TIMP4

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

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

OMIM ID:`OMIM ID 601915 `_

NCBI Phenotypes

No phenotypes found linked to this gene.

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

KEGG Pathways

No pathways found linked to this gene.

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]

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

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