Disease relevance of ATP6V0A2

• The mRNA for J6B7 is expressed specifically in some T cells, but not in the thymoma BW5147 or liver cells [1].
• BACKGROUND AND OBJECTIVES: Hemoglobin Constant Spring (Hb CS), caused by a termination codon mutation (TAA-->CAA) in the a2 gene, is the most common non-deletional type of a thalassemia in Southeast Asia. This mutation can most easily be detected by loss of an MseI-restriction site (T/TAA) spanning the termination codon [2].
• TJ6 was not expressed on CD3+ lymphocytes from either group but was expressed on CD56+ cells from a small population of pregnant women which preliminary data indicate may correlate with the occurrence of spontaneous abortion in these women [3].
• We also begin to characterize the expression of TJ6 isoforms in an acute lymphocytic leukemia cell line (SB), murine thymus, and the developing murine fetoplacental unit, as well as the expression of a membrane form of TJ6 present on human lymphocytes during pregnancy [3].
• Laboratory findings, bone marrow morphology and molecular investigations supported this diagnosis, including b3/a2 as well as b2/a2 chimeric mRNA expression in support of a Philadelphia chromosome positive chronic myeloproliferation [4].

High impact information on ATP6V0A2

• The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis [5].
• However, it cannot be ruled out that the a2 peptide-class II interaction forms different T-cell ligands in the two strains either because the two class II MHC molecules are different or that the peptide is processed and reveals a different antigenic activity (Fox et al. 1988) [6].
• Using pair-wise comparison of aligned nucleotide sequences of distinct and complete human MHC class I molecules, we have constructed triangular tables to study the similarities and differences of various a1 (exon 2) and a2 (exon 3) region sequences [7].
• Although hTJ6 was found to be a poor substrate for tyrosine-phosphorylating enzymes, suggesting that its ITAM sequence is non-functional in protein tyrosine kinase-mediated signaling pathways, its role in organellar H+ pumping suggests that hTJ6 function may participate in protein trafficking/processing [8].
• Over-expression of hTJ6 in HEK 293 cells increased H+ uptake into intracellular organelles, an effect that was sensitive to inhibition by bafilomycin, a selective inhibitor of vacuolar H+ pump [8].

Biological context of ATP6V0A2

• The nucleotide and deduced amino acid sequences of J6B7 did not reveal significant homology to any published sequences [1].
• J6B7 is 2937 nucleotides in length and contains one open reading frame encoding for a peptide of predicted Mr of 98,042 [1].
• Cloning, expression and functional characterization of the putative regeneration and tolerance factor (RTF/TJ6) as a functional vacuolar ATPase proton pump regulatory subunit with a conserved sequence of immunoreceptor tyrosine-based activation motif [8].
• A human expressed sequence tag showing partial homology to the murine TJ6 (mTJ6) gene and encoding a putative ITAM sequence has been identified and used to clone the human TJ6 (hTJ6) gene from an HL-60-derived cDNA library. hTJ6 was found to encode a protein of 856 residues with a calculated mass of 98 155 Da [8].
• Initial studies indicated that when mice were treated with an anti-TJ6 binding mAb early in pregnancy, the pregnancies were completely ablated and that TJ6 expression is enhanced dramatically during pregnancy [3].

Anatomical context of ATP6V0A2

• Expression of a membrane form of the pregnancy-associated protein TJ6 on lymphocytes [3].
• Flow cytometric analysis also demonstrated that similar to the CD19+ B cells from pregnant women, TJ6 is expressed on the surface of SB cells [3].
• Here we also show that TJ6 transcripts are highly expressed in the developing fetoplacental unit as well as in the developing thymus [3].
• TJ6, a newly described protein produced locally in the uterine decidua during pregnancy, may be involved in maintaining a unique immunological environment at the maternal-fetal interface [9].
• These studies have demonstrated that TJ6m protein can be measured in women prior to a spontaneous abortion based on expression of TJ6 on CD56-positive NK cells [10].

Analytical, diagnostic and therapeutic context of ATP6V0A2

• Northern blot analysis demonstrates that isoform a2 is highly expressed in lung, kidney, and spleen [11].
• Prostate tissue from pre-pubertal, pubertal, and adult mice were analyzed by Western blot and RT-PCR analysis for Foxa1, a2, and a3 expression [12].
• TJ6 is a novel protein which has immunosuppressive activity and may have a functional role in fetal allograft survival during pregnancy [3].
• In order to determine if TJ6 and DSF are the same or different proteins, we used affinity column purified TGF-beta 2-DSF and stained Western blots with anti-TJ6 [13].
• RESULTS: Immunoblotting showed that TJ6 protein was expressed on most of the placenta-associated mononuclear cells, and the size was 70-72 kDa at all stages of pregnancy [14].

References