A3LT2_HUMAN
ID A3LT2_HUMAN Reviewed; 340 AA.
AC U3KPV4;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Alpha-1,3-galactosyltransferase 2 {ECO:0000312|HGNC:HGNC:30005};
DE EC=2.4.1.87 {ECO:0000250|UniProtKB:Q3V1N9};
DE AltName: Full=Isoglobotriaosylceramide synthase;
DE Short=iGb3 synthase {ECO:0000303|PubMed:18630988};
DE Short=iGb3S {ECO:0000303|PubMed:18630988};
GN Name=A3GALT2 {ECO:0000312|HGNC:HGNC:30005};
GN Synonyms=A3GALT2P {ECO:0000312|HGNC:HGNC:30005},
GN IGBS3S {ECO:0000303|PubMed:18630988};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP MISCELLANEOUS.
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).
RN [3]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=23378701; DOI=10.1080/07328303.2012.741637;
RA Tahiri F., Li Y., Hawke D., Ganiko L., Almeida I., Levery S., Zhou D.;
RT "Lack of iGb3 and isoglobo-Series glycosphingolipids in pig organs used for
RT xenotransplantation: implications for natural killer T-cell biology.";
RL J. Carbohydr. Chem. 32:44-67(2013).
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 {ECO:0000305|PubMed:23378701}.
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:0000250|UniProtKB:A0A4Z3};
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; Evidence={ECO:0000250};
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 -!- TISSUE SPECIFICITY: Expressed in thymus and monocyte derived dendritic
CC cells. {ECO:0000269|PubMed:23378701}.
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 -!- SIMILARITY: Belongs to the glycosyltransferase 6 family. {ECO:0000305}.
CC -!- CAUTION: According to a report, the spliced A3GALT2 mRNA is not
CC detected in human tissues (PubMed:18630988). The functional activity of
CC human A3GALT2 tested by expressing a chimeric protein containing the
CC catalytic domain of human A3GALT2 is unable to synthesize isogloboside
CC 3 (iGb3). Futhermore mutagenesis experiments in rat, show that the
CC mutant 'Asn-253' of human A3GALT2 completely eliminates alpha-1,3-
CC galactosyltransferase activity (PubMed:18630988).
CC {ECO:0000303|PubMed:18630988}.
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DR EMBL; AL513327; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS60080.1; -.
DR RefSeq; NP_001073907.1; NM_001080438.1.
DR AlphaFoldDB; U3KPV4; -.
DR SMR; U3KPV4; -.
DR STRING; 9606.ENSP00000475261; -.
DR GlyGen; U3KPV4; 2 sites.
DR BioMuta; A3GALT2; -.
DR PeptideAtlas; U3KPV4; -.
DR PRIDE; U3KPV4; -.
DR Antibodypedia; 76335; 3 antibodies from 1 providers.
DR DNASU; 127550; -.
DR Ensembl; ENST00000442999.3; ENSP00000475261.1; ENSG00000184389.9.
DR GeneID; 127550; -.
DR KEGG; hsa:127550; -.
DR MANE-Select; ENST00000442999.3; ENSP00000475261.1; NM_001080438.1; NP_001073907.1.
DR UCSC; uc031plq.1; human.
DR CTD; 127550; -.
DR DisGeNET; 127550; -.
DR GeneCards; A3GALT2; -.
DR HGNC; HGNC:30005; A3GALT2.
DR HPA; ENSG00000184389; Not detected.
DR MIM; 619850; gene.
DR neXtProt; NX_U3KPV4; -.
DR OpenTargets; ENSG00000184389; -.
DR VEuPathDB; HostDB:ENSG00000184389; -.
DR eggNOG; ENOG502QW2H; Eukaryota.
DR GeneTree; ENSGT00950000182858; -.
DR HOGENOM; CLU_062445_1_0_1; -.
DR OMA; QSVVYYV; -.
DR OrthoDB; 1204439at2759; -.
DR PhylomeDB; U3KPV4; -.
DR PathwayCommons; U3KPV4; -.
DR SignaLink; U3KPV4; -.
DR BioGRID-ORCS; 127550; 11 hits in 981 CRISPR screens.
DR GenomeRNAi; 127550; -.
DR Pharos; U3KPV4; Tdark.
DR PRO; PR:U3KPV4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; U3KPV4; protein.
DR Bgee; ENSG00000184389; Expressed in blood and 68 other tissues.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
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; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0030259; P:lipid glycosylation; IBA:GO_Central.
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 Glycoprotein; Glycosyltransferase; Golgi apparatus; Lipid metabolism;
KW Manganese; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..340
FT /note="Alpha-1,3-galactosyltransferase 2"
FT /id="PRO_0000436524"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 13..32
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..340
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT BINDING 199
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 340 AA; 38754 MW; 129B673AC0DCE037 CRC64;
MALKEGLRAW KRIFWRQILL TLGLLGLFLY GLPKFRHLEA LIPMGVCPSA TMSQLRDNFT
GALRPWARPE VLTCTPWGAP IIWDGSFDPD VAKQEARQQN LTIGLTIFAV GRYLEKYLER
FLETAEQHFM AGQSVMYYVF TELPGAVPRV ALGPGRRLPV ERVARERRWQ DVSMARMRTL
HAALGGLPGR EAHFMFCMDV DQHFSGTFGP EALAESVAQL HSWHYHWPSW LLPFERDAHS
AAAMAWGQGD FYNHAAVFGG SVAALRGLTA HCAGGLDWDR ARGLEARWHD ESHLNKFFWL
HKPAKVLSPE FCWSPDIGPR AEIRRPRLLW APKGYRLLRN
