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
Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase.
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Human wild-type ALG12 transduction normalizes the F142V patient-cell precursor defect, supporting eighth-mannose addition in LLO assembly.
"the pathological phenotype of the fibroblasts of the patient was largely normalized upon transduction with the wild type gene"
Deficiency of dolichyl-P-Man:Man7GlcNAc2-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig.
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Wild-type ALG12 expression normalizes the reduced mannosyltransferase activity in patient fibroblasts.
"Retroviral expression of the wild-type Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol mannosyltransferase cDNA in patient's fibroblasts normalized the mannosyltransferase activity."
ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
Defining the membrane proteome of NK cells.
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The study surveys membrane proteins in the YTS NK-like cell line; the specific ALG12 hit is curator-reported and its peptide table was not independently recovered.
"The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS."
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
ALG12 transfers Man to N-glycan precursor (GlcNAc)2 (Man)7 (PP-Dol)1
Defective ALG12 does not add mannose to the N-glycan precursor
UniProtKB Q9BV10 (ALG12_HUMAN) curated entry
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ALG12 is an ER membrane, multi-pass Dol-P-Man-dependent alpha-1,6-mannosyltransferase (EC 2.4.1.260) of the glycosyltransferase 22 family that adds the eighth mannose onto Man7GlcNAc2-PP-dolichol in the ER lumen; defects cause CDG type Ig.
"adds the eighth mannose residue in an alpha-1,6 linkage onto"
Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core.
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The study tests chicken ALG12 rather than human ALG12; the human cell line is the expression host, and purified chicken enzyme processes shortened lipid-linked substrates.
"On the basis of these results, we selected ALG3 from Saccharomyces cerevisiae (ScALG3), ALG9 from Homo sapiens (HsALG9) and ALG12 from Gallus gallus (GgALG12) for structural and functional studies"
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The E35Q ALG12 construct facilitates a substrate-bound structure and is distinguished from the wild-type enzyme used for the positive transfer assays.
"To facilitate the trapping of pseudo-Michaelis complexes, we substituted the residues providing the putative catalytic base in ScALG3 (D71N), HsALG9 (D82A) and GgALG12 (E35Q) to either an alanine or the corresponding carboxamide side chain."
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The pathway description places ALG12 C-branch initiation after completion of the B branch; this is an ordering claim, while the measured ALG12 enzyme in this study is the chicken ortholog.
"Only when the B branch is complete does ALG12 initiate the C branch with the addition of the α1,6-linked j mannose"
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The chicken ALG12 ternary structure shows an acceptor cavity accommodating the completed B branch. This ortholog structure supports the specificity model without claiming a measured human ALG12 structure.
"The ALG12 ternary structure reveals that this is implemented by a deep binding cavity that accommodates the B branch of the acceptor glycan"
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The discussion relates complete glycan branches to efficient processing by glucosidases and UGGT in the downstream folding cycle. It does not show that ALG12 itself folds polypeptides or that truncated glycans are universally inactive.
"the glucosidases and UGGT require a fully mannosylated glycan with complete B and C branches for efficient removal or addition of glucose"