HYAS3_MOUSE
ID HYAS3_MOUSE Reviewed; 554 AA.
AC O08650; Q8CEB9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Hyaluronan synthase 3;
DE EC=2.4.1.212 {ECO:0000269|PubMed:10455188, ECO:0000269|PubMed:16014622};
DE AltName: Full=Hyaluronate synthase 3;
DE AltName: Full=Hyaluronic acid synthase 3;
DE Short=HA synthase 3;
GN Name=Has3;
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], AND DEVELOPMENTAL STAGE.
RC STRAIN=129/SvJ, and C57BL/6J;
RX PubMed=9083017; DOI=10.1074/jbc.272.14.8957;
RA Spicer A.P., Olson J.S., McDonald J.A.;
RT "Molecular cloning and characterization of a cDNA encoding the third
RT putative mammalian hyaluronan synthase.";
RL J. Biol. Chem. 272:8957-8961(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
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 [5]
RP SUBCELLULAR LOCATION, FUCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP ASP-216.
RX PubMed=16014622; DOI=10.1074/jbc.m504736200;
RA Rilla K., Siiskonen H., Spicer A.P., Hyttinen J.M., Tammi M.I., Tammi R.H.;
RT "Plasma membrane residence of hyaluronan synthase is coupled to its
RT enzymatic activity.";
RL J. Biol. Chem. 280:31890-31897(2005).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=24790187; DOI=10.1523/jneurosci.3458-13.2014;
RA Arranz A.M., Perkins K.L., Irie F., Lewis D.P., Hrabe J., Xiao F.,
RA Itano N., Kimata K., Hrabetova S., Yamaguchi Y.;
RT "Hyaluronan deficiency due to Has3 knock-out causes altered neuronal
RT activity and seizures via reduction in brain extracellular space.";
RL J. Neurosci. 34:6164-6176(2014).
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 three
CC isoenzymes responsible for cellular hyaluronan synthesis.
CC {ECO:0000269|PubMed:10455188, ECO:0000269|PubMed:16014622}.
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, ECO:0000269|PubMed:16014622};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466;
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, ECO:0000269|PubMed:16014622};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529;
CC Evidence={ECO:0000269|PubMed:10455188};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.2 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=0.3 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 {ECO:0000269|PubMed:10455188, ECO:0000269|PubMed:16014622}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10455188,
CC ECO:0000269|PubMed:16014622}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:16014622};
CC Multi-pass membrane protein {ECO:0000255}. Golgi apparatus, trans-Golgi
CC network membrane {ECO:0000269|PubMed:16014622}; Multi-pass membrane
CC protein {ECO:0000255}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:16014622}. Note=Travels through endoplasmic
CC reticulum (ER), Golgi, plasma membrane, and endocytic vesicles
CC (PubMed:16014622). Actives only when present in plasma membrane
CC (PubMed:16014622). O-GlcNAcylation controls its membrane localization
CC (By similarity). A rapid recycling of HAS3 between plasma membrane and
CC endosomes is controlled by the cytosolic levels of UDP-GlcUA and UDP-
CC GlcNAc (By similarity). {ECO:0000250|UniProtKB:O00219,
CC ECO:0000269|PubMed:16014622}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 17.5 dpc.
CC {ECO:0000269|PubMed:9083017}.
CC -!- PTM: O-GlcNAcylation increases the hyaluronan synthase activity, HAS3
CC stability and its plasma membrane residence. The concentration of UDP-
CC GlcNAc controls the level of O-GlcNAc modification.
CC {ECO:0000250|UniProtKB:O00219}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable and fertile however
CC absence of HAS3 increases the excitability of neural networks and
CC drives the formation of epileptic seizures.
CC {ECO:0000269|PubMed:24790187}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
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DR EMBL; U86408; AAC53128.1; -; mRNA.
DR EMBL; AK028582; BAC26017.1; -; mRNA.
DR EMBL; BC138152; AAI38153.1; -; mRNA.
DR CCDS; CCDS22640.1; -.
DR RefSeq; NP_001317977.1; NM_001331048.1.
DR RefSeq; NP_032243.2; NM_008217.4.
DR RefSeq; XP_006530763.1; XM_006530700.3.
DR RefSeq; XP_006530764.1; XM_006530701.2.
DR AlphaFoldDB; O08650; -.
DR STRING; 10090.ENSMUSP00000034385; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR GlyGen; O08650; 1 site.
DR PhosphoSitePlus; O08650; -.
DR PaxDb; O08650; -.
DR PRIDE; O08650; -.
DR ProteomicsDB; 273063; -.
DR Antibodypedia; 29818; 267 antibodies from 32 providers.
DR DNASU; 15118; -.
DR Ensembl; ENSMUST00000034385; ENSMUSP00000034385; ENSMUSG00000031910.
DR Ensembl; ENSMUST00000176144; ENSMUSP00000135303; ENSMUSG00000031910.
DR GeneID; 15118; -.
DR KEGG; mmu:15118; -.
DR UCSC; uc009ngn.2; mouse.
DR CTD; 3038; -.
DR MGI; MGI:109599; Has3.
DR VEuPathDB; HostDB:ENSMUSG00000031910; -.
DR eggNOG; KOG2571; Eukaryota.
DR GeneTree; ENSGT00390000010337; -.
DR HOGENOM; CLU_029695_3_0_1; -.
DR InParanoid; O08650; -.
DR OMA; DVIVPCF; -.
DR OrthoDB; 332363at2759; -.
DR PhylomeDB; O08650; -.
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; 15118; 2 hits in 71 CRISPR screens.
DR PRO; PR:O08650; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O08650; protein.
DR Bgee; ENSMUSG00000031910; Expressed in inner dental epithelium and 106 other tissues.
DR ExpressionAtlas; O08650; baseline and differential.
DR Genevisible; O08650; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036117; C:hyaluranon cable; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
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: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:1900106; P:positive regulation of hyaluranon cable assembly; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Membrane; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..554
FT /note="Hyaluronan synthase 3"
FT /id="PRO_0000197179"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..44
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..399
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..409
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..441
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 442..462
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 463..474
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 475..495
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 496..516
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 517..537
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 538..554
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 216
FT /note="D->A: Not detectable on the plasma membrane.
FT Abolishes hyaluronan synthase activity."
FT /evidence="ECO:0000269|PubMed:16014622"
FT CONFLICT 85
FT /note="P -> S (in Ref. 1; AAC53128)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 554 AA; 63349 MW; BFFF239C901251DE CRC64;
MPVQLTTALR VVGTSLFALV VLGGILAAYV TGYQFIHTEK HYLSFGLYGA ILGLHLLIQS
LFAFLEHRRM RRAGRPLKLH CSQRPRSVAL CIAAYQEDPE YLRKCLRSAQ RIAFPNLKVV
MVVDGNRQED TYMLDIFHEV LGGTEQAGFF VWRSNFHEAG EGETEASLQE GMERVRAVVW
ASTFSCIMQK WGGKREVMYT AFKALGNSVD YIQVCDSDTV LDPACTIEML RVLEEDPQVG
GVGGDVQILN KYDSWISFLS SVRYWMAFNV ERACQSYFGC VQCISGPLGM YRNSLLQQFL
EDWYHQKFLG SKCSFGDDRH LTNRVLSLGY RTKYTARSKC LTETPTRYLR WLNQQTRWSK
SYFREWLYNS LWFHKHHLWM TYESVVTGFF PFFLIATVIQ LFYRGRIWNI LLFLLTVQLV
GIIKATYACF LRGNAEMIFM SLYSLLYMSS LLPAKIFAIA TINKSGWGTS GRKTIVVNFI
GLIPVSIWVA VLLGGLAYTA YCQDLFSETE LAFLVSGAIL YGCYWVALLM LYLAIIARRC
GKKPEQYSLA FAEV
