GMPPB
Developmental stage
Isoform 2
Higher expression levels in fetal skeletal muscle and brain than in adult.
Domain
The N-terminal substrate-binding domain adopts a Rossman-like fold and has a binding pocket for GTP or GDP-alpha-D-mannose (PubMed:33986552). Substrate binding is coordinated by an Mg(2+) ion (PubMed:33986552).
The C-terminal domain consists of a series of tandem hexapeptide repeats that adopt a beta-helix conformation (PubMed:33986552). The beta-helix forms several protein interaction surfaces involved in assembly of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552).
Function
Catalytic subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552). Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids (PubMed:33986552). Can catalyze the reverse reaction in vitro (PubMed:33986552). Together with GMPPA regulates GDP-alpha-D-mannose levels (PubMed:33986552).
Involvement in disease
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A14
MDDGA14
An autosomal recessive disorder characterized by congenital muscular dystrophy associated with brain anomalies, eye malformations, and profound intellectual disability. The disorder includes a severe form designated as Walker-Warburg syndrome and a less severe phenotype known as muscle-eye-brain disease. MDDGA14 features include increased muscle tone, microcephaly, cleft palate, feeding difficulties, severe muscle weakness, sensorineural hearing loss, cerebellar hypoplasia, ataxia, and retinal dysfunction.
None
The disease is caused by variants affecting the gene represented in this entry.
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B14
MDDGB14
A congenital muscular dystrophy characterized by severe muscle weakness apparent in infancy and intellectual disability. Some patients may have additional features, such as microcephaly, cardiac dysfunction, seizures, or cerebellar hypoplasia.
None
The disease is caused by variants affecting the gene represented in this entry.
Muscular dystrophy-dystroglycanopathy limb-girdle C14
MDDGC14
An autosomal recessive form of muscular dystrophy characterized by mild proximal muscle weakness with onset in early childhood. Some patients may have additional features, such as mild intellectual disability or seizures.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Nucleotide-sugar biosynthesis; GDP-alpha-D-mannose biosynthesis; GDP-alpha-D-mannose from alpha-D-mannose 1-phosphate (GTP route): step 1/1.
Sequence Similarities
Belongs to the transferase hexapeptide repeat family.
Tissue Specificity
Isoform 1
Ubiquitously expressed, including in brain and skeletal muscle.
Isoform 2
Weakly expressed with highest expression in skeletal muscle, brain and gonads.
Cellular localization
- Cytoplasm
Alternative names
Mannose-1-phosphate guanylyltransferase catalytic subunit beta, GDP-mannose pyrophosphorylase B, GTP-mannose-1-phosphate guanylyltransferase beta, GMPPB