Biology:TIMP2

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Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene family. The protein is thought to be a metastasis suppressor.[citation needed]

Function

The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases (MMP), a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix.[1] TIMP2 functions as both an MMP inhibitor and an activator. TIMPs inhibit active MMPs, but different TIMPs inhibit different MMPs better than others. For example, TIMP-1 inhibits MMP-7, MMP-9, MMP-1 and MMP-3 better than TIMP-2, and TIMP-2 inhibits MMP-2 more effectively than other TIMPs.[2]

In melanocytic cells TIMP2 gene expression may be regulated by MITF.[3]

A more recent discovery is that TIMP2 plays an important role in hippocampal function and cognitive function. It plays a critical role in the benefit conferred to old mice when given human umbilical cord blood.[4][5]

Interactions

TIMP2 has been shown to interact with:

See also

References

  1. ↑ "Entrez Gene: TIMP2 TIMP metallopeptidase inhibitor 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7077. 
  2. ↑ "Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion". Seminars in Cancer Biology 20 (3): 161–8. Jun 2010. doi:10.1016/j.semcancer.2010.05.002. PMID 20470890. 
  3. ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  4. ↑ Joseph Castellano (Apr 27, 2017). "Human umbilical cord plasma proteins revitalize hippocampal function in aged mice". Nature 544 (7651): 488–492. doi:10.1038/nature22067. PMID 28424512. Bibcode: 2017Natur.544..488C. 
  5. ↑ "Blood from human babies makes brains of elderly mice young again". New Scientist. Apr 29, 2017. https://www.newscientist.com/article/mg23431235-100. 
  6. ↑ "Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1-matrix metalloproteinase 1 (MT1-MMP)". J. Biol. Chem. 273 (2): 1216–22. January 1998. doi:10.1074/jbc.273.2.1216. PMID 9422789. 
  7. ↑ "Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7414–9. May 2002. doi:10.1073/pnas.102185399. PMID 12032297. Bibcode: 2002PNAS...99.7414M. 
  8. ↑ "Domain interactions in the gelatinase A.TIMP-2.MT1-MMP activation complex. The ectodomain of the 44-kDa form of membrane type-1 matrix metalloproteinase does not modulate gelatinase A activation". J. Biol. Chem. 275 (50): 39497–506. December 2000. doi:10.1074/jbc.M005932200. PMID 10991943. 
  9. ↑ "Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2". J. Biol. Chem. 272 (24): 15496–500. June 1997. doi:10.1074/jbc.272.24.15496. PMID 9182583. 
  10. ↑ "Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. The importance of acidic residues in binding the MMP-2 hemopexin C-domain". J. Biol. Chem. 277 (50): 48696–707. December 2002. doi:10.1074/jbc.M209177200. PMID 12374789. 

Further reading

External links

  • The MEROPS online database for peptidases and their inhibitors: I35.002
  • Overview of all the structural information available in the PDB for UniProt: P16035 (Metalloproteinase inhibitor 2) at the PDBe-KB.





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