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Gene Review

ARIH2  -  ariadne RBR E3 ubiquitin protein ligase 2

Homo sapiens

Synonyms: ARI-2, ARI2, E3 ubiquitin-protein ligase ARIH2, HT005, Protein ariadne-2 homolog, ...
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Disease relevance of ARIH2


Psychiatry related information on ARIH2


High impact information on ARIH2

  • Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis [11].
  • Partial absence of the sacrum is a rare congenital defect which also occurs as an autosomal dominant trait; association with anterior meningocoele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad (MIM 176450) [12].
  • The structure defines a new class of serine protease with respect to global-fold topology and has a catalytic triad consisting of Ser-132, His-63, and His-157 in contrast with the Ser-His-Asp triads found in other serine proteases [5].
  • The simultaneous demonstration of low plasma glucose, high immunoreactive insulin and suppressed C-peptide immunoreactivity represents a triad of results pathognomonic of exogenous insulin administration [13].
  • Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates [14].

Chemical compound and disease context of ARIH2

  • This outcome was associated with previous heavy nitrite inhalant use, with the presence of night sweats, with leucopenia, and with the triad of constitutional symptoms, splenomegaly, and leucopenia [15].
  • Poliovirus thiol proteinase 3C can utilize a serine nucleophile within the putative catalytic triad [16].
  • L-Histidine, 90% 13C enriched at the C2 position, was incorporated into the catalytic triad of alpha-lytic protease (EC with the aid of histidine-requiring mutant of Lysobacter enzymogenes (ATC 29487), and the pH dependence of the coupling constant between this carbon atom and its directly bonded proton was reinvestigated [17].
  • The mutated glutamine is not only highly conserved in evolution (conserved also in Escherichia coli and Saccharomyces cerevisiae), but is also two amino acid residues downstream from the active site histidine-proline-histidine triad and results in about 10% of normal enzymatic activity [18].
  • Structural disturbance of this triad as a result from a number of point mutations found in patients with antenatal Bartter syndrome shifts the pK(a) of the lysine residue off the neutral pH range and results in channels permanently inactivated under physiological conditions [19].

Biological context of ARIH2


Anatomical context of ARIH2

  • Here we show, by using voltage-clamped single fibres and confocal imaging, that stochastic calcium-release events, visualized as Ca2+ sparks, occur in skeletal muscle and originate at the triad [25].
  • A cancer cell metalloprotease triad regulates the basement membrane transmigration program [26].
  • Herein, a triad of membrane-anchored proteases, termed membrane type-1, type-2, and type-3 metalloproteinases, are identified as the triggering agents that independently confer cancer cells with the ability to proteolytically efface the BM scaffolding, initiate the assembly of invasive pseudopodia, and propagate transmigration [26].
  • The data suggest that the triad of HLA identity, pancreatic islet cell antibodies, and depressed insulin secretion identifies those sibs who are at high risk of developing insulin-dependent diabetes mellitus [27].
  • Mycotic aneurysm of the external iliac artery. A triad of clinical signs facilitating early diagnosis [28].

Associations of ARIH2 with chemical compounds

  • Unlike the other lipases and serine proteases, the catalytic triad of GCL is Ser-His-Glu, with glutamic acid replacing the usual aspartate [29].
  • The 'catalytic triad' mechanism, which involves a serine, histidine and aspartic acid, has become synonymous with serine proteases [30].
  • The presence of the invariant Cys-His-Asp/Asn catalytic triad and the oxyanion-hole glutamine residue characteristic of papain-like cysteine proteases indicate that ECEPE proteins might function as proteases [31].
  • The consequent synaptic triad provides an ideal configuration for dopamine modulation of glutamatergic transmission [32].
  • In the last few years evidence has been accumulated to suggest that allergen-reactive type 2 T helper (Th2) cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in the allergic inflammation [33].

Physical interactions of ARIH2

  • An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition [34].
  • The structural core of FIH-1 consists of a jellyroll-like beta-barrel containing the conserved ferrous-binding triad residues, confirming that FIH-1 is a member of the 2-oxoglutarate-dependent dioxygenase family [35].
  • CONCLUSIONS: The helices present in 17 beta-HSD that were not in the two previous short-chain dehydrogenase structures are located at one end of the substrate-binding cleft away from the catalytic triad [36].
  • Tuberous sclerosis complex is an autosomal-dominant disorder characterized by the triad of mental retardation, epilepsy and adenoma sebaceum [37].
  • A new model for the agonistic binding site on the histamine H2-receptor: the catalytic triad in serine proteases as a model for the binding site of histamine H2-receptor agonists [38].

Regulatory relationships of ARIH2


Other interactions of ARIH2

  • The prostase cDNA encodes a putative 254-aa polypeptide with a conserved serine protease catalytic triad and an amino-terminal pre-propeptide sequence, indicating a potential secretory function [43].
  • Human lipoprotein lipase. Analysis of the catalytic triad by site-directed mutagenesis of Ser-132, Asp-156, and His-241 [44].
  • Functional and structural studies have shown that NAT1 catalytic activity is based on a cysteine protease-like catalytic triad, containing a reactive cysteine residue [45].
  • Enzymatic activities and kinetic analysis of the pure enzyme forms showed that wild type LCAT and both mutants were reactive with the water-soluble substrate, p-nitrophenyl butyrate, indicating the presence of an intact core active site and catalytic triad [46].
  • CAP37 does not possess serine protease activity probably due to mutations in two of three residues in the catalytic triad of the "charge relay system." Whereas CAP37 is expressed in undifferentiated HL-60 cells no message is detected in mature neutrophils [47].

Analytical, diagnostic and therapeutic context of ARIH2

  • Although most medical educators believe that education, research, and patient care are inseparable and essential to their academic mission, the educational component of this triad has never been given adequate, earmarked support [48].
  • By combining NAIM with site-directed mutagenesis, a new tertiary interaction, kappa-kappa', was identified between this region and the most catalytically important section of D5, adjacent to the AGC triad in stem 1 [49].
  • Our approach allows for joint analysis of data from both triad and case-control study designs [50].
  • The addition of MRI to the more commonly available triad of mammography, ultrasound, and breast examination identified two additional invasive breast cancers that would otherwise have been missed [51].
  • Mutation of His(320), a residue predicted from sequence analysis to belong to the catalytic triad of the enzyme, considerably slowed down the second half-reaction [52].


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  19. pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome. Schulte, U., Hahn, H., Konrad, M., Jeck, N., Derst, C., Wild, K., Weidemann, S., Ruppersberg, J.P., Fakler, B., Ludwig, J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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