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Details on Person UniProt:Q07973 CYP24A1

Class:Id	ReferenceGeneProduct:52630
_chainChangeLog	transit peptide:1-35 added on Sat February 7 2015;chain:36-514 added on Sat February 7 2015
_displayName	UniProt:Q07973 CYP24A1
_timestamp	2025-02-21 18:35:22
chain	transit peptide:1-35 chain:36-514
checksum	8862F63771981195
comment	FUNCTION A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:11012668, PubMed:15574355, PubMed:16617161, PubMed:24893882, PubMed:29461981, PubMed:8679605). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:15574355, PubMed:24893882). With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product (PubMed:11012668, PubMed:8679605). Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:8679605).CATALYTIC ACTIVITY calcitriol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = calcitetrol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY calcitetrol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (1S)-1,25-dihydroxy-24-oxocalciol + 2 oxidized [adrenodoxin] + 2 H2OCATALYTIC ACTIVITY (1S)-1,25-dihydroxy-24-oxocalciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (1S)-1,23,25-trihydroxy-24-oxocalciol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY (1S)-1,23-dihydroxy-24,25,26,27-tetranorcalciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + 2 oxidized [adrenodoxin] + 2 H2OCATALYTIC ACTIVITY (1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + 2 reduced [adrenodoxin] + O2 + H(+) = calcitroate + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY calcitriol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 1alpha,23S,25-trihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY calcidiol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = secalciferol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY secalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 25-hydroxy-24-oxocalciol + 2 oxidized [adrenodoxin] + 2 H2OCATALYTIC ACTIVITY 25-hydroxy-24-oxocalciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 23S,25-dihydroxy-24-oxocholecalciferol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY calcidiol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (23S)-23,25-dihydroxycalciol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY 20S-hydroxycholecalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 20S,25-dihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY 20S-hydroxycholecalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 20S,24R-dihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2OCATALYTIC ACTIVITY 20S,23-dihydroxycholecalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 20S,23,25-trihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2OCOFACTOR The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Specifically expressed in macrophages. Lacks the transit peptide. May be a dominant negative-acting isoform possibly by sequestering vitamin D metabolites.SIMILARITY Belongs to the cytochrome P450 family.
description	recommendedName: fullName evidence="12"1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial shortName: 24-OHase shortName: Vitamin D(3) 24-hydroxylase ecNumber evidence="3 4 5 6 9"1.14.15.16 alternativeName: Cytochrome P450 24A1 alternativeName: Cytochrome P450-CC24
geneName	CYP24A1 CYP24
identifier	Q07973
isSequenceChanged	FALSE
keyword	Alternative splicing Disease variant Heme Iron Lipid metabolism Metal-binding Mitochondrion Monooxygenase Oxidoreductase Proteomics identification Reference proteome Transit peptide
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	CYP24A1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8999986] ENSEMBL:ENSG00000019186 CYP24A1 [Homo sapiens]
secondaryIdentifier	CP24A_HUMAN Q15807 Q32ML3 Q5I2W7
sequenceLength	514
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8966505] UniProt:Q07973-1 CYP24A1 [Homo sapiens] [ReferenceIsoform:8966506] UniProt:Q07973-2 CYP24A1 [Homo sapiens] [ReferenceIsoform:8966507] UniProt:Q07973-3 CYP24A1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:209969] CYP24A1 [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:5601991] CYP24A1 E143del [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:5601992] CYP24A1 E322K [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:5601997] CYP24A1 E151* [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:5602003] CYP24A1 R396W [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:5602011] CYP24A1 C477Lfs*14 [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:5602018] CYP24A1 R159Q [mitochondrial inner membrane] [Homo sapiens]
(referenceSequence)	[ReplacedResidue:5602007] L-glutamic acid 322 replaced with L-lysine [FragmentReplacedModification:5602009] Replacement of residues 477 to 489 by LDCPQIRHPGHRQ [ReplacedResidue:5602012] L-arginine 396 replaced with L-tryptophan [ReplacedResidue:5602017] L-arginine 159 replaced with L-glutamine [FragmentDeletionModification:5602022] Deletion of residues 143 to 143 [NonsenseMutation:9827825] Nonsense mutation at L-glutamic acid 151
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No pathways have been reviewed or authored by UniProt:Q07973 CYP24A1 (52630)