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O88428

- PAPS2_MOUSE

UniProt

O88428 - PAPS2_MOUSE

Protein

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2

Gene

Papss2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. May have a important role in skeletogenesis during postnatal growth.

    Catalytic activityi

    ATP + sulfate = diphosphate + adenylyl sulfate.
    ATP + adenylyl sulfate = ADP + 3'-phosphoadenylyl sulfate.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei124 – 1241Phosphoserine intermediateBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi50 – 578ATPSequence Analysis

    GO - Molecular functioni

    1. adenylylsulfate kinase activity Source: MGI
    2. ATP binding Source: UniProtKB-KW
    3. nucleotidyltransferase activity Source: UniProtKB
    4. sulfate adenylyltransferase (ATP) activity Source: UniProtKB

    GO - Biological processi

    1. blood coagulation Source: MGI
    2. bone development Source: MGI
    3. sulfate assimilation Source: MGI

    Keywords - Molecular functioni

    Kinase, Nucleotidyltransferase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_214239. Transport and synthesis of PAPS.
    UniPathwayiUPA00097.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2
    Short name:
    PAPS synthase 2
    Short name:
    PAPSS 2
    Alternative name(s):
    Sulfurylase kinase 2
    Short name:
    SK 2
    Short name:
    SK2
    Including the following 2 domains:
    Sulfate adenylyltransferase (EC:2.7.7.4)
    Alternative name(s):
    ATP-sulfurylase
    Sulfate adenylate transferase
    Short name:
    SAT
    Adenylyl-sulfate kinase (EC:2.7.1.25)
    Alternative name(s):
    3'-phosphoadenosine-5'-phosphosulfate synthase
    APS kinase
    Adenosine-5'-phosphosulfate 3'-phosphotransferase
    Adenylylsulfate 3'-phosphotransferase
    Gene namesi
    Name:Papss2
    Synonyms:Atpsk2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 19

    Organism-specific databases

    MGIiMGI:1330223. Papss2.

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Papss2 are the cause of brachymorphism (bm), a autosomal recessive disease, which is characterized by abnormal hepatic detoxification, bleeding times and postnatal growth, such as dome-shaped skull, short thick tail, and shortened but not widened limbs. The abnormal postnatal growth has been attributed to undersulfation of cartilage proteoglycans.

    Keywords - Diseasei

    Disease mutation

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 621621Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2PRO_0000105962Add
    BLAST

    Proteomic databases

    MaxQBiO88428.
    PaxDbiO88428.
    PRIDEiO88428.

    PTM databases

    PhosphoSiteiO88428.

    Expressioni

    Tissue specificityi

    Expressed in liver, cartilage, skin and brain.

    Gene expression databases

    BgeeiO88428.
    CleanExiMM_PAPSS2.
    GenevestigatoriO88428.

    Interactioni

    Protein-protein interaction databases

    IntActiO88428. 4 interactions.
    MINTiMINT-1856155.

    Structurei

    3D structure databases

    ProteinModelPortaliO88428.
    SMRiO88428. Positions 22-619.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – ?211211Adenylyl-sulfate kinaseAdd
    BLAST
    Regioni?212 – 621410Sulfate adenylyltransferaseAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi517 – 5215PP-motif

    Sequence similaritiesi

    In the N-terminal section; belongs to the APS kinase family.Curated
    In the C-terminal section; belongs to the sulfate adenylyltransferase family.Curated

    Phylogenomic databases

    eggNOGiCOG0529.
    GeneTreeiENSGT00390000009613.
    HOGENOMiHOG000069045.
    HOVERGENiHBG053503.
    InParanoidiQ5BKP4.
    KOiK13811.
    OMAiHGIPCYS.
    OrthoDBiEOG74TWZ4.
    TreeFamiTF313143.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    3.40.50.620. 1 hit.
    HAMAPiMF_00065. Adenylyl_sulf_kinase.
    InterProiIPR002891. APS_kinase.
    IPR025980. ATP-Sase_PUA-like_dom.
    IPR027417. P-loop_NTPase.
    IPR015947. PUA-like_domain.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR024951. Sulfurylase_cat_dom.
    IPR002650. Sulphate_adenylyltransferase.
    [Graphical view]
    PfamiPF01583. APS_kinase. 1 hit.
    PF01747. ATP-sulfurylase. 1 hit.
    PF14306. PUA_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    SSF88697. SSF88697. 1 hit.
    TIGRFAMsiTIGR00455. apsK. 1 hit.
    TIGR00339. sopT. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    O88428-1 [UniParc]FASTAAdd to Basket

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    MSANFKMNHK RDQQKSTNVV YQAHHVSRNK RGQVVGTRGG FRGCTVWLTG    50
    LSGAGKTTIS FALEEYLVSH AIPCYSLDGD NVRHGLNKNL GFSAGDREEN 100
    IRRIAEVARL FADAGLVCIT SFISPFAKDR ENARKIHESA GLPFFEIFVD 150
    APLNICESRD VKGLYKRARA GEIKGFTGID SDYEKPETPE CVLKTNLSSV 200
    SDCVQQVVEL LQEQNIVPHT TIKGIHELFV PENKVDQIRA EAETLPSLPI 250
    TKLDLQWVQI LSEGWATPLK GFMREKEYLQ TLHFDTLLDG VVPRDGVINM 300
    SIPIVLPVSA DDKARLEGCS KFALMYEGRR VALLQDPEFY EHRKEERCSR 350
    VWGTATAKHP HIKMVMESGD WLVGGDLQVL ERIRWDDGLD QYRLTPLELK 400
    QKCKDMNADA VFAFQLRNPV HNGHALLMQD TRRRLLERGY KHPVLLLHPL 450
    GGWTKDDDVP LEWRMKQHAA VLEERVLDPK STIVAIFPSP MLYAGPTEVQ 500
    WHCRCRMIAG ANFYIVGRDP AGMPHPETKK DLYEPTHGGK VLSMAPGLTS 550
    VEIIPFRVAA YNKIKKAMDF YDPARHEEFD FISGTRMRKL AREGEDPPDG 600
    FMAPKAWKVL TDYYRSLEKT N 621
    Length:621
    Mass (Da):70,351
    Last modified:July 27, 2011 - v2
    Checksum:i27FD5377A79EFD61
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti5 – 51F → S in AAC40191. (PubMed:9671738)Curated
    Sequence conflicti290 – 2945Missing in AAC98687. (PubMed:9771708)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti79 – 791G → R in bm; activity abolished. 2 Publications
    Natural varianti109 – 1091R → K.1 Publication

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF052453 mRNA. Translation: AAC40191.1.
    AF085144 mRNA. Translation: AAC98687.1.
    BC090997 mRNA. Translation: AAH90997.1.
    CCDSiCCDS37960.1.
    RefSeqiNP_035994.2. NM_011864.3.
    UniGeneiMm.203916.

    Genome annotation databases

    EnsembliENSMUST00000025833; ENSMUSP00000025833; ENSMUSG00000024899.
    GeneIDi23972.
    KEGGimmu:23972.
    UCSCiuc008hfl.2. mouse.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF052453 mRNA. Translation: AAC40191.1 .
    AF085144 mRNA. Translation: AAC98687.1 .
    BC090997 mRNA. Translation: AAH90997.1 .
    CCDSi CCDS37960.1.
    RefSeqi NP_035994.2. NM_011864.3.
    UniGenei Mm.203916.

    3D structure databases

    ProteinModelPortali O88428.
    SMRi O88428. Positions 22-619.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O88428. 4 interactions.
    MINTi MINT-1856155.

    PTM databases

    PhosphoSitei O88428.

    Proteomic databases

    MaxQBi O88428.
    PaxDbi O88428.
    PRIDEi O88428.

    Protocols and materials databases

    DNASUi 23972.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000025833 ; ENSMUSP00000025833 ; ENSMUSG00000024899 .
    GeneIDi 23972.
    KEGGi mmu:23972.
    UCSCi uc008hfl.2. mouse.

    Organism-specific databases

    CTDi 9060.
    MGIi MGI:1330223. Papss2.

    Phylogenomic databases

    eggNOGi COG0529.
    GeneTreei ENSGT00390000009613.
    HOGENOMi HOG000069045.
    HOVERGENi HBG053503.
    InParanoidi Q5BKP4.
    KOi K13811.
    OMAi HGIPCYS.
    OrthoDBi EOG74TWZ4.
    TreeFami TF313143.

    Enzyme and pathway databases

    UniPathwayi UPA00097 .
    Reactomei REACT_214239. Transport and synthesis of PAPS.

    Miscellaneous databases

    NextBioi 303861.
    PROi O88428.
    SOURCEi Search...

    Gene expression databases

    Bgeei O88428.
    CleanExi MM_PAPSS2.
    Genevestigatori O88428.

    Family and domain databases

    Gene3Di 3.40.50.300. 1 hit.
    3.40.50.620. 1 hit.
    HAMAPi MF_00065. Adenylyl_sulf_kinase.
    InterProi IPR002891. APS_kinase.
    IPR025980. ATP-Sase_PUA-like_dom.
    IPR027417. P-loop_NTPase.
    IPR015947. PUA-like_domain.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR024951. Sulfurylase_cat_dom.
    IPR002650. Sulphate_adenylyltransferase.
    [Graphical view ]
    Pfami PF01583. APS_kinase. 1 hit.
    PF01747. ATP-sulfurylase. 1 hit.
    PF14306. PUA_2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 1 hit.
    SSF88697. SSF88697. 1 hit.
    TIGRFAMsi TIGR00455. apsK. 1 hit.
    TIGR00339. sopT. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "A member of a new family of sulfate activating enzymes causes murine brachymorphism."
      Kurima K., Warman M.L., Krishnan S., Domowicz M., Krueger R.C. Jr., Deyrup A., Schwartz N.B.
      Proc. Natl. Acad. Sci. U.S.A. 95:8681-8685(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT BM ARG-79.
      Tissue: Liver.
    2. "Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse."
      ul Haque M.F., King L.M., Krakow D., Cantor R.M., Rusiniak M.E., Swank R.T., Superti-Furga A., Haque S., Abbas H., Ahmad W., Ahmad M., Cohn D.H.
      Nat. Genet. 20:157-162(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT BM ARG-79, VARIANT LYS-109.
      Strain: PWK.
      Tissue: Spleen.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.

    Entry informationi

    Entry nameiPAPS2_MOUSE
    AccessioniPrimary (citable) accession number: O88428
    Secondary accession number(s): Q5BKP4, Q9Z274
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 110 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3