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Database: UniProt
Entry: PAPS2_HUMAN
LinkDB: PAPS2_HUMAN
Original site: PAPS2_HUMAN 
ID   PAPS2_HUMAN             Reviewed;         614 AA.
AC   O95340; Q9BZL2; Q9P0G6; Q9UHM1; Q9UKD3; Q9UP30;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2002, sequence version 2.
DT   27-MAR-2024, entry version 214.
DE   RecName: Full=Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2 {ECO:0000305|PubMed:23824674};
DE            Short=PAPS synthase 2;
DE            Short=PAPSS 2;
DE   AltName: Full=Sulfurylase kinase 2;
DE            Short=SK 2;
DE            Short=SK2;
DE   Includes:
DE     RecName: Full=Sulfate adenylyltransferase {ECO:0000305|PubMed:23824674};
DE              EC=2.7.7.4 {ECO:0000305|PubMed:11773860, ECO:0000305|PubMed:19474428, ECO:0000305|PubMed:23824674, ECO:0000305|PubMed:25594860};
DE     AltName: Full=ATP-sulfurylase;
DE     AltName: Full=Sulfate adenylate transferase;
DE              Short=SAT;
DE   Includes:
DE     RecName: Full=Adenylyl-sulfate kinase {ECO:0000305|PubMed:23824674};
DE              EC=2.7.1.25 {ECO:0000305|PubMed:11773860, ECO:0000305|PubMed:19474428, ECO:0000305|PubMed:23824674, ECO:0000305|PubMed:25594860};
DE     AltName: Full=3'-phosphoadenosine-5'-phosphosulfate synthase;
DE     AltName: Full=APS kinase;
DE     AltName: Full=Adenosine-5'-phosphosulfate 3'-phosphotransferase;
DE     AltName: Full=Adenylylsulfate 3'-phosphotransferase;
GN   Name=PAPSS2; Synonyms=ATPSK2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND INVOLVEMENT IN BCYM4.
RC   TISSUE=Fetal cartilage;
RX   PubMed=9771708; DOI=10.1038/2458;
RA   ul Haque M.F., King L.M., Krakow D., Cantor R.M., Rusiniak M.E.,
RA   Swank R.T., Superti-Furga A., Haque S., Abbas H., Ahmad W., Ahmad M.,
RA   Cohn D.H.;
RT   "Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia
RT   and the brachymorphic mouse.";
RL   Nat. Genet. 20:157-162(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RA   Franzon V.L., Gibson M.A., Hatzinikolas G., Cleary E.G., Woolatt E.,
RA   Sutherland G.R.;
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RA   Fuda H., Shimizu C., Strott C.A.;
RT   "Human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase:
RT   differential expression of isoforms and effect of polymorphisms on
RT   activity.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
RX   PubMed=10679223; DOI=10.1006/bbrc.2000.2123;
RA   Xu Z.-H., Otterness D.M., Freimuth R.R., Carlini E.J., Wood T.C.,
RA   Mitchell S., Moon E., Kim U.-J., Xu J.-P., Siciliano M.J.,
RA   Weinshilboum R.M.;
RT   "Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and
RT   PAPSS2: gene cloning, characterization and chromosomal localization.";
RL   Biochem. Biophys. Res. Commun. 268:437-444(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC   TISSUE=Liver;
RX   PubMed=10559207; DOI=10.1074/jbc.274.47.33306;
RA   Kurima K., Singh B., Schwartz N.B.;
RT   "Genomic organization of the mouse and human genes encoding the ATP
RT   sulfurylase/adenosine 5'-phosphosulfate kinase isoform SK2.";
RL   J. Biol. Chem. 274:33306-33312(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RA   Venkatachalam K.V., Fuda H., Strott C.A.;
RT   "3'-phosphoadenosine 5'-phosphosulfate synthase 2b isoform.";
RL   Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   TISSUE=Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   INVOLVEMENT IN BCYM4.
RX   PubMed=9714015;
RX   DOI=10.1002/(sici)1096-8628(19980806)78:5<468::aid-ajmg13>3.3.co;2-2;
RA   Ahmad M., Haque M.F., Ahmad W., Abbas H., Haque S., Krakow D., Rimoin D.L.,
RA   Lachman R.S., Cohn D.H.;
RT   "Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia
RT   segregating in an inbred Pakistani kindred.";
RL   Am. J. Med. Genet. 78:468-473(1998).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, VARIANT BCYM4 ARG-48,
RP   CHARACTERIZATION OF VARIANT BCYM4 ARG-48, AND TISSUE SPECIFICITY.
RX   PubMed=19474428; DOI=10.1056/nejmoa0810489;
RA   Noordam C., Dhir V., McNelis J.C., Schlereth F., Hanley N.A., Krone N.,
RA   Smeitink J.A., Smeets R., Sweep F.C., Claahsen-van der Grinten H.L.,
RA   Arlt W.;
RT   "Inactivating PAPSS2 mutations in a patient with premature pubarche.";
RL   N. Engl. J. Med. 360:2310-2318(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 21-218 IN COMPLEX WITH ATP.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of the kinase domain of PAPSS 2.";
RL   Submitted (SEP-2005) to the PDB data bank.
RN   [13]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, VARIANTS LYS-10; LEU-281; MET-291
RP   AND LYS-432, AND CHARACTERIZATION OF VARIANTS LYS-10 AND MET-291.
RX   PubMed=11773860; DOI=10.1097/00008571-200201000-00003;
RA   Xu Z.-H., Freimuth R.R., Eckloff B., Wieben E., Weinshilboum R.M.;
RT   "Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2)
RT   pharmacogenetics: gene resequencing, genetic polymorphisms and functional
RT   characterization of variant allozymes.";
RL   Pharmacogenetics 12:11-21(2002).
RN   [14]
RP   INVOLVEMENT IN BCYM4.
RX   PubMed=23633440; DOI=10.1002/ajmg.a.35906;
RA   Tueysuez B., Yilmaz S., Guel E., Kolb L., Bilguvar K., Evliyaoglu O.,
RA   Guenel M.;
RT   "Spondyloepimetaphyseal dysplasia Pakistani type: expansion of the
RT   phenotype.";
RL   Am. J. Med. Genet. A 161A:1300-1308(2013).
RN   [15]
RP   VARIANTS BCYM4 TYR-43 AND GLN-76, CHARACTERIZATION OF VARIANTS BCYM4 TYR-43
RP   AND GLN-76, VARIANT LYS-183, CHARACTERIZATION OF VARIANT LYS-183, FUNCTION,
RP   CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=23824674; DOI=10.1002/humu.22377;
RA   Iida A., Simsek-Kiper P.O., Mizumoto S., Hoshino T., Elcioglu N.,
RA   Horemuzova E., Geiberger S., Yesil G., Kayserili H., Utine G.E.,
RA   Boduroglu K., Watanabe S., Ohashi H., Alanay Y., Sugahara K., Nishimura G.,
RA   Ikegawa S.;
RT   "Clinical and radiographic features of the autosomal recessive form of
RT   brachyolmia caused by PAPSS2 mutations.";
RL   Hum. Mutat. 34:1381-1386(2013).
RN   [16]
RP   VARIANT BCYM4 ASP-270, CHARACTERIZATION OF VARIANTS BCYM4 ARG-48 AND
RP   ASP-270, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=25594860; DOI=10.1210/jc.2014-3556;
RA   Oostdijk W., Idkowiak J., Mueller J.W., House P.J., Taylor A.E.,
RA   O'Reilly M.W., Hughes B.A., de Vries M.C., Kant S.G., Santen G.W.,
RA   Verkerk A.J., Uitterlinden A.G., Wit J.M., Losekoot M., Arlt W.;
RT   "PAPSS2 deficiency causes androgen excess via impaired DHEA sulfation - in
RT   vitro and in vivo studies in a family harboring two novel PAPSS2
RT   mutations.";
RL   J. Clin. Endocrinol. Metab. 2015:JC20143556-JC20143556(2015).
CC   -!- FUNCTION: Bifunctional enzyme with both ATP sulfurylase and APS kinase
CC       activity, which mediates two steps in the sulfate activation pathway.
CC       The first step is the transfer of a sulfate group to ATP to yield
CC       adenosine 5'-phosphosulfate (APS), and the second step is the transfer
CC       of a phosphate group from ATP to APS yielding 3'-
CC       phosphoadenylylsulfate/PAPS, the activated sulfate donor used by
CC       sulfotransferases (PubMed:19474428, PubMed:11773860, PubMed:23824674,
CC       PubMed:25594860). In mammals, PAPS is the sole source of sulfate while
CC       APS appears to only be an intermediate in the sulfate-activation
CC       pathway (PubMed:19474428, PubMed:11773860, PubMed:23824674,
CC       PubMed:25594860). Plays indirectly an important role in skeletogenesis
CC       during postnatal growth (PubMed:9771708). {ECO:0000269|PubMed:11773860,
CC       ECO:0000269|PubMed:19474428, ECO:0000269|PubMed:23824674,
CC       ECO:0000269|PubMed:25594860, ECO:0000269|PubMed:9771708}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H(+) + sulfate = adenosine 5'-phosphosulfate +
CC         diphosphate; Xref=Rhea:RHEA:18133, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16189, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:58243; EC=2.7.7.4; Evidence={ECO:0000305|PubMed:11773860,
CC         ECO:0000305|PubMed:19474428, ECO:0000305|PubMed:23824674,
CC         ECO:0000305|PubMed:25594860};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18134;
CC         Evidence={ECO:0000305|PubMed:19474428};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=adenosine 5'-phosphosulfate + ATP = 3'-phosphoadenylyl sulfate
CC         + ADP + H(+); Xref=Rhea:RHEA:24152, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:58243, ChEBI:CHEBI:58339,
CC         ChEBI:CHEBI:456216; EC=2.7.1.25;
CC         Evidence={ECO:0000305|PubMed:11773860, ECO:0000305|PubMed:19474428,
CC         ECO:0000305|PubMed:23824674};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24153;
CC         Evidence={ECO:0000305|PubMed:19474428};
CC   -!- PATHWAY: Sulfur metabolism; sulfate assimilation.
CC       {ECO:0000269|PubMed:11773860, ECO:0000269|PubMed:19474428,
CC       ECO:0000269|PubMed:23824674, ECO:0000269|PubMed:25594860}.
CC   -!- INTERACTION:
CC       O95340; Q96LK0: CEP19; NbExp=6; IntAct=EBI-1053912, EBI-741885;
CC       O95340; O75031: HSF2BP; NbExp=3; IntAct=EBI-1053912, EBI-7116203;
CC       O95340; Q96CV9: OPTN; NbExp=3; IntAct=EBI-1053912, EBI-748974;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=A;
CC         IsoId=O95340-1; Sequence=Displayed;
CC       Name=B;
CC         IsoId=O95340-2; Sequence=VSP_001259;
CC   -!- TISSUE SPECIFICITY: Expressed in cartilage and adrenal gland.
CC       {ECO:0000269|PubMed:19474428}.
CC   -!- DISEASE: Brachyolmia type 4 with mild epiphyseal and metaphyseal
CC       changes (BCYM4) [MIM:612847]: A form of brachyolmia, a clinically and
CC       genetically heterogeneous skeletal dysplasia primarily affecting the
CC       spine and characterized by a short trunk, short stature, and
CC       platyspondyly. BCYM4 is an autosomal recessive form with mild
CC       epiphyseal and metaphyseal changes. Clinical features include short
CC       stature evidenced at birth, short and bowed lower limbs, mild
CC       brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints.
CC       Some BCYM4 patients may manifest premature pubarche and
CC       hyperandrogenism associated with skeletal dysplasia and short stature.
CC       {ECO:0000269|PubMed:19474428, ECO:0000269|PubMed:23633440,
CC       ECO:0000269|PubMed:23824674, ECO:0000269|PubMed:25594860,
CC       ECO:0000269|PubMed:9714015, ECO:0000269|PubMed:9771708}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the APS kinase
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the sulfate
CC       adenylyltransferase family. {ECO:0000305}.
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DR   EMBL; AF091242; AAC64583.1; -; mRNA.
DR   EMBL; AF074331; AAD38423.1; -; mRNA.
DR   EMBL; AF313907; AAK00296.1; -; mRNA.
DR   EMBL; AF160509; AAF40307.2; -; Genomic_DNA.
DR   EMBL; AF160503; AAF40307.2; JOINED; Genomic_DNA.
DR   EMBL; AF160504; AAF40307.2; JOINED; Genomic_DNA.
DR   EMBL; AF160505; AAF40307.2; JOINED; Genomic_DNA.
DR   EMBL; AF160506; AAF40307.2; JOINED; Genomic_DNA.
DR   EMBL; AF160507; AAF40307.2; JOINED; Genomic_DNA.
DR   EMBL; AF160508; AAF40307.2; JOINED; Genomic_DNA.
DR   EMBL; AF173365; AAF12761.1; -; mRNA.
DR   EMBL; AF150754; AAF20366.2; -; mRNA.
DR   EMBL; BC009894; AAH09894.1; -; mRNA.
DR   CCDS; CCDS44453.1; -. [O95340-2]
DR   CCDS; CCDS7385.1; -. [O95340-1]
DR   RefSeq; NP_001015880.1; NM_001015880.1. [O95340-2]
DR   RefSeq; NP_004661.2; NM_004670.3. [O95340-1]
DR   PDB; 2AX4; X-ray; 2.50 A; A/B/C/D=21-218.
DR   PDB; 7FH3; X-ray; 1.80 A; A/B=223-614.
DR   PDB; 7FHA; X-ray; 2.00 A; A/B=223-614.
DR   PDB; 8I1N; X-ray; 2.80 A; A/B/C/D=22-218.
DR   PDB; 8I1O; X-ray; 2.40 A; A/B/C/D=16-218.
DR   PDBsum; 2AX4; -.
DR   PDBsum; 7FH3; -.
DR   PDBsum; 7FHA; -.
DR   PDBsum; 8I1N; -.
DR   PDBsum; 8I1O; -.
DR   AlphaFoldDB; O95340; -.
DR   SMR; O95340; -.
DR   BioGRID; 114521; 61.
DR   IntAct; O95340; 8.
DR   STRING; 9606.ENSP00000406157; -.
DR   BindingDB; O95340; -.
DR   ChEMBL; CHEMBL4105790; -.
DR   GlyGen; O95340; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O95340; -.
DR   MetOSite; O95340; -.
DR   PhosphoSitePlus; O95340; -.
DR   SwissPalm; O95340; -.
DR   BioMuta; PAPSS2; -.
DR   EPD; O95340; -.
DR   jPOST; O95340; -.
DR   MassIVE; O95340; -.
DR   MaxQB; O95340; -.
DR   PaxDb; 9606-ENSP00000406157; -.
DR   PeptideAtlas; O95340; -.
DR   ProteomicsDB; 50808; -. [O95340-1]
DR   ProteomicsDB; 50809; -. [O95340-2]
DR   Pumba; O95340; -.
DR   TopDownProteomics; O95340-1; -. [O95340-1]
DR   Antibodypedia; 30161; 303 antibodies from 25 providers.
DR   DNASU; 9060; -.
DR   Ensembl; ENST00000361175.8; ENSP00000354436.4; ENSG00000198682.13. [O95340-1]
DR   Ensembl; ENST00000456849.2; ENSP00000406157.1; ENSG00000198682.13. [O95340-2]
DR   GeneID; 9060; -.
DR   KEGG; hsa:9060; -.
DR   MANE-Select; ENST00000456849.2; ENSP00000406157.1; NM_001015880.2; NP_001015880.1. [O95340-2]
DR   UCSC; uc001kew.4; human. [O95340-1]
DR   AGR; HGNC:8604; -.
DR   CTD; 9060; -.
DR   DisGeNET; 9060; -.
DR   GeneCards; PAPSS2; -.
DR   HGNC; HGNC:8604; PAPSS2.
DR   HPA; ENSG00000198682; Tissue enhanced (adrenal).
DR   MalaCards; PAPSS2; -.
DR   MIM; 603005; gene.
DR   MIM; 612847; phenotype.
DR   neXtProt; NX_O95340; -.
DR   OpenTargets; ENSG00000198682; -.
DR   Orphanet; 448242; Autosomal recessive brachyolmia.
DR   Orphanet; 93282; Spondyloepimetaphyseal dysplasia, PAPSS2 type.
DR   PharmGKB; PA383; -.
DR   VEuPathDB; HostDB:ENSG00000198682; -.
DR   eggNOG; KOG4238; Eukaryota.
DR   GeneTree; ENSGT00390000009613; -.
DR   HOGENOM; CLU_009463_3_0_1; -.
DR   InParanoid; O95340; -.
DR   OMA; TENCTPE; -.
DR   OrthoDB; 22780at2759; -.
DR   PhylomeDB; O95340; -.
DR   TreeFam; TF313143; -.
DR   BioCyc; MetaCyc:HS07544-MONOMER; -.
DR   BRENDA; 2.7.1.25; 2681.
DR   BRENDA; 2.7.7.4; 2681.
DR   PathwayCommons; O95340; -.
DR   Reactome; R-HSA-174362; Transport and synthesis of PAPS.
DR   Reactome; R-HSA-2408550; Metabolism of ingested H2SeO4 and H2SeO3 into H2Se.
DR   Reactome; R-HSA-3560796; Defective PAPSS2 causes SEMD-PA.
DR   SABIO-RK; O95340; -.
DR   SignaLink; O95340; -.
DR   UniPathway; UPA00097; -.
DR   BioGRID-ORCS; 9060; 15 hits in 1151 CRISPR screens.
DR   ChiTaRS; PAPSS2; human.
DR   EvolutionaryTrace; O95340; -.
DR   GeneWiki; PAPSS2; -.
DR   GenomeRNAi; 9060; -.
DR   Pharos; O95340; Tbio.
DR   PRO; PR:O95340; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; O95340; Protein.
DR   Bgee; ENSG00000198682; Expressed in tibia and 189 other cell types or tissues.
DR   ExpressionAtlas; O95340; baseline and differential.
DR   Genevisible; O95340; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0004020; F:adenylylsulfate kinase activity; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016779; F:nucleotidyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0004781; F:sulfate adenylyltransferase (ATP) activity; ISS:UniProtKB.
DR   GO; GO:0050428; P:3'-phosphoadenosine 5'-phosphosulfate biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0007596; P:blood coagulation; IEA:Ensembl.
DR   GO; GO:0060348; P:bone development; IEA:Ensembl.
DR   GO; GO:0042445; P:hormone metabolic process; IMP:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0000103; P:sulfate assimilation; IMP:UniProtKB.
DR   CDD; cd02027; APSK; 1.
DR   CDD; cd00517; ATPS; 1.
DR   Gene3D; 3.40.50.620; HUPs; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   Gene3D; 3.10.400.10; Sulfate adenylyltransferase; 1.
DR   HAMAP; MF_00065; Adenylyl_sulf_kinase; 1.
DR   InterPro; IPR002891; APS_kinase.
DR   InterPro; IPR025980; ATP-Sase_PUA-like_dom.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR015947; PUA-like_sf.
DR   InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR   InterPro; IPR024951; Sulfurylase_cat_dom.
DR   InterPro; IPR002650; Sulphate_adenylyltransferase.
DR   NCBIfam; TIGR00455; apsK; 1.
DR   NCBIfam; TIGR00339; sopT; 1.
DR   PANTHER; PTHR11055; BIFUNCTIONAL 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE SYNTHASE; 1.
DR   PANTHER; PTHR11055:SF16; BIFUNCTIONAL 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE SYNTHASE 2; 1.
DR   Pfam; PF01583; APS_kinase; 1.
DR   Pfam; PF01747; ATP-sulfurylase; 1.
DR   Pfam; PF14306; PUA_2; 1.
DR   SUPFAM; SSF52374; Nucleotidylyl transferase; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF88697; PUA domain-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Disease variant; Dwarfism;
KW   Kinase; Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW   Reference proteome; Transferase.
FT   CHAIN           1..614
FT                   /note="Bifunctional 3'-phosphoadenosine 5'-phosphosulfate
FT                   synthase 2"
FT                   /id="PRO_0000105961"
FT   REGION          1..215
FT                   /note="Adenylyl-sulfate kinase"
FT                   /evidence="ECO:0000305"
FT   REGION          224..614
FT                   /note="Sulfate adenylyltransferase"
FT                   /evidence="ECO:0000305"
FT   BINDING         52..57
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|Ref.12, ECO:0007744|PDB:2AX4"
FT   BINDING         79..82
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         91
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         96..99
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         122..123
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         161
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         174..175
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         197
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|Ref.12, ECO:0007744|PDB:2AX4"
FT   BINDING         409..412
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         511..515
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         553
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   VAR_SEQ         288
FT                   /note="D -> DGMALP (in isoform B)"
FT                   /evidence="ECO:0000303|PubMed:10559207, ECO:0000303|Ref.6"
FT                   /id="VSP_001259"
FT   VARIANT         10
FT                   /note="E -> K (decreased sulfate assimilation;
FT                   dbSNP:rs17173698)"
FT                   /evidence="ECO:0000269|PubMed:11773860"
FT                   /id="VAR_029136"
FT   VARIANT         43
FT                   /note="C -> Y (in BCYM4; reduced 3'-phosphoadenosine 5'-
FT                   phosphosulfate biosynthetic process)"
FT                   /evidence="ECO:0000269|PubMed:23824674"
FT                   /id="VAR_073026"
FT   VARIANT         48
FT                   /note="T -> R (in BCYM4; patient with premature pubarche
FT                   and hyperandrogenism; decreased sulfate assimilation;
FT                   increases ubiquitin-dependent protein instability;
FT                   dbSNP:rs121908951)"
FT                   /evidence="ECO:0000269|PubMed:19474428,
FT                   ECO:0000269|PubMed:25594860"
FT                   /id="VAR_063049"
FT   VARIANT         76
FT                   /note="L -> Q (in BCYM4; reduced 3'-phosphoadenosine 5'-
FT                   phosphosulfate biosynthetic process)"
FT                   /evidence="ECO:0000269|PubMed:23824674"
FT                   /id="VAR_073027"
FT   VARIANT         183
FT                   /note="E -> K (no effect on 3'-phosphoadenosine 5'-
FT                   phosphosulfate biosynthetic process; dbSNP:rs774709274)"
FT                   /evidence="ECO:0000269|PubMed:23824674"
FT                   /id="VAR_073028"
FT   VARIANT         270
FT                   /note="G -> D (in BCYM4; increases ubiquitin-dependent
FT                   protein instability; dbSNP:rs138943074)"
FT                   /evidence="ECO:0000269|PubMed:25594860"
FT                   /id="VAR_073029"
FT   VARIANT         281
FT                   /note="M -> L (in dbSNP:rs45624631)"
FT                   /evidence="ECO:0000269|PubMed:11773860"
FT                   /id="VAR_029137"
FT   VARIANT         291
FT                   /note="V -> M (decreased sulfate assimilation;
FT                   dbSNP:rs45467596)"
FT                   /evidence="ECO:0000269|PubMed:11773860"
FT                   /id="VAR_022077"
FT   VARIANT         432
FT                   /note="R -> K (in dbSNP:rs17129133)"
FT                   /evidence="ECO:0000269|PubMed:11773860"
FT                   /id="VAR_029138"
FT   CONFLICT        166
FT                   /note="R -> K (in Ref. 2; AAD38423)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        361
FT                   /note="E -> G (in Ref. 3; AAK00296)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        426
FT                   /note="R -> C (in Ref. 1; AAC64583)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        567
FT                   /note="P -> L (in Ref. 2; AAD38423)"
FT                   /evidence="ECO:0000305"
FT   HELIX           27..33
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          34..37
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          43..48
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           55..68
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          73..76
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           78..81
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   TURN            82..88
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           93..113
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          116..120
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           126..138
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          143..149
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           152..158
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          160..162
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           163..168
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          171..174
FT                   /evidence="ECO:0007829|PDB:8I1N"
FT   TURN            176..178
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   STRAND          189..193
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   TURN            194..196
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           199..212
FT                   /evidence="ECO:0007829|PDB:8I1O"
FT   HELIX           231..233
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           234..241
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          246..248
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           251..261
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   TURN            262..267
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           274..283
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          284..286
FT                   /evidence="ECO:0007829|PDB:7FHA"
FT   STRAND          287..290
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          300..302
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           304..310
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          314..320
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          323..335
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           338..346
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           354..360
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          364..375
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           384..386
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           390..399
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          403..412
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           416..431
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          437..444
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           455..467
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           473..475
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          476..478
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           489..502
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          506..509
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   TURN            520..522
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          524..527
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           531..538
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          546..548
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          553..556
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   TURN            557..560
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   STRAND          561..564
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           567..572
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           578..586
FT                   /evidence="ECO:0007829|PDB:7FH3"
FT   HELIX           598..610
FT                   /evidence="ECO:0007829|PDB:7FH3"
SQ   SEQUENCE   614 AA;  69501 MW;  52F4B6D972DDA91E CRC64;
     MSGIKKQKTE NQQKSTNVVY QAHHVSRNKR GQVVGTRGGF RGCTVWLTGL SGAGKTTISF
     ALEEYLVSHA IPCYSLDGDN VRHGLNRNLG FSPGDREENI RRIAEVAKLF ADAGLVCITS
     FISPFAKDRE NARKIHESAG LPFFEIFVDA PLNICESRDV KGLYKRARAG EIKGFTGIDS
     DYEKPETPER VLKTNLSTVS DCVHQVVELL QEQNIVPYTI IKDIHELFVP ENKLDHVRAE
     AETLPSLSIT KLDLQWVQVL SEGWATPLKG FMREKEYLQV MHFDTLLDDG VINMSIPIVL
     PVSAEDKTRL EGCSKFVLAH GGRRVAILRD AEFYEHRKEE RCSRVWGTTC TKHPHIKMVM
     ESGDWLVGGD LQVLEKIRWN DGLDQYRLTP LELKQKCKEM NADAVFAFQL RNPVHNGHAL
     LMQDTRRRLL ERGYKHPVLL LHPLGGWTKD DDVPLDWRMK QHAAVLEEGV LDPKSTIVAI
     FPSPMLYAGP TEVQWHCRSR MIAGANFYIV GRDPAGMPHP ETKKDLYEPT HGGKVLSMAP
     GLTSVEIIPF RVAAYNKAKK AMDFYDPARH NEFDFISGTR MRKLAREGEN PPDGFMAPKA
     WKVLTDYYRS LEKN
//
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