ID HYAS1_HUMAN Reviewed; 578 AA.
AC Q92839; Q14470; Q9NS49;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 24-JAN-2024, entry version 184.
DE RecName: Full=Hyaluronan synthase 1;
DE EC=2.4.1.212;
DE AltName: Full=Hyaluronate synthase 1;
DE AltName: Full=Hyaluronic acid synthase 1;
DE Short=HA synthase 1;
DE Short=HuHAS1;
GN Name=HAS1; Synonyms=HAS;
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], VARIANT ARG-14, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=8651928; DOI=10.1006/bbrc.1996.0827;
RA Itano N., Kimata K.;
RT "Molecular cloning of human hyaluronan synthase.";
RL Biochem. Biophys. Res. Commun. 222:816-820(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-14.
RC TISSUE=Lymph node;
RX PubMed=8798544; DOI=10.1074/jbc.271.38.23395;
RA Shyjan A.M., Heldin P., Butcher E.C., Yoshino T., Briskin M.J.;
RT "Functional cloning of the cDNA for a human hyaluronan synthase.";
RL J. Biol. Chem. 271:23395-23399(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) 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. This is one of the isozymes
CC catalyzing that reaction. Also able to catalyze the synthesis of chito-
CC oligosaccharide depending on the substrate (By similarity).
CC {ECO:0000250}.
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 -!- 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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC -!- INTERACTION:
CC Q92839; Q92839: HAS1; NbExp=9; IntAct=EBI-1052423, EBI-1052423;
CC Q92839; Q92819: HAS2; NbExp=9; IntAct=EBI-1052423, EBI-16628852;
CC Q92839; O00219: HAS3; NbExp=9; IntAct=EBI-1052423, EBI-16628799;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in ovary
CC followed by spleen, thymus, prostate, testes and large intestine.
CC Weakly expressed in small intestine. {ECO:0000269|PubMed:8651928}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA12351.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D84424; BAA12351.1; ALT_INIT; mRNA.
DR EMBL; U59269; AAC50706.1; -; mRNA.
DR EMBL; AC018755; AAF87845.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW72038.1; -; Genomic_DNA.
DR CCDS; CCDS12838.1; -.
DR PIR; JC4812; JC4812.
DR RefSeq; NP_001514.2; NM_001523.3.
DR AlphaFoldDB; Q92839; -.
DR SMR; Q92839; -.
DR BioGRID; 109286; 9.
DR CORUM; Q92839; -.
DR IntAct; Q92839; 2.
DR STRING; 9606.ENSP00000222115; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR TCDB; 4.D.1.1.10; the putative vectorial glycosyl polymerization (vgp) family.
DR iPTMnet; Q92839; -.
DR PhosphoSitePlus; Q92839; -.
DR BioMuta; HAS1; -.
DR DMDM; 209572627; -.
DR MassIVE; Q92839; -.
DR PaxDb; 9606-ENSP00000222115; -.
DR PeptideAtlas; Q92839; -.
DR ProteomicsDB; 75530; -.
DR Antibodypedia; 52809; 265 antibodies from 30 providers.
DR DNASU; 3036; -.
DR Ensembl; ENST00000222115.5; ENSP00000222115.1; ENSG00000105509.11.
DR GeneID; 3036; -.
DR KEGG; hsa:3036; -.
DR UCSC; uc002pxo.1; human.
DR AGR; HGNC:4818; -.
DR CTD; 3036; -.
DR DisGeNET; 3036; -.
DR GeneCards; HAS1; -.
DR HGNC; HGNC:4818; HAS1.
DR HPA; ENSG00000105509; Tissue enhanced (adipose tissue, ovary).
DR MIM; 601463; gene.
DR neXtProt; NX_Q92839; -.
DR OpenTargets; ENSG00000105509; -.
DR PharmGKB; PA29194; -.
DR VEuPathDB; HostDB:ENSG00000105509; -.
DR eggNOG; KOG2571; Eukaryota.
DR GeneTree; ENSGT00390000010337; -.
DR InParanoid; Q92839; -.
DR OrthoDB; 1361850at2759; -.
DR PhylomeDB; Q92839; -.
DR TreeFam; TF332506; -.
DR BRENDA; 2.4.1.212; 2681.
DR PathwayCommons; Q92839; -.
DR Reactome; R-HSA-2142850; Hyaluronan biosynthesis and export.
DR SignaLink; Q92839; -.
DR UniPathway; UPA00341; -.
DR BioGRID-ORCS; 3036; 17 hits in 1150 CRISPR screens.
DR GeneWiki; HAS1; -.
DR GenomeRNAi; 3036; -.
DR Pharos; Q92839; Tbio.
DR PRO; PR:Q92839; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92839; Protein.
DR Bgee; ENSG00000105509; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 112 other cell types or tissues.
DR ExpressionAtlas; Q92839; baseline and differential.
DR Genevisible; Q92839; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050501; F:hyaluronan synthase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IDA: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:0006024; P:glycosaminoglycan biosynthetic process; TAS:ProtInc.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; IBA:GO_Central.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IMP:UniProtKB.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR22913; HYALURONAN SYNTHASE; 1.
DR PANTHER; PTHR22913:SF4; HYALURONAN SYNTHASE 1; 1.
DR Pfam; PF13641; Glyco_tranf_2_3; 1.
DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
PE 1: Evidence at protein level;
KW Glycosyltransferase; Membrane; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..578
FT /note="Hyaluronan synthase 1"
FT /id="PRO_0000197169"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..46
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..52
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..399
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..420
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 421..430
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..451
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 452..457
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..478
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479..497
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 519..540
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 541..561
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 562..578
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT VARIANT 14
FT /note="C -> R (in dbSNP:rs7248778)"
FT /evidence="ECO:0000269|PubMed:8651928,
FT ECO:0000269|PubMed:8798544"
FT /id="VAR_047025"
FT CONFLICT 1..2
FT /note="MR -> RS (in Ref. 1; BAA12351)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="G -> A (in Ref. 1; BAA12351)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="L -> V (in Ref. 1; BAA12351)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 64832 MW; 2FE3A44B0D5380FF CRC64;
MRQQDAPKPT PAACRCSGLA RRVLTIAFAL LILGLMTWAY AAGVPLASDR YGLLAFGLYG
AFLSAHLVAQ SLFAYLEHRR VAAAARGPLD AATARSVALT ISAYQEDPAY LRQCLASARA
LLYPRARLRV LMVVDGNRAE DLYMVDMFRE VFADEDPATY VWDGNYHQPW EPAAAGAVGA
GAYREVEAED PGRLAVEALV RTRRCVCVAQ RWGGKREVMY TAFKALGDSV DYVQVCDSDT
RLDPMALLEL VRVLDEDPRV GAVGGDVRIL NPLDSWVSFL SSLRYWVAFN VERACQSYFH
CVSCISGPLG LYRNNLLQQF LEAWYNQKFL GTHCTFGDDR HLTNRMLSMG YATKYTSRSR
CYSETPSSFL RWLSQQTRWS KSYFREWLYN ALWWHRHHAW MTYEAVVSGL FPFFVAATVL
RLFYAGRPWA LLWVLLCVQG VALAKAAFAA WLRGCLRMVL LSLYAPLYMC GLLPAKFLAL
VTMNQSGWGT SGRRKLAANY VPLLPLALWA LLLLGGLVRS VAHEARADWS GPSRAAEAYH
LAAGAGAYVG YWVAMLTLYW VGVRRLCRRR TGGYRVQV
//
