CYP27A1 (sterol 27-hydroxylase / sterol 26-hydroxylase, EC 1.14.15.15) is a mitochondrial cytochrome P450 that receives electrons from the adrenodoxin (ferredoxin) / ferredoxin reductase electron-transfer system and hydroxylates the sterol side chain at C27 (C26). Acting on 5-beta-cholestane intermediates, it initiates side-chain oxidation in bile-acid biosynthesis, converting 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol through the C27 alcohol and aldehyde to the C27 acid (di-/tri-hydroxycoprostanoic acids, DHCA/THCA). It also converts cholesterol to 27-hydroxycholesterol, the first committed step of the acidic (alternative) bile-acid pathway, and can further oxidize this product to 3-beta-hydroxy-5-cholestenoic acid. Through the same terminal-methyl hydroxylase chemistry it acts on additional sterols and oxysterols, including 7-ketocholesterol (detoxification in retinal pigment epithelium) and, secondarily, vitamin D3 intermediates. The enzyme is a heme-thiolate P450 (axial cysteine ligand) that is post-translationally imported into mitochondria and associates as a membrane-extrinsic protein with the matrix face of the mitochondrial inner membrane. Loss of CYP27A1 activity causes cerebrotendinous xanthomatosis (CTX), an autosomal-recessive sterol storage disorder with cholestanol and bile-alcohol accumulation, tendon xanthomas, cataracts, and progressive neurological decline that is treatable with chenodeoxycholic acid.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAN-GO) inference that CYP27A1 is active in the mitochondrion. Correct: CYP27A1 is a mitochondrial P450 imported into mitochondria and associated with the inner membrane. Accept as a core localization. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| 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. Supporting Evidence: PMID:9660774 alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27 |
| GO:0030343 vitamin D 25-hydroxylase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of vitamin D 25-hydroxylase activity. CYP27A1 has historically been considered a vitamin D3 25-hydroxylase, but PMID:15465040 shows that toward vitamin D2 CYP27A1 hydroxylates at C-24 and C-27 (not C-25) and that CYP2R1 is the physiologically important 25-hydroxylase (26-fold higher kcat/Km). This is a minor, non-core side activity rather than the enzyme's primary sterol 27-hydroxylase function; keep as non-core. Reason: Physiological vitamin D 25-hydroxylation is attributed to CYP2R1; CYP27A1's vitamin D activity is low-efficiency and not its core function. Supporting Evidence: PMID:15465040 CYP2R1 hydroxylated vitamin D(2) at the C-25 position while CYP27A1 hydroxylated it at positions C-24 and C-27 |
| 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. Supporting Evidence: PMID:9660774 27-hydroxylation of cholesterol catalyzed by P450c27 |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt Cytochrome P450 monooxygenase that catalyzes regio- and |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt axial binding residue |
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic ARBA annotation for mitochondrial localization. Correct; duplicates the IBA and HTP mitochondrion annotations. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| 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. 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. Supporting Evidence: PMID:1708392 catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Electronic ARBA annotation to the very broad lipid biosynthetic process parent. Not wrong (bile acids and oxysterols are lipids) but uninformatively general; the specific biological processes are better captured by bile acid biosynthesis (GO:0006699). Mark as over-annotated. Reason: Overly general; CYP27A1's biosynthetic contributions are specifically to bile acids and oxysterols, already captured by more precise terms. |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt Cytochrome P450 monooxygenase that catalyzes regio- and |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic RHEA/EC (EC:1.14.15.15) annotation. Despite the misleading GO label, the GO definition of GO:0047748 is the sterol 26-hydroxylase reaction (5-beta-cholestane-3a,7a,12a-triol -> (25R)-THCA-26-oate; RHEA:34631), which is the core catalytic activity of CYP27A1. Accept; supported by multiple EXP/IDA annotations. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt EC=1.14.15.15 |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt Cytochrome P450 monooxygenase that catalyzes regio- and |
| GO:0045880 positive regulation of smoothened signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl-projected orthology annotation (from mouse Cyp27a1). CYP27A1 produces 7-keto,27-hydroxycholesterol, an oxysterol that can activate smoothened. This is an indirect downstream consequence of an enzymatic product, not a molecular activity of CYP27A1; keep as a non-core biological-process annotation. Reason: Effect on smoothened signaling is mediated indirectly by an oxysterol product; it is a peripheral role, not the enzyme's core hydroxylase function. |
| GO:1901755 vitamin D3 biosynthetic process | IDA PMID:15465040 Metabolism of vitamin D by human microsomal CYP2R1. | KEEP AS NON CORE | Summary: IDA from a study that concludes CYP2R1, not CYP27A1, is the physiologically important vitamin D 25-hydroxylase, and that CYP27A1 hydroxylates vitamin D2 at C-24/C-27 rather than C-25. CYP27A1 may play a redundant role in vitamin D biosynthesis, so this is a non-core, secondary process for the gene. Reason: CYP27A1's role in vitamin D3 biosynthesis is minor/redundant relative to CYP2R1; retain but do not treat as a core function. Supporting Evidence: PMID:15465040 These results strongly suggest that CYP2R1 plays a physiologically important role in the vitamin D 25-hydroxylation in humans. |
| 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. Supporting Evidence: PMID:1708392 catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis 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). Supporting Evidence: PMID:1708392 catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis 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. Supporting Evidence: PMID:9660774 alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27 |
| 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. Supporting Evidence: PMID:1708392 catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway |
| 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. Supporting Evidence: PMID:1708392 catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway |
| 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. Supporting Evidence: PMID:9660774 alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27 |
| 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. 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: ISS annotation transferred from mouse (MGI:88594). As with the Ensembl-projected equivalent, this reflects an indirect effect of a CYP27A1 oxysterol product on smoothened, not a core molecular activity. Keep as non-core. Reason: Peripheral, indirect (oxysterol-mediated) effect on smoothened signaling; not the enzyme's core hydroxylase function. |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| 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. Supporting Evidence: PMID:1708392 the expression of active enzyme capable of catalyzing multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates of the bile acid synthesis pathway |
| 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. 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. 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: Experimental annotation from a CTX study: an Arg362Ser mutation in the adrenodoxin-binding residue causes deficiency in sterol 27-hydroxylase activity, confirming the core catalytic (EC 1.14.15.15) function and its dependence on adrenodoxin. Accept. Supporting Evidence: PMID:9790667 was responsible for deficiency in the sterol 27-hydroxylase activity |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput mitochondrial proteomics (MitoCoP) supporting mitochondrial localization. Consistent with the known mitochondrial P450 identity of CYP27A1 and with the IBA/IEA mitochondrion annotations. Accept. Supporting Evidence: PMID:34800366 we combined subtractive proteomics, spatial proteomics, mitochondria-specific importomics |
| 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. Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:9660774 27-hydroxylation of cholesterol catalyzed by P450c27 |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193713 | ACCEPT | Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193780 | ACCEPT | Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-193787 | ACCEPT | Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| 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). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-5602170 | ACCEPT | Summary: Reactome TAS from a 'CYP27A1 does not 27-hydroxylate ...' reaction record, but annotated as enabling steroid hydroxylase activity. The general MF is correct for CYP27A1; accept (duplicate). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| GO:0008395 steroid hydroxylase activity | TAS Reactome:R-HSA-9035960 | ACCEPT | Summary: Reactome TAS (defective CYP27A1 reaction record) annotated as enabling steroid hydroxylase activity; the general MF is correct for wild-type CYP27A1. Accept (duplicate). Supporting Evidence: PMID:1708392 multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates |
| GO:0006699 bile acid biosynthetic process | IDA PMID:11412116 Putative helix F contributes to regioselectivity of hydroxyl... | ACCEPT | Summary: IDA from the helix-F regioselectivity study, which characterized CYP27A1 hydroxylation of bile-acid sterol intermediates. Core biological process. Accept. Supporting Evidence: PMID:11412116 regioselectivity of P450 27A1-dependent hydroxylation reactions |
| 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. Supporting Evidence: PMID:9660774 alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27 |
| 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. Supporting Evidence: PMID:9660774 recombinant human P450c27 is also able to further oxidize 27-hydroxycholesterol giving first an aldehyde and then 3beta-hydroxy-5-cholestenoic acid |
| 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. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; |
| GO:0030343 vitamin D 25-hydroxylase activity | IDA PMID:15465040 Metabolism of vitamin D by human microsomal CYP2R1. | KEEP AS NON CORE | Summary: IDA for vitamin D 25-hydroxylase activity. The cited study actually shows CYP27A1 hydroxylates vitamin D2 at C-24/C-27 (not C-25) and that CYP2R1 is the physiologically relevant 25-hydroxylase (26-fold higher catalytic efficiency). Retained as a low-efficiency, non-physiological side activity; keep as non-core. Reason: Physiological vitamin D 25-hydroxylation is attributed to CYP2R1; CYP27A1 is low-efficiency and hydroxylates vitamin D2 at C-24/C-27 rather than C-25. 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. Supporting Evidence: PMID:12077124 4 beta-hydroxycholesterol was 7 alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1 |
| 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. Supporting Evidence: PMID:9660774 27-hydroxylation of cholesterol catalyzed by P450c27 |
| GO:0047748 cholestanetetraol 26-dehydrogenase activity | IDA PMID:11412116 Putative helix F contributes to regioselectivity of hydroxyl... | ACCEPT | Summary: IDA for the EC 1.14.15.15 sterol 26-hydroxylase activity (GO:0047748 definition is this reaction), from the helix-F regioselectivity study of P450 27A1 hydroxylation. Core molecular function. Accept. Supporting Evidence: PMID:11412116 the regioselectivity of P450 27A1-dependent hydroxylation reactions |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-5602170 | KEEP AS NON CORE | Summary: Reactome TAS placing CYP27A1 in the mitochondrial matrix. Consistent with UniProt: after import into the matrix, CYP27A1 associates with the inner membrane as a membrane-extrinsic protein, so it faces the matrix. Keep as non-core; the specific location is the inner membrane (matrix face). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9035960 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-191999 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-192042 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-192054 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-192123 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193393 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193460 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193497 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193713 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193719 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193737 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193780 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193787 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-193792 | KEEP AS NON CORE | Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above). Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane. Supporting Evidence: file:human/CYP27A1/CYP27A1-uniprot.txt associates with the inner membrane as a membrane extrinsic protein. |
| GO:0008395 steroid hydroxylase activity | TAS PMID:9790667 A novel Arg362Ser mutation in the sterol 27-hydroxylase gene... | ACCEPT | Summary: TAS for steroid hydroxylase activity, citing a CTX mutation study that confirms the sterol 27-hydroxylase activity of CYP27A1. Steroid hydroxylase is a correct general parent MF. Accept. Supporting Evidence: PMID:9790667 was responsible for deficiency in the sterol 27-hydroxylase activity |
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