TIMP2

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TIMP metallopeptidase inhibitor 2
Protein TIMP2 PDB 1bqq.png
PDB rendering based on 1bqq.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TIMP2 ; CSC-21K
External IDs OMIM188825 MGI98753 HomoloGene2444 GeneCards: TIMP2 Gene
RNA expression pattern
PBB GE TIMP2 203167 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7077 21858
Ensembl ENSG00000035862 ENSMUSG00000017466
UniProt P16035 B1AQJ3
RefSeq (mRNA) NM_003255 NM_011594
RefSeq (protein) NP_003246 NP_035724
Location (UCSC) Chr 17:
76.85 – 76.92 Mb
Chr 11:
118.3 – 118.36 Mb
PubMed search [1] [2]

TIMP metallopeptidase inhibitor 2, a tissue inhibitor of metalloproteinases, also known as TIMP2, is a human gene, thought to be a metastasis suppressor.

This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, 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]

In melanocytic cells TIMP2 gene expression may be regulated by MITF.[2]

Interactions[edit]

TIMP2 has been shown to interact with MMP14[3] and MMP2.[4][5][6][7]

See also[edit]

References[edit]

  1. ^ "Entrez Gene: TIMP2 TIMP metallopeptidase inhibitor 2". 
  2. ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  3. ^ Zucker, S; Drews M; Conner C; Foda H D; DeClerck Y A; Langley K E; Bahou W F; Docherty A J; Cao J (January 1998). "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. (UNITED STATES) 273 (2): 1216–22. doi:10.1074/jbc.273.2.1216. ISSN 0021-9258. PMID 9422789. 
  4. ^ Morgunova, Ekaterina; Tuuttila Ari; Bergmann Ulrich; Tryggvason Karl (May 2002). "Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (11): 7414–9. doi:10.1073/pnas.102185399. ISSN 0027-8424. PMC 124245. PMID 12032297. 
  5. ^ Overall, C M; Tam E; McQuibban G A; Morrison C; Wallon U M; Bigg H F; King A E; Roberts C R (December 2000). "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. (UNITED STATES) 275 (50): 39497–506. doi:10.1074/jbc.M005932200. ISSN 0021-9258. PMID 10991943. 
  6. ^ Bigg, H F; Shi Y E; Liu Y E; Steffensen B; Overall C M (June 1997). "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. (UNITED STATES) 272 (24): 15496–500. doi:10.1074/jbc.272.24.15496. ISSN 0021-9258. PMID 9182583. 
  7. ^ Kai, Heidi S-T; Butler Georgina S; Morrison Charlotte J; King Angela E; Pelman Gayle R; Overall Christopher M (December 2002). "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. (United States) 277 (50): 48696–707. doi:10.1074/jbc.M209177200. ISSN 0021-9258. PMID 12374789. 

Further reading[edit]

  • Liotta LA, Stetler-Stevenson W, Steeg PS (1991). "Metastasis suppressor genes.". Important Adv. Oncol.: 85–100. PMID 1869284. 
  • Stetler-Stevenson WG, Seo DW (2005). "TIMP-2: an endogenous inhibitor of angiogenesis.". Trends in molecular medicine 11 (3): 97–103. doi:10.1016/j.molmed.2005.01.007. PMID 15760767. 

External links[edit]

  • The MEROPS online database for peptidases and their inhibitors: I35.002