A3LT2_RAT
ID A3LT2_RAT Reviewed; 339 AA.
AC A0A4Z3; A2JQW1;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Alpha-1,3-galactosyltransferase 2 {ECO:0000250|UniProtKB:U3KPV4};
DE EC=2.4.1.87 {ECO:0000269|PubMed:10854427};
DE AltName: Full=Isoglobotriaosylceramide synthase;
DE Short=iGb3 synthase {ECO:0000303|PubMed:10854427};
DE Short=iGb3S {ECO:0000303|PubMed:18630988};
GN Name=A3galt2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF
RP 198-ASP--ASP-200, AND CATALYTIC ACTIVITY.
RC STRAIN=Sprague-Dawley; TISSUE=Placenta;
RX PubMed=10854427; DOI=10.1074/jbc.m002629200;
RA Keusch J.J., Manzella S.M., Nyame K.A., Cummings R.D., Baenziger J.U.;
RT "Expression cloning of a new member of the ABO blood group
RT glycosyltransferases, iGb3 synthase, that directs the synthesis of
RT isoglobo-glycosphingolipids.";
RL J. Biol. Chem. 275:25308-25314(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12626403; DOI=10.1093/glycob/cwg030;
RA Taylor S.G., McKenzie I.F., Sandrin M.S.;
RT "Characterization of the rat alpha(1,3)galactosyltransferase: evidence for
RT two independent genes encoding glycosyltransferases that synthesize
RT Galalpha(1,3)Gal by two separate glycosylation pathways.";
RL Glycobiology 13:327-337(2003).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17206613; DOI=10.1002/cne.21233;
RA Fullmer J.M., Riedl M., Williams F.G., Sandrin M., Elde R.;
RT "Enzymes that synthesize the IB4 epitope are not sufficient to impart IB4
RT binding in dorsal root ganglia of rat.";
RL J. Comp. Neurol. 501:70-82(2007).
RN [5]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-187 AND TYR-252.
RX PubMed=18630988; DOI=10.1371/journal.pbio.0060172;
RA Christiansen D., Milland J., Mouhtouris E., Vaughan H., Pellicci D.G.,
RA McConville M.J., Godfrey D.I., Sandrin M.S.;
RT "Humans lack iGb3 due to the absence of functional iGb3-synthase:
RT implications for NKT cell development and transplantation.";
RL PLoS Biol. 6:E172-E172(2008).
CC -!- FUNCTION: Synthesizes the galactose-alpha(1,3)-galactose group on the
CC glycosphingolipid isoglobotrihexosylceramide or isogloboside 3 (iGb3)
CC by catalyzing the transfer of galactose from UDP-Galactose to its
CC acceptor molecule Gal-beta-1,4-Glc-ceramide. Can also catalyze the
CC addition of galactose to iGb3 itself to form polygalactose structures.
CC Synthesis of iGb3 is the initial step in the formation of the isoglobo-
CC series glycolipid pathway and is the precursor to isogloboside 4 (iGb4)
CC and isoForssman glycolipids. Can glycosylate only lipids and not
CC proteins and is solely responsible for initiating the synthesis of
CC isoglobo-series glycosphingolipids. {ECO:0000269|PubMed:10854427,
CC ECO:0000269|PubMed:12626403, ECO:0000269|PubMed:17206613}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl
CC derivative + UDP-alpha-D-galactose = an alpha-D-galactosyl-(1->3)-
CC beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative +
CC H(+) + UDP; Xref=Rhea:RHEA:13013, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:66914, ChEBI:CHEBI:133507,
CC ChEBI:CHEBI:138024; EC=2.4.1.87;
CC Evidence={ECO:0000269|PubMed:10854427};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13014;
CC Evidence={ECO:0000305|PubMed:10854427};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + UDP-
CC alpha-D-galactose = H(+) + isogloboside iGb3Cer (d18:1(4E)) + UDP;
CC Xref=Rhea:RHEA:42000, ChEBI:CHEBI:15378, ChEBI:CHEBI:17950,
CC ChEBI:CHEBI:52570, ChEBI:CHEBI:58223, ChEBI:CHEBI:66914;
CC Evidence={ECO:0000269|PubMed:10854427};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42001;
CC Evidence={ECO:0000305|PubMed:10854427};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=globoside Gb3Cer + UDP-alpha-D-galactose = GalGb3Cer + H(+) +
CC UDP; Xref=Rhea:RHEA:56740, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:66914, ChEBI:CHEBI:88154, ChEBI:CHEBI:140743;
CC Evidence={ECO:0000269|PubMed:10854427};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56741;
CC Evidence={ECO:0000305|PubMed:10854427};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P14769};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000250|UniProtKB:P14769};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:17206613, ECO:0000269|PubMed:18630988}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:17206613,
CC ECO:0000269|PubMed:18630988}. Note=Also found in numerous large
CC vesicles throughout the cytoplasm of the soma.
CC -!- TISSUE SPECIFICITY: Dorsal root ganglia neurons (at protein level).
CC High levels in spleen, thymus and skeletal muscle, intermediate levels
CC in lung, uterus, pituitary and heart, low levels in brain, and
CC undetected in adrenal gland and liver. {ECO:0000269|PubMed:10854427,
CC ECO:0000269|PubMed:12626403, ECO:0000269|PubMed:17206613}.
CC -!- DOMAIN: The conserved DXD motif is involved in cofactor binding. The
CC manganese ion interacts with the beta-phosphate group of UDP and may
CC also have a role in catalysis.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 6 family. {ECO:0000305}.
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DR EMBL; AF248543; AAF82757.1; -; mRNA.
DR EMBL; BC061714; AAH61714.1; -; mRNA.
DR RefSeq; NP_612533.1; NM_138524.2.
DR AlphaFoldDB; A0A4Z3; -.
DR SMR; A0A4Z3; -.
DR STRING; 10116.ENSRNOP00000007851; -.
DR SwissLipids; SLP:000000794; -.
DR CAZy; GT6; Glycosyltransferase Family 6.
DR GlyGen; A0A4Z3; 2 sites.
DR PaxDb; A0A4Z3; -.
DR GeneID; 171553; -.
DR KEGG; rno:171553; -.
DR CTD; 127550; -.
DR RGD; 727913; A3galt2.
DR VEuPathDB; HostDB:ENSRNOG00000005935; -.
DR eggNOG; ENOG502QW2H; Eukaryota.
DR HOGENOM; CLU_062445_1_0_1; -.
DR InParanoid; A0A4Z3; -.
DR OMA; QSVVYYV; -.
DR OrthoDB; 1204439at2759; -.
DR PhylomeDB; A0A4Z3; -.
DR TreeFam; TF330991; -.
DR PRO; PR:A0A4Z3; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000005935; Expressed in jejunum and 18 other tissues.
DR Genevisible; A0A4Z3; RN.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0001962; F:alpha-1,3-galactosyltransferase activity; IDA:MGI.
DR GO; GO:0016757; F:glycosyltransferase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0047276; F:N-acetyllactosaminide 3-alpha-galactosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0071287; P:cellular response to manganese ion; IDA:RGD.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030259; P:lipid glycosylation; IDA:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR005076; Glyco_trans_6.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR10462; PTHR10462; 1.
DR Pfam; PF03414; Glyco_transf_6; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Manganese; Membrane;
KW Metal-binding; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..339
FT /note="Alpha-1,3-galactosyltransferase 2"
FT /id="PRO_0000314872"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..31
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..339
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 290
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 107..112
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 198..200
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 198
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 200
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 220..223
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 332..338
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 187
FT /note="L->P: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:18630988"
FT MUTAGEN 198..200
FT /note="DVD->AVA: Catalytically inactive."
FT /evidence="ECO:0000269|PubMed:10854427"
FT MUTAGEN 252
FT /note="Y->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:18630988"
SQ SEQUENCE 339 AA; 39548 MW; 171A191001F0C6CF CRC64;
MALEGLRAKK RLLWRLFLSA FGLLGLYHYW FKIFRLFEVF IPMGICPMAI MPLLKDNFTG
VLRHWARPEV LTCTSWGAPI IWDETFDPHV AEREARRQNL TIGLTVFAVG RYLEKYLEHF
LVSAEQYFMV GQNVVYYVFT DRPEAVPHVA LGQGRLLRVK PVRREKRWQD VSMARMLTLH
EALGGQLGRE ADYVFCLDVD QYFSGNFGPE VLADLVAQLH AWHFRWPRWM LPYERDKRSA
AALSLSEGDF YYHAAVFGGS VAALLKLTAH CATGQQLDRE HGIEARWHDE SHLNKFFWLS
KPTKLLSPEF CWAEEIGWRP EIHHPRLIWA PKEYALVRT
