HYAS2_BOVIN
ID HYAS2_BOVIN Reviewed; 552 AA.
AC O97711;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 101.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Einspanier R., Patzner K., Lauer B., Berisha B.;
RT "Hyaluronan synthase is expressed during cumulus-oocyte complex maturation
RT in the cow.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 267-469.
RA Yamashita H., Usui T., Suzuki K.;
RT "HAS2.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=10067958;
RA Usui T., Suzuki K., Kaji Y., Amano S., Miyata K., Heldin P., Yamashita H.;
RT "Hyaluronan synthase expression in bovine eyes.";
RL Invest. Ophthalmol. Vis. Sci. 40:563-567(1999).
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 -!- TISSUE SPECIFICITY: Expressed in corneal endothelial cells.
CC {ECO:0000269|PubMed:10067958}.
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 USP17 and USP4. USP17
CC efficiently removes 'Lys-63'- and 'Lys-48'-linked polyubiquitin chains,
CC whereas USP4 preferentially removes monoubiquitination and, partially,
CC both 'Lys-63'- and 'Lys-48'-linked polyubiquitin chain.
CC {ECO:0000250|UniProtKB:Q92819}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
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DR EMBL; AJ004951; CAA06239.1; -; mRNA.
DR EMBL; AB017804; BAA76547.1; -; mRNA.
DR RefSeq; NP_776504.1; NM_174079.2.
DR AlphaFoldDB; O97711; -.
DR STRING; 9913.ENSBTAP00000026503; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR PaxDb; O97711; -.
DR PRIDE; O97711; -.
DR GeneID; 281220; -.
DR KEGG; bta:281220; -.
DR CTD; 3037; -.
DR eggNOG; KOG2571; Eukaryota.
DR InParanoid; O97711; -.
DR OrthoDB; 332363at2759; -.
DR UniPathway; UPA00341; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:InterPro.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0050501; F:hyaluronan synthase activity; ISS:UniProtKB.
DR GO; GO:0036302; P:atrioventricular canal development; ISS:UniProtKB.
DR GO; GO:0090500; P:endocardial cushion to mesenchymal transition; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0035810; P:positive regulation of urine volume; ISS:UniProtKB.
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 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_0000197172"
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"
FT CONFLICT 406
FT /note="T -> I (in Ref. 2; BAA76547)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="S -> C (in Ref. 2; BAA76547)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 552 AA; 63459 MW; 85AD256435A5EB64 CRC64;
MHCERFLCIL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG AFLASHLIIQ
SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR KCLQSVKRLT YPGIKVVMVI
DGNSEDDLYM MDIFSEVMGR DKSATYIWKN NYHVKGPGET DESHKESSQH VTQLVLSNKS
ICTMQKWGGK REVMYTAFRA LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG
DVQILNKYDS WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
NQEFMGSQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ QTRWSKSYFR
EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR GKIWNTLLFL LTVQLVGLIK
SSFASCLRGN IVMVFMSLYS VLYMSSLLPA KMFAIATINK AGWGTSGRKT IVVNFIGLIP
VSVWFTILLG GVIFTIYKES KKPFSESKQT VLIVGTLLYA CYWVMLLTLY VVLINKCGRR
KKGQQYDMVL DV
