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Gene Review

ARG2  -  arginase 2

Homo sapiens

Synonyms: Arginase-2, mitochondrial, Kidney-type arginase, Non-hepatic arginase, Type II arginase
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Disease relevance of ARG2


Psychiatry related information on ARG2


High impact information on ARG2

  • Furthermore, immunohistochemistry for DDIT3 and ARG2 showed consistent staining for carcinoma in an independent set 59 follicular tumors (estimated concordance, 0.76; 95% confidence interval, [0.59, 0.93]) [8].
  • The C5 sequence allowed to derive a nested set of six additional peptides with 8-11 residues containing the core octamer sequence and the Arg2 motif of HLA-B27, none of which was found in the B27-bound pool [9].
  • We now show that His183 and Asp281, both located in the extracellular domain of the AT1 receptor, are involved in binding the NH2-terminal Asp1 and Arg2 residues of angiotensin II, respectively [10].
  • The Arg2 analog was nearly as potent as PTH(3-34) as an in vitro PTH antagonist in osteoblast derived cells [11].
  • We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif) [12].

Biological context of ARG2


Anatomical context of ARG2


Associations of ARG2 with chemical compounds

  • Since NO synthase is found in human clitoral corpus cavernosum and vagina, we hypothesized that human arginase II is similarly present in these tissues and functions to regulate l-arginine bioavailability to NO synthase [6].
  • The X-ray crystal structure of a fully active, truncated form of human arginase II complexed with a boronic acid transition state analogue inhibitor has been determined at 2.7 A resolution [6].
  • We found that the cationic amino acid transporter (CAT)2, arginase I, and arginase II were particularly prominent among the allergen-induced gene transcripts [18].
  • Unlike the other urea cycle enzymes, a second gene encoding arginase, with similar structural properties and enzyme characteristics, exists and has been named Arginase II (AII) [19].
  • Induction of arginase II in human Caco-2 tumor cells by cyclic AMP [20].

Regulatory relationships of ARG2


Other interactions of ARG2

  • Regulation of arginase II by interferon regulatory factor 3 and the involvement of polyamines in the antiviral response [21].
  • Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and mitochondrial arginase II [15].
  • Arginase II protein was detected in cells exposed to IL-10 [24].
  • Further characterization of these pathways with real-time polymerase chain reaction and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels [25].
  • For three reactions catalyzed by the enzymes AMP deaminase (EC code, triose phosphate isomerase (EC code, and arginase II (EC code, we show how a 3D model of these intermediates can be superimposed onto known inhibitors of these enzymes by a program that uses a genetic algorithm [26].

Analytical, diagnostic and therapeutic context of ARG2


  1. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. Xu, W., Kaneko, F.T., Zheng, S., Comhair, S.A., Janocha, A.J., Goggans, T., Thunnissen, F.B., Farver, C., Hazen, S.L., Jennings, C., Dweik, R.A., Arroliga, A.C., Erzurum, S.C. FASEB J. (2004) [Pubmed]
  2. Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO. Rouzaut, A., Subirá, M.L., de Miguel, C., Domingo-de-Miguel, E., González, A., Santiago, E., López-Moratalla, N. Biochim. Biophys. Acta (1999) [Pubmed]
  3. The structural gene encoding human enterotoxigenic Escherichia coli PCFO20 is homologous to that for porcine 987P. Viboud, G.I., Jonson, G., Dean-Nystrom, E., Svennerholm, A.M. Infect. Immun. (1996) [Pubmed]
  4. Synthesis and immunological effect of thymic humoral factor-gamma-2 analogues. Abiko, T., Ogawa, R. Prep. Biochem. Biotechnol. (2002) [Pubmed]
  5. L-arginine depletion in preeclampsia orients nitric oxide synthase toward oxidant species. Noris, M., Todeschini, M., Cassis, P., Pasta, F., Cappellini, A., Bonazzola, S., Macconi, D., Maucci, R., Porrati, F., Benigni, A., Picciolo, C., Remuzzi, G. Hypertension (2004) [Pubmed]
  6. Human arginase II: crystal structure and physiological role in male and female sexual arousal. Cama, E., Colleluori, D.M., Emig, F.A., Shin, H., Kim, S.W., Kim, N.N., Traish, A.M., Ash, D.E., Christianson, D.W. Biochemistry (2003) [Pubmed]
  7. Increased expression of arginase II in human diabetic corpus cavernosum: in diabetic-associated erectile dysfunction. Bivalacqua, T.J., Hellstrom, W.J., Kadowitz, P.J., Champion, H.C. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  8. A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. Cerutti, J.M., Delcelo, R., Amadei, M.J., Nakabashi, C., Maciel, R.M., Peterson, B., Shoemaker, J., Riggins, G.J. J. Clin. Invest. (2004) [Pubmed]
  9. Limited diversity of peptides related to an alloreactive T cell epitope in the HLA-B27-bound peptide repertoire results from restrictions at multiple steps along the processing-loading pathway. Paradela, A., Alvarez, I., García-Peydró, M., Sesma, L., Ramos, M., Vázquez, J., López De Castro, J.A. J. Immunol. (2000) [Pubmed]
  10. The docking of Arg2 of angiotensin II with Asp281 of AT1 receptor is essential for full agonism. Feng, Y.H., Noda, K., Saad, Y., Liu, X.P., Husain, A., Karnik, S.S. J. Biol. Chem. (1995) [Pubmed]
  11. Mutational analysis of the receptor-activating region of human parathyroid hormone. Gardella, T.J., Axelrod, D., Rubin, D., Keutmann, H.T., Potts, J.T., Kronenberg, H.M., Nussbaum, S.R. J. Biol. Chem. (1991) [Pubmed]
  12. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. Li, H., Romieu, I., Sienra-Monge, J.J., Ramirez-Aguilar, M., Estela Del Rio-Navarro, B., Kistner, E.O., Gjessing, H.K., Lara-Sanchez, I.d.e.l. .C., Chiu, G.Y., London, S.J. J. Allergy Clin. Immunol. (2006) [Pubmed]
  13. Identification of arginase in human placental villi. Ishikawa, T., Harada, T., Koi, H., Kubota, T., Azuma, H., Aso, T. Placenta (2007) [Pubmed]
  14. Further characterization of auxin-regulated mRNAs in hypocotyl sections of mung bean [Vigna radiata (L.) Wilczek]: sequence homology to genes for fatty-acid desaturases and atypical late-embryogenesis-abundant protein, and the mode of expression of the mRNAs. Yamamoto, K.T. Planta (1994) [Pubmed]
  15. Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells. Topal, J.L., Brunet, A., Walch, L., Boucher, J.L., David-Dufilho, M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  16. Chromosomal localization of the human arginase II gene and tissue distribution of its mRNA. Gotoh, T., Araki, M., Mori, M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  17. Production of nitric oxide and self-nitration of proteins during monocyte differentiation to dendritic cells. Fernández-Ruiz, V., López-Moratalla, N., González, A. Journal of physiology and biochemistry. (2005) [Pubmed]
  18. Arginine in asthma and lung inflammation. King, N.E., Rothenberg, M.E., Zimmermann, N. J. Nutr. (2004) [Pubmed]
  19. Hyperargininemia due to liver arginase deficiency. Crombez, E.A., Cederbaum, S.D. Mol. Genet. Metab. (2005) [Pubmed]
  20. Induction of arginase II in human Caco-2 tumor cells by cyclic AMP. Wei, L.H., Morris, S.M., Cederbaum, S.D., Mori, M., Ignarro, L.J. Arch. Biochem. Biophys. (2000) [Pubmed]
  21. Regulation of arginase II by interferon regulatory factor 3 and the involvement of polyamines in the antiviral response. Grandvaux, N., Gaboriau, F., Harris, J., tenOever, B.R., Lin, R., Hiscott, J. FEBS J. (2005) [Pubmed]
  22. Involvement of arginase in regulating myometrial contractions during gestation in the rat. Hirata, M., Obayashi, S., Sakamoto, S., Aso, T., Imamura, M., Azuma, H. Mol. Hum. Reprod. (2006) [Pubmed]
  23. Increased expression of arginase II in patients with different forms of arthritis. Implications of the regulation of nitric oxide. Corraliza, I., Moncada, S. J. Rheumatol. (2002) [Pubmed]
  24. Regulation of arginase expression by T-helper II cytokines and isoproterenol. Barksdale, A.R., Bernard, A.C., Maley, M.E., Gellin, G.L., Kearney, P.A., Boulanger, B.R., Tsuei, B.J., Ochoa, J.B. Surgery (2004) [Pubmed]
  25. Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease. Raghavachari, N., Xu, X., Harris, A., Villagra, J., Logun, C., Barb, J., Solomon, M.A., Suffredini, A.F., Danner, R.L., Kato, G., Munson, P.J., Morris, S.M., Gladwin, M.T. Circulation (2007) [Pubmed]
  26. Query generation to search for inhibitors of enzymatic reactions. Reitz, M., Homeyer, A., Gasteiger, J. Journal of chemical information and modeling (2006) [Pubmed]
  27. Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signaling. Ryoo, S., Lemmon, C.A., Soucy, K.G., Gupta, G., White, A.R., Nyhan, D., Shoukas, A., Romer, L.H., Berkowitz, D.E. Circ. Res. (2006) [Pubmed]
  28. Insights into the interaction of human arginase II with substrate and manganese ions by site-directed mutagenesis and kinetic studies. Alteration of substrate specificity by replacement of Asn149 with Asp. López, V., Alarcón, R., Orellana, M.S., Enríquez, P., Uribe, E., Martínez, J., Carvajal, N. FEBS J. (2005) [Pubmed]
  29. The binding of Arg- and Lys-peptides to single stranded polyribonucleotides and its effect on the polymer conformation. Porschke, D. Biophys. Chem. (1979) [Pubmed]
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