TIMP2

TIMP2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BR9, 1GXD, 2TMP, 4ILW
Identifiers
Aliases	TIMP2, CSC-21K, DDC8, TIMP metallopeptidase inhibitor 2
External IDs	OMIM: 188825; MGI: 98753; HomoloGene: 2444; GeneCards: TIMP2; OMA:TIMP2 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q25.3 Start 78,852,977 bp[1] End 78,925,387 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 E2|11 83.09 cM Start 118,191,895 bp[2] End 118,246,566 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tendon of biceps brachii synovial joint stromal cell of endometrium tibia urethra Descending thoracic aorta trigeminal ganglion ascending aorta right coronary artery visceral pleura Top expressed in calvaria stroma of bone marrow ankle skin of external ear body of femur ventromedial nucleus subiculum anterior amygdaloid area endothelial cell of lymphatic vessel retinal pigment epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity enzyme inhibitor activity metal ion binding integrin binding protein binding protease binding metalloendopeptidase inhibitor activity zinc ion binding Cellular component growth cone extracellular region cell surface neuronal cell body neuron projection extracellular exosome extracellular matrix extracellular space specific granule lumen tertiary granule lumen ficolin-1-rich granule lumen collagen-containing extracellular matrix Biological process negative regulation of proteolysis response to cytokine negative regulation of peptidase activity positive regulation of adenylate cyclase activity human ageing extracellular matrix disassembly negative regulation of Ras protein signal transduction central nervous system development positive regulation of neuron differentiation response to hormone negative regulation of membrane protein ectodomain proteolysis positive regulation of MAPK cascade negative regulation of cell population proliferation negative regulation of mitotic cell cycle regulation of Rap protein signal transduction negative regulation of endopeptidase activity neutrophil degranulation negative regulation of metallopeptidase activity response to organic substance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7077 21858 Ensembl ENSG00000035862 ENSMUSG00000017466 UniProt P16035 P25785 RefSeq (mRNA) NM_003255 NM_011594 RefSeq (protein) NP_003246 n/a Location (UCSC) Chr 17: 78.85 – 78.93 Mb Chr 11: 118.19 – 118.25 Mb PubMed search [3] [4]
Wikidata
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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.^[5] 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.^[6]

In melanocytic cells TIMP2 gene expression may be regulated by MITF.^[7]

A 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.^[8][9] Its role in hippocampal function was later described to be related to its interactions with the extracellular matrix to regulate neurogenesis and dendritic spines plasticity.^[10]

Interactions

TIMP2 has been shown to interact with:

• MMP14^[11] and
• MMP2.^{[12][13][14][15]}

See also

• TIMP1, TIMP3, TIMP4

References

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.

This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by expanding it.

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