PAPS1_HUMAN
ID PAPS1_HUMAN Reviewed; 624 AA.
AC O43252; O43841; O75332; Q6IAX6; Q96FB1; Q96TF4; Q9P1P9; Q9UE98;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1;
DE Short=PAPS synthase 1;
DE Short=PAPSS 1;
DE AltName: Full=Sulfurylase kinase 1;
DE Short=SK 1;
DE Short=SK1;
DE Includes:
DE RecName: Full=Sulfate adenylyltransferase;
DE EC=2.7.7.4 {ECO:0000269|PubMed:14747722, ECO:0000269|PubMed:9576487, ECO:0000269|PubMed:9648242, ECO:0000269|PubMed:9668121};
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 {ECO:0000269|PubMed:14747722, ECO:0000269|PubMed:17276460, ECO:0000269|PubMed:17540769, ECO:0000269|PubMed:9576487, ECO:0000269|PubMed:9648242, ECO:0000269|PubMed:9668121};
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=PAPSS1; Synonyms=ATPSK1, PAPSS;
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Tonsil;
RX PubMed=9576487; DOI=10.1096/fasebj.12.7.603;
RA Girard J.-P., Baekkevold E.S., Amalric F.;
RT "Sulfation in high endothelial venules: cloning and expression of the human
RT PAPS synthetase.";
RL FASEB J. 12:603-612(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP AND VARIANTS PHE-270 AND LEU-587.
RC TISSUE=Fetal brain;
RX PubMed=9668121; DOI=10.1074/jbc.273.30.19311;
RA Venkatachalam K.V., Akita H., Strott C.A.;
RT "Molecular cloning, expression, and characterization of human bifunctional
RT 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional
RT domains.";
RL J. Biol. Chem. 273:19311-19320(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC TISSUE=Brain;
RX PubMed=9648242; DOI=10.1271/bbb.62.1037;
RA Yanagisawa K., Sakakibara Y., Suiko M., Takami Y., Nakayama T.,
RA Nakajima H., Takayanagi K., Natori Y., Liu M.-C.;
RT "cDNA cloning, expression, and characterization of the human bifunctional
RT ATP sulfurylase/adenosine 5'-phosphosulfate kinase enzyme.";
RL Biosci. Biotechnol. Biochem. 62:1037-1040(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-587.
RA Deyrup A.T.;
RT "Human ATP sulfurylase/APS kinase.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT LEU-587.
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea {ECO:0000312|EMBL:BAF85463.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Uterus;
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 [10]
RP MUTAGENESIS OF HIS-425; ASN-426; GLY-427 AND HIS-428.
RX PubMed=9915785; DOI=10.1074/jbc.274.5.2601;
RA Venkatachalam K.V., Fuda H., Koonin E.V., Strott C.A.;
RT "Site-selected mutagenesis of a conserved nucleotide binding HXGH motif
RT located in the ATP sulfurylase domain of human bifunctional 3'-
RT phosphoadenosine 5'-phosphosulfate synthase.";
RL J. Biol. Chem. 274:2601-2604(1999).
RN [11]
RP CRYSTALLIZATION, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND PATHWAY.
RX PubMed=14747722; DOI=10.1107/s0907444903027628;
RA Harjes S., Scheidig A., Bayer P.;
RT "Expression, purification and crystallization of human 3'-phosphoadenosine-
RT 5'-phosphosulfate synthetase 1.";
RL Acta Crystallogr. D 60:350-352(2004).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEXES WITH ATP ANALOGS,
RP SUBUNIT, AND DOMAIN.
RX PubMed=15755455; DOI=10.1016/j.jmb.2005.01.005;
RA Harjes S., Bayer P., Scheidig A.J.;
RT "The crystal structure of human PAPS synthetase 1 reveals asymmetry in
RT substrate binding.";
RL J. Mol. Biol. 347:623-635(2005).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 51-226 IN COMPLEXES WITH ATP AND
RP 3'-PHOSPHO-5'-ADENYLYL SULFATE ANALOGS, CATALYTIC ACTIVITY, SUBUNIT,
RP MUTAGENESIS OF ARG-37 AND ARG-40, DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=17540769; DOI=10.1074/jbc.m701713200;
RA Sekulic N., Konrad M., Lavie A.;
RT "Structural mechanism for substrate inhibition of the adenosine 5'-
RT phosphosulfate kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate
RT synthetase 1 and its ramifications for enzyme regulation.";
RL J. Biol. Chem. 282:22112-22121(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 25-227 IN COMPLEXES WITH
RP 3'-PHOSPHO-5'-ADENYLYL SULFATE AND ADENOSINE-5'-PHOSPHOSULFATE, CATALYTIC
RP ACTIVITY, AND DOMAIN.
RX PubMed=17276460; DOI=10.1016/j.jmb.2007.01.025;
RA Sekulic N., Dietrich K., Paarmann I., Ort S., Konrad M., Lavie A.;
RT "Elucidation of the active conformation of the APS-kinase domain of human
RT PAPS synthetase 1.";
RL J. Mol. Biol. 367:488-500(2007).
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 (PubMed:9576487,
CC PubMed:9668121, PubMed:9648242, PubMed:14747722). Required for normal
CC biosynthesis of sulfated L-selectin ligands in endothelial cells
CC (PubMed:9576487). {ECO:0000269|PubMed:14747722,
CC ECO:0000269|PubMed:9576487, ECO:0000269|PubMed:9648242,
CC ECO:0000269|PubMed:9668121}.
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:0000269|PubMed:14747722,
CC ECO:0000269|PubMed:9576487, ECO:0000269|PubMed:9648242,
CC ECO:0000269|PubMed:9668121};
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:0000269|PubMed:14747722, ECO:0000269|PubMed:17276460,
CC ECO:0000269|PubMed:17540769, ECO:0000269|PubMed:9576487,
CC ECO:0000269|PubMed:9648242, ECO:0000269|PubMed:9668121};
CC -!- ACTIVITY REGULATION: Inhibited by chlorate (PubMed:9576487). The kinase
CC activity is subject to inhibition by the substrate adenylyl sulfate
CC (PubMed:17540769). {ECO:0000269|PubMed:17540769,
CC ECO:0000269|PubMed:9576487}.
CC -!- PATHWAY: Sulfur metabolism; sulfate assimilation.
CC {ECO:0000269|PubMed:14747722, ECO:0000269|PubMed:9576487,
CC ECO:0000269|PubMed:9648242, ECO:0000269|PubMed:9668121}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:14747722,
CC ECO:0000269|PubMed:15755455, ECO:0000269|PubMed:17540769}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, pancreas, kidney, thymus,
CC prostate, ovary, small intestine, colon, leukocytes and liver. Also
CC expressed in high endothelial venules (HEV) cells and in cartilage.
CC {ECO:0000269|PubMed:9576487}.
CC -!- DOMAIN: The N-terminal first 50 residues are required for inhibition by
CC the substrate adenylyl sulfate. {ECO:0000269|PubMed:17540769}.
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; Y10387; CAA71413.1; -; mRNA.
DR EMBL; U53447; AAC39894.1; -; Genomic_DNA.
DR EMBL; AF033026; AAC28429.1; -; mRNA.
DR EMBL; AF016496; AAD09325.1; -; mRNA.
DR EMBL; AF105227; AAF40236.1; -; mRNA.
DR EMBL; AF097721; AAF40235.1; -; Genomic_DNA.
DR EMBL; AF097710; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097711; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097712; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097713; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097714; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097715; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097716; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097717; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097718; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097719; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AF097720; AAF40235.1; JOINED; Genomic_DNA.
DR EMBL; AK292774; BAF85463.1; -; mRNA.
DR EMBL; CR457028; CAG33309.1; -; mRNA.
DR EMBL; CH471057; EAX06210.1; -; Genomic_DNA.
DR EMBL; BC011392; AAH11392.1; -; mRNA.
DR EMBL; BC050627; AAH50627.1; -; mRNA.
DR CCDS; CCDS3676.1; -.
DR PIR; JW0087; JW0087.
DR RefSeq; NP_005434.4; NM_005443.4.
DR RefSeq; XP_011530702.1; XM_011532400.1.
DR RefSeq; XP_011530703.1; XM_011532401.1.
DR PDB; 1X6V; X-ray; 1.75 A; A/B=1-624.
DR PDB; 1XJQ; X-ray; 2.06 A; A/B=1-624.
DR PDB; 1XNJ; X-ray; 1.98 A; A/B=1-624.
DR PDB; 2OFW; X-ray; 2.05 A; A/B/C/D/E/F/G/H=24-225.
DR PDB; 2OFX; X-ray; 1.90 A; A/B=25-227.
DR PDB; 2PEY; X-ray; 1.88 A; A/B=51-226.
DR PDB; 2PEZ; X-ray; 1.40 A; A/B=51-226.
DR PDB; 2QJF; X-ray; 2.20 A; A/B=220-624.
DR PDBsum; 1X6V; -.
DR PDBsum; 1XJQ; -.
DR PDBsum; 1XNJ; -.
DR PDBsum; 2OFW; -.
DR PDBsum; 2OFX; -.
DR PDBsum; 2PEY; -.
DR PDBsum; 2PEZ; -.
DR PDBsum; 2QJF; -.
DR AlphaFoldDB; O43252; -.
DR SMR; O43252; -.
DR BioGRID; 114522; 67.
DR IntAct; O43252; 26.
DR STRING; 9606.ENSP00000265174; -.
DR DrugBank; DB03708; Adenosine 5'-phosphosulfate.
DR DrugBank; DB02661; Adenosine-5'-diphosphate-2',3'-vanadate.
DR DrugBank; DB09462; Glycerin.
DR GlyGen; O43252; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43252; -.
DR MetOSite; O43252; -.
DR PhosphoSitePlus; O43252; -.
DR BioMuta; PAPSS1; -.
DR CPTAC; CPTAC-248; -.
DR CPTAC; CPTAC-249; -.
DR EPD; O43252; -.
DR jPOST; O43252; -.
DR MassIVE; O43252; -.
DR PaxDb; O43252; -.
DR PeptideAtlas; O43252; -.
DR PRIDE; O43252; -.
DR ProteomicsDB; 48837; -.
DR Antibodypedia; 26233; 176 antibodies from 28 providers.
DR DNASU; 9061; -.
DR Ensembl; ENST00000265174.5; ENSP00000265174.4; ENSG00000138801.9.
DR GeneID; 9061; -.
DR KEGG; hsa:9061; -.
DR MANE-Select; ENST00000265174.5; ENSP00000265174.4; NM_005443.5; NP_005434.4.
DR UCSC; uc003hyk.4; human.
DR CTD; 9061; -.
DR DisGeNET; 9061; -.
DR GeneCards; PAPSS1; -.
DR HGNC; HGNC:8603; PAPSS1.
DR HPA; ENSG00000138801; Low tissue specificity.
DR MIM; 603262; gene.
DR neXtProt; NX_O43252; -.
DR OpenTargets; ENSG00000138801; -.
DR PharmGKB; PA384; -.
DR VEuPathDB; HostDB:ENSG00000138801; -.
DR eggNOG; KOG4238; Eukaryota.
DR GeneTree; ENSGT00390000009613; -.
DR HOGENOM; CLU_009463_3_0_1; -.
DR OMA; ESQCKKV; -.
DR OrthoDB; 528280at2759; -.
DR PhylomeDB; O43252; -.
DR TreeFam; TF313143; -.
DR BioCyc; MetaCyc:HS06566-MON; -.
DR BRENDA; 2.7.1.25; 2681.
DR BRENDA; 2.7.7.4; 2681.
DR PathwayCommons; O43252; -.
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-6802952; Signaling by BRAF and RAF1 fusions.
DR SABIO-RK; O43252; -.
DR SignaLink; O43252; -.
DR UniPathway; UPA00097; -.
DR BioGRID-ORCS; 9061; 18 hits in 1085 CRISPR screens.
DR ChiTaRS; PAPSS1; human.
DR EvolutionaryTrace; O43252; -.
DR GeneWiki; PAPSS1; -.
DR GenomeRNAi; 9061; -.
DR Pharos; O43252; Tbio.
DR PRO; PR:O43252; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O43252; protein.
DR Bgee; ENSG00000138801; Expressed in inferior vagus X ganglion and 209 other tissues.
DR Genevisible; O43252; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004020; F:adenylylsulfate kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016779; F:nucleotidyltransferase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0004781; F:sulfate adenylyltransferase (ATP) activity; IDA:UniProtKB.
DR GO; GO:0050428; P:3'-phosphoadenosine 5'-phosphosulfate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0000103; P:sulfate assimilation; IDA:UniProtKB.
DR CDD; cd02027; APSK; 1.
DR CDD; cd00517; ATPS; 1.
DR Gene3D; 3.40.50.300; -; 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; Acetylation; ATP-binding; Kinase; Multifunctional enzyme;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT CHAIN 1..624
FT /note="Bifunctional 3'-phosphoadenosine 5'-phosphosulfate
FT synthase 1"
FT /id="PRO_0000105959"
FT REGION 1..225
FT /note="Adenylyl-sulfate kinase"
FT /evidence="ECO:0000305|PubMed:15755455,
FT ECO:0000305|PubMed:17276460, ECO:0000305|PubMed:17540769"
FT REGION 234..624
FT /note="Sulfate adenylyltransferase"
FT /evidence="ECO:0000305|PubMed:15755455"
FT BINDING 62..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15755455,
FT ECO:0000269|PubMed:17276460, ECO:0000269|PubMed:17540769,
FT ECO:0007744|PDB:1X6V, ECO:0007744|PDB:1XJQ,
FT ECO:0007744|PDB:1XNJ, ECO:0007744|PDB:2OFX,
FT ECO:0007744|PDB:2PEY, ECO:0007744|PDB:2PEZ"
FT BINDING 89..92
FT /ligand="adenosine 5'-phosphosulfate"
FT /ligand_id="ChEBI:CHEBI:58243"
FT /evidence="ECO:0000305|PubMed:17276460,
FT ECO:0007744|PDB:2OFX"
FT BINDING 101
FT /ligand="adenosine 5'-phosphosulfate"
FT /ligand_id="ChEBI:CHEBI:58243"
FT /evidence="ECO:0000305|PubMed:17276460,
FT ECO:0007744|PDB:2OFX"
FT BINDING 106..109
FT /ligand="adenosine 5'-phosphosulfate"
FT /ligand_id="ChEBI:CHEBI:58243"
FT /evidence="ECO:0000305|PubMed:17276460,
FT ECO:0000305|PubMed:17540769, ECO:0007744|PDB:2OFX,
FT ECO:0007744|PDB:2PEZ"
FT BINDING 132..133
FT /ligand="adenosine 5'-phosphosulfate"
FT /ligand_id="ChEBI:CHEBI:58243"
FT /evidence="ECO:0000305|PubMed:17276460,
FT ECO:0000305|PubMed:17540769, ECO:0007744|PDB:2OFX,
FT ECO:0007744|PDB:2PEZ"
FT BINDING 171
FT /ligand="adenosine 5'-phosphosulfate"
FT /ligand_id="ChEBI:CHEBI:58243"
FT /evidence="ECO:0000305|PubMed:17276460,
FT ECO:0007744|PDB:2OFX"
FT BINDING 184..185
FT /ligand="adenosine 5'-phosphosulfate"
FT /ligand_id="ChEBI:CHEBI:58243"
FT /evidence="ECO:0000305|PubMed:17276460,
FT ECO:0000305|PubMed:17540769, ECO:0007744|PDB:2OFX,
FT ECO:0007744|PDB:2PEZ"
FT BINDING 207
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15755455,
FT ECO:0000269|PubMed:17276460, ECO:0000269|PubMed:17540769,
FT ECO:0007744|PDB:1X6V, ECO:0007744|PDB:1XJQ,
FT ECO:0007744|PDB:1XNJ, ECO:0007744|PDB:2OFW,
FT ECO:0007744|PDB:2OFX, ECO:0007744|PDB:2PEY,
FT ECO:0007744|PDB:2PEZ"
FT BINDING 212
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17276460,
FT ECO:0007744|PDB:2OFX"
FT BINDING 419..422
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15755455,
FT ECO:0007744|PDB:1XJQ, ECO:0007744|PDB:1XNJ,
FT ECO:0007744|PDB:2QJF"
FT BINDING 521..525
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15755455,
FT ECO:0007744|PDB:1XJQ, ECO:0007744|PDB:1XNJ,
FT ECO:0007744|PDB:2QJF"
FT BINDING 563
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15755455,
FT ECO:0007744|PDB:1XJQ, ECO:0007744|PDB:1XNJ,
FT ECO:0007744|PDB:2QJF"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 12
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60967"
FT VARIANT 270
FT /note="L -> F (in dbSNP:rs1127008)"
FT /evidence="ECO:0000269|PubMed:9668121"
FT /id="VAR_014065"
FT VARIANT 587
FT /note="S -> L (in dbSNP:rs1127014)"
FT /evidence="ECO:0000269|PubMed:10679223,
FT ECO:0000269|PubMed:9668121, ECO:0000269|Ref.4"
FT /id="VAR_014064"
FT MUTAGEN 37
FT /note="R->A: Abolishes inhibition by the substrate adenylyl
FT sulfate."
FT /evidence="ECO:0000269|PubMed:17540769"
FT MUTAGEN 40
FT /note="R->A: Abolishes inhibition by the substrate adenylyl
FT sulfate."
FT /evidence="ECO:0000269|PubMed:17540769"
FT MUTAGEN 425
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9915785"
FT MUTAGEN 426
FT /note="N->K: Increased activity."
FT /evidence="ECO:0000269|PubMed:9915785"
FT MUTAGEN 427..428
FT /note="GH->AA: Loss of activity."
FT MUTAGEN 427
FT /note="G->A: 30% decrease in activity."
FT /evidence="ECO:0000269|PubMed:9915785"
FT MUTAGEN 428
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9915785"
FT CONFLICT 456
FT /note="G -> A (in Ref. 1; CAA71413)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="Missing (in Ref. 2; AAC39894)"
FT /evidence="ECO:0000305"
FT CONFLICT 519..520
FT /note="IV -> MC (in Ref. 4; AAD09325)"
FT /evidence="ECO:0000305"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 65..78
FT /evidence="ECO:0007829|PDB:2PEZ"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:2PEZ"
FT TURN 92..98
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 103..122
FT /evidence="ECO:0007829|PDB:2PEZ"
FT STRAND 126..130
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 136..148
FT /evidence="ECO:0007829|PDB:2PEZ"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 162..168
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:2PEZ"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:2OFX"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:2PEZ"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:2PEZ"
FT TURN 204..206
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 209..222
FT /evidence="ECO:0007829|PDB:2PEZ"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 261..271
FT /evidence="ECO:0007829|PDB:1X6V"
FT TURN 272..277
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 314..320
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 324..330
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 333..345
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 348..356
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 364..371
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 374..383
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 400..409
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 413..422
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 426..442
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 445..454
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 465..477
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 483..485
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 499..512
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 516..520
FT /evidence="ECO:0007829|PDB:1X6V"
FT TURN 530..532
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 534..537
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 541..548
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 556..559
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 563..566
FT /evidence="ECO:0007829|PDB:1X6V"
FT TURN 567..570
FT /evidence="ECO:0007829|PDB:1X6V"
FT STRAND 571..574
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 588..596
FT /evidence="ECO:0007829|PDB:1X6V"
FT HELIX 608..621
FT /evidence="ECO:0007829|PDB:1X6V"
SQ SEQUENCE 624 AA; 70833 MW; A3DC9B943E68CDD6 CRC64;
MEIPGSLCKK VKLSNNAQNW GMQRATNVTY QAHHVSRNKR GQVVGTRGGF RGCTVWLTGL
SGAGKTTVSM ALEEYLVCHG IPCYTLDGDN IRQGLNKNLG FSPEDREENV RRIAEVAKLF
ADAGLVCITS FISPYTQDRN NARQIHEGAS LPFFEVFVDA PLHVCEQRDV KGLYKKARAG
EIKGFTGIDS EYEKPEAPEL VLKTDSCDVN DCVQQVVELL QERDIVPVDA SYEVKELYVP
ENKLHLAKTD AETLPALKIN KVDMQWVQVL AEGWATPLNG FMREREYLQC LHFDCLLDGG
VINLSVPIVL TATHEDKERL DGCTAFALMY EGRRVAILRN PEFFEHRKEE RCARQWGTTC
KNHPYIKMVM EQGDWLIGGD LQVLDRVYWN DGLDQYRLTP TELKQKFKDM NADAVFAFQL
RNPVHNGHAL LMQDTHKQLL ERGYRRPVLL LHPLGGWTKD DDVPLMWRMK QHAAVLEEGV
LNPETTVVAI FPSPMMYAGP TEVQWHCRAR MVAGANFYIV GRDPAGMPHP ETGKDLYEPS
HGAKVLTMAP GLITLEIVPF RVAAYNKKKK RMDYYDSEHH EDFEFISGTR MRKLAREGQK
PPEGFMAPKA WTVLTEYYKS LEKA
