Metalloproteinase inhibitor 2

NameMetalloproteinase inhibitor 2
Synonyms
  • CSC-21K
  • TIMP-2
  • Tissue inhibitor of metalloproteinases 2
Gene NameTIMP2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019753|Metalloproteinase inhibitor 2
MGAAARTLRLALGLLLLATLLRPADACSCSPVHPQQAFCNADVVIRAKAVSEKEVDSGND
IYGNPIKRIQYEIKQIKMFKGPEKDIEFIYTAPSSAVCGVSLDVGGKKEYLIAGKAEGDG
KMHITLCDFIVPWDTLSTTQKKSLNHRYQMGCECKITRCPMIPCYISSPDECLWMDWVTE
KNINGHQAKFFACIKRSDGSCAWYRGAAPPKQEFLDIEDP
Number of residues220
Molecular Weight24398.995
Theoretical pINot Available
GO Classification
Functions
  • protease binding
  • enzyme activator activity
  • metal ion binding
  • metalloendopeptidase inhibitor activity
Processes
  • aging
  • response to drug
  • response to cytokine
  • response to hormone
  • positive regulation of MAPK cascade
  • cellular response to organic substance
  • central nervous system development
  • negative regulation of Ras protein signal transduction
  • negative regulation of membrane protein ectodomain proteolysis
  • extracellular matrix disassembly
  • negative regulation of mitotic cell cycle
  • extracellular matrix organization
  • regulation of Rap protein signal transduction
  • negative regulation of cell proliferation
  • negative regulation of metalloenzyme activity
  • positive regulation of adenylate cyclase activity
  • positive regulation of neuron differentiation
Components
  • extracellular region
  • extracellular space
  • proteinaceous extracellular matrix
  • cell surface
  • basement membrane
  • extracellular exosome
  • growth cone
  • neuronal cell body
General FunctionProtease binding
Specific FunctionComplexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP16035
UniProtKB Entry NameTIMP2_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0019754|Metalloproteinase inhibitor 2 (TIMP2)
ATGGGCGCCGCGGCCCGCACCCTGCGGCTGGCGCTCGGCCTCCTGCTGCTGGCGACGCTG
CTTCGCCCGGCCGACGCCTGCAGCTGCTCCCCGGTGCACCCGCAACAGGCGTTTTGCAAT
GCAGATGTAGTGATCAGGGCCAAAGCGGTCAGTGAGAAGGAAGTGGACTCTGGAAACGAC
ATTTATGGCAACCCTATCAAGAGGATCCAGTATGAGATCAAGCAGATAAAGATGTTCAAA
GGGCCTGAGAAGGATATAGAGTTTATCTACACGGCCCCCTCCTCGGCAGTGTGTGGGGTC
TCGCTGGACGTTGGAGGAAAGAAGGAATATCTCATTGCAGGAAAGGCCGAGGGGGACGGC
AAGATGCACATCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCTGAGCACCACCCAG
AAGAAGAGCCTGAACCACAGGTACCAGATGGGCTGCGAGTGCAAGATCACGCGCTGCCCC
ATGATCCCGTGCTACATCTCCTCCCCGGACGAGTGCCTCTGGATGGACTGGGTCACAGAG
AAGAACATCAACGGGCACCAGGCCAAGTTCTTCGCCTGCATCAAGAGAAGTGACGGCTCC
TGTGCGTGGTACCGCGGCGCGGCGCCCCCCAAGCAGGAGTTTCTCGACATCGAGGACCCA
TAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:11821
Chromosome Location17
LocusNot Available
References
  1. Stetler-Stevenson WG, Brown PD, Onisto M, Levy AT, Liotta LA: Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J Biol Chem. 1990 Aug 15;265(23):13933-8. 2380196
  2. Boone TC, Johnson MJ, De Clerck YA, Langley KE: cDNA cloning and expression of a metalloproteinase inhibitor related to tissue inhibitor of metalloproteinases. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2800-4. 2157214
  3. Hammani K, Blakis A, Morsette D, Bowcock AM, Schmutte C, Henriet P, DeClerck YA: Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene. J Biol Chem. 1996 Oct 11;271(41):25498-505. 8810321
  4. 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. 15489334
  5. Stetler-Stevenson WG, Krutzsch HC, Liotta LA: Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family. J Biol Chem. 1989 Oct 15;264(29):17374-8. 2793861
  6. Stetler-Stevenson WG, Krutzsch HC, Liotta LA: TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family. Matrix Suppl. 1992;1:299-306. 1480041
  7. Goldberg GI, Marmer BL, Grant GA, Eisen AZ, Wilhelm S, He CS: Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8207-11. 2554304
  8. Osthues A, Knauper V, Oberhoff R, Reinke H, Tschesche H: Isolation and characterization of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) from human rheumatoid synovial fluid. FEBS Lett. 1992 Jan 13;296(1):16-20. 1730286
  9. De Clerck YA, Darville MI, Eeckhout Y, Rousseau GG: Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2). Gene. 1994 Feb 25;139(2):185-91. 8112602
  10. Howard EW, Banda MJ: Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites on human 72-kDa gelatinase. Identification of a stabilization site. J Biol Chem. 1991 Sep 25;266(27):17972-7. 1655733
  11. Chattopadhyay N, Mitra A, Frei E, Chatterjee A: Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol. 2001 Nov;127(11):653-8. 11710594
  12. Williamson RA, Martorell G, Carr MD, Murphy G, Docherty AJ, Freedman RB, Feeney J: Solution structure of the active domain of tissue inhibitor of metalloproteinases-2. A new member of the OB fold protein family. Biochemistry. 1994 Oct 4;33(39):11745-59. 7918391
  13. Muskett FW, Frenkiel TA, Feeney J, Freedman RB, Carr MD, Williamson RA: High resolution structure of the N-terminal domain of tissue inhibitor of metalloproteinases-2 and characterization of its interaction site with matrix metalloproteinase-3. J Biol Chem. 1998 Aug 21;273(34):21736-43. 9705310
  14. Tuuttila A, Morgunova E, Bergmann U, Lindqvist Y, Maskos K, Fernandez-Catalan C, Bode W, Tryggvason K, Schneider G: Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution. J Mol Biol. 1998 Dec 11;284(4):1133-40. 9837731
  15. Morgunova E, Tuuttila A, Bergmann U, Tryggvason K: Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7414-9. 12032297