TIMP4

TIMP metallopeptidase inhibitor 4
Identifiers
Symbols	TIMP4;
External IDs	OMIM: 601915 MGI: 109125 HomoloGene: 37748 GeneCards: TIMP4 Gene
Gene Ontology Molecular function • enzyme inhibitor activity • metalloendopeptidase inhibitor activity • metal ion binding Cellular component • extracellular region • extracellular space • sarcomere Biological process • central nervous system development • biological_process • response to lipopolysaccharide • response to cytokine stimulus • response to drug • ovulation cycle • response to peptide hormone stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7079	110595
Ensembl	ENSG00000157150	ENSMUSG00000030317
UniProt	Q99727	Q3USH7
RefSeq (mRNA)	NM_003256	NM_080639.3
RefSeq (protein)	NP_003247	NP_542370.3
Location (UCSC)	Chr 3: 12.19 – 12.2 Mb	Chr 6: 115.2 – 115.2 Mb
PubMed search	[1]	[2]

Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene.

This gene belongs to the tissue inhibitor of metalloproteinases 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.

Interactions

TIMP4 has been shown to interact with MMP2.

Further reading

• Bigg HF, Shi YE, Liu YE et al (1997). "Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2". J. Biol. Chem. 272 (24): 15496–15500. doi:10.1074/jbc.272.24.15496. PMID 9182583. 
• Pohar N, Godenschwege TA, Buchner E (1999). "Invertebrate tissue inhibitor of metalloproteinase: structure and nested gene organization within the synapsin locus is conserved from Drosophila to human". Genomics 57 (2): 293–296. doi:10.1006/geno.1999.5776. PMID 10198170. 
• Hernandez-Barrantes S, Shimura Y, Soloway PD et al (2001). "Differential roles of TIMP-4 and TIMP-2 in pro-MMP-2 activation by MT1-MMP". Biochem. Biophys. Res. Commun. 281 (1): 126–130. doi:10.1006/bbrc.2001.4323. PMID 11178970. 
• Huang W, Li WQ, Dehnade F, Zafarullah M (2002). "Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage". J. Cell. Biochem. 85 (2): 295–303. doi:10.1002/jcb.10138. PMID 11948685. 
• Zhang J, Cao YJ, Zhao YG et al (2003). "Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3". Mol. Hum. Reprod. 8 (7): 659–666. doi:10.1093/molehr/8.7.659. PMID 12087081. 
• Kai HS, Butler GS, Morrison CJ et al (2003). "Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. The importance of acidic residues in binding the MMP-2 hemopexin C-domain". J. Biol. Chem. 277 (50): 48696–48707. doi:10.1074/jbc.M209177200. PMID 12374789. 
• Radomski A, Jurasz P, Sanders EJ et al (2003). "Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets". Br. J. Pharmacol. 137 (8): 1330–1338. doi:10.1038/sj.bjp.0704936. PMC 1573597. PMID 12466243. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1573597. 
• Troeberg L, Tanaka M, Wait R et al (2003). "E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP-2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A)". Biochemistry 41 (50): 15025–15035. doi:10.1021/bi026454l. PMID 12475252. 
• Strausberg RL, Feingold EA, Grouse LH et al (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Chegini N, Rhoton-Vlasak A, Williams RS (2003). "Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding". Fertil. Steril. 80 (3): 564–570. doi:10.1016/S0015-0282(03)00797-0. PMID 12969699. 
• Zhao YG, Xiao AZ, Park HI et al (2004). "Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion". Cancer Res. 64 (2): 590–598. doi:10.1158/0008-5472.CAN-03-1932. PMID 14744773. 
• Pilka R, Domanski H, Hansson S et al (2005). "Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26". Mol. Hum. Reprod. 10 (9): 641–650. doi:10.1093/molehr/gah092. PMID 15273280. 
• Gerhard DS, Wagner L, Feingold EA et al (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Lee MH, Rapti M, Murphy G (2005). "Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme.". J. Biol. Chem. 280 (16): 15967–75. doi:10.1074/jbc.M500897200. PMID 15713681. 
• Lizarraga F, Espinosa M, Maldonado V, Melendez-Zajgla J (2005). "Tissue inhibitor of metalloproteinases-4 is expressed in cervical cancer patients". Anticancer Res. 25 (1B): 623–7. PMID 15816637. 
• Rual JF, Venkatesan K, Hao T et al (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514. 
• Koskivirta I, Rahkonen O, Mäyränpää M et al (2007). "Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology". Histochem. Cell Biol. 126 (3): 335–342. doi:10.1007/s00418-006-0163-8. PMID 16521002. 
• Pilka R, Noskova V, Domanski H et al (2006). "Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid". Mol. Hum. Reprod. 12 (8): 497–503. doi:10.1093/molehr/gal055. PMID 16809379. 

External Links

• The MEROPS online database for peptidases and their inhibitors: I35.004