HYAS2_HETGA
ID HYAS2_HETGA Reviewed; 552 AA.
AC G5AY81;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 44.
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;
GN Name=Has2;
OS Heterocephalus glaber (Naked mole rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Bathyergidae;
OC Heterocephalus.
OX NCBI_TaxID=10181;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21993625; DOI=10.1038/nature10533;
RA Kim E.B., Fang X., Fushan A.A., Huang Z., Lobanov A.V., Han L.,
RA Marino S.M., Sun X., Turanov A.A., Yang P., Yim S.H., Zhao X.,
RA Kasaikina M.V., Stoletzki N., Peng C., Polak P., Xiong Z., Kiezun A.,
RA Zhu Y., Chen Y., Kryukov G.V., Zhang Q., Peshkin L., Yang L., Bronson R.T.,
RA Buffenstein R., Wang B., Han C., Li Q., Chen L., Zhao W., Sunyaev S.R.,
RA Park T.J., Zhang G., Wang J., Gladyshev V.N.;
RT "Genome sequencing reveals insights into physiology and longevity of the
RT naked mole rat.";
RL Nature 479:223-227(2011).
RN [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23783513; DOI=10.1038/nature12234;
RA Tian X., Azpurua J., Hine C., Vaidya A., Myakishev-Rempel M., Ablaeva J.,
RA Mao Z., Nevo E., Gorbunova V., Seluanov A.;
RT "High-molecular-mass hyaluronan mediates the cancer resistance of the naked
RT mole rat.";
RL Nature 499:346-349(2013).
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: Overexpressed in skin fibroblasts.
CC {ECO:0000269|PubMed:23783513}.
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 -!- MISCELLANEOUS: Via the strong production of high molecular mass
CC hyaluronan (HMM-HA) may be in part responsible for the low
CC susceptibility to cancers observed with those rodents.
CC {ECO:0000305|PubMed:23783513}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=an unexpected turn of events
CC - Issue 155 of December 2013;
CC URL="https://web.expasy.org/spotlight/back_issues/155/";
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DR EMBL; JH167500; EHB01992.1; -; Genomic_DNA.
DR AlphaFoldDB; G5AY81; -.
DR STRING; 10181.XP_004838067.1; -.
DR eggNOG; KOG2571; Eukaryota.
DR InParanoid; G5AY81; -.
DR OMA; KSATYVW; -.
DR UniPathway; UPA00341; -.
DR Proteomes; UP000006813; Unassembled WGS sequence.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
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:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0050501; F:hyaluronan synthase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
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:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1900625; P:positive regulation of monocyte aggregation; IEA:Ensembl.
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_0000424266"
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; 63442 MW; 36C8A97AD5E3729E CRC64;
MHCERFLCIL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG AFLASHLIIQ
SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR KCLQSVKRLT YPGIKVVMVI
DGNSDDDLYM MDIFSEVMGR DKSATYIWKN NFHEKGPGET DESHKESSQH VTQLVLSSKS
VCIMQKWGGK REVMYTAFRA LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG
DVQILNKYDS WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
SQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ QTRWSKSYFR
EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR GKIWNILLFL LTVQLVGLIK
SSFASCLRGN IVMVFMSLYS VLYMSSLLPA KMFAIATINK AGWGTSGRKT IVVNFIGLIP
VSVWFTILLG GVIFTIYKES KKPFSESKQT VLIVGTLLYA CYWVMLLTLY VVLINKCGRR
KKGQQYDMVL DV