UniProtKB - Q9WVK8 (CP46A_MOUSE)
Protein
Cholesterol 24-hydroxylase
Gene
Cyp46a1
Organism
Mus musculus (Mouse)
Status
Functioni
P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation (PubMed:10377398, PubMed:16505352, PubMed:28190002). By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning (PubMed:16505352). Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis (By similarity). Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain (By similarity). May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole (By similarity).By similarity3 Publications
Catalytic activityi
- cholesterol + O2 + reduced [NADPH—hemoprotein reductase] = (24S)-hydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationEC:1.14.14.251 PublicationThis reaction proceeds in the forward1 Publication direction.
- cholestanol + O2 + reduced [NADPH—hemoprotein reductase] = (24S)-hydroxycholestanol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forward1 Publication direction.
- cholesta-5,7-dien-3β-ol + O2 + reduced [NADPH—hemoprotein reductase] = cholesta-5,7-dien-3β,24S-diol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- cholesta-5,7-dien-3β-ol + O2 + reduced [NADPH—hemoprotein reductase] = cholesta-5,7-dien-3β,25-diol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- cholesta-5,24-dien-3β-ol + O2 + reduced [NADPH—hemoprotein reductase] = cholesta-5,24Z-dien-3β,27-diol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- cholesta-5,24-dien-3β-ol + O2 + reduced [NADPH—hemoprotein reductase] = (24S)-25-epoxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- 4β-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = 4β,24S-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- (24S)-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = (24S,25R)-24,26-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- (24S)-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = 24S,25-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- 7α-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = (24S)-7α-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- O2 + progesterone + reduced [NADPH—hemoprotein reductase] = 17α-hydroxyprogesterone + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- O2 + reduced [NADPH—hemoprotein reductase] + testosterone = 16β,17β-dihydroxyandrost-4-en-3-one + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- O2 + reduced [NADPH—hemoprotein reductase] + testosterone = 2-hydroxytestosterone + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
- O2 + reduced [NADPH—hemoprotein reductase] + testosterone = 6β,17β-dihydroxyandrost-4-en-3-one + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardCurated direction.
Cofactori
hemeBy similarity
: cholesterol degradation Pathwayi
This protein is involved in the pathway cholesterol degradation, which is part of Steroid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway cholesterol degradation and in Steroid metabolism.
Pathwayi: C21-steroid hormone metabolism
This protein is involved in the pathway C21-steroid hormone metabolism, which is part of Lipid metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway C21-steroid hormone metabolism and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 437 | Iron (heme axial ligand)By similarity | 1 |
GO - Molecular functioni
- cholesterol 24-hydroxylase activity Source: UniProtKB
- heme binding Source: UniProtKB
- iron ion binding Source: InterPro
- steroid hydroxylase activity Source: UniProtKB
GO - Biological processi
- cholesterol catabolic process Source: UniProtKB
- progesterone metabolic process Source: UniProtKB
- protein localization to membrane raft Source: ARUK-UCL
- regulation of long-term synaptic potentiation Source: UniProtKB
- xenobiotic metabolic process Source: UniProtKB
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.14.13.98, 3474 |
Reactomei | R-MMU-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-MMU-211976, Endogenous sterols |
UniPathwayi | UPA00229 UPA01058 |
Names & Taxonomyi
Protein namesi | Recommended name: Cholesterol 24-hydroxylase1 Publication (EC:1.14.14.251 Publication)Short name: CH24H Alternative name(s): Cholesterol 24-monooxygenase Cholesterol 24S-hydroxylase1 Publication Cytochrome P450 46A11 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1341877, Cyp46a1 |
Subcellular locationi
Endoplasmic reticulum
Other locations
- postsynapse 1 Publication
- presynapse 1 Publication
- dendrite 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
Other locations
- dendrite Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- postsynapse Source: UniProtKB
- presynapse Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 3 – 23 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cell junction, Cell projection, Endoplasmic reticulum, Membrane, Microsome, SynapsePathology & Biotechi
Disruption phenotypei
Mutant mice are deficient in spatial, associative and motor learning.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000051995 | 1 – 500 | Cholesterol 24-hydroxylaseAdd BLAST | 500 |
Proteomic databases
MaxQBi | Q9WVK8 |
PaxDbi | Q9WVK8 |
PRIDEi | Q9WVK8 |
PTM databases
iPTMneti | Q9WVK8 |
PhosphoSitePlusi | Q9WVK8 |
SwissPalmi | Q9WVK8 |
Expressioni
Tissue specificityi
Expressed in high level in the pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, and neuronal cell bodies in layers II/III, V, and VI of the cortex. Expressed in hippocampal and cerebellar interneurons, in retinal ganglion cells, and in a subset of retinal cells localized to the inner nuclear layer (at protein level).2 Publications
Gene expression databases
Bgeei | ENSMUSG00000021259, Expressed in primary visual cortex and 146 other tissues |
ExpressionAtlasi | Q9WVK8, baseline and differential |
Genevisiblei | Q9WVK8, MM |
Interactioni
Protein-protein interaction databases
BioGRIDi | 199032, 1 interactor |
STRINGi | 10090.ENSMUSP00000021684 |
Miscellaneous databases
RNActi | Q9WVK8, protein |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 493 – 499 | Poly-Pro | 7 |
Sequence similaritiesi
Belongs to the cytochrome P450 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0157, Eukaryota |
GeneTreei | ENSGT00940000156927 |
HOGENOMi | CLU_001570_5_1_1 |
InParanoidi | Q9WVK8 |
OMAi | IAGRTMF |
OrthoDBi | 825914at2759 |
PhylomeDBi | Q9WVK8 |
TreeFami | TF352037 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR039983, CYP46A1 IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
PANTHERi | PTHR24293, PTHR24293, 1 hit |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q9WVK8-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSPGLLLLGS AVLLAFGLCC TFVHRARSRY EHIPGPPRPS FLLGHLPYFW
60 70 80 90 100
KKDEDCGRVL QDVFLDWAKK YGPVVRVNVF YKTSVIVTSP ESVKKFLMST
110 120 130 140 150
KYNKDSKMYR ALQTVFGERL FGQGLVSECD YGRWYKQRKV MDLAFSRSSL
160 170 180 190 200
VSLMETFNEK AEQLVEILEA KADGQTPVSM QDMLTCATID ILAKAAFGME
210 220 230 240 250
TSMLLGAQKP LSQAVKVMLE GISASRNTLA KFMPGKRKQL REIRESIRLL
260 270 280 290 300
RQVGKDWVQR RREALKRGED MPADILTQIL KAEEGAQDDE VLLDNFVTFF
310 320 330 340 350
IAGHETSANH LAFTVMELSR QPEIVARLQA EVDEVVGSKR HLDYEDLGRL
360 370 380 390 400
QYLSQVLKES LRLYPPAWGT FRLLEEETLI DGVRVPGNTP LLFSTYVMGR
410 420 430 440 450
MDTYFEDPLT FNPDRFGPGA PKPRFTYFPF SLGHRSCIGQ QFAQMEVKVV
460 470 480 490 500
MAKLLQRIEF RLVPGQRFGL QEQATLKPLD PVLCTLRPRG WQPAPPPPPC
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A1Y7VM34 | A0A1Y7VM34_MOUSE | Cholesterol 24-hydroxylase | Cyp46a1 | 112 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF094479 mRNA Translation: AAD41243.1 BC018307 mRNA Translation: AAH18307.1 |
CCDSi | CCDS26160.1 |
RefSeqi | NP_034140.1, NM_010010.1 |
Genome annotation databases
Ensembli | ENSMUST00000021684; ENSMUSP00000021684; ENSMUSG00000021259 |
GeneIDi | 13116 |
KEGGi | mmu:13116 |
UCSCi | uc007ozo.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF094479 mRNA Translation: AAD41243.1 BC018307 mRNA Translation: AAH18307.1 |
CCDSi | CCDS26160.1 |
RefSeqi | NP_034140.1, NM_010010.1 |
3D structure databases
SMRi | Q9WVK8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 199032, 1 interactor |
STRINGi | 10090.ENSMUSP00000021684 |
PTM databases
iPTMneti | Q9WVK8 |
PhosphoSitePlusi | Q9WVK8 |
SwissPalmi | Q9WVK8 |
Proteomic databases
MaxQBi | Q9WVK8 |
PaxDbi | Q9WVK8 |
PRIDEi | Q9WVK8 |
Protocols and materials databases
Antibodypediai | 14316, 287 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000021684; ENSMUSP00000021684; ENSMUSG00000021259 |
GeneIDi | 13116 |
KEGGi | mmu:13116 |
UCSCi | uc007ozo.1, mouse |
Organism-specific databases
CTDi | 10858 |
MGIi | MGI:1341877, Cyp46a1 |
Phylogenomic databases
eggNOGi | KOG0157, Eukaryota |
GeneTreei | ENSGT00940000156927 |
HOGENOMi | CLU_001570_5_1_1 |
InParanoidi | Q9WVK8 |
OMAi | IAGRTMF |
OrthoDBi | 825914at2759 |
PhylomeDBi | Q9WVK8 |
TreeFami | TF352037 |
Enzyme and pathway databases
UniPathwayi | UPA00229 UPA01058 |
BRENDAi | 1.14.13.98, 3474 |
Reactomei | R-MMU-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-MMU-211976, Endogenous sterols |
Miscellaneous databases
BioGRID-ORCSi | 13116, 0 hits in 17 CRISPR screens |
PROi | PR:Q9WVK8 |
RNActi | Q9WVK8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000021259, Expressed in primary visual cortex and 146 other tissues |
ExpressionAtlasi | Q9WVK8, baseline and differential |
Genevisiblei | Q9WVK8, MM |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR039983, CYP46A1 IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
PANTHERi | PTHR24293, PTHR24293, 1 hit |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CP46A_MOUSE | |
Accessioni | Q9WVK8Primary (citable) accession number: Q9WVK8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 24, 2001 |
Last sequence update: | November 1, 1999 | |
Last modified: | December 2, 2020 | |
This is version 164 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families