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Protein

Hyaluronan synthase 2

Gene

Has2

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

Functioni

Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction and it is particularly responsible for the synthesis of high molecular mass hyaluronan. Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development. May also play a role in vasculogenesis. High molecular mass hyaluronan also play a role in early contact inhibition a process which stops cell growth when cells come into contact with each other or the extracellular matrix.1 Publication

Catalytic activityi

UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-(nascent hyaluronan) = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-(nascent hyaluronan).1 Publication
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-(nascent hyaluronan) = UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-(nascent hyaluronan).1 Publication

Cofactori

Kineticsi

  1. KM=0.2 mM for UDP-Glc-NAc (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2)1 Publication
  2. KM=0.3 mM for UDP-Glc-UA (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2)1 Publication

    Pathway:ihyaluronan biosynthesis

    This protein is involved in the pathway hyaluronan biosynthesis, which is part of Glycan biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway hyaluronan biosynthesis and in Glycan biosynthesis.

    GO - Molecular functioni

    • hyaluronan synthase activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Glycosyltransferase, Transferase

    Enzyme and pathway databases

    BRENDAi2.4.1.212. 3474.
    UniPathwayiUPA00341.

    Protein family/group databases

    CAZyiGT2. Glycosyltransferase Family 2.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hyaluronan synthase 2 (EC:2.4.1.212)
    Alternative name(s):
    Hyaluronate synthase 2
    Hyaluronic acid synthase 2
    Short name:
    HA synthase 2
    Gene namesi
    Name:Has2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 15

    Organism-specific databases

    MGIiMGI:107821. Has2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1111CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei12 – 3221Helical; Name=1Sequence AnalysisAdd
    BLAST
    Topological domaini33 – 4513ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei46 – 6621Helical; Name=2Sequence AnalysisAdd
    BLAST
    Topological domaini67 – 374308CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei375 – 39521Helical; Name=3Sequence AnalysisAdd
    BLAST
    Topological domaini396 – 4027ExtracellularSequence Analysis
    Transmembranei403 – 42321Helical; Name=4Sequence AnalysisAdd
    BLAST
    Topological domaini424 – 4296CytoplasmicSequence Analysis
    Transmembranei430 – 45021Helical; Name=5Sequence AnalysisAdd
    BLAST
    Topological domaini451 – 47525ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei476 – 49621Helical; Name=6Sequence AnalysisAdd
    BLAST
    Topological domaini497 – 51014CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei511 – 53121Helical; Name=7Sequence AnalysisAdd
    BLAST
    Topological domaini532 – 55221ExtracellularSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    • cytoplasm Source: CACAO
    • integral component of plasma membrane Source: MGI
    Complete GO annotation...

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Embryonic lethal. At day E9.5, the distribution of homozygous embryos approaches Mendelian frequency while only occasional viable embryos were found at E10.5. Embryos exhibited growth retardation, scant numbers of red blood cells, and lacked vitelline vessels in the yolk sac. The visceral endoderm and mesoderm forming the yolk sac was not fused except at discrete foci. The heart was thinwalled and relatively bloodless, and often exhibited marked pericardial swelling. The heart lacks cardiac jelly, endocardial cushions and trabeculae. A marked reduction in vessels in homozygous embryos is also observed. Somites were present but distorted. Some of the E9.5 embryos had failed to turn, and exhibited posterior defects as well as cephalic mesenchyme abnormalities.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 552552Hyaluronan synthase 2PRO_0000197174Add
    BLAST

    Proteomic databases

    PRIDEiP70312.

    PTM databases

    PhosphoSiteiP70312.

    Expressioni

    Tissue specificityi

    Expressed in heart, brain, spleen, lung and skeletal muscle.

    Developmental stagei

    Detected from E7.5 through birth. At E8.5, predominantly expressed in the epithelium of the foregut diverticulum, the cephalic mesenchyme, the allantois, and in the myocardium and endocardium of the heart. At E9.5, prominent expression is detected in cephalic, foregut and periaortic mesenchymes, the septum transversum and the cardiovascular system. Also present in the atrial and ventricular endothelium and the myocardium of the atrioventricular canal region. By E10.5, highly expressed in endothelial cells in the atrioventricular canal and outflow tract that transform into mesenchymal cells and invade the underlying matrix. Later, expressed by mesenchymal cells during elevation of the secondary palate and by hypertrophic chondrocytes within epiphysial growth plates.1 Publication

    Gene expression databases

    BgeeiP70312.
    CleanExiMM_HAS2.
    GenevisibleiP70312. MM.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000062212.

    Structurei

    3D structure databases

    ProteinModelPortaliP70312.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the NodC/HAS family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1215.
    GeneTreeiENSGT00390000010337.
    HOGENOMiHOG000112847.
    HOVERGENiHBG000189.
    InParanoidiP70312.
    KOiK00752.
    OMAiTAYIMGY.
    OrthoDBiEOG77WWBZ.
    TreeFamiTF332506.

    Family and domain databases

    Gene3Di3.90.550.10. 1 hit.
    InterProiIPR001173. Glyco_trans_2-like.
    IPR026107. HAS/NodC.
    IPR028371. HAS2.
    IPR029044. Nucleotide-diphossugar_trans.
    [Graphical view]
    PANTHERiPTHR22913. PTHR22913. 1 hit.
    PTHR22913:SF7. PTHR22913:SF7. 1 hit.
    PfamiPF00535. Glycos_transf_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF53448. SSF53448. 2 hits.

    Sequencei

    Sequence statusi: Complete.

    P70312-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MHCERFLCVL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG
    60 70 80 90 100
    AFLASHLIIQ SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR
    110 120 130 140 150
    KCLQSVKRLT YPGIKVVMVI DGNSDDDLYM MDIFSEVMGR DKSATYIWKN
    160 170 180 190 200
    NFHEKGPGET EESHKESSQH VTQLVLSNKS ICIMQKWGGK REVMYTAFRA
    210 220 230 240 250
    LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG DVQILNKYDS
    260 270 280 290 300
    WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
    310 320 330 340 350
    NQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ
    360 370 380 390 400
    QTRWSKSYFR EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR
    410 420 430 440 450
    GKIWNILLFL LTVQLVGLIK SSFASCLRGN IVMVFMSLYS VLYMSSLLPA
    460 470 480 490 500
    KMFAIATINK AGWGTSGRKT IVVNFIGLIP VSVWFTILLG GVIFTIYKES
    510 520 530 540 550
    KKPFSESKQT VLIVGTLIYA CYWVMLLTLY VVLINKCGRR KKGQQYDMVL

    DV
    Length:552
    Mass (Da):63,510
    Last modified:July 27, 2011 - v4
    Checksum:iB840BABC6D2260D5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti138 – 1381M → I in AAC53309 (PubMed:8798545).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U52524 mRNA. Translation: AAC53309.2.
    U69695 mRNA. Translation: AAB17609.1.
    AK079729 mRNA. Translation: BAC37733.1.
    CH466545 Genomic DNA. Translation: EDL29280.1.
    BC080281 mRNA. Translation: AAH80281.1.
    U53222 Genomic DNA. Translation: AAC52651.1.
    CCDSiCCDS27480.1.
    RefSeqiNP_032242.3. NM_008216.3.
    UniGeneiMm.5148.

    Genome annotation databases

    EnsembliENSMUST00000050544; ENSMUSP00000062212; ENSMUSG00000022367.
    GeneIDi15117.
    KEGGimmu:15117.
    UCSCiuc007vsl.2. mouse.

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    an unexpected turn of events - Issue 155 of December 2013

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U52524 mRNA. Translation: AAC53309.2.
    U69695 mRNA. Translation: AAB17609.1.
    AK079729 mRNA. Translation: BAC37733.1.
    CH466545 Genomic DNA. Translation: EDL29280.1.
    BC080281 mRNA. Translation: AAH80281.1.
    U53222 Genomic DNA. Translation: AAC52651.1.
    CCDSiCCDS27480.1.
    RefSeqiNP_032242.3. NM_008216.3.
    UniGeneiMm.5148.

    3D structure databases

    ProteinModelPortaliP70312.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000062212.

    Protein family/group databases

    CAZyiGT2. Glycosyltransferase Family 2.

    PTM databases

    PhosphoSiteiP70312.

    Proteomic databases

    PRIDEiP70312.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000050544; ENSMUSP00000062212; ENSMUSG00000022367.
    GeneIDi15117.
    KEGGimmu:15117.
    UCSCiuc007vsl.2. mouse.

    Organism-specific databases

    CTDi3037.
    MGIiMGI:107821. Has2.

    Phylogenomic databases

    eggNOGiCOG1215.
    GeneTreeiENSGT00390000010337.
    HOGENOMiHOG000112847.
    HOVERGENiHBG000189.
    InParanoidiP70312.
    KOiK00752.
    OMAiTAYIMGY.
    OrthoDBiEOG77WWBZ.
    TreeFamiTF332506.

    Enzyme and pathway databases

    UniPathwayiUPA00341.
    BRENDAi2.4.1.212. 3474.

    Miscellaneous databases

    NextBioi287534.
    PROiP70312.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP70312.
    CleanExiMM_HAS2.
    GenevisibleiP70312. MM.

    Family and domain databases

    Gene3Di3.90.550.10. 1 hit.
    InterProiIPR001173. Glyco_trans_2-like.
    IPR026107. HAS/NodC.
    IPR028371. HAS2.
    IPR029044. Nucleotide-diphossugar_trans.
    [Graphical view]
    PANTHERiPTHR22913. PTHR22913. 1 hit.
    PTHR22913:SF7. PTHR22913:SF7. 1 hit.
    PfamiPF00535. Glycos_transf_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF53448. SSF53448. 2 hits.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular cloning and characterization of a putative mouse hyaluronan synthase."
      Spicer A.P., Augustine M.L., McDonald J.A.
      J. Biol. Chem. 271:23400-23406(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6J.
    2. Spicer A.P., Augustine M.L., McDonald J.A.
      Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO 138.
    3. "Coding sequence of a hyaluronan synthase homologue expressed during expansion of the mouse cumulus-oocyte complex."
      Fueloep C., Salustri A., Hascall V.C.
      Arch. Biochem. Biophys. 337:261-266(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: CD-1.
    4. "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.
      Tissue: Thymus.
    5. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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/6.
      Tissue: Brain.
    7. "Homologs of the Xenopus developmental gene DG42 are present in zebrafish and mouse and are involved in the synthesis of Nod-like chitin oligosaccharides during early embryogenesis."
      Semino C.E., Specht C.A., Raimondi A., Robbins P.W.
      Proc. Natl. Acad. Sci. U.S.A. 93:4548-4553(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 215-348.
      Strain: Swiss Webster.
      Tissue: Embryo.
    8. Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, KINETIC PARAMETERS.
    9. "Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme."
      Camenisch T.D., Spicer A.P., Brehm-Gibson T., Biesterfeldt J., Augustine M.L., Calabro A. Jr., Kubalak S., Klewer S.E., McDonald J.A.
      J. Clin. Invest. 106:349-360(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiHYAS2_MOUSE
    AccessioniPrimary (citable) accession number: P70312
    Secondary accession number(s): P70411, Q62405, Q68EF7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: July 27, 2011
    Last modified: July 22, 2015
    This is version 113 of the entry and version 4 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.