GCNT3_HUMAN
ID GCNT3_HUMAN Reviewed; 438 AA.
AC O95395;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3;
DE EC=2.4.1.102 {ECO:0000269|PubMed:9915862};
DE EC=2.4.1.148 {ECO:0000269|PubMed:9915862};
DE EC=2.4.1.150 {ECO:0000269|PubMed:9915862};
DE AltName: Full=C2GnT-mucin type;
DE Short=C2GnT-M;
DE Short=hC2GnT-M;
DE AltName: Full=Core 2/core 4 beta-1,6-N-acetylglucosaminyltransferase;
DE Short=C2/4GnT;
GN Name=GCNT3;
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], FUNCTION, ENZYME ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9915862; DOI=10.1074/jbc.274.5.3215;
RA Yeh J.-C., Ong E., Fukuda M.;
RT "Molecular cloning and expression of a novel beta-1, 6-N-
RT acetylglucosaminyltransferase that forms core 2, core 4, and I branches.";
RL J. Biol. Chem. 274:3215-3221(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9988682; DOI=10.1074/jbc.274.8.4504;
RA Schwientek T., Nomoto M., Levery S.B., Merkx G., van Kessel A.G.,
RA Bennett E.P., Hollingsworth M.A., Clausen H.;
RT "Control of O-glycan branch formation. Molecular cloning of human cDNA
RT encoding a novel beta1,6-N-acetylglucosaminyltransferase forming core 2 and
RT core 4.";
RL J. Biol. Chem. 274:4504-4512(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=17303715; DOI=10.1165/rcmb.2006-0334oc;
RA Tan S., Cheng P.-W.;
RT "Mucin biosynthesis: identification of the cis-regulatory elements of human
RT C2GnT-M gene.";
RL Am. J. Respir. Cell Mol. Biol. 36:737-745(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP INDUCTION.
RX PubMed=15864435; DOI=10.1007/s10719-005-0292-7;
RA Ishibashi Y., Inouye Y., Okano T., Taniguchi A.;
RT "Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an
RT airway carcinoma cell line.";
RL Glycoconj. J. 22:53-62(2005).
RN [6]
RP INDUCTION.
RX PubMed=16418723; DOI=10.1038/sj.onc.1209350;
RA Huang M.-C., Chen H.-Y., Huang H.-C., Huang J., Liang J.-T., Shen T.-L.,
RA Lin N.-Y., Ho C.-C., Cho I.-M., Hsu S.-M.;
RT "C2GnT-M is downregulated in colorectal cancer and its re-expression causes
RT growth inhibition of colon cancer cells.";
RL Oncogene 25:3267-3276(2006).
CC -!- FUNCTION: Glycosyltransferase that can synthesize all known mucin beta
CC 6 N-acetylglucosaminides. Mediates core 2 and core 4 O-glycan
CC branching, 2 important steps in mucin-type biosynthesis. Has also I-
CC branching enzyme activity by converting linear into branched poly-N-
CC acetyllactosaminoglycans, leading to introduce the blood group I
CC antigen during embryonic development. {ECO:0000269|PubMed:9915862}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O(3)-[beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-
CC galactosaminyl]-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine
CC = 3-O-{beta-D-galactosyl-(1->3)-[N-acetyl-beta-D-glucosaminyl-
CC (1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + H(+) +
CC UDP; Xref=Rhea:RHEA:56212, Rhea:RHEA-COMP:13922, Rhea:RHEA-
CC COMP:14419, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:137949, ChEBI:CHEBI:139605; EC=2.4.1.102;
CC Evidence={ECO:0000269|PubMed:9915862};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O(3)-[beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-
CC galactosaminyl]-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-
CC glucosamine = 3-O-{beta-D-galactosyl-(1->3)-[N-acetyl-beta-D-
CC glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-
CC [protein] + H(+) + UDP; Xref=Rhea:RHEA:56216, Rhea:RHEA-COMP:13923,
CC Rhea:RHEA-COMP:14420, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:137950, ChEBI:CHEBI:139607;
CC EC=2.4.1.102; Evidence={ECO:0000269|PubMed:9915862};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-GlcNAc derivative + UDP-N-acetyl-alpha-D-glucosamine = a beta-
CC D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-[beta-D-GlcNAc-(1->6)]-beta-D-Gal-
CC (1->4)-N-acetyl-beta-D-glucosaminyl derivative + H(+) + UDP;
CC Xref=Rhea:RHEA:54820, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:138371, ChEBI:CHEBI:138372;
CC EC=2.4.1.150; Evidence={ECO:0000269|PubMed:9915862};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-N-acetyl-alpha-D-
CC galactosaminyl]-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine
CC = 3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-[N-acetyl-beta-D-
CC glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl]-L-seryl-
CC [protein] + H(+) + UDP; Xref=Rhea:RHEA:56188, Rhea:RHEA-COMP:11691,
CC Rhea:RHEA-COMP:14412, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:87079, ChEBI:CHEBI:139581;
CC EC=2.4.1.148; Evidence={ECO:0000269|PubMed:9915862};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-N-acetyl-alpha-D-
CC galactosaminyl]-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-
CC glucosamine = 3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-[N-acetyl-
CC beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl]-L-
CC threonyl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:56192, Rhea:RHEA-
CC COMP:11692, Rhea:RHEA-COMP:14413, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:87080,
CC ChEBI:CHEBI:139580; EC=2.4.1.148;
CC Evidence={ECO:0000269|PubMed:9915862};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in mucus-secreting tissues.
CC Expressed in colon, kidney, small intestine, trachea, and stomach,
CC where mucin is produced. {ECO:0000269|PubMed:17303715,
CC ECO:0000269|PubMed:9915862}.
CC -!- INDUCTION: By all-trans retinoic acid (ATRA), TNF and IL13/interleukin-
CC 13. Strongly down-regulated in colorectal cancer.
CC {ECO:0000269|PubMed:15864435, ECO:0000269|PubMed:16418723,
CC ECO:0000269|PubMed:17303715}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 14 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GCNT3ID44105ch15q21.html";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=Core
CC 2/core 4 beta-1,6-N-acetylglucosaminyltransferase;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_544";
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DR EMBL; AF102542; AAD10824.1; -; mRNA.
DR EMBL; AF038650; AAD21525.1; -; mRNA.
DR EMBL; EF152283; ABM21534.1; -; mRNA.
DR EMBL; BC017032; AAH17032.1; -; mRNA.
DR CCDS; CCDS10172.1; -.
DR RefSeq; NP_004742.1; NM_004751.2.
DR AlphaFoldDB; O95395; -.
DR SMR; O95395; -.
DR BioGRID; 114671; 24.
DR IntAct; O95395; 13.
DR STRING; 9606.ENSP00000379377; -.
DR CAZy; GT14; Glycosyltransferase Family 14.
DR GlyGen; O95395; 1 site.
DR iPTMnet; O95395; -.
DR PhosphoSitePlus; O95395; -.
DR BioMuta; GCNT3; -.
DR jPOST; O95395; -.
DR MassIVE; O95395; -.
DR MaxQB; O95395; -.
DR PaxDb; O95395; -.
DR PeptideAtlas; O95395; -.
DR PRIDE; O95395; -.
DR ProteomicsDB; 50846; -.
DR Antibodypedia; 2476; 401 antibodies from 32 providers.
DR DNASU; 9245; -.
DR Ensembl; ENST00000396065.3; ENSP00000379377.1; ENSG00000140297.13.
DR Ensembl; ENST00000560585.5; ENSP00000452741.1; ENSG00000140297.13.
DR GeneID; 9245; -.
DR KEGG; hsa:9245; -.
DR MANE-Select; ENST00000396065.3; ENSP00000379377.1; NM_004751.3; NP_004742.1.
DR UCSC; uc002agd.4; human.
DR CTD; 9245; -.
DR DisGeNET; 9245; -.
DR GeneCards; GCNT3; -.
DR HGNC; HGNC:4205; GCNT3.
DR HPA; ENSG00000140297; Tissue enhanced (gallbladder, intestine, salivary gland).
DR MIM; 606836; gene.
DR neXtProt; NX_O95395; -.
DR OpenTargets; ENSG00000140297; -.
DR PharmGKB; PA28620; -.
DR VEuPathDB; HostDB:ENSG00000140297; -.
DR eggNOG; KOG0799; Eukaryota.
DR GeneTree; ENSGT00940000159331; -.
DR HOGENOM; CLU_032341_1_2_1; -.
DR InParanoid; O95395; -.
DR OMA; IHQRAVC; -.
DR OrthoDB; 868849at2759; -.
DR PhylomeDB; O95395; -.
DR TreeFam; TF315534; -.
DR BioCyc; MetaCyc:HS06698-MON; -.
DR BRENDA; 2.4.1.102; 2681.
DR BRENDA; 2.4.1.150; 2681.
DR PathwayCommons; O95395; -.
DR Reactome; R-HSA-913709; O-linked glycosylation of mucins.
DR SignaLink; O95395; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 9245; 20 hits in 1057 CRISPR screens.
DR ChiTaRS; GCNT3; human.
DR GenomeRNAi; 9245; -.
DR Pharos; O95395; Tbio.
DR PRO; PR:O95395; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O95395; protein.
DR Bgee; ENSG00000140297; Expressed in palpebral conjunctiva and 139 other tissues.
DR ExpressionAtlas; O95395; baseline and differential.
DR Genevisible; O95395; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0106325; F:acetylgalactosaminyl-O-glycosyl-seryl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0106326; F:acetylgalactosaminyl-O-glycosyl-threonyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IBA:GO_Central.
DR GO; GO:0003829; F:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase activity; TAS:Reactome.
DR GO; GO:0008109; F:N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase activity; TAS:ProtInc.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0050892; P:intestinal absorption; IEA:Ensembl.
DR GO; GO:0060993; P:kidney morphogenesis; IEA:Ensembl.
DR GO; GO:0016266; P:O-glycan processing; TAS:Reactome.
DR GO; GO:0006493; P:protein O-linked glycosylation; TAS:ProtInc.
DR GO; GO:0048729; P:tissue morphogenesis; IEA:Ensembl.
DR InterPro; IPR003406; Glyco_trans_14.
DR Pfam; PF02485; Branch; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Glycosyltransferase; Golgi apparatus;
KW Membrane; Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..438
FT /note="Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-
FT 1,6-N-acetylglucosaminyltransferase 3"
FT /id="PRO_0000288545"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..26
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..438
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 70..227
FT /evidence="ECO:0000250"
FT DISULFID 161..382
FT /evidence="ECO:0000250"
FT DISULFID 182..209
FT /evidence="ECO:0000250"
FT DISULFID 391..423
FT /evidence="ECO:0000250"
SQ SEQUENCE 438 AA; 50864 MW; 1FF0A7B451C88407 CRC64;
MVQWKRLCQL HYLWALGCYM LLATVALKLS FRLKCDSDHL GLESRESQSQ YCRNILYNFL
KLPAKRSINC SGVTRGDQEA VLQAILNNLE VKKKREPFTD THYLSLTRDC EHFKAERKFI
QFPLSKEEVE FPIAYSMVIH EKIENFERLL RAVYAPQNIY CVHVDEKSPE TFKEAVKAII
SCFPNVFIAS KLVRVVYASW SRVQADLNCM EDLLQSSVPW KYFLNTCGTD FPIKSNAEMV
QALKMLNGRN SMESEVPPKH KETRWKYHFE VVRDTLHLTN KKKDPPPYNL TMFTGNAYIV
ASRDFVQHVL KNPKSQQLIE WVKDTYSPDE HLWATLQRAR WMPGSVPNHP KYDISDMTSI
ARLVKWQGHE GDIDKGAPYA PCSGIHQRAI CVYGAGDLNW MLQNHHLLAN KFDPKVDDNA
LQCLEEYLRY KAIYGTEL
