Disease relevance of PAPSS1

• In addition, the 1-268 fragment and full-length hPAPSS were overexpressed in Escherichia coli and column purified [1].

High impact information on PAPSS1

• We found that PAPSS2, which localizes to the cytoplasm when ectopically expressed in mammalian cells, is relocated to the nucleus when coexpressed with PAPSS1 [2].
• Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells [2].
• Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells [2].
• Sulfation in high endothelial venules: cloning and expression of the human PAPS synthetase [3].
• Here, we report the molecular characterization of a novel 2.5 kb human cDNA from MECA-79+ HEV-derived endothelial cells that encodes the target of chlorate, PAPS synthetase, a multifunctional enzyme containing domains for both ATP sulfurylase and adenosine-5'-phosphosulfate kinase [3].

Biological context of PAPSS1

• 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 [4].
• We have cloned and characterized the genes for human PAPSS1 and PAPSS2 to make it possible to study the pharmacogenomics of these enzymes [4].
• 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 [4].
• PAPSS1 mapped to human chromosome band 4q24 while PAPSS2 mapped to 10q22-23 by fluorescence in situ hybridization analysis [4].
• These observations represent a step toward testing the hypothesis that genetic variation in PAPS synthesis catalyzed by PAPSS1 might alter in vivo sulfate conjugation [5].

Anatomical context of PAPSS1

• 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 [6].
• PAPSS1 located in the chromosome 4q23 deficiency and consequent effect in lymphocyte recruitment in High Endothelial Venules has been reported [7].
• 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 [7].
• The cDNA for human PAPS synthase (hPAPSS) along with polymerase chain reaction products corresponding to several NH2- and COOH-terminal fragments were cloned and expressed in COS-1 cells [1].
• As a result of SK1 overexpression, migration and Ca(2+)-response of human pulmonary artery endothelial cells (HPAEC) to stimulation with external S1P, but not thrombin, was strongly impaired [8].

Associations of PAPSS1 with chemical compounds

• Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2: gene cloning, characterization and chromosomal localization [4].
• In humans, PAPS is synthesized from adenosine 5'-triphosphate (ATP) and inorganic sulfate (SO2-4) by two isoforms, PAPSS1 and PAPSS2 [9].
• The bifunctional PAPSS1 is comprised of NH2-terminal APS kinase domain (approximately 1-260 aa), and a COOH-terminal ATP sulfurylase domain (approximately 220-623 aa) [7].
• Phenylalanine, reported to be an inhibitor of brain ATP sulfurylase, was without effect on PAPS synthetase isoform 1 [10].
• 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase (PAPSS) catalyzes the biosynthesis of PAPS which serves as the universal sulfonate donor compound for all sulfotransferase reactions [7].

Other interactions of PAPSS1

• This coupled assay uses the sulfation of 17beta-[(3)H]estradiol catalyzed by recombinant human SULT1E1 to measure PAPS, which has been generated by PAPSS during the initial step of the assay [6].

Analytical, diagnostic and therapeutic context of PAPSS1

• Northern blot analysis showed that the major PAPSS1 and PAPSS2 transcripts were approximately 2.7 and 4.2 kb in length, respectively [4].
• Gene sequence analysis of PAPSS1 (approximately 106 kB) and PAPSS2 (approximately 86.5 kB), revealed a total of 12 exons [7].
• Molecular cloning, expression, and characterization of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional domains [1].
• Additionally, transplantation of both amino and carboxyl termini of rSK1 onto hSK1 subunits, normally forming functional homomeric channel, hinders their functional expression, while hSK1 channels containing only the rSK1 carboxyl terminus are functional [11].

References