ID   PAPS2_MOUSE             Reviewed;         621 AA.
AC   O88428; Q5BKP4; Q9Z274;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2 {ECO:0000305|PubMed:10559207};
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:10559207};
DE              EC=2.7.7.4 {ECO:0000269|PubMed:10559207};
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:10559207};
DE              EC=2.7.1.25 {ECO:0000269|PubMed:10559207};
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT BM ARG-79.
RC   TISSUE=Liver;
RX   PubMed=9671738; DOI=10.1073/pnas.95.15.8681;
RA   Kurima K., Warman M.L., Krishnan S., Domowicz M., Krueger R.C. Jr.,
RA   Deyrup A., Schwartz N.B.;
RT   "A member of a new family of sulfate activating enzymes causes murine
RT   brachymorphism.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:8681-8685(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT BM ARG-79, AND VARIANT
RP   LYS-109.
RC   STRAIN=PWK; TISSUE=Spleen;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND REGION.
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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, Liver, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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:10559207). In mammals, PAPS is the sole
CC       source of sulfate while APS appears to only be an intermediate in the
CC       sulfate-activation pathway. May have an important role in
CC       skeletogenesis during postnatal growth. {ECO:0000269|PubMed:10559207}.
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         Evidence={ECO:0000269|PubMed:10559207};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18134;
CC         Evidence={ECO:0000305|PubMed:10559207};
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:10559207};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24153;
CC         Evidence={ECO:0000305|PubMed:10559207};
CC   -!- PATHWAY: Sulfur metabolism; sulfate assimilation.
CC       {ECO:0000305|PubMed:10559207}.
CC   -!- TISSUE SPECIFICITY: Expressed in liver, cartilage, skin and brain.
CC   -!- DISEASE: Note=Defects in Papss2 are the cause of brachymorphism (bm), a
CC       autosomal recessive disease, which is characterized by abnormal hepatic
CC       detoxification, bleeding times and postnatal growth, such as dome-
CC       shaped skull, short thick tail, and shortened but not widened limbs.
CC       The abnormal postnatal growth has been attributed to undersulfation of
CC       cartilage proteoglycans.
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; AF052453; AAC40191.1; -; mRNA.
DR   EMBL; AF085144; AAC98687.1; -; mRNA.
DR   EMBL; BC090997; AAH90997.1; -; mRNA.
DR   CCDS; CCDS37960.1; -.
DR   RefSeq; NP_035994.2; NM_011864.3.
DR   AlphaFoldDB; O88428; -.
DR   SMR; O88428; -.
DR   STRING; 10090.ENSMUSP00000025833; -.
DR   iPTMnet; O88428; -.
DR   PhosphoSitePlus; O88428; -.
DR   SwissPalm; O88428; -.
DR   EPD; O88428; -.
DR   jPOST; O88428; -.
DR   MaxQB; O88428; -.
DR   PaxDb; 10090-ENSMUSP00000025833; -.
DR   PeptideAtlas; O88428; -.
DR   ProteomicsDB; 288059; -.
DR   Pumba; O88428; -.
DR   Antibodypedia; 30161; 303 antibodies from 25 providers.
DR   DNASU; 23972; -.
DR   Ensembl; ENSMUST00000025833.7; ENSMUSP00000025833.7; ENSMUSG00000024899.8.
DR   GeneID; 23972; -.
DR   KEGG; mmu:23972; -.
DR   UCSC; uc008hfl.2; mouse.
DR   AGR; MGI:1330223; -.
DR   CTD; 9060; -.
DR   MGI; MGI:1330223; Papss2.
DR   VEuPathDB; HostDB:ENSMUSG00000024899; -.
DR   eggNOG; KOG4238; Eukaryota.
DR   GeneTree; ENSGT00390000009613; -.
DR   HOGENOM; CLU_009463_3_0_1; -.
DR   InParanoid; O88428; -.
DR   OMA; TENCTPE; -.
DR   OrthoDB; 22780at2759; -.
DR   PhylomeDB; O88428; -.
DR   TreeFam; TF313143; -.
DR   Reactome; R-MMU-174362; Transport and synthesis of PAPS.
DR   UniPathway; UPA00097; -.
DR   BioGRID-ORCS; 23972; 0 hits in 77 CRISPR screens.
DR   ChiTaRS; Papss2; mouse.
DR   PRO; PR:O88428; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; O88428; Protein.
DR   Bgee; ENSMUSG00000024899; Expressed in prostate gland ventral lobe and 318 other cell types or tissues.
DR   ExpressionAtlas; O88428; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0004020; F:adenylylsulfate kinase activity; IDA:MGI.
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; IDA:MGI.
DR   GO; GO:0050428; P:3'-phosphoadenosine 5'-phosphosulfate biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0007596; P:blood coagulation; IMP:MGI.
DR   GO; GO:0060348; P:bone development; IMP:MGI.
DR   GO; GO:0042445; P:hormone metabolic process; ISO:MGI.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0000103; P:sulfate assimilation; IDA:MGI.
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.
DR   Genevisible; O88428; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Disease variant; Kinase; Multifunctional enzyme;
KW   Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW   Transferase.
FT   CHAIN           1..621
FT                   /note="Bifunctional 3'-phosphoadenosine 5'-phosphosulfate
FT                   synthase 2"
FT                   /id="PRO_0000105962"
FT   REGION          1..216
FT                   /note="Adenylyl-sulfate kinase"
FT                   /evidence="ECO:0000305"
FT   REGION          225..621
FT                   /note="Sulfate adenylyltransferase"
FT                   /evidence="ECO:0000305"
FT   BINDING         53..58
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         80..83
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         92
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         97..100
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         123..124
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         162
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         175..176
FT                   /ligand="adenosine 5'-phosphosulfate"
FT                   /ligand_id="ChEBI:CHEBI:58243"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         198
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:O95340"
FT   BINDING         415..418
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         517..521
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   BINDING         559
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:O43252"
FT   VARIANT         79
FT                   /note="G -> R (in bm; activity abolished)"
FT                   /evidence="ECO:0000269|PubMed:9671738,
FT                   ECO:0000269|PubMed:9771708"
FT   VARIANT         109
FT                   /note="R -> K"
FT                   /evidence="ECO:0000269|PubMed:9771708"
FT   CONFLICT        5
FT                   /note="F -> S (in Ref. 1; AAC40191)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        290..294
FT                   /note="Missing (in Ref. 2; AAC98687)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   621 AA;  70351 MW;  27FD5377A79EFD61 CRC64;
     MSANFKMNHK RDQQKSTNVV YQAHHVSRNK RGQVVGTRGG FRGCTVWLTG LSGAGKTTIS
     FALEEYLVSH AIPCYSLDGD NVRHGLNKNL GFSAGDREEN IRRIAEVARL FADAGLVCIT
     SFISPFAKDR ENARKIHESA GLPFFEIFVD APLNICESRD VKGLYKRARA GEIKGFTGID
     SDYEKPETPE CVLKTNLSSV SDCVQQVVEL LQEQNIVPHT TIKGIHELFV PENKVDQIRA
     EAETLPSLPI TKLDLQWVQI LSEGWATPLK GFMREKEYLQ TLHFDTLLDG VVPRDGVINM
     SIPIVLPVSA DDKARLEGCS KFALMYEGRR VALLQDPEFY EHRKEERCSR VWGTATAKHP
     HIKMVMESGD WLVGGDLQVL ERIRWDDGLD QYRLTPLELK QKCKDMNADA VFAFQLRNPV
     HNGHALLMQD TRRRLLERGY KHPVLLLHPL GGWTKDDDVP LEWRMKQHAA VLEERVLDPK
     STIVAIFPSP MLYAGPTEVQ WHCRCRMIAG ANFYIVGRDP AGMPHPETKK DLYEPTHGGK
     VLSMAPGLTS VEIIPFRVAA YNKIKKAMDF YDPARHEEFD FISGTRMRKL AREGEDPPDG
     FMAPKAWKVL TDYYRSLEKT N
//