ABCD4

Function

Lysosomal membrane protein that transports cobalamin (Vitamin B12) from the lysosomal lumen to the cytosol in an ATP-dependent manner (PubMed:22922874, PubMed:28572511, PubMed:31467407, PubMed:33845046). Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane (PubMed:27456980). Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791).

Involvement in disease

Methylmalonic aciduria and homocystinuria type cblJ

MAHCJ

A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include feeding difficulties, poor growth, hypotonia, lethargy, anemia, and developmental delay.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence Similarities

Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.

Tissue Specificity

Ubiquitous.

Cellular localization

• Endoplasmic reticulum membrane
• Multi-pass membrane protein
• Lysosome membrane
• Multi-pass membrane protein
• Targeted by LMBRD1 lysosomal chaperone to the lysosomal membrane.

Alternative names

PXMP1L, ABCD4, Lysosomal cobalamin transporter ABCD4, ATP-binding cassette sub-family D member 4, PMP70-related protein, Peroxisomal membrane protein 1-like, Peroxisomal membrane protein 69, P70R, PXMP1-L, PMP69

Database links

swissprot:O14678 genbank:NM_005050 entrezGene:5826 omim:603214