TIMP1

TIMP1
Available structures
PDB	Ortholog search:PDBeRCSB
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;OMA:TIMP1 - orthologs
Gene location (Human)
Chr.	X chromosome (human)
End	47,586,789bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	20,740,974bp
RNA expressionpattern
	Top expressed in
	right coronary artery; ; gallbladder; ; left coronary artery; ; Descending thoracic aorta; ; ascending aorta; ; stromal cell of endometrium; ; islet of Langerhans; ; pericardium; ; beta cell; ; right adrenal gland;
	Top expressed in
	calvaria; ; endothelial cell of lymphatic vessel; ; stroma of bone marrow; ; body of femur; ; ankle joint; ; ankle; ; gastrula; ; lactiferous gland; ; fossa; ; belly cord;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	peptidase inhibitor activity; enzyme inhibitor activity; cytokine activity; metal ion binding; protease binding; 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 space; endoplasmic reticulum lumen; collagen;
Biological process	response to cytokine; negative regulation of peptidase activity; human ageing; 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 population proliferation; response to hormone; negative regulation of membrane protein ectodomain proteolysis; negative regulation of endopeptidase activity; negative regulation of catalytic activity; negative regulation of metallopeptidase activity; post-translational protein modification; regulation of signaling receptor activity; connective tissue replacement involved in inflammatory response wound healing; cytokine-mediated signaling pathway;
	Sources:Amigo/QuickGO
Orthologs
	7076
	21857
	ENSG00000102265
	ENSMUSG00000001131
	P01033; Q6FGX5
	P12032
	NM_003254
	NM_001044384; NM_001294280; NM_011593
	NP_003245; NP_003245.1
	NP_001037849; NP_001281209; NP_035723
	Wikidata
View/Edit Human	View/Edit Mouse

TIMP metallopeptidase inhibitor 1,also known asTIMP1,atissue inhibitor of metalloproteinases,is a glycoprotein with a molecular weight of 28 kDa.^[5]TIMP1 is expressed from several tissues of organisms.

This protein is a member of theTIMP family.Theglycoproteinis a naturalinhibitorof thematrix metalloproteinases(MMPs), a group of peptidases involved in degradation of theextracellular matrix.In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promotecellproliferation in a wide range of cell types, and may also have an anti-apoptotic function.

Function

TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs), and disintegrin-metalloproteinases (ADAMs and ADAMTSs).^[6]In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing,^[7]and pregnancy.^[8]^[9]^[10]

The dysregulated activity of TIMP1 has been implicated in cancer.^[11]In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium.^[12]Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy.^[13]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 manipulatedin vitrousing techniques, like the TIMP1 knock-out.^[14]^[15]^[16]

Other names

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

Regulation of TIMP expression

Transcriptionof thisgeneis highly inducible in response to manycytokinesandhormones.In addition, the expression from some but not all inactiveX chromosomessuggests that this gene inactivation is polymorphic inhuman females.This gene is located within intron 6 of thesynapsin Igene and is transcribed in the opposite direction.^[17]

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.^[18]

Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such aslaryngeal carcinoma^[19]ormelanoma.^[20]

References

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000102265–Ensembl,May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000001131–Ensembl,May 2017
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Nee, Larine E.; Mcmorrow, Tara; Campbell, Eric; Slattery, Craig; Ryan, Michael P. (2004-10-01)."TNF-α and IL-1β–mediated regulation of MMP-9 and TIMP-1 in renal proximal tubular cells".Kidney International.66(4): 1376–1386.doi:10.1111/j.1523-1755.2004.00900.x.ISSN 0085-2538.PMID 15458430.
^Brew K, Nagase H (January 2010)."The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity".Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.1803(1): 55–71.doi:10.1016/j.bbamcr.2010.01.003.PMC2853873.PMID 20080133.
^Brew K, Dinakarpandian D, Nagase H (March 2000). "Tissue inhibitors of metalloproteinases: evolution, structure and function".Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.1477(1–2): 267–83.doi:10.1016/S0167-4838(99)00279-4.PMID 10708863.
^Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID 1652588.S2CID 3145982.
^Nothnick WB, Soloway P, Curry TE (May 1997)."Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene".Biology of Reproduction.56(5): 1181–8.doi:10.1095/biolreprod56.5.1181.PMID 9160717.
^Nothnick WB (September 2000)."Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice".Biology of Reproduction.63(3): 905–12.doi:10.1095/biolreprod63.3.905.PMID 10952938.
^Kim YS, Kim SH, Kang JG, Ko JH (2012)."Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression".BMB Reports.45(11): 623–8.doi:10.5483/BMBRep.2012.45.11.233.PMC4133808.PMID 23187000.
^Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID 1652588.S2CID 3145982.
^Vincent ZL, Mitchell MD, Ponnampalam AP (December 2015)."Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine".Reproductive Biology and Endocrinology.13:136.doi:10.1186/s12958-015-0132-y.PMC4687108.PMID 26691525.
^Gong Y, Scott E, Lu R, Xu Y, Oh WK, Yu Q (2013-10-15)."TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression".PLOS ONE.8(10): e77366.Bibcode:2013PLoSO...877366G.doi:10.1371/journal.pone.0077366.PMC3797040.PMID 24143225.
^Jourquin J, Tremblay E, Bernard A, Charton G, Chaillan FA, Marchetti E, Roman FS, Soloway PD, Dive V, Yiotakis A, Khrestchatisky M, Rivera S (November 2005). "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory".The European Journal of Neuroscience.22(10): 2569–78.doi:10.1111/j.1460-9568.2005.04426.x.PMID 16307599.S2CID 18499513.
^Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID 1652588.S2CID 3145982.
^"Entrez Gene: TIMP1 TIMP metallopeptidase inhibitor 1".
^Reichenstein M, Reich R, LeHoux JG, Hanukoglu I (February 2004). "ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells".Molecular and Cellular Endocrinology.215(1–2): 109–14.CiteSeerX10.1.1.538.7614.doi:10.1016/j.mce.2003.11.011.PMID 15026182.S2CID 6836003.
^Ma J, Wang J, Fan W, Pu X, Zhang D, Fan C, Xiong L, Zhu H, Xu N, Chen R, Liu S (Dec 2013)."Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma".International Journal of Clinical and Experimental Pathology.7(1): 246–54.PMC3885479.PMID 24427345.
^Tarhini AA, Lin Y, Yeku O, LaFramboise WA, Ashraf M, Sander C, Lee S, Kirkwood JM (January 2014)."A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma".Journal of Translational Medicine.12:19.doi:10.1186/1479-5876-12-19.PMC3909384.PMID 24457057.

External links

TheMEROPSonline database for peptidases and their inhibitors:I35.001
Overview of all the structural information available in thePDBforUniProt:P01033(Metalloproteinase inhibitor 1) at thePDBe-KB.

This article on ageneon the humanX chromosomeand/or its associatedproteinis astub.You can help Wikipedia byexpanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000102265–Ensembl,May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000001131–Ensembl,May 2017

[3] "Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Nee, Larine E.; Mcmorrow, Tara; Campbell, Eric; Slattery, Craig; Ryan, Michael P. (2004-10-01)."TNF-α and IL-1β–mediated regulation of MMP-9 and TIMP-1 in renal proximal tubular cells".Kidney International.66(4): 1376–1386.doi:10.1111/j.1523-1755.2004.00900.x.ISSN 0085-2538.PMID 15458430.

[6] Brew K, Nagase H (January 2010)."The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity".Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.1803(1): 55–71.doi:10.1016/j.bbamcr.2010.01.003.PMC2853873.PMID 20080133.

[7] Brew K, Dinakarpandian D, Nagase H (March 2000). "Tissue inhibitors of metalloproteinases: evolution, structure and function".Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.1477(1–2): 267–83.doi:10.1016/S0167-4838(99)00279-4.PMID 10708863.

[8] Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID 1652588.S2CID 3145982.

[9] Nothnick WB, Soloway P, Curry TE (May 1997)."Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene".Biology of Reproduction.56(5): 1181–8.doi:10.1095/biolreprod56.5.1181.PMID 9160717.

[10] Nothnick WB (September 2000)."Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice".Biology of Reproduction.63(3): 905–12.doi:10.1095/biolreprod63.3.905.PMID 10952938.

[pmid23187000-11] Kim YS, Kim SH, Kang JG, Ko JH (2012)."Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression".BMB Reports.45(11): 623–8.doi:10.5483/BMBRep.2012.45.11.233.PMC4133808.PMID 23187000.

[12] Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID 1652588.S2CID 3145982.

[13] Vincent ZL, Mitchell MD, Ponnampalam AP (December 2015)."Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine".Reproductive Biology and Endocrinology.13:136.doi:10.1186/s12958-015-0132-y.PMC4687108.PMID 26691525.

[14] Gong Y, Scott E, Lu R, Xu Y, Oh WK, Yu Q (2013-10-15)."TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression".PLOS ONE.8(10): e77366.Bibcode:2013PLoSO...877366G.doi:10.1371/journal.pone.0077366.PMC3797040.PMID 24143225.

[15] Jourquin J, Tremblay E, Bernard A, Charton G, Chaillan FA, Marchetti E, Roman FS, Soloway PD, Dive V, Yiotakis A, Khrestchatisky M, Rivera S (November 2005). "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory".The European Journal of Neuroscience.22(10): 2569–78.doi:10.1111/j.1460-9568.2005.04426.x.PMID 16307599.S2CID 18499513.

[16] Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID 1652588.S2CID 3145982.

[17] "Entrez Gene: TIMP1 TIMP metallopeptidase inhibitor 1".

[pmid15026182-18] Reichenstein M, Reich R, LeHoux JG, Hanukoglu I (February 2004). "ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells".Molecular and Cellular Endocrinology.215(1–2): 109–14.CiteSeerX10.1.1.538.7614.doi:10.1016/j.mce.2003.11.011.PMID 15026182.S2CID 6836003.

[pmid_=_24427345-19] Ma J, Wang J, Fan W, Pu X, Zhang D, Fan C, Xiong L, Zhu H, Xu N, Chen R, Liu S (Dec 2013)."Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma".International Journal of Clinical and Experimental Pathology.7(1): 246–54.PMC3885479.PMID 24427345.

[pmid_=_24457057-20] Tarhini AA, Lin Y, Yeku O, LaFramboise WA, Ashraf M, Sander C, Lee S, Kirkwood JM (January 2014)."A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma".Journal of Translational Medicine.12:19.doi:10.1186/1479-5876-12-19.PMC3909384.PMID 24457057.

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