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Protein

Hyaluronan synthase 1

Gene

Has1

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. Also able to catalyze the synthesis of chito-oligosaccharide depending on the substrate.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=0.8 mM for UDP-Glc-NAc (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2)1 Publication
  2. KM=0.7 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.
    ReactomeiREACT_299251. Hyaluronan biosynthesis and export.
    UniPathwayiUPA00341.

    Protein family/group databases

    CAZyiGT2. Glycosyltransferase Family 2.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hyaluronan synthase 1 (EC:2.4.1.212)
    Alternative name(s):
    Hyaluronate synthase 1
    Hyaluronic acid synthase 1
    Short name:
    HA synthase 1
    Gene namesi
    Name:Has1
    Synonyms:Has
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 17

    Organism-specific databases

    MGIiMGI:106590. Has1.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2424CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei25 – 4521Helical; Name=1Sequence AnalysisAdd
    BLAST
    Topological domaini46 – 516ExtracellularSequence Analysis
    Transmembranei52 – 7221Helical; Name=2Sequence AnalysisAdd
    BLAST
    Topological domaini73 – 404332CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei405 – 42521Helical; Name=3Sequence AnalysisAdd
    BLAST
    Topological domaini426 – 43510ExtracellularSequence Analysis
    Transmembranei436 – 45621Helical; Name=4Sequence AnalysisAdd
    BLAST
    Topological domaini457 – 4626CytoplasmicSequence Analysis
    Transmembranei463 – 48321Helical; Name=5Sequence AnalysisAdd
    BLAST
    Topological domaini484 – 50118ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei502 – 52221Helical; Name=6Sequence AnalysisAdd
    BLAST
    Topological domaini523 – 54523CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei546 – 56621Helical; Name=7Sequence AnalysisAdd
    BLAST
    Topological domaini567 – 58317ExtracellularSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi242 – 2421D → E: Loss of both activities. 1 Publication
    Mutagenesisi311 – 3111S → N: No effect. 1 Publication
    Mutagenesisi312 – 3121G → P: No effect. 1 Publication
    Mutagenesisi313 – 3131P → G: No effect. 1 Publication
    Mutagenesisi314 – 3141L → I: 75% decrease of both activities. 1 Publication
    Mutagenesisi314 – 3141L → V: Loss of HA activity. 1 Publication
    Mutagenesisi344 – 3441D → E: Loss of both activities. 1 Publication
    Mutagenesisi380 – 3801Q → N: 85%-90% decrease of both activities. 1 Publication
    Mutagenesisi383 – 3831R → K: 85%-90% decrease of both activities. 1 Publication
    Mutagenesisi384 – 3841W → Y: Loss of both activities. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 583583Hyaluronan synthase 1PRO_0000197170Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi489 – 4891N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PRIDEiQ61647.

    PTM databases

    PhosphoSiteiQ61647.

    Expressioni

    Gene expression databases

    BgeeiQ61647.
    CleanExiMM_HAS1.
    ExpressionAtlasiQ61647. baseline and differential.
    GenevisibleiQ61647. MM.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000003762.

    Structurei

    3D structure databases

    ProteinModelPortaliQ61647.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi81 – 844Poly-Ala
    Compositional biasi516 – 5194Poly-Leu

    Sequence similaritiesi

    Belongs to the NodC/HAS family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1215.
    GeneTreeiENSGT00390000010337.
    HOGENOMiHOG000112847.
    HOVERGENiHBG000189.
    InParanoidiQ61647.
    KOiK00752.
    OMAiRTHRCVC.
    OrthoDBiEOG77WWBZ.
    PhylomeDBiQ61647.
    TreeFamiTF332506.

    Family and domain databases

    Gene3Di3.90.550.10. 2 hits.
    InterProiIPR026107. HAS/NodC.
    IPR028385. HAS1.
    IPR029044. Nucleotide-diphossugar_trans.
    [Graphical view]
    PANTHERiPTHR22913. PTHR22913. 1 hit.
    PTHR22913:SF4. PTHR22913:SF4. 1 hit.
    SUPFAMiSSF53448. SSF53448. 2 hits.

    Sequencei

    Sequence statusi: Complete.

    Q61647-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MRQDMPKPSE AARCCSGLAR RALTIIFALL ILGLMTWAYA AGVPLASDRY
    60 70 80 90 100
    GLLAFGLYGA FLSAHLVAQS LFAYLEHRRV AAAARRSLAK GPLDAATARS
    110 120 130 140 150
    VALTISAYQE DPAYLRQCLT SARALLYPHT RLRVLMVVDG NRAEDLYMVD
    160 170 180 190 200
    MFREVFADED PATYVWDGNY HQPWEPAEAT GAVGEGAYRE VEAEDPGRLA
    210 220 230 240 250
    VEALVRTRRC VCVAQRWGGK REVMYTAFKA LGDSVDYVQV CDSDTRLDPM
    260 270 280 290 300
    ALLELVRVLD EDPRVGAVGG DVRILNPLDS WVSFLSSLRY WVAFNVERAC
    310 320 330 340 350
    QSYFHCVSCI SGPLGLYRNN LLQQFLEAWY NQKFLGTHCT FGDDRHLTNR
    360 370 380 390 400
    MLSMGYATKY TSRSRCYSET PSSFLRWLSQ QTRWSKSYFR EWLYNALWWH
    410 420 430 440 450
    RHHAWMTYEA VVSGLFPFFV AATVLRLFYA GRPWALLWVL LCVQGVALAK
    460 470 480 490 500
    AAFAAWLRGC VRMVLLSLYA PLYMCGLLPA KFLALVTMNQ SGWGTSGRKK
    510 520 530 540 550
    LAANYVPVLP LALWALLLLG GLARSVAQEA RADWSGPSRA AEAYHLAAGA
    560 570 580
    GAYVAYWVVM LTIYWVGVRR LCRRRSGGYR VQV
    Length:583
    Mass (Da):65,545
    Last modified:November 1, 1996 - v1
    Checksum:i7AF9273E7B314728
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D82964 mRNA. Translation: BAA11654.1.
    CCDSiCCDS37459.1.
    RefSeqiNP_032241.1. NM_008215.2.
    UniGeneiMm.255701.

    Genome annotation databases

    EnsembliENSMUST00000003762; ENSMUSP00000003762; ENSMUSG00000003665.
    GeneIDi15116.
    KEGGimmu:15116.
    UCSCiuc008apr.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D82964 mRNA. Translation: BAA11654.1.
    CCDSiCCDS37459.1.
    RefSeqiNP_032241.1. NM_008215.2.
    UniGeneiMm.255701.

    3D structure databases

    ProteinModelPortaliQ61647.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000003762.

    Protein family/group databases

    CAZyiGT2. Glycosyltransferase Family 2.

    PTM databases

    PhosphoSiteiQ61647.

    Proteomic databases

    PRIDEiQ61647.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000003762; ENSMUSP00000003762; ENSMUSG00000003665.
    GeneIDi15116.
    KEGGimmu:15116.
    UCSCiuc008apr.2. mouse.

    Organism-specific databases

    CTDi3036.
    MGIiMGI:106590. Has1.

    Phylogenomic databases

    eggNOGiCOG1215.
    GeneTreeiENSGT00390000010337.
    HOGENOMiHOG000112847.
    HOVERGENiHBG000189.
    InParanoidiQ61647.
    KOiK00752.
    OMAiRTHRCVC.
    OrthoDBiEOG77WWBZ.
    PhylomeDBiQ61647.
    TreeFamiTF332506.

    Enzyme and pathway databases

    UniPathwayiUPA00341.
    BRENDAi2.4.1.212. 3474.
    ReactomeiREACT_299251. Hyaluronan biosynthesis and export.

    Miscellaneous databases

    NextBioi287530.
    PROiQ61647.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ61647.
    CleanExiMM_HAS1.
    ExpressionAtlasiQ61647. baseline and differential.
    GenevisibleiQ61647. MM.

    Family and domain databases

    Gene3Di3.90.550.10. 2 hits.
    InterProiIPR026107. HAS/NodC.
    IPR028385. HAS1.
    IPR029044. Nucleotide-diphossugar_trans.
    [Graphical view]
    PANTHERiPTHR22913. PTHR22913. 1 hit.
    PTHR22913:SF4. PTHR22913:SF4. 1 hit.
    SUPFAMiSSF53448. SSF53448. 2 hits.
    ProtoNetiSearch...

    Publicationsi

    1. "Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase."
      Itano N., Kimata K.
      J. Biol. Chem. 271:9875-9878(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Lubec G., Sunyer B., Chen W.-Q.
      Submitted (JAN-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 199-206, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: OF1.
      Tissue: Hippocampus.
    3. Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, KINETIC PARAMETERS.
    4. "In vitro synthesis of hyaluronan by a single protein derived from mouse HAS1 gene and characterization of amino acid residues essential for the activity."
      Yoshida M., Itano N., Yamada Y., Kimata K.
      J. Biol. Chem. 275:497-506(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS.

    Entry informationi

    Entry nameiHYAS1_MOUSE
    AccessioniPrimary (citable) accession number: Q61647
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: November 1, 1996
    Last modified: July 22, 2015
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, 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

    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.