HAS_PASMD
ID HAS_PASMD Reviewed; 972 AA.
AC Q7BLV3; O68389; O85457;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Hyaluronan synthase;
DE EC=2.4.1.212;
DE Includes:
DE RecName: Full=Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-beta-N-acetylglucosaminyltransferase;
DE AltName: Full=UDP-GlcNAc transferase;
DE Includes:
DE RecName: Full=N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase;
DE EC=2.4.1.226;
DE AltName: Full=UDP-GlcUA transferase;
GN Name=hyaD;
OS Pasteurella multocida.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Pasteurella.
OX NCBI_TaxID=747;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Serogroup A:1 / X73;
RX PubMed=9770287; DOI=10.1111/j.1574-6968.1998.tb13903.x;
RA Chung J.Y., Zhang Y., Adler B.;
RT "The capsule biosynthetic locus of Pasteurella multocida A:1.";
RL FEMS Microbiol. Lett. 166:289-296(1998).
RN [2]
RP SEQUENCE REVISION TO 855-972.
RA Chung J.Y., Zhang Y., Adler B.;
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 15742 / P1059;
RX PubMed=9525958; DOI=10.1074/jbc.273.14.8454;
RA DeAngelis P.L., Jing W., Drake R.R., Achyuthan A.M.;
RT "Identification and molecular cloning of a unique hyaluronan synthase from
RT Pasteurella multocida.";
RL J. Biol. Chem. 273:8454-8458(1998).
RN [4]
RP SEQUENCE REVISION TO 43.
RA DeAngelis P.L., Jing W., Achyuthan A.M.;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10873488; DOI=10.1006/mpat.2000.0365;
RA Fuller T.E., Kennedy M.J., Lowery D.E.;
RT "Identification of Pasteurella multocida virulence genes in a septicemic
RT mouse model using signature-tagged mutagenesis.";
RL Microb. Pathog. 29:25-38(2000).
RN [6]
RP CHARACTERIZATION, AND MUTAGENESIS OF ASP-196 AND ASP-477.
RC STRAIN=ATCC 15742 / P1059;
RX PubMed=10988250; DOI=10.1093/glycob/10.9.883;
RA Jing W., DeAngelis P.L.;
RT "Dissection of the two transferase activities of the Pasteurella multocida
RT hyaluronan synthase: two active sites exist in one polypeptide.";
RL Glycobiology 10:883-889(2000).
RN [7]
RP CHARACTERIZATION, AND MUTAGENESIS OF ASP-247; ASP-249; GLU-369; ASP-370;
RP ASP-527; ASP-529 AND ASP-563.
RX PubMed=12799342; DOI=10.1093/glycob/cwg085;
RA Jing W., DeAngelis P.L.;
RT "Analysis of the two active sites of the hyaluronan synthase and the
RT chondroitin synthase of Pasteurella multocida.";
RL Glycobiology 13:661-671(2003).
CC -!- FUNCTION: Catalyzes the polymerization of hyaluronan, a polysaccharide
CC composed of a repeating disaccharide of N-acetylglucosamine (GlcNAc)
CC and glucuronic acid (GlcUA) units. Each unit has the composition in
CC beta-(1->4)-GlcUA-beta-(1->3)-GlcNAc.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-
CC (1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP-alpha-D-
CC glucuronate = 3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-
CC GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-
CC [protein] + H(+) + UDP; Xref=Rhea:RHEA:23428, Rhea:RHEA-COMP:12575,
CC Rhea:RHEA-COMP:14058, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:132105, ChEBI:CHEBI:138442;
CC EC=2.4.1.226;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-([beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)](n)-beta-D-
CC GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-(beta-
CC D-GlcA-(1->3)-[beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)](n)-beta-D-
CC GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:54996,
CC Rhea:RHEA-COMP:14060, Rhea:RHEA-COMP:14061, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:138444,
CC ChEBI:CHEBI:138445; EC=2.4.1.226;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=160 uM for UDP-N-acetyl-D-glucosamine;
CC KM=140 uM for UDP-D-glucuronate;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. CS/HAS
CC subfamily. {ECO:0000305}.
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DR EMBL; AF067175; AAC67250.2; -; Genomic_DNA.
DR EMBL; AF036004; AAC38318.2; -; Genomic_DNA.
DR EMBL; AF237926; AAF68412.1; -; Genomic_DNA.
DR PIR; T09595; T09595.
DR RefSeq; WP_005754202.1; NZ_MAPR01000001.1.
DR RefSeq; WP_016504510.1; NZ_UGSU01000002.1.
DR AlphaFoldDB; Q7BLV3; -.
DR SMR; Q7BLV3; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR BRENDA; 2.4.1.212; 4558.
DR SABIO-RK; Q7BLV3; -.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050501; F:hyaluronan synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0050510; F:N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.90.550.10; -; 2.
DR InterPro; IPR001173; Glyco_trans_2-like.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF00535; Glycos_transf_2; 2.
DR SUPFAM; SSF53448; SSF53448; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Glycosyltransferase; Membrane; Multifunctional enzyme;
KW Repeat; Transferase.
FT CHAIN 1..972
FT /note="Hyaluronan synthase"
FT /id="PRO_0000059259"
FT REGION 152..325
FT /note="A1"
FT REGION 432..604
FT /note="A2"
FT MUTAGEN 196
FT /note="D->E,K,N: Complete loss of GlcNAc transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:10988250"
FT MUTAGEN 247
FT /note="D->E,K,N: Complete loss of GlcNAc transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 249
FT /note="D->E,K,N: Complete loss of GlcNAc transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 369
FT /note="E->D: Complete loss of GlcNAc transferase activity.
FT Regains 30% of wild-type activity at high UDP-GlcNAc
FT concentrations."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 369
FT /note="E->H,Q: Complete loss of GlcNAc transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 370
FT /note="D->E,K,N: Complete loss of GlcNAc transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 477
FT /note="D->E,K,N: Complete loss of GlcUA transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:10988250"
FT MUTAGEN 527
FT /note="D->E,K,N: Complete loss of GlcUA transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 529
FT /note="D->E: 90% loss of GlcUA transferase activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 529
FT /note="D->K,N: Complete loss of GlcUA transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12799342"
FT MUTAGEN 563
FT /note="D->E,K,N: No effect."
FT /evidence="ECO:0000269|PubMed:12799342"
FT CONFLICT 17
FT /note="Q -> E (in Ref. 1; AAC67250)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="K -> Q (in Ref. 5; AAF68412)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 972 AA; 111839 MW; D933BD8C1E923685 CRC64;
MNTLSQAIKA YNSNDYQLAL KLFEKSAEIY GRKIVEFQIT KCKEKLSAHP SVNSAHLSVN
KEEKVNVCDS PLDIATQLLL SNVKKLVLSD SEKNTLKNKW KLLTEKKSEN AEVRAVALVP
KDFPKDLVLA PLPDHVNDFT WYKKRKKRLG IKPEHQHVGL SIIVTTFNRP AILSITLACL
VNQKTHYPFE VIVTDDGSQE DLSPIIRQYE NKLDIRYVRQ KDNGFQASAA RNMGLRLAKY
DFIGLLDCDM APNPLWVHSY VAELLEDDDL TIIGPRKYID TQHIDPKDFL NNASLLESLP
EVKTNNSVAA KGEGTVSLDW RLEQFEKTEN LRLSDSPFRF FAAGNVAFAK KWLNKSGFFD
EEFNHWGGED VEFGYRLFRY GSFFKTIDGI MAYHQEPPGK ENETDREAGK NITLDIMREK
VPYIYRKLLP IEDSHINRVP LVSIYIPAYN CANYIQRCVD SALNQTVVDL EVCICNDGST
DNTLEVINKL YGNNPRVRIM SKPNGGIASA SNAAVSFAKG YYIGQLDSDD YLEPDAVELC
LKEFLKDKTL ACVYTTNRNV NPDGSLIANG YNWPEFSREK LTTAMIAHHF RMFTIRAWHL
TDGFNEKIEN AVDYDMFLKL SEVGKFKHLN KICYNRVLHG DNTSIKKLGI QKKNHFVVVN
QSLNRQGITY YNYDEFDDLD ESRKYIFNKT AEYQEEIDIL KDIKIIQNKD AKIAVSIFYP
NTLNGLVKKL NNIIEYNKNI FVIVLHVDKN HLTPDIKKEI LAFYHKHQVN ILLNNDISYY
TSNRLIKTEA HLSNINKLSQ LNLNCEYIIF DNHDSLFVKN DSYAYMKKYD VGMNFSALTH
DWIEKINAHP PFKKLIKTYF NDNDLKSMNV KGASQGMFMT YALAHELLTI IKEVITSCQS
IDSVPEYNTE DIWFQFALLI LEKKTGHVFN KTSTLTYMPW ERKLQWTNEQ IESAKRGENI
PVNKFIINSI TL
