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Database: UniProt
Entry: HYAS1_MOUSE
LinkDB: HYAS1_MOUSE
Original site: HYAS1_MOUSE 
ID   HYAS1_MOUSE             Reviewed;         583 AA.
AC   Q61647;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   08-MAY-2019, entry version 142.
DE   RecName: Full=Hyaluronan synthase 1;
DE            EC=2.4.1.212;
DE   AltName: Full=Hyaluronate synthase 1;
DE   AltName: Full=Hyaluronic acid synthase 1;
DE            Short=HA synthase 1;
GN   Name=Has1; Synonyms=Has;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8626618; DOI=10.1074/jbc.271.17.9875;
RA   Itano N., Kimata K.;
RT   "Expression cloning and molecular characterization of HAS protein, a
RT   eukaryotic hyaluronan synthase.";
RL   J. Biol. Chem. 271:9875-9878(1996).
RN   [2]
RP   PROTEIN SEQUENCE OF 199-206, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   KINETIC PARAMETERS.
RX   PubMed=10455188; DOI=10.1074/jbc.274.35.25085;
RA   Itano N., Sawai T., Yoshida M., Lenas P., Yamada Y., Imagawa M.,
RA   Shinomura T., Hamaguchi M., Yoshida Y., Ohnuki Y., Miyauchi S.,
RA   Spicer A.P., McDonald J.A., Kimata K.;
RT   "Three isoforms of mammalian hyaluronan synthases have distinct
RT   enzymatic properties.";
RL   J. Biol. Chem. 274:25085-25092(1999).
RN   [4]
RP   MUTAGENESIS.
RX   PubMed=10617644; DOI=10.1074/jbc.275.1.497;
RA   Yoshida M., Itano N., Yamada Y., Kimata K.;
RT   "In vitro synthesis of hyaluronan by a single protein derived from
RT   mouse HAS1 gene and characterization of amino acid residues essential
RT   for the activity.";
RL   J. Biol. Chem. 275:497-506(2000).
CC   -!- FUNCTION: Catalyzes the addition of GlcNAc or GlcUA
CC       monosaccharides to the nascent hyaluronan polymer. Therefore, it
CC       is essential to hyaluronan synthesis a major component of most
CC       extracellular matrices that has a structural role in tissues
CC       architectures and regulates cell adhesion, migration and
CC       differentiation. This is one of the isozymes catalyzing that
CC       reaction. Also able to catalyze the synthesis of chito-
CC       oligosaccharide depending on the substrate.
CC       {ECO:0000269|PubMed:10455188}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[hyaluronan](n) + UDP-N-acetyl-alpha-D-glucosamine = H(+)
CC         + N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP;
CC         Xref=Rhea:RHEA:20465, Rhea:RHEA-COMP:12583, Rhea:RHEA-
CC         COMP:12585, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705,
CC         ChEBI:CHEBI:58223, ChEBI:CHEBI:132153, ChEBI:CHEBI:132154;
CC         EC=2.4.1.212; Evidence={ECO:0000269|PubMed:10455188};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) +
CC         UDP-alpha-D-glucuronate = [hyaluronan](n+1) + H(+) + UDP;
CC         Xref=Rhea:RHEA:12528, Rhea:RHEA-COMP:12585, Rhea:RHEA-
CC         COMP:12587, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC         ChEBI:CHEBI:58223, ChEBI:CHEBI:132153, ChEBI:CHEBI:132154;
CC         EC=2.4.1.212; Evidence={ECO:0000269|PubMed:10455188};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.8 mM for UDP-Glc-NAc (at pH 7.1 and 37 degrees Celsius, in
CC         the presence of 15 mM MgCl2) {ECO:0000269|PubMed:10455188};
CC         KM=0.7 mM for UDP-Glc-UA (at pH 7.1 and 37 degrees Celsius, in
CC         the presence of 15 mM MgCl2) {ECO:0000269|PubMed:10455188};
CC   -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
DR   EMBL; D82964; BAA11654.1; -; mRNA.
DR   CCDS; CCDS37459.1; -.
DR   RefSeq; NP_032241.1; NM_008215.2.
DR   STRING; 10090.ENSMUSP00000003762; -.
DR   CAZy; GT2; Glycosyltransferase Family 2.
DR   iPTMnet; Q61647; -.
DR   PhosphoSitePlus; Q61647; -.
DR   PaxDb; Q61647; -.
DR   PRIDE; Q61647; -.
DR   Ensembl; ENSMUST00000003762; ENSMUSP00000003762; ENSMUSG00000003665.
DR   GeneID; 15116; -.
DR   KEGG; mmu:15116; -.
DR   UCSC; uc008apr.2; mouse.
DR   CTD; 3036; -.
DR   MGI; MGI:106590; Has1.
DR   eggNOG; KOG2571; Eukaryota.
DR   eggNOG; COG1215; LUCA.
DR   GeneTree; ENSGT00390000010337; -.
DR   HOGENOM; HOG000112847; -.
DR   InParanoid; Q61647; -.
DR   KO; K00752; -.
DR   OMA; RALQYPR; -.
DR   OrthoDB; 332363at2759; -.
DR   PhylomeDB; Q61647; -.
DR   TreeFam; TF332506; -.
DR   BRENDA; 2.4.1.212; 3474.
DR   Reactome; R-MMU-2142850; Hyaluronan biosynthesis and export.
DR   UniPathway; UPA00341; -.
DR   PRO; PR:Q61647; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   Bgee; ENSMUSG00000003665; Expressed in 48 organ(s), highest expression level in ankle joint.
DR   Genevisible; Q61647; MM.
DR   GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR   GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0050501; F:hyaluronan synthase activity; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; ISO:MGI.
DR   GO; GO:0044849; P:estrous cycle; IEA:Ensembl.
DR   GO; GO:0085029; P:extracellular matrix assembly; IDA:UniProtKB.
DR   GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0030213; P:hyaluronan biosynthetic process; IDA:MGI.
DR   GO; GO:0010764; P:negative regulation of fibroblast migration; ISO:MGI.
DR   InterPro; IPR028385; HAS1.
DR   InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR   PANTHER; PTHR22913:SF4; PTHR22913:SF4; 1.
DR   SUPFAM; SSF53448; SSF53448; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Direct protein sequencing; Glycoprotein;
KW   Glycosyltransferase; Membrane; Reference proteome; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN         1    583       Hyaluronan synthase 1.
FT                                /FTId=PRO_0000197170.
FT   TOPO_DOM      1     24       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     25     45       Helical; Name=1. {ECO:0000255}.
FT   TOPO_DOM     46     51       Extracellular. {ECO:0000255}.
FT   TRANSMEM     52     72       Helical; Name=2. {ECO:0000255}.
FT   TOPO_DOM     73    404       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    405    425       Helical; Name=3. {ECO:0000255}.
FT   TOPO_DOM    426    435       Extracellular. {ECO:0000255}.
FT   TRANSMEM    436    456       Helical; Name=4. {ECO:0000255}.
FT   TOPO_DOM    457    462       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    463    483       Helical; Name=5. {ECO:0000255}.
FT   TOPO_DOM    484    501       Extracellular. {ECO:0000255}.
FT   TRANSMEM    502    522       Helical; Name=6. {ECO:0000255}.
FT   TOPO_DOM    523    545       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    546    566       Helical; Name=7. {ECO:0000255}.
FT   TOPO_DOM    567    583       Extracellular. {ECO:0000255}.
FT   COMPBIAS     81     84       Poly-Ala.
FT   COMPBIAS    516    519       Poly-Leu.
FT   CARBOHYD    489    489       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   MUTAGEN     242    242       D->E: Loss of both activities.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     311    311       S->N: No effect.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     312    312       G->P: No effect.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     313    313       P->G: No effect.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     314    314       L->I: 75% decrease of both activities.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     314    314       L->V: Loss of HA activity.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     344    344       D->E: Loss of both activities.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     380    380       Q->N: 85%-90% decrease of both
FT                                activities.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     383    383       R->K: 85%-90% decrease of both
FT                                activities.
FT                                {ECO:0000269|PubMed:10617644}.
FT   MUTAGEN     384    384       W->Y: Loss of both activities.
FT                                {ECO:0000269|PubMed:10617644}.
SQ   SEQUENCE   583 AA;  65545 MW;  7AF9273E7B314728 CRC64;
     MRQDMPKPSE AARCCSGLAR RALTIIFALL ILGLMTWAYA AGVPLASDRY GLLAFGLYGA
     FLSAHLVAQS LFAYLEHRRV AAAARRSLAK GPLDAATARS VALTISAYQE DPAYLRQCLT
     SARALLYPHT RLRVLMVVDG NRAEDLYMVD MFREVFADED PATYVWDGNY HQPWEPAEAT
     GAVGEGAYRE VEAEDPGRLA VEALVRTRRC VCVAQRWGGK REVMYTAFKA LGDSVDYVQV
     CDSDTRLDPM ALLELVRVLD EDPRVGAVGG DVRILNPLDS WVSFLSSLRY WVAFNVERAC
     QSYFHCVSCI SGPLGLYRNN LLQQFLEAWY NQKFLGTHCT FGDDRHLTNR MLSMGYATKY
     TSRSRCYSET PSSFLRWLSQ QTRWSKSYFR EWLYNALWWH RHHAWMTYEA VVSGLFPFFV
     AATVLRLFYA GRPWALLWVL LCVQGVALAK AAFAAWLRGC VRMVLLSLYA PLYMCGLLPA
     KFLALVTMNQ SGWGTSGRKK LAANYVPVLP LALWALLLLG GLARSVAQEA RADWSGPSRA
     AEAYHLAAGA GAYVAYWVVM LTIYWVGVRR LCRRRSGGYR VQV
//
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