Disease relevance of LY6E

• LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009) [1].
• IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia [1].
• The neurodegenerative disorder spinocerebellar ataxia type 2 is caused by a trinucleotide expansion in the SCA2 gene encoding a lengthened polyglutamine stretch in the gene product ataxin-2, which seems to be implicated in cellular RNA-processing pathways and translational regulation [2].
• In two mouse models of cryptococcosis, the tsa1 Delta mutant is significantly less virulent [3].
• Clinical and genetic analysis of a Tunisian family with autosomal dominant cerebellar ataxia type 1 linked to the SCA2 locus [4].

High impact information on LY6E

• A trypomastigote surface antigen, TSA-1, and two amastigote surface molecules, ASP-1 and ASP-2, were recently identified as targets of CD8(+) cytotoxic T lymphocytes (CTL) in T. cruzi-infected mice [5].
• The RIG-E coded protein shares some homology with CD59 and with a number of growth factor receptors [6].
• RIG-E, a human homolog of the murine Ly-6 family, is induced by retinoic acid during the differentiation of acute promyelocytic leukemia cell [6].
• We also report that TSA-1-deficient adrenal glands have significantly reduced levels of the catecholamines noradrenaline and adrenaline [7].
• Thymic shared antigen 1 (TSA-1) is a plasma membrane protein of the Ly-6 superfamily expressed on thymocytes, thymic stromal cells, and other cells of the hematopoietic system [7].

Biological context of LY6E

• Here we report that, through the application of bioinformatics analysis to the dbEST database, we obtained the sequence of human TSA-1/SCA-2, a new member of the human Ly-6 family [8].
• In genomic organization this gene resembles genes encoding murine Ly-6 glycoproteins, a human homologue of the Ly-6 family called RIG-E, and CD59; products of these genes, known as GPI-anchored proteins, are variously involved in signal transduction, cell-cell adhesion, and cell-matrix attachment [9].
• Finally, tyrosine phosphorylation of CD3zeta chains was induced after stimulation with anti-TSA-1, suggesting that a functional association between these two molecules also exists [10].
• We have previously demonstrated that a signal via TSA-1/Sca-2 inhibits T cell receptor (TCR)-mediated T cell activation and apoptosis [10].
• Like mouse TSA-1, it has a broad tissue distribution with varied expression levels in normal human tissues and tumor cell lines [11].

Anatomical context of LY6E

• SF20/IL-25, a novel bone marrow stroma-derived growth factor that binds to mouse thymic shared antigen-1 and supports lymphoid cell proliferation [12].
• Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex [10].
• Fluorescence in situ hybridization of metaphase spreads of chromosome 8, containing hybrid cell line 706-B6 clone 17 (CL-17) with cosmid c101F1, placed the 9804 gene close to the telomere at 8q24 [11].
• Here we show that deletion of both TSA-1 alleles results in abnormal adrenal gland development and midgestational lethality due to cardiac abnormalities [7].
• The recombinant TSA-1 Ab recognized the acrosomal, equatorial, mid-piece, and tail regions of human sperm cell in indirect immunofluorescence, bound to live human sperm in the immunobeads binding technique (IBT) and caused a significant concentration-dependent inhibition of human sperm acrosome reaction [13].

Associations of LY6E with chemical compounds

• The tsa1 Delta mutant shows sensitivity to hydrogen peroxide and t-butylhydroperoxide, as well as significant growth retardation at 25 degrees C and 38.5 degrees C. The tsa1 Delta mutant is also sensitive to NO, demonstrating a link between oxidative and nitrosative stress pathways [3].
• Human TSA1 exhibited high catalytic activity for the reduction of the fatty acid hydroperoxide as indicated by K(m) and V(max) (89.9 microM for linoleic acid hydroperoxide, 28.64 micromol(-1) min(-1) mg(-1), respectively) [14].
• Based on the results of in vitro transcription and translation experiments, the TSA-1 (ORF) was subcloned into pGEX-6P-3 vector and expressed using the glutathione S-transferase gene fusion system [13].
• Linear regression of theophylline concentrations determined by the Vision Theophylline II assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9804; P less than .05) and for venipuncture samples (r = .9875; P less than .05) [15].

Other interactions of LY6E

• 3. Genes encoding at least two other GPI-anchored molecules, E48 and RIG-E, are also located in this region [9].
• Furthermore, a pathological study suggested that the levels of UGT2B4, rpP0, dek, and vitronectin increased and the level of RIG-E decreased with the histological grading [16].
• Prostate stem cell antigen (PSCA, named for its strong sequence homology to the thymocyte marker stem cell antigen 2) is a cell surface antigen expressed in normal prostate and associated with human and murine prostate cancer [17].
• Among mannoproteins, heat shock proteins and glycolytic enzymes we found thiol-specific antioxidant-like protein 1 (Tsa1p) to be differentially localized depending on the conditions applied [18].
• Antibodies (Ab) against the purified recombinant protein specifically recognized the approximately 17 kDa recombinant TSA-1, and a approximately 24 kDa band in human sperm extract in the Western blot procedure [13].

Analytical, diagnostic and therapeutic context of LY6E

• To address the function of TSA-1, we generated mutant mice in which TSA-1 expression was inactivated by gene targeting [7].
• The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis [19].
• They had been treated with surgery only (n = 9804), radiotherapy (n = 4099), chemotherapy and radiotherapy (n = 493) or chemotherapy alone (n = 97) [20].
• Extensive analysis for tissue-specificity by Northern blots and RT-PCR-Southern blot procedures using various human tissues indicated that TSA-1 was specifically expressed only in the human testis [13].

References