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 03-AUG-2022, entry version 155.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 KINETIC
RP 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 enzymatic
RT 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 mouse
RT HAS1 gene and characterization of amino acid residues essential for the
RT activity.";
RL J. Biol. Chem. 275:497-506(2000).
CC -!- FUNCTION: Catalyzes the addition of GlcNAc or GlcUA monosaccharides to
CC the nascent hyaluronan polymer. Therefore, it is essential to
CC hyaluronan synthesis a major component of most extracellular matrices
CC that has a structural role in tissues architectures and regulates cell
CC adhesion, migration and differentiation. This is one of the isozymes
CC catalyzing that 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(+) + N-
CC acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP;
CC Xref=Rhea:RHEA:20465, Rhea:RHEA-COMP:12583, Rhea:RHEA-COMP:12585,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132153, ChEBI:CHEBI:132154; EC=2.4.1.212;
CC Evidence={ECO:0000269|PubMed:10455188};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP-
CC alpha-D-glucuronate = [hyaluronan](n+1) + H(+) + UDP;
CC Xref=Rhea:RHEA:12528, Rhea:RHEA-COMP:12585, Rhea:RHEA-COMP:12587,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132153, ChEBI:CHEBI:132154; EC=2.4.1.212;
CC 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 the
CC 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 the
CC 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}.
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DR EMBL; D82964; BAA11654.1; -; mRNA.
DR CCDS; CCDS37459.1; -.
DR RefSeq; NP_032241.1; NM_008215.2.
DR AlphaFoldDB; Q61647; -.
DR STRING; 10090.ENSMUSP00000003762; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR GlyGen; Q61647; 1 site.
DR iPTMnet; Q61647; -.
DR PhosphoSitePlus; Q61647; -.
DR PaxDb; Q61647; -.
DR PRIDE; Q61647; -.
DR ProteomicsDB; 273291; -.
DR Antibodypedia; 52809; 225 antibodies from 30 providers.
DR DNASU; 15116; -.
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 VEuPathDB; HostDB:ENSMUSG00000003665; -.
DR eggNOG; KOG2571; Eukaryota.
DR GeneTree; ENSGT00390000010337; -.
DR HOGENOM; CLU_029695_3_0_1; -.
DR InParanoid; Q61647; -.
DR OMA; CILRRDM; -.
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 BioGRID-ORCS; 15116; 4 hits in 72 CRISPR screens.
DR PRO; PR:Q61647; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q61647; protein.
DR Bgee; ENSMUSG00000003665; Expressed in ankle joint and 40 other tissues.
DR Genevisible; Q61647; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma 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 Gene3D; 3.90.550.10; -; 1.
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 Direct protein sequencing; Glycoprotein; Glycosyltransferase; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..583
FT /note="Hyaluronan synthase 1"
FT /id="PRO_0000197170"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..51
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..404
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 405..425
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 426..435
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 436..456
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 457..462
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 463..483
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 484..501
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 502..522
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 523..545
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 546..566
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 567..583
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 242
FT /note="D->E: Loss of both activities."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 311
FT /note="S->N: No effect."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 312
FT /note="G->P: No effect."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 313
FT /note="P->G: No effect."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 314
FT /note="L->I: 75% decrease of both activities."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 314
FT /note="L->V: Loss of HA activity."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 344
FT /note="D->E: Loss of both activities."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 380
FT /note="Q->N: 85%-90% decrease of both activities."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 383
FT /note="R->K: 85%-90% decrease of both activities."
FT /evidence="ECO:0000269|PubMed:10617644"
FT MUTAGEN 384
FT /note="W->Y: Loss of both activities."
FT /evidence="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
