{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:32:16Z","timestamp":1790976736116,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,1,3]],"date-time":"2008-01-03T00:00:00Z","timestamp":1199318400000},"content-version":"vor","delay-in-days":1828,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>3'\u2010phosphoadenosine 5'\u2010phosphosulfate (PAPS) synthase (PAPSS) catalyzes the biosynthesis of PAPS which serves as the universal sulfonate donor compound for all sulfotransferase reactions. PAPSS forms PAPS in two sequential steps. First inorganic sulfate combines with ATP to form adenosine 5'\u2010phosphosulfate (APS) and pyrophosphate catalyzed by ATP sulfurylase domain and in the second step, APS combines with another molecule of ATP to form PAPS and ADP catalyzed by APS kinase domain. The bifunctional PAPSS1 is comprised of NH2\u2010terminal APS kinase domain (\u223c1\u2010260 aa), and a COOH\u2010terminal ATP sulfurylase domain (\u223c220\u2010623 aa). In humans there are two major isoforms PAPSS1 and PAPSS2. 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. The deduced amino acid sequences of the two isoforms reveal 77% identity between PAPSS1 and PAPSS2. In addition there is a splice variant PAPSS2b which contains notably an extra five amino acid sequence GMALP. From human tissues PAPSS1 and a splice variant PAPSS2b has been molecularly cloned, overexpressed, purified and have been biochemically characterized partially. PAPSS2b exhibited an apparent difference towards varying ATP concentration showing a sigmoidal response, with a 0.5 [v\/Vmax] at 1.4 mM ATP whereas PAPSS1 exhibited a hyperbolic response with a 0.5 [v\/Vmax] at 0.25 mM ATP. Although this being the case, comparison of PAPSS1 and PAPSS2 crude extracts, did not show marked difference in the kinetic properties with either substrates ATP or sulfate leading to speculate that the extra GMALP pentapeptide present in PAPSS2b could be altering the kinetic behavior. The ATP binding sites of the \u03b1\u2010\u03b2\u2010ATP hydrolysis, active site motif HxxH (425\u2010428 aa) is present in the ATP sulfurylase domain and the \u03b2\u2010\u03b3\u2010hydrolase motif GxxGxxK (59\u201065 aa) is present in the APS kinase domain. The motifs are highly conserved between both isoforms. Gene sequence analysis of PAPSS1 (\u223c106 kB) and PAPSS2 (\u223c86.5 kB), revealed a total of 12 exons. Among exons 2\u201011 the sizes are highly conserved, although intron sizes varied remarkably. Exons 1 and 12 varied in sizes, contained 5'\u2010UTR and 3'\u2010UTR respectively. PAPSS1 and PAPSS2 contained no putative TATA box and CCAAT box. However both PAPSS1 and PAPSS2 possessed many GC boxes. From promoter analysis, it is apparent that both PAPSS1 and PAPSS2 are inducible, perhaps at various time periods, regulated by specific transcription factors. The deficiency of PAPSS2 results in osteochondrodysplasias. Osteochondrodysplasias are genetically heterogeneous group of disorders that affects skeletal development, linear growth, and the maintenance of cartilage and bone. A large inbred family with a distinct form of recessively inherited, spondyloepimetaphyseal dysplasia (SEMD) was mapped to PAPSS2 isoform located in the chromosome region of 10q23\u201024. PAPSS1 located in the chromosome 4q23 deficiency and consequent effect in lymphocyte recruitment in High Endothelial Venules has been reported. Several single nucleotide polymorphism (SNP) of PAPSS has been identified, some of which are in the coding region (cSNPs), has been shown to have altered enzyme activity. IUBMB Life, 55: 1\u201011, 2003<\/jats:p>","DOI":"10.1080\/1521654031000072148","type":"journal-article","created":{"date-parts":[[2003,11,25]],"date-time":"2003-11-25T23:01:17Z","timestamp":1069801277000},"page":"1-11","source":"Crossref","is-referenced-by-count":115,"title":["Human 3'\u2010phosphoadenosine 5'\u2010phosphosulfate (PAPS) Synthase: Biochemistry, Molecular Biology and Genetic Deficiency"],"prefix":"10.1002","volume":"55","author":[{"given":"KV","family":"Venkatachalam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,3]]},"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1080%2F1521654031000072148","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1080\/1521654031000072148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T15:12:07Z","timestamp":1700233927000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1080\/1521654031000072148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1080\/1521654031000072148"],"URL":"https:\/\/doi.org\/10.1080\/1521654031000072148","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]}}}