HYAS3_XENLA
ID HYAS3_XENLA Reviewed; 557 AA.
AC O57426; Q6W9J2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Hyaluronan synthase 3;
DE EC=2.4.1.212 {ECO:0000250|UniProtKB:O08650};
DE AltName: Full=Hyaluronate synthase 3;
DE AltName: Full=Hyaluronic acid synthase 3;
DE Short=HA synthase 3;
DE Short=xHAS3;
GN Name=has3;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14667843; DOI=10.1016/s0945-053x(03)00082-9;
RA Vigetti D., Viola M., Gornati R., Ori M., Nardi I., Passi A., De Luca G.,
RA Bernardini G.;
RT "Molecular cloning, genomic organization and developmental expression of
RT the Xenopus laevis hyaluronan synthase 3.";
RL Matrix Biol. 22:511-517(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 265-454.
RX PubMed=9442026; DOI=10.1074/jbc.273.4.1923;
RA Spicer A.P., McDonald J.A.;
RT "Characterization and molecular evolution of a vertebrate hyaluronan
RT synthase gene family.";
RL J. Biol. Chem. 273:1923-1932(1998).
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.
CC {ECO:0000250|UniProtKB:O08650}.
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:O08650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466;
CC Evidence={ECO:0000250|UniProtKB:O08650};
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:O08650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529;
CC Evidence={ECO:0000250|UniProtKB:O08650};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC {ECO:0000250|UniProtKB:O08650}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O08650};
CC Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O08650}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:O08650}; Multi-pass membrane protein.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:O08650}. Note=Travels
CC through endoplasmic reticulum (ER), Golgi, plasma membrane, and
CC endocytic vesicles (By similarity). Actives only when present in plasma
CC membrane (By similarity). O-GlcNAcylation controls its membrane
CC localization (By similarity). A rapid recycling of HAS3 between plasma
CC membrane and endosomes is controlled by the cytosolic levels of UDP-
CC GlcUA and UDP-GlcNAc (By similarity). {ECO:0000250|UniProtKB:O00219,
CC ECO:0000250|UniProtKB:O08650}.
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 -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
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DR EMBL; AF015778; AAB94539.1; -; Genomic_DNA.
DR EMBL; AY302252; AAP58398.1; -; mRNA.
DR RefSeq; NP_001083642.1; NM_001090173.1.
DR AlphaFoldDB; O57426; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR GeneID; 399037; -.
DR CTD; 399037; -.
DR Xenbase; XB-GENE-987831; has3.S.
DR OrthoDB; 332363at2759; -.
DR UniPathway; UPA00341; -.
DR Proteomes; UP000186698; Genome assembly.
DR Bgee; 399037; Expressed in egg cell and 9 other tissues.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050501; F:hyaluronan synthase activity; 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; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasmic vesicle; Glycosyltransferase; Golgi apparatus;
KW Membrane; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..557
FT /note="Hyaluronan synthase 3"
FT /id="PRO_0000197181"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 11..31
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..44
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 45..65
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 368..388
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..398
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 399..419
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 431..451
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 452..463
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 464..484
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..501
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 502..522
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 523..557
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="K -> N (in Ref. 2; AAB94539)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 557 AA; 64061 MW; F81478B685BF7AD5 CRC64;
MPGKFQTGLR VLATCLFALL VLGGILVAYV TGYQFIHTDR HHLSFGLYGA ILGLHLLSQS
LFAFLEHRKM RGGGRCPSGK STVVLCIAAY QEDPEYLRKC LRSVRRLSYP HLRVIMVVDG
NTEEDRYMMD IFREVMGSEG TCCYIWDKNY HESEEGGQEG ERGVQEMVKN FQYVCIMQKW
GGKREVTYTA FRALGDSVAY VQVCDSDTVL DPACTAEMLR ILEEDPEVGG VGGDVQILNK
YESWISFLSS FRYWMAFNVE RACQSYFGCV QCISGPLGMY RNSLLQYFLE DWYHQTFLGQ
KCSFGDDRHL TNRVLSMGFR TKYTARSRCL TETPTRYLRW LNQQTRWSKS YFREWLYNAL
WFHKHHLWMT YESVVTGFFP FFLVATVVQL FYRGRVWNIL LFLLTVQLVG ILKATYACIL
RGNAEMIFMS LYSLLYMTSL LPAKIFAVIT IKKSGWGTSG RRKLVVNFMG MVPVSVWFCI
LLGGLVYTAY CQSHDPFTET ELLFLLTGAI LYGCYWVALL SLYLALIARR CGKRQELYNL
ALEEVSEPEP AAKAIKP
