Disease relevance of PAPSS2

• CONCLUSIONS: The bm mutant, which develops severe articular cartilage lesions of the knee joint by approximately 12 months of age, represents a novel example of murine degenerative joint disease, possibly representing a model of human PAPSS2 deficiency-associated arthrosis [1].
• The deficiency of PAPSS2 results in osteochondrodysplasias [2].
• Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis [3].

Psychiatry related information on PAPSS2

• To determine whether more common genetic polymorphisms that do not completely inactivate the enzyme might be one factor responsible for individual differences in sulfate conjugation, we previously cloned the human PAPSS2 gene [4].
• Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation [5].

High impact information on PAPSS2

• A. borkumensis SK2 has a streamlined genome with a paucity of mobile genetic elements and energy generation-related genes, but with a plethora of genes accounting for its wide hydrocarbon substrate range and efficient oil-degradation capabilities [6].
• This activation is direct and appears to extend to other xenobiotic sulfotransferases as well as to 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2), an enzyme that generates the donor cofactor for the reaction [7].
• We found that PAPSS2, which localizes to the cytoplasm when ectopically expressed in mammalian cells, is relocated to the nucleus when coexpressed with PAPSS1 [8].
• We have determined the order of human BAC clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes oriented as are their Fugu orthologs [9].
• Furthermore, differential expression was detected for FLJ11218 and PAPSS2 [10].

Biological context of PAPSS2

• The gene locus for PAPSS2 was identified on chromosome 10 at 10q23.1-q23 [11].
• We have cloned and characterized the genes for human PAPSS1 and PAPSS2 to make it possible to study the pharmacogenomics of these enzymes [12].
• The 5'-flanking region of PAPSS1 did not include a TATA box sequence near the site of transcription initiation, but PAPSS2 had a TATA motif located 21 bp upstream from the site of transcription initiation [12].
• Cloning and structural characterization of PAPSS1 and PAPSS2 will make it possible to perform molecular genetic and pharmacogenomic studies of these important enzymes in humans [12].
• PAPSS1 mapped to human chromosome band 4q24 while PAPSS2 mapped to 10q22-23 by fluorescence in situ hybridization analysis [12].

Anatomical context of PAPSS2

• After optimal PAPSS assay conditions had been established, substrate kinetic studies were performed with cytosol preparations from human liver and cerebral cortex, two tissues with very different expression patterns for PAPSS1 and PAPSS2 mRNA [13].
• In brain and skin PAPSS1 is the major expressed isoform, whereas in liver, cartilage and adrenal glands PAPSS2 isoform expression predominates and in various other tissues the proportions of the isoform expressions is purported to vary [2].
• Using a highly selective and sensitive LC-MS/MS approach, here we show that SK1 overexpression, but not SK2, in different primary cells and cultured cell lines results in predominant upregulation of the synthesis of dihydrosphingosine-1-phosphate (DHS1P) compared to S1P [14].
• Cytomedical therapy for human interleukin-6 transgenic mice (hIL-6 Tgm) was implemented by the intraperitoneal injection of alginate-poly(L)lysine-alginate (APA) membranes microencapsulating SK2 hybridoma cells (APA-SK2 cells) which secrete anti-hIL-6 monoclonal antibodies (SK2 mAb) [15].

Associations of PAPSS2 with chemical compounds

• Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2: gene cloning, characterization and chromosomal localization [12].
• It will now be possible to test the hypothesis that these common, functionally significant PAPSS2 genetic polymorphisms might contribute to variations in sulfate conjugation in vivo [4].
• In humans, PAPS is synthesized from adenosine 5'-triphosphate (ATP) and inorganic sulfate (SO2-4) by two isoforms, PAPSS1 and PAPSS2 [4].

Other interactions of PAPSS2

• Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2 [3].

Analytical, diagnostic and therapeutic context of PAPSS2

• Northern blot analysis showed that the major PAPSS1 and PAPSS2 transcripts were approximately 2.7 and 4.2 kb in length, respectively [12].
• Gene sequence analysis of PAPSS1 (approximately 106 kB) and PAPSS2 (approximately 86.5 kB), revealed a total of 12 exons [2].

References