Polypeptide N-acetylgalactosaminyltransferase 2
Domain
There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.
The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
Function
Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region. Involved in O-linked glycosylation of APOC-III, ANGPTL3 and PLTP. It participates in the regulation of HDL-C metabolism (PubMed:27508872, PubMed:32293671).
Involvement in disease
Congenital disorder of glycosylation 2T
CDG2T
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2T is an autosomal recessive form characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioral abnormalities, epilepsy, chronic insomnia, white matter changes on brain imaging, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein glycosylation.
Sequence Similarities
Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
Tissue Specificity
Detected in urine (at protein level) (PubMed:37453717). Widely expressed.
Cellular localization
- Golgi apparatus
- Golgi stack membrane
- Single-pass type II membrane protein
- Secreted
- Resides preferentially in the trans and medial parts of the Golgi stack. A secreted form also exists.
Alternative names
Polypeptide N-acetylgalactosaminyltransferase 2, Polypeptide GalNAc transferase 2, Protein-UDP acetylgalactosaminyltransferase 2, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 2, GalNAc-T2, pp-GaNTase 2, GALNT2