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Protein

Cholesterol 24-hydroxylase

Gene

CYP46A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

    Keywordsi

    Molecular functionMonooxygenase, Oxidoreductase
    Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism
    LigandHeme, Iron, Metal-binding

    Enzyme and pathway databases

    BRENDAi1.14.13.98 2681
    ReactomeiR-HSA-193775 Synthesis of bile acids and bile salts via 24-hydroxycholesterol
    R-HSA-211976 Endogenous sterols
    SABIO-RKiQ9Y6A2

    Chemistry databases

    SwissLipidsiSLP:000001220 [Q9Y6A2-1]
    SLP:000001720

    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

    EuPathDBiHostDB:ENSG00000036530.8
    HGNCiHGNC:2641 CYP46A1
    MIMi604087 gene
    neXtProtiNX_Q9Y6A2

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

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

    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
    ProteomicsDBi86640

    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 Expressed in 138 organ(s), highest expression level in caudate nucleus
    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

    3D structure databases

    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
    GeneTreeiENSGT00900000140779
    HOGENOMiHOG000290190
    HOVERGENiHBG102502
    InParanoidiQ9Y6A2
    KOiK07440
    OMAiTMILAGH
    OrthoDBiEOG091G0AII
    PhylomeDBiQ9Y6A2
    TreeFamiTF352037

    Family and domain databases

    Gene3Di1.10.630.10, 1 hit
    InterProiView protein in InterPro
    IPR039983 CYP46A1
    IPR001128 Cyt_P450
    IPR017972 Cyt_P450_CS
    IPR002401 Cyt_P450_E_grp-I
    IPR036396 Cyt_P450_sf
    PANTHERiPTHR24293 PTHR24293, 1 hit
    PfamiView protein in Pfam
    PF00067 p450, 1 hit
    PRINTSiPR00463 EP450I
    PR00385 P450
    SUPFAMiSSF48264 SSF48264, 1 hit
    PROSITEiView protein in PROSITE
    PS00086 CYTOCHROME_P450, 1 hit

    Sequences (3+)i

    Sequence statusi: Complete.

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

    This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    G3V366G3V366_HUMAN
    Cholesterol 24-hydroxylase
    CYP46A1
    96Annotation score:
    H0YJI0H0YJI0_HUMAN
    Cholesterol 24-hydroxylase
    CYP46A1
    164Annotation score:
    H0YJU5H0YJU5_HUMAN
    Cholesterol 24-hydroxylase
    CYP46A1
    51Annotation score:

    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

    Similar proteinsi

    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]
    SLP:000001720

    PTM databases

    iPTMnetiQ9Y6A2
    PhosphoSitePlusiQ9Y6A2

    Polymorphism and mutation databases

    BioMutaiCYP46A1
    DMDMi12585217

    Proteomic databases

    PaxDbiQ9Y6A2
    PeptideAtlasiQ9Y6A2
    PRIDEiQ9Y6A2
    ProteomicsDBi86640

    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
    EuPathDBiHostDB:ENSG00000036530.8
    GeneCardsiCYP46A1
    HGNCiHGNC:2641 CYP46A1
    HPAiHPA040702
    MIMi604087 gene
    neXtProtiNX_Q9Y6A2
    OpenTargetsiENSG00000036530
    PharmGKBiPA27117
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0157 Eukaryota
    COG2124 LUCA
    GeneTreeiENSGT00900000140779
    HOGENOMiHOG000290190
    HOVERGENiHBG102502
    InParanoidiQ9Y6A2
    KOiK07440
    OMAiTMILAGH
    OrthoDBiEOG091G0AII
    PhylomeDBiQ9Y6A2
    TreeFamiTF352037

    Enzyme and pathway databases

    BRENDAi1.14.13.98 2681
    ReactomeiR-HSA-193775 Synthesis of bile acids and bile salts via 24-hydroxycholesterol
    R-HSA-211976 Endogenous sterols
    SABIO-RKiQ9Y6A2

    Miscellaneous databases

    ChiTaRSiCYP46A1 human
    EvolutionaryTraceiQ9Y6A2
    GeneWikiiCYP46A1
    GenomeRNAii10858
    PROiPR:Q9Y6A2
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000036530 Expressed in 138 organ(s), highest expression level in caudate nucleus
    CleanExiHS_CYP46A1
    ExpressionAtlasiQ9Y6A2 baseline and differential
    GenevisibleiQ9Y6A2 HS

    Family and domain databases

    Gene3Di1.10.630.10, 1 hit
    InterProiView protein in InterPro
    IPR039983 CYP46A1
    IPR001128 Cyt_P450
    IPR017972 Cyt_P450_CS
    IPR002401 Cyt_P450_E_grp-I
    IPR036396 Cyt_P450_sf
    PANTHERiPTHR24293 PTHR24293, 1 hit
    PfamiView protein in Pfam
    PF00067 p450, 1 hit
    PRINTSiPR00463 EP450I
    PR00385 P450
    SUPFAMiSSF48264 SSF48264, 1 hit
    PROSITEiView protein in PROSITE
    PS00086 CYTOCHROME_P450, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCP46A_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y6A2
    Secondary accession number(s): B4DHP8, E7EQG9, Q8N2B0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
    Last sequence update: November 1, 1999
    Last modified: November 7, 2018
    This is version 165 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    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. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
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