CYP27A1 is a mitochondrial heme-thiolate cytochrome P450 that oxidizes the terminal side chain of cholesterol and several oxygenated sterols. Using electrons supplied through adrenodoxin and adrenodoxin reductase, it forms a side-chain alcohol and can carry out further oxidation to an aldehyde and carboxylic acid. These reactions supply bile-acid intermediates and contribute to cholesterol disposal. The precursor is imported into mitochondria and processed to a mature enzyme associated peripherally with the matrix face of the inner membrane. CYP27A1 also hydroxylates vitamin D3 at C25 and generates oxysterols with context-dependent signaling activities. Loss of CYP27A1 activity causes cerebrotendinous xanthomatosis.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
CYP27A1_MATUREPRO_0000003618 (residues 34-531) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | TOO GENERAL | Summary: The valid PAINT inference places CYP27A1 in mitochondria. The broad organelle annotation is TOO_GENERAL relative to the retained matrix and inner-membrane locations; its inherited biological support is preserved. Reason: The current PTHR24291 tree places the exact 531-residue human target below the mitochondrial IBD at PTN001209853. The literal rat donor RGD:727915 is retained, and no target-path loss record was found. This agrees with the mitochondrial import and matrix-side membrane association of CYP27A1; the older PTHR24279 snapshot omitting the target is a family-version issue, not evidence of biological loss. The annotation remains biologically supported, but the broad organelle term adds no spatial coverage beyond the accepted matrix and inner-membrane placements and the catalytic-core locations. TOO_GENERAL concerns informativeness, not a failed localization inference. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001209853 SUPPORTS TRANSFER Actual on-path IBD in current PTHR24291; historical family snapshot missing the target is not a loss event. The inherited node assertion is sound; the target review already resolves the catalytic compartment more specifically. |
| GO:0008203 cholesterol metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that CYP27A1 is involved in cholesterol metabolism. Correct and core: CYP27A1 27-hydroxylates cholesterol and channels excess cholesterol into bile-acid pathways. Reason: The cholesterol-metabolism IBD at PTN002801037 lies on the actual human target path. Its human self-source and rat experimental descendant are legitimate evidence for that ancestral assertion. Recombinant human enzyme converts cholesterol to side-chain oxygenated products, providing direct performed chemistry rather than merely disease or expression evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002801037 SUPPORTS TRANSFER Actual on-path IBD in current PTHR24291; historical family snapshot missing the target is not a loss event. Supporting Evidence: |
| GO:0030343 vitamin D 25-hydroxylase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The on-lineage PAINT assertion supports secondary vitamin D3 25-hydroxylation. Lower catalytic efficiency than CYP2R1 does not establish absent or nonphysiological activity, and vitamin D2 product positions do not refute the D3 activity. Reason: The vitamin-D hydroxylase IBD is on the actual target lineage and has direct human and rat experimental grounding. CYP27A1 hydroxylates vitamin D3 at C25. The CYP2R1 comparison measures lower CYP27A1 catalytic efficiency but does not establish absent or nonphysiological activity. D2 C24/C27 products must not be used to reject the D3-specific definition. Retain this secondary activity outside the dominant sterol/bile-acid synthesis cores; the exact CYP27A1 comparator preparation in the 2004 paper remains unverified from its inaccessible full Methods. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002801037 SUPPORTS TRANSFER Actual on-path IBD in current PTHR24291; historical family snapshot missing the target is not a loss event. |
| GO:0031073 cholesterol 26-hydroxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of cholesterol 26(27)-hydroxylase activity. This is a core molecular function of CYP27A1, directly supported by experimental IDA annotations. Reason: The cholesterol 26-hydroxylase IBD at PTN002801037 is on the human path, with the literal human and rat descendant evidence. Direct recombinant human cholesterol hydroxylation independently supports the conserved reaction. Historical 27-hydroxylation and current stereospecific 26-hydroxylation nomenclature refer to the terminal side-chain oxidation here. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002801037 SUPPORTS TRANSFER Actual on-path IBD in current PTHR24291; historical family snapshot missing the target is not a loss event. Supporting Evidence: |
| GO:0004497 monooxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic InterPro/ARBA annotation to the general monooxygenase parent. Correct but less specific than the sterol 26/27-hydroxylase activity; accept as a valid general classification of this cytochrome P450 monooxygenase. Reason: The combined InterPro/ARBA source identifies a monooxygenase class. Independently, reconstituted human CYP27A1 incorporates oxygen into sterol substrates using the adrenodoxin electron-transfer system. Thus the broad molecular-function annotation is correct; it is not accepted solely because an automatic rule repeats the label. |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic InterPro annotation for iron binding. Correct: CYP27A1 is a heme-thiolate P450 whose heme iron is ligated by an axial cysteine (residue 476). Core cofactor function. Reason: The InterPro mapping is consistent with the heme-thiolate P450 fold and the current Cys476 axial iron ligand. Heme content and catalytic reconstitution of human CYP27A1 provide biochemical support for the cofactor association. Iron binding is part of the catalytic apparatus, not a separate iron-storage role. |
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | TOO GENERAL | Summary: The matching ARBA inference correctly places CYP27A1 in mitochondria. Retain its positive source assessment but mark the broad compartment TOO_GENERAL relative to matrix and inner-membrane annotations. Reason: The actual ARBA branch matches the recorded family/taxon profile, but mitochondrial localization is supported independently by targeting and import evidence. Rat CYP27A1 import experiments resolve entry into the matrix and peripheral inner-membrane association; the human precursor has the corresponding targeting segment. No claim of a new human localization experiment is made from the rat study. The annotation remains biologically supported, but the broad organelle term adds no spatial coverage beyond the accepted matrix and inner-membrane placements and the catalytic-core locations. TOO_GENERAL concerns informativeness, not a failed localization inference. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic UniProt subcellular-location mapping to mitochondrial inner membrane. Correct and represents the specific location: CYP27A1 associates with the inner membrane as a membrane-extrinsic protein after import into the matrix. Core. Reason: The UniProt subcellular-location mapping describes peripheral association with the mitochondrial inner membrane after matrix import. Rat import/protease-protection and carbonate-extraction experiments support this topology. Retain inner-membrane localization without converting the enzyme into an integral transmembrane protein or excluding matrix placement. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0008202 steroid metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic ARBA annotation to the broad steroid metabolic process. Correct but general; the specific processes (bile acid biosynthesis, cholesterol catabolism) are captured elsewhere. Accept as a valid parent term. Reason: CYP27A1 directly catalyzes reactions involving steroid substrates. The saved ARBA condition set matches the human family/taxon profile, and human biochemical experiments independently substantiate the broad metabolic process. Its absence from the newer 67-record metadata snapshot does not contradict the preserved historical assertion. |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: Lipid biosynthesis is a true but redundant parent of the retained vitamin D3 biosynthetic process. Mark the broad source assertion TOO_GENERAL without proposing another already represented process. Reason: The source assertion is biologically true, but GO:0008610 is an ancestor of the retained GO:1901755 vitamin D3 biosynthetic process in the current ontology. It adds no process coverage beyond that more specific secondary annotation and is therefore TOO_GENERAL. Bile acid biosynthesis is independently represented by six retained GO:0006699 annotations, but the current GO graph does not make GO:0006699 a descendant of GO:0008610; it is not used as an entailment argument or proposed as a redundant replacement. The matching ARBA source and original supporting excerpt remain preserved. Supporting Evidence: PMID:1708392 bile acid synthesis pathway |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to the broad oxidoreductase/monooxygenase MF parent. Correct but general; accept as a valid higher-level classification of the P450 activity. Reason: The paired-donor oxygenation definition fits sterol oxidation coupled to the adrenodoxin/reductase system. Direct reconstitution establishes this general redox class. It does not mean that CYP27A1 itself is the NADPH reductase or that the reaction runs by reducing NADP+. |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic InterPro annotation for heme binding. Correct: CYP27A1 is a heme-thiolate cytochrome P450 with an axial-cysteine-ligated heme. Core cofactor function; duplicates the IDA heme binding annotation. Reason: InterPro identifies the P450 cofactor-binding architecture, and recombinant human enzyme contains heme. The current precursor Cys476 is the axial ligand (mature-chain Cys443 in the 1991 numbering). This binding supports catalysis and is integrated into the two chemistry cores. |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The defined GO:0047748 reaction is sequential terminal-side-chain oxidation of a bile-acid sterol intermediate to its carboxylate. Human CYP27A1 biochemistry supports this catalytic assignment despite the historical dehydrogenase label. Reason: Despite its historical dehydrogenase label, the current GO definition is the oxygen/adrenodoxin-dependent three-step oxidation of cholestane triol to the corresponding carboxylate. Human CYP27A1 performs that side-chain chemistry. The EC/RHEA mapping is assessed against the actual reaction and original biochemical evidence, not used as an independent proof merely by repeating an EC number. |
| GO:0016716 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-projected orthology annotation (from mouse Cyp27a1, Q9DBG1) to the specific monooxygenase MF parent. Correct as a general classification; also directly supported by an IDA (PMID:21411718). Accept. Reason: The literal Ensembl source is mouse Cyp27a1 Q9DBG1, whose experimental record was checked. Human recombinant CYP27A1 independently performs oxygen-incorporating sterol oxidation, including 7-ketocholesterol conversion, so the transferred broad monooxygenase class is well supported. |
| GO:0045880 positive regulation of smoothened signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse perturbation and oxysterol rescue support CYP27A1-dependent production of Smoothened-activating metabolites. Retain the human ortholog inference as a non-core process, without assigning direct receptor binding or a human pathway assay. Reason: The Ensembl mouse-to-human source is verified. Mouse Cyp27a1 depletion in Ptch1-null fibroblasts reduced Hedgehog signaling, and downstream 7-keto-27-hydroxycholesterol or 7beta,27-dihydroxycholesterol rescued the response whereas the precursor 7-ketocholesterol did not. Together with CYP27A1-dependent oxysterol production, this supports a performed enzymatic contribution to positive Smoothened regulation. It is a context-dependent process rather than direct CYP27A1 receptor binding or ciliary localization; transfer to human remains an ortholog inference, not a human pathway assay. |
| GO:1901755 vitamin D3 biosynthetic process | IDA PMID:15465040 Metabolism of vitamin D by human microsomal CYP2R1. | KEEP AS NON CORE | Summary: CYP27A1 D3 25-hydroxylation supports the secondary vitamin D3 process under the current GO part_of convention. Neither the CYP2R1 efficiency comparison nor D2 C24/C27 chemistry negates that activity. Reason: The source supports CYP27A1 D3 25-hydroxylation, not D2 C25 activity. The current ontology places D3 25-hydroxylase activity part_of vitamin D3 biosynthesis, despite the process label suggesting only formation of unmodified D3. Retain the existing process as secondary under that convention. GO:0036378 is obsolete and must not be proposed as a replacement. Full CYP27A1 comparator Methods were not recovered, and the greater CYP2R1 efficiency does not prove zero physiological contribution. Supporting Evidence: |
| GO:0006699 bile acid biosynthetic process | TAS Reactome:R-HSA-193368 | ACCEPT | Summary: Reactome TAS (bile acid/bile salt synthesis via 7alpha-hydroxycholesterol, the neutral pathway). Core biological process: CYP27A1 performs the side-chain oxidation steps of bile-acid biosynthesis. Accept. Reason: The actual Reactome pathway for the 7alpha-hydroxycholesterol route contains a target-linked CYP27A1 catalyst, rather than only an upstream substrate association. CYP27A1 performs terminal side-chain oxidation that supplies bile-acid intermediates. The pathway context is consistent with direct human enzyme chemistry; it does not imply that CYP27A1 catalyzes every reaction in the pathway. |
| GO:0006699 bile acid biosynthetic process | TAS Reactome:R-HSA-193775 | ACCEPT | Summary: Reactome TAS (bile acid synthesis via 24-hydroxycholesterol pathway). Core biological process for CYP27A1; accept (duplicate of the bile-acid biosynthesis annotation). Reason: The actual Reactome pathway for the 24-hydroxycholesterol route contains a target-linked CYP27A1 catalyst, rather than only an upstream substrate association. CYP27A1 performs terminal side-chain oxidation that supplies bile-acid intermediates. The pathway context is consistent with direct human enzyme chemistry; it does not imply that CYP27A1 catalyzes every reaction in the pathway. |
| GO:0006699 bile acid biosynthetic process | TAS Reactome:R-HSA-193807 | ACCEPT | Summary: Reactome TAS (bile acid synthesis via 27-hydroxycholesterol, the acidic/alternative pathway that CYP27A1 initiates). Core biological process; accept. Reason: The actual Reactome pathway for the 27-hydroxycholesterol route contains a target-linked CYP27A1 catalyst, rather than only an upstream substrate association. CYP27A1 performs terminal side-chain oxidation that supplies bile-acid intermediates. The pathway context is consistent with direct human enzyme chemistry; it does not imply that CYP27A1 catalyzes every reaction in the pathway. |
| GO:0016125 sterol metabolic process | TAS Reactome:R-HSA-211976 | ACCEPT | Summary: Reactome TAS (endogenous sterols) to the broad sterol metabolic process. Correct but general; the specific cholesterol/bile-acid processes are captured by more precise terms. Accept as a valid parent. Reason: The actual endogenous-sterol pathway contains CYP27A1-linked reaction entities. Direct hydroxylation and further oxidation of cholesterol and related sterols support this broad metabolic classification. Pathway membership is resolved to the target catalyst, not inferred from the pathway title alone. |
| GO:0006699 bile acid biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: Electronic UniPathway (UPA00221, bile acid biosynthesis) mapping. Correct and core; duplicates the experimental/TAS bile-acid biosynthesis annotations. Accept. Reason: The UniPathway mapping to bile-acid biosynthesis is consistent with CYP27A1 directly performing the side-chain oxidation steps of steroid intermediates. The evidence concerns catalysis of pathway reactions, not only the CTX phenotype. |
| GO:0006707 cholesterol catabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: Electronic UniPathway (UPA01058, cholesterol degradation) mapping. Correct and core: 27-hydroxylation directs cholesterol into catabolic bile-acid pathways. Duplicates the IDA cholesterol catabolic process annotation. Accept. Reason: The cholesterol-degradation vocabulary mapping describes the entry of cholesterol into side-chain oxidation and bile-acid catabolism. Direct recombinant human cholesterol-to-alcohol/aldehyde/acid conversion substantiates the performed contribution; no exclusive fate is asserted for every oxysterol product. Supporting Evidence: |
| GO:0016716 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen | IDA PMID:21411718 Conversion of 7-ketocholesterol to oxysterol metabolites by ... | ACCEPT | Summary: IDA from the study of 7-ketocholesterol conversion by recombinant CYP27A1, which demonstrated CYP27A1 monooxygenase (hydroxylase) activity producing 7KCh-27OH and 7KCh-27COOH. This is a valid specific-monooxygenase MF classification; the underlying activity is core 26/27-hydroxylase chemistry acting on an oxysterol. Accept. Reason: The original Methods use recombinant human CYP27A1 with adrenodoxin, adrenodoxin reductase and an NADPH-regenerating system. Product analysis demonstrates oxygenation of 7-ketocholesterol and further side-chain oxidation. Bovine retinal tissue metabolism and separate human RPE protein measurements are distinguished from this direct human recombinant activity assay. Supporting Evidence: PMID:21411718 7KCh is metabolized at a 4-fold higher rate than cholesterol in the reconstituted system in vitro |
| GO:0045880 positive regulation of smoothened signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The curated mouse-to-human transfer supports a contextual enzymatic contribution to Smoothened activation through oxysterol production. Retain it as non-core, with the performed chemistry distinguished from direct receptor binding. Reason: The literal ISS donor MGI:88594 is mouse Cyp27a1, with direct source annotations from PMID:30340023. Mouse Cyp27a1 depletion in Ptch1-null fibroblasts reduced Hedgehog signaling, and downstream 7-keto-27-hydroxycholesterol or 7beta,27-dihydroxycholesterol rescued the response whereas the precursor 7-ketocholesterol did not. Together with CYP27A1-dependent oxysterol production, this supports a performed enzymatic contribution to positive Smoothened regulation. It is a context-dependent process rather than direct CYP27A1 receptor binding or ciliary localization; transfer to human remains an ortholog inference, not a human pathway assay. |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation (from ortholog UniProtKB:P17178, rat CYP27A1) for mitochondrial inner membrane localization. Correct and core; duplicates the IEA subcellular-location annotation. Accept. Reason: The literal donor P17178 is rat CYP27A1. The original rat-cDNA experiments show mitochondrial import, digitonin/trypsin protection and mostly carbonate-extractable membrane association, supporting a matrix-side peripheral inner-membrane protein. This is a justified ortholog localization inference, not a direct human assay or evidence for an integral membrane segment. |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | EXP PMID:1708392 Characterization of human sterol 27-hydroxylase. A mitochond... | ACCEPT | Summary: Experimental characterization of human sterol 27-hydroxylase showing multi-step oxidation (R-CH3 -> R-CH2OH -> R-COOH) at carbon 27 of bile-acid sterol intermediates. The GO:0047748 definition is the EC 1.14.15.15 sterol 26-hydroxylase reaction, so this is the core molecular function. Accept. Reason: The original human liver cDNA was expressed in COS-M6 cells with bovine adrenodoxin. Triol and tetrol substrates were converted to a carboxylic-acid product, with radiolabel/TLC and mock-transfection controls. This supports the multistep reaction in the actual GO definition. The 33-residue targeting sequence and 498-residue mature-chain boundary were predicted from sequence, not established by direct human N-terminal sequencing. Supporting Evidence: |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | EXP PMID:2019602 Mutations in the bile acid biosynthetic enzyme sterol 27-hyd... | ACCEPT | Summary: Experimental annotation from the CTX study: CTX-causing CYP27 mutations produce immunoreactive sterol 27-hydroxylase protein with greatly diminished activity, confirming the sterol 26/27-hydroxylase (EC 1.14.15.15) core function. Accept. Reason: The complete abstract reports human CTX variants expressed in cultured cells and greatly reduced sterol 27-hydroxylase activity despite immunoreactive protein. The original full Methods were not recovered, so exact construct processing and substrate details are not claimed. Retain the curator-supported catalytic assertion with independent direct human chemistry corroboration; do not use variant loss of activity to assign absence of activity to normal CYP27A1. Supporting Evidence: PMID:2019602 the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished enzyme activity |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | EXP PMID:9186905 Novel homozygous and compound heterozygous mutations of ster... | ACCEPT | Summary: Experimental annotation from a CTX study: transfection of mutant CYP27 cDNAs into COS cells gave markedly reduced sterol 27-hydroxylase activity, confirming the core catalytic function. Accept. Reason: The complete abstract explicitly describes human CYP27 variants and reduced sterol 27-hydroxylase activity after transfection of mutant cDNAs into COS cells. The historical residue numbering is retained as reported rather than silently converted to the current precursor. Full Methods remain unavailable; the established target chemistry and curator evidence support retaining this annotation. Supporting Evidence: PMID:9186905 Transfection of the two mutant cDNAs into COS cells resulted in markedly reduced sterol 27-hydroxylase activity |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | EXP PMID:9790667 A novel Arg362Ser mutation in the sterol 27-hydroxylase gene... | ACCEPT | Summary: The historical human Arg362Ser variant loses sterol 27-hydroxylase activity in COS-1 cells. Retain the catalytic assignment with curator deference and independent human biochemistry; the accessible abstract does not establish a direct adrenodoxin-binding assay. Reason: The complete abstract reports the human historical Arg362Ser variant, activity loss in transfected COS-1 cells and a separate minigene-splicing experiment. These observations support the target enzyme assignment but do not establish every step of wild-type oxidation from the abstract alone. Retain the experimental assertion with curator deference and independent human biochemical evidence; do not interpret the pathogenic splice result as an official alternative protein product. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | TOO GENERAL | Summary: MitoCoP lists CYP27A1 as literature-pool 4 entry NotID_076, with experimental-identification and validation fields blank. The supported mitochondrial placement is TOO_GENERAL, and this catalogue entry is not a new CYP27A1 proteomic detection. Reason: The original MitoCoP workbook lists Q02318 as NotID_076 in the literature-derived pool 4. Its experimental-identification and validation fields are blank: this study did not measure a CYP27A1 proteomic signal in its own dataset. The mitochondrial placement remains well supported by independent targeting/import evidence and the catalogue inclusion, so retain the correct compartment while preserving the original HTP source fields and explicitly limiting what this source demonstrates. The annotation remains biologically supported, but the broad organelle term adds no spatial coverage beyond the accepted matrix and inner-membrane placements and the catalytic-core locations. TOO_GENERAL concerns informativeness, not a failed localization inference. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-191999 | ACCEPT | Summary: Reactome TAS (CYP27A1 27-hydroxylates 5b-cholestane-3a,7a,12a-triol). Correct; a general parent of the specific sterol 26/27-hydroxylase activity. Accept. Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-192042 | ACCEPT | Summary: Reactome TAS for a CYP27A1 side-chain oxidation step in bile-acid biosynthesis; steroid hydroxylase is a correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-192054 | ACCEPT | Summary: Reactome TAS for a CYP27A1 bile-acid side-chain oxidation step; steroid hydroxylase is a correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-192123 | ACCEPT | Summary: Reactome TAS (CYP27A1 27-hydroxylates cholesterol); steroid hydroxylase is a correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193393 | ACCEPT | Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193460 | ACCEPT | Summary: Reactome TAS for a CYP27A1 side-chain oxidation step; correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193497 | ACCEPT | Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193713 | ACCEPT | Summary: The historical Reactome reaction is currently unavailable. Retain the broad wild-type steroid hydroxylase function using independent human biochemistry, without inventing a source-specific substrate or recovered reaction title. Reason: The historical Reactome identifier now returns 404 in two saved requests, and its particular reaction record was not recovered. This is not evidence that the human enzyme lacks steroid hydroxylase activity. Retain the curator-supplied broad activity because direct human sterol oxygenation is independently established; no specific reaction name or substrate is invented for the unavailable record. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193719 | ACCEPT | Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193737 | ACCEPT | Summary: Reactome TAS for a CYP27A1 side-chain oxidation step; correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193780 | ACCEPT | Summary: The historical Reactome reaction is currently unavailable. Retain the broad wild-type steroid hydroxylase function using independent human biochemistry, without inventing a source-specific substrate or recovered reaction title. Reason: The historical Reactome identifier now returns 404 in two saved requests, and its particular reaction record was not recovered. This is not evidence that the human enzyme lacks steroid hydroxylase activity. Retain the curator-supplied broad activity because direct human sterol oxygenation is independently established; no specific reaction name or substrate is invented for the unavailable record. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193787 | ACCEPT | Summary: The historical Reactome reaction is currently unavailable. Retain the broad wild-type steroid hydroxylase function using independent human biochemistry, without inventing a source-specific substrate or recovered reaction title. Reason: The historical Reactome identifier now returns 404 in two saved requests, and its particular reaction record was not recovered. This is not evidence that the human enzyme lacks steroid hydroxylase activity. Retain the curator-supplied broad activity because direct human sterol oxygenation is independently established; no specific reaction name or substrate is invented for the unavailable record. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193792 | ACCEPT | Summary: Reactome TAS (CYP27A1 27-hydroxylates 5b-CHOL3a,7a,24(s)-triol); correct general parent MF. Accept (duplicate). Reason: The actual Reactome catalyst/entity path reaches mature human Q02318. The referenced side-chain oxidation is part of the CYP27A1 sterol-oxygenation sequence; direct human biochemical studies support the broad steroid hydroxylase class. Some current Reactome catalyst metadata use an NAD(P)H-acceptor term, which is not adopted as evidence for reverse redox chemistry. The annotation does not assert that every sequential alcohol-to-acid step is a single net hydroxyl-product reaction. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-5602170 | ACCEPT | Summary: The Reactome event describes defective variants linked to a normal reaction. Retain the established wild-type steroid hydroxylase function without treating the failed event as a NOT annotation or evidence of retained mutant activity. Reason: This Reactome record models defective CYP27A1 variants and explicitly links a normal hydroxylation reaction. Its negative event is not a NOT assertion about normal human CYP27A1. Retain the broad wild-type steroid hydroxylase function using the normal-reaction context and direct human biochemical corroboration; do not claim the disease variants retain normal activity. |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-9035960 | ACCEPT | Summary: The defective-variant Reactome event retains a normal-reaction context. The broad wild-type steroid hydroxylase assignment is supported independently; no activity is imputed to the defective products. Reason: This Reactome record models defective CYP27A1 variants and explicitly links a normal hydroxylation reaction. Its negative event is not a NOT assertion about normal human CYP27A1. Retain the broad wild-type steroid hydroxylase function using the normal-reaction context and direct human biochemical corroboration; do not claim the disease variants retain normal activity. |
| GO:0006699 bile acid biosynthetic process | IDA PMID:11412116 Putative helix F contributes to regioselectivity of hydroxyl... | ACCEPT | Summary: The human regioselectivity study and independent CYP27A1 biochemistry support bile-acid-intermediate oxidation. Full original Methods remain unavailable, so exact constructs and wild-type assay substrates are deferred to the curator. Reason: The complete abstract compares wild-type human CYP27A1 with F/G-helix mutants and supports its established role in sterol-intermediate oxidation. Full Methods were not recovered, so exact substrates and constructs are deferred to the original curator. Mutant-acquired carbon–carbon cleavage is not assigned to the wild-type enzyme. Independent human biochemical studies support its performed contribution to bile-acid synthesis. |
| GO:0006699 bile acid biosynthetic process | IDA PMID:9660774 Activities of recombinant human cytochrome P450c27 (CYP27) w... | ACCEPT | Summary: IDA from the study of recombinant P450c27 producing intermediates of the alternative bile-acid pathways. Core biological process. Accept. Reason: Purified recombinant human CYP27A1 expressed in E. coli, reconstituted with bovine adrenodoxin/reductase and NADPH, produces side-chain oxidized cholesterol products. HPLC and GC-MS separate alcohol, aldehyde and acid products. These are actual catalytic contributions to alternative bile-acid pathways; the exact N-terminal engineering was referred to an earlier preparation and is not assumed to match the full precursor. Supporting Evidence: |
| GO:0006707 cholesterol catabolic process | IDA PMID:9660774 Activities of recombinant human cytochrome P450c27 (CYP27) w... | ACCEPT | Summary: IDA: 27-hydroxylation of cholesterol by recombinant P450c27 directs cholesterol into catabolic bile-acid pathways. Core biological process. Accept. Reason: The original recombinant study demonstrates successive cholesterol side-chain oxidation, including a carboxylic-acid product, with adrenodoxin/NADPH dependence. This directly supplies intermediates for cholesterol disposal. Retain the process without asserting that every product is committed exclusively to bile acids. Supporting Evidence: |
| GO:0020037 heme binding | IDA PMID:9660774 Activities of recombinant human cytochrome P450c27 (CYP27) w... | ACCEPT | Summary: IDA for heme binding, consistent with CYP27A1 being a heme-thiolate cytochrome P450. Core cofactor function. Accept. Reason: The original recombinant human preparation reports heme content and uses the P450 enzyme in redox reconstitution. This supports actual cofactor binding, rather than a conclusion based only on an EC label or protein name. Heme coordination is integrated with sterol catalysis in the core synthesis. Supporting Evidence: |
| GO:0030343 vitamin D 25-hydroxylase activity | IDA PMID:15465040 Metabolism of vitamin D by human microsomal CYP2R1. | KEEP AS NON CORE | Summary: The human enzyme performs vitamin D3 25-hydroxylation as a secondary activity. Greater CYP2R1 catalytic efficiency does not establish that CYP27A1 activity is nonphysiological; full comparator Methods remain unavailable. Reason: The source compares vitamin D3 25-hydroxylation by CYP2R1 and CYP27A1 and separately shows CYP27A1 D2 hydroxylation at C24/C27. The 26-fold efficiency difference favors CYP2R1 in that comparison but does not negate CYP27A1 D3 activity or establish that it is nonphysiological. Retain the secondary catalytic activity, with full CYP27A1 comparator Methods unavailable. Supporting Evidence: PMID:15465040 The k(cat)/K(m) value of CYP2R1 was 26-fold higher than that of CYP27A1. |
| GO:0031073 cholesterol 26-hydroxylase activity | IDA PMID:12077124 Metabolism of 4 beta -hydroxycholesterol in humans. | ACCEPT | Summary: IDA for cholesterol 26(27)-hydroxylase activity, from a study establishing CYP27A1 metabolism of cholesterol-derived oxysterols. Core molecular function. Accept. Reason: The original selected Methods and Results test recombinant human CYP27A1 with adrenodoxin/reductase, comparing cholesterol with 4beta-hydroxycholesterol and identifying terminal side-chain oxygenated products by chromatography/mass spectrometry. This directly supports cholesterol 26-hydroxylase activity. The inherited quotation about CYP7A1 7alpha-hydroxylation concerns a different enzyme and is not retained as supporting evidence. Supporting Evidence: |
| GO:0031073 cholesterol 26-hydroxylase activity | IDA PMID:9660774 Activities of recombinant human cytochrome P450c27 (CYP27) w... | ACCEPT | Summary: IDA for cholesterol 26(27)-hydroxylase activity: recombinant P450c27 converts cholesterol to 27-hydroxycholesterol (and further). Core molecular function. Accept. Reason: Recombinant human CYP27A1 converts cholesterol to its terminal side-chain alcohol, with subsequent aldehyde and acid products resolved by HPLC/GC-MS. The reaction requires adrenodoxin and NADPH in the reconstituted system. This is direct support for the cholesterol 26-hydroxylase molecular function. Supporting Evidence: |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | IDA PMID:11412116 Putative helix F contributes to regioselectivity of hydroxyl... | ACCEPT | Summary: Retain the curated human multistep sterol-side-chain oxidation assignment with independent biochemical corroboration. The accessible regioselectivity abstract does not resolve every wild-type assay detail or justify transferring mutant carbon–carbon cleavage to wild type. Reason: The curator assigned the defined multistep sterol-side-chain oxidation to the human regioselectivity study. The available abstract establishes wild-type/mutant enzymology but does not resolve the exact wild-type assay substrate or preparation. Retain the correct catalytic assertion with explicit curator deference and corroboration from independent human enzyme studies. Do not transfer the mutant carbon–carbon cleavage reaction to wild type. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-5602170 | ACCEPT | Summary: The defective-variant Reactome event places the mature CYP27A1 entity in the mitochondrial matrix. Retain this functional location with matrix-facing membrane association; it does not imply that the defective variants retain catalytic activity. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. The event models defective variants; that does not establish absence of the wild-type compartment or catalytic capability. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9035960 | ACCEPT | Summary: The defective-variant Reactome event places the mature CYP27A1 entity in the mitochondrial matrix. Retain this functional location with matrix-facing membrane association; it does not imply that the defective variants retain catalytic activity. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. The event models defective variants; that does not establish absence of the wild-type compartment or catalytic capability. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-191999 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-192042 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-192054 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-192123 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193393 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193460 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193497 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193713 | ACCEPT | Summary: The historical Reactome record is unavailable, but independent targeting evidence and other actual CYP27A1 entities support the mitochondrial matrix location. This is compatible with peripheral association on the inner-membrane matrix face. Reason: The particular historical Reactome record is currently unavailable (two 404 responses); no source-specific entity path is claimed. Independent imported-enzyme topology and the other actual Q02318 reaction entities support the retained compartment. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193719 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193737 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193780 | ACCEPT | Summary: The historical Reactome record is unavailable, but independent targeting evidence and other actual CYP27A1 entities support the mitochondrial matrix location. This is compatible with peripheral association on the inner-membrane matrix face. Reason: The particular historical Reactome record is currently unavailable (two 404 responses); no source-specific entity path is claimed. Independent imported-enzyme topology and the other actual Q02318 reaction entities support the retained compartment. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193787 | ACCEPT | Summary: The historical Reactome record is unavailable, but independent targeting evidence and other actual CYP27A1 entities support the mitochondrial matrix location. This is compatible with peripheral association on the inner-membrane matrix face. Reason: The particular historical Reactome record is currently unavailable (two 404 responses); no source-specific entity path is claimed. Independent imported-enzyme topology and the other actual Q02318 reaction entities support the retained compartment. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193792 | ACCEPT | Summary: The actual Reactome entity path places mature CYP27A1 in the mitochondrial matrix. Retain this functional location, which is compatible with peripheral association on the inner-membrane matrix face rather than an exclusively free-soluble pool. Reason: The actual Reactome entity path places mature human Q02318 in the mitochondrial matrix. Matrix placement and peripheral association with the inner membrane are compatible spatial statements, not an ancestor/descendant specificity pair. Rat protease-protection and carbonate-extraction experiments support a matrix-facing membrane-extrinsic enzyme. Accept this functional location without claiming an exclusively free-soluble pool or a direct human localization measurement from the rat study. |
| GO:0008395 steroid hydroxylase activity | TAS PMID:9790667 A novel Arg362Ser mutation in the sterol 27-hydroxylase gene... | ACCEPT | Summary: The human CTX variant study supports loss of sterol 27-hydroxylase activity, while independent wild-type assays establish the general steroid hydroxylase function. Full original Methods remain unavailable. Reason: The abstract reports reduced sterol 27-hydroxylase activity of the historical human Arg362Ser variant in a cellular assay. The broad steroid hydroxylase function of normal CYP27A1 is independently established. Full original Methods remain unavailable, so the TAS source is not represented as a newly inspected quantitative wild-type assay. Supporting Evidence: PMID:9790667 was responsible for deficiency in the sterol 27-hydroxylase activity |
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Download this section (compressed HTML)Q: How much does CYP27A1 contribute to vitamin D3 25-hydroxylation in specific human tissues and physiological states, beyond the catalytic capacity measured in recombinant systems?
Q: Should the historical GO:0047748 label and vitamin-D process placement be clarified to match their current reaction and part_of definitions without resurrecting obsolete GO:0036378?
Q: How is matrix-facing CYP27A1 substrate access coordinated with sterol movement across mitochondrial membranes and with adrenodoxin availability?
Experiment: Measure isotope-labeled cholesterol, bile-acid-intermediate and vitamin D3 flux in matched human cells after selective CYP27A1 depletion and rescue, quantifying enzyme abundance and redox-partner availability. Distinguish direct catalytic products from downstream signaling and compare CYP2R1-dependent D3 conversion.
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