UniProt functional annotation for P33897



	UniProt functional annotation for P33897

UniProt code: P33897.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Plays a role in the transport of free very-long-chain fatty acids (VLCFAs) as well as their CoA-esters across the peroxisomal membrane by acting as an ATP-specific binding subunit releasing ADP after ATP hydrolysis (PubMed:15682271, PubMed:11248239, PubMed:16946495, PubMed:18757502). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:23671276). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance. Controls also the cellular response to oxidative stress by regulating mitochondrial function like, mitochondrial oxidative phosphorylation and depolarization. And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (By similarity). {ECO:0000250|UniProtKB:P48410, ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:15682271, ECO:0000269|PubMed:16946495, ECO:0000269|PubMed:18757502, ECO:0000269|PubMed:23671276}.

Catalytic activity: Reaction=an acyl-CoA(out) + ATP + H2O = ADP + an acyl-CoA(in) + H(+) + phosphate; Xref=Rhea:RHEA:15181, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58342, ChEBI:CHEBI:456216; EC=7.6.2.4; Evidence={ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:15682271, ECO:0000269|PubMed:16946495};

Catalytic activity: Reaction=(9Z)-octadecenoyl-CoA(in) = (9Z)-octadecenoyl-CoA(out); Xref=Rhea:RHEA:45956, ChEBI:CHEBI:57387; Evidence={ECO:0000269|PubMed:18757502}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45958; Evidence={ECO:0000269|PubMed:18757502};

Subunit: Can form homooligomers, homodimers and heterodimers with ABCD2/ALDR and ABCD3/PMP70. Dimerization is necessary to form an active transporter (PubMed:17609205, PubMed:10551832). Interacts with PEX19; facilitates ABCD1 insertion into the peroxisome membrane (PubMed:10777694, PubMed:10704444). {ECO:0000269|PubMed:10551832, ECO:0000269|PubMed:10704444, ECO:0000269|PubMed:10777694, ECO:0000269|PubMed:17609205, ECO:0000305|PubMed:18757502}.

Subcellular location: Peroxisome membrane {ECO:0000269|PubMed:10777694, ECO:0000269|PubMed:16946495, ECO:0000269|PubMed:17609205, ECO:0000269|PubMed:18757502}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion membrane {ECO:0000269|PubMed:16946495}; Multi-pass membrane protein. Lysosome membrane {ECO:0000269|PubMed:16946495}; Multi-pass membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:16946495}; Multi-pass membrane protein.

Induction: Up-regulated by degradation or export of cholesterol. {ECO:0000269|PubMed:16213491}.

Domain: The NH2-terminal transmembrane domaine (TMD) is involved in the recognition of substrates, and undergoes a conformational change upon ATP binding to the COOH-terminal nucleotide binding domain (NBD). {ECO:0000269|PubMed:15682271}.

Ptm: Tyrosine-phosphorylated. {ECO:0000250|UniProtKB:D3ZHR2}.

Disease: Adrenoleukodystrophy (ALD) [MIM:300100]: A peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype. {ECO:0000269|PubMed:10369742, ECO:0000269|PubMed:10480364, ECO:0000269|PubMed:10551832, ECO:0000269|PubMed:10737980, ECO:0000269|PubMed:10980539, ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:11438993, ECO:0000269|PubMed:11810273, ECO:0000269|PubMed:15643618, ECO:0000269|PubMed:21700483, ECO:0000269|PubMed:21889498, ECO:0000269|PubMed:23651979, ECO:0000269|PubMed:26686776, ECO:0000269|PubMed:7581394, ECO:0000269|PubMed:7717396, ECO:0000269|PubMed:7825602, ECO:0000269|PubMed:7849723, ECO:0000269|PubMed:7904210, ECO:0000269|PubMed:8040304, ECO:0000269|PubMed:8566952, ECO:0000269|PubMed:8651290, ECO:0000269|PubMed:9452087}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=The promoter region of ABCD1 is deleted in the chromosome Xq28 deletion syndrome which involves ABCD1 and the neighboring gene BCAP31. {ECO:0000269|PubMed:11992258}.

Similarity: Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Plays a role in the transport of free very-long-chain fatty acids (VLCFAs) as well as their CoA-esters across the peroxisomal membrane by acting as an ATP-specific binding subunit releasing ADP after ATP hydrolysis (PubMed:15682271, PubMed:11248239, PubMed:16946495, PubMed:18757502). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:23671276). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance. Controls also the cellular response to oxidative stress by regulating mitochondrial function like, mitochondrial oxidative phosphorylation and depolarization. And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (By similarity). {ECO:0000250\|UniProtKB:P48410, ECO:0000269\|PubMed:11248239, ECO:0000269\|PubMed:15682271, ECO:0000269\|PubMed:16946495, ECO:0000269\|PubMed:18757502, ECO:0000269\|PubMed:23671276}.


Catalytic activity:		Reaction=an acyl-CoA(out) + ATP + H2O = ADP + an acyl-CoA(in) + H(+) + phosphate; Xref=Rhea:RHEA:15181, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58342, ChEBI:CHEBI:456216; EC=7.6.2.4; Evidence={ECO:0000269\|PubMed:11248239, ECO:0000269\|PubMed:15682271, ECO:0000269\|PubMed:16946495};
Catalytic activity:		Reaction=(9Z)-octadecenoyl-CoA(in) = (9Z)-octadecenoyl-CoA(out); Xref=Rhea:RHEA:45956, ChEBI:CHEBI:57387; Evidence={ECO:0000269\|PubMed:18757502}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45958; Evidence={ECO:0000269\|PubMed:18757502};
Subunit:		Can form homooligomers, homodimers and heterodimers with ABCD2/ALDR and ABCD3/PMP70. Dimerization is necessary to form an active transporter (PubMed:17609205, PubMed:10551832). Interacts with PEX19; facilitates ABCD1 insertion into the peroxisome membrane (PubMed:10777694, PubMed:10704444). {ECO:0000269\|PubMed:10551832, ECO:0000269\|PubMed:10704444, ECO:0000269\|PubMed:10777694, ECO:0000269\|PubMed:17609205, ECO:0000305\|PubMed:18757502}.
Subcellular location:		Peroxisome membrane {ECO:0000269\|PubMed:10777694, ECO:0000269\|PubMed:16946495, ECO:0000269\|PubMed:17609205, ECO:0000269\|PubMed:18757502}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion membrane {ECO:0000269\|PubMed:16946495}; Multi-pass membrane protein. Lysosome membrane {ECO:0000269\|PubMed:16946495}; Multi-pass membrane protein. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:16946495}; Multi-pass membrane protein.
Induction:		Up-regulated by degradation or export of cholesterol. {ECO:0000269\|PubMed:16213491}.
Domain:		The NH2-terminal transmembrane domaine (TMD) is involved in the recognition of substrates, and undergoes a conformational change upon ATP binding to the COOH-terminal nucleotide binding domain (NBD). {ECO:0000269\|PubMed:15682271}.
Ptm:		Tyrosine-phosphorylated. {ECO:0000250\|UniProtKB:D3ZHR2}.
Disease:		Adrenoleukodystrophy (ALD) [MIM:300100]: A peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype. {ECO:0000269\|PubMed:10369742, ECO:0000269\|PubMed:10480364, ECO:0000269\|PubMed:10551832, ECO:0000269\|PubMed:10737980, ECO:0000269\|PubMed:10980539, ECO:0000269\|PubMed:11248239, ECO:0000269\|PubMed:11438993, ECO:0000269\|PubMed:11810273, ECO:0000269\|PubMed:15643618, ECO:0000269\|PubMed:21700483, ECO:0000269\|PubMed:21889498, ECO:0000269\|PubMed:23651979, ECO:0000269\|PubMed:26686776, ECO:0000269\|PubMed:7581394, ECO:0000269\|PubMed:7717396, ECO:0000269\|PubMed:7825602, ECO:0000269\|PubMed:7849723, ECO:0000269\|PubMed:7904210, ECO:0000269\|PubMed:8040304, ECO:0000269\|PubMed:8566952, ECO:0000269\|PubMed:8651290, ECO:0000269\|PubMed:9452087}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=The promoter region of ABCD1 is deleted in the chromosome Xq28 deletion syndrome which involves ABCD1 and the neighboring gene BCAP31. {ECO:0000269\|PubMed:11992258}.
Similarity:		Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily. {ECO:0000305}.