.. _TIMP4: TIMP4 ^^^^^ .. contents:: :local: General Information ******************* :Full gene name: TIMP metallopeptidase inhibitor 4 :Entrez Gene ID: 7079 :Location: 3p25 :Synonyms: :Type: protein-coding User SNPs ********* SNPs given by the user that are near or inside this gene: +-----------+---------------+-----------+ | SNP | Distance (bp) | Direction | +===========+===============+===========+ | rs1801282 | 192274 | upstream | +-----------+---------------+-----------+ .. _TIMP4 Gene summary: NCBI Summary ************ This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulation and endometrial tissue remodeling. [provided by RefSeq, Jul 2008] .. _OMIM ID 601915 : http://omim.org/entry/601915 .. _TIMP4 OMIM Text: OMIM **** :OMIM ID: `OMIM ID 601915 `_ .. _TIMP4 Phenotype: NCBI Phenotypes *************** No phenotypes found linked to this gene. .. _TIMP4 GO Term: Gene Ontology ************* * response to peptide hormone stimulus * ovulation cycle * response to cytokine stimulus * metalloendopeptidase inhibitor activity * extracellular region * central nervous system development * response to lipopolysaccharide * response to drug * extracellular space * metal ion binding * biological_process * sarcomere .. _TIMP4 Pathway: KEGG Pathways ************* No pathways found linked to this gene. .. _TIMP4 GeneRIF: GeneRIFs ******** * TIMP-4 displayed negligible activity against TACE, N-TIMP-4 is a slow tight-binding inhibitor with low nanomolar binding affinity [`PMID 15713681`_] * MMP-10 and -7 abundance increased, accompanied by decreased TIMP-4 in dilated cardiomyopathy failing hearts compared with non-failing hearts. [`PMID 20219015`_] * TIMP-4 is expressed de novo in cervical cancer [`PMID 15816637`_] * C/T polymorphism which is located on the 3'-untranslational regions of the TIMP-4 gene might be associated with susceptibility to Osteoarthritis in a Korean population [`PMID 18301898`_] * Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) [`PMID 18818748`_] * Peaks during the early to mid-luteal phase. Seems to play role in hormonal regulation and endometrial tissue remodeling. [`PMID 12969699`_] * this work provides the first evidence of a TIMP-4/CD63 association in astrocytoma tumor cells [`PMID 20693981`_] * Progress curve analysis of MMP inhibition by TIMP-4 indicates that association rate constants and inhibition constants are similar to those for other TIMPs; TIMP-4 has a 5-fold lower binding affinity for proMMP-2 than does TIMP-2. [`PMID 12475252`_] * Peroxynitrite-induced nitration and oligomerization of TIMP-4 attenuated its inhibitory activity against MMP-2 activity and endothelial or tumor cell invasiveness. [`PMID 18336787`_] * An imbalance between TIMP-1 and TIMP-4 serum levels is present in inflammatory bowel disease (ulcerative colitis and Crohn's disease) patients. [`PMID 19036126`_] * TIMP4 expression is a downstream target of GCM1 [`PMID 21406447`_] * TIMP4 is related to the development of KD with CALs in Korean children. [`PMID 19048177`_] * Maximal expression of TIMP-4 in the early and mid-secretory phase suggests its role during implantation and results show that TIMP-4 control the the relaese of MMP-26 in both stroma and uterine fluid. [`PMID 16809379`_] * Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [`PMID 20628086`_] * TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis [`PMID 19700750`_] * investigation of structural and functional differences between TIMP-4 and TIMP-2 by mutagenesis into C-terminal tails [`PMID 12374789`_] * Reconstituted Complex [`PMID 12374789`_] * Results suggest a functional relationship between TIMP-4 mRNA and MMP-26 mRNA, and possibly a role in human implantation. [`PMID 15273280`_] * Heterogeneous methylation in the promoter region of TIMP4 was associated with cancer progression in non-small cell lung cancer. [`PMID 22018271`_] * a cardiopulmonary vasculature-specific role of TIMP-4 activation in systemic sclerosis. [`PMID 19190762`_] * In conclusion, the data demonstrate upregulation of TIMP4 in human cardiovascular disorders exhibiting inflammation, suggesting its future use as a novel systemic marker for vascular inflammation. [`PMID 16521002`_] * TIMP-4 is the major intraplatelet matrix metalloproteinase inhibitor and it is involved in regulation of platelet aggregation and recruitment. [`PMID 12466243`_] * Expressions of MMP1, MMP9, TIMP4, and EMMPRIN were significantly unbalanced in the myocardium of congestive heart failure patients with rheumatic heart diseases. [`PMID 19734590`_] * Enzyme immunoassays showed the levels of type 4 tissue inhibitor of metalloproteinases were virtually the same in colorectal cancer and mucosa. [`PMID 18214300`_] * Results indicate that MMP-26 and TIMP-4 may play an integral role during the conversion of high-grade prostatic intraepithelial neoplasia to invasive cancer and may also serve as markers for early prostate cancer diagnosis. [`PMID 16940965`_] * Plasma TIMP-4 has a role in the prediction of LV remodeling and the pathophysiology of the heart postinfarction [`PMID 21624734`_] * Observational study of gene-disease association. (HuGE Navigator) [`PMID 20587546`_] * MMP-3 and TIMP-4 polymorphisms affect angiographic coronary plaque progression in type 2 diabetic and non-diabetic patients [`PMID 19376102`_] * TIMP-4 overexpression is associated with joint tissue remodeling and pathogenesis of osteoarthritic cartilage [`PMID 11948685`_] * MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in breast cancer cells. [`PMID 14744773`_] * A trend toward increased serum levels of MMP-9/TIMP-4 was found in patients with successful arteriovenous fistulas. [`PMID 21620625`_] .. _PMID 15713681: http://www.ncbi.nlm.nih.gov/pubmed/15713681 .. _PMID 20219015: http://www.ncbi.nlm.nih.gov/pubmed/20219015 .. _PMID 15816637: http://www.ncbi.nlm.nih.gov/pubmed/15816637 .. _PMID 18301898: http://www.ncbi.nlm.nih.gov/pubmed/18301898 .. _PMID 18818748: http://www.ncbi.nlm.nih.gov/pubmed/18818748 .. _PMID 12969699: http://www.ncbi.nlm.nih.gov/pubmed/12969699 .. _PMID 20693981: http://www.ncbi.nlm.nih.gov/pubmed/20693981 .. _PMID 12475252: http://www.ncbi.nlm.nih.gov/pubmed/12475252 .. _PMID 18336787: http://www.ncbi.nlm.nih.gov/pubmed/18336787 .. _PMID 19036126: http://www.ncbi.nlm.nih.gov/pubmed/19036126 .. _PMID 21406447: http://www.ncbi.nlm.nih.gov/pubmed/21406447 .. _PMID 19048177: http://www.ncbi.nlm.nih.gov/pubmed/19048177 .. _PMID 16809379: http://www.ncbi.nlm.nih.gov/pubmed/16809379 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 19700750: http://www.ncbi.nlm.nih.gov/pubmed/19700750 .. _PMID 12374789: http://www.ncbi.nlm.nih.gov/pubmed/12374789 .. _PMID 15273280: http://www.ncbi.nlm.nih.gov/pubmed/15273280 .. _PMID 22018271: http://www.ncbi.nlm.nih.gov/pubmed/22018271 .. _PMID 19190762: http://www.ncbi.nlm.nih.gov/pubmed/19190762 .. _PMID 16521002: http://www.ncbi.nlm.nih.gov/pubmed/16521002 .. _PMID 12466243: http://www.ncbi.nlm.nih.gov/pubmed/12466243 .. _PMID 19734590: http://www.ncbi.nlm.nih.gov/pubmed/19734590 .. _PMID 18214300: http://www.ncbi.nlm.nih.gov/pubmed/18214300 .. _PMID 16940965: http://www.ncbi.nlm.nih.gov/pubmed/16940965 .. _PMID 21624734: http://www.ncbi.nlm.nih.gov/pubmed/21624734 .. _PMID 20587546: http://www.ncbi.nlm.nih.gov/pubmed/20587546 .. _PMID 19376102: http://www.ncbi.nlm.nih.gov/pubmed/19376102 .. _PMID 11948685: http://www.ncbi.nlm.nih.gov/pubmed/11948685 .. _PMID 14744773: http://www.ncbi.nlm.nih.gov/pubmed/14744773 .. _PMID 21620625: http://www.ncbi.nlm.nih.gov/pubmed/21620625 .. _TIMP4 Pubmed: PubMed Articles *************** *Recent articles:* * Azhikina T et al. "Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non-small cell lung cancer and surrounding tissues." Cancer Genet. 2011 Sep;204(9):492-500. `PMID 22018271`_ * Lee ES et al. "Serum metalloproteinases MMP-2, MMP-9, and metalloproteinase tissue inhibitors in patients are associated with arteriovenous fistula maturation." J Vasc Surg. 2011 Aug;54(2):454-9; discussion 459-60. `PMID 21620625`_ * Weir RA et al. "Plasma TIMP-4 predicts left ventricular remodeling after acute myocardial infarction." J Card Fail. 2011 Jun;17(6):465-71. `PMID 21624734`_ * Drewlo S et al. "Glial cell missing-1 mediates over-expression of tissue inhibitor of metalloproteinase-4 in severe pre-eclamptic placental villi." Hum Reprod. 2011 May;26(5):1025-34. `PMID 21406447`_ * Wei Y et al. "Type-specific dysregulation of matrix metalloproteinases and their tissue inhibitors in end-stage heart failure patients: relationship between MMP-10 and LV remodelling." J Cell Mol Med. 2011 Apr;15(4):773-82. `PMID 20219015`_ * Bailey SD et al. "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study." Diabetes Care. 2010 Oct;33(10):2250-3. `PMID 20628086`_ * Rorive S et al. "TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas." Mod Pathol. 2010 Oct;23(10):1418-28. `PMID 20693981`_ * Wojciechowski R et al. "Association of matrix metalloproteinase gene polymorphisms with refractive error in Amish and Ashkenazi families." Invest Ophthalmol Vis Sci. 2010 Oct;51(10):4989-95. `PMID 20484597`_ * Nalpas B et al. "Interferon gamma receptor 2 gene variants are associated with liver fibrosis in patients with chronic hepatitis C infection." Gut. 2010 Aug;59(8):1120-6. `PMID 20587546`_ * Ryckman KK et al. "Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth." PLoS One. 2010 Feb 3;5(2):e9040. `PMID 20140262`_ .. _PMID 21406447: http://www.ncbi.nlm.nih.gov/pubmed/21406447 .. _PMID 20219015: http://www.ncbi.nlm.nih.gov/pubmed/20219015 .. _PMID 21624734: http://www.ncbi.nlm.nih.gov/pubmed/21624734 .. _PMID 22018271: http://www.ncbi.nlm.nih.gov/pubmed/22018271 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 20140262: http://www.ncbi.nlm.nih.gov/pubmed/20140262 .. _PMID 20693981: http://www.ncbi.nlm.nih.gov/pubmed/20693981 .. _PMID 20484597: http://www.ncbi.nlm.nih.gov/pubmed/20484597 .. _PMID 21620625: http://www.ncbi.nlm.nih.gov/pubmed/21620625 .. _PMID 20587546: http://www.ncbi.nlm.nih.gov/pubmed/20587546 *Top Pubmed articles linked to gene TIMP4 matching any search term:* * Li TS et al. "Diabetic impairment of C-kit bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules." PLoS One. 2011;6(10):e25543. `PMID 21984919`_ * Wei Y et al. "Type-specific dysregulation of matrix metalloproteinases and their tissue inhibitors in end-stage heart failure patients: relationship between MMP-10 and LV remodelling." J Cell Mol Med. 2011 Apr;15(4):773-82. `PMID 20219015`_ * Bailey SD et al. "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study." Diabetes Care. 2010 Oct;33(10):2250-3. `PMID 20628086`_ * MacLaren RE et al. "Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects." BMC Med Genomics. 2010 Jan 27;3:3. `PMID 20105310`_ * Cardellini M et al. "TIMP3 is reduced in atherosclerotic plaques from subjects with type 2 diabetes and increased by SirT1." Diabetes. 2009 Oct;58(10):2396-401. `PMID 19581416`_ * Chen QJ et al. "Polymorphisms of MMP-3 and TIMP-4 genes affect angiographic coronary plaque progression in non-diabetic and type 2 diabetic patients." Clin Chim Acta. 2009 Jul;405(1-2):97-103. `PMID 19376102`_ * Barth JL et al. "Oxidised, glycated LDL selectively influences tissue inhibitor of metalloproteinase-3 gene expression and protein production in human retinal capillary pericytes." Diabetologia. 2007 Oct;50(10):2200-8. `PMID 17676308`_ .. _PMID 19581416: http://www.ncbi.nlm.nih.gov/pubmed/19581416 .. _PMID 17676308: http://www.ncbi.nlm.nih.gov/pubmed/17676308 .. _PMID 20105310: http://www.ncbi.nlm.nih.gov/pubmed/20105310 .. _PMID 20219015: http://www.ncbi.nlm.nih.gov/pubmed/20219015 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 19376102: http://www.ncbi.nlm.nih.gov/pubmed/19376102 .. _PMID 21984919: http://www.ncbi.nlm.nih.gov/pubmed/21984919