Defective C1GALT1C1 does not bind C1GALT1

Stable Identifier
R-HSA-6785524
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1GALT1; MIM:610555) mediates the transfer of Galactose (Gal) from UDP-galactose to single O-linked GalNAc residues (Tn antigens) to form Core 1 structures on glycoproteins. C1GALT1 is active when in complex with the molecular chaperone C1GALT1C1 (aka COSMC; MIM:300611) which assists the folding and/or stability of C1GALT1. Defects in C1GALT1C1 causes somatic Tn polyagglutination syndrome (TNPS; MIM:300622), characterised by the polyagglutination of erythrocytes by naturally occurring anti-Tn antibodies following exposure of the Tn antigen on their surface. Defects in C1GALT1C1 render C1GALT1 inactive and results in the accumulation of the incompletely glycosylated Tn antigen. The Tn antigen is tumour-associated, found in a majority of human carcinomas, and is not normally expressed in peripheral tissues or blood cells (Crew et al. 2008, Ju et al. 2014). C1GALT1 and C1GALT1C1 belong to the CAZy family GT31 (www.cazy.org).

Defects in C1GALT1C1 render C1GALT1 inactive and results in the accumulation of the incompletely glycosylated Tn antigen. Mutations in C1GALT1C1 causing TNPS include R68*, D131E, E152K, S193P and M1I (Ju & Cummings 2005, Crew et al. 2008).

Literature References
PubMed ID Title Journal Year
16251947 Protein glycosylation: chaperone mutation in Tn syndrome

Ju, T, Cummings, RD

Nature 2005
24643043 The Cosmc connection to the Tn antigen in cancer

Ju, T, Aryal, RP, Kudelka, MR, Wang, Y, Cummings, RD

Cancer Biomark 2014
18537974 New mutations in C1GALT1C1 in individuals with Tn positive phenotype

Crew, VK, Singleton, BK, Green, C, Parsons, SF, Daniels, G, Anstee, DJ

Br. J. Haematol. 2008
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity of C1GALT1:C1GALT1C1 mutants [Golgi membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
carcinoma 305 epithelioma, malignant Epithelioma
Authored
Reviewed
Created
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