Disease relevance of ARG2

• Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension [1].
• Human monocyte subsets, isolated from cultures of mononuclear cells, or freshly obtained from patients with multiple sclerosis, Graves' disease or pemphigus vulgaris, differed in phenotype, apoptotic features, mRNA levels of arginase II (A-II) and the inducible form of nitric oxide synthase (iNOS) [2].
• The gene encoding the structural subunit of PCFO20 fimbriae, fotA, was cloned from strain ARG-2 in the expression phage vector lambda ZAP Express [3].
• Three other peptides, [beta-Ala4]-, [Arg2]-, and [Gln2]-THF-gamma-2, did not show any restoring activity on the impaired blastogenic response of uremic patients with infectious disease [4].
• In preeclampsia, a lower than normal l-arginine concentration caused by arginase II overexpression redirects ecNOS toward peroxynitrite [5].

Psychiatry related information on ARG2

• Therefore, arginase II is a potential target for the treatment of male and female sexual arousal disorders [6].
• Increased expression of arginase II in human diabetic corpus cavernosum: in diabetic-associated erectile dysfunction [7].

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

• Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2) [12].
• RT-PCR and Western blot analysis showed expression of A-I and A-II in the first trimester and at term in human placental villi [13].
• Immunohistochemistry showed different distribution patterns of the arginase isoforms during gestation: A-I was observed only in cytotrophoblasts, while A-II was observed in both cytotrophoblasts and syncytiotrophoblasts [13].
• The amino-acid sequence encoded by another auxin-regulated gene, ARG2, is 39% identical to that of an atypical late-embryogenesis-abundant (LEA) protein of cotton, LEA5-A [14].
• Determination of the distribution and kinetics of induction of mRNAs transcribed from the five auxin-regulated genes of mung bean, which include Aux22s and SAUR as well as ARG1 and ARG2, shows that they are heterogeneous in their mode of gene expression [14].

Anatomical context of ARG2

• Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells [15].
• These data suggest that endothelial NO synthesis depends on the activity of arginase II in mitochondria and l-arginine carriers in cell membrane [15].
• 3. Dot-blot analysis showed that arginase II mRNA is expressed strongly in the adult human kidney and weakly in the prostate, pituitary gland, lung, liver, thyroid gland, and small intestine [16].
• Fluorescence in situ hybridization mapping and PCR mapping studies with somatic cell hybrid panels and a radiation hybrid panel localized the arginase II gene to chromosome 14q24.1-24 [16].
• The expression of arginase II, but not arginase I, isoform was detected in monocytes and dendritic cells [17].

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

• In this study, we report that the arginase II gene (ArgII) as well as ArgII protein concentrations and enzymatic activity are induced in IRF-3 5D-expressing and Sendai virus-infected Jurkat cells in an IFN-independent manner [21].
• Whereas, the enhanced overall arginase activity at term gestation seems to be because of the induced functional arginase I in concert with the attenuated arginase II expression [22].
• CONCLUSION: Arginase II expression is upregulated in RA and may increase cell proliferation by providing L-ornithine, which is the substrate of polyamine biosynthesis [23].

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 3.5.4.6), triose phosphate isomerase (EC code 5.3.1.1), and arginase II (EC code 3.5.3.1), 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

• One ARG2 SNP was related to the number of positive skin tests (P = .027) [12].
• Immunofluorescence analysis revealed an association of arginase II with the microtubule cytoskeleton [27].
• 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 [28].
• The interactions between basic oligopeptides (Lys2, Lys3, Arg2 and Arg3) and single stranded polynucleotides (poly(A), poly(C), poly(I) and poly(U) were investigated at low ion concentration by UV spectroscopy, circular dichroism and field jump relaxation [29].

References