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Protein

Cholesterol 24-hydroxylase

Gene

CYP46A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. Has also activity with xenobiotic compounds, such as clotrimazole.2 Publications

Catalytic activityi

Cholesterol + [reduced NADPH--hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3-beta,24-diol + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication

Cofactori

heme3 Publications

Kineticsi

  1. KM=2.2 µM for 24(S)-hydroxycholesterol1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi437Iron (heme axial ligand)1

    GO - Molecular functioni

    • cholesterol 24-hydroxylase activity Source: UniProtKB
    • heme binding Source: UniProtKB
    • iron ion binding Source: InterPro
    • steroid hydroxylase activity Source: ProtInc

    GO - Biological processi

    • bile acid biosynthetic process Source: Reactome
    • cholesterol catabolic process Source: UniProtKB
    • nervous system development Source: ProtInc
    • sterol metabolic process Source: Reactome
    • xenobiotic metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Biological processi

    Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciZFISH:HS00517-MONOMER.
    BRENDAi1.14.13.98. 2681.
    ReactomeiR-HSA-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
    R-HSA-211976. Endogenous sterols.
    SABIO-RKQ9Y6A2.

    Chemistry databases

    SwissLipidsiSLP:000001220. [Q9Y6A2-1]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cholesterol 24-hydroxylase (EC:1.14.14.251 Publication)
    Short name:
    CH24H
    Alternative name(s):
    Cytochrome P450 46A1
    Gene namesi
    Name:CYP46A1
    Synonyms:CYP46
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:2641. CYP46A1.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei3 – 23HelicalSequence analysisAdd BLAST21

    GO - Cellular componenti

    • endoplasmic reticulum Source: ProtInc
    • endoplasmic reticulum membrane Source: Reactome
    • integral component of membrane Source: UniProtKB-KW
    • organelle membrane Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi10858.
    OpenTargetsiENSG00000036530.
    PharmGKBiPA27117.

    Polymorphism and mutation databases

    BioMutaiCYP46A1.
    DMDMi12585217.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000519941 – 500Cholesterol 24-hydroxylaseAdd BLAST500

    Proteomic databases

    PaxDbiQ9Y6A2.
    PeptideAtlasiQ9Y6A2.
    PRIDEiQ9Y6A2.

    PTM databases

    iPTMnetiQ9Y6A2.
    PhosphoSitePlusiQ9Y6A2.

    Expressioni

    Tissue specificityi

    Expressed in brain. The mRNA was broadly distributed with higher levels in gray matter zones and lower levels in regions rich in white matter. Not detected in fetal sample but its expression increases linearly with age.

    Gene expression databases

    BgeeiENSG00000036530.
    CleanExiHS_CYP46A1.
    ExpressionAtlasiQ9Y6A2. baseline and differential.
    GenevisibleiQ9Y6A2. HS.

    Organism-specific databases

    HPAiHPA040702.

    Interactioni

    Protein-protein interaction databases

    BioGridi116069. 2 interactors.
    IntActiQ9Y6A2. 1 interactor.
    STRINGi9606.ENSP00000261835.

    Structurei

    Secondary structure

    1500
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi60 – 71Combined sources12
    Beta strandi73 – 79Combined sources7
    Beta strandi82 – 87Combined sources6
    Helixi90 – 97Combined sources8
    Helixi106 – 113Combined sources8
    Beta strandi118 – 121Combined sources4
    Turni125 – 127Combined sources3
    Helixi131 – 141Combined sources11
    Helixi142 – 145Combined sources4
    Helixi147 – 151Combined sources5
    Helixi154 – 170Combined sources17
    Beta strandi173 – 176Combined sources4
    Helixi180 – 197Combined sources18
    Helixi203 – 205Combined sources3
    Helixi209 – 227Combined sources19
    Helixi230 – 232Combined sources3
    Helixi234 – 236Combined sources3
    Helixi237 – 266Combined sources30
    Helixi275 – 282Combined sources8
    Turni283 – 285Combined sources3
    Beta strandi287 – 289Combined sources3
    Helixi290 – 302Combined sources13
    Helixi305 – 318Combined sources14
    Helixi322 – 335Combined sources14
    Turni336 – 338Combined sources3
    Helixi344 – 349Combined sources6
    Helixi351 – 363Combined sources13
    Beta strandi370 – 374Combined sources5
    Beta strandi378 – 380Combined sources3
    Beta strandi383 – 385Combined sources3
    Beta strandi387 – 393Combined sources7
    Helixi395 – 399Combined sources5
    Turni402 – 404Combined sources3
    Beta strandi405 – 407Combined sources3
    Helixi413 – 416Combined sources4
    Beta strandi424 – 426Combined sources3
    Helixi433 – 435Combined sources3
    Helixi440 – 457Combined sources18
    Beta strandi458 – 462Combined sources5
    Beta strandi470 – 480Combined sources11
    Beta strandi483 – 488Combined sources6

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2Q9FX-ray1.90A51-500[»]
    2Q9GX-ray2.40A51-500[»]
    3MDMX-ray1.60A51-500[»]
    3MDRX-ray2.00A/B51-500[»]
    3MDTX-ray2.30A/B51-500[»]
    3MDVX-ray2.40A/B51-500[»]
    4ENHX-ray2.50A51-500[»]
    4FIAX-ray2.10A51-500[»]
    4J14X-ray2.50A51-500[»]
    ProteinModelPortaliQ9Y6A2.
    SMRiQ9Y6A2.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9Y6A2.

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi493 – 499Poly-Pro7

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00800000124060.
    HOGENOMiHOG000290190.
    HOVERGENiHBG102502.
    InParanoidiQ9Y6A2.
    KOiK07440.
    OMAiCTLQPRG.
    OrthoDBiEOG091G0AII.
    PhylomeDBiQ9Y6A2.
    TreeFamiTF352037.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9Y6A2-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MSPGLLLLGS AVLLAFGLCC TFVHRARSRY EHIPGPPRPS FLLGHLPCFW
    60 70 80 90 100
    KKDEVGGRVL QDVFLDWAKK YGPVVRVNVF HKTSVIVTSP ESVKKFLMST
    110 120 130 140 150
    KYNKDSKMYR ALQTVFGERL FGQGLVSECN YERWHKQRRV IDLAFSRSSL
    160 170 180 190 200
    VSLMETFNEK AEQLVEILEA KADGQTPVSM QDMLTYTAMD ILAKAAFGME
    210 220 230 240 250
    TSMLLGAQKP LSQAVKLMLE GITASRNTLA KFLPGKRKQL REVRESIRFL
    260 270 280 290 300
    RQVGRDWVQR RREALKRGEE VPADILTQIL KAEEGAQDDE GLLDNFVTFF
    310 320 330 340 350
    IAGHETSANH LAFTVMELSR QPEIVARLQA EVDEVIGSKR YLDFEDLGRL
    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
    MAKLLQRLEF RLVPGQRFGL QEQATLKPLD PVLCTLRPRG WQPAPPPPPC
    Length:500
    Mass (Da):56,821
    Last modified:November 1, 1999 - v1
    Checksum:iAB9307749D9E5FDA
    GO
    Isoform 2 (identifier: Q9Y6A2-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-97: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:403
    Mass (Da):45,976
    Checksum:iE47E531F99EAA940
    GO
    Isoform 3 (identifier: Q9Y6A2-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-153: Missing.
         383-392: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:337
    Mass (Da):38,315
    Checksum:i43E23CB22A230FD7
    GO

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0538581 – 153Missing in isoform 3. 1 PublicationAdd BLAST153
    Alternative sequenceiVSP_0538591 – 97Missing in isoform 2. 1 PublicationAdd BLAST97
    Alternative sequenceiVSP_053860383 – 392Missing in isoform 3. 1 Publication10

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF094480 mRNA. Translation: AAD41244.1.
    AK090886 mRNA. Translation: BAC03539.1.
    AK295216 mRNA. Translation: BAG58210.1.
    AL136000 Genomic DNA. No translation available.
    AL160313 Genomic DNA. No translation available.
    BC022539 mRNA. Translation: AAH22539.1.
    CCDSiCCDS9954.1. [Q9Y6A2-1]
    RefSeqiNP_006659.1. NM_006668.1. [Q9Y6A2-1]
    UniGeneiHs.25121.

    Genome annotation databases

    EnsembliENST00000261835; ENSP00000261835; ENSG00000036530. [Q9Y6A2-1]
    ENST00000380228; ENSP00000369577; ENSG00000036530. [Q9Y6A2-2]
    GeneIDi10858.
    KEGGihsa:10858.
    UCSCiuc001ygo.4. human. [Q9Y6A2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF094480 mRNA. Translation: AAD41244.1.
    AK090886 mRNA. Translation: BAC03539.1.
    AK295216 mRNA. Translation: BAG58210.1.
    AL136000 Genomic DNA. No translation available.
    AL160313 Genomic DNA. No translation available.
    BC022539 mRNA. Translation: AAH22539.1.
    CCDSiCCDS9954.1. [Q9Y6A2-1]
    RefSeqiNP_006659.1. NM_006668.1. [Q9Y6A2-1]
    UniGeneiHs.25121.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2Q9FX-ray1.90A51-500[»]
    2Q9GX-ray2.40A51-500[»]
    3MDMX-ray1.60A51-500[»]
    3MDRX-ray2.00A/B51-500[»]
    3MDTX-ray2.30A/B51-500[»]
    3MDVX-ray2.40A/B51-500[»]
    4ENHX-ray2.50A51-500[»]
    4FIAX-ray2.10A51-500[»]
    4J14X-ray2.50A51-500[»]
    ProteinModelPortaliQ9Y6A2.
    SMRiQ9Y6A2.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116069. 2 interactors.
    IntActiQ9Y6A2. 1 interactor.
    STRINGi9606.ENSP00000261835.

    Chemistry databases

    SwissLipidsiSLP:000001220. [Q9Y6A2-1]

    PTM databases

    iPTMnetiQ9Y6A2.
    PhosphoSitePlusiQ9Y6A2.

    Polymorphism and mutation databases

    BioMutaiCYP46A1.
    DMDMi12585217.

    Proteomic databases

    PaxDbiQ9Y6A2.
    PeptideAtlasiQ9Y6A2.
    PRIDEiQ9Y6A2.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000261835; ENSP00000261835; ENSG00000036530. [Q9Y6A2-1]
    ENST00000380228; ENSP00000369577; ENSG00000036530. [Q9Y6A2-2]
    GeneIDi10858.
    KEGGihsa:10858.
    UCSCiuc001ygo.4. human. [Q9Y6A2-1]

    Organism-specific databases

    CTDi10858.
    DisGeNETi10858.
    GeneCardsiCYP46A1.
    HGNCiHGNC:2641. CYP46A1.
    HPAiHPA040702.
    MIMi604087. gene.
    neXtProtiNX_Q9Y6A2.
    OpenTargetsiENSG00000036530.
    PharmGKBiPA27117.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00800000124060.
    HOGENOMiHOG000290190.
    HOVERGENiHBG102502.
    InParanoidiQ9Y6A2.
    KOiK07440.
    OMAiCTLQPRG.
    OrthoDBiEOG091G0AII.
    PhylomeDBiQ9Y6A2.
    TreeFamiTF352037.

    Enzyme and pathway databases

    BioCyciZFISH:HS00517-MONOMER.
    BRENDAi1.14.13.98. 2681.
    ReactomeiR-HSA-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
    R-HSA-211976. Endogenous sterols.
    SABIO-RKQ9Y6A2.

    Miscellaneous databases

    ChiTaRSiCYP46A1. human.
    EvolutionaryTraceiQ9Y6A2.
    GeneWikiiCYP46A1.
    GenomeRNAii10858.
    PROiQ9Y6A2.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000036530.
    CleanExiHS_CYP46A1.
    ExpressionAtlasiQ9Y6A2. baseline and differential.
    GenevisibleiQ9Y6A2. HS.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCP46A_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y6A2
    Secondary accession number(s): B4DHP8, E7EQG9, Q8N2B0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 24, 2001
    Last sequence update: November 1, 1999
    Last modified: November 30, 2016
    This is version 153 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.