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NameMetalloproteinase inhibitor 1
Synonyms
  • CLGI
  • Collagenase inhibitor
  • EPA
  • Erythroid-potentiating activity
  • Fibroblast collagenase inhibitor
  • TIMP
  • TIMP-1
  • Tissue inhibitor of metalloproteinases 1
Gene NameTIMP1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019751|Metalloproteinase inhibitor 1
MAPFEPLASGILLLLWLIAPSRACTCVPPHPQTAFCNSDLVIRAKFVGTPEVNQTTLYQR
YEIKMTKMYKGFQALGDAADIRFVYTPAMESVCGYFHRSHNRSEEFLIAGKLQDGLLHIT
TCSFVAPWNSLSLAQRRGFTKTYTVGCEECTVFPCLSIPCKLQSGTHCLWTDQLLQGSEK
GFQSRHLACLPREPGLCTWQSLRSQIA
Number of residues207
Molecular Weight23170.64
Theoretical pINot Available
GO Classification
Functions
  • protease binding
  • cytokine activity
  • metal ion binding
  • metalloendopeptidase inhibitor activity
Processes
  • aging
  • response to cytokine
  • response to hormone
  • platelet activation
  • cartilage development
  • negative regulation of membrane protein ectodomain proteolysis
  • regulation of integrin-mediated signaling pathway
  • extracellular matrix disassembly
  • negative regulation of metalloenzyme activity
  • extracellular matrix organization
  • negative regulation of trophoblast cell migration
  • response to peptide hormone
  • negative regulation of apoptotic process
  • platelet degranulation
  • positive regulation of cell proliferation
  • blood coagulation
  • negative regulation of endopeptidase activity
Components
  • extracellular region
  • extracellular space
  • proteinaceous extracellular matrix
  • basement membrane
  • extracellular exosome
  • platelet alpha granule lumen
General FunctionProtease binding
Specific FunctionMetalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP01033
UniProtKB Entry NameTIMP1_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0019752|Metalloproteinase inhibitor 1 (TIMP1)
ATGGCCCCCTTTGAGCCCCTGGCTTCTGGCATCCTGTTGTTGCTGTGGCTGATAGCCCCC
AGCAGGGCCTGCACCTGTGTCCCACCCCACCCACAGACGGCCTTCTGCAATTCCGACCTC
GTCATCAGGGCCAAGTTCGTGGGGACACCAGAAGTCAACCAGACCACCTTATACCAGCGT
TATGAGATCAAGATGACCAAGATGTATAAAGGGTTCCAAGCCTTAGGGGATGCCGCTGAC
ATCCGGTTCGTCTACACCCCCGCCATGGAGAGTGTCTGCGGATACTTCCACAGGTCCCAC
AACCGCAGCGAGGAGTTTCTCATTGCTGGAAAACTGCAGGATGGACTCTTGCACATCACT
ACCTGCAGTTTTGTGGCTCCCTGGAACAGCCTGAGCTTAGCTCAGCGCCGGGGCTTCACC
AAGACCTACACTGTTGGCTGTGAGGAATGCACAGTGTTTCCCTGTTTATCCATCCCCTGC
AAACTGCAGAGTGGCACTCATTGCTTGTGGACGGACCAGCTCCTCCAAGGCTCTGAAAAG
GGCTTCCAGTCCCGTCACCTTGCCTGCCTGCCTCGGGAGCCAGGGCTGTGCACCTGGCAG
TCCCTGCGGTCCCAGATAGCCTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:11820
Chromosome LocationX
LocusNot Available
References
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  2. Gasson JC, Golde DW, Kaufman SE, Westbrook CA, Hewick RM, Kaufman RJ, Wong GG, Temple PA, Leary AC, Brown EL, et al.: Molecular characterization and expression of the gene encoding human erythroid-potentiating activity. Nature. 1985 Jun 27-Jul 3;315(6022):768-71. 3839290
  3. Carmichael DF, Sommer A, Thompson RC, Anderson DC, Smith CG, Welgus HG, Stricklin GP: Primary structure and cDNA cloning of human fibroblast collagenase inhibitor. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2407-11. 3010309
  4. Rapp G, Freudenstein J, Klaudiny J, Mucha J, Wempe F, Zimmer M, Scheit KH: Characterization of three abundant mRNAs from human ovarian granulosa cells. DNA Cell Biol. 1990 Sep;9(7):479-85. 2171551
  5. Opbroek A, Kenney MC, Brown D: Characterization of a human corneal metalloproteinase inhibitor (TIMP-1). Curr Eye Res. 1993 Oct;12(10):877-83. 7507419
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  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
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  10. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. 15340161
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  13. Chesler L, Golde DW, Bersch N, Johnson MD: Metalloproteinase inhibition and erythroid potentiation are independent activities of tissue inhibitor of metalloproteinases-1. Blood. 1995 Dec 15;86(12):4506-15. 8541540
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  22. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. 22905912
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  29. Arumugam S, Van Doren SR: Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual dipolar couplings. Biochemistry. 2003 Jul 8;42(26):7950-8. 12834347
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  32. Batra J, Robinson J, Soares AS, Fields AP, Radisky DC, Radisky ES: Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure. J Biol Chem. 2012 May 4;287(19):15935-46. doi: 10.1074/jbc.M112.341156. Epub 2012 Mar 16. 22427646