TIMP4

TIMP4
Identifiers
Aliases	TIMP4, TIMP metallopeptidase inhibitor 4, TIMP-4
External IDs	OMIM: 601915; MGI: 109125; GeneCards: TIMP4
Gene location (Human)
Chr.	Chromosome 3 (human)
End	12,158,912 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	115,229,166 bp
RNA expression pattern
	Top expressed in
	abdominal fat; ; subcutaneous adipose tissue; ; thoracic aorta; ; left coronary artery; ; ascending aorta; ; apex of heart; ; synovial joint; ; right hemisphere of cerebellum; ; Descending thoracic aorta; ; popliteal artery;
	Top expressed in
	interventricular septum; ; white adipose tissue; ; lobe of cerebellum; ; cerebellar vermis; ; lumbar subsegment of spinal cord; ; motor neuron; ; deep cerebellar nuclei; ; tunica media of zone of aorta; ; substantia nigra; ; brown adipose tissue;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	peptidase inhibitor activity; enzyme inhibitor activity; metal ion binding; protease binding; metalloendopeptidase inhibitor activity;
Cellular component	sarcomere; extracellular region; extracellular space; extracellular matrix;
Biological process	Notch signaling pathway; negative regulation of peptidase activity; response to peptide hormone; central nervous system development; response to lipopolysaccharide; ovarian cycle; negative regulation of membrane protein ectodomain proteolysis; negative regulation of catalytic activity; negative regulation of endopeptidase activity; response to hormone; response to cytokine; biological process; response to organic substance;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	7079
	110595
	ENSG00000157150
	ENSMUSG00000030317
	Q99727
	Q9JHB3
	NM_003256
	NM_080639; NM_001356406
	NP_003247
	NP_542370; NP_001343335
	Wikidata
View/Edit Human	View/Edit Mouse

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.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000157150 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030317 – 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.
↑ Greene J, Wang M, Liu YE, Raymond LA, Rosen C, Shi YE (Jan 1997). "Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4". J Biol Chem. 271 (48): 30375–30380. doi:10.1074/jbc.271.48.30375. PMID 8939999.
↑ Olson TM, Hirohata S, Ye J, Leco K, Seldin MF, Apte SS (Sep 1998). "Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and Timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively". Genomics. 51 (1): 148–151. doi:10.1006/geno.1998.5362. PMID 9693046.
1 2 "Entrez Gene: TIMP4 TIMP metallopeptidase inhibitor 4".
↑ Bigg HF, Shi Y E, Liu Y E, Steffensen B, Overall C M (Jun 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. ISSN 0021-9258. PMID 9182583.
↑ Kai HS, Butler Georgina S, Morrison Charlotte J, King Angela E, Pelman Gayle R, Overall Christopher M (Dec 2002). "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. ISSN 0021-9258. PMID 12374789.

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. S2CID 43053515.
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.
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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
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. S2CID 15342778.
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.
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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
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. S2CID 10581957.
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

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000157150 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030317 – 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.

[pmid8939999-5] Greene J, Wang M, Liu YE, Raymond LA, Rosen C, Shi YE (Jan 1997). "Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4". J Biol Chem. 271 (48): 30375–30380. doi:10.1074/jbc.271.48.30375. PMID 8939999.

[pmid9693046-6] Olson TM, Hirohata S, Ye J, Leco K, Seldin MF, Apte SS (Sep 1998). "Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and Timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively". Genomics. 51 (1): 148–151. doi:10.1006/geno.1998.5362. PMID 9693046.

[entrez-7] 1 2 "Entrez Gene: TIMP4 TIMP metallopeptidase inhibitor 4".

[pmid9182583-8] Bigg HF, Shi Y E, Liu Y E, Steffensen B, Overall C M (Jun 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. ISSN 0021-9258. PMID 9182583.

[pmid12374789-9] Kai HS, Butler Georgina S, Morrison Charlotte J, King Angela E, Pelman Gayle R, Overall Christopher M (Dec 2002). "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. ISSN 0021-9258. PMID 12374789.

TIMP4

Interactions

See also

References

Further reading

External links