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Protein

Heparan sulfate 2-O-sulfotransferase 1

Gene

Hs2st1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the transfer of sulfate to the C2-position of selected hexuronic acid residues within the maturing heparan sulfate (HS). 2-O-sulfation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high-affinity ligand-binding interactions and signaling processes. Required for metanephric development of kidney formation, suggesting that 2-O-sulfation within HS is essential for signaling between ureteric bud and metanephric mesenchyme. Mediates 2-O-sulfation of both L-iduronyl and D-glucuronyl residues.3 Publications

Kineticsi

  1. KM=3.7 µM for iduronic acid-containing substrate disaccharide units1 Publication
  2. KM=19.3 µM for glucuronic acid-containing substrate disaccharide units1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei140 – 1401By similarity

    GO - Molecular functioni

    • heparan sulfate 2-O-sulfotransferase activity Source: MGI

    GO - Biological processi

    • heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process Source: MGI
    • heparin metabolic process Source: MGI
    • ureteric bud formation Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Enzyme and pathway databases

    ReactomeiR-MMU-2022928. HS-GAG biosynthesis.
    SABIO-RKQ8R3H7.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Heparan sulfate 2-O-sulfotransferase 1 (EC:2.8.2.-)
    Short name:
    2-O-sulfotransferase
    Short name:
    2-OST
    Short name:
    2OST
    Gene namesi
    Name:Hs2st1
    Synonyms:Hs2st
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 3

    Organism-specific databases

    MGIiMGI:1346049. Hs2st1.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1111CytoplasmicSequence analysisAdd
    BLAST
    Transmembranei12 – 2817Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
    BLAST
    Topological domaini29 – 356328LumenalSequence analysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Golgi apparatus, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice die in the neonatal period, exhibiting bilateral renal agenesis and defects of the eye and the skeleton. Uronate 2-O-sulfates are not detected in such mice, however, the domain structure of the HS is conserved, due to a compensatory increase in N- and 6-O-sulfation maintain the overall charge density.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 356356Heparan sulfate 2-O-sulfotransferase 1PRO_0000207675Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence analysis
    Glycosylationi127 – 1271N-linked (GlcNAc...)Sequence analysis
    Disulfide bondi201 ↔ 209By similarity
    Disulfide bondi222 ↔ 228By similarity

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    EPDiQ8R3H7.
    MaxQBiQ8R3H7.
    PaxDbiQ8R3H7.
    PRIDEiQ8R3H7.

    PTM databases

    PhosphoSiteiQ8R3H7.

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed at higher level in lung and brain. Weakly expressed in spleen.2 Publications

    Developmental stagei

    At 7.5 dpc, it is expressed in all three germ layers, although it appears to be more expressed in the embryonic ectoderm and the node. Widespread expression persists at 8.5 dpc, although it is clearly expressed at higher level in rhombomeres 2 and 4 and branchial arches 1 and 2 (which are populated by neural crest from these rhombomeres). At 10.5 dpc, the dorsal and ventral aspects of the neural tube, brain and midbrain-hindbrain junction show the most intense expression. A day later in development, elevated expression is found in the floor plate and the sclerotome. At 12.5 dpc, both the floor plate and the roofplate exhibit strong expression as the mesenchyme of the limb and of the developing whisker follicles. At 13.5 dpc, it is predominantly expressed in embryonic mesenchyme, especially at sites of epithelial-mesenchymal interactions such as the developing teeth and whisker follicles. Strong expression is also apparent in the perichondria of the cartilaginous skeleton, an important site for the regulation of skeletal differentiation.

    Gene expression databases

    BgeeiQ8R3H7.
    CleanExiMM_HS2ST1.
    ExpressionAtlasiQ8R3H7. baseline and differential.
    GenevisibleiQ8R3H7. MM.

    Interactioni

    Subunit structurei

    Homotrimer (By similarity). Interacts with the C5-epimerase GLCE.By similarity1 Publication

    Protein-protein interaction databases

    IntActiQ8R3H7. 1 interaction.
    MINTiMINT-4105542.
    STRINGi10090.ENSMUSP00000043066.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8R3H7.
    SMRiQ8R3H7. Positions 69-355.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the sulfotransferase 3 family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3922. Eukaryota.
    ENOG410XTA1. LUCA.
    GeneTreeiENSGT00530000063408.
    HOGENOMiHOG000220833.
    HOVERGENiHBG053202.
    InParanoidiQ8R3H7.
    KOiK02513.
    OMAiLPNQIQF.
    OrthoDBiEOG7PS1J6.
    PhylomeDBiQ8R3H7.
    TreeFamiTF315238.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR007734. Heparan_SO4_2-O-STrfase.
    IPR027417. P-loop_NTPase.
    IPR005331. Sulfotransferase.
    [Graphical view]
    PANTHERiPTHR12129. PTHR12129. 1 hit.
    PfamiPF03567. Sulfotransfer_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q8R3H7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MGLLRIMMPP KLQLLAVVAF AVAMLFLENQ IQKLEESRAK LERAIARHEV
    60 70 80 90 100
    REIEQRHTMD GPRQDATLDE EEDIIIIYNR VPKTASTSFT NIAYDLCAKN
    110 120 130 140 150
    RYHVLHINTT KNNPVMSLQD QVRFVKNITT WNEMKPGFYH GHISYLDFAK
    160 170 180 190 200
    FGVKKKPIYI NVIRDPIERL VSYYYFLRFG DDYRPGLRRR KQGDKKTFDE
    210 220 230 240 250
    CVAEGGSDCA PEKLWLQIPF FCGHSSECWN VGSRWAMDQA KSNLINEYFL
    260 270 280 290 300
    VGVTEELEDF IMLLEAALPR FFRGATDLYR TGKKSHLRKT TEKKLPTKQT
    310 320 330 340 350
    IAKLQQSDIW KMENEFYEFA LEQFQFIRAH AVREKDGDLY ILAQNFFYEK

    IYPKSN
    Length:356
    Mass (Da):41,813
    Last modified:June 7, 2005 - v2
    Checksum:iE83D315141E57475
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti271 – 2711F → V in AAC40135 (PubMed:9637690).Curated
    Sequence conflicti333 – 3331R → H in AAH25443 (PubMed:15489334).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF060178 mRNA. Translation: AAC40135.1.
    AF169243 mRNA. Translation: AAF59900.1.
    AK088698 mRNA. Translation: BAC40511.1.
    AK165112 mRNA. Translation: BAE38041.1.
    BC025443 mRNA. Translation: AAH25443.1.
    BC059008 mRNA. Translation: AAH59008.1.
    CCDSiCCDS17883.1.
    RefSeqiNP_035958.3. NM_011828.3.
    UniGeneiMm.12863.

    Genome annotation databases

    EnsembliENSMUST00000043325; ENSMUSP00000043066; ENSMUSG00000040151.
    GeneIDi23908.
    KEGGimmu:23908.
    UCSCiuc012cyx.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF060178 mRNA. Translation: AAC40135.1.
    AF169243 mRNA. Translation: AAF59900.1.
    AK088698 mRNA. Translation: BAC40511.1.
    AK165112 mRNA. Translation: BAE38041.1.
    BC025443 mRNA. Translation: AAH25443.1.
    BC059008 mRNA. Translation: AAH59008.1.
    CCDSiCCDS17883.1.
    RefSeqiNP_035958.3. NM_011828.3.
    UniGeneiMm.12863.

    3D structure databases

    ProteinModelPortaliQ8R3H7.
    SMRiQ8R3H7. Positions 69-355.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ8R3H7. 1 interaction.
    MINTiMINT-4105542.
    STRINGi10090.ENSMUSP00000043066.

    PTM databases

    PhosphoSiteiQ8R3H7.

    Proteomic databases

    EPDiQ8R3H7.
    MaxQBiQ8R3H7.
    PaxDbiQ8R3H7.
    PRIDEiQ8R3H7.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000043325; ENSMUSP00000043066; ENSMUSG00000040151.
    GeneIDi23908.
    KEGGimmu:23908.
    UCSCiuc012cyx.1. mouse.

    Organism-specific databases

    CTDi9653.
    MGIiMGI:1346049. Hs2st1.

    Phylogenomic databases

    eggNOGiKOG3922. Eukaryota.
    ENOG410XTA1. LUCA.
    GeneTreeiENSGT00530000063408.
    HOGENOMiHOG000220833.
    HOVERGENiHBG053202.
    InParanoidiQ8R3H7.
    KOiK02513.
    OMAiLPNQIQF.
    OrthoDBiEOG7PS1J6.
    PhylomeDBiQ8R3H7.
    TreeFamiTF315238.

    Enzyme and pathway databases

    ReactomeiR-MMU-2022928. HS-GAG biosynthesis.
    SABIO-RKQ8R3H7.

    Miscellaneous databases

    ChiTaRSiHs2st1. mouse.
    PROiQ8R3H7.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ8R3H7.
    CleanExiMM_HS2ST1.
    ExpressionAtlasiQ8R3H7. baseline and differential.
    GenevisibleiQ8R3H7. MM.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR007734. Heparan_SO4_2-O-STrfase.
    IPR027417. P-loop_NTPase.
    IPR005331. Sulfotransferase.
    [Graphical view]
    PANTHERiPTHR12129. PTHR12129. 1 hit.
    PfamiPF03567. Sulfotransfer_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase."
      Bullock S.L., Fletcher J.M., Beddington R.S.P., Wilson V.A.
      Genes Dev. 12:1894-1906(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
      Strain: C57BL/6J.
    2. "Expression of heparan sulphate L-iduronyl 2-O-sulphotransferase in human kidney 293 cells results in increased D-glucuronyl 2-O-sulphation."
      Rong J., Habuchi H., Kimata K., Lindahl U., Kusche-Gullberg M.
      Biochem. J. 346:463-468(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY.
      Tissue: Mast cell.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J and NOD.
      Tissue: Ovary and Thymus.
    4. "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].
      Strain: C57BL/6J and Czech II.
      Tissue: Brain and Mammary tumor.
    5. "Substrate specificity of the heparan sulfate hexuronic acid 2-O-sulfotransferase."
      Rong J., Habuchi H., Kimata K., Lindahl U., Kusche-Gullberg M.
      Biochemistry 40:5548-5555(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
    6. Cited for: FUNCTION.
    7. "Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase and 2-O-sulfotransferase interact in vivo."
      Pinhal M.A.S., Smith B., Olson S., Aikawa J., Kimata K., Esko J.D.
      Proc. Natl. Acad. Sci. U.S.A. 98:12984-12989(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH GLCE.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Lung.

    Entry informationi

    Entry nameiHS2ST_MOUSE
    AccessioniPrimary (citable) accession number: Q8R3H7
    Secondary accession number(s): O88464, Q3TNP7, Q9JLK2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: June 7, 2005
    Last modified: June 8, 2016
    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, Reference proteome

    Documents

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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.