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{{Infobox_gene}}
{{PBB_Controls
'''Metalloproteinase inhibitor 4''' is an [[enzyme]] that in humans is encoded by the ''TIMP4'' [[gene]].<ref name="pmid8939999">{{cite journal |vauthors=Greene J, Wang M, Liu YE, Raymond LA, Rosen C, Shi YE | title = Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4 | journal = J Biol Chem | volume = 271 | issue = 48 | pages = 30375–30380 |date=Jan 1997 | pmid = 8939999 | pmc =  | doi =10.1074/jbc.271.48.30375 }}</ref><ref name="pmid9693046">{{cite journal |vauthors=Olson TM, Hirohata S, Ye J, Leco K, Seldin MF, Apte SS | title = 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 | journal = Genomics | volume = 51 | issue = 1 | pages = 148–151 |date=Sep 1998 | pmid = 9693046 | pmc =  | doi = 10.1006/geno.1998.5362 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TIMP4 TIMP metallopeptidase inhibitor 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7079| accessdate = }}</ref>
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{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = TIMP metallopeptidase inhibitor 4
| HGNCid = 11823
| Symbol = TIMP4
| AltSymbols =;
| OMIM = 601915
| ECnumber =
| Homologene = 37748
| MGIid = 109125
  | GeneAtlas_image1 = PBB_GE_TIMP4_206243_at_tn.png
  | Function = {{GNF_GO|id=GO:0004857 |text = enzyme inhibitor activity}} {{GNF_GO|id=GO:0008191 |text = metalloendopeptidase inhibitor activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005578 |text = proteinaceous extracellular matrix}}
| Process = {{GNF_GO|id=GO:0008150 |text = biological_process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7079
    | Hs_Ensembl = ENSG00000157150
    | Hs_RefseqProtein = NP_003247
    | Hs_RefseqmRNA = NM_003256
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 12169578
    | Hs_GenLoc_end = 12175851
    | Hs_Uniprot = Q99727
    | Mm_EntrezGene = 110595
    | Mm_Ensembl = ENSMUSG00000030317
    | Mm_RefseqmRNA = NM_080639
    | Mm_RefseqProtein = NP_542370
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 115211438
    | Mm_GenLoc_end = 115217467
    | Mm_Uniprot = Q3USH7
  }}
}}
'''TIMP metallopeptidase inhibitor 4''', also known as '''TIMP4''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TIMP4 TIMP metallopeptidase inhibitor 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7079| accessdate = }}</ref>


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{{PBB_Summary
{{PBB Summary
| section_title =  
| section_title =  
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: TIMP4 TIMP metallopeptidase inhibitor 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7079| accessdate = }}</ref>
| summary_text = 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.<ref name="entrez" />
}}
}}
==Interactions==
TIMP4 has been shown to [[Protein-protein interaction|interact]] with [[MMP2]].<ref name=pmid9182583>{{cite journal |last=Bigg |first=H F |authorlink= |author2=Shi Y E |author3=Liu Y E |author4=Steffensen B |author5=Overall C M  |date=Jun 1997 |title=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 |journal=J. Biol. Chem. |volume=272 |issue=24 |pages=15496–15500 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 9182583 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1074/jbc.272.24.15496 }}</ref><ref name=pmid12374789>{{cite journal |last=Kai |first=Heidi S-T |authorlink= |author2=Butler Georgina S |author3=Morrison Charlotte J |author4=King Angela E |author5=Pelman Gayle R |author6=Overall Christopher M  |date=Dec 2002 |title=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 |journal=J. Biol. Chem. |volume=277 |issue=50 |pages=48696–48707 |publisher= |location = United States| issn = 0021-9258| pmid = 12374789 |doi = 10.1074/jbc.M209177200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>
==See also==
* [[TIMP1]], [[TIMP2]], [[TIMP3]]


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Greene J, Wang M, Liu YE, ''et al.'' |title=Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. |journal=J. Biol. Chem. |volume=271 |issue= 48 |pages= 30375-80 |year= 1997 |pmid= 8939999 |doi= }}
*{{cite journal  | author=Bigg HF |title=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 |journal=J. Biol. Chem. |volume=272 |issue= 24 |pages= 15496–15500 |year= 1997 |pmid= 9182583 |doi=10.1074/jbc.272.24.15496  |name-list-format=vanc| author2=Shi YE  | author3=Liu YE  | display-authors=3  | last4=Steffensen  | first4=B  | last5=Overall  | first5=CM }}
*{{cite journal  | author=Bigg HF, Shi YE, Liu YE, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=272 |issue= 24 |pages= 15496-500 |year= 1997 |pmid= 9182583 |doi=  }}
*{{cite journal  |vauthors=Pohar N, Godenschwege TA, Buchner E |title=Invertebrate tissue inhibitor of metalloproteinase: structure and nested gene organization within the synapsin locus is conserved from Drosophila to human |journal=Genomics |volume=57 |issue= 2 |pages= 293–296 |year= 1999 |pmid= 10198170 |doi= 10.1006/geno.1999.5776 }}
*{{cite journal  | author=Olson TM, Hirohata S, Ye J, ''et al.'' |title=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. |journal=Genomics |volume=51 |issue= 1 |pages= 148-51 |year= 1998 |pmid= 9693046 |doi= 10.1006/geno.1998.5362 }}
*{{cite journal  | author=Hernandez-Barrantes S |title=Differential roles of TIMP-4 and TIMP-2 in pro-MMP-2 activation by MT1-MMP |journal=Biochem. Biophys. Res. Commun. |volume=281 |issue= 1 |pages= 126–130 |year= 2001 |pmid= 11178970 |doi= 10.1006/bbrc.2001.4323 |name-list-format=vanc| author2=Shimura Y | author3=Soloway PD | display-authors=3  | last4=Sang  | first4=QA  | last5=Fridman  | first5=R }}
*{{cite journal  | author=Pohar N, Godenschwege TA, Buchner E |title=Invertebrate tissue inhibitor of metalloproteinase: structure and nested gene organization within the synapsin locus is conserved from Drosophila to human. |journal=Genomics |volume=57 |issue= 2 |pages= 293-6 |year= 1999 |pmid= 10198170 |doi= 10.1006/geno.1999.5776 }}
*{{cite journal  |vauthors=Huang W, Li WQ, Dehnade F, Zafarullah M |title=Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage |journal=J. Cell. Biochem. |volume=85 |issue= 2 |pages= 295–303 |year= 2002 |pmid= 11948685 |doi=10.1002/jcb.10138  }}
*{{cite journal | author=Hernandez-Barrantes S, Shimura Y, Soloway PD, ''et al.'' |title=Differential roles of TIMP-4 and TIMP-2 in pro-MMP-2 activation by MT1-MMP. |journal=Biochem. Biophys. Res. Commun. |volume=281 |issue= 1 |pages= 126-30 |year= 2001 |pmid= 11178970 |doi= 10.1006/bbrc.2001.4323 }}
*{{cite journal  | author=Zhang J |title=Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3 |journal=Mol. Hum. Reprod. |volume=8 |issue= 7 |pages= 659–666 |year= 2003 |pmid= 12087081 |doi=10.1093/molehr/8.7.659 |name-list-format=vanc| author2=Cao YJ | author3=Zhao YG  | display-authors=3  | last4=Sang  | first4=QX  | last5=Duan  | first5=EK  }}
*{{cite journal  | author=Huang W, Li WQ, Dehnade F, Zafarullah M |title=Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage. |journal=J. Cell. Biochem. |volume=85 |issue= 2 |pages= 295-303 |year= 2002 |pmid= 11948685 |doi=  }}
*{{cite journal  | author=Kai HS |title=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 |journal=J. Biol. Chem. |volume=277 |issue= 50 |pages= 48696–48707 |year= 2003 |pmid= 12374789 |doi= 10.1074/jbc.M209177200  |name-list-format=vanc| author2=Butler GS  | author3=Morrison CJ  | display-authors=3  | last4=King  | first4=AE  | last5=Pelman  | first5=GR  | last6=Overall  | first6=CM }}
*{{cite journal  | author=Zhang J, Cao YJ, Zhao YG, ''et al.'' |title=Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3. |journal=Mol. Hum. Reprod. |volume=8 |issue= 7 |pages= 659-66 |year= 2003 |pmid= 12087081 |doi=  }}
*{{cite journal  | author=Radomski A |title=Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets |journal=Br. J. Pharmacol. |volume=137 |issue= 8 |pages= 1330–1338 |year= 2003 |pmid= 12466243 |doi= 10.1038/sj.bjp.0704936  | pmc=1573597 |name-list-format=vanc| author2=Jurasz P | author3=Sanders EJ  | display-authors=3  | last4=Overall  | first4=Christopher M  | last5=Bigg  | first5=Heather F  | last6=Edwards  | first6=Dylan R  | last7=Radomski  | first7=Marek W }}
*{{cite journal | author=Kai HS, Butler GS, Morrison CJ, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=277 |issue= 50 |pages= 48696-707 |year= 2003 |pmid= 12374789 |doi= 10.1074/jbc.M209177200 }}
*{{cite journal  | author=Troeberg L |title=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) |journal=Biochemistry |volume=41 |issue= 50 |pages= 15025–15035 |year= 2003 |pmid= 12475252 |doi=10.1021/bi026454l |name-list-format=vanc| author2=Tanaka M  | author3=Wait R  | display-authors=3  | last4=Shi  | first4=Yeunian E.  | last5=Brew  | first5=Keith  | last6=Nagase  | first6=Hideaki }}
*{{cite journal | author=Radomski A, Jurasz P, Sanders EJ, ''et al.'' |title=Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets. |journal=Br. J. Pharmacol. |volume=137 |issue= 8 |pages= 1330-8 |year= 2003 |pmid= 12466243 |doi= 10.1038/sj.bjp.0704936 }}
*{{cite journal  | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–16903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241  |name-list-format=vanc| author2=Feingold EA  | author3=Grouse LH  | display-authors=3  | last4=Derge  | first4=JG  | last5=Klausner  | first5=RD  | last6=Collins | first6=FS  | last7=Wagner  | first7=L  | last8=Shenmen  | first8=CM  | last9=Schuler  | first9=GD |bibcode=2002PNAS...9916899M}}
*{{cite journal  | author=Troeberg L, Tanaka M, Wait R, ''et al.'' |title=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). |journal=Biochemistry |volume=41 |issue= 50 |pages= 15025-35 |year= 2003 |pmid= 12475252 |doi=  }}
*{{cite journal  |vauthors=Chegini N, Rhoton-Vlasak A, Williams RS |title=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 |journal=Fertil. Steril. |volume=80 |issue= 3 |pages= 564–570 |year= 2003 |pmid= 12969699 |doi=10.1016/S0015-0282(03)00797-0 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Zhao YG |title=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 |journal=Cancer Res. |volume=64 |issue= 2 |pages= 590–598 |year= 2004 |pmid= 14744773 |doi=10.1158/0008-5472.CAN-03-1932 |name-list-format=vanc| author2=Xiao AZ  | author3=Park HI  | display-authors=3  | last4=Newcomer  | first4=RG  | last5=Yan  | first5=M  | last6=Man  | first6=YG  | last7=Heffelfinger  | first7=SC  | last8=Sang  | first8=QX  }}
*{{cite journal  | author=Chegini N, Rhoton-Vlasak A, Williams RS |title=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. |journal=Fertil. Steril. |volume=80 |issue= 3 |pages= 564-70 |year= 2003 |pmid= 12969699 |doi= }}
*{{cite journal  | author=Pilka R |title=Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26 |journal=Mol. Hum. Reprod. |volume=10 |issue= 9 |pages= 641–650 |year= 2005 |pmid= 15273280 |doi= 10.1093/molehr/gah092  |name-list-format=vanc| author2=Domanski H  | author3=Hansson S  | display-authors=3  | last4=Eriksson  | first4=P  | last5=Casslén  | first5=B }}
*{{cite journal | author=Zhao YG, Xiao AZ, Park HI, ''et al.'' |title=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. |journal=Cancer Res. |volume=64 |issue= 2 |pages= 590-8 |year= 2004 |pmid= 14744773 |doi=  }}
*{{cite journal  | author=Gerhard DS |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–2127 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928  |name-list-format=vanc| author2=Wagner L  | author3=Feingold EA  | display-authors=3  | last4=Shenmen  | first4=CM  | last5=Grouse  | first5=LH  | last6=Schuler  | first6=G  | last7=Klein  | first7=SL  | last8=Old  | first8=S  | last9=Rasooly  | first9=R }}
*{{cite journal  | author=Pilka R, Domanski H, Hansson S, ''et al.'' |title=Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26. |journal=Mol. Hum. Reprod. |volume=10 |issue= 9 |pages= 641-50 |year= 2005 |pmid= 15273280 |doi= 10.1093/molehr/gah092 }}
*{{cite journal  |vauthors=Lee MH, Rapti M, Murphy G |title=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. |journal=J. Biol. Chem. |volume=280 |issue= 16 |pages= 15967–75 |year= 2005 |pmid= 15713681 |doi= 10.1074/jbc.M500897200 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  |vauthors=Lizarraga F, Espinosa M, Maldonado V, Melendez-Zajgla J |title=Tissue inhibitor of metalloproteinases-4 is expressed in cervical cancer patients |journal=Anticancer Res. |volume=25 |issue= 1B |pages= 623–7 |year= 2005 |pmid= 15816637 |doi=  }}
*{{cite journal | author=Lee MH, Rapti M, Murphy G |title=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. |journal=J. Biol. Chem. |volume=280 |issue= 16 |pages= 15967-75 |year= 2005 |pmid= 15713681 |doi= 10.1074/jbc.M500897200 }}
*{{cite journal  | author=Rual JF |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–1178 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209  |name-list-format=vanc| author2=Venkatesan K  | author3=Hao T  | display-authors=3  | last4=Hirozane-Kishikawa  | first4=Tomoko  | last5=Dricot  | first5=Amélie  | last6=Li  | first6=Ning  | last7=Berriz  | first7=Gabriel F.  | last8=Gibbons  | first8=Francis D.  | last9=Dreze  | first9=Matija |bibcode=2005Natur.437.1173R}}
*{{cite journal | author=Lizarraga F, Espinosa M, Maldonado V, Melendez-Zajgla J |title=Tissue inhibitor of metalloproteinases-4 is expressed in cervical cancer patients. |journal=Anticancer Res. |volume=25 |issue= 1B |pages= 623-7 |year= 2005 |pmid= 15816637 |doi=  }}
*{{cite journal  | author=Koskivirta I |title=Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology |journal=Histochem. Cell Biol. |volume=126 |issue= 3 |pages= 335–342 |year= 2007 |pmid= 16521002 |doi= 10.1007/s00418-006-0163-8  |name-list-format=vanc| author2=Rahkonen O  | author3=Mäyränpää M  | display-authors=3  | last4=Pakkanen  | first4=Sari  | last5=Husheem  | first5=Michael  | last6=Sainio  | first6=Annele  | last7=Hakovirta  | first7=Harri  | last8=Laine  | first8=Jukka  | last9=Jokinen  | first9=Eero }}
*{{cite journal  | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal  | author=Pilka R |title=Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid |journal=Mol. Hum. Reprod. |volume=12 |issue= 8 |pages= 497–503 |year= 2006 |pmid= 16809379 |doi= 10.1093/molehr/gal055  |name-list-format=vanc| author2=Noskova V  | author3=Domanski H  | display-authors=3  | last4=Andersson  | first4=C  | last5=Hansson  | first5=S  | last6=Casslén  | first6=B }}
*{{cite journal | author=Koskivirta I, Rahkonen O, Mäyränpää M, ''et al.'' |title=Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology. |journal=Histochem. Cell Biol. |volume=126 |issue= 3 |pages= 335-42 |year= 2007 |pmid= 16521002 |doi= 10.1007/s00418-006-0163-8 }}
*{{cite journal  | author=Pilka R, Noskova V, Domanski H, ''et al.'' |title=Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid. |journal=Mol. Hum. Reprod. |volume=12 |issue= 8 |pages= 497-503 |year= 2006 |pmid= 16809379 |doi= 10.1093/molehr/gal055 }}
}}
}}
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{{protein-stub}}
==External links==
{{WikiDoc Sources}}
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=I35.004 I35.004]
 
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Latest revision as of 19:12, 26 June 2018

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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Wikidata
View/Edit Human

Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene.[1][2][3]

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.[3]

Interactions

TIMP4 has been shown to interact with MMP2.[4][5]

See also

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 3.0 3.1 "Entrez Gene: TIMP4 TIMP metallopeptidase inhibitor 4".
  4. ↑ Bigg, H F; 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. UNITED STATES. 272 (24): 15496–15500. doi:10.1074/jbc.272.24.15496. ISSN 0021-9258. PMID 9182583.
  5. ↑ Kai, Heidi S-T; 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. United States. 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.
  • 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.
  • 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.
  • 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


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