MAN1B1

This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1, 2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause autosomal-recessive intellectual disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11.

Full Name

mannosidase, alpha, class 1B, member 1

Function

Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2).

Biological Process

Endoplasmic reticulum mannose trimmingManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Mannose trimming involved in glycoprotein ERAD pathwayManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
N-glycan processingManual Assertion Based On ExperimentIBA:GO_Central
Oligosaccharide metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Protein alpha-1,2-demannosylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Protein glycosylationIEA:UniProtKB-UniPathway
Trimming of first mannose on A branchTAS:Reactome
Trimming of second mannose on A branchTAS:Reactome
Trimming of terminal mannose on B branchManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Trimming of terminal mannose on C branchTAS:Reactome
Ubiquitin-dependent ERAD pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Viral protein processingTAS:Reactome

Cellular Location

Endoplasmic reticulum membrane

Involvement in disease

Rafiq syndrome (RAFQS):
An autosomal recessive disorder characterized by variably impaired intellectual and motor development, a characteristic facial dysmorphism, truncal obesity, and hypotonia. The facial dysmorphism comprises prominent eyebrows with lateral thinning, downward-slanting palpebral fissures, bulbous tip of the nose, large ears, and a thin upper lip. Behavioral problems, including overeating, verbal and physical aggression, have been reported in some cases. Serum transferrin isoelectric focusing shows a type 2 pattern.

Topology

Cytoplasmic: 1-84
Helical: 85-105
Lumenal: 106-699