{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8R4G6","uniProtkbId":"MGT5A_MOUSE","entryAudit":{"firstPublicDate":"2005-06-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-06-01","entryVersion":153,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12122020"}],"value":"2.4.1.155"}]},"alternativeNames":[{"fullName":{"value":"Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase"}},{"fullName":{"value":"GlcNAc-T V"},"shortNames":[{"value":"GNT-V"}]},{"fullName":{"value":"Mannoside acetylglucosaminyltransferase 5"}},{"fullName":{"value":"N-acetylglucosaminyl-transferase V"}}],"contains":[{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Secreted beta-1,6-N-acetylglucosaminyltransferase V"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Secreted GNT-V"}]}]}],"flag":"Precursor"},"genes":[{"geneName":{"value":"Mgat5"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11217864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12122020"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14561752"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15459394"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22715095"}],"value":"Catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides (PubMed:10700233, PubMed:14561752, PubMed:22715095). Catalyzes an important step in the biosynthesis of branched, complex-type N-glycans, such as those found on EGFR, TGFR (TGF-beta receptor) and CDH2 (PubMed:10700233, PubMed:12122020, PubMed:14561752, PubMed:15459394, PubMed:22715095). Via its role in the biosynthesis of complex N-glycans, plays an important role in the activation of cellular signaling pathways, reorganization of the actin cytoskeleton, cell-cell adhesion and cell migration (PubMed:10700233, PubMed:14561752, PubMed:15459394). MGAT5-dependent EGFR N-glycosylation enhances the interaction between EGFR and LGALS3 and thereby prevents rapid EGFR endocytosis and prolongs EGFR signaling (PubMed:15459394). Required for efficient interaction between TGFB1 and its receptor (PubMed:15459394). Enhances activation of intracellular signaling pathways by several types of growth factors, including FGF2, PDGF, IGF, TGFB1 and EGF (PubMed:15459394). MGAT5-dependent CDH2 N-glycosylation inhibits CDH2-mediated homotypic cell-cell adhesion and contributes to the regulation of downstream signaling pathways (PubMed:14561752). Promotes cell migration (PubMed:14561752, PubMed:15459394). Contributes to the regulation of the inflammatory response (PubMed:11217864, PubMed:15459394). MGAT5-dependent TCR N-glycosylation enhances the interaction between TCR and LGALS3, limits agonist-induced TCR clustering, and thereby dampens TCR-mediated responses to antigens (PubMed:11217864). Required for normal leukocyte evasation and accumulation at sites of inflammation (PubMed:15459394). Inhibits attachment of monocytes to the vascular endothelium and subsequent monocyte diapedesis (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"}],"value":"Promotes proliferation of umbilical vein endothelial cells and angiogenesis, at least in part by promoting the release of the growth factor FGF2 from the extracellular matrix"}],"commentType":"FUNCTION","molecule":"Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"N(4)-{beta-D-GlcNAc-(1->2)-[beta-D-GlcNAc-(1->4)]-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = N(4)-{beta-D-GlcNAc-(1->2)-[beta-D-GlcNAc-(1->4)]-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-[beta-D-GlcNAc-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:16921"},{"database":"Rhea","id":"RHEA-COMP:14374"},{"database":"Rhea","id":"RHEA-COMP:14377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57705"},{"database":"ChEBI","id":"CHEBI:58223"},{"database":"ChEBI","id":"CHEBI:139507"},{"database":"ChEBI","id":"CHEBI:139510"}],"ecNumber":"2.4.1.155","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12122020"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12122020"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22715095"}],"value":"Protein modification; protein glycosylation"}],"commentType":"PATHWAY"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P97259"}],"value":"Golgi apparatus membrane","id":"SL-0134"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"}],"value":"Single-pass type II membrane protein","id":"SL-9906"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"}],"value":"Perikaryon","id":"SL-0197"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"}],"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"}],"value":"Detected in cerebellum"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"}],"value":"N-glycosylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"}],"value":"A secreted form is released from the membrane after cleavage by gamma-secretase"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10700233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11217864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14561752"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22715095"}],"value":"Mice are born at the expected Mendelian rate and have no visible phenotype at birth. Adult mice display abnormal leukocyte recruitment to inflamed tissues, hypersensitivity of T cells to agonists that activate T cell receptors, an age-related decrease in the cellularity of kidney glomeruli and a tendency to develop proliferative glomerulonephritis, plus defective nurturing behavior (PubMed:10700233, PubMed:11217864). Mutant mice show increased responsiveness to treatments that cause delayed-type hypersensitivity (PubMed:11217864). Mice show increased incidence of autoimmune encephalomyelitis in response to injections with MBP (PubMed:11217864). Transgenic mice that express polyomavirus middle T antigen develop mammary tumors; 50% of female wild-type mice have detectable tumors after 16 weeks, but it takes 24 weeks until 50% of the female mice that lack Mgat5 develop mammary tumors. Male mice that express polyomavirus middle T antigen develop mammary tumors after 6 to 9 months; males that lack Mgat5 develop tumors after 10 to 13 months. Formation of lung metastases is about 5% of wild-type (PubMed:10700233). Tumor initiation is not decreased in mice that lack Mgat5, but tumor growth is strongly decreased (PubMed:10700233). Tumor cells from mutant mice show impaired membrane ruffling, probably due to decreased activation of phosphoinositide-3-kinase (PI3K) (PubMed:10700233). Embryonic fibroblasts from Mgat5-deficient mice display increased Cdh2-mediated cell-cell adhesion (PubMed:14561752). Mutant mice that lack both Mgat5 and Mgat5b display no visible changes in brain anatomy, but their brains display defective biosynthesis of both O-mannosyl glycans and N-linked glycans (PubMed:22715095)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the glycosyltransferase 18 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":740,"modifier":"EXACT"}},"description":"Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A","featureId":"PRO_0000080523"},{"type":"Chain","location":{"start":{"value":31,"modifier":"EXACT"},"end":{"value":740,"modifier":"EXACT"}},"description":"Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q09328"}],"featureId":"PRO_0000445693"},{"type":"Topological 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