POMGNT1
Domain
Amino acid residues between 299-311 are important for both protein expression and enzymatic activity. The minimal catalytic domain is located between positions 299-651. Single amino acid substitutions in the stem domain from MEB patients abolished the activity of the membrane-bound form but not the soluble form. This suggests that the stem domain of the soluble form is unnecessary for activity, but that some amino acids play a crucial role in the membrane-bound form.
The GG-type lectin domain is known as the stem domain in POMGnT1. It mediates specific interaction with beta-linked N-acetylglucosamine moieties of O-glycosylated proteins. It also interacts with its product, N-acetyl-beta-D-glucosaminyl-(1->2)-O-alpha-D-mannosylprotein.
Function
Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins, providing the necessary basis for the addition of further carbohydrate moieties (PubMed:11709191, PubMed:27493216). Is specific for alpha linked terminal mannose and does not have MGAT3, MGAT4, MGAT5, MGAT7 or MGAT8 activity.
Involvement in disease
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3
MDDGA3
An autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, cobblestone lissencephaly, and cerebellar and pontine hypoplasia. Patients present severe congenital myopia, congenital glaucoma, pallor of the optic disks, retinal hypoplasia, intellectual disability, hydrocephalus, abnormal electroencephalograms, generalized muscle weakness and myoclonic jerks. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease.
None
The disease is caused by variants affecting the gene represented in this entry.
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B3
MDDGB3
An autosomal recessive disorder characterized by congenital muscular dystrophy associated with intellectual disability and mild structural brain abnormalities. Clinical features include intellectual disability, white matter changes, cerebellar cysts, pontine hypoplasia, myopia, optic atrophy, decreased alpha-dystroglycan on muscle biopsy and increased serum creatine kinase.
None
The disease is caused by variants affecting the gene represented in this entry.
Muscular dystrophy-dystroglycanopathy limb-girdle C3
MDDGC3
A rare form of limb-girdle muscular dystrophy with normal cognition. Muscle biopsy shows dystrophic changes with variable staining for glycosylated alpha-dystroglycan.
None
The disease is caused by variants affecting the gene represented in this entry.
Retinitis pigmentosa 76
RP76
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP76 inheritance is autosomal recessive.
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 13 family.
Tissue Specificity
Constitutively expressed. An additional weaker band is also detected in spinal cord, lymph node, and trachea. Expressed especially in astrocytes. Also expressed in immature and mature neurons.
Cellular localization
- Golgi apparatus membrane
- Single-pass type II membrane protein
Alternative names
MGAT1.2, UNQ746/PRO1475, POMGNT1, POMGnT1, GnT I.2