LMBRD1 : LMBR1 domain containing 1

Description

The LMBRD1 (LMBR1 domain containing 1) is a protein-coding gene located on chromosome 6.

The LMBRD1 gene provides instructions for making a protein, called LMBD1, that is involved in the conversion of vitamin B12 (also known as cobalamin) into one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain protein building blocks (amino acids), fats (lipids), and cholesterol. AdoCbl is called a cofactor because it helps methylmalonyl CoA mutase carry out its function. MeCbl is also a cofactor, but for an enzyme known as methionine synthase. This enzyme converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds. The LMBD1 protein is found in the membrane that surrounds cell structures called lysosomes. Lysosomes are compartments within cells in which enzymes digest and recycle materials. In the lysosomal membrane, the LMBD1 protein interacts with another protein called ABCD4 (produced from the ABCD4 gene). Together, these two proteins transport vitamin B12 out of lysosomes, making it available for further processing into AdoCbl and MeCbl. Studies suggest that the LMBD1 protein is also found in the membrane that surrounds the cell (the plasma membrane). Here, the protein appears to be involved in removing another protein called the insulin receptor from the membrane. Removal of this receptor helps regulate insulin signaling, which controls levels of blood glucose, also called blood sugar. Another version (isoform) of the LMBD1 protein, sometimes called NESI, can also be produced from the LMBRD1 gene. This protein interacts with a region called the nuclear export signal (NES) of a protein that forms a piece of the hepatitis D virus. It is thought that interaction with NESI aids in the assembly of the virus. The hepatitis D virus can cause liver disease, although infection is rare and requires co-infection with a related virus called hepatitis B.

LMBD1 is a lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors. LMBD1 targets ABCD4 transporter from the endoplasmic reticulum to the lysosome. LMBD1 forms a complex with lysosomal ABCD4 and cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane. LMBD1 acts as an adapter protein which plays an important role in mediating and regulating the internalization of the insulin receptor (INSR). LMBD1 is involved in clathrin-mediated endocytosis of INSR via its interaction with adapter protein complex 2. LMBD1 is essential for the initiation of gastrulation and early formation of mesoderm structures during embryogenesis.

LMBRD1 is also known as C6orf209, LMBD1, MAHCF, NESI.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing