TIMP2

TIMP metallopeptidase inhibitor 2

PDB rendering based on 1bqq.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1BR9, 1GXD, 2TMP, 4ILW

Identifiers

Symbols

TIMP2 ; CSC-21K; DDC8

External IDs

OMIM: 188825 MGI: 98753 HomoloGene: 2444 GeneCards: TIMP2 Gene

Gene ontology
Molecular function	• integrin binding • protein binding • enzyme activator activity • metalloendopeptidase inhibitor activity • metal ion binding
Cellular component	• extracellular region • basement membrane • extracellular space • cell surface • growth cone • motile cilium • neuronal cell body • extracellular vesicular exosome
Biological process	• central nervous system development • aging • negative regulation of cell proliferation • negative regulation of endopeptidase activity • extracellular matrix disassembly • extracellular matrix organization • regulation of Rap protein signal transduction • response to cytokine • response to drug • positive regulation of MAPK cascade • positive regulation of neuron differentiation • positive regulation of adenylate cyclase activity • negative regulation of proteolysis • negative regulation of mitotic cell cycle • negative regulation of Ras protein signal transduction • cellular response to organic substance
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 17:
76.85 – 76.92 Mb

Chr 11:
118.3 – 118.36 Mb

PubMed search

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

Function

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

TIMP2 has been shown to interact with:

MMP14^[3] and
MMP2.^[4]^[5]^[6]^[7]

References

↑ "Entrez Gene: TIMP2 TIMP metallopeptidase inhibitor 2".
↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO 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.
↑ Zucker S, Drews M, Conner C, Foda HD, DeClerck YA, Langley KE et al. (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. 273 (2): 1216–22. doi:10.1074/jbc.273.2.1216. PMID 9422789.
↑ Morgunova E, Tuuttila A, Bergmann U, Tryggvason K (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. 99 (11): 7414–9. doi:10.1073/pnas.102185399. PMC 124245. PMID 12032297.
↑ Overall CM, Tam E, McQuibban GA, Morrison C, Wallon UM, Bigg HF et al. (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. 275 (50): 39497–506. doi:10.1074/jbc.M005932200. PMID 10991943.
↑ Bigg HF, Shi YE, Liu YE, Steffensen B, Overall CM (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. 272 (24): 15496–500. doi:10.1074/jbc.272.24.15496. PMID 9182583.
↑ Kai HS, Butler GS, Morrison CJ, King AE, Pelman GR, Overall CM (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. 277 (50): 48696–707. doi:10.1074/jbc.M209177200. PMID 12374789.