A3LT2_MOUSE
ID A3LT2_MOUSE Reviewed; 370 AA.
AC Q3V1N9; B2KGX5; B2KGX6; M9MMK2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Alpha-1,3-galactosyltransferase 2 {ECO:0000250|UniProtKB:U3KPV4};
DE EC=2.4.1.87 {ECO:0000269|PubMed:16456004};
DE AltName: Full=Isoglobotriaosylceramide synthase;
DE Short=iGb3 synthase {ECO:0000303|PubMed:16456004};
DE Short=iGb3S {ECO:0000303|PubMed:16456004};
GN Name=A3galt2; Synonyms=Igb3s;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 2),
RP FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Thymocyte;
RX PubMed=16456004; DOI=10.4049/jimmunol.176.4.2448;
RA Milland J., Christiansen D., Lazarus B.D., Taylor S.G., Xing P.X.,
RA Sandrin M.S.;
RT "The molecular basis for galalpha(1,3)gal expression in animals with a
RT deletion of the alpha1,3galactosyltransferase gene.";
RL J. Immunol. 176:2448-2454(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-291.
RC STRAIN=NOD;
RA Kerry G.;
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP FUNCTION.
RX PubMed=15539565; DOI=10.1126/science.1103440;
RA Zhou D., Mattner J., Cantu C. III, Schrantz N., Yin N., Gao Y., Sagiv Y.,
RA Hudspeth K., Wu Y.P., Yamashita T., Teneberg S., Wang D., Proia R.L.,
RA Levery S.B., Savage P.B., Teyton L., Bendelac A.;
RT "Lysosomal glycosphingolipid recognition by NKT cells.";
RL Science 306:1786-1789(2004).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=17372206; DOI=10.1073/pnas.0611139104;
RA Porubsky S., Speak A.O., Luckow B., Cerundolo V., Platt F.M., Grone H.J.;
RT "Normal development and function of invariant natural killer T cells in
RT mice with isoglobotrihexosylceramide (iGb3) deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5977-5982(2007).
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:15539565,
CC ECO:0000269|PubMed:16456004}.
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:16456004};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13014;
CC Evidence={ECO:0000250|UniProtKB:A0A4Z3};
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:0000250|UniProtKB:A0A4Z3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42001;
CC Evidence={ECO:0000250|UniProtKB:A0A4Z3};
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:0000250|UniProtKB:A0A4Z3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56741;
CC Evidence={ECO:0000250|UniProtKB:A0A4Z3};
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:0000250|UniProtKB:A0A4Z3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:A0A4Z3}. Note=Also found in numerous large
CC vesicles throughout the cytoplasm of the soma.
CC {ECO:0000250|UniProtKB:A0A4Z3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3V1N9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3V1N9-2; Sequence=VSP_054297;
CC -!- TISSUE SPECIFICITY: Thymus and lung. {ECO:0000269|PubMed:16456004}.
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 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are fertile, develop normally and exhibit no
CC overt behavioral abnormalities. However, compared to heterozygous mice
CC they lack expression of the glycosphingolipid
CC isoglobotrihexosylceramide (iGb3) in the dorsal root ganglion.
CC {ECO:0000269|PubMed:17372206}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 6 family. {ECO:0000305}.
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DR EMBL; AY491982; AAS66769.1; -; mRNA.
DR EMBL; AK132334; BAE21111.1; -; mRNA.
DR EMBL; CU467499; CAQ52295.1; -; Genomic_DNA.
DR EMBL; CU467499; CAQ52296.1; -; Genomic_DNA.
DR EMBL; AL611983; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18675.1; -. [Q3V1N9-1]
DR RefSeq; NP_001009819.1; NM_001009819.2. [Q3V1N9-1]
DR AlphaFoldDB; Q3V1N9; -.
DR SMR; Q3V1N9; -.
DR STRING; 10090.ENSMUSP00000030585; -.
DR CAZy; GT6; Glycosyltransferase Family 6.
DR GlyGen; Q3V1N9; 2 sites.
DR PaxDb; Q3V1N9; -.
DR PRIDE; Q3V1N9; -.
DR Antibodypedia; 76335; 3 antibodies from 1 providers.
DR DNASU; 215493; -.
DR Ensembl; ENSMUST00000030585; ENSMUSP00000030585; ENSMUSG00000028794. [Q3V1N9-1]
DR Ensembl; ENSMUST00000106077; ENSMUSP00000101687; ENSMUSG00000028794. [Q3V1N9-2]
DR GeneID; 215493; -.
DR KEGG; mmu:215493; -.
DR UCSC; uc008uvm.1; mouse. [Q3V1N9-1]
DR CTD; 127550; -.
DR MGI; MGI:2685279; A3galt2.
DR VEuPathDB; HostDB:ENSMUSG00000028794; -.
DR eggNOG; ENOG502QW2H; Eukaryota.
DR GeneTree; ENSGT00950000182858; -.
DR HOGENOM; CLU_062445_1_0_1; -.
DR InParanoid; Q3V1N9; -.
DR OMA; QSVVYYV; -.
DR OrthoDB; 1204439at2759; -.
DR PhylomeDB; Q3V1N9; -.
DR TreeFam; TF330991; -.
DR BioGRID-ORCS; 215493; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Phc2; mouse.
DR PRO; PR:Q3V1N9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q3V1N9; protein.
DR Bgee; ENSMUSG00000028794; Expressed in epiblast (generic) and 21 other tissues.
DR GO; GO:0005794; C:Golgi apparatus; ISS: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; ISS:UniProtKB.
DR GO; GO:0001962; F:alpha-1,3-galactosyltransferase activity; IGI:MGI.
DR GO; GO:0016757; F:glycosyltransferase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0047276; F:N-acetyllactosaminide 3-alpha-galactosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0071287; P:cellular response to manganese ion; ISO:MGI.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IGI:MGI.
DR GO; GO:0030259; P:lipid glycosylation; ISS: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 2: Evidence at transcript level;
KW Alternative splicing; Glycoprotein; Glycosyltransferase; Golgi apparatus;
KW Lipid metabolism; Manganese; Membrane; Metal-binding; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..370
FT /note="Alpha-1,3-galactosyltransferase 2"
FT /id="PRO_0000314871"
FT TOPO_DOM 1..42
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..65
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..370
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 321
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 138..143
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 229..231
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 229
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 231
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 251..254
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT BINDING 363..369
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14769"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..37
FT /note="MALGTELGVSWPGSHGSCREQEGQRQRGPGKPTWGLS -> MALIEF (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054297"
FT VARIANT 291
FT /note="S -> N (in strain: NOD)"
FT /evidence="ECO:0000269|Ref.3"
SQ SEQUENCE 370 AA; 42649 MW; 12F4AEB917F2C380 CRC64;
MALGTELGVS WPGSHGSCRE QEGQRQRGPG KPTWGLSRAK KRLLWRFFLS AFGFLGLYHY
RFIIIRLIEG SIPMGTCPTA IMPLPRDNFT GVLHHWARPE VLTCTSWGAP IIWDGTFDPH
VAQQEARRRN LTIGLTVFAV GRYLEKYLEH FLVSAEQHFM VGQNVVYYVF TDRPEAVPYV
ALGQGRLLRA KPVQRERRWQ DVSMARMPTL HEALGGQLGQ EADFVFCLDV DQYFTGNFGP
EVLADLVAQL HAWHYRWPRW LLPYERDKRS AAALSLSEGD FYYHAAVFGG SVAALLKLTA
HCATGQQLDH KRGIEALWHD ESHLNKFFWL NKPTKLLSPE FCWAEEIIWR REIHHPRLLW
APKEYTLVRN
