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   24-JAN-2024, entry version 102.
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 = an isogloboside iGb3Cer (d18:1(4E)) + H(+) + 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=a globoside Gb3Cer + UDP-alpha-D-galactose = a globoside
CC         GalGb3Cer + H(+) + UDP; Xref=Rhea:RHEA:56740, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:58223, ChEBI:CHEBI:66914, ChEBI:CHEBI:88154,
CC         ChEBI:CHEBI:140743; 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   GlyCosmos; A0A4Z3; 2 sites, No reported glycans.
DR   GlyGen; A0A4Z3; 2 sites.
DR   PaxDb; 10116-ENSRNOP00000007851; -.
DR   Ensembl; ENSRNOT00055049651; ENSRNOP00055040851; ENSRNOG00055028687.
DR   Ensembl; ENSRNOT00060028244; ENSRNOP00060022759; ENSRNOG00060016470.
DR   Ensembl; ENSRNOT00065054014; ENSRNOP00065044444; ENSRNOG00065031329.
DR   GeneID; 171553; -.
DR   KEGG; rno:171553; -.
DR   AGR; RGD:727913; -.
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   OrthoDB; 4223357at2759; -.
DR   PhylomeDB; A0A4Z3; -.
DR   TreeFam; TF330991; -.
DR   PRO; PR:A0A4Z3; -.
DR   Proteomes; UP000002494; Chromosome 5.
DR   Bgee; ENSRNOG00000005935; Expressed in jejunum and 18 other cell types or tissues.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
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   CDD; cd02515; Glyco_transf_6; 1.
DR   InterPro; IPR005076; Glyco_trans_6.
DR   InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR   PANTHER; PTHR10462:SF33; ALPHA-1,3-GALACTOSYLTRANSFERASE 2; 1.
DR   PANTHER; PTHR10462; GLYCOSYLTRANSFERASE-RELATED; 1.
DR   Pfam; PF03414; Glyco_transf_6; 1.
DR   SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
DR   Genevisible; A0A4Z3; RN.
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
//