ABCD1 encodes ALDP, a peroxisomal membrane ABC half-transporter that assembles principally as a homodimer. It recognizes fatty-acyl-CoA substrates, especially saturated very-long-chain species, and couples ATP utilization to import supporting peroxisomal beta-oxidation and fatty-acid homeostasis. Biochemical preparations exhibit acyl-CoA thioesterase activity, although whether native transport releases intact acyl-CoA or a fatty acid after thioester cleavage remains unresolved. PEX19 recognizes nascent ABCD1 as a membrane-protein client during targeting. Loss of ABCD1 function causes X-linked adrenoleukodystrophy, with accumulation of very-long-chain fatty acids and tissue-dependent neurological and adrenal injury. Mitochondrial dysfunction, oxidative stress, inflammation and axonal/myelin pathology can follow the primary lipid-handling defect.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000038 very long-chain fatty acid metabolic process | IDA PMID:29397936 Characterization of human ATP-binding cassette protein subfa... | ACCEPT | Summary: ABCD1 directly participates in very-long-chain fatty acid metabolism through import and associated acyl-CoA handling. Reason: PMID:29397936 reports reconstituted human ABCD proteins with ATPase and acyl-CoA thioesterase activities. Human fibroblast and substrate-specific complementation studies independently establish the ABCD1-dependent metabolic entry step, rather than a generic downstream disease association. |
| GO:0000038 very long-chain fatty acid metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse metabolic phenotype supports conserved human VLCFA handling. Reason: Mouse P48410 has an experimental source in PMID:15489218 showing VLCFA accumulation after Abcd1 loss and rescue by ABCD2. Human transport and fibroblast studies independently establish the same core pathway; donor tracing does not rely solely on its additional human-derived inferred rows. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse P48410 has an experimental source in PMID:15489218 showing VLCFA accumulation after Abcd1 loss and rescue by ABCD2. Human transport and fibroblast studies independently establish the same core pathway; donor tracing does not rely solely on its additional human-derived inferred rows. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. Mouse P48410 has an experimental source in PMID:15489218 showing VLCFA accumulation after Abcd1 loss and rescue by ABCD2. Human transport and fibroblast studies independently establish the same core pathway; donor tracing does not rely solely on its additional human-derived inferred rows. |
| GO:0002082 regulation of oxidative phosphorylation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial oxidative-phosphorylation changes are downstream of impaired peroxisomal lipid handling. Reason: The P48410 source PMID:23604518 combines human X-ALD fibroblast observations with Abcd1-deficient mouse spinal cord studies. Excess C26:0 induces mitochondrial oxidative damage and impaired OXPHOS. Retain this regulatory consequence as non-core; ABCD1 is not a respiratory-chain subunit or a demonstrated mitochondrial ATP transporter. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The P48410 source PMID:23604518 combines human X-ALD fibroblast observations with Abcd1-deficient mouse spinal cord studies. Excess C26:0 induces mitochondrial oxidative damage and impaired OXPHOS. Retain this regulatory consequence as non-core; ABCD1 is not a respiratory-chain subunit or a demonstrated mitochondrial ATP transporter. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. The P48410 source PMID:23604518 combines human X-ALD fibroblast observations with Abcd1-deficient mouse spinal cord studies. Excess C26:0 induces mitochondrial oxidative damage and impaired OXPHOS. Retain this regulatory consequence as non-core; ABCD1 is not a respiratory-chain subunit or a demonstrated mitochondrial ATP transporter. |
| GO:0002082 regulation of oxidative phosphorylation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial oxidative-phosphorylation changes are downstream of impaired peroxisomal lipid handling. Reason: The P48410 source PMID:23604518 combines human X-ALD fibroblast observations with Abcd1-deficient mouse spinal cord studies. Excess C26:0 induces mitochondrial oxidative damage and impaired OXPHOS. Retain this regulatory consequence as non-core; ABCD1 is not a respiratory-chain subunit or a demonstrated mitochondrial ATP transporter. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The P48410 source PMID:23604518 combines human X-ALD fibroblast observations with Abcd1-deficient mouse spinal cord studies. Excess C26:0 induces mitochondrial oxidative damage and impaired OXPHOS. Retain this regulatory consequence as non-core; ABCD1 is not a respiratory-chain subunit or a demonstrated mitochondrial ATP transporter. |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | EXP PMID:11500517 Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunction... | UNDECIDED | Summary: The original experimental source does not resolve the particular transporter assay from its accessible abstract. Reason: PMID:11500517 examines DHA retroconversion and reports normal DHA synthesis in X-ALD fibroblasts. This does not refute ABCD1 fatty-acid transport, which is independently established, but the full text was unavailable and the exact evidence underlying this EXP row could not be checked. Do not allege wrong-gene curation from the title or abstract. The unresolved point is this source-specific experimental provenance; the independently established transporter function and the suitability of GO:0015607 are not in doubt. |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | IBA GO_REF:0000033 | MODIFY | Summary: ABCD1 recognizes fatty-acyl-CoA substrates for ATP-dependent peroxisomal import. Reason: The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. Purified human DeltaN1-54 ABCD1 in PMID:36810450 shows C26:0-CoA-stimulated ATPase, without stimulation by free C26:0 or acetyl-CoA. PMID:36374178 adds human mutant-dependent HEK293F lipid measurements and separate DeltaN1-54 ATPase assays; its cellular readout is a transport-related proxy, not purified membrane flux. These sources corroborate the refinement without resolving thioester fate. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity Supporting Evidence: PMID:36810450 C26:0-CoA stimulated ATP hydrolysis by two-fold at saturation concentrations PMID:36374178 All six disease-derived mutants exhibit decreased transport toward three species of VLCFA-CoA. |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | IEA GO_REF:0000120 | MODIFY | Summary: ABCD1 recognizes fatty-acyl-CoA substrates for ATP-dependent peroxisomal import. Reason: The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. Purified human DeltaN1-54 ABCD1 in PMID:36810450 shows C26:0-CoA-stimulated ATPase, without stimulation by free C26:0 or acetyl-CoA. PMID:36374178 adds human mutant-dependent HEK293F lipid measurements and separate DeltaN1-54 ATPase assays; its cellular readout is a transport-related proxy, not purified membrane flux. These sources corroborate the refinement without resolving thioester fate. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. InterPro:IPR005283 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity Supporting Evidence: PMID:36810450 C26:0-CoA stimulated ATP hydrolysis by two-fold at saturation concentrations PMID:36374178 All six disease-derived mutants exhibit decreased transport toward three species of VLCFA-CoA. |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | IGI PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | MODIFY | Summary: ABCD1 recognizes fatty-acyl-CoA substrates for ATP-dependent peroxisomal import. Reason: The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. Purified human DeltaN1-54 ABCD1 in PMID:36810450 shows C26:0-CoA-stimulated ATPase, without stimulation by free C26:0 or acetyl-CoA. PMID:36374178 adds human mutant-dependent HEK293F lipid measurements and separate DeltaN1-54 ATPase assays; its cellular readout is a transport-related proxy, not purified membrane flux. These sources corroborate the refinement without resolving thioester fate. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity Supporting Evidence: PMID:36810450 C26:0-CoA stimulated ATP hydrolysis by two-fold at saturation concentrations PMID:36374178 All six disease-derived mutants exhibit decreased transport toward three species of VLCFA-CoA. |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | TAS Reactome:R-HSA-5684043 | MODIFY | Summary: ABCD1 recognizes fatty-acyl-CoA substrates for ATP-dependent peroxisomal import. Reason: The broader fatty-acid transporter assignment is biologically related, but ABC-type fatty-acyl-CoA transporter activity captures the demonstrated input and energy coupling more informatively. PMID:18757502 tests human ABCD1 in yeast complementation; PMID:35676282 resolves bound acyl-CoA. This term is retained in its established transport sense while the fate of the CoA thioester during native translocation remains unresolved, as discussed in PMID:35013584 and PMID:33500543. The mutant Reactome event informs normal transport by contrast. Purified human DeltaN1-54 ABCD1 in PMID:36810450 shows C26:0-CoA-stimulated ATPase, without stimulation by free C26:0 or acetyl-CoA. PMID:36374178 adds human mutant-dependent HEK293F lipid measurements and separate DeltaN1-54 ATPase assays; its cellular readout is a transport-related proxy, not purified membrane flux. These sources corroborate the refinement without resolving thioester fate. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity Supporting Evidence: PMID:36810450 C26:0-CoA stimulated ATP hydrolysis by two-fold at saturation concentrations PMID:36374178 All six disease-derived mutants exhibit decreased transport toward three species of VLCFA-CoA. |
| GO:0005515 protein binding | IPI PMID:10551832 Homo- and heterodimerization of peroxisomal ATP-binding cass... | MODIFY | Summary: ABCD1 can form a heterodimeric interaction with ABCD3. Reason: The cited interaction is more informative than generic protein binding. PMID:10551832 reports two-hybrid/co-immunoprecipitation evidence and PMID:17609205 demonstrates ABCD1/ABCD3 heterodimer FRET in living cells, although ABCD1 homodimers predominate. Replace with protein heterodimerization activity without treating every heterodimer as the principal physiological transport unit. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:10551832 Homo- and heterodimerization of peroxisomal ATP-binding cass... | UNDECIDED | Summary: The cross-species ABCD1 interaction does not by itself establish homodimerization. Reason: The seeded interactor P48410 is mouse Abcd1, so this particular row describes a human-mouse pair rather than two identical human proteins. Native human ABCD1 homodimerization is independently established, but that fact does not resolve which constructs support this source-specific interaction in PMID:10551832. The full study was unavailable; leave this generic interaction unresolved rather than replace it with homodimerization on the basis of a xenolog pair alone. |
| GO:0005515 protein binding | IPI PMID:10777694 Human adrenoleukodystrophy protein and related peroxisomal A... | MODIFY | Summary: ABCD1 binds the PEX19 chaperone as a membrane-protein client. Reason: PMID:10777694 identifies PEX19 binding to the ABCD1 targeting region; PMID:11883941 shows interaction of PEX19 splice variants with ALDP. The live GO:0051087 definition includes binding a chaperone that supports folding or transport. This identifies the clientβchaperone interaction more precisely without assigning PEX19 chaperone activity, receptor activity or membrane-insertion machinery to ABCD1. The original partner isoform fields are preserved. Proposed replacements: protein-folding chaperone binding |
| GO:0005515 protein binding | IPI PMID:11883941 Two splice variants of human PEX19 exhibit distinct function... | MODIFY | Summary: ABCD1 binds the PEX19 chaperone as a membrane-protein client. Reason: PMID:10777694 identifies PEX19 binding to the ABCD1 targeting region; PMID:11883941 shows interaction of PEX19 splice variants with ALDP. The live GO:0051087 definition includes binding a chaperone that supports folding or transport. This identifies the clientβchaperone interaction more precisely without assigning PEX19 chaperone activity, receptor activity or membrane-insertion machinery to ABCD1. The original partner isoform fields are preserved. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:11883941 Both interact with peroxisomal ABC transporters (ALDP, ALDRP, PMP70) |
| GO:0005515 protein binding | IPI PMID:11883941 Two splice variants of human PEX19 exhibit distinct function... | MODIFY | Summary: ABCD1 binds the PEX19 chaperone as a membrane-protein client. Reason: PMID:10777694 identifies PEX19 binding to the ABCD1 targeting region; PMID:11883941 shows interaction of PEX19 splice variants with ALDP. The live GO:0051087 definition includes binding a chaperone that supports folding or transport. This identifies the clientβchaperone interaction more precisely without assigning PEX19 chaperone activity, receptor activity or membrane-insertion machinery to ABCD1. The original partner isoform fields are preserved. Proposed replacements: protein-folding chaperone binding |
| GO:0005515 protein binding | IPI PMID:11883941 Two splice variants of human PEX19 exhibit distinct function... | MODIFY | Summary: ABCD1 binds the PEX19 chaperone as a membrane-protein client. Reason: PMID:10777694 identifies PEX19 binding to the ABCD1 targeting region; PMID:11883941 shows interaction of PEX19 splice variants with ALDP. The live GO:0051087 definition includes binding a chaperone that supports folding or transport. This identifies the clientβchaperone interaction more precisely without assigning PEX19 chaperone activity, receptor activity or membrane-insertion machinery to ABCD1. The original partner isoform fields are preserved. Proposed replacements: protein-folding chaperone binding |
| GO:0005515 protein binding | IPI PMID:17609205 Live cell FRET microscopy: homo- and heterodimerization of t... | MODIFY | Summary: ABCD1 can form a heterodimeric interaction with ABCD3. Reason: The cited interaction is more informative than generic protein binding. PMID:10551832 reports two-hybrid/co-immunoprecipitation evidence and PMID:17609205 demonstrates ABCD1/ABCD3 heterodimer FRET in living cells, although ABCD1 homodimers predominate. Replace with protein heterodimerization activity without treating every heterodimer as the principal physiological transport unit. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:17609205 Live cell FRET microscopy: homo- and heterodimerization of t... | UNDECIDED | Summary: The source-specific ABCD1βABCD2 interaction needs full-text verification. Reason: PMID:17609205 primarily describes live-cell ABCD1/ABCD3 FRET in the accessible abstract, while this row names ABCD2/Q9UBJ2. The full text was not accessible to verify the specific ABCD2 experiment. Do not infer a misattribution from that abstract: other human interaction work supports ABCD1βABCD2 association, but does not establish this exact source assay. |
| GO:0005515 protein binding | IPI PMID:20531392 The peroxisomal receptor Pex19p forms a helical mPTS recogni... | UNDECIDED | Summary: The precise ABCD1 construct in the PEX19 recognition-domain study could not be checked. Reason: PMID:20531392 establishes PEX19 as a receptor/chaperone for PMP targeting signals, but the accessible abstract does not identify the particular ABCD1 client experiment. Full text was unavailable. The general PEX19 interaction is corroborated by PMID:10777694 and PMID:11883941; retain uncertainty for this source-specific generic binding row rather than inventing its assay. |
| GO:0005524 ATP binding | IBA GO_REF:0000033 | ACCEPT | Summary: ABCD1 binds ATP through its conserved nucleotide-binding domain. Reason: PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. |
| GO:0005524 ATP binding | IDA PMID:11248239 Characterization and functional analysis of the nucleotide b... | ACCEPT | Summary: ABCD1 binds ATP through its conserved nucleotide-binding domain. Reason: PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. |
| GO:0005524 ATP binding | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | ACCEPT | Summary: ABCD1 binds ATP through its conserved nucleotide-binding domain. Reason: PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ABCD1 binds ATP through its conserved nucleotide-binding domain. Reason: PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. These direct data independently corroborate the InterPro ATP-binding-domain assignment. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR003439 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. InterPro:IPR005283 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. InterPro:IPR017871 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. InterPro:IPR036640 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 directly measures binding and hydrolysis using human ABCD1 nucleotide-binding-fold constructs. PMID:16946495 tests ATP/ADP-agarose binding of full-length human ABCD1 expressed in Sf21 membranes, and modern human structures directly resolve the nucleotide-bound transporter. This supports the PAINT/domain inference independently of donor number or target self-inclusion. |
| GO:0005737 cytoplasm | IDA PMID:17761426 Distribution and cellular localization of adrenoleukodystrop... | MODIFY | Summary: Peroxisomal membrane is the specific established intracellular location. Reason: The human tissue distribution study PMID:17761426 supports intracellular ABCD1 staining, and multiple independent targeting and localization studies place the functional transporter in the peroxisomal membrane. Refining the broad cytoplasm term does not imply that cytoplasm excludes membrane-bound organelles or that the original staining was soluble. Proposed replacements: peroxisomal membrane |
| GO:0005765 lysosomal membrane | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | MARK AS OVER ANNOTATED | Summary: The non-peroxisomal location was observed during heterologous overexpression, not established as normal human residence. Reason: The full publisher PDF of PMID:16946495 (https://www.jstage.jst.go.jp/article/bpb/29/9/29_9_1836/_pdf) reports in Results/Figure 2BβC (pp. 1838β1839) ALDPHis distributed among mitochondria, lysosomes and ER in baculovirus-infected Sf21 insect cells. At later times nuclear aggregates appeared. These are real model-system observations, but extrapolating them to physiological human lysosomal, ER or mitochondrial location overstates that experiment. Native peroxisomal membrane localization is independently supported; the derived UniProt subcellular-location mapping inherits this context problem. Supporting Evidence: |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: The non-peroxisomal location was observed during heterologous overexpression, not established as normal human residence. Reason: The full publisher PDF of PMID:16946495 (https://www.jstage.jst.go.jp/article/bpb/29/9/29_9_1836/_pdf) reports in Results/Figure 2BβC (pp. 1838β1839) ALDPHis distributed among mitochondria, lysosomes and ER in baculovirus-infected Sf21 insect cells. At later times nuclear aggregates appeared. These are real model-system observations, but extrapolating them to physiological human lysosomal, ER or mitochondrial location overstates that experiment. Native peroxisomal membrane localization is independently supported; the derived UniProt subcellular-location mapping inherits this context problem. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB-SubCell:SL-0157 SUPPORTS SOURCE BUT NOT TARGET UniProt location mapping inherits the Sf21 overexpression context of PMID:16946495; it is not additional native human localization evidence. Supporting Evidence: |
| GO:0005777 peroxisome | IDA PMID:10777694 Human adrenoleukodystrophy protein and related peroxisomal A... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:10777694 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:14533738 Targeting of the human adrenoleukodystrophy protein to the p... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:14533738 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:17542813 Adrenoleukodystrophy: subcellular localization and degradati... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:17542813 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. The mutant-localization experiments do not assign mutant mistargeting to the wild-type protein. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:17761426 Distribution and cellular localization of adrenoleukodystrop... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:17761426 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:18757502 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:20810565 Peroxisomal localization of the proopiomelanocortin-derived ... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:20810565 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. The POMC study uses ABCD1 as a peroxisomal marker; colocalization does not establish that ABCD1 transports the peptide. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:9425230 Suppression of peroxisomal membrane protein defects by perox... | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source PMID:9425230 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IEA GO_REF:0000002 | MODIFY | Summary: ABCD1 is integrated into the peroxisomal membrane rather than specified only at whole-organelle resolution. Reason: The original source GO_REF:0000002 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement of the broad peroxisome term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR005283 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. The original source GO_REF:0000002 is consistent with peroxisomal localization. Independent human targeting and membrane-integration experiments (PMID:14533738; PMID:10777694) establish the more specific membrane compartment. This is a specificity refinement; neither the POMC colocalization study nor mutant-localization work is interpreted as assigning their unrelated substrate or defect to wild-type ABCD1. Proposed replacements: peroxisomal membrane |
| GO:0005778 peroxisomal membrane | EXP PMID:10777694 Human adrenoleukodystrophy protein and related peroxisomal A... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: PMID:10777694 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | EXP PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: PMID:18757502 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: GO_REF:0000033 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. GO_REF:0000033 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | IDA PMID:10640429 Intraperoxisomal localization of very-long-chain fatty acyl-... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: PMID:10640429 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: The full publisher text of PMID:16946495 detects human ALDP-His in a peroxisomal pool as well as other membranes after baculovirus overexpression in Sf21 cells. The authors identify catalase-less peroxisomes by their established fractionation behavior and attribute the additional distribution to limited peroxisome capacity under high expression. This source-specific result supports a peroxisomal membrane pool in that system. Independent native human targeting and localization studies establish the physiological peroxisomal membrane location; the Sf21 extra-peroxisomal distribution is evaluated separately. |
| GO:0005778 peroxisomal membrane | IDA PMID:17609205 Live cell FRET microscopy: homo- and heterodimerization of t... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: PMID:17609205 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | IDA PMID:29397936 Characterization of human ATP-binding cassette protein subfa... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: PMID:29397936 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: GO_REF:0000120 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028584 UNRESOLVED The rule identifier is recorded in GOA, but its learned predicates and training support were not independently inspected. The annotation-level judgment rests on the cited primary ABCD1 biology, not validation of the internal ARBA rule. GO_REF:0000120 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. UniProtKB:P48410 SUPPORTS TRANSFER GO_REF:0000120 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. GO_REF:0000120 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. UniProtKB-SubCell:SL-0203 SUPPORTS TRANSFER UniProt location mapping inherits the Sf21 overexpression context of PMID:16946495; it is not additional native human localization evidence. |
| GO:0005778 peroxisomal membrane | NAS PMID:8441467 Putative X-linked adrenoleukodystrophy gene shares unexpecte... | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: PMID:8441467 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-2046087 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-2046087 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-2046093 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-2046093 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-382575 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-382575 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-382613 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-382613 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-390393 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-390393 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-5684043 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-5684043 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. The disease-variant event describes failed transport; it does not redefine the native localization. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9603775 | ACCEPT | Summary: The peroxisomal membrane is the principal functional site of ABCD1. Reason: Reactome:R-HSA-9603775 is consistent with a membrane-integrated peroxisomal transporter. Human targeting studies, cell localization and modern membrane-reconstituted structures corroborate this location. This dissociation event explicitly leaves the class I PMP inserted in the membrane and releases PEX19 to cytosol. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | MARK AS OVER ANNOTATED | Summary: The non-peroxisomal location was observed during heterologous overexpression, not established as normal human residence. Reason: The full publisher PDF of PMID:16946495 (https://www.jstage.jst.go.jp/article/bpb/29/9/29_9_1836/_pdf) reports in Results/Figure 2BβC (pp. 1838β1839) ALDPHis distributed among mitochondria, lysosomes and ER in baculovirus-infected Sf21 insect cells. At later times nuclear aggregates appeared. These are real model-system observations, but extrapolating them to physiological human lysosomal, ER or mitochondrial location overstates that experiment. Native peroxisomal membrane localization is independently supported; the derived UniProt subcellular-location mapping inherits this context problem. Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: The non-peroxisomal location was observed during heterologous overexpression, not established as normal human residence. Reason: The full publisher PDF of PMID:16946495 (https://www.jstage.jst.go.jp/article/bpb/29/9/29_9_1836/_pdf) reports in Results/Figure 2BβC (pp. 1838β1839) ALDPHis distributed among mitochondria, lysosomes and ER in baculovirus-infected Sf21 insect cells. At later times nuclear aggregates appeared. These are real model-system observations, but extrapolating them to physiological human lysosomal, ER or mitochondrial location overstates that experiment. Native peroxisomal membrane localization is independently supported; the derived UniProt subcellular-location mapping inherits this context problem. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB-SubCell:SL-0097 SUPPORTS SOURCE BUT NOT TARGET UniProt location mapping inherits the Sf21 overexpression context of PMID:16946495; it is not additional native human localization evidence. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-382613 | KEEP AS NON CORE | Summary: Nascent ABCD1 can be a PEX19-bound cytosolic client before membrane insertion. Reason: Reactome:R-HSA-382613 models class I PMP capture or docking: the cytosolic input is a nascent PMP or PEX19:PMP complex. The live Reactome participants support this transient biosynthetic stage, consistent with PMID:10777694. Retain as non-core location; it is not the mature transporter's active compartment and does not make ABCD1 a soluble transport receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9603775 | MODIFY | Summary: This dissociation event leaves the ABCD1-class cargo in the peroxisomal membrane. Reason: Live Reactome:R-HSA-9603775 has PEX3:PEX19:class I PMP as membrane input and outputs cytosolic PEX19, membrane PEX3 and membrane class I PMPs. The cytosolic product is the chaperone, not the inserted ABCD1 cargo. Refine this particular event-derived cytosol annotation to peroxisomal membrane; the separate nascent-client cytosol events remain non-core. Proposed replacements: peroxisomal membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9603784 | KEEP AS NON CORE | Summary: Nascent ABCD1 can be a PEX19-bound cytosolic client before membrane insertion. Reason: Reactome:R-HSA-9603784 models class I PMP capture or docking: the cytosolic input is a nascent PMP or PEX19:PMP complex. The live Reactome participants support this transient biosynthetic stage, consistent with PMID:10777694. Retain as non-core location; it is not the mature transporter's active compartment and does not make ABCD1 a soluble transport receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9603804 | KEEP AS NON CORE | Summary: Nascent ABCD1 can be a PEX19-bound cytosolic client before membrane insertion. Reason: Reactome:R-HSA-9603804 models class I PMP capture or docking: the cytosolic input is a nascent PMP or PEX19:PMP complex. The live Reactome participants support this transient biosynthetic stage, consistent with PMID:10777694. Retain as non-core location; it is not the mature transporter's active compartment and does not make ABCD1 a soluble transport receptor. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000107 | UNDECIDED | Summary: Mouse GO-CAMs place Abcd1 transport within fatty-acid biosynthesis, but the exact genetic experiment remains unresolved. Reason: The mouse P48410/MGI:MGI:1349215 donor is explicitly represented in cached GO-CAM models 675b862c00001162 and 675b862c00001348 as a peroxisomal long-chain fatty-acid transporter participating in GO:0006633, with IGI evidence PMID:16223892 and Abcd2 (MGI:MGI:1349467). Thus the curator models a transport contribution to a biosynthetic pathway, not elongase or synthase catalysis by Abcd1. The accessible abstract does not resolve the specific Abcd1 genetic result, and full text was unavailable. Retain source-specific uncertainty without disputing the modeled participation or inferring paralog misattribution from the title. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P48410 UNRESOLVED The mouse P48410/MGI:MGI:1349215 donor is explicitly represented in cached GO-CAM models 675b862c00001162 and 675b862c00001348 as a peroxisomal long-chain fatty-acid transporter participating in GO:0006633, with IGI evidence PMID:16223892 and Abcd2 (MGI:MGI:1349467). Thus the curator models a transport contribution to a biosynthetic pathway, not elongase or synthase catalysis by Abcd1. The accessible abstract does not resolve the specific Abcd1 genetic result, and full text was unavailable. Retain source-specific uncertainty without disputing the modeled participation or inferring paralog misattribution from the title. ensembl:ENSMUSP00000002084 UNRESOLVED ENSMUSP00000002084 corresponds to the same mouse Abcd1 donor, not an independent experiment. The mouse P48410/MGI:MGI:1349215 donor is explicitly represented in cached GO-CAM models 675b862c00001162 and 675b862c00001348 as a peroxisomal long-chain fatty-acid transporter participating in GO:0006633, with IGI evidence PMID:16223892 and Abcd2 (MGI:MGI:1349467). Thus the curator models a transport contribution to a biosynthetic pathway, not elongase or synthase catalysis by Abcd1. The accessible abstract does not resolve the specific Abcd1 genetic result, and full text was unavailable. Retain source-specific uncertainty without disputing the modeled participation or inferring paralog misattribution from the title. |
| GO:0006635 fatty acid beta-oxidation | IBA GO_REF:0000033 | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: GO_REF:0000033 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. GO_REF:0000033 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. |
| GO:0006635 fatty acid beta-oxidation | IDA PMID:17542813 Adrenoleukodystrophy: subcellular localization and degradati... | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: PMID:17542813 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. Supporting Evidence: PMID:23671276 the Ξ²-oxidation defect in X-ALD is directly caused by ABCD1 dysfunction |
| GO:0006635 fatty acid beta-oxidation | IDA PMID:9425230 Suppression of peroxisomal membrane protein defects by perox... | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: PMID:9425230 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000120 | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: GO_REF:0000120 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028692 UNRESOLVED The rule identifier is recorded in GOA, but its learned predicates and training support were not independently inspected. The annotation-level judgment rests on the cited primary ABCD1 biology, not validation of the internal ARBA rule. GO_REF:0000120 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. UniProtKB:P48410 SUPPORTS TRANSFER GO_REF:0000120 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. GO_REF:0000120 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. |
| GO:0006635 fatty acid beta-oxidation | IGI PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: PMID:18757502 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. |
| GO:0006635 fatty acid beta-oxidation | IGI PMID:21145416 Differential substrate specificities of human ABCD1 and ABCD... | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: PMID:21145416 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. |
| GO:0006635 fatty acid beta-oxidation | IMP PMID:23671276 Impaired very long-chain acyl-CoA Ξ²-oxidation in human X-lin... | ACCEPT | Summary: ABCD1 supplies substrates to peroxisomal fatty-acid beta-oxidation through the import step. Reason: PMID:23671276 fits the established pathway role. Human ABCD1 rescues fatty-acid oxidation in the yeast Pxa1/Pxa2 system (PMID:18757502; PMID:21145416); patient fibroblast and antibody-blocking experiments link impaired acyl-CoA oxidation directly to ABCD1 dysfunction (PMID:23671276). The protein performs transport work that supplies the pathway, not the oxidation chemistry itself. |
| GO:0007031 peroxisome organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Peroxisome-organization evidence reflects a complementation context beyond the main transport activity. Reason: PMID:9425230 reports that ABCD1 or ABCD3 expression can rescue peroxisome biogenesis in Pex2-deficient cells. This provides evidence for the existing broad organization assertion but does not establish ABCD1 as the primary import/insertion machinery. The original 1993 homology-based source is less specific; later complementation supports a contextual interpretation. For PAINT, retain the inherited broad association without treating donor count or ABCD1 self-inclusion as circular. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT node links ABCD1/ABCD3 to broad peroxisome organization. Retained only as contextual complementation evidence from PMID:9425230, not primary peroxisomal insertion machinery; no donor-count or target-self objection. |
| GO:0007031 peroxisome organization | IDA PMID:9425230 Suppression of peroxisomal membrane protein defects by perox... | KEEP AS NON CORE | Summary: Peroxisome-organization evidence reflects a complementation context beyond the main transport activity. Reason: PMID:9425230 reports that ABCD1 or ABCD3 expression can rescue peroxisome biogenesis in Pex2-deficient cells. This provides evidence for the existing broad organization assertion but does not establish ABCD1 as the primary import/insertion machinery. |
| GO:0007031 peroxisome organization | NAS PMID:8441467 Putative X-linked adrenoleukodystrophy gene shares unexpecte... | KEEP AS NON CORE | Summary: Peroxisome-organization evidence reflects a complementation context beyond the main transport activity. Reason: PMID:9425230 reports that ABCD1 or ABCD3 expression can rescue peroxisome biogenesis in Pex2-deficient cells. This provides evidence for the existing broad organization assertion but does not establish ABCD1 as the primary import/insertion machinery. The original 1993 homology-based source is less specific; later complementation supports a contextual interpretation. |
| GO:0015607 ABC-type fatty-acyl-CoA transporter activity | IDA PMID:15682271 Probing substrate-induced conformational alterations in adre... | ACCEPT | Summary: ABCD1 recognizes fatty-acyl-CoA substrates in an ATP-coupled peroxisomal import cycle. Reason: PMID:15682271 detects substrate-dependent conformational changes; PMID:18757502 tests human transporter function by yeast complementation. Human cell studies and substrate-bound structures corroborate acyl-CoA recognition and import. The exact chemical species crossing the membrane remains unresolved between intact-CoA and hydrolysis/re-esterification models. Retain this established activity annotation without claiming that substrate-bound structures alone prove intact-ester translocation. Supporting Evidence: PMID:18757502 ALDP can function as a homodimer PMID:35013584 It is currently unclear whether the fatty acyl chain is separated from its CoA ester for subsequent re-esterification |
| GO:0015607 ABC-type fatty-acyl-CoA transporter activity | IGI PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: ABCD1 recognizes fatty-acyl-CoA substrates in an ATP-coupled peroxisomal import cycle. Reason: PMID:15682271 detects substrate-dependent conformational changes; PMID:18757502 tests human transporter function by yeast complementation. Human cell studies and substrate-bound structures corroborate acyl-CoA recognition and import. The exact chemical species crossing the membrane remains unresolved between intact-CoA and hydrolysis/re-esterification models. Retain this established activity annotation without claiming that substrate-bound structures alone prove intact-ester translocation. |
| GO:0015910 long-chain fatty acid import into peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: ABCD1 imports fatty-acid substrates into peroxisomes. Reason: Human ABCD1 complementation of the yeast import defect in PMID:18757502 and differential substrate studies in PMID:21145416 establish this direction of transport. Long-chain as well as very-long-chain substrates are recognized, although saturated C24/C26 handling is most characteristic. The established process does not settle whether the thioester bond remains intact during crossing. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. Human ABCD1 complementation of the yeast import defect in PMID:18757502 and differential substrate studies in PMID:21145416 establish this direction of transport. Long-chain as well as very-long-chain substrates are recognized, although saturated C24/C26 handling is most characteristic. The established process does not settle whether the thioester bond remains intact during crossing. |
| GO:0015910 long-chain fatty acid import into peroxisome | IEA GO_REF:0000002 | ACCEPT | Summary: ABCD1 imports fatty-acid substrates into peroxisomes. Reason: Human ABCD1 complementation of the yeast import defect in PMID:18757502 and differential substrate studies in PMID:21145416 establish this direction of transport. Long-chain as well as very-long-chain substrates are recognized, although saturated C24/C26 handling is most characteristic. The established process does not settle whether the thioester bond remains intact during crossing. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR005283 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. Human ABCD1 complementation of the yeast import defect in PMID:18757502 and differential substrate studies in PMID:21145416 establish this direction of transport. Long-chain as well as very-long-chain substrates are recognized, although saturated C24/C26 handling is most characteristic. The established process does not settle whether the thioester bond remains intact during crossing. |
| GO:0015910 long-chain fatty acid import into peroxisome | IGI PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: ABCD1 imports fatty-acid substrates into peroxisomes. Reason: Human ABCD1 complementation of the yeast import defect in PMID:18757502 and differential substrate studies in PMID:21145416 establish this direction of transport. Long-chain as well as very-long-chain substrates are recognized, although saturated C24/C26 handling is most characteristic. The established process does not settle whether the thioester bond remains intact during crossing. |
| GO:0015916 fatty-acyl-CoA transport | IEA GO_REF:0000108 | ACCEPT | Summary: Acyl-CoA transport is the established pathway-level description of ABCD1 substrate import. Reason: The GO:0015607 parent activity logically supports this process, corroborated by human fibroblast and substrate-recognition studies. Here acyl-CoA denotes the supplied substrate and pathway entry; the exact chemistry of thioester cleavage during native translocation is qualified in the molecular-function review. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0015607 SUPPORTS TRANSFER The GO:0015607 parent activity logically supports this process, corroborated by human fibroblast and substrate-recognition studies. Here acyl-CoA denotes the supplied substrate and pathway entry; the exact chemistry of thioester cleavage during native translocation is qualified in the molecular-function review. |
| GO:0015919 peroxisomal membrane transport | NAS PMID:8441467 Putative X-linked adrenoleukodystrophy gene shares unexpecte... | ACCEPT | Summary: ABCD1 performs ATP-dependent transport across the peroxisomal membrane. Reason: The early gene-identification paper PMID:8441467 inferred a transporter from ABC homology. Later human complementation, biochemical and structural studies establish the peroxisomal transport role independently, so the broad process is retained. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: The generic membrane annotation can be localized to the peroxisomal membrane. Reason: The high-throughput membrane proteome or InterPro membrane-domain assignment is compatible with the multi-pass protein. Independent targeting and localization studies identify the more informative functional compartment. This refinement does not allege an error in the proteomic detection or imply that a generic membrane term means soluble protein. Proposed replacements: peroxisomal membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The generic membrane annotation can be localized to the peroxisomal membrane. Reason: The high-throughput membrane proteome or InterPro membrane-domain assignment is compatible with the multi-pass protein. Independent targeting and localization studies identify the more informative functional compartment. This refinement does not allege an error in the proteomic detection or imply that a generic membrane term means soluble protein. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR005283 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. The high-throughput membrane proteome or InterPro membrane-domain assignment is compatible with the multi-pass protein. Independent targeting and localization studies identify the more informative functional compartment. This refinement does not allege an error in the proteomic detection or imply that a generic membrane term means soluble protein. InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. The high-throughput membrane proteome or InterPro membrane-domain assignment is compatible with the multi-pass protein. Independent targeting and localization studies identify the more informative functional compartment. This refinement does not allege an error in the proteomic detection or imply that a generic membrane term means soluble protein. InterPro:IPR036640 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. The high-throughput membrane proteome or InterPro membrane-domain assignment is compatible with the multi-pass protein. Independent targeting and localization studies identify the more informative functional compartment. This refinement does not allege an error in the proteomic detection or imply that a generic membrane term means soluble protein. Proposed replacements: peroxisomal membrane |
| GO:0016887 ATP hydrolysis activity | IDA PMID:11248239 Characterization and functional analysis of the nucleotide b... | ACCEPT | Summary: ABCD1 directly hydrolyzes ATP to drive its transport cycle. Reason: PMID:11248239 measures purified human nucleotide-domain activity; PMID:16946495 measures increased activity in ABCD1-expressing insect membranes; PMID:33500543 and modern human reconstitution studies independently substantiate ATP hydrolysis. The 2006 detergent-purified preparation lost activity, which is an assay-context limitation rather than evidence that membrane ABCD1 lacks ATPase activity. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | ACCEPT | Summary: ABCD1 directly hydrolyzes ATP to drive its transport cycle. Reason: PMID:11248239 measures purified human nucleotide-domain activity; PMID:16946495 measures increased activity in ABCD1-expressing insect membranes; PMID:33500543 and modern human reconstitution studies independently substantiate ATP hydrolysis. The 2006 detergent-purified preparation lost activity, which is an assay-context limitation rather than evidence that membrane ABCD1 lacks ATPase activity. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:33500543 Acyl-CoA thioesterase activity of peroxisomal ABC protein AB... | ACCEPT | Summary: ABCD1 directly hydrolyzes ATP to drive its transport cycle. Reason: PMID:11248239 measures purified human nucleotide-domain activity; PMID:16946495 measures increased activity in ABCD1-expressing insect membranes; PMID:33500543 and modern human reconstitution studies independently substantiate ATP hydrolysis. The 2006 detergent-purified preparation lost activity, which is an assay-context limitation rather than evidence that membrane ABCD1 lacks ATPase activity. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: ABCD1 directly hydrolyzes ATP to drive its transport cycle. Reason: PMID:11248239 measures purified human nucleotide-domain activity; PMID:16946495 measures increased activity in ABCD1-expressing insect membranes; PMID:33500543 and modern human reconstitution studies independently substantiate ATP hydrolysis. The 2006 detergent-purified preparation lost activity, which is an assay-context limitation rather than evidence that membrane ABCD1 lacks ATPase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR003439 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 measures purified human nucleotide-domain activity; PMID:16946495 measures increased activity in ABCD1-expressing insect membranes; PMID:33500543 and modern human reconstitution studies independently substantiate ATP hydrolysis. The 2006 detergent-purified preparation lost activity, which is an assay-context limitation rather than evidence that membrane ABCD1 lacks ATPase activity. InterPro:IPR017871 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. PMID:11248239 measures purified human nucleotide-domain activity; PMID:16946495 measures increased activity in ABCD1-expressing insect membranes; PMID:33500543 and modern human reconstitution studies independently substantiate ATP hydrolysis. The 2006 detergent-purified preparation lost activity, which is an assay-context limitation rather than evidence that membrane ABCD1 lacks ATPase activity. |
| GO:0019217 regulation of fatty acid metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fatty-acid metabolic regulation is a broad consequence of substrate transport. Reason: The ARBA assignment is consistent with altered fatty-acid pools, oxidation and compensatory elongation after ABCD1 deficiency. Retain the broad regulatory association as non-core; the activity-centered description is acyl-CoA-dependent import supplying peroxisomal catabolism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00084953 UNRESOLVED The rule identifier is recorded in GOA, but its learned predicates and training support were not independently inspected. The annotation-level judgment rests on the cited primary ABCD1 biology, not validation of the internal ARBA rule. The ARBA assignment is consistent with altered fatty-acid pools, oxidation and compensatory elongation after ABCD1 deficiency. Retain the broad regulatory association as non-core; the activity-centered description is acyl-CoA-dependent import supplying peroxisomal catabolism. |
| GO:0019899 enzyme binding | IPI PMID:16781659 Molecular organization of peroxisomal enzymes: protein-prote... | KEEP AS NON CORE | Summary: ABCD1 physically interacts with a very-long-chain acyl-CoA synthetase in an experimental system. Reason: PMID:16781659 uses yeast two-hybrid and surface plasmon resonance to report the ALDPβVLCS interaction. This supports enzyme binding as a contextual association, but the paper does not establish that ABCD1 itself activates acyl-CoA or identify an enzyme-regulator mechanism sufficient to replace it. Later import studies distinguish ABCD1 transport from the synthetase step. |
| GO:0030497 fatty acid elongation | IEA GO_REF:0000107 | UNDECIDED | Summary: Increased elongation after Abcd1 loss is a verified phenotype, but the basis for assigning ABCD1 participation in elongation remains unresolved. Reason: The mouse donor PMID:26108493 reports increased microsomal C20:0-CoA elongation in three-week-old Abcd1-deficient brain. This perturbation establishes an effect on elongation, not that ABCD1 performs an elongation step. ABCD1 supplies peroxisomal fatty-acid import, whereas this assay measures microsomal chain extension. The full original study and any experiment establishing direct participation were not recovered. Preserve the transferred assertion for curator follow-up, without converting it into a new regulation annotation or claiming that the donor experiment is wrong. The existing GO:0019217 row separately retains a broad non-core metabolic association. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P48410 UNRESOLVED P48410 and ENSMUSP00000002084 identify the same mouse Abcd1 donor, not independent experiments. The accessible original abstract shows increased microsomal elongation after Abcd1 deficiency. The full study was unavailable, so the evidence establishing participation rather than a downstream metabolic response remains unverified. No replacement regulation term is asserted. ensembl:ENSMUSP00000002084 UNRESOLVED P48410 and ENSMUSP00000002084 identify the same mouse Abcd1 donor, not independent experiments. The accessible original abstract shows increased microsomal elongation after Abcd1 deficiency. The full study was unavailable, so the evidence establishing participation rather than a downstream metabolic response remains unverified. No replacement regulation term is asserted. Supporting Evidence: PMID:26108493 microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice |
| GO:0030497 fatty acid elongation | ISS GO_REF:0000024 | UNDECIDED | Summary: Increased elongation after Abcd1 loss is a verified phenotype, but the basis for assigning ABCD1 participation in elongation remains unresolved. Reason: The mouse donor PMID:26108493 reports increased microsomal C20:0-CoA elongation in three-week-old Abcd1-deficient brain. This perturbation establishes an effect on elongation, not that ABCD1 performs an elongation step. ABCD1 supplies peroxisomal fatty-acid import, whereas this assay measures microsomal chain extension. The full original study and any experiment establishing direct participation were not recovered. Preserve the transferred assertion for curator follow-up, without converting it into a new regulation annotation or claiming that the donor experiment is wrong. The existing GO:0019217 row separately retains a broad non-core metabolic association. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P48410 UNRESOLVED P48410 and ENSMUSP00000002084 identify the same mouse Abcd1 donor, not independent experiments. The accessible original abstract shows increased microsomal elongation after Abcd1 deficiency. The full study was unavailable, so the evidence establishing participation rather than a downstream metabolic response remains unverified. No replacement regulation term is asserted. Supporting Evidence: PMID:26108493 microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice |
| GO:0031966 mitochondrial membrane | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | MARK AS OVER ANNOTATED | Summary: The non-peroxisomal location was observed during heterologous overexpression, not established as normal human residence. Reason: The full publisher PDF of PMID:16946495 (https://www.jstage.jst.go.jp/article/bpb/29/9/29_9_1836/_pdf) reports in Results/Figure 2BβC (pp. 1838β1839) ALDPHis distributed among mitochondria, lysosomes and ER in baculovirus-infected Sf21 insect cells. At later times nuclear aggregates appeared. These are real model-system observations, but extrapolating them to physiological human lysosomal, ER or mitochondrial location overstates that experiment. Native peroxisomal membrane localization is independently supported; the derived UniProt subcellular-location mapping inherits this context problem. Supporting Evidence: |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: The non-peroxisomal location was observed during heterologous overexpression, not established as normal human residence. Reason: The full publisher PDF of PMID:16946495 (https://www.jstage.jst.go.jp/article/bpb/29/9/29_9_1836/_pdf) reports in Results/Figure 2BβC (pp. 1838β1839) ALDPHis distributed among mitochondria, lysosomes and ER in baculovirus-infected Sf21 insect cells. At later times nuclear aggregates appeared. These are real model-system observations, but extrapolating them to physiological human lysosomal, ER or mitochondrial location overstates that experiment. Native peroxisomal membrane localization is independently supported; the derived UniProt subcellular-location mapping inherits this context problem. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB-SubCell:SL-0171 SUPPORTS SOURCE BUT NOT TARGET UniProt location mapping inherits the Sf21 overexpression context of PMID:16946495; it is not additional native human localization evidence. Supporting Evidence: |
| GO:0031998 regulation of fatty acid beta-oxidation | IEA GO_REF:0000107 | MODIFY | Summary: The direct role is substrate import supporting beta-oxidation. Reason: Mouse P48410 sources include PMID:25255441, which attributes the impaired oxidation and compensatory ABCD2 effects to transport of VLCFAs into peroxisomes. This supports direct participation in fatty acid beta-oxidation through its import step more clearly than a separate upstream regulatory mechanism. Other older knockout sources likewise measure the pathway output, not a distinct regulatory enzyme. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse P48410 sources include PMID:25255441, which attributes the impaired oxidation and compensatory ABCD2 effects to transport of VLCFAs into peroxisomes. This supports direct participation in fatty acid beta-oxidation through its import step more clearly than a separate upstream regulatory mechanism. Other older knockout sources likewise measure the pathway output, not a distinct regulatory enzyme. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. Mouse P48410 sources include PMID:25255441, which attributes the impaired oxidation and compensatory ABCD2 effects to transport of VLCFAs into peroxisomes. This supports direct participation in fatty acid beta-oxidation through its import step more clearly than a separate upstream regulatory mechanism. Other older knockout sources likewise measure the pathway output, not a distinct regulatory enzyme. Proposed replacements: fatty acid beta-oxidation |
| GO:0031998 regulation of fatty acid beta-oxidation | ISS GO_REF:0000024 | MODIFY | Summary: The direct role is substrate import supporting beta-oxidation. Reason: Mouse P48410 sources include PMID:25255441, which attributes the impaired oxidation and compensatory ABCD2 effects to transport of VLCFAs into peroxisomes. This supports direct participation in fatty acid beta-oxidation through its import step more clearly than a separate upstream regulatory mechanism. Other older knockout sources likewise measure the pathway output, not a distinct regulatory enzyme. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse P48410 sources include PMID:25255441, which attributes the impaired oxidation and compensatory ABCD2 effects to transport of VLCFAs into peroxisomes. This supports direct participation in fatty acid beta-oxidation through its import step more clearly than a separate upstream regulatory mechanism. Other older knockout sources likewise measure the pathway output, not a distinct regulatory enzyme. Proposed replacements: fatty acid beta-oxidation |
| GO:0032000 positive regulation of fatty acid beta-oxidation | IEA GO_REF:0000107 | MODIFY | Summary: ABCD1 supports beta-oxidation by delivering the substrate. Reason: PMID:23123468 measures reduced VLCFA oxidation in human U87 cells and mouse astrocytes after ABCD1 loss, while resolving additional ABCD1-independent peroxisomal/mitochondrial routes. The most precise mechanistic assertion is involvement in beta-oxidation via import, rather than an additional positive-regulatory activity. Mouse donor studies PMID:18723473 and PMID:18854420 are compatible with this supply role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER PMID:23123468 measures reduced VLCFA oxidation in human U87 cells and mouse astrocytes after ABCD1 loss, while resolving additional ABCD1-independent peroxisomal/mitochondrial routes. The most precise mechanistic assertion is involvement in beta-oxidation via import, rather than an additional positive-regulatory activity. Mouse donor studies PMID:18723473 and PMID:18854420 are compatible with this supply role. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. PMID:23123468 measures reduced VLCFA oxidation in human U87 cells and mouse astrocytes after ABCD1 loss, while resolving additional ABCD1-independent peroxisomal/mitochondrial routes. The most precise mechanistic assertion is involvement in beta-oxidation via import, rather than an additional positive-regulatory activity. Mouse donor studies PMID:18723473 and PMID:18854420 are compatible with this supply role. Proposed replacements: fatty acid beta-oxidation |
| GO:0032000 positive regulation of fatty acid beta-oxidation | IMP PMID:23123468 Very long chain fatty acid Ξ²-oxidation in astrocytes: contri... | MODIFY | Summary: ABCD1 supports beta-oxidation by delivering the substrate. Reason: PMID:23123468 measures reduced VLCFA oxidation in human U87 cells and mouse astrocytes after ABCD1 loss, while resolving additional ABCD1-independent peroxisomal/mitochondrial routes. The most precise mechanistic assertion is involvement in beta-oxidation via import, rather than an additional positive-regulatory activity. Mouse donor studies PMID:18723473 and PMID:18854420 are compatible with this supply role. Proposed replacements: fatty acid beta-oxidation |
| GO:0032000 positive regulation of fatty acid beta-oxidation | ISS GO_REF:0000024 | MODIFY | Summary: ABCD1 supports beta-oxidation by delivering the substrate. Reason: PMID:23123468 measures reduced VLCFA oxidation in human U87 cells and mouse astrocytes after ABCD1 loss, while resolving additional ABCD1-independent peroxisomal/mitochondrial routes. The most precise mechanistic assertion is involvement in beta-oxidation via import, rather than an additional positive-regulatory activity. Mouse donor studies PMID:18723473 and PMID:18854420 are compatible with this supply role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER PMID:23123468 measures reduced VLCFA oxidation in human U87 cells and mouse astrocytes after ABCD1 loss, while resolving additional ABCD1-independent peroxisomal/mitochondrial routes. The most precise mechanistic assertion is involvement in beta-oxidation via import, rather than an additional positive-regulatory activity. Mouse donor studies PMID:18723473 and PMID:18854420 are compatible with this supply role. Proposed replacements: fatty acid beta-oxidation |
| GO:0036109 alpha-linolenic acid metabolic process | TAS Reactome:R-HSA-2046106 | KEEP AS NON CORE | Summary: Polyunsaturated-fatty-acid pathway participation is broader and less characteristic than saturated VLCFA import. Reason: The Reactome pathway includes peroxisomal import of elongated polyunsaturated intermediates for a final shortening step. ABCD1 has overlapping substrate capacity with ABCD2/3, but PMID:21145416 favors C24:0/C26:0 for ABCD1 and polyunsaturated substrates for ABCD2. PMID:11500517 reports normal DHA synthesis in X-ALD fibroblasts. Retain the curated pathway context as non-core without asserting that ABCD1 is uniquely required for DHA/DPA synthesis. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IBA GO_REF:0000033 | MODIFY | Summary: The generic ATP-driven transporter activity can be made substrate-specific. Reason: ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008319914 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity Supporting Evidence: file:human/ABCD1/ABCD1-deep-research-falcon.md VLCFA-CoA is the cytosolic loading/recognition substrate |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IDA PMID:29397936 Characterization of human ATP-binding cassette protein subfa... | MODIFY | Summary: The generic ATP-driven transporter activity can be made substrate-specific. Reason: The original PMID:29397936 reports stable ATPase and ACOT activities after human ABCD1-4 expression, purification and reconstitution into liposomes; its accessible abstract does not directly measure substrate flux. Independent ABCD1 complementation and acyl-CoA binding/structural evidence support the more informative ABC-type fatty-acyl-CoA transporter activity. Retain ATP-coupled import as the biological interpretation while distinguishing the original enzymatic assays from a direct transport assay and leaving the thioester-cleavage sequence unresolved. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: The generic ATP-driven transporter activity can be made substrate-specific. Reason: ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR005283 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity |
| GO:0042626 ATPase-coupled transmembrane transporter activity | NAS PMID:8441467 Putative X-linked adrenoleukodystrophy gene shares unexpecte... | MODIFY | Summary: The generic ATP-driven transporter activity can be made substrate-specific. Reason: ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity |
| GO:0042758 long-chain fatty acid catabolic process | IGI PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: ABCD1 supplies fatty acids for peroxisomal catabolism. Reason: The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. |
| GO:0042760 very long-chain fatty acid catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: ABCD1 supplies fatty acids for peroxisomal catabolism. Reason: The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004256010 SUPPORTS TRANSFER PAINT ancestral-node assignment assessed as inherited function, not pairwise donor counting. Human ABCD1 experimental evidence corroborates the core transport/localization/ATP-binding role; target self-inclusion is expected. The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. |
| GO:0042760 very long-chain fatty acid catabolic process | IDA PMID:9425230 Suppression of peroxisomal membrane protein defects by perox... | ACCEPT | Summary: ABCD1 supplies fatty acids for peroxisomal catabolism. Reason: The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. |
| GO:0042760 very long-chain fatty acid catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: ABCD1 supplies fatty acids for peroxisomal catabolism. Reason: The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00088525 UNRESOLVED The rule identifier is recorded in GOA, but its learned predicates and training support were not independently inspected. The annotation-level judgment rests on the cited primary ABCD1 biology, not validation of the internal ARBA rule. The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. UniProtKB:P48410 SUPPORTS TRANSFER Mouse Abcd1 loss and Abcd1/Abcd2 compensation experiments in macrophages (PMID:25255441) link this donor to VLCFA oxidation and accumulation. These provide donor-side pathway support; human complementation and patient-fibroblast studies independently corroborate substrate provision to fatty-acid catabolism. ABCD1 supplies the import step and does not catalyze the downstream oxidation reactions. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the same mouse Abcd1 donor chain as P48410. Mouse Abcd1 loss and Abcd1/Abcd2 compensation experiments in macrophages (PMID:25255441) link this donor to VLCFA oxidation and accumulation. These provide donor-side pathway support; human complementation and patient-fibroblast studies independently corroborate substrate provision to fatty-acid catabolism. ABCD1 supplies the import step and does not catalyze the downstream oxidation reactions. |
| GO:0042760 very long-chain fatty acid catabolic process | IGI PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: ABCD1 supplies fatty acids for peroxisomal catabolism. Reason: The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. |
| GO:0042760 very long-chain fatty acid catabolic process | IGI PMID:21145416 Differential substrate specificities of human ABCD1 and ABCD... | ACCEPT | Summary: ABCD1 supplies fatty acids for peroxisomal catabolism. Reason: The transporter directly performs the entry step required for oxidation. PMID:18757502 and PMID:21145416 use human ABCD1 complementation and substrate comparisons; PMID:23671276 links human acyl-CoA oxidation to ABCD1 activity. Saturated very-long-chain substrates are the principal physiological emphasis, with overlapping long-chain capacity. No direct oxidation catalytic activity is assigned to ABCD1. |
| GO:0042802 identical protein binding | IPI PMID:10551832 Homo- and heterodimerization of peroxisomal ATP-binding cass... | MODIFY | Summary: The identical-protein interaction reflects ABCD1 homodimer assembly. Reason: PMID:10551832 reports ABCD1 homodimerization, subsequently supported by live-cell FRET and human cryo-EM structures. Replace generic identical-protein binding with the already evidenced homodimerization activity, without proposing an additional redundant NEW annotation. Proposed replacements: protein homodimerization activity |
| GO:0042803 protein homodimerization activity | IDA PMID:17609205 Live cell FRET microscopy: homo- and heterodimerization of t... | ACCEPT | Summary: ABCD1 homodimers constitute a functional transporter unit. Reason: Live-cell FRET (PMID:17609205), sole-human-ABCD1 rescue in yeast (PMID:18757502; PMID:21145416) and human structures (PMID:35013584) support homodimer assembly. Reports of heterodimers do not negate the predominant functional homodimer. |
| GO:0042803 protein homodimerization activity | IDA PMID:18757502 The human peroxisomal ABC half transporter ALDP functions as... | ACCEPT | Summary: ABCD1 homodimers constitute a functional transporter unit. Reason: Live-cell FRET (PMID:17609205), sole-human-ABCD1 rescue in yeast (PMID:18757502; PMID:21145416) and human structures (PMID:35013584) support homodimer assembly. Reports of heterodimers do not negate the predominant functional homodimer. |
| GO:0042803 protein homodimerization activity | IDA PMID:21145416 Differential substrate specificities of human ABCD1 and ABCD... | ACCEPT | Summary: ABCD1 homodimers constitute a functional transporter unit. Reason: Live-cell FRET (PMID:17609205), sole-human-ABCD1 rescue in yeast (PMID:18757502; PMID:21145416) and human structures (PMID:35013584) support homodimer assembly. Reports of heterodimers do not negate the predominant functional homodimer. |
| GO:0043217 myelin maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myelin maintenance is a downstream tissue consequence of lipid homeostasis. Reason: Mouse P48410 sources PMID:11875044 and PMID:15489218 describe late-onset axonal and myelin pathology after Abcd1 loss, with rescue/modification by ABCD2. Retain this disease-relevant maintenance association as non-core; it is not direct myelin structural assembly by the transporter. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse P48410 sources PMID:11875044 and PMID:15489218 describe late-onset axonal and myelin pathology after Abcd1 loss, with rescue/modification by ABCD2. Retain this disease-relevant maintenance association as non-core; it is not direct myelin structural assembly by the transporter. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. Mouse P48410 sources PMID:11875044 and PMID:15489218 describe late-onset axonal and myelin pathology after Abcd1 loss, with rescue/modification by ABCD2. Retain this disease-relevant maintenance association as non-core; it is not direct myelin structural assembly by the transporter. |
| GO:0043217 myelin maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myelin maintenance is a downstream tissue consequence of lipid homeostasis. Reason: Mouse P48410 sources PMID:11875044 and PMID:15489218 describe late-onset axonal and myelin pathology after Abcd1 loss, with rescue/modification by ABCD2. Retain this disease-relevant maintenance association as non-core; it is not direct myelin structural assembly by the transporter. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse P48410 sources PMID:11875044 and PMID:15489218 describe late-onset axonal and myelin pathology after Abcd1 loss, with rescue/modification by ABCD2. Retain this disease-relevant maintenance association as non-core; it is not direct myelin structural assembly by the transporter. |
| GO:0043531 ADP binding | IDA PMID:16946495 ATP-binding and -hydrolysis activities of ALDP (ABCD1) and A... | ACCEPT | Summary: ABCD1 can bind ADP within its nucleotide cycle. Reason: The full publisher text of PMID:16946495 shows binding of human ALDPHis in Sf21 membranes to ADP-agarose, competed by free ADP, and similar binding for rat liver ALDP. The assay directly supports nucleotide binding, independently of the nonphysiological extra-peroxisomal distribution in the same overexpression system. |
| GO:0043651 linoleic acid metabolic process | TAS Reactome:R-HSA-2046105 | KEEP AS NON CORE | Summary: Polyunsaturated-fatty-acid pathway participation is broader and less characteristic than saturated VLCFA import. Reason: The Reactome pathway includes peroxisomal import of elongated polyunsaturated intermediates for a final shortening step. ABCD1 has overlapping substrate capacity with ABCD2/3, but PMID:21145416 favors C24:0/C26:0 for ABCD1 and polyunsaturated substrates for ABCD2. PMID:11500517 reports normal DHA synthesis in X-ALD fibroblasts. Retain the curated pathway context as non-core without asserting that ABCD1 is uniquely required for DHA/DPA synthesis. |
| GO:0045834 positive regulation of lipid metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of lipid metabolism is a broad downstream description. Reason: The ARBA mapping is compatible with ABCD1-dependent lipid oxidation and homeostasis. Retain as a broad non-core regulatory association; the specific transport and catabolic participation annotations capture the direct molecular role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00086378 UNRESOLVED The rule identifier is recorded in GOA, but its learned predicates and training support were not independently inspected. The annotation-level judgment rests on the cited primary ABCD1 biology, not validation of the internal ARBA rule. The ARBA mapping is compatible with ABCD1-dependent lipid oxidation and homeostasis. Retain as a broad non-core regulatory association; the specific transport and catabolic participation annotations capture the direct molecular role. |
| GO:0047617 fatty acyl-CoA hydrolase activity | IDA PMID:29397936 Characterization of human ATP-binding cassette protein subfa... | ACCEPT | Summary: ABCD1 preparations exhibit fatty-acyl-CoA thioesterase activity. Reason: PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. Supporting Evidence: PMID:33500543 The expressed ABCD1 possessed both ATPase and ACOT activities. |
| GO:0047617 fatty acyl-CoA hydrolase activity | IDA PMID:33500543 Acyl-CoA thioesterase activity of peroxisomal ABC protein AB... | ACCEPT | Summary: ABCD1 preparations exhibit fatty-acyl-CoA thioesterase activity. Reason: PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:17761426 Distribution and cellular localization of adrenoleukodystrop... | UNDECIDED | Summary: The precise perinuclear distribution requires the full human tissue study. Reason: PMID:17761426 surveys human tissue and cell-type expression, but the accessible abstract does not expose the imaging evidence for this particular subcellular distribution. Full text could not be obtained. Preserve source-specific uncertainty instead of treating a perinuclear signal as incompatible with peroxisomal membranes. |
| GO:0051900 regulation of mitochondrial depolarization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial depolarization is an indirect lipid-stress consequence. Reason: The mouse P48410 source PMID:25583114 shows increased vulnerability of Abcd1-deficient astrocytes to prolonged, supraphysiological VLCFA exposure and mitochondrial depolarization. Isolated mitochondria from mutant and control mice respond similarly. This supports a contextual protective/regulatory consequence of cellular lipid handling, not direct mitochondrial membrane transport by ABCD1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The mouse P48410 source PMID:25583114 shows increased vulnerability of Abcd1-deficient astrocytes to prolonged, supraphysiological VLCFA exposure and mitochondrial depolarization. Isolated mitochondria from mutant and control mice respond similarly. This supports a contextual protective/regulatory consequence of cellular lipid handling, not direct mitochondrial membrane transport by ABCD1. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. The mouse P48410 source PMID:25583114 shows increased vulnerability of Abcd1-deficient astrocytes to prolonged, supraphysiological VLCFA exposure and mitochondrial depolarization. Isolated mitochondria from mutant and control mice respond similarly. This supports a contextual protective/regulatory consequence of cellular lipid handling, not direct mitochondrial membrane transport by ABCD1. |
| GO:0051900 regulation of mitochondrial depolarization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial depolarization is an indirect lipid-stress consequence. Reason: The mouse P48410 source PMID:25583114 shows increased vulnerability of Abcd1-deficient astrocytes to prolonged, supraphysiological VLCFA exposure and mitochondrial depolarization. Isolated mitochondria from mutant and control mice respond similarly. This supports a contextual protective/regulatory consequence of cellular lipid handling, not direct mitochondrial membrane transport by ABCD1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The mouse P48410 source PMID:25583114 shows increased vulnerability of Abcd1-deficient astrocytes to prolonged, supraphysiological VLCFA exposure and mitochondrial depolarization. Isolated mitochondria from mutant and control mice respond similarly. This supports a contextual protective/regulatory consequence of cellular lipid handling, not direct mitochondrial membrane transport by ABCD1. |
| GO:0052816 long-chain fatty acyl-CoA hydrolase activity | IEA GO_REF:0000116 | ACCEPT | Summary: ABCD1 preparations exhibit fatty-acyl-CoA thioesterase activity. Reason: PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:40783 SUPPORTS TRANSFER The fetched UniProt catalytic-activity record explicitly identifies RHEA:40783 as docosanoyl-CoA hydrolysis, linked to PMID:33500543. This verifies the reaction identity rather than an independent enzyme experiment. The underlying study uses analogue hydrolysis and native-acyl-CoA competition; the existing substrate-class assertion is retained with unresolved native kinetics and obligatory coupling to transport. |
| GO:0052817 very long-chain fatty acyl-CoA hydrolase activity | EXP PMID:29397936 Characterization of human ATP-binding cassette protein subfa... | ACCEPT | Summary: ABCD1 preparations exhibit fatty-acyl-CoA thioesterase activity. Reason: PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. |
| GO:0052817 very long-chain fatty acyl-CoA hydrolase activity | EXP PMID:33500543 Acyl-CoA thioesterase activity of peroxisomal ABC protein AB... | ACCEPT | Summary: ABCD1 preparations exhibit fatty-acyl-CoA thioesterase activity. Reason: PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. Supporting Evidence: PMID:33500543 The expressed ABCD1 possessed both ATPase and ACOT activities. |
| GO:0052817 very long-chain fatty acyl-CoA hydrolase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ABCD1 preparations exhibit fatty-acyl-CoA thioesterase activity. Reason: PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00098229 UNRESOLVED The rule identifier is recorded in GOA, but its learned predicates and training support were not independently inspected. The annotation-level judgment rests on the cited primary ABCD1 biology, not validation of the internal ARBA rule. PMID:29397936 reports ACOT activity in reconstituted ABCD proteins, and PMID:33500543 directly measures NBD-acyl-CoA hydrolysis by human ABCD1 preparations with matched control protein, substrate-competition, chemical-inhibition and covalent-labeling experiments. Retain the reported hydrolase activity and substrate-class mappings. The assay relies heavily on fluorescent substrate analogues and competition, so it does not fully establish native substrate kinetics, the catalytic residue or an obligatory cleavage/re-esterification mechanism in every transport cycle. Structural work PMID:35013584 explicitly leaves the chemistry unsettled. RHEA:40787 SUPPORTS TRANSFER The fetched UniProt catalytic-activity record explicitly identifies RHEA:40787 as tetracosanoyl-CoA hydrolysis, linked to PMID:33500543. This verifies the reaction identity rather than an independent enzyme experiment. The underlying study uses analogue hydrolysis and native-acyl-CoA competition; the existing substrate-class assertion is retained with unresolved native kinetics and obligatory coupling to transport. RHEA:40791 SUPPORTS TRANSFER The fetched UniProt catalytic-activity record explicitly identifies RHEA:40791 as hexacosanoyl-CoA hydrolysis, linked to PMID:33500543. This verifies the reaction identity rather than an independent enzyme experiment. The underlying study uses analogue hydrolysis and native-acyl-CoA competition; the existing substrate-class assertion is retained with unresolved native kinetics and obligatory coupling to transport. RHEA:67072 SUPPORTS TRANSFER The fetched UniProt catalytic-activity record explicitly identifies RHEA:67072 as generic very-long-chain fatty-acyl-CoA hydrolysis, linked to PMID:33500543 and PMID:29397936. This verifies the reaction identity rather than an independent enzyme experiment. The underlying study uses analogue hydrolysis and native-acyl-CoA competition; the existing substrate-class assertion is retained with unresolved native kinetics and obligatory coupling to transport. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: The broad membrane-transport process can be refined to peroxisomal fatty-acid import. Reason: InterPro:IPR011527 identifies the ABC membrane domain, while human complementation and localization identify the transported substrate class and organelle direction. Refine to long-chain fatty acid import into peroxisome, retaining the acknowledged very-long-chain preference and unresolved CoA-cleavage chemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. InterPro:IPR011527 identifies the ABC membrane domain, while human complementation and localization identify the transported substrate class and organelle direction. Refine to long-chain fatty acid import into peroxisome, retaining the acknowledged very-long-chain preference and unresolved CoA-cleavage chemistry. Proposed replacements: long-chain fatty acid import into peroxisome |
| GO:0055089 fatty acid homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: ABCD1 maintains fatty-acid homeostasis through peroxisomal substrate delivery. Reason: Mouse knockout and rescue studies show VLCFA accumulation and correction by a compensating transporter (PMID:15489218), while human fibroblast experiments establish the import-dependent oxidation defect. This is a direct homeostatic consequence of the core transport function rather than an unrelated downstream injury phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse knockout and rescue studies show VLCFA accumulation and correction by a compensating transporter (PMID:15489218), while human fibroblast experiments establish the import-dependent oxidation defect. This is a direct homeostatic consequence of the core transport function rather than an unrelated downstream injury phenotype. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. Mouse knockout and rescue studies show VLCFA accumulation and correction by a compensating transporter (PMID:15489218), while human fibroblast experiments establish the import-dependent oxidation defect. This is a direct homeostatic consequence of the core transport function rather than an unrelated downstream injury phenotype. |
| GO:0055089 fatty acid homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: ABCD1 maintains fatty-acid homeostasis through peroxisomal substrate delivery. Reason: Mouse knockout and rescue studies show VLCFA accumulation and correction by a compensating transporter (PMID:15489218), while human fibroblast experiments establish the import-dependent oxidation defect. This is a direct homeostatic consequence of the core transport function rather than an unrelated downstream injury phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse knockout and rescue studies show VLCFA accumulation and correction by a compensating transporter (PMID:15489218), while human fibroblast experiments establish the import-dependent oxidation defect. This is a direct homeostatic consequence of the core transport function rather than an unrelated downstream injury phenotype. |
| GO:0055092 sterol homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sterol-homeostasis changes are secondary to altered lipid handling. Reason: The P48410 source PMID:16213491 reports altered plasma cholesterol, hepatic cholesterol-regulatory responses and species-dependent effects in X-ALD models. These findings support a contextual sterol-homeostasis association; they do not establish cholesterol as an ABCD1 transported substrate or a core sterol-export activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The P48410 source PMID:16213491 reports altered plasma cholesterol, hepatic cholesterol-regulatory responses and species-dependent effects in X-ALD models. These findings support a contextual sterol-homeostasis association; they do not establish cholesterol as an ABCD1 transported substrate or a core sterol-export activity. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. The P48410 source PMID:16213491 reports altered plasma cholesterol, hepatic cholesterol-regulatory responses and species-dependent effects in X-ALD models. These findings support a contextual sterol-homeostasis association; they do not establish cholesterol as an ABCD1 transported substrate or a core sterol-export activity. |
| GO:0055092 sterol homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sterol-homeostasis changes are secondary to altered lipid handling. Reason: The P48410 source PMID:16213491 reports altered plasma cholesterol, hepatic cholesterol-regulatory responses and species-dependent effects in X-ALD models. These findings support a contextual sterol-homeostasis association; they do not establish cholesterol as an ABCD1 transported substrate or a core sterol-export activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER The P48410 source PMID:16213491 reports altered plasma cholesterol, hepatic cholesterol-regulatory responses and species-dependent effects in X-ALD models. These findings support a contextual sterol-homeostasis association; they do not establish cholesterol as an ABCD1 transported substrate or a core sterol-export activity. |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: The generic ATP-driven transporter activity can be made substrate-specific. Reason: ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping is compatible with ABCD1 architecture. ABCD1 is a genuine ATP-coupled peroxisomal transporter, unlike regulatory ABC-family proteins. The established substrate-recognition and genetic-complementation evidence supports ABC-type fatty-acyl-CoA transporter activity. Its exact thioester-cleavage sequence remains unresolved; the refinement identifies substrate and energy coupling, not a fully proven chemical intermediate. Proposed replacements: ABC-type fatty-acyl-CoA transporter activity |
| GO:1900016 negative regulation of cytokine production involved in inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ABCD1-dependent lipid handling indirectly restrains inflammatory cytokine induction. Reason: PMID:18723473 silences Abcd1/Abcd2 in mouse astrocytes and links VLCFA accumulation to inflammatory transcription factors and cytokine expression; metabolic correction reduces the response. Retain the regulatory consequence as non-core and qualify the dual-gene/model context rather than treating ABCD1 as a cytokine-signaling enzyme. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER PMID:18723473 silences Abcd1/Abcd2 in mouse astrocytes and links VLCFA accumulation to inflammatory transcription factors and cytokine expression; metabolic correction reduces the response. Retain the regulatory consequence as non-core and qualify the dual-gene/model context rather than treating ABCD1 as a cytokine-signaling enzyme. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. PMID:18723473 silences Abcd1/Abcd2 in mouse astrocytes and links VLCFA accumulation to inflammatory transcription factors and cytokine expression; metabolic correction reduces the response. Retain the regulatory consequence as non-core and qualify the dual-gene/model context rather than treating ABCD1 as a cytokine-signaling enzyme. |
| GO:1900016 negative regulation of cytokine production involved in inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ABCD1-dependent lipid handling indirectly restrains inflammatory cytokine induction. Reason: PMID:18723473 silences Abcd1/Abcd2 in mouse astrocytes and links VLCFA accumulation to inflammatory transcription factors and cytokine expression; metabolic correction reduces the response. Retain the regulatory consequence as non-core and qualify the dual-gene/model context rather than treating ABCD1 as a cytokine-signaling enzyme. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER PMID:18723473 silences Abcd1/Abcd2 in mouse astrocytes and links VLCFA accumulation to inflammatory transcription factors and cytokine expression; metabolic correction reduces the response. Retain the regulatory consequence as non-core and qualify the dual-gene/model context rather than treating ABCD1 as a cytokine-signaling enzyme. |
| GO:1900407 regulation of cellular response to oxidative stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Oxidative-stress response is a downstream consequence of VLCFA homeostasis. Reason: PMID:18344354 describes early oxidative lesions and altered antioxidant responses in Abcd1-deficient models and human cells; PMID:25583114 probes VLCFA-exposed astrocytes. The conserved lipid-transport defect can influence redox homeostasis, but these effects are secondary to the peroxisomal import function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER PMID:18344354 describes early oxidative lesions and altered antioxidant responses in Abcd1-deficient models and human cells; PMID:25583114 probes VLCFA-exposed astrocytes. The conserved lipid-transport defect can influence redox homeostasis, but these effects are secondary to the peroxisomal import function. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. PMID:18344354 describes early oxidative lesions and altered antioxidant responses in Abcd1-deficient models and human cells; PMID:25583114 probes VLCFA-exposed astrocytes. The conserved lipid-transport defect can influence redox homeostasis, but these effects are secondary to the peroxisomal import function. |
| GO:1900407 regulation of cellular response to oxidative stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Oxidative-stress response is a downstream consequence of VLCFA homeostasis. Reason: PMID:18344354 describes early oxidative lesions and altered antioxidant responses in Abcd1-deficient models and human cells; PMID:25583114 probes VLCFA-exposed astrocytes. The conserved lipid-transport defect can influence redox homeostasis, but these effects are secondary to the peroxisomal import function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER PMID:18344354 describes early oxidative lesions and altered antioxidant responses in Abcd1-deficient models and human cells; PMID:25583114 probes VLCFA-exposed astrocytes. The conserved lipid-transport defect can influence redox homeostasis, but these effects are secondary to the peroxisomal import function. |
| GO:1903427 negative regulation of reactive oxygen species biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ABCD1 deficiency increases ROS indirectly through lipid and cellular stress. Reason: Mouse-source studies PMID:18723473, PMID:22521832 and PMID:25583114 measure increased oxidative stress/ROS following transporter silencing or VLCFA exposure. Retain a protective regulatory association in those contexts; ABCD1 is not assigned ROS-scavenging enzyme activity or direct control of a mitochondrial electron-transfer reaction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse-source studies PMID:18723473, PMID:22521832 and PMID:25583114 measure increased oxidative stress/ROS following transporter silencing or VLCFA exposure. Retain a protective regulatory association in those contexts; ABCD1 is not assigned ROS-scavenging enzyme activity or direct control of a mitochondrial electron-transfer reaction. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. Mouse-source studies PMID:18723473, PMID:22521832 and PMID:25583114 measure increased oxidative stress/ROS following transporter silencing or VLCFA exposure. Retain a protective regulatory association in those contexts; ABCD1 is not assigned ROS-scavenging enzyme activity or direct control of a mitochondrial electron-transfer reaction. |
| GO:1903427 negative regulation of reactive oxygen species biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ABCD1 deficiency increases ROS indirectly through lipid and cellular stress. Reason: Mouse-source studies PMID:18723473, PMID:22521832 and PMID:25583114 measure increased oxidative stress/ROS following transporter silencing or VLCFA exposure. Retain a protective regulatory association in those contexts; ABCD1 is not assigned ROS-scavenging enzyme activity or direct control of a mitochondrial electron-transfer reaction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse-source studies PMID:18723473, PMID:22521832 and PMID:25583114 measure increased oxidative stress/ROS following transporter silencing or VLCFA exposure. Retain a protective regulatory association in those contexts; ABCD1 is not assigned ROS-scavenging enzyme activity or direct control of a mitochondrial electron-transfer reaction. |
| GO:1990535 neuron projection maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Axonal maintenance depends downstream on intact peroxisomal lipid metabolism. Reason: Mouse Abcd1 knockout causes late-onset axonal pathology and ABCD2 expression modifies or prevents it (PMID:11875044; PMID:15489218). This supports the maintenance association, distinct from direct construction or elongation of neuronal projections. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse Abcd1 knockout causes late-onset axonal pathology and ABCD2 expression modifies or prevents it (PMID:11875044; PMID:15489218). This supports the maintenance association, distinct from direct construction or elongation of neuronal projections. ensembl:ENSMUSP00000002084 SUPPORTS TRANSFER ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. Mouse Abcd1 knockout causes late-onset axonal pathology and ABCD2 expression modifies or prevents it (PMID:11875044; PMID:15489218). This supports the maintenance association, distinct from direct construction or elongation of neuronal projections. |
| GO:1990535 neuron projection maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axonal maintenance depends downstream on intact peroxisomal lipid metabolism. Reason: Mouse Abcd1 knockout causes late-onset axonal pathology and ABCD2 expression modifies or prevents it (PMID:11875044; PMID:15489218). This supports the maintenance association, distinct from direct construction or elongation of neuronal projections. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P48410 SUPPORTS TRANSFER Mouse Abcd1 knockout causes late-onset axonal pathology and ABCD2 expression modifies or prevents it (PMID:11875044; PMID:15489218). This supports the maintenance association, distinct from direct construction or elongation of neuronal projections. |
| GO:2001280 positive regulation of unsaturated fatty acid biosynthetic process | IEA GO_REF:0000107 | UNDECIDED | Summary: The ABCD1-specific positive unsaturated-fatty-acid synthesis assertion needs the complete donor study. Reason: PMID:18854420 primarily evaluates ABCD2-related DHA synthesis but also explicitly assays Abcd1 knockout brain slices. The accessible abstract does not resolve the exact Abcd1-specific positive biosynthesis result. Do not claim a paralog misattribution from the title; retain uncertainty pending full text, particularly given normal DHA synthesis in the human X-ALD fibroblast comparison PMID:11500517. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P48410 UNRESOLVED PMID:18854420 primarily evaluates ABCD2-related DHA synthesis but also explicitly assays Abcd1 knockout brain slices. The accessible abstract does not resolve the exact Abcd1-specific positive biosynthesis result. Do not claim a paralog misattribution from the title; retain uncertainty pending full text, particularly given normal DHA synthesis in the human X-ALD fibroblast comparison PMID:11500517. ensembl:ENSMUSP00000002084 UNRESOLVED ENSMUSP00000002084 is the mouse Abcd1 donor chain corresponding to P48410, not an independent experiment. PMID:18854420 primarily evaluates ABCD2-related DHA synthesis but also explicitly assays Abcd1 knockout brain slices. The accessible abstract does not resolve the exact Abcd1-specific positive biosynthesis result. Do not claim a paralog misattribution from the title; retain uncertainty pending full text, particularly given normal DHA synthesis in the human X-ALD fibroblast comparison PMID:11500517. |
| GO:2001280 positive regulation of unsaturated fatty acid biosynthetic process | ISS GO_REF:0000024 | UNDECIDED | Summary: The ABCD1-specific positive unsaturated-fatty-acid synthesis assertion needs the complete donor study. Reason: PMID:18854420 primarily evaluates ABCD2-related DHA synthesis but also explicitly assays Abcd1 knockout brain slices. The accessible abstract does not resolve the exact Abcd1-specific positive biosynthesis result. Do not claim a paralog misattribution from the title; retain uncertainty pending full text, particularly given normal DHA synthesis in the human X-ALD fibroblast comparison PMID:11500517. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P48410 UNRESOLVED PMID:18854420 primarily evaluates ABCD2-related DHA synthesis but also explicitly assays Abcd1 knockout brain slices. The accessible abstract does not resolve the exact Abcd1-specific positive biosynthesis result. Do not claim a paralog misattribution from the title; retain uncertainty pending full text, particularly given normal DHA synthesis in the human X-ALD fibroblast comparison PMID:11500517. |
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Download this section (compressed HTML)Q: Does native human ABCD1 move intact acyl-CoA, or does its measured thioesterase subactivity cleave substrates during transport and require intraperoxisomal reactivation?
Q: Which residues catalyze ABCD1 ACOT activity, and can hydrolysis be separated genetically from ATPase, folding and substrate binding?
Q: What source experiments resolve the cross-species interaction in PMID:10551832, ABCD2-associated binding row in PMID:17609205, ABCD1 client assay in PMID:20531392, and biosynthetic mouse transfers in PMID:16223892 and PMID:18854420?
Q: How do ABCD1/ABCD2/ABCD3 combinations and tissue-specific expression alter native substrate spectra without conflating rescue capacity with the dominant physiological transporter?
Experiment: Reconstitute purified, orientation-defined human ABCD1 with isotopically distinguishable acyl and CoA labels, monitor both molecules and thioester integrity on each side of the membrane, and compare matched ATPase/ACOT perturbations while controlling passive lipid partitioning.
Experiment: Quantify native acyl-CoA chain-length-specific hydrolysis and flux in gene-corrected human cells and purified complexes, separating direct catalytic products from competitive binding or ATPase-stimulation readouts.
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