The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

DDAH2  -  dimethylarginine dimethylaminohydrolase 2

Homo sapiens

Synonyms: DDAH, DDAH-2, DDAHII, Dimethylargininase-2, Dimethylarginine dimethylaminohydrolase 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DDAH2


Psychiatry related information on DDAH2

  • The discovery of a functional polymorphism within the DDAH2 promoter suggests that there may be common, individual differences in the ability to metabolise ADMA in vivo, that in turn, might underlie susceptibility to cardiovascular disease [6].
  • Motor neuron generation depends on two critical periods of SHH signaling: an early period during which naive neural plate cells are converted into ventralized progenitors and a late period that extends well into S phase of the final progenitor cell division, during which SHH drives the differentiation of ventralized progenitors into motor neurons [7].
  • At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle [8].
  • These data suggest that, when planning and interpreting quantitative data and perturbation experiments, consideration must be given to the role of serine-threonine kinases and transcription factors during decision making in M phase as well as in G1-S phase [9].

High impact information on DDAH2


Chemical compound and disease context of DDAH2


Biological context of DDAH2


Anatomical context of DDAH2


Associations of DDAH2 with chemical compounds


Physical interactions of DDAH2


Enzymatic interactions of DDAH2

  • It has been shown previously that RPA32 is phosphorylated both during the S-phase of a normal cell cycle and in response to DNA damage [33].
  • Cdc25 A regulates entry into S-phase by dephosphorylating Cdk2, it cooperates with activated oncogenes in inducing transformation and is overexpressed in several human tumors [34].
  • Considering recent in vitro studies, these data are consistent with a proposed model in which Cdc6 is serine-54 phosphorylated during S phase and functions as a chromatin-bound signal that prevents reformation of prereplication complexes [35].
  • This is the first demonstration that Skp2 is induced and phosphorylated in the late G1 and S phase of hepatocytes in vivo in regenerating liver as well as in vitro in mitogen-stimulated hepatocytes [36].
  • These results, together with the functions of Cdc7p in yeast, suggest that HsCdc7 may phosphorylate critical substrate(s) that regulate the G1/S phase transition and/or DNA replication in mammalian cells [37].

Co-localisations of DDAH2


Regulatory relationships of DDAH2


Other interactions of DDAH2

  • Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins [22].
  • Knocking down the DDAH2 gene reduced VEGF production, and DDAH2 overexpression enhanced both proliferation and migration of endothelial cells [21].
  • Decreased DDAH activity and DDAH-2 protein expression may cause accumulation of endogenous inhibitors of endothelial NOS, thereby contributing to endothelial dysfunction in the failing heart [23].
  • The G6 gene encodes a regulatory nuclear chloride ion channel protein, while the G6A gene encodes a putative homologue of the enzyme N omega,N omega-dimethylarginine dimethylaminohydrolase, which is thought to be involved in regulating nitric oxide synthesis [44].
  • Experiments with phospho-amino acid-specific antibodies indicate that the S phase-specific mobility shift is due to the phosphorylation at specific N-terminal (S/T)(S/T)P residues of the MCM4 protein [45].

Analytical, diagnostic and therapeutic context of DDAH2


  1. Haplotypic association of DDAH1 with susceptibility to pre-eclampsia. Akbar, F., Heinonen, S., Pirskanen, M., Uimari, P., Tuomainen, T.P., Salonen, J.T. Mol. Hum. Reprod. (2005) [Pubmed]
  2. Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension. Pullamsetti, S., Kiss, L., Ghofrani, H.A., Voswinckel, R., Haredza, P., Klepetko, W., Aigner, C., Fink, L., Muyal, J.P., Weissmann, N., Grimminger, F., Seeger, W., Schermuly, R.T. FASEB J. (2005) [Pubmed]
  3. beta-Catenin Overexpression Reduces Myocardial Infarct Size through Differential Effects on Cardiomyocytes and Cardiac Fibroblasts. Hahn, J.Y., Cho, H.J., Bae, J.W., Yuk, H.S., Kim, K.I., Park, K.W., Koo, B.K., Chae, I.H., Shin, C.S., Oh, B.H., Choi, Y.S., Park, Y.B., Kim, H.S. J. Biol. Chem. (2006) [Pubmed]
  4. Molecular mechanism for elevation of asymmetric dimethylarginine and its role for hypertension in chronic kidney disease. Matsuguma, K., Ueda, S., Yamagishi, S., Matsumoto, Y., Kaneyuki, U., Shibata, R., Fujimura, T., Matsuoka, H., Kimoto, M., Kato, S., Imaizumi, T., Okuda, S. J. Am. Soc. Nephrol. (2006) [Pubmed]
  5. Characterization of a transient covalent adduct formed during dimethylarginine dimethylaminohydrolase catalysis. Stone, E.M., Person, M.D., Costello, N.J., Fast, W. Biochemistry (2005) [Pubmed]
  6. Common genetic variation in a basal promoter element alters DDAH2 expression in endothelial cells. Jones, L.C., Tran, C.T., Leiper, J.M., Hingorani, A.D., Vallance, P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  7. Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Ericson, J., Morton, S., Kawakami, A., Roelink, H., Jessell, T.M. Cell (1996) [Pubmed]
  8. Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. Dinges, D.F., Douglas, S.D., Zaugg, L., Campbell, D.E., McMann, J.M., Whitehouse, W.G., Orne, E.C., Kapoor, S.C., Icaza, E., Orne, M.T. J. Clin. Invest. (1994) [Pubmed]
  9. Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells. Liu, J., Puscheck, E.E., Wang, F., Trostinskaia, A., Barisic, D., Maniere, G., Wygle, D., Zhong, W., Rings, E.H., Rappolee, D.A. Reproduction (2004) [Pubmed]
  10. Immunopharmacology of rapamycin. Abraham, R.T., Wiederrecht, G.J. Annu. Rev. Immunol. (1996) [Pubmed]
  11. Re-Evaluating Cell-Cycle Regulation by E2Fs. Rowland, B.D., Bernards, R. Cell (2006) [Pubmed]
  12. Wapl controls the dynamic association of cohesin with chromatin. Kueng, S., Hegemann, B., Peters, B.H., Lipp, J.J., Schleiffer, A., Mechtler, K., Peters, J.M. Cell (2006) [Pubmed]
  13. A novel human p53 isoform is an essential element of the ATR-intra-S phase checkpoint. Rohaly, G., Chemnitz, J., Dehde, S., Nunez, A.M., Heukeshoven, J., Deppert, W., Dornreiter, I. Cell (2005) [Pubmed]
  14. CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Mailand, N., Diffley, J.F. Cell (2005) [Pubmed]
  15. Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase. Stone, E.M., Schaller, T.H., Bianchi, H., Person, M.D., Fast, W. Biochemistry (2005) [Pubmed]
  16. Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. Clark, G.M., Dressler, L.G., Owens, M.A., Pounds, G., Oldaker, T., McGuire, W.L. N. Engl. J. Med. (1989) [Pubmed]
  17. A novel chromosome abnormality in human neuroblastoma and antifolate-resistant Chinese hamster cell lives in culture. Biedler, J.L., Spengler, B.A. J. Natl. Cancer Inst. (1976) [Pubmed]
  18. Selective killing of oncogenic human cells cocultivated with normal human fibroblasts. Warrington, R.C. J. Natl. Cancer Inst. (1978) [Pubmed]
  19. Tyrosine aminotransferase sensitivity to bromodeoxyuridine during restricted intervals of S phase in hepatoma cells. O'Brien, J.C. J. Cell Biol. (1980) [Pubmed]
  20. Dimethylarginine dimethylaminohydrolase-2 overexpression improves impaired nitric oxide synthesis of endothelial cells induced by glycated protein. Lu, C.W., Xiong, Y., He, P. Nitric Oxide (2007) [Pubmed]
  21. Dimethylarginine dimethylaminohydrolase 2 increases vascular endothelial growth factor expression through Sp1 transcription factor in endothelial cells. Hasegawa, K., Wakino, S., Tanaka, T., Kimoto, M., Tatematsu, S., Kanda, T., Yoshioka, K., Homma, K., Sugano, N., Kurabayashi, M., Saruta, T., Hayashi, K. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  22. Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Tran, C.T., Fox, M.F., Vallance, P., Leiper, J.M. Genomics (2000) [Pubmed]
  23. Dimethylarginine dimethylaminohydrolase and endothelial dysfunction in failing hearts. Chen, Y., Li, Y., Zhang, P., Traverse, J.H., Hou, M., Xu, X., Kimoto, M., Bache, R.J. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  24. Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype. Smith, C.L., Birdsey, G.M., Anthony, S., Arrigoni, F.I., Leiper, J.M., Vallance, P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  25. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Leiper, J., Murray-Rust, J., McDonald, N., Vallance, P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  26. ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Böger, R.H., Zoccali, C. Atherosclerosis. Supplements. (2003) [Pubmed]
  27. Erythropoietin increases asymmetric dimethylarginine in endothelial cells: role of dimethylarginine dimethylaminohydrolase. Scalera, F., Kielstein, J.T., Martens-Lobenhoffer, J., Postel, S.C., Täger, M., Bode-Böger, S.M. J. Am. Soc. Nephrol. (2005) [Pubmed]
  28. S-phase arrest and apoptosis induced in normal mammary epithelial cells by a novel retinoid. Zhang, Y., Rishi, A.K., Dawson, M.I., Tschang, R., Farhana, L., Boyanapalli, M., Reichert, U., Shroot, B., Van Buren, E.C., Fontana, J.A. Cancer Res. (2000) [Pubmed]
  29. Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partners. Frouin, I., Maga, G., Denegri, M., Riva, F., Savio, M., Spadari, S., Prosperi, E., Scovassi, A.I. J. Biol. Chem. (2003) [Pubmed]
  30. Transforming growth factor beta activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site. Li, J.M., Nichols, M.A., Chandrasekharan, S., Xiong, Y., Wang, X.F. J. Biol. Chem. (1995) [Pubmed]
  31. pRb2/p130 and p107 control cell growth by multiple strategies and in association with different compartments within the nucleus. Zini, N., Trimarchi, C., Claudio, P.P., Stiegler, P., Marinelli, F., Maltarello, M.C., La Sala, D., De Falco, G., Russo, G., Ammirati, G., Maraldi, N.M., Giordano, A., Cinti, C. J. Cell. Physiol. (2001) [Pubmed]
  32. The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression. Gu, L., Ying, H., Zheng, H., Murray, S.A., Xiao, Z.X. FEBS Lett. (2003) [Pubmed]
  33. Hyperphosphorylation of replication protein A middle subunit (RPA32) in apoptosis. Treuner, K., Okuyama, A., Knippers, R., Fackelmayer, F.O. Nucleic Acids Res. (1999) [Pubmed]
  34. Dual mode of degradation of Cdc25 A phosphatase. Donzelli, M., Squatrito, M., Ganoth, D., Hershko, A., Pagano, M., Draetta, G.F. EMBO J. (2002) [Pubmed]
  35. Cdc6 chromatin affinity is unaffected by serine-54 phosphorylation, S-phase progression, and overexpression of cyclin A. Alexandrow, M.G., Hamlin, J.L. Mol. Cell. Biol. (2004) [Pubmed]
  36. Skp2 induction and phosphorylation is associated with the late G1 phase of proliferating rat hepatocytes. Bilodeau, M., Talarmin, H., Ilyin, G., Rescan, C., Glaise, D., Cariou, S., Loyer, P., Guguen-Guillouzo, C., Baffet, G. FEBS Lett. (1999) [Pubmed]
  37. Identification and characterization of a human protein kinase related to budding yeast Cdc7p. Jiang, W., Hunter, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  38. DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation. Nikiforov, A., Svetlova, M., Solovjeva, L., Sasina, L., Siino, J., Nazarov, I., Bradbury, M., Tomilin, N. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  39. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Leone, G., DeGregori, J., Yan, Z., Jakoi, L., Ishida, S., Williams, R.S., Nevins, J.R. Genes Dev. (1998) [Pubmed]
  40. The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase. Baeg, G.H., Matsumine, A., Kuroda, T., Bhattacharjee, R.N., Miyashiro, I., Toyoshima, K., Akiyama, T. EMBO J. (1995) [Pubmed]
  41. The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis. Brown, D.R., Thomas, C.A., Deb, S.P. EMBO J. (1998) [Pubmed]
  42. G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK complexes. Kudoh, T., Ishidate, T., Moriyama, M., Toyoshima, K., Akiyama, T. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  43. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. Lukas, J., Petersen, B.O., Holm, K., Bartek, J., Helin, K. Mol. Cell. Biol. (1996) [Pubmed]
  44. Genes encoding three new members of the leukocyte antigen 6 superfamily and a novel member of Ig superfamily, together with genes encoding the regulatory nuclear chloride ion channel protein (hRNCC) and an N omega-N omega-dimethylarginine dimethylaminohydrolase homologue, are found in a 30-kb segment of the MHC class III region. Ribas, G., Neville, M., Wixon, J.L., Cheng, J., Campbell, R.D. J. Immunol. (1999) [Pubmed]
  45. Phosphorylation of MCM4 by Cdc7 Kinase Facilitates Its Interaction with Cdc45 on the Chromatin. Masai, H., Taniyama, C., Ogino, K., Matsui, E., Kakusho, N., Matsumoto, S., Kim, J.M., Ishii, A., Tanaka, T., Kobayashi, T., Tamai, K., Ohtani, K., Arai, K. J. Biol. Chem. (2006) [Pubmed]
  46. Probucol decreases asymmetrical dimethylarginine level by alternation of protein arginine methyltransferase I and dimethylarginine dimethylaminohydrolase activity. Jiang, J.L., Zhang, X.H., Li, N.S., Rang, W.Q., Feng-Ye, n.u.l.l., Hu, C.P., Li, Y.J., Deng, H.W. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy (2006) [Pubmed]
  47. Dimethylarginine dimethylaminohydrolase overexpression suppresses graft coronary artery disease. Tanaka, M., Sydow, K., Gunawan, F., Jacobi, J., Tsao, P.S., Robbins, R.C., Cooke, J.P. Circulation (2005) [Pubmed]
  48. An enzyme hydrolyzing methylated inhibitors of nitric oxide synthase is present in circulating human red blood cells. Kang, E.S., Cates, T.B., Harper, D.N., Chiang, T.M., Myers, L.K., Acchiardo, S.R., Kimoto, M. Free Radic. Res. (2001) [Pubmed]
WikiGenes - Universities