Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc.
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Establishes Cosmc as an ER-localised chaperone that binds human T-synthase directly, separating the chaperone's compartment from the Golgi compartment of its client.
"We show that Cosmc is an endoplasmic reticulum (ER)-localized adenosine triphosphate binding chaperone that binds directly to human T-synthase."
Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
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Shotgun proteomic catalogue of the human parotid saliva exosome fraction, in which C1GALT1C1 is one of 491 proteins detected. Provides no gene-specific functional or localisation experiment.
"we catalogued 491 proteins in the exosome fraction of human parotid saliva"
The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase.
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In vitro refolding assays with purified components show Cosmc assists refolding of denatured T-synthase, and that a Tn-syndrome Cosmc mutant is less effective, isolating chaperone activity from any catalytic contribution.
"These results show that mutated Cosmc is not as effective as soluble wild-type Cosmc in this in vitro assay in assisting refolding activity of T-synthase."
The transmembrane domain of the molecular chaperone Cosmc directs its localization to the endoplasmic reticulum.
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Maps the ER-retention determinant of Cosmc to its 18-residue transmembrane domain, which is sufficient to confer ER retention on chimeras.
"Here we show that the 18 amino acid transmembrane domain (TMD) of Cosmc is essential for ER localization and confers ER retention to select chimeras."
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A single TMD cysteine is required for disulfide-bonded Cosmc dimers and for ER retention, giving a mechanism for the retention rather than only an observation of steady-state location.
"Moreover, mutations of a single Cys residue within the TMD of Cosmc prevent formation of disulfide-bonded dimers of Cosmc and eliminate ER retention."
Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice.
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Somatic C1GALT1C1 (Cosmc) mutations were identified in Tn-antigen-positive colonic epithelium of ulcerative colitis patients, linking loss of Cosmc function in vivo to failure of core 1 O-glycan biosynthesis.
"Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia"
Co-translational function of Cosmc, core 1 synthase specific molecular chaperone, revealed by a cell-free translation system.
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In a wheat-germ cell-free translation system, active C1GalT is produced only when Cosmc is present during translation; recombinant Cosmc added after translation is ineffective. Establishes Cosmc as a co-translational chaperone that likely prevents client aggregation.
"These results indicate that Cosmc mediates the co-translational activation of C1GalT"
Germline C1GALT1C1 mutation causes a multisystem chaperonopathy.
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Germline hypomorphic C1GALT1C1 variants reduce Cosmc protein abundance and secondarily reduce T-synthase activity, causing a multisystem chaperonopathy that is a congenital disorder of glycosylation.
"This variant leads to a significant loss of Cosmc chaperone expression and subsequently causes a substantial reduction in T-synthase activity"
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The paper states unambiguously that Cosmc is an ER-localised chaperone whereas the T-synthase encoded by C1GALT1 is the Golgi enzyme, which separates the chaperone's compartment and function from its client's.
"Cosmc is an ER-localized molecular chaperone required for T-synthase function."
C1GALT1 transfers Galactose to the Tn antigen forming Core 1 glycoproteins (T antigens)
Defective C1GALT1C1 does not bind C1GALT1
OpenScientist hypothesis report: C1GALT1C1 has Golgi membrane (GO:0000139)
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Independent blinded assessment refuted the Golgi membrane localisation and identified the annotation as compartment carry-over from the Reactome reaction of the Golgi-resident client enzyme, corroborating the MODIFY to endoplasmic reticulum membrane.
"The GO:0000139 (Golgi membrane) annotation is **TAS from Reactome:R-HSA-1964505**, a pathway model of Golgi-lumenal O-glycosylation. It is best explained as a **compartment carry-over**"
OpenScientist hypothesis report: C1GALT1C1 does not have N-acetylgalactosaminide beta-1,3-galactosyltransferase activity (GO:0016263)
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Independent blinded assessment returned SUPPORTED (high confidence) for the negation, and traced the term's positive experimental grounding to the paralogous client C1GALT1 rather than to C1GALT1C1.
"The catalytic activity GO:0016263 (synthesis of Galβ1-3GalNAc-α-Ser/Thr, the T antigen) belongs to **C1GALT1, the client enzyme — not to C1GALT1C1**."