Metalloproteinase inhibitor 3

Details

Name
Metalloproteinase inhibitor 3
Synonyms
  • Protein MIG-5
  • TIMP-3
  • Tissue inhibitor of metalloproteinases 3
Gene Name
TIMP3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020674|Metalloproteinase inhibitor 3
MTPWLGLIVLLGSWSLGDWGAEACTCSPSHPQDAFCNSDIVIRAKVVGKKLVKEGPFGTL
VYTIKQMKMYRGFTKMPHVQYIHTEASESLCGLKLEVNKYQYLLTGRVYDGKMYTGLCNF
VERWDQLTLSQRKGLNYRYHLGCNCKIKSCYYLPCFVTSKNECLWTDMLSNFGYPGYQSK
HYACIRQKGGYCSWYRGWAPPDKSIINATDP
Number of residues
211
Molecular Weight
24144.83
Theoretical pI
8.86
GO Classification
Functions
metal ion binding / metalloendopeptidase inhibitor activity / protease binding
Processes
aging / cellular response to organic substance / central nervous system development / negative regulation of endopeptidase activity / negative regulation of membrane protein ectodomain proteolysis / negative regulation of metalloenzyme activity / response to cytokine / response to estrogen / response to folic acid / response to hormone / response to mechanical stimulus / tissue regeneration / visual perception
Components
basement membrane / cytoplasm / extracellular exosome / extracellular space / nucleus / proteinaceous extracellular matrix
General Function
Protease binding
Specific Function
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0020675|Metalloproteinase inhibitor 3 (TIMP3)
ATGACCCCTTGGCTCGGGCTCATCGTGCTCCTGGGCAGCTGGAGCCTGGGGGACTGGGGC
GCCGAGGCGTGCACATGCTCGCCCAGCCACCCCCAGGACGCCTTCTGCAACTCCGACATC
GTGATCCGGGCCAAGGTGGTGGGGAAGAAGCTGGTAAAGGAGGGGCCCTTCGGCACGCTG
GTCTACACCATCAAGCAGATGAAGATGTACCGAGGCTTCACCAAGATGCCCCATGTGCAG
TACATCCATACGGAAGCTTCCGAGAGTCTCTGTGGCCTTAAGCTGGAGGTCAACAAGTAC
CAGTACCTGCTGACAGGTCGCGTCTATGATGGCAAGATGTACACGGGGCTGTGCAACTTC
GTGGAGAGGTGGGACCAGCTCACCCTCTCCCAGCGCAAGGGGCTGAACTATCGGTATCAC
CTGGGTTGTAACTGCAAGATCAAGTCCTGCTACTACCTGCCTTGCTTTGTGACTTCCAAG
AACGAGTGTCTCTGGACCGACATGCTCTCCAATTTCGGTTACCCTGGCTACCAGTCCAAA
CACTACGCCTGCATCCGGCAGAAGGGCGGCTACTGCAGCTGGTACCGAGGATGGGCCCCC
CCGGATAAAAGCATCATCAATGCCACAGACCCCTGA
Chromosome Location
22
Locus
22q12.1-q13.2|22q12.3
External Identifiers
ResourceLink
UniProtKB IDP35625
UniProtKB Entry NameTIMP3_HUMAN
GenBank Gene IDX76227
GenAtlas IDTIMP3
HGNC IDHGNC:11822
General References
  1. Uria JA, Ferrando AA, Velasco G, Freije JM, Lopez-Otin C: Structure and expression in breast tumors of human TIMP-3, a new member of the metalloproteinase inhibitor family. Cancer Res. 1994 Apr 15;54(8):2091-4. [PubMed:8174111]
  2. Wilde CG, Hawkins PR, Coleman RT, Levine WB, Delegeane AM, Okamoto PM, Ito LY, Scott RW, Seilhamer JJ: Cloning and characterization of human tissue inhibitor of metalloproteinases-3. DNA Cell Biol. 1994 Jul;13(7):711-8. [PubMed:7772252]
  3. Silbiger SM, Jacobsen VL, Cupples RL, Koski RA: Cloning of cDNAs encoding human TIMP-3, a novel member of the tissue inhibitor of metalloproteinase family. Gene. 1994 Apr 20;141(2):293-7. [PubMed:8163205]
  4. Wick M, Burger C, Brusselbach S, Lucibello FC, Muller R: A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence. J Biol Chem. 1994 Jul 22;269(29):18953-60. [PubMed:8034652]
  5. Stohr H, Roomp K, Felbor U, Weber BH: Genomic organization of the human tissue inhibitor of metalloproteinases-3 (TIMP3) Genome Res. 1995 Dec;5(5):483-7. [PubMed:8808469]
  6. Ruiz A, Brett P, Bok D: TIMP-3 is expressed in the human retinal pigment epithelium. Biochem Biophys Res Commun. 1996 Sep 13;226(2):467-74. [PubMed:8806658]
  7. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. [PubMed:15461802]
  8. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  9. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed:10591208]
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  11. Apte SS, Mattei MG, Olsen BR: Cloning of the cDNA encoding human tissue inhibitor of metalloproteinases-3 (TIMP-3) and mapping of the TIMP3 gene to chromosome 22. Genomics. 1994 Jan 1;19(1):86-90. [PubMed:8188246]
  12. Kishnani NS, Staskus PW, Yang TT, Masiarz FR, Hawkes SP: Identification and characterization of human tissue inhibitor of metalloproteinase-3 and detection of three additional metalloproteinase inhibitor activities in extracellular matrix. Matrix Biol. 1995 Feb;14(6):479-88. [PubMed:7795886]
  13. Hammani K, Henriet P, Silbiger SM, DeClerck YA: Cloning and partial structure of the gene encoding human tissue inhibitor of metalloproteinases-3. Gene. 1996 May 8;170(2):287-8. [PubMed:8666262]
  14. Klenotic PA, Munier FL, Marmorstein LY, Anand-Apte B: Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations. J Biol Chem. 2004 Jul 16;279(29):30469-73. Epub 2004 Apr 28. [PubMed:15123717]
  15. Wisniewska M, Goettig P, Maskos K, Belouski E, Winters D, Hecht R, Black R, Bode W: Structural determinants of the ADAM inhibition by TIMP-3: crystal structure of the TACE-N-TIMP-3 complex. J Mol Biol. 2008 Sep 19;381(5):1307-19. doi: 10.1016/j.jmb.2008.06.088. Epub 2008 Jul 7. [PubMed:18638486]
  16. Weber BH, Vogt G, Pruett RC, Stohr H, Felbor U: Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat Genet. 1994 Dec;8(4):352-6. [PubMed:7894485]
  17. Felbor U, Stohr H, Amann T, Schonherr U, Weber BH: A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy with unusual clinical features. Hum Mol Genet. 1995 Dec;4(12):2415-6. [PubMed:8634721]
  18. Jacobson SG, Cideciyan AV, Regunath G, Rodriguez FJ, Vandenburgh K, Sheffield VC, Stone EM: Night blindness in Sorsby's fundus dystrophy reversed by vitamin A. Nat Genet. 1995 Sep;11(1):27-32. [PubMed:7550309]
  19. Felbor U, Stohr H, Amann T, Schonherr U, Apfelstedt-Sylla E, Weber BH: A second independent Tyr168Cys mutation in the tissue inhibitor of metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy. J Med Genet. 1996 Mar;33(3):233-6. [PubMed:8728699]
  20. Felbor U, Suvanto EA, Forsius HR, Eriksson AW, Weber BH: Autosomal recessive Sorsby fundus dystrophy revisited: molecular evidence for dominant inheritance. Am J Hum Genet. 1997 Jan;60(1):57-62. [PubMed:8981947]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05383PimagedineinvestigationalunknownDetails