Literature summary for 7.6.2.8 extracted from

Kawaguchi, K.; Okamoto, T.; Morita, M.; Imanaka, T.
Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 (2016), Sci. Rep., 6, 30183 .

Search for more literature for 7.6.2.8

Cloned(Commentary)

Cloned (Comment)	Organism
gene ABCD4, stable recombinant expression of human ABCD4 in CHO cells, recombinant expression of N-terminally MBP-tagged enzyme, stable recombinant expression of wild-type and mutant HA-tagged ABCD4 in human hepatoma HuH7 cells and additional transient coexpression of wild-type and mutant GFP-tagged LMBRD1	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	generation of chimeric ABCD4 proteins that are exchanged in terms of the corresponding putative transmembrane helix with ABCD1 (based on the secondary structure of the eukaryotic P-glycoprotein homolog CmABCB1) in HEK-293 cells, endogenous human ABCD1 does not interact with LMBD1. Construction of ABCD4 chimeras 1-6 and analysis of the localization of chimeric ABCD4s in CHO cells stably expressing LMBD1-GFP. The wild-type ABCD4 co-expressed with LMBD1 exhibits a punctate distribution that is superimposable on the distribution pattern of LMBD1. The distribution patterns of the ABCD4 chimeras 1, 3, 4 and 6 also display the same pattern as LMBD1. But ABCD4 chimeras 2 and 5 do not exhibit a punctate pattern, but rather, a reticulum-like distribution pattern that is not superimposable on LMBD1	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
endoplasmic reticulum membrane	translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1	Homo sapiens	5789	-
lysosomal membrane	translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1	Homo sapiens	5765	-
additional information	LMBD1 associates with ABCD4 at the ER membrane and transports ABCD4 to lysosomes, ABCD4 interacts with LMBD1. The translocation depends on the lysosomal targeting ability of LMBD1. Endogenous ABCD4 is localized to both lysosomes and the endoplasmic reticulum. ABCD4 lacks the NH2-teminal hydrophobic region that is responsible for the targeting to peroxisomes. ABCD4 and LMBD1 form complex in vitro. The regions around transmembrane helix 2 and 5 of ABCD4 are critically important for the translocation of ABCD4 to lysosomes along with LMBD1	Homo sapiens	-	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + H2O + vitamin B12-[cobalamin-binding protein][side 1]	Homo sapiens	-	ADP + phosphate + vitamin B12[side 2] + [cobalamin-binding protein][side 1]	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O14678	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + H2O + vitamin B12-[cobalamin-binding protein][side 1]	-	Homo sapiens	ADP + phosphate + vitamin B12[side 2] + [cobalamin-binding protein][side 1]	-	?

Subunits

Subunits	Comment	Organism
homodimer	2 * 67000, about, SDS-PAGE	Homo sapiens
More	the regions around transmembrane domains (TMs) 2, 5 and 3 are critical for the correct dimerization of ABCD4	Homo sapiens

Synonyms

Synonyms	Comment	Organism
ABC transporter	-	Homo sapiens
ABCD4	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	mutations in ABCD4 result in a failure to release vitamin B12 from lysosomes. A similar phenotype is caused by mutations in gene LMBRD1, which encodes the lysosomal membrane protein LMBD1. ABCD4 lysosomal localization is disturbed by knockout of LMBRD. Mutation of ABCD4, which is known as the cblJ complementation group, results in the failure of the release of cobalamin from lysosomes. A similar phenotype in patients within the cblF group is caused by mutations of LMBD1, a lysosomal membrane protein. Mistargeting of mutant LMBD1 affects the distribution of ABCD4. Thus, mutations of ABCD4 and LMBD1 result in a quite similar phenotype. A putative region of ABCD4 that interacts with LMBD1 might be masked by the exchange of the regions around transmembrane domains (TMs) 2 and 5	Homo sapiens
physiological function	ABCD4 is a transporter of cobalamin and forms a complex with LMBD1 for the proper targeting or functioning, or both. The two proteins function as a complex	Homo sapiens

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Release 2023.1 (January 2023)