HYAS2_HUMAN
ID HYAS2_HUMAN Reviewed; 552 AA.
AC Q92819; Q32MM3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Hyaluronan synthase 2;
DE EC=2.4.1.212 {ECO:0000269|PubMed:20507985, ECO:0000269|PubMed:21228273, ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:32993960, ECO:0000305|PubMed:22887999, ECO:0000305|PubMed:30394292};
DE AltName: Full=Hyaluronate synthase 2;
DE AltName: Full=Hyaluronic acid synthase 2;
DE Short=HA synthase 2;
GN Name=HAS2 {ECO:0000312|HGNC:HGNC:4819};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=8798477; DOI=10.1074/jbc.271.38.22945;
RA Watanabe K., Yamaguchi Y.;
RT "Molecular identification of a putative human hyaluronan synthase.";
RL J. Biol. Chem. 271:22945-22948(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP CHROMOSOMAL REARRANGEMENT WITH PLAG1.
RX PubMed=15642402; DOI=10.1016/j.cancergencyto.2004.04.017;
RA Morerio C., Rapella A., Rosanda C., Tassano E., Gambini C., Romagnoli G.,
RA Panarello C.;
RT "PLAG1-HAS2 fusion in lipoblastoma with masked 8q intrachromosomal
RT rearrangement.";
RL Cancer Genet. Cytogenet. 156:183-184(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=23303191; DOI=10.1074/jbc.m112.443879;
RA Rilla K., Oikari S., Jokela T.A., Hyttinen J.M., Kaernae R., Tammi R.H.,
RA Tammi M.I.;
RT "Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc
RT concentration than HAS2 and HAS3.";
RL J. Biol. Chem. 288:5973-5983(2013).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, UBIQUITINATION AT LYS-190,
RP MUTAGENESIS OF LYS-190, INTERACTION WITH HAS3, AND ACTIVITY REGULATION.
RX PubMed=20507985; DOI=10.1074/jbc.m110.127050;
RA Karousou E., Kamiryo M., Skandalis S.S., Ruusala A., Asteriou T., Passi A.,
RA Yamashita H., Hellman U., Heldin C.H., Heldin P.;
RT "The activity of hyaluronan synthase 2 is regulated by dimerization and
RT ubiquitination.";
RL J. Biol. Chem. 285:23647-23654(2010).
RN [6]
RP PHOSPHORYLATION AT THR-110, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS
RP OF THR-110.
RX PubMed=21228273; DOI=10.1074/jbc.m110.193656;
RA Vigetti D., Clerici M., Deleonibus S., Karousou E., Viola M., Moretto P.,
RA Heldin P., Hascall V.C., De Luca G., Passi A.;
RT "Hyaluronan synthesis is inhibited by adenosine monophosphate-activated
RT protein kinase through the regulation of HAS2 activity in human aortic
RT smooth muscle cells.";
RL J. Biol. Chem. 286:7917-7924(2011).
RN [7]
RP GLYCOSYLATION AT SER-221, FUNCTION, ACTIVITY REGULATION, CATALYTIC
RP ACTIVITY, MUTAGENESIS OF SER-221, AND SUBCELLULAR LOCATION.
RX PubMed=22887999; DOI=10.1074/jbc.m112.402347;
RA Vigetti D., Deleonibus S., Moretto P., Karousou E., Viola M., Bartolini B.,
RA Hascall V.C., Tammi M., De Luca G., Passi A.;
RT "Role of UDP-N-acetylglucosamine (GlcNAc) and O-GlcNAcylation of hyaluronan
RT synthase 2 in the control of chondroitin sulfate and hyaluronan
RT synthesis.";
RL J. Biol. Chem. 287:35544-35555(2012).
RN [8]
RP SUBUNIT, INTERACTION WITH HAS1 AND HAS3, AND SUBCELLULAR LOCATION.
RX PubMed=25795779; DOI=10.1074/jbc.m115.640581;
RA Bart G., Vico N.O., Hassinen A., Pujol F.M., Deen A.J., Ruusala A.,
RA Tammi R.H., Squire A., Heldin P., Kellokumpu S., Tammi M.I.;
RT "Fluorescence resonance energy transfer (FRET) and proximity ligation
RT assays reveal functionally relevant homo- and heteromeric complexes among
RT hyaluronan synthases HAS1, HAS2, and HAS3.";
RL J. Biol. Chem. 290:11479-11490(2015).
RN [9]
RP DEUBIQUITINATION BY USP4, AND INDUCTION.
RX PubMed=28604766; DOI=10.1038/oncsis.2017.45;
RA Mehic M., de Sa V.K., Hebestreit S., Heldin C.H., Heldin P.;
RT "The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2
RT and differentially affect its function.";
RL Oncogenesis 6:e348-e348(2017).
RN [10]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF THR-110; LYS-190 AND SER-221, ACTIVITY
RP REGULATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30394292; DOI=10.1016/j.matbio.2018.10.004;
RA Melero-Fernandez de Mera R.M., Arasu U.T., Kaernae R., Oikari S., Rilla K.,
RA Vigetti D., Passi A., Heldin P., Tammi M.I., Deen A.J.;
RT "Effects of mutations in the post-translational modification sites on the
RT trafficking of hyaluronan synthase 2 (HAS2).";
RL Matrix Biol. 80:85-103(2019).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT
RP THR-328, AND MUTAGENESIS OF THR-328.
RX PubMed=32993960; DOI=10.1016/j.bbrc.2020.08.093;
RA Kasai K., Kuroda Y., Takabuchi Y., Nitta A., Kobayashi T., Nozaka H.,
RA Miura T., Nakamura T.;
RT "Phosphorylation of Thr328 in hyaluronan synthase 2 is essential for
RT hyaluronan synthesis.";
RL Biochem. Biophys. Res. Commun. 533:732-738(2020).
CC -!- FUNCTION: Catalyzes the addition of GlcNAc or GlcUA monosaccharides to
CC the nascent hyaluronan polymer (PubMed:20507985, PubMed:32993960,
CC PubMed:23303191, PubMed:21228273) (Probable). Therefore, it is
CC 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 (PubMed:8798477, PubMed:21228273, PubMed:20507985).
CC This is one of three isoenzymes responsible for cellular hyaluronan
CC synthesis and it is particularly responsible for the synthesis of high
CC molecular mass hyaluronan (By similarity).
CC {ECO:0000250|UniProtKB:P70312, ECO:0000269|PubMed:20507985,
CC ECO:0000269|PubMed:21228273, ECO:0000269|PubMed:23303191,
CC ECO:0000269|PubMed:32993960, ECO:0000269|PubMed:8798477,
CC ECO:0000305|PubMed:22887999, ECO:0000305|PubMed:30394292}.
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:20507985, ECO:0000269|PubMed:21228273,
CC ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:32993960,
CC ECO:0000305|PubMed:22887999, ECO:0000305|PubMed:30394292};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466;
CC Evidence={ECO:0000305|PubMed:20507985};
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:20507985, ECO:0000269|PubMed:21228273,
CC ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:32993960,
CC ECO:0000305|PubMed:22887999, ECO:0000305|PubMed:30394292};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529;
CC Evidence={ECO:0000305|PubMed:20507985};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Regulated by several post-translational
CC modifications such as ubiquitination/deubiquitination, phosphorylation
CC and O-GlcNAcylation (PubMed:32993960, PubMed:30394292, PubMed:28604766,
CC PubMed:22887999, PubMed:20507985, PubMed:21228273). The enzymatic
CC activity depends on the availability of UDP-GlcUA and UDP-GlcNAc
CC (PubMed:23303191, PubMed:22887999). {ECO:0000269|PubMed:20507985,
CC ECO:0000269|PubMed:21228273, ECO:0000269|PubMed:22887999,
CC ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:28604766,
CC ECO:0000269|PubMed:30394292, ECO:0000269|PubMed:32993960}.
CC -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC {ECO:0000269|PubMed:20507985}.
CC -!- SUBUNIT: Homodimer; dimerization promotes enzymatic activity
CC (PubMed:20507985, PubMed:25795779). Forms heterodimer with HAS3
CC (PubMed:20507985, PubMed:25795779). Forms heterodimer with HAS1
CC (PubMed:25795779). {ECO:0000269|PubMed:20507985,
CC ECO:0000269|PubMed:25795779}.
CC -!- INTERACTION:
CC Q92819; Q92839: HAS1; NbExp=9; IntAct=EBI-16628852, EBI-1052423;
CC Q92819; O00219: HAS3; NbExp=10; IntAct=EBI-16628852, EBI-16628799;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22887999,
CC ECO:0000269|PubMed:25795779, ECO:0000269|PubMed:30394292,
CC ECO:0000269|PubMed:8798477}; Multi-pass membrane protein {ECO:0000255}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:30394292}; Multi-
CC pass membrane protein {ECO:0000255}. Vesicle
CC {ECO:0000269|PubMed:30394292}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:25795779, ECO:0000269|PubMed:30394292}; Multi-pass
CC membrane protein {ECO:0000255}. Lysosome {ECO:0000269|PubMed:30394292}.
CC Note=Travels from endoplasmic reticulum (ER), Golgi to plasma membrane
CC and either back to endosomes and lysosomes, or out into extracellular
CC vesicles (PubMed:30394292). Post-translational modifications control
CC HAS2 trafficking (PubMed:30394292). {ECO:0000269|PubMed:30394292}.
CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts.
CC -!- INDUCTION: During cell cycle progression is induced at the G1-S and G2-
CC M transitions. Up-regulated in a panel of cancer cell lines.
CC {ECO:0000269|PubMed:28604766}.
CC -!- PTM: Phosphorylation at Thr-328 is essential for hyaluronan synthase
CC activity (PubMed:32993960). Phosphorylation at Thr-110 is required for
CC transport from ER to Golgi (PubMed:30394292).
CC {ECO:0000269|PubMed:30394292, ECO:0000269|PubMed:32993960}.
CC -!- PTM: O-GlcNAcylation at Ser-221 increases the stability of HAS2 and
CC plasma membrane localization. {ECO:0000269|PubMed:22887999}.
CC -!- PTM: Ubiquitination at Lys-190; this ubiquitination is essential for
CC hyaluronan synthase activity and homo- or hetero-oligomerization. Can
CC also be poly-ubiquitinated (PubMed:20507985). Deubiquitinated by USP17
CC and USP4. USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked
CC polyubiquitin chains, whereas USP4 preferentially removes
CC monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked
CC polyubiquitin chain (PubMed:28604766). {ECO:0000269|PubMed:20507985,
CC ECO:0000269|PubMed:28604766}.
CC -!- DISEASE: Note=A chromosomal aberration involving HAS2 may be a cause of
CC lipoblastomas, which are benign tumors resulting from transformation of
CC adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1
CC intrachromosomal rearrangement with PLAG1.
CC {ECO:0000269|PubMed:15642402}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HAS2ID412ch8q24.html";
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DR EMBL; U54804; AAC50692.1; -; mRNA.
DR EMBL; BC069353; AAH69353.1; -; mRNA.
DR EMBL; BC109071; AAI09072.1; -; mRNA.
DR EMBL; BC109072; AAI09073.1; -; mRNA.
DR CCDS; CCDS6335.1; -.
DR RefSeq; NP_005319.1; NM_005328.2.
DR AlphaFoldDB; Q92819; -.
DR BioGRID; 109287; 4.
DR CORUM; Q92819; -.
DR IntAct; Q92819; 2.
DR STRING; 9606.ENSP00000306991; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR TCDB; 4.D.1.1.18; the putative vectorial glycosyl polymerization (vgp) family.
DR GlyGen; Q92819; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92819; -.
DR PhosphoSitePlus; Q92819; -.
DR BioMuta; HAS2; -.
DR DMDM; 7387737; -.
DR jPOST; Q92819; -.
DR MassIVE; Q92819; -.
DR PaxDb; Q92819; -.
DR PeptideAtlas; Q92819; -.
DR PRIDE; Q92819; -.
DR ProteomicsDB; 75495; -.
DR Antibodypedia; 55587; 180 antibodies from 24 providers.
DR DNASU; 3037; -.
DR Ensembl; ENST00000303924.5; ENSP00000306991.4; ENSG00000170961.7.
DR GeneID; 3037; -.
DR KEGG; hsa:3037; -.
DR MANE-Select; ENST00000303924.5; ENSP00000306991.4; NM_005328.3; NP_005319.1.
DR UCSC; uc003yph.3; human.
DR CTD; 3037; -.
DR DisGeNET; 3037; -.
DR GeneCards; HAS2; -.
DR HGNC; HGNC:4819; HAS2.
DR HPA; ENSG00000170961; Tissue enhanced (adipose tissue, urinary bladder).
DR MIM; 601636; gene.
DR neXtProt; NX_Q92819; -.
DR OpenTargets; ENSG00000170961; -.
DR PharmGKB; PA29195; -.
DR VEuPathDB; HostDB:ENSG00000170961; -.
DR eggNOG; KOG2571; Eukaryota.
DR GeneTree; ENSGT00390000010337; -.
DR HOGENOM; CLU_029695_3_0_1; -.
DR InParanoid; Q92819; -.
DR OMA; KSATYVW; -.
DR OrthoDB; 332363at2759; -.
DR PhylomeDB; Q92819; -.
DR TreeFam; TF332506; -.
DR BRENDA; 2.4.1.212; 2681.
DR PathwayCommons; Q92819; -.
DR Reactome; R-HSA-2142850; Hyaluronan biosynthesis and export.
DR SignaLink; Q92819; -.
DR SIGNOR; Q92819; -.
DR UniPathway; UPA00341; -.
DR BioGRID-ORCS; 3037; 12 hits in 1065 CRISPR screens.
DR ChiTaRS; HAS2; human.
DR GeneWiki; HAS2; -.
DR GenomeRNAi; 3037; -.
DR Pharos; Q92819; Tbio.
DR PRO; PR:Q92819; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q92819; protein.
DR Bgee; ENSG00000170961; Expressed in cartilage tissue and 131 other tissues.
DR Genevisible; Q92819; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IEA:Ensembl.
DR GO; GO:0050501; F:hyaluronan synthase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0036302; P:atrioventricular canal development; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; IEA:Ensembl.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IEP:BHF-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:BHF-UCL.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:BHF-UCL.
DR GO; GO:0090500; P:endocardial cushion to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0044849; P:estrous cycle; IEA:Ensembl.
DR GO; GO:0085029; P:extracellular matrix assembly; ISS:UniProtKB.
DR GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; IEA:Ensembl.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; IEA:Ensembl.
DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; IEA:Ensembl.
DR GO; GO:1900625; P:positive regulation of monocyte aggregation; IMP:BHF-UCL.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0035810; P:positive regulation of urine volume; ISS:UniProtKB.
DR GO; GO:1901201; P:regulation of extracellular matrix assembly; IEA:Ensembl.
DR GO; GO:0070295; P:renal water absorption; ISS:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR028371; HAS2.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR22913:SF7; PTHR22913:SF7; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Chromosomal rearrangement; Endoplasmic reticulum;
KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Isopeptide bond;
KW Lysosome; Membrane; Phosphoprotein; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..552
FT /note="Hyaluronan synthase 2"
FT /id="PRO_0000197173"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..45
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..374
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 396..402
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..429
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..450
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 451..475
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 476..496
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 497..510
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 511..531
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 532..552
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT MOD_RES 110
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21228273"
FT MOD_RES 328
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:32993960"
FT CARBOHYD 221
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:22887999"
FT CROSSLNK 190
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20507985"
FT MUTAGEN 110
FT /note="T->A: Completely abolishes hyaluronan synthase
FT activity. Not detected in cytoplasmic vesicles nor at cell
FT membrane. Inability to travel from ER to Golgi.
FT Unresponsive to AMPK-mediated inactivation."
FT /evidence="ECO:0000269|PubMed:21228273,
FT ECO:0000269|PubMed:30394292"
FT MUTAGEN 190
FT /note="K->R: Completely abolishes hyaluronan synthase
FT activity. Cumulates at plasma membrane."
FT /evidence="ECO:0000269|PubMed:20507985,
FT ECO:0000269|PubMed:30394292"
FT MUTAGEN 221
FT /note="S->A: Prevents O-GlcNAcylation. Increases protein
FT stability. Reduces hyaluronan synthase activity."
FT /evidence="ECO:0000269|PubMed:22887999,
FT ECO:0000269|PubMed:30394292"
FT MUTAGEN 221
FT /note="S->D: Increases protein degradation. Abolishes
FT hyaluronan synthase activity. Does not affect subcellular
FT location."
FT /evidence="ECO:0000269|PubMed:30394292"
FT MUTAGEN 221
FT /note="S->E: Increases protein degradation. Abolishes
FT hyaluronan synthase activity. Does not affect subcellular
FT location."
FT /evidence="ECO:0000269|PubMed:30394292"
FT MUTAGEN 328
FT /note="T->A: Abolishes hyaluronan synthase activity."
FT /evidence="ECO:0000269|PubMed:32993960"
SQ SEQUENCE 552 AA; 63566 MW; EEEF58D97B131F9D CRC64;
MHCERFLCIL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG AFLASHLIIQ
SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR KCLQSVKRLT YPGIKVVMVI
DGNSEDDLYM MDIFSEVMGR DKSATYIWKN NFHEKGPGET DESHKESSQH VTQLVLSNKS
ICIMQKWGGK REVMYTAFRA LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG
DVQILNKYDS WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
NQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ QTRWSKSYFR
EWLYNAMWFH KHHLWMTYEA IITGFFPFFL IATVIQLFYR GKIWNILLFL LTVQLVGLIK
SSFASCLRGN IVMVFMSLYS VLYMSSLLPA KMFAIATINK AGWGTSGRKT IVVNFIGLIP
VSVWFTILLG GVIFTIYKES KRPFSESKQT VLIVGTLLYA CYWVMLLTLY VVLINKCGRR
KKGQQYDMVL DV
