Protein-coding gene in the species Homo sapiens
TIMP4 |
---|
|
Identifiers |
---|
Aliases | TIMP4, TIMP metallopeptidase inhibitor 4, TIMP-4 |
---|
External IDs | OMIM: 601915; MGI: 109125; HomoloGene: 37748; GeneCards: TIMP4; OMA:TIMP4 - orthologs |
---|
Gene location (Human) |
---|
![Chromosome 3 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/3/39/Ideogram_human_chromosome_3.svg/300px-Ideogram_human_chromosome_3.svg.png) | Chr. | Chromosome 3 (human)[1] |
---|
| Band | 3p25.2 | Start | 12,153,068 bp[1] |
---|
End | 12,158,912 bp[1] |
---|
|
Gene location (Mouse) |
---|
![Chromosome 6 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/c/c0/Ideogram_house_mouse_chromosome_6.svg/260px-Ideogram_house_mouse_chromosome_6.svg.png) | Chr. | Chromosome 6 (mouse)[2] |
---|
| Band | 6 E3|6 53.29 cM | Start | 115,218,853 bp[2] |
---|
End | 115,229,166 bp[2] |
---|
|
RNA expression pattern |
---|
Bgee | Human | Mouse (ortholog) |
---|
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 |
|
---|
BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/6/6a/PBB_GE_TIMP4_206243_at_fs.png/250px-PBB_GE_TIMP4_206243_at_fs.png) | 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
- ovulation 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 |
---|
Species | Human | Mouse |
---|
Entrez | | |
---|
Ensembl | | |
---|
UniProt | | |
---|
RefSeq (mRNA) | | |
---|
RefSeq (protein) | | |
---|
Location (UCSC) | Chr 3: 12.15 – 12.16 Mb | Chr 6: 115.22 – 115.23 Mb |
---|
PubMed search | [3] | [4] |
---|
|
Wikidata |
View/Edit Human | View/Edit Mouse |
|
Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene.[5][6][7]
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.[7]
Interactions
TIMP4 has been shown to interact with MMP2.[8][9]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000157150 – Ensembl, May 2017
- ^ a b c 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.
- ^ a b "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.
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. 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