Human 3′-Phosphoadenosine 5′-Phosphosulfate Synthetase 1 (PAPSS1) and PAPSS2: Gene Cloning, Characterization and Chromosomal Localization

Xu, Zhen; Otterness, Diane M.; Freimuth, Robert R.; Carlini, Edward J.; Wood, Thomas O.; Mitchell, Steven; Moon, Eunpyo; Kim, Ung Jin; Xu, Jing; Siciliano, Michael J.; Weinshilboum, Richard M.

doi:10.1006/bbrc.2000.2123

Cited by 65 publications

(49 citation statements)

References 30 publications

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“…it is the one tissue to solely express PAPS synthase 2b, which forms the dominant PAPS synthase isoform in that tissue. The relatively low expression of PAPS synthase 1 in the liver is consistent with previous reports based on Northern blot analysis [7,17]. The physiological significance of the differential expression of the 2a and 2b subtypes is not understood.…”

Section: Discussionsupporting

confidence: 87%

“…The RT-PCR data are novel in that mRNA expression of the PAPS synthase 2 subtypes could be distinguished ; something that is not possible with Northern blot analysis [17]. Those tissues expressing both the 2a and 2b subtypes usually favoured expression of one or the other, with the exception of the adrenal gland, which was the one tissue in our study that appeared to express both subtypes similarly ; we have not examined the adrenal cortex and medulla separately (a phaeochromocytoma was found to contain only the 2a subtype).…”

Section: Discussionmentioning

confidence: 99%

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Characterization and expression of human bifunctional 3′-phosphoadenosine 5′-phosphosulphate synthase isoforms

Fuda

Shimizu

Lee

et al. 2002

Biochemical Journal

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Sulphonation, a fundamental process essential for normal growth and development, requires the sulphonate donor molecule 3h-phosphoadenosine 5h-phosphosulphate (PAPS), which is produced from ATP and inorganic sulphate by the bifunctional enzyme PAPS synthase. In humans, two genes encode isoenzymes that are 77 % identical at the amino acid level, and alternative splicing creates two subtypes of PAPS synthase 2. The question as to whether distinctions in amino acid composition are reflected in differences in activity has been examined. The specific activity of the PAPS synthase 2 subtypes is 10-to 15-fold higher than that for PAPS synthase 1. The greater catalytic efficiency of the PAPS synthase 2 subtypes is demonstrated further by the 3-to 6-fold higher k cat \K m ratios for ATP and inorganic sulphate as compared with the ratios for PAPS synthase 1. In humans, PAPS synthase 1 is expressed ubiquitously, and is the dominant isoform in most tissues, whereas expression of the PAPS synthase 2

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Characterization and expression of human bifunctional 3′-phosphoadenosine 5′-phosphosulphate synthase isoforms

Fuda

Shimizu

Lee

et al. 2002

Biochemical Journal

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“…The exon-intron junction and the transcription start site of PAPSS2 had been previously determined (Xu et al 2000), and the reference sequence was obtained from the GenBank database (AF160505-9). All 12 exons and their flanking regions, as well as a 1-kb sequence upstream of the transcription start site, were analyzed by direct sequencing of polymerase chain reaction (PCR) products from genomic DNA.…”

Section: Identification Of Polymorphisms In Papss2 and Slc26a2mentioning

confidence: 99%

“…These chondrodysplasias usually show early degen-erative changes in articular cartilage in multiple joints and thus can be considered monogenic models of idiopathic OA. PAPSS2 protein possesses both ATP sulfurylase and adenosine 5Ј-phosphosulfate (APS) kinase activities and generates 3Ј-phosphoadenosine 5Ј-phosphosulfate (PAPS), the universal sulfate donor used in all known posttranslational sulfation reactions (Geller et al 1987;Xu et al 2000). SLC26A2 is a transmembrane glycoprotein with sulfate transporter activity (Hastbacka et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis

Ikeda¹,

Mabuchi²,

Fukuda

et al. 2001

J Hum Genet

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Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular matrix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfationrelated genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3Ј-phosphoadenosine 5Ј-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P ϭ 0.043, odds ratio ϭ 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA.Key words Association analysis · Osteoarthritis · Polymorphisms · Sulfation · Haplotype analysis · PAPSS2 (3Ј-phosphoadenosine 5Ј-phosphosulfate synthase 2) · SLC26A2 (solute carrier family 26, member 2)

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“…There are two isoforms of PAPSS, PAPSS-1 and PAPSS-2. These two enzymes differ in their tissue distribution, with PAPPS-1 mRNA found abundantly in brain and PAPPS-2 highly expressed in the liver (Xu et al, 2000). These isoforms may also differ in their subcellular localization.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of human cytosolic sulfotransferases

2006

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Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes that are involved in the biotransformation of a wide variety of structurally diverse endo-and xenobiotics, including many therapeutic agents and endogenous steroids. Single-nucleotide polymorphisms (SNPs) in SULTs have functional consequences on the translated protein. For the most part, these SNPs are fairly uncommon in the population, but some, most notably for SULT isoform 1A1, are commonly found and have been associated with cancer risk for a variety of tumor sites and also with response to therapeutic agents. SNPs in the hydroxysteroid sulfotransferase, SULT2A1, have been identified in African-American subjects and influence the ratio of plasma DHEA:DHEA-S. This modification could potentially influence cancer risk in steroidogenic tissues. SNPs in many SULTs are ethnically distributed, another factor that could influence SULT pharmacogenetics. Finally, genetic variation has also been identified in 3 0 -phosphoadenoside 5 0 -phosphosulfate synthetase (PAPPS), the enzymes responsible for producing the obligatory cosubstrate for all sulfotransferases. Taken together, this variability could substantially influence the disposition of drugs metabolized by SULTs. Elucidation of the basis and effect of variability in sulfation could greatly impact individualized therapy in the future.

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Human 3′-Phosphoadenosine 5′-Phosphosulfate Synthetase 1 (PAPSS1) and PAPSS2: Gene Cloning, Characterization and Chromosomal Localization

Cited by 65 publications

References 30 publications

Characterization and expression of human bifunctional 3′-phosphoadenosine 5′-phosphosulphate synthase isoforms

Characterization and expression of human bifunctional 3′-phosphoadenosine 5′-phosphosulphate synthase isoforms

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis

Pharmacogenetics of human cytosolic sulfotransferases

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