MGAT3_HUMAN
ID MGAT3_HUMAN Reviewed; 533 AA.
AC Q09327; A6NGD0; Q14CK5; Q6IC49; Q9UH32;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase {ECO:0000305};
DE EC=2.4.1.144 {ECO:0000305|PubMed:19403558};
DE AltName: Full=N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase III;
DE Short=GNT-III;
DE Short=GlcNAc-T III;
DE Short=N-acetylglucosaminyltransferase III;
GN Name=MGAT3 {ECO:0000312|HGNC:HGNC:7046}; Synonyms=GGNT3;
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].
RX PubMed=8370666; DOI=10.1093/oxfordjournals.jbchem.a124105;
RA Ihara Y., Nishikawa A., Toma T., Soejima H., Niikawa N., Taniguchi N.;
RT "cDNA cloning, expression, and chromosomal localization of human N-
RT acetylglucosaminyltransferase III (GnT-III).";
RL J. Biochem. 113:692-698(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum, and Fetal brain;
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 FUNCTION, AND INDUCTION BY E-CADHERIN.
RX PubMed=19403558; DOI=10.1093/hmg/ddp194;
RA Pinho S.S., Reis C.A., Paredes J., Magalhaes A.M., Ferreira A.C.,
RA Figueiredo J., Xiaogang W., Carneiro F., Gaertner F., Seruca R.;
RT "The role of N-acetylglucosaminyltransferase III and V in the post-
RT transcriptional modifications of E-cadherin.";
RL Hum. Mol. Genet. 18:2599-2608(2009).
RN [6]
RP FUNCTION.
RX PubMed=26801611; DOI=10.1074/jbc.m115.712836;
RA Lu J., Isaji T., Im S., Fukuda T., Kameyama A., Gu J.;
RT "Expression of N-Acetylglucosaminyltransferase III Suppresses alpha2,3-
RT Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed
RT to alpha2,6-Sialylation Levels.";
RL J. Biol. Chem. 291:5708-5720(2016).
CC -!- FUNCTION: It is involved in the regulation of the biosynthesis and
CC biological function of glycoprotein oligosaccharides. Catalyzes the
CC addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked
CC mannose of the trimannosyl core of N-linked sugar chains, called
CC bisecting N-acetylglucosamine (GlcNAc). It is one of the most important
CC enzymes involved in the regulation of the biosynthesis of glycoprotein
CC oligosaccharides. The addition of this bisecting GlcNAc residue alters
CC not only the composition, but also the conformation of the N-glycan.
CC The introduction of the bisecting GlcNAc residue results in the
CC suppression of further processing and elongation of N-glycans,
CC precluding the formation of beta-1,6 GlcNAc branching, catalyzed by
CC MGAT5 since it is unable to use the bisected oligosaccharide as a
CC substrate (PubMed:19403558). Addition of bisecting N-acetylglucosamine
CC to CDH1/E-cadherin modulates CDH1 cell membrane location
CC (PubMed:19403558). Inhibits NeuAc-alpha-2,3-Gal-beta-1,4-
CC GlcNAc- formation which modulates sialylation levels and plays a role
CC in cell migration regulation (PubMed:26801611). In brain, addition of
CC bisecting N-acetylglucosamine to BACE1 blocks its lysosomal targeting
CC in response to oxidative stress and further degradation which increases
CC its location to early endosome and the APP cleavage (By similarity).
CC {ECO:0000250|UniProtKB:Q10470, ECO:0000269|PubMed:19403558,
CC ECO:0000269|PubMed:26801611}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-
CC (1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-N-acetyl-alpha-D-
CC glucosamine = H(+) + N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-
CC [beta-D-GlcNAc-(1->4)]-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-
CC beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-
CC [protein] + UDP; Xref=Rhea:RHEA:15509, Rhea:RHEA-COMP:13526,
CC Rhea:RHEA-COMP:14371, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:60651, ChEBI:CHEBI:139504;
CC EC=2.4.1.144; Evidence={ECO:0000305|PubMed:19403558};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000305|PubMed:19403558}.
CC -!- SUBUNIT: Interacts with MGAT4D. {ECO:0000250|UniProtKB:Q10470}.
CC -!- INTERACTION:
CC Q09327; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-18058216, EBI-749370;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- INDUCTION: Expression is up-regulated by CDH1/E-cadherin-mediated cell-
CC cell interaction. {ECO:0000269|PubMed:19403558}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 17 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02937.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=Beta-1,4-
CC mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_540";
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DR EMBL; D13789; BAA02937.1; ALT_INIT; mRNA.
DR EMBL; CR456519; CAG30405.1; -; mRNA.
DR EMBL; AL022312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075025; AAH75025.1; -; mRNA.
DR EMBL; BC075026; AAH75026.1; -; mRNA.
DR EMBL; BC113383; AAI13384.1; -; mRNA.
DR EMBL; BC113718; AAI13719.1; -; mRNA.
DR CCDS; CCDS13994.2; -.
DR PIR; JN0586; JN0586.
DR RefSeq; NP_001091740.1; NM_001098270.1.
DR RefSeq; NP_002400.3; NM_002409.4.
DR RefSeq; XP_005261666.1; XM_005261609.2.
DR RefSeq; XP_011528486.1; XM_011530184.2.
DR RefSeq; XP_011528487.1; XM_011530185.2.
DR RefSeq; XP_011528488.1; XM_011530186.2.
DR RefSeq; XP_011528489.1; XM_011530187.2.
DR RefSeq; XP_011528490.1; XM_011530188.2.
DR RefSeq; XP_011528491.1; XM_011530189.2.
DR RefSeq; XP_011528492.1; XM_011530190.2.
DR RefSeq; XP_011528493.1; XM_011530191.2.
DR RefSeq; XP_011528494.1; XM_011530192.2.
DR RefSeq; XP_011528496.1; XM_011530194.2.
DR RefSeq; XP_016884291.1; XM_017028802.1.
DR AlphaFoldDB; Q09327; -.
DR BioGRID; 110404; 3.
DR IntAct; Q09327; 1.
DR STRING; 9606.ENSP00000345270; -.
DR BindingDB; Q09327; -.
DR ChEMBL; CHEMBL2375206; -.
DR CAZy; GT17; Glycosyltransferase Family 17.
DR GlyGen; Q09327; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q09327; -.
DR PhosphoSitePlus; Q09327; -.
DR BioMuta; MGAT3; -.
DR DMDM; 61252497; -.
DR MassIVE; Q09327; -.
DR PaxDb; Q09327; -.
DR PeptideAtlas; Q09327; -.
DR PRIDE; Q09327; -.
DR ProteomicsDB; 58718; -.
DR Antibodypedia; 12672; 238 antibodies from 27 providers.
DR DNASU; 4248; -.
DR Ensembl; ENST00000341184.7; ENSP00000345270.6; ENSG00000128268.12.
DR GeneID; 4248; -.
DR KEGG; hsa:4248; -.
DR MANE-Select; ENST00000341184.7; ENSP00000345270.6; NM_002409.5; NP_002400.3.
DR UCSC; uc003axv.6; human.
DR CTD; 4248; -.
DR DisGeNET; 4248; -.
DR GeneCards; MGAT3; -.
DR HGNC; HGNC:7046; MGAT3.
DR HPA; ENSG00000128268; Tissue enhanced (brain, intestine).
DR MIM; 604621; gene.
DR neXtProt; NX_Q09327; -.
DR OpenTargets; ENSG00000128268; -.
DR PharmGKB; PA30781; -.
DR VEuPathDB; HostDB:ENSG00000128268; -.
DR eggNOG; ENOG502QUBY; Eukaryota.
DR GeneTree; ENSGT00390000008221; -.
DR HOGENOM; CLU_029534_0_0_1; -.
DR InParanoid; Q09327; -.
DR OMA; DTRNAHI; -.
DR OrthoDB; 886866at2759; -.
DR PhylomeDB; Q09327; -.
DR TreeFam; TF323781; -.
DR BioCyc; MetaCyc:HS05168-MON; -.
DR BRENDA; 2.4.1.144; 2681.
DR PathwayCommons; Q09327; -.
DR Reactome; R-HSA-975574; Reactions specific to the hybrid N-glycan synthesis pathway.
DR SignaLink; Q09327; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 4248; 17 hits in 1077 CRISPR screens.
DR ChiTaRS; MGAT3; human.
DR GeneWiki; MGAT3; -.
DR GenomeRNAi; 4248; -.
DR Pharos; Q09327; Tchem.
DR PRO; PR:Q09327; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q09327; protein.
DR Bgee; ENSG00000128268; Expressed in right hemisphere of cerebellum and 183 other tissues.
DR ExpressionAtlas; Q09327; baseline and differential.
DR Genevisible; Q09327; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0003830; F:beta-1,4-mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase activity; IMP:UniProtKB.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0050890; P:cognition; ISS:UniProtKB.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IBA:GO_Central.
DR GO; GO:1905166; P:negative regulation of lysosomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IDA:UniProtKB.
DR InterPro; IPR006813; Glyco_trans_17.
DR PANTHER; PTHR12224; PTHR12224; 1.
DR Pfam; PF04724; Glyco_transf_17; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Membrane;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..533
FT /note="Beta-1,4-mannosyl-glycoprotein 4-beta-N-
FT acetylglucosaminyltransferase"
FT /id="PRO_0000188842"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..23
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..533
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 119..158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..533
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 346
FT /note="K -> T (in Ref. 1; BAA02937)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 61313 MW; 11F56C44A6B173AB CRC64;
MKMRRYKLFL MFCMAGLCLI SFLHFFKTLS YVTFPRELAS LSPNLVSSFF WNNAPVTPQA
SPEPGGPDLL RTPLYSHSPL LQPLPPSKAA EELHRVDLVL PEDTTEYFVR TKAGGVCFKP
GTKMLERPPP GRPEEKPEGA NGSSARRPPR YLLSARERTG GRGARRKWVE CVCLPGWHGP
SCGVPTVVQY SNLPTKERLV PREVPRRVIN AINVNHEFDL LDVRFHELGD VVDAFVVCES
NFTAYGEPRP LKFREMLTNG TFEYIRHKVL YVFLDHFPPG GRQDGWIADD YLRTFLTQDG
VSRLRNLRPD DVFIIDDADE IPARDGVLFL KLYDGWTEPF AFHMRKSLYG FFWKQPGTLE
VVSGCTVDML QAVYGLDGIR LRRRQYYTMP NFRQYENRTG HILVQWSLGS PLHFAGWHCS
WCFTPEGIYF KLVSAQNGDF PRWGDYEDKR DLNYIRGLIR TGGWFDGTQQ EYPPADPSEH
MYAPKYLLKN YDRFHYLLDN PYQEPRSTAA GGWRHRGPEG RPPARGKLDE AEV
