Reactome | ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (gut mucosal cells)

ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (gut mucosal cells)

Stable Identifier

R-HSA-5223313

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, lysosomal lumen, lysosomal membrane

Synonyms

an R-cob(III)alamin(out) + ATP + H2O => ADP + an R-cob(III)alamin(in) + H(+) + phosphate

ReviewStatus

5/5

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ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (gut mucosal cells)

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In the mucosal cells of the distal ileum, ATP binding cassette sub family D member 4 (ABCD4) associated with lysosomal cobalamin transport escort protein (LMBRD1) mediates the ATP-dependent export of cobalamins (RCbl) from the lysosome into the cytosol. ABCD4 by itself in liposomes can mediate RCbl transport, indicating that ABCD4, not LBRD1, is directly responsible for intracellular RCbl transport (Kitai et al. 2021). Consistent with this in vitro observation, mutations affecting the ATPase activity of ABCD4 inhibit RCbl transport 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). LMBRD1 stabilizes ABCD4 in the lysosomal membrane (Kawaguchi et al. 2016) and defects in this protein are associated with a disease phenotype (CblF; MAHCF; MIM: 277380) that mimics CblJ (Rosenblatt et al. 1985, Rutsch et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
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
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
27456980	Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 Kawaguchi, K, Okamoto, T, Morita, M, Imanaka, T	Sci Rep	2016
19136951	Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism Rutsch, F, Gailus, S, Miousse, IR, Suormala, T, Sagné, C, Toliat, MR, Nürnberg, G, Wittkampf, T, Buers, I, Sharifi, A, Stucki, M, Becker, C, Baumgartner, M, Robenek, H, Marquardt, T, Höhne, W, Gasnier, B, Rosenblatt, DS, Fowler, B, Nürnberg, P	Nat. Genet.	2009
4001945	Defect in vitamin B12 release from lysosomes: newly described inborn error of vitamin B12 metabolism Rosenblatt, DS, Hosack, A, Matiaszuk, NV, Cooper, BA, Laframboise, R	Science	1985