LMBRD1
Function
Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors (PubMed:19136951). Targets ABCD4 transporter from the endoplasmic reticulum to the lysosome (PubMed:27456980). Then forms a complex with lysosomal ABCD4 and cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791). Acts as an adapter protein which plays an important role in mediating and regulating the internalization of the insulin receptor (INSR) (By similarity). Involved in clathrin-mediated endocytosis of INSR via its interaction with adapter protein complex 2 (By similarity). Essential for the initiation of gastrulation and early formation of mesoderm structures during embryogenesis (By similarity).
Isoform 3
(Microbial infection) May play a role in the assembly of hepatitis delta virus (HDV).
Involvement in disease
Methylmalonic aciduria and homocystinuria, cblF type
MAHCF
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). It is due to accumulation of free cobalamin in lysosomes, thus hindering its conversion to cofactors. Clinical features include developmental delay, stomatitis, glossitis, seizures and methylmalonic aciduria responsive to vitamin B12.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the LIMR family. LMBRD1 subfamily.
Tissue Specificity
Isoform 3 is expressed in liver.
Cellular localization
- Endoplasmic reticulum membrane
- Lysosome membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle
- Clathrin-coated vesicle
Alternative names
C6orf209, NESI, BM-021, CD001, MSTP044, LMBRD1, Lysosomal cobalamin transport escort protein LMBD1, LMBD1, HDAg-L-interacting protein NESI, LMBR1 domain-containing protein 1, Nuclear export signal-interacting protein