MGAT3_MOUSE
ID MGAT3_MOUSE Reviewed; 538 AA.
AC Q10470; P70386;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase {ECO:0000305};
DE EC=2.4.1.144 {ECO:0000305|PubMed:25592972};
DE AltName: Full=N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase III;
DE Short=GNT-III {ECO:0000303|PubMed:26467158};
DE Short=GlcNAc-T III;
DE Short=N-acetylglucosaminyltransferase III {ECO:0000303|PubMed:26467158};
GN Name=Mgat3 {ECO:0000312|MGI:MGI:104532};
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 [GENOMIC DNA].
RC STRAIN=129/Sv; TISSUE=Liver;
RX PubMed=7590346; DOI=10.1016/0378-1119(95)00260-d;
RA Bhaumik M., Seldin M.F., Stanley P.;
RT "Cloning and chromosomal mapping of the mouse Mgat3 gene encoding N-
RT acetylglucosaminyltransferase III.";
RL Gene 164:295-300(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ; TISSUE=Liver;
RX PubMed=9061364; DOI=10.1093/glycob/7.1.45;
RA Priatel J.J., Sarkar M., Schachter H., Marth J.D.;
RT "Isolation, characterization and inactivation of the mouse Mgat3 gene: the
RT bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears
RT dispensable for viability and reproduction.";
RL Glycobiology 7:45-56(1997).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=11986323; DOI=10.1074/jbc.m202276200;
RA Bhattacharyya R., Bhaumik M., Raju T.S., Stanley P.;
RT "Truncated, inactive N-acetylglucosaminyltransferase III (GlcNAc-TIII)
RT induces neurological and other traits absent in mice that lack GlcNAc-
RT TIII.";
RL J. Biol. Chem. 277:26300-26309(2002).
RN [4]
RP INDUCTION BY CELL-CELL INTERACTION.
RX PubMed=16537539; DOI=10.1074/jbc.m601961200;
RA Iijima J., Zhao Y., Isaji T., Kameyama A., Nakaya S., Wang X., Ihara H.,
RA Cheng X., Nakagawa T., Miyoshi E., Kondo A., Narimatsu H., Taniguchi N.,
RA Gu J.;
RT "Cell-cell interaction-dependent regulation of N-
RT acetylglucosaminyltransferase III and the bisected N-glycans in GE11
RT epithelial cells. Involvement of E-cadherin-mediated cell adhesion.";
RL J. Biol. Chem. 281:13038-13046(2006).
RN [5]
RP INTERACTION WITH MGAT4D.
RX PubMed=20805325; DOI=10.1083/jcb.201004102;
RA Huang H.H., Stanley P.;
RT "A testis-specific regulator of complex and hybrid N-glycan synthesis.";
RL J. Cell Biol. 190:893-910(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX PubMed=25592972; DOI=10.15252/emmm.201404438;
RA Kizuka Y., Kitazume S., Fujinawa R., Saito T., Iwata N., Saido T.C.,
RA Nakano M., Yamaguchi Y., Hashimoto Y., Staufenbiel M., Hatsuta H.,
RA Murayama S., Manya H., Endo T., Taniguchi N.;
RT "An aberrant sugar modification of BACE1 blocks its lysosomal targeting in
RT Alzheimer's disease.";
RL EMBO Mol. Med. 7:175-189(2015).
RN [7]
RP FUNCTION.
RX PubMed=26467158; DOI=10.1042/bj20150607;
RA Kizuka Y., Nakano M., Kitazume S., Saito T., Saido T.C., Taniguchi N.;
RT "Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative
RT stress conditions.";
RL Biochem. J. 473:21-30(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 (PubMed:25592972, PubMed:11986323). The addition of
CC this bisecting GlcNAc residue alters not only the composition, but also
CC the conformation of the N-glycan. The introduction of the bisecting
CC GlcNAc residue results in the suppression of further processing and
CC elongation of N-glycans, precluding the formation of beta-1,6 GlcNAc
CC branching, catalyzed by MGAT5 since it is unable to use the bisected
CC oligosaccharide as a substrate (By similarity). Addition of bisecting
CC N-acetylglucosamine to CDH1/E-cadherin modulates CDH1 cell membrane
CC location. Inhibits NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc- formation which
CC modulates sialylation levels and plays a role in cell migration
CC regulation (By similarity). In brain, addition of bisecting N-
CC acetylglucosamine to BACE1 blocks its lysosomal targeting in response
CC to oxidative stress and further degradation which increases its
CC location to early endosome and the APP cleavage (PubMed:25592972,
CC PubMed:26467158). {ECO:0000250|UniProtKB:Q09327,
CC ECO:0000269|PubMed:11986323, ECO:0000269|PubMed:25592972,
CC ECO:0000269|PubMed:26467158}.
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:25592972};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000305|PubMed:25592972}.
CC -!- SUBUNIT: Interacts with MGAT4D. {ECO:0000269|PubMed:20805325}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II
CC membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and kidney and to a much
CC lesser extent in stomach, heart, intestine, uterus, testis, ovary and
CC lung. Not present in spleen, liver and muscle. In brain, expressed in
CC neurons of hippocampus (PubMed:11986323).
CC {ECO:0000269|PubMed:11986323}.
CC -!- DEVELOPMENTAL STAGE: Expressed in brain at 10.5 dpc and thereafter.
CC {ECO:0000269|PubMed:11986323}.
CC -!- INDUCTION: Expression is up-regulated by CDH1/E-cadherin-mediated cell-
CC cell interaction. {ECO:0000269|PubMed:16537539}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are generally healthy, fertile, and
CC behaviorally normal (PubMed:20805325). They have altered leg clasp
CC reflex (PubMed:11986323). They show a lack of N-glycan species with an
CC additional bisecting N-acetylglucosamine (PubMed:11986323). Knockout
CC mice crossed with Alzheimer disease model mice have significantly lower
CC levels of the beta-C-terminal fragment of APP (betaCTF) and soluble APP
CC cleaved at the beta-site (sAPPbeta) in their brains than Alzheimer
CC disease model mice. They have markedly decreased the number of amyloid-
CC beta plaques and ameliorated cognitive function (PubMed:20805325).
CC {ECO:0000269|PubMed:11986323, ECO:0000269|PubMed:20805325}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 17 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB71422.1; 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 beta 1,4-GlcNAc T III (Mgat3);
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_585";
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DR EMBL; L39373; AAB71422.1; ALT_INIT; Genomic_DNA.
DR EMBL; U66844; AAC53064.1; -; Genomic_DNA.
DR CCDS; CCDS27660.1; -.
DR PIR; JC4362; JC4362.
DR AlphaFoldDB; Q10470; -.
DR STRING; 10090.ENSMUSP00000043077; -.
DR CAZy; GT17; Glycosyltransferase Family 17.
DR GlyGen; Q10470; 3 sites.
DR iPTMnet; Q10470; -.
DR PhosphoSitePlus; Q10470; -.
DR MaxQB; Q10470; -.
DR PaxDb; Q10470; -.
DR PeptideAtlas; Q10470; -.
DR PRIDE; Q10470; -.
DR ProteomicsDB; 292233; -.
DR MGI; MGI:104532; Mgat3.
DR eggNOG; ENOG502QUBY; Eukaryota.
DR InParanoid; Q10470; -.
DR PhylomeDB; Q10470; -.
DR Reactome; R-MMU-975574; Reactions specific to the hybrid N-glycan synthesis pathway.
DR UniPathway; UPA00378; -.
DR PRO; PR:Q10470; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q10470; protein.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IEA:GOC.
DR GO; GO:0003830; F:beta-1,4-mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase activity; IMP:MGI.
DR GO; GO:0016757; F:glycosyltransferase activity; IDA:MGI.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IMP:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:MGI.
DR GO; GO:0050890; P:cognition; IMP:MGI.
DR GO; GO:1905146; P:lysosomal protein catabolic process; IMP:MGI.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA:MGI.
DR GO; GO:1905166; P:negative regulation of lysosomal protein catabolic process; IMP:MGI.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; IMP:MGI.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:1902946; P:protein localization to early endosome; IMP:MGI.
DR GO; GO:0006487; P:protein N-linked glycosylation; IMP:MGI.
DR GO; GO:0030334; P:regulation of cell migration; ISS: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..538
FT /note="Beta-1,4-mannosyl-glycoprotein 4-beta-N-
FT acetylglucosaminyltransferase"
FT /id="PRO_0000188843"
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..538
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 120..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 46
FT /note="I -> V (in strain: 129/SvJ)"
FT VARIANT 66
FT /note="D -> G (in strain: 129/SvJ)"
FT VARIANT 137
FT /note="T -> P (in strain: 129/SvJ)"
FT VARIANT 159
FT /note="S -> T (in strain: 129/SvJ)"
FT VARIANT 243
FT /note="D -> E (in strain: 129/SvJ)"
FT VARIANT 526
FT /note="S -> P (in strain: 129/SvJ)"
FT VARIANT 536
FT /note="A -> V (in strain: 129/SvJ)"
SQ SEQUENCE 538 AA; 62003 MW; E5B7CF71C2022994 CRC64;
MKMRRYKLFL MFCMAGLCLI SFLHFFKTLS YVTFPRELAS LSPNLISSFF WNNAPVTPQA
SPEPGDPDLL RTPLYSHSPL LQPLSPSKAT EELHRVDFVL PEDTTEYFVR TKAGGVCFKP
GTRMLEKPSP GRTEEKTEVS EGSSARGPAR RPMRHVLSSR ERLGSRGTRR KWVECVCLPG
WHGPSCGVPT VVQYSNLPTK ERLVPREVPR RVINAININH EFDLLDVRFH ELGDVVDAFV
VCDSNFTAYG EPRPLKFREM LTNGTFEYIR HKVLYVFLDH FPPGGRQDGW IADDYLRTFL
TQDGVSRLRN LRPDDVFIID DADEIPARDG VLFLKLYDGW TEPFAFHMRK SLYGFFWKQP
GTLEVVSGCT MDMLQAVYGL DGIRLRRRQY YTMPNFRQYE NRTGHILVQW SLGSPLHFAG
WHCSWCFTPE GIYFKLVSAQ NGDFPRWGDY EDKRDLNYIR SLIRTGGWFD GTQQEYPPAD
PSEHMYAPKY LLKNYDQFRY LLENPYREPK STVEGGRQNQ GSDGRSSAVR GKLDTAEG
