ID B4GN2_HUMAN Reviewed; 566 AA.
AC Q8NHY0; B4DZE4; Q14CP1; Q86Y40;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 24-JAN-2024, entry version 148.
DE RecName: Full=Beta-1,4 N-acetylgalactosaminyltransferase 2;
DE EC=2.4.1.-;
DE AltName: Full=Sd(a) beta-1,4-GalNAc transferase;
DE AltName: Full=UDP-GalNAc:Neu5Aca2-3Galb-R b1,4-N-acetylgalactosaminyltransferase;
GN Name=B4GALNT2; Synonyms=GALGT2;
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 [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, AND VARIANT ASP-40.
RX PubMed=12678917; DOI=10.1042/bj20021892;
RA Montiel M.D., Krzewinski-Recchi M.A., Delannoy P., Harduin-Lepers A.;
RT "Molecular cloning, gene organization and expression of the human UDP-
RT GalNAc:Neu5Acalpha2-3Galbeta-R beta1,4-N-acetylgalactosaminyltransferase
RT responsible for the biosynthesis of the blood group Sda/Cad antigen:
RT evidence for an unusual extended cytoplasmic domain.";
RL Biochem. J. 373:369-379(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND VARIANT ASP-40.
RX PubMed=14688233; DOI=10.1093/jb/mvg192;
RA Lo Presti L., Cabuy E., Chiricolo M., Dall'Olio F.;
RT "Molecular cloning of the human beta1,4 N-acetylgalactosaminyltransferase
RT responsible for the biosynthesis of the Sd(a) histo-blood group antigen:
RT the sequence predicts a very long cytoplasmic domain.";
RL J. Biochem. 134:675-682(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-40.
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-459.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [9]
RP VARIANTS ARG-436; ARG-466 AND TRP-523, INVOLVEMENT IN SDPS, AND
RP POLYMORPHISM.
RX PubMed=31367682; DOI=10.1016/j.bbrep.2019.100659;
RA Stenfelt L., Hellberg A., Moeller M., Thornton N., Larson G., Olsson M.L.;
RT "Missense mutations in the C-terminal portion of the B4GALNT2-encoded
RT glycosyltransferase underlying the Sd(a-) phenotype.";
RL Biochem. Biophys. Rep. 19:100659-100659(2019).
CC -!- FUNCTION: Involved in the synthesis of the Sd(a) antigen (Sia-alpha2,3-
CC [GalNAc-beta1,4]Gal-beta1,4-GlcNAc), a carbohydrate determinant
CC expressed on erythrocytes, the colonic mucosa and other tissues.
CC Transfers a beta-1,4-linked GalNAc to the galactose residue of an
CC alpha-2,3-sialylated chain. {ECO:0000269|PubMed:12678917,
CC ECO:0000269|PubMed:14688233}.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- INTERACTION:
CC Q8NHY0; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-1042940, EBI-11343438;
CC Q8NHY0; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-1042940, EBI-11532900;
CC Q8NHY0; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-1042940, EBI-18304435;
CC Q8NHY0; P32243-2: OTX2; NbExp=3; IntAct=EBI-1042940, EBI-9087860;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NHY0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHY0-2; Sequence=VSP_017131;
CC Name=3;
CC IsoId=Q8NHY0-3; Sequence=VSP_045195;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in colon and to
CC a lesser extent in kidney, stomach, ileum and rectum.
CC {ECO:0000269|PubMed:12678917}.
CC -!- POLYMORPHISM: The Sd(a) antigen on red blood cells defines the SID
CC blood group system. There is considerable variability in the strength
CC of antigen expression, ranging from ordinary Sd(a+) to strong Sd(a++)
CC expression [MIM:615018]. Lack of Sd(a) antigen results in the Sd(a-)
CC phenotype, due to genetic variants in B4GALNT2.
CC {ECO:0000269|PubMed:31367682}.
CC -!- DISEASE: Sd(a) polyagglutination syndrome (SDPS) [MIM:615018]: A
CC condition characterized by red blood cells agglutination upon exposure
CC to almost all human sera, but not to autologous serum or the sera of
CC newborns. The condition becomes apparent during blood typing and cross-
CC matching in the laboratory. SDPS depends on the strength of expression
CC of the Sd(a) antigen on red blood cells. Most people have weak anti-
CC Sd(a) antibodies in their serum, which is usually of no clinical
CC importance, but can result in red cell agglutination if they are
CC transfused with cells showing strong Sd(a) expression.
CC {ECO:0000269|PubMed:31367682}. Note=The gene represented in this entry
CC is involved in disease pathogenesis.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=Beta-1,4
CC N-acetylgalactosaminyltransferase 2;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_482";
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DR EMBL; AJ517770; CAD57148.1; -; mRNA.
DR EMBL; AJ517771; CAD57149.1; -; mRNA.
DR EMBL; AF510036; AAM34756.1; -; mRNA.
DR EMBL; AK302876; BAG64056.1; -; mRNA.
DR EMBL; AC069454; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94691.1; -; Genomic_DNA.
DR EMBL; BC113675; AAI13676.1; -; mRNA.
DR EMBL; BC113677; AAI13678.1; -; mRNA.
DR CCDS; CCDS11544.1; -. [Q8NHY0-1]
DR CCDS; CCDS54139.1; -. [Q8NHY0-2]
DR CCDS; CCDS54140.1; -. [Q8NHY0-3]
DR RefSeq; NP_001152859.1; NM_001159387.1. [Q8NHY0-2]
DR RefSeq; NP_001152860.1; NM_001159388.1. [Q8NHY0-3]
DR RefSeq; NP_703147.2; NM_153446.2. [Q8NHY0-1]
DR RefSeq; XP_016879662.1; XM_017024173.1. [Q8NHY0-3]
DR AlphaFoldDB; Q8NHY0; -.
DR BioGRID; 125896; 6.
DR IntAct; Q8NHY0; 5.
DR STRING; 9606.ENSP00000300404; -.
DR CAZy; GT12; Glycosyltransferase Family 12.
DR GlyGen; Q8NHY0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NHY0; -.
DR PhosphoSitePlus; Q8NHY0; -.
DR BioMuta; B4GALNT2; -.
DR DMDM; 296434406; -.
DR MassIVE; Q8NHY0; -.
DR MaxQB; Q8NHY0; -.
DR PaxDb; 9606-ENSP00000300404; -.
DR PeptideAtlas; Q8NHY0; -.
DR ProteomicsDB; 5593; -.
DR ProteomicsDB; 73783; -. [Q8NHY0-1]
DR ProteomicsDB; 73784; -. [Q8NHY0-2]
DR Antibodypedia; 2589; 87 antibodies from 22 providers.
DR DNASU; 124872; -.
DR Ensembl; ENST00000300404.2; ENSP00000300404.2; ENSG00000167080.9. [Q8NHY0-1]
DR Ensembl; ENST00000393354.7; ENSP00000377022.3; ENSG00000167080.9. [Q8NHY0-2]
DR Ensembl; ENST00000504681.5; ENSP00000425510.1; ENSG00000167080.9. [Q8NHY0-3]
DR GeneID; 124872; -.
DR KEGG; hsa:124872; -.
DR MANE-Select; ENST00000393354.7; ENSP00000377022.3; NM_001159387.2; NP_001152859.1. [Q8NHY0-2]
DR UCSC; uc002ion.3; human. [Q8NHY0-1]
DR AGR; HGNC:24136; -.
DR CTD; 124872; -.
DR DisGeNET; 124872; -.
DR GeneCards; B4GALNT2; -.
DR HGNC; HGNC:24136; B4GALNT2.
DR HPA; ENSG00000167080; Tissue enhanced (intestine).
DR MalaCards; B4GALNT2; -.
DR MIM; 111730; gene.
DR MIM; 615018; phenotype.
DR neXtProt; NX_Q8NHY0; -.
DR OpenTargets; ENSG00000167080; -.
DR PharmGKB; PA134988070; -.
DR VEuPathDB; HostDB:ENSG00000167080; -.
DR eggNOG; ENOG502QTK7; Eukaryota.
DR GeneTree; ENSGT00390000006679; -.
DR HOGENOM; CLU_036051_1_0_1; -.
DR InParanoid; Q8NHY0; -.
DR OMA; GDCIHRR; -.
DR OrthoDB; 3831416at2759; -.
DR PhylomeDB; Q8NHY0; -.
DR TreeFam; TF332297; -.
DR BRENDA; 2.4.1.165; 2681.
DR PathwayCommons; Q8NHY0; -.
DR Reactome; R-HSA-446203; Asparagine N-linked glycosylation.
DR Reactome; R-HSA-9037629; Lewis blood group biosynthesis.
DR SignaLink; Q8NHY0; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 124872; 11 hits in 1144 CRISPR screens.
DR ChiTaRS; B4GALNT2; human.
DR GeneWiki; B4GALNT2; -.
DR GenomeRNAi; 124872; -.
DR Pharos; Q8NHY0; Tbio.
DR PRO; PR:Q8NHY0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8NHY0; Protein.
DR Bgee; ENSG00000167080; Expressed in mucosa of transverse colon and 52 other cell types or tissues.
DR Genevisible; Q8NHY0; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0008376; F:acetylgalactosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0030259; P:lipid glycosylation; IEA:InterPro.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0009312; P:oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0017038; P:protein import; IEA:Ensembl.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0098528; P:skeletal muscle fiber differentiation; IEA:Ensembl.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IEA:Ensembl.
DR GO; GO:0019276; P:UDP-N-acetylgalactosamine metabolic process; IDA:UniProtKB.
DR GO; GO:0006047; P:UDP-N-acetylglucosamine metabolic process; IBA:GO_Central.
DR CDD; cd00761; Glyco_tranf_GTA_type; 1.
DR InterPro; IPR001173; Glyco_trans_2-like.
DR InterPro; IPR011143; GM2_synthase.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR15046:SF2; BETA-1,4 N-ACETYLGALACTOSAMINYLTRANSFERASE 2; 1.
DR PANTHER; PTHR15046; GLYCO_TRANS_2-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00535; Glycos_transf_2; 1.
DR PIRSF; PIRSF000474; GM2_GD2_synthase; 1.
DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycosyltransferase; Golgi apparatus; Membrane;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..566
FT /note="Beta-1,4 N-acetylgalactosaminyltransferase 2"
FT /id="PRO_0000059103"
FT TOPO_DOM 1..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..566
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..86
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045195"
FT VAR_SEQ 1..64
FT /note="MGSAGFSVGKFHVEVASRGRECVSGTPECGNRLGSAGFGALCLELRGADPAW
FT GPFAAHGRSRRQ -> MTSG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12678917"
FT /id="VSP_017131"
FT VARIANT 40
FT /note="A -> D (in dbSNP:rs7207403)"
FT /evidence="ECO:0000269|PubMed:12678917,
FT ECO:0000269|PubMed:14688233, ECO:0000269|PubMed:15489334"
FT /id="VAR_049238"
FT VARIANT 436
FT /note="Q -> R (found in individuals with Sd(a-) phenotype;
FT dbSNP:rs148441237)"
FT /evidence="ECO:0000269|PubMed:31367682"
FT /id="VAR_086499"
FT VARIANT 459
FT /note="P -> H (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035990"
FT VARIANT 466
FT /note="C -> R (found in individuals with Sd(a-) phenotype;
FT dbSNP:rs7224888)"
FT /evidence="ECO:0000269|PubMed:31367682"
FT /id="VAR_049239"
FT VARIANT 523
FT /note="R -> W (found in individuals with Sd(a-) phenotype;
FT dbSNP:rs61743617)"
FT /evidence="ECO:0000269|PubMed:31367682"
FT /id="VAR_086500"
SQ SEQUENCE 566 AA; 63258 MW; 14B7DEBA30CB4E93 CRC64;
MGSAGFSVGK FHVEVASRGR ECVSGTPECG NRLGSAGFGA LCLELRGADP AWGPFAAHGR
SRRQGSRFLW LLKILVIILV LGIVGFMFGS MFLQAVFSSP KPELPSPAPG VQKLKLLPEE
RLRNLFSYDG IWLFPKNQCK CEANKEQGGY NFQDAYGQSD LPAVKARRQA EFEHFQRREG
LPRPLPLLVQ PNLPFGYPVH GVEVMPLHTV PIPGLQFEGP DAPVYEVTLT ASLGTLNTLA
DVPDSVVQGR GQKQLIISTS DRKLLKFILQ HVTYTSTGYQ HQKVDIVSLE SRSSVAKFPV
TIRHPVIPKL YDPGPERKLR NLVTIATKTF LRPHKLMIML RSIREYYPDL TVIVADDSQK
PLEIKDNHVE YYTMPFGKGW FAGRNLAISQ VTTKYVLWVD DDFLFNEETK IEVLVDVLEK
TELDVVGGSV LGNVFQFKLL LEQSENGACL HKRMGFFQPL DGFPSCVVTS GVVNFFLAHT
ERLQRVGFDP RLQRVAHSEF FIDGLGTLLV GSCPEVIIGH QSRSPVVDSE LAALEKTYNT
YRSNTLTRVQ FKLALHYFKN HLQCAA
//
