HYAS2_RAT
ID HYAS2_RAT Reviewed; 552 AA.
AC O35776;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Hyaluronan synthase 2;
DE EC=2.4.1.212 {ECO:0000250|UniProtKB:Q92819};
DE AltName: Full=Hyaluronate synthase 2;
DE AltName: Full=Hyaluronic acid synthase 2;
DE Short=HA synthase 2;
GN Name=Has2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sakaguchi K., Midura R.J.;
RT "Molecular cloning of rat hyaluronan synthase 2 and regulation of its
RT expression in a rat osteoblastic cell line.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). This is one of
CC three isoenzymes responsible for cellular hyaluronan synthesis and it
CC is particularly responsible for the synthesis of high molecular mass
CC hyaluronan (By similarity). {ECO:0000250|UniProtKB:P70312,
CC ECO:0000250|UniProtKB:Q92819}.
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:0000250|UniProtKB:Q92819};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466;
CC Evidence={ECO:0000250|UniProtKB:Q92819};
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:0000250|UniProtKB:Q92819};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529;
CC Evidence={ECO:0000250|UniProtKB:Q92819};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC {ECO:0000250|UniProtKB:Q92819}.
CC -!- SUBUNIT: Homodimer; dimerization promotes enzymatic activity. Forms
CC heterodimer with HAS3. Forms heterodimer with HAS1.
CC {ECO:0000250|UniProtKB:Q92819}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q92819};
CC Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein
CC {ECO:0000255}. Vesicle {ECO:0000250|UniProtKB:Q92819}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome {ECO:0000250|UniProtKB:Q92819}. Note=Travels
CC from endoplasmic reticulum (ER), Golgi to plasma membrane and either
CC back to endosomes and lysosomes, or out into extracellular vesicles.
CC Post-translational modifications control HAS2 trafficking.
CC {ECO:0000250|UniProtKB:Q92819}.
CC -!- PTM: Phosphorylation at Thr-328 is essential for hyaluronan synthase
CC activity. {ECO:0000250|UniProtKB:Q92819}.
CC -!- PTM: O-GlcNAcylation at Ser-221 increases the stability of HAS2 and
CC plasma membrane localization. {ECO:0000250|UniProtKB:Q92819}.
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. Deubiquitinated by USP17L22/USP17 and USP4.
CC USP17L22/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. {ECO:0000250|UniProtKB:Q92819}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
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DR EMBL; AF008201; AAB63209.1; -; mRNA.
DR RefSeq; NP_037285.1; NM_013153.1.
DR AlphaFoldDB; O35776; -.
DR STRING; 10116.ENSRNOP00000006517; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR PaxDb; O35776; -.
DR Ensembl; ENSRNOT00000006517; ENSRNOP00000006517; ENSRNOG00000004854.
DR GeneID; 25694; -.
DR KEGG; rno:25694; -.
DR CTD; 3037; -.
DR RGD; 2781; Has2.
DR eggNOG; KOG2571; Eukaryota.
DR GeneTree; ENSGT00390000010337; -.
DR HOGENOM; CLU_029695_3_0_1; -.
DR InParanoid; O35776; -.
DR OMA; KSATYVW; -.
DR OrthoDB; 332363at2759; -.
DR PhylomeDB; O35776; -.
DR TreeFam; TF332506; -.
DR BRENDA; 2.4.1.212; 5301.
DR Reactome; R-RNO-2142850; Hyaluronan biosynthesis and export.
DR UniPathway; UPA00341; -.
DR PRO; PR:O35776; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000004854; Expressed in quadriceps femoris and 10 other tissues.
DR Genevisible; O35776; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:1903561; C:extracellular vesicle; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; ISO:RGD.
DR GO; GO:0050501; F:hyaluronan synthase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0036302; P:atrioventricular canal development; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; ISO:RGD.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISO:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:RGD.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; ISO:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0090500; P:endocardial cushion to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0044849; P:estrous cycle; IEP:RGD.
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; IEP:UniProtKB.
DR GO; GO:0030212; P:hyaluronan metabolic process; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; IDA:RGD.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; IDA:RGD.
DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; IMP:RGD.
DR GO; GO:1900625; P:positive regulation of monocyte aggregation; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:RGD.
DR GO; GO:0035810; P:positive regulation of urine volume; IEP:UniProtKB.
DR GO; GO:1901201; P:regulation of extracellular matrix assembly; IMP:RGD.
DR GO; GO:0070295; P:renal water absorption; IEP:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR001173; Glyco_trans_2-like.
DR InterPro; IPR028371; HAS2.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR22913:SF7; PTHR22913:SF7; 1.
DR Pfam; PF00535; Glycos_transf_2; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Isopeptide bond; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..552
FT /note="Hyaluronan synthase 2"
FT /id="PRO_0000197175"
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:0000250|UniProtKB:Q92819"
FT MOD_RES 328
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92819"
FT CARBOHYD 221
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q92819"
FT CROSSLNK 190
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q92819"
SQ SEQUENCE 552 AA; 63534 MW; 1DCAA244E3A4E9BC CRC64;
MHCERFLCVL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG AFLASHLIIQ
SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR KCLQSVKRLT YPGIKVVMVI
DGNSDDDLYM MDIFSEVMGR DKSVTYIWKN NFHERGPGET EESHKESSQH VTQLVLSNKS
ICIMQKWGGK REVMYTAFRA LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG
DVQILNKYDS WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
NQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ QTRWSKSYFR
EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR GKIWNILLFL LTVQLVGLIK
SSFASCLRGN IVMVFMSLYS VLYMSSLLPA KMFAIATINK AGWGTSGRKT IVVNFIGLIP
VSVWFTILLG GVIFTIYKES KKPFSESKQT VLIVGTLIYA CYWVVLLTLY VVLINKCGRR
KKGQQYDMVL DV
