Disease relevance of OCA2

• In the present study, we show that albinism in one Native American population, the Navajo, is caused by a LINE-mediated 122.5-kilobase deletion of the P gene, thus demonstrating that albinism in this population is OCA2 [1].
• Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci [2].
• Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma [3].
• The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer [3].
• The mouse pink-eyed dilution gene: association with hypopigmentation in Prader-Willi and Angelman syndromes and with human OCA2 [4].

Psychiatry related information on OCA2

• Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency [5].

High impact information on OCA2

• The pathogen-inducible nitric oxide synthase (iNOS) in plants is a variant of the P protein of the glycine decarboxylase complex [6].
• One of the two major autosomal recessive forms involves the tyrosinase gene (OCA1), while the other form (OCA2) has recently been associated with alterations of the P gene on chromosome 15 [7].
• The P protein is a transmembrane polypeptide that may transport small molecules such as tyrosine, the precursor of melanin [8].
• The human P gene corresponds to the D15S12 locus within the chromosome segment 15q11-q13, which is typically deleted in patients with Prader-Willi and Angelman syndrome (see ref. 5 for review) [9].
• Moreover, lentiviral-mediated delivery of PED antisense DNA resulted in dramatic down-regulation of the endogenous gene expression and sensitization of primitive neural cells to apoptosis mediated by inflammatory cytokines and DRs [10].

Chemical compound and disease context of OCA2

• BACKGROUND: Oculocutaneous albinism (OCA) is a genetically inherited autosomal recessive condition and OCA2, tyrosine-positive albinism, is the most prevalent type found throughout Africa. Due to the lack of melanin, people with albinism are more susceptible to the harmful effects of ultraviolet radiation exposure [11].
• Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia [12].
• Bacillus subtilis ribonuclease P protein (P protein) is predominantly unfolded (D) at physiological pH and low ionic strength; however, small molecule anionic ligands (e.g., sulfate) directly bind to and stabilize the folded state (NL2) [13].
• Role of NH(2)- and COOH-terminal domains of the P protein of human parainfluenza virus type 3 in transcription and replication [14].
• To determine which human respiratory syncytial virus (HRSV) P protein serine residues are modified by cellular protein kinase(s), several mutated versions of P protein were expressed in the absence of other viral proteins [15].

Biological context of OCA2

• We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations [16].
• This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color [17].
• Interactive effects of MC1R and OCA2 on melanoma risk phenotypes [17].
• To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color [17].
• MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs [17].

Anatomical context of OCA2

• The P protein, with 12 transmembrane domains localized to the melanosome, has no assigned function as of yet but is responsible for OCA2 when dysfunctional [18].
• There was no difference in expression levels of biallelically expressed genes (for example, OCA2) from within 15q11-q13 when comparing UPD cell lines with controls [19].
• Thus, absence of caspase 8 and high expression of PED constitute two levels of protection from apoptosis induced by DRs and inflammatory cytokines in neural stem and progenitor cells [10].
• No P protein activity was detected when the mutant P protein with this amino acid substitution was expressed in COS 7 cells [20].
• We looked at the outcome of doppler velocimetry of the umbilical artery in three groups of pregnancies: those with positive end diastolic velocities (PED; n = 214), absent end diastolic velocities (AED; n = 178) and reversed end diastolic velocities (RED; n = 67) [21].

Associations of OCA2 with chemical compounds

• A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation [22].
• To isolate the putative 15q11-q13 candidate AD gene, a genomic contig and physical map of the approximately 1.2-Mb region from the GABA receptor gene cluster to the OCA2 locus was generated [23].
• Partial inactivation of P-protein could result secondarily from impaired metabolism of glycine resulting from deficiency in the activity of H-protein [24].
• This is the first reported crystal structure of a P-protein, and it reveals that P-proteins do not involve the alpha(2)-type active dimer universally observed in the evolutionarily related pyridoxal 5'-phosphate (PLP)-dependent enzymes [12].
• In the phlobaphene pathway, a subset of C1-regulated genes, including a1, are activated by the Myb domain P protein independently of B/R [25].

Physical interactions of OCA2

• We replaced the L8 complex in E. coli 50 S subunits with the rat counterpart P protein complex consisting of P1, P2, and P0 [26].

Enzymatic interactions of OCA2

• Active transcription could also be reconstituted using bacterially synthesized recombinant P protein provided the P protein was phosphorylated by cellular casein kinase II [27].

Regulatory relationships of OCA2

• The P-protein complex of eukaryotic ribosomes forms a lateral stalk structure in the active site of the large ribosomal subunit and is thought to assist in the elongation phase of translation by stimulating GTPase activity of elongation factor-2 and removal of deacylated tRNA [28].

Other interactions of OCA2

• We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation [16].
• The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)[29]
• Furthermore, the role of LC8 in cellular mechanisms other than transport, e.g., inhibition of neuronal nitric oxide synthase, suggests that the P protein interactions could be involved in physiopathological mechanisms of rabies virus-induced pathogenesis [30].
• Using fluorescence in situ hybridization and YAC mapping, we have found that at least one D15F37 locus is centromeric to D15S9 and at least two are between OCA2 and D15S24 [31].
• In addition, a second gamma-aminobutyric acid (GABAA) receptor, the alpha 5 subunit, has been localized within the reference map to between GABRB3 and D15S12 [32].

Analytical, diagnostic and therapeutic context of OCA2

• The role of carrier protein in the sensitivity of enzyme-linked immunosorbent assay for antiribosomal P protein antibodies: further comment on the article by Yoshio et al [33].
• Sera were studied for the presence of anti-P using 2 assays: Western blot with ribosomes as antigen, and an enzyme-linked immunosorbent assay with the COOH-terminal 22 amino acids of the ribosomal P protein in a multiantigenic peptide format as antigen [34].
• The molecular weight of P protein by gel filtration was 210,000, indicating that this enzyme has a native homodimer conformation [35].
• Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis [36].
• In order to better diagnose B. catarrhalis infections, an enzyme-linked immunoassay has been developed using P-protein as antigen to measure antibodies to B. catarrhalis [37].

References