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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   12-AUG-2020, entry version 196.
DE   RecName: Full=Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2;
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;
DE              EC=2.7.7.4;
DE     AltName: Full=ATP-sulfurylase;
DE     AltName: Full=Sulfate adenylate transferase;
DE              Short=SAT;
DE   Includes:
DE     RecName: Full=Adenylyl-sulfate kinase;
DE              EC=2.7.1.25;
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).
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>3.0.co;2-d;
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   TISSUE SPECIFICITY, VARIANT BCYM4 ARG-48, AND CHARACTERIZATION OF VARIANT
RP   BCYM4 ARG-48.
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   VARIANTS LYS-10; LEU-281; MET-291 AND LYS-432, AND CHARACTERIZATION OF
RP   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, AND CHARACTERIZATION OF VARIANT LYS-183.
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, AND CHARACTERIZATION OF VARIANTS BCYM4 ARG-48 AND
RP   ASP-270.
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'-phosphoadenylylsulfate
CC       (PAPS: activated sulfate donor used by sulfotransferase). In mammals,
CC       PAPS is the sole source of sulfate; APS appears to be only an
CC       intermediate in the sulfate-activation pathway. May have an important
CC       role in skeletogenesis during postnatal growth (By similarity).
CC       {ECO:0000250}.
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;
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   -!- PATHWAY: Sulfur metabolism; sulfate assimilation.
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   -!- 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}. Note=The disease is caused by mutations
CC       affecting the gene represented in this 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}.
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   PDBsum; 2AX4; -.
DR   SMR; O95340; -.
DR   BioGRID; 114521; 22.
DR   IntAct; O95340; 6.
DR   STRING; 9606.ENSP00000406157; -.
DR   BindingDB; O95340; -.
DR   ChEMBL; CHEMBL4105790; -.
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   PaxDb; O95340; -.
DR   PeptideAtlas; O95340; -.
DR   PRIDE; O95340; -.
DR   ProteomicsDB; 50808; -. [O95340-1]
DR   ProteomicsDB; 50809; -. [O95340-2]
DR   TopDownProteomics; O95340-1; -. [O95340-1]
DR   Antibodypedia; 30161; 233 antibodies.
DR   DNASU; 9060; -.
DR   Ensembl; ENST00000361175; ENSP00000354436; ENSG00000198682. [O95340-1]
DR   Ensembl; ENST00000456849; ENSP00000406157; ENSG00000198682. [O95340-2]
DR   GeneID; 9060; -.
DR   KEGG; hsa:9060; -.
DR   UCSC; uc001kew.4; human. [O95340-1]
DR   CTD; 9060; -.
DR   DisGeNET; 9060; -.
DR   EuPathDB; HostDB:ENSG00000198682.12; -.
DR   GeneCards; PAPSS2; -.
DR   HGNC; HGNC:8604; PAPSS2.
DR   HPA; ENSG00000198682; Tissue enhanced (adrenal gland, liver).
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   eggNOG; KOG4238; Eukaryota.
DR   GeneTree; ENSGT00390000009613; -.
DR   HOGENOM; CLU_009463_3_0_1; -.
DR   KO; K13811; -.
DR   OMA; TVNECIQ; -.
DR   OrthoDB; 528280at2759; -.
DR   PhylomeDB; O95340; -.
DR   TreeFam; TF313143; -.
DR   BioCyc; MetaCyc:HS07544-MONOMER; -.
DR   BRENDA; 2.7.1.25; 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   UniPathway; UPA00097; -.
DR   BioGRID-ORCS; 9060; 3 hits in 871 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 metanephros and 225 other 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; IEA:UniProtKB-EC.
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; IBA:GO_Central.
DR   GO; GO:0007596; P:blood coagulation; IEA:Ensembl.
DR   GO; GO:0060348; P:bone development; IEA:Ensembl.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   GO; GO:0000103; P:sulfate assimilation; IBA:GO_Central.
DR   CDD; cd02027; APSK; 1.
DR   CDD; cd00517; ATPS; 1.
DR   Gene3D; 3.40.50.620; -; 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   Pfam; PF01747; ATP-sulfurylase; 1.
DR   Pfam; PF14306; PUA_2; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   SUPFAM; SSF88697; SSF88697; 1.
DR   TIGRFAMs; TIGR00455; apsK; 1.
DR   TIGRFAMs; TIGR00339; sopT; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Disease mutation;
KW   Dwarfism; Kinase; Multifunctional enzyme; Nucleotide-binding;
KW   Nucleotidyltransferase; Polymorphism; Reference proteome; Transferase.
FT   CHAIN           1..614
FT                   /note="Bifunctional 3'-phosphoadenosine 5'-phosphosulfate
FT                   synthase 2"
FT                   /id="PRO_0000105961"
FT   NP_BIND         52..57
FT                   /note="ATP 1"
FT                   /evidence="ECO:0000244|PDB:2AX4, ECO:0000269|Ref.12"
FT   NP_BIND         409..412
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   NP_BIND         511..515
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   REGION          1..215
FT                   /note="Adenylyl-sulfate kinase"
FT                   /evidence="ECO:0000305"
FT   REGION          79..82
FT                   /note="Adenylyl sulfate binding"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   REGION          96..99
FT                   /note="Adenylyl sulfate binding"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   REGION          122..123
FT                   /note="Adenylyl sulfate binding"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   REGION          174..175
FT                   /note="Adenylyl sulfate binding"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   REGION          224..614
FT                   /note="Sulfate adenylyltransferase"
FT                   /evidence="ECO:0000305"
FT   BINDING         91
FT                   /note="Adenylyl sulfate"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         161
FT                   /note="Adenylyl sulfate"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         197
FT                   /note="ATP 1; via carbonyl oxygen"
FT                   /evidence="ECO:0000244|PDB:2AX4, ECO:0000269|Ref.12"
FT   BINDING         553
FT                   /note="ATP 2; via amide nitrogen and carbonyl oxygen"
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 (significant decrease of activity;
FT                   dbSNP:rs17173698)"
FT                   /evidence="ECO:0000269|PubMed:11773860"
FT                   /id="VAR_029136"
FT   VARIANT         43
FT                   /note="C -> Y (in BCYM4; reduces strongly PAPS synthase
FT                   activity)"
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; results in partial loss of activity;
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; reduces strongly PAPS synthase
FT                   activity)"
FT                   /evidence="ECO:0000269|PubMed:23824674"
FT                   /id="VAR_073027"
FT   VARIANT         183
FT                   /note="E -> K (polymorphism; similar PAPS synthase activity
FT                   as the wild-type; 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 (significant decrease of activity;
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:0000244|PDB:2AX4"
FT   STRAND          34..37
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   STRAND          43..48
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           55..68
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   STRAND          73..76
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           78..81
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   TURN            82..88
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           93..112
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   STRAND          116..120
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           126..138
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   STRAND          143..149
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           152..158
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   STRAND          160..162
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           163..168
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   TURN            176..178
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   STRAND          189..193
FT                   /evidence="ECO:0000244|PDB:2AX4"
FT   HELIX           199..212
FT                   /evidence="ECO:0000244|PDB:2AX4"
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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