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 24-JAN-2024, entry version 170. 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="https://atlasgeneticsoncology.org/gene/412/HAS2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; 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 GlyCosmos; Q92819; 1 site, 1 glycan. DR GlyGen; Q92819; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q92819; -. DR PhosphoSitePlus; Q92819; -. DR SwissPalm; Q92819; -. DR BioMuta; HAS2; -. DR DMDM; 7387737; -. DR jPOST; Q92819; -. DR MassIVE; Q92819; -. DR PaxDb; 9606-ENSP00000306991; -. DR PeptideAtlas; Q92819; -. DR ProteomicsDB; 75495; -. DR Antibodypedia; 55587; 222 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 AGR; HGNC:4819; -. 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; 1361850at2759; -. 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 1145 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 132 other cell types or tissues. 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: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 CDD; cd06434; GT2_HAS; 1. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR PANTHER; PTHR22913; HYALURONAN SYNTHASE; 1. DR PANTHER; PTHR22913:SF7; HYALURONAN SYNTHASE 2; 1. DR Pfam; PF03142; Chitin_synth_2; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. DR Genevisible; Q92819; HS. 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 //