Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Combined Automated Annotation using Multiple IEA Methods
A novel human beta1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAcbeta1-3GlcNAc.
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Biochemical characterization establishing B3GALNT2 (beta3GalNAc-T2) as a beta-1,3-N-acetylgalactosaminyltransferase that transfers GalNAc onto terminal beta-GlcNAc, forming GalNAc-beta1-3-GlcNAc on N- and O-glycans.
"Its N-acetylgalactosaminyltransferase activity was observed when N-acetylglucosamine (GlcNAc) beta1-O-benzyl was used as an acceptor substrate. The enzyme product was determined to have a beta1,3-linkage by NMR spectroscopic analysis, and was therefore named beta1,3-N-acetylgalactosaminyltransferase-II (beta3GalNAc-T2)."
Mutations in B3GALNT2 cause congenital muscular dystrophy and hypoglycosylation of α-dystroglycan.
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Biallelic B3GALNT2 mutations cause dystroglycanopathy with muscle and brain involvement via reduced functional glycosylation of alpha-dystroglycan; B3GALNT2 localizes to the ER and some missense variants perturb this localization.
"B3GALNT2 localized to the endoplasmic reticulum, and this localization was perturbed by some of the missense mutations identified."
SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function.
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B3GALNT2 acts coordinately with POMGNT2/GTDC2 on protein O-mannose: it transfers GalNAc onto GlcNAc-beta4-Man to build the core M3 trisaccharide GalNAc-beta3-GlcNAc-beta4-Man, which is the substrate for POMK 6-O-phosphorylation of the mannose.
"MALDI-TOF/MS analysis confirmed that B3GALNT2 could transfer a GalNAc residue to the acceptor (Fig. 2A), suggesting that B3GALNT2 and GTDC2 can synthesize GalNAc-β3-GlcNAc-β4-Man."
FutureHouse Falcon deep-research report for B3GALNT2
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Deep-research synthesis: B3GALNT2 is best supported as an ER glycosyltransferase acting in the alpha-dystroglycan core M3 O-mannosylation pathway; ER localization is favoured over Golgi for the active enzyme.
"primary experimental evidence more strongly supports ER localization for active B3GALNT2"
Identification of mammalian glycoproteins with type-I LacdiNAc structures synthesized by the glycosyltransferase B3GALNT2.
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Beyond the alpha-dystroglycan O-mannosyl glycan, B3GALNT2 also synthesizes type-I LacdiNAc (GalNAc-beta1,3-GlcNAc) on the N-glycans of mainly intracellular glycoproteins (e.g. LRP1 and nicastrin), demonstrating a broader acceptor scope than alpha-DG alone.
"Our results further revealed that LDN presence on low-density lipoprotein receptor-related protein 1 and nicastrin depends on B3GALNT2, indicating the occurrence of type-I LDN in vivo in mammalian cells."
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B3GALNT2 preferentially modifies intracellular (especially ER-resident) glycoproteins, in contrast to the Golgi-resident type-II LDN synthases B4GALNT3/B4GALNT4 that act on extracellular glycoproteins.
"B3GALNT2 primarily transferred LDN to intracellular glycoproteins, thereby clearly delineating proteins that carry type-I or type-II LDNs."
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Independent localization evidence: B3GALNT2 mainly localizes to the ER and partly to the Golgi apparatus, reconciling the experimentally supported ER location with the family-default Golgi annotation.
"B3GALNT2 mainly localizes in the ER and partly in the Golgi apparatus"
A reference map of the human binary protein interactome.
B3GALNT2 transfers GalNAc to GlcNAc-Man-DAG1
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Reactome reaction modeling the ER-membrane-associated transfer of GalNAc by B3GALNT2 onto GlcNAc-Man-DAG1 during alpha-dystroglycan core M3 synthesis.
"ER membrane-associated UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to GlcNAc-Man-DAG1 via a 1-3 glycosidic bond"
DAG1 core M3 glycosylations
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Reactome pathway for alpha-dystroglycan core M3 O-mannosyl glycan synthesis, within which B3GALNT2 acts; basis of the TAS O-linked glycosylation process annotation.
"DAG1 core M3 glycosylations"