TIMP1

 TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms.

TIMP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1D2B, 1OO9, 1UEA, 2J0T, 3MA2, 3V96
Identifiers
Aliases	TIMP1, CLGI, EPA, EPO, HCI, TIMP, TIMP-1, TIMP metallopeptidase inhibitor 1
External IDs	OMIM: 305370 MGI: 98752 HomoloGene: 36321 GeneCards: TIMP1
Gene location (Human) Chr. X chromosome (human)[1] Band Xp11.3 Start 47,582,408 bp[1] End 47,586,789 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A1.3|X 16.38 cM Start 20,870,166 bp[2] End 20,874,735 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • peptidase inhibitor activity • GO:0048551 enzyme inhibitor activity • cytokine activity • metal ion binding • protease binding • GO:0001948 protein binding • metalloendopeptidase inhibitor activity • growth factor activity • zinc ion binding Cellular component • extracellular matrix • extracellular region • basement membrane • extracellular exosome • platelet alpha granule lumen • extracellular • endoplasmic reticulum lumen • collagen Biological process • response to cytokine • negative regulation of peptidase activity • aging • response to peptide hormone • platelet degranulation • wound healing • negative regulation of apoptotic process • extracellular matrix disassembly • negative regulation of trophoblast cell migration • response to organic substance • cell activation • cartilage development • regulation of integrin-mediated signaling pathway • positive regulation of cell proliferation • response to hormone • negative regulation of membrane protein ectodomain proteolysis • negative regulation of endopeptidase activity • GO:0048553 negative regulation of catalytic activity • negative regulation of metallopeptidase activity • post-translational modification • cellular protein metabolic process • regulation of receptor activity • connective tissue replacement involved in inflammatory response wound healing • cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7076	21857
Ensembl	ENSG00000102265	ENSMUSG00000001131
UniProt	P01033 Q6FGX5	P12032
RefSeq (mRNA)	NM_003254	NM_001044384 NM_001294280 NM_011593
RefSeq (protein)	NP_003245 NP_003245.1	NP_001037849 NP_001281209 NP_035723
Location (UCSC)	Chr X: 47.58 – 47.59 Mb	Chr X: 20.87 – 20.87 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This protein is a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.

FunctionEdit

TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs), and disintegrin-metalloproteinases (ADAMs and ADAMTSs).^[5] In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing,^[6] and pregnancy.^[7][8][9]

The dysregulated activity of TIMP1 has been implicated in cancer.^[10] In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium.^[11] Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy.^[12] Studies attribute this role to a mechanism involving the chromatin structure at the TIMP1 promoter region, implicating new pharmaceutical possibilities for the therapeutic regulation of TIMP1. Accordingly, TIMP1 can be manipulated in vitro using techniques, like the TIMP1 knock-out.^[13][14][15]

Other namesEdit

• Erythroid potentiating activity (EPA)
• Human collagenase inhibitor (HCI)

Regulation of TIMP expressionEdit

Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I gene and is transcribed in the opposite direction.^[16]

In adrenocortical cells the trophic hormone ACTH induces expression of TIMP-1 and the increase in TIMP expression is also associated with decreased collagenase activity.^[17]

Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such as laryngeal carcinoma ^[18] or melanoma.^[19]

This article uses material from the Wikipedia article  Metasyntactic variable, which is released under the  Creative Commons Attribution-ShareAlike 3.0 Unported License.