Reactome | UniProt:O14678 ABCD4

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UniProt:O14678 ABCD4 Show undefined attributes

chain	chain:1-606
checksum	2D88DEFED0EA0777
comment	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).CATALYTIC ACTIVITY an R-cob(III)alamin(out) + ATP + H2O = an R-cob(III)alamin(in) + ADP + phosphate + H(+)BIOPHYSICOCHEMICAL PROPERTIES Homodimer or heterodimer (PubMed:27456980, PubMed:33845046). Interacts with LMBRD1; this interaction induces the translocation of ABCD4 from the ER to the lysosome membrane (PubMed:27456980, PubMed:28572511). Interacts with LMBRD1 and MMACHC; this interaction ensures the transport of cobalamin from the lysosome to the cytosol (PubMed:25535791).INTERACTION Targeted by LMBRD1 lysosomal chaperone to the lysosomal membrane.TISSUE SPECIFICITY Ubiquitous.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.CAUTION Originally proposed to be a peroxisomal protein (PubMed:9266848). Recent studies have suggested its localization to the endoplasmic reticulum and within the lysosome (PubMed:27456980).ONLINE INFORMATION Database for mutations in ABC proteins
crossReference	[DatabaseIdentifier:12419385] RefSeq:NP_005041.1 [DatabaseIdentifier:12287551] Pharos - Targets:O14678 [DatabaseIdentifier:12247951] PRO:O14678 [DatabaseIdentifier:12191707] PDB:6JBJ [DatabaseIdentifier:12135195] Orphanet:ABCD4 [DatabaseIdentifier:12127318] OpenTargets:ENSG00000119688 [DatabaseIdentifier:11850486] IntEnz:7.6.2.8 [DatabaseIdentifier:11842725] HPA:ENSG00000119688-ABCD4 [DatabaseIdentifier:11789699] GeneCards:ABCD4 [DatabaseIdentifier:11726318] ENSEMBL:ENST00000356924 [DatabaseIdentifier:11603619] ENSEMBL:ENSP00000349396 [DatabaseIdentifier:11495439] ENSEMBL:ENSG00000119688
databaseName	UniProt
dbId	49434
description	recommendedName: fullName evidence="18"Lysosomal cobalamin transporter ABCD4 ecNumber evidence="12 19 20"7.6.2.8 alternativeName: fullName evidence="22"ATP-binding cassette sub-family D member 4 alternativeName: PMP70-related protein shortName: P70R alternativeName: Peroxisomal membrane protein 1-like shortName: PXMP1-L alternativeName: Peroxisomal membrane protein 69 shortName: PMP69
displayName	UniProt:O14678 ABCD4
geneName	ABCD4 PXMP1L
identifier	O14678
isSequenceChanged	false
keyword	3D-structure ATP-binding Disease variant Endoplasmic reticulum Lysosome Membrane Nucleotide-binding Proteomics identification Reference proteome Translocase Transmembrane Transmembrane helix Transport
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	ABCD4
otherIdentifier	11718612_a_at 11718613_a_at 11752625_a_at 16794656 203981_PM_s_at 203981_s_at 203982_PM_s_at 203982_s_at 3571816 3571817 3571818 3571819 3571820 3571821 3571822 3571823 3571824 3571825 3571826 3571827 3571828 3571829 3571830 3571831 3571832 3571833 3571834 3571835 3571836 3571837 3571838 3571839 3571840 3571841 3571842 3571843 3571844 3571845 3571846 3571847 3571848 3571849 3571850 3571851 3571852 3571853 3571854 3571855 3571856 3571857 3571858 3571859 3571860 3571861 3571862 3571863 3571864 3571865 3571866 3571867 3571873 3571874 39121_at 5826 7980115 86229_r_at A_23_P37327 GE60314 GE85283 GO:0000166 GO:0005215 GO:0005324 GO:0005515 GO:0005524 GO:0005764 GO:0005765 GO:0005777 GO:0005778 GO:0005783 GO:0005789 GO:0006629 GO:0006635 GO:0007031 GO:0009235 GO:0015420 GO:0015889 GO:0015910 GO:0016020 GO:0016787 GO:0016887 GO:0042626 GO:0042760 GO:0042802 GO:0043190 GO:0043226 GO:0055085 GO:0140359 GO:1990830 HMNXSV003000322 HMNXSV003008959 HMNXSV003026042 HMNXSV003052681 Hs.94395.4.S1_3p_a_at ILMN_1651501 ILMN_1737656 ILMN_1746032 ILMN_2343917 PH_hs_0005175 TC14001304.hg TC14002086.hg g4826957_3p_a_at p4581
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5683320] ABCD4 E583Lfs*9 [lysosomal membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683326] ABCD4 Y319C [lysosomal membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5215924] ABCD4 [lysosomal membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12700072] UCSC:O14678 ABCD4 [ReferenceDNASequence:12112208] OMIM:603214 ABCD4 [ReferenceDNASequence:12074989] NCBI Gene:5826 ABCD4 [ReferenceDNASequence:11990896] Monarch:5826 ABCD4 [ReferenceDNASequence:11900103] KEGG:hsa:5826 ABCD4 [ReferenceDNASequence:11821355] HGNC:68 ABCD4 [ReferenceDNASequence:11430292] dbSNP Gene:5826 ABCD4 [ReferenceDNASequence:11416527] CTD Gene:5826 ABCD4 [ReferenceDNASequence:11394236] COSMIC - genes:ABCD4 ABCD4 [ReferenceDNASequence:11361107] BioGPS Gene:5826 ABCD4 [ReferenceDNASequence:ensembl:ENSG00000119688] ENSEMBL:ENSG00000119688 ABCD4
referenceTranscript	[ReferenceRNASequence:12601041] RefSeq:NM_005050.4 ABCD4
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ABCD4_HUMAN A8K5L7 Q6IAQ0 Q96E75
sequenceLength	606
species	[Species:48887] Homo sapiens
stId	uniprot:O14678
url	http://purl.uniprot.org/uniprot/O14678

Referrals

(interactor)	[UndirectedInteraction:11289751] UniProt:P23945 <-> UniProt:O14678 (IntAct)
(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-5683320] ABCD4 E583Lfs*9 [lysosomal membrane] [EntityWithAccessionedSequence:R-HSA-5683326] ABCD4 Y319C [lysosomal membrane] [EntityWithAccessionedSequence:R-HSA-5215924] ABCD4 [lysosomal membrane]
(referenceSequence)	[FragmentReplacedModification:5683330] Replacement of residues 583 to 590 by LRSFIPWF [ReplacedResidue:5683322] L-tyrosine 319 replaced with L-cysteine