ABCD4:LMBRD1 transports Cbl from lysosomal lumen to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
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ATP-binding cassette sub-family D member 4 (ABCD4), originally thought to be localised to the peroxisomal membrane, has since been demonstrated to colocalise with the lysosomal proteins LAMP1 and LMBD1. Mutations modifying the ATPase domain of ABCD4 inhibit cobalamin (Cbl, aka vitamin B12) from the lysosome to the cytosol (Coelho et al. 2012), causing methylmalonic aciduria and homocystinuria type CblJ (MAHCJ; MIM:614857), a disorder of Cbl metabolism characterised by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). This disease mimics the cblF defect caused by LMBRD1 mutations (Coelho et al. 2012). ABCD4 and LMBRD1 form complexes in the lysosomal membrane, and ABCD4 by itself in liposomes can mediate Cbl transport, indicating that ABCD4, not LBRD1, is directly responsible for intracellular Cbl transport (Kitay et al. 2021).

Literature References
PubMed ID Title Journal Year
33845046 The lysosomal protein ABCD4 can transport vitamin B12 across liposomal membranes in vitro

Kitai, K, Kawaguchi, K, Tomohiro, T, Morita, M, So, T, Imanaka, T

J Biol Chem 2021
22922874 Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism

Coelho, D, Kim, JC, Miousse, IR, Fung, S, du Moulin, M, Buers, I, Suormala, T, Burda, P, Frapolli, M, Stucki, M, Nürnberg, P, Thiele, H, Robenek, H, Höhne, W, Longo, N, Pasquali, M, Mengel, E, Watkins, D, Shoubridge, EA, Majewski, J, Rosenblatt, DS, Fowler, B, Rutsch, F, Baumgartner, MR

Nat. Genet. 2012
Catalyst Activity

ABC-type vitamin B12 transporter activity of ABCD4:LMBRD1 [lysosomal membrane]

Orthologous Events
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