| IED ID | IndEnz0010000485 |
| Enzyme Type ID | esterase000485 |
| Protein Name |
ATP-binding cassette sub-family D member 1 EC 3.1.2.- EC 7.6.2.- Adrenoleukodystrophy protein ALDP |
| Gene Name | ABCD1 ALD |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MPVLSRPRPWRGNTLKRTAVLLALAAYGAHKVYPLVRQCLAPARGLQAPAGEPTQEASGVAAAKAGMNRVFLQRLLWLLRLLFPRVLCRETGLLALHSAALVSRTFLSVYVARLDGRLARCIVRKDPRAFGWQLLQWLLIALPATFVNSAIRYLEGQLALSFRSRLVAHAYRLYFSQQTYYRVSNMDGRLRNPDQSLTEDVVAFAASVAHLYSNLTKPLLDVAVTSYTLLRAARSRGAGTAWPSAIAGLVVFLTANVLRAFSPKFGELVAEEARRKGELRYMHSRVVANSEEIAFYGGHEVELALLQRSYQDLASQINLILLERLWYVMLEQFLMKYVWSASGLLMVAVPIITATGYSESDAEAVKKAALEKKEEELVSERTEAFTIARNLLTAAADAIERIMSSYKEVTELAGYTARVHEMFQVFEDVQRCHFKRPRELEDAQAGSGTIGRSGVRVEGPLKIRGQVVDVEQGIICENIPIVTPSGEVVVASLNIRVEEGMHLLITGPNGCGKSSLFRILGGLWPTYGGVLYKPPPQRMFYIPQRPYMSVGSLRDQVIYPDSVEDMQRKGYSEQDLEAILDVVHLHHILQREGGWEAMCDWKDVLSGGEKQRIGMARMFYHRPKYALLDECTSAVSIDVEGKIFQAAKDAGIALLSITHRPSLWKYHTHLLQFDGEGGWKFEKLDSAARLSLTEEKQRLEQQLAGIPKMQRRLQELCQILGEAVAPAHVPAPSPQGPGGLQGAST |
| Enzyme Length | 745 |
| Uniprot Accession Number | P33897 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: The cysteine-reactive reagent p-chloromercuribenzoic acid (pCMB) strongly decreased the ACOT activity. The serine esterase inhibitors phenylmethylsulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP) and bis-(4-nitrophenyl)phosphate (BNPP) moderately reduced the ACOT activity. The histidine-reacting reagent diethyl pyrocarbonate (DEPC) has no effect on the ACOT activity. {ECO:0000269|PubMed:33500543}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a very long-chain fatty acyl-CoA + H2O = a very long-chain fatty acid + CoA + H(+); Xref=Rhea:RHEA:67072, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:58950, ChEBI:CHEBI:138261; Evidence={ECO:0000269|PubMed:29397936, ECO:0000269|PubMed:33500543};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67073; Evidence={ECO:0000305|PubMed:33500543}; CATALYTIC ACTIVITY: Reaction=a very long-chain fatty acid(in) + ATP + H2O = a very long-chain fatty acid(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:67080, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58950, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:29397936, ECO:0000269|PubMed:33500543, ECO:0000305|PubMed:16946495, ECO:0000305|PubMed:21145416, ECO:0000305|PubMed:23671276};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67081; Evidence={ECO:0000305|PubMed:33500543}; CATALYTIC ACTIVITY: Reaction=H2O + tetracosanoyl-CoA = CoA + H(+) + tetracosanoate; Xref=Rhea:RHEA:40787, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:31014, ChEBI:CHEBI:57287, ChEBI:CHEBI:65052; Evidence={ECO:0000269|PubMed:33500543};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40788; Evidence={ECO:0000305|PubMed:33500543}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + tetracosanoate(in) = ADP + H(+) + phosphate + tetracosanoate(out); Xref=Rhea:RHEA:67088, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:31014, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:21145416};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67089; Evidence={ECO:0000305|PubMed:33500543}; CATALYTIC ACTIVITY: Reaction=H2O + hexacosanoyl-CoA = CoA + H(+) + hexacosanoate; Xref=Rhea:RHEA:40791, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:31013, ChEBI:CHEBI:57287, ChEBI:CHEBI:64868; Evidence={ECO:0000269|PubMed:33500543};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40792; Evidence={ECO:0000305|PubMed:33500543}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + hexacosanoate(in) = ADP + H(+) + hexacosanoate(out) + phosphate; Xref=Rhea:RHEA:67084, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:31013, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:21145416, ECO:0000305|PubMed:23671276};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67085; Evidence={ECO:0000305|PubMed:21145416}; CATALYTIC ACTIVITY: Reaction=docosanoyl-CoA + H2O = CoA + docosanoate + H(+); Xref=Rhea:RHEA:40783, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:23858, ChEBI:CHEBI:57287, ChEBI:CHEBI:65059; Evidence={ECO:0000269|PubMed:33500543};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40784; Evidence={ECO:0000305|PubMed:33500543}; CATALYTIC ACTIVITY: Reaction=ATP + docosanoate(in) + H2O = ADP + docosanoate(out) + H(+) + phosphate; Xref=Rhea:RHEA:67092, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:23858, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:23671276};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67093; Evidence={ECO:0000305|PubMed:23671276}; |
| DNA Binding | |
| EC Number | 3.1.2.-; 7.6.2.- |
| Enzyme Function | FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed:15682271, PubMed:16946495, PubMed:18757502, PubMed:21145416, PubMed:23671276, PubMed:29397936, PubMed:33500543). Coupled to the ATP-dependent transporter activity has also a fatty acyl-CoA thioesterase activity (ACOT) and hydrolyzes VLCFA-CoA into VLCFA prior their ATP-dependent transport into peroxisomes, the ACOT activity is essential during this transport process (PubMed:33500543, PubMed:29397936). 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, PubMed:21145416). 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 functions such as 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:21145416, ECO:0000269|PubMed:23671276, ECO:0000269|PubMed:29397936, ECO:0000269|PubMed:33500543}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 507..514; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00434 |
| Features | Chain (1); Domain (2); Glycosylation (1); Modified residue (1); Mutagenesis (18); Natural variant (148); Nucleotide binding (1); Region (3); Sequence conflict (2); Transmembrane (5) |
| Keywords | 3D-structure;ATP-binding;Disease variant;Endoplasmic reticulum;Glycoprotein;Hydrolase;Lysosome;Membrane;Mitochondrion;Nucleotide-binding;Peroxisome;Phosphoprotein;Reference proteome;Translocase;Transmembrane;Transmembrane helix;Transport |
| Interact With | Itself; P28288; P40855; P48410 |
| Induction | INDUCTION: Up-regulated by degradation or export of cholesterol. {ECO:0000269|PubMed:16213491}. |
| Subcellular Location | SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:10777694, ECO:0000269|PubMed:16946495, ECO:0000269|PubMed:17609205, ECO:0000269|PubMed:18757502, ECO:0000269|PubMed:29397936}; 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. |
| Modified Residue | MOD_RES 733; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976" |
| Post Translational Modification | PTM: Tyrosine-phosphorylated. {ECO:0000250|UniProtKB:D3ZHR2}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (4) |
| Cross Reference PDB | 7RR9; 7RRA; 7SHM; 7SHN; |
| Mapped Pubmed ID | 10430017; 11390669; 11402059; 11453642; 11500517; 11590176; 11883941; 12175782; 12509471; 12530690; 12579499; 12624723; 12751901; 12897190; 12924628; 14556192; 14709540; 14767898; 15001567; 15007061; 15209530; 15713480; 15772093; 15811009; 16018167; 16087056; 16280322; 16331554; 16791427; 16895967; 16980692; 17069900; 17285533; 17504626; 17542813; 17662307; 17761426; 17828604; 18174172; 18481121; 18782765; 18973459; 19204726; 19343046; 19406751; 19787628; 20042197; 20376793; 20531392; 20554521; 20661612; 21102411; 21273699; 21966424; 21988832; 22176151; 22280810; 22624858; 22994209; 23123468; 23300730; 23460677; 23469258; 23566833; 23606334; 23628762; 23835273; 24154795; 24480483; 24597975; 24658140; 24719134; 25062251; 25234129; 25275259; 25393703; 25517356; 25835712; 26454440; 26496610; 26777132; 27084228; 27337030; 27766264; 28281558; 28325759; 28601575; 28911205; 29136088; 29966135; 31074578; 31665121; 32075856; 32416190; 33127985; 33373044; 34056752; 34069712; 34198763; 34347682; 34649108; 34754073; 34946879; 35013584; 35053399; 8411712; 8507690; 8656081; 9345306; 9418908; 9684854; |
| Motif | |
| Gene Encoded By | |
| Mass | 82,937 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:67072; RHEA:67073; RHEA:67080; RHEA:67081; RHEA:40787; RHEA:40788; RHEA:67088; RHEA:67089; RHEA:40791; RHEA:40792; RHEA:67084; RHEA:67085; RHEA:40783; RHEA:40784; RHEA:67092; RHEA:67093 |
| Cross Reference Brenda | 7.6.2.4; |