Gene Symbol: TIMP2
Description: TIMP metallopeptidase inhibitor 2
Alias: metalloproteinase inhibitor 2, TIMP-2, collagenase inhibitor, tissue inhibitor of metalloproteinases 2, tissue inhibitor of mettaloproteinase 2
Species: cow
Products:     TIMP2

Top Publications

  1. De Clerck Y, Yean T, Ratzkin B, Lu H, Langley K. Purification and characterization of two related but distinct metalloproteinase inhibitors secreted by bovine aortic endothelial cells. J Biol Chem. 1989;264:17445-53 pubmed
    ..The presence of these inhibitors in endothelial cells suggests that they may play important roles in protecting the integrity of the vascular basement membrane. ..
  2. Murray J, Allison K, Sudhalter J, Langer R. Purification and partial amino acid sequence of a bovine cartilage-derived collagenase inhibitor. J Biol Chem. 1986;261:4154-9 pubmed
    ..bovine cartilage-derived inhibitor exhibits greater than 65% homology over the first 23 residues with a collagenase inhibitor purified from human skin fibroblasts maintained in cell culture...
  3. DeClerck Y, Yean T, Lee Y, Tomich J, Langley K. Characterization of the functional domain of tissue inhibitor of metalloproteinases-2 (TIMP-2). Biochem J. 1993;289 ( Pt 1):65-9 pubmed
    ..The fragment retains the ability to inhibit activated interstitial collagenase and to block the autocatalytic activation of procollagenase. ..
  4. Fernandez Catalan C, Bode W, Huber R, Turk D, Calvete J, Lichte A, et al. Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor. EMBO J. 1998;17:5238-48 pubmed
    ..The lower affinity of TIMP-1 for MT1-MMP compared with TIMP-2 might be explained by a reduced number of favourable interactions. ..
  5. Zhang B, Moses M, Tsang P. Temporal and spatial expression of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2) in the bovine corpus luteum. Reprod Biol Endocrinol. 2003;1:85 pubmed
    ..Furthermore, the distinct localization of these two inhibitors in the vascular compartment indicates that they may serve diverse physiological functions during different stages of luteal angiogenesis. ..
  6. Mandal M, Mandal A, Das S, Chakraborti T, Chakraborti S. Identification, purification and partial characterization of tissue inhibitor of matrix metalloproteinase-2 in bovine pulmonary artery smooth muscle. Mol Cell Biochem. 2003;254:275-87 pubmed
    ..Treatment of the inhibitor with hydrogen peroxide, superoxide generating system (hypoxanthine plus xanthine oxidase) and peroxynitrite inactivated the inhibitor. ..
  7. Ulbrich S, Meyer S, Zitta K, Hiendleder S, Sinowatz F, Bauersachs S, et al. Bovine endometrial metallopeptidases MMP14 and MMP2 and the metallopeptidase inhibitor TIMP2 participate in maternal preparation of pregnancy. Mol Cell Endocrinol. 2011;332:48-57 pubmed publisher
    ..In this study we observed distinct changes in expression of MMP2, MMP14, and the metallopeptidase inhibitor TIMP2 between different phases of the estrous cycle indicating an endocrine regulation...
  8. Mandal A, Chakraborti T, Choudhury R, Ghosh B, Ghosh A, Das S, et al. Role of MMP-2 in inhibiting Na+ dependent Ca2+ uptake by H2O2 in microsomes isolated from pulmonary smooth muscle. Mol Cell Biochem. 2005;270:79-87 pubmed
    ..Thus, one of the mechanisms by which H2O2 activates MMP-2 could be due to inactivation of TIMP-2 by the oxidant. The resulting activation of MMP-2 subsequently inhibits Na+ dependent Ca2+ uptake in the microsomes. ..
  9. Ledgard A, Lee R, Peterson A. Bovine endometrial legumain and TIMP-2 regulation in response to presence of a conceptus. Mol Reprod Dev. 2009;76:65-74 pubmed publisher
    ..These events at the conceptus-maternal interface may provide localised control of protease activity necessary for controlling trophoblast invasion of the endometrium. ..

More Information


  1. Moreira L, de Carvalho E, Caldas Bussiere M. Differential immunohistochemical expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in cow uteri with adenomyosis during follicular phase. Vet Res Commun. 2011;35:261-9 pubmed publisher
    ..In conclusion, a differential pattern of matrix metalloproteinase-2 and Tissue inhibitor metalloproteinase-2 was observed in cow uteri with adenomyosis. ..
  2. Dilly M, Hambruch N, Shenavai S, Schuler G, Froehlich R, Haeger J, et al. Expression of matrix metalloproteinase (MMP)-2, MMP-14 and tissue inhibitor of matrix metalloproteinase (TIMP)-2 during bovine placentation and at term with or without placental retention. Theriogenology. 2011;75:1104-14 pubmed publisher
    ..The presence of the activated enzyme was confirmed by zymography. In conclusion, MMP-14, MMP-2 and TIMP-2 are co-localized in the fetal compartment and therefore could influence the timely release of fetal membranes in cattle. ..
  3. Maskos K, Lang R, Tschesche H, Bode W. Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2. J Mol Biol. 2007;366:1222-31 pubmed
  4. Das S, Mandal M, Chakraborti T, Mandal A, Chakraborti S. Isolation of MMP-2 from MMP-2/TIMP-2 complex: characterization of the complex and the free enzyme in pulmonary vascular smooth muscle plasma membrane. Biochim Biophys Acta. 2004;1674:158-74 pubmed
    ..We have also presented additional data indicating that the isolated preparation of 72-kDa gelatinase exhibited properties that are identical with MMP-2 obtained from different sources. ..
  5. Balcerzak D, Querengesser L, Dixon W, Baracos V. Coordinate expression of matrix-degrading proteinases and their activators and inhibitors in bovine skeletal muscle. J Anim Sci. 2001;79:94-107 pubmed
  6. Saunders W, Bohnsack B, Faske J, Anthis N, Bayless K, Hirschi K, et al. Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J Cell Biol. 2006;175:179-91 pubmed
  7. Boone T, Johnson M, De Clerck Y, Langley K. cDNA cloning and expression of a metalloproteinase inhibitor related to tissue inhibitor of metalloproteinases. Proc Natl Acad Sci U S A. 1990;87:2800-4 pubmed
    ..The amino acid sequence of mature human MI is 38% identical to the sequence for human TIMP, and the 12 cysteines in MI and TIMP are aligned almost identically. Thus MI and TIMP comprise an inhibitor family. ..
  8. Hirata M, Sato T, Tsumagari M, Shimada A, Nakano H, Hashizume K, et al. Differential regulation of the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases by cytokines and growth factors in bovine endometrial stromal cells and trophoblast cell line BT-1 in vitro. Biol Reprod. 2003;68:1276-81 pubmed
    ..Furthermore, as in humans and rodents, MMPs and TIMPs may contribute to the control of degradation and reconstitution of extracellular matrix in bovine endometrium during embryonic implantation and early placentation. ..
  9. Takagi M, Yamamoto D, Ohtani M, Miyamoto A. Quantitative analysis of messenger RNA expression of matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor-2 of matrix metalloproteinases (TIMP-2), and steroidogenic enzymes in bovine placentomes during gestation and postpartum. Mol Reprod Dev. 2007;74:801-7 pubmed
  10. Roy S, Chakraborti T, Chowdhury A, Chakraborti S. Role of PKC-? in NF-?B-MT1-MMP-mediated activation of proMMP-2 by TNF-? in pulmonary artery smooth muscle cells. J Biochem. 2013;153:289-302 pubmed publisher