PAPS2_MOUSE
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 03-AUG-2022, entry version 157.
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 EPD; O88428; -.
DR jPOST; O88428; -.
DR MaxQB; O88428; -.
DR PaxDb; O88428; -.
DR PeptideAtlas; O88428; -.
DR PRIDE; O88428; -.
DR ProteomicsDB; 288059; -.
DR Antibodypedia; 30161; 253 antibodies from 25 providers.
DR DNASU; 23972; -.
DR Ensembl; ENSMUST00000025833; ENSMUSP00000025833; ENSMUSG00000024899.
DR GeneID; 23972; -.
DR KEGG; mmu:23972; -.
DR UCSC; uc008hfl.2; mouse.
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; DQMYERP; -.
DR OrthoDB; 528280at2759; -.
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 72 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 315 other tissues.
DR ExpressionAtlas; O88428; baseline and differential.
DR Genevisible; O88428; MM.
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; 3.40.50.300; -; 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 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
