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	MGI: 98753 HomoloGene: 2444 GeneCards: TIMP2
Genetically Related Diseases
periodontitis, obesity[1]
Gene ontology Molecular function • peptidase inhibitor activity • enzyme inhibitor activity • metal ion binding • protease binding • integrin binding • protein binding • metalloendopeptidase inhibitor activity Cellular component • growth cone • proteinaceous extracellular matrix • extracellular fluid • extracellular region • cell surface • neuronal cell body • neuron projection • extracellular exosome • extracellular matrix Biological process • negative regulation of proteolysis • response to cytokine • negative regulation of peptidase activity • positive regulation of adenylate cyclase activity • aging • 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 • response to drug • positive regulation of MAPK cascade • negative regulation of cell proliferation • negative regulation of mitotic cell cycle • regulation of Rap protein signal transduction • negative regulation of endopeptidase activity Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7077	21858
Ensembl	ENSG00000035862	ENSMUSG00000017466
UniProt	P16035	P25785
RefSeq (mRNA)	NM_003255	NM_011594
RefSeq (protein)	NP_003246.1	n/a
Location (UCSC)	Chr 17: 78.85 – 78.93 Mb	Chr 11: 118.3 – 118.36 Mb
PubMed search	[2]	[3]
Wikidata

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.^[4] TIMP-2 functions as both an MMP inhibitor and an activator. TIMPs inhibit all active MMPs, but different TIMPs inhibit different MMPs better than other TIMPs. 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.^[5]

In melanocytic cells TIMP2 gene expression may be regulated by MITF.^[6]

Interactions

TIMP2 has been shown to interact with:

• MMP14^[7] and
• MMP2.^{[8][9][10][11]}

See also

• TIMP1, TIMP3, TIMP4

References

Further reading

External links

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

PDB gallery
1bqq: CRYSTAL STRUCTURE OF THE MT1-MMP--TIMP-2 COMPLEX  1br9: HUMAN TISSUE INHIBITOR OF METALLOPROTEINASE-2  1buv: CRYSTAL STRUCTURE OF THE MT1-MMP-TIMP-2 COMPLEX  1gxd: PROMMP-2/TIMP-2 COMPLEX  2e2d: Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2  2tmp: N-TERMINAL DOMAIN OF TISSUE INHIBITOR OF METALLOPROTEINASE-2 (N-TIMP-2), NMR, 49 STRUCTURES