Defective C1GALT1C1 does not bind C1GALT1

Stable Identifier
R-HSA-6785524
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Golgi membrane, Golgi lumen
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective C1GALT1C1 does not bind C1GALT1
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
24643043 The Cosmc connection to the Tn antigen in cancer

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

Cancer Biomark 2014
16251947 Protein glycosylation: chaperone mutation in Tn syndrome

Cummings, RD, Ju, T

Nature 2005
18537974 New mutations in C1GALT1C1 in individuals with Tn positive phenotype

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

Br. J. Haematol. 2008
Participants
Input
Participates
as an event of
Catalyst Activity

glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity of C1GALT1:C1GALT1C1 mutants [Golgi membrane]

Physical Entity
C1GALT1:C1GALT1C1 mutants [Golgi membrane] (Homo sapiens)
Activity
glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity (GO:0016263)
Normal reaction
C1GALT1 transfers Galactose to the Tn antigen forming Core 1 glycoproteins (T antigens) (Homo sapiens)
Functional status

Loss of function of C1GALT1:C1GALT1C1 mutants [Golgi membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
carcinoma DOID:305 epithelioma, malignant Epithelioma
Authored
Jassal, B  (2015-06-29)
Reviewed
Hansen, L  (2015-12-18)
Joshi, HJ  (2015-12-18)
Created
Jassal, B  (2015-06-29)
Cite Us!