Scott, AM; Wiseman, G; World, S; Adjei, A; Lee, FT; Hopkins, W; Divgi, CR; Hanson, LH et al. (2003). A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. In: Clinical Cancer Research 9 (5): 1639-47. PMID 12738716
  6. ↑ Kloft, C; Graefe, EU; Tanswell, P; Scott, AM; Hofheinz, R; Amelsberg, A; Karlsson, MO (2004). Population pharmacokinetics of sibrotuzumab, a novel therapeutic monoclonal antibody, in cancer patients. In: Investigational New Drugs 22 (1): 39-52. doi : 10.1023 / B: DRUG.0000006173.72210.1c . PMID 14707493