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P15392

- CP2A4_MOUSE

UniProt

P15392 - CP2A4_MOUSE

Protein

Cytochrome P450 2A4

Gene

Cyp2a4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 3 (03 Oct 2012)
      Previous versions | rss
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    Functioni

    Highly active in the 15-alpha-hydroxylation of testosterone. Also active in the 15-alpha-hydroxylation of progesterone and androstenedione. Little or no activity on corticosterone, pregnenolone, dehydroepiandrosterone, estradiol or estriol.

    Catalytic activityi

    RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.

    Cofactori

    Heme group.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi439 – 4391Iron (heme axial ligand)

    GO - Molecular functioni

    1. aromatase activity Source: UniProtKB-EC
    2. heme binding Source: InterPro
    3. iron ion binding Source: InterPro

    GO - Biological processi

    1. response to stilbenoid Source: UniProtKB

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 2A4 (EC:1.14.14.1)
    Alternative name(s):
    CYPIIA4
    Cytochrome P450-15-alpha
    Cytochrome P450-IIA3.1
    Testosterone 15-alpha-hydroxylase
    Gene namesi
    Name:Cyp2a4
    Synonyms:Cyp2a-4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:88596. Cyp2a4.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 494494Cytochrome P450 2A4PRO_0000051666Add
    BLAST

    Proteomic databases

    PaxDbiP15392.
    PRIDEiP15392.

    PTM databases

    PhosphoSiteiP15392.

    Expressioni

    Tissue specificityi

    Kidney and lung. Expressed in liver, with a strong circadian rhythmicity. Circadian expression is regulated by DBP.1 Publication

    Gene expression databases

    GenevestigatoriP15392.

    Interactioni

    Protein-protein interaction databases

    MINTiMINT-4080270.
    STRINGi10090.ENSMUSP00000096254.

    Structurei

    3D structure databases

    ProteinModelPortaliP15392.
    SMRiP15392. Positions 31-494.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00670000097868.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiP15392.
    KOiK07411.
    OMAiEAVIHEM.
    OrthoDBiEOG7RBZ85.
    TreeFamiTF352043.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01684. EP450ICYP2A.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P15392-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLTSGLLLVA AVAFLSVLVL MSVWKQRKLS GKLPPGPTPL PFVGNFLQLN    50
    TEQMYNSLMK ISQRYGPVFT IYLGSRRIVV LCGQETVKEA LVDQAEEFSG 100
    RGEQATFDWL FKGYGIAFSS GERAKQLRRF SITTLRDFGV GKRGIEERIQ 150
    EEAGFLIDSF RKTNGAFIDP TFYLSRTVSN VISSIVFGDR FDYEDKEFLS 200
    LLRMMLGSLQ FTATSMGQVY EMFSSVMKHL PGPQQQAFKE LQGLEDFITK 250
    KVEHNQRTLD PNSPRDFIDS FLIRMLEEKK NPNTEFYMKN LVLTTLNLFF 300
    AGTETVSTTL RYGFLLLMKY PDIEAKVHEE IDRVIGRNRQ PKYEDRMKMP 350
    YTEAVIHEIQ RFADLIPMGL ARRVTKDTKF RDFLLPKGTE VFPMLGSVLK 400
    DPKFFSNPKD FNPKHFLDDK GQFKKSDAFV PFSIGKRYCF GEGLARMELF 450
    LFLTNIMQNF HFKSTQEPQD IDVSPRLVGF VTIPPTYTMS FLSR 494
    Length:494
    Mass (Da):56,782
    Last modified:October 3, 2012 - v3
    Checksum:iB75D17F6EAF4A8EC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti86 – 861T → A in AAA37797. (PubMed:2703500)Curated
    Sequence conflicti86 – 861T → A in AAA40426. (PubMed:3346244)Curated
    Sequence conflicti86 – 861T → A in AAA40429. (PubMed:3346244)Curated
    Sequence conflicti129 – 1291R → S in AAA37797. (PubMed:2703500)Curated
    Sequence conflicti129 – 1291R → S in AAA40426. (PubMed:3346244)Curated
    Sequence conflicti129 – 1291R → S in AAA40429. (PubMed:3346244)Curated
    Sequence conflicti133 – 1331T → A in AAA37797. (PubMed:2703500)Curated
    Sequence conflicti133 – 1331T → A in AAA40426. (PubMed:3346244)Curated
    Sequence conflicti133 – 1331T → A in AAA40429. (PubMed:3346244)Curated
    Sequence conflicti296 – 2961L → Q in AAA40426. (PubMed:3346244)Curated
    Sequence conflicti296 – 2961L → Q in AAA40429. (PubMed:3346244)Curated
    Sequence conflicti306 – 3061V → G in AAA40426. (PubMed:3346244)Curated
    Sequence conflicti306 – 3061V → G in AAA40429. (PubMed:3346244)Curated
    Sequence conflicti467 – 4671E → A in AAA37797. (PubMed:2703500)Curated
    Sequence conflicti467 – 4671E → A in AAA40426. (PubMed:3346244)Curated
    Sequence conflicti467 – 4671E → A in AAA40429. (PubMed:3346244)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M26208
    , M25146, M25147, M26202, M26203, M26205, M26206, M26207 Genomic DNA. Translation: AAA37797.1.
    J03549 mRNA. Translation: AAA40426.1.
    M19319 mRNA. Translation: AAA40429.1.
    AC161798 Genomic DNA. No translation available.
    BC010761 mRNA. Translation: AAH10761.1.
    BC063778 mRNA. Translation: AAH63778.1.
    CCDSiCCDS21002.1.
    PIRiA33531.
    S03979.
    S16068.
    RefSeqiNP_034127.2. NM_009997.2.
    UniGeneiMm.154643.
    Mm.389848.

    Genome annotation databases

    EnsembliENSMUST00000098657; ENSMUSP00000096254; ENSMUSG00000074254.
    GeneIDi13086.
    KEGGimmu:13086.
    UCSCiuc009fui.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M26208
    , M25146 , M25147 , M26202 , M26203 , M26205 , M26206 , M26207 Genomic DNA. Translation: AAA37797.1 .
    J03549 mRNA. Translation: AAA40426.1 .
    M19319 mRNA. Translation: AAA40429.1 .
    AC161798 Genomic DNA. No translation available.
    BC010761 mRNA. Translation: AAH10761.1 .
    BC063778 mRNA. Translation: AAH63778.1 .
    CCDSi CCDS21002.1.
    PIRi A33531.
    S03979.
    S16068.
    RefSeqi NP_034127.2. NM_009997.2.
    UniGenei Mm.154643.
    Mm.389848.

    3D structure databases

    ProteinModelPortali P15392.
    SMRi P15392. Positions 31-494.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-4080270.
    STRINGi 10090.ENSMUSP00000096254.

    PTM databases

    PhosphoSitei P15392.

    Proteomic databases

    PaxDbi P15392.
    PRIDEi P15392.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000098657 ; ENSMUSP00000096254 ; ENSMUSG00000074254 .
    GeneIDi 13086.
    KEGGi mmu:13086.
    UCSCi uc009fui.1. mouse.

    Organism-specific databases

    CTDi 13086.
    MGIi MGI:88596. Cyp2a4.

    Phylogenomic databases

    eggNOGi COG2124.
    GeneTreei ENSGT00670000097868.
    HOGENOMi HOG000036992.
    HOVERGENi HBG015789.
    InParanoidi P15392.
    KOi K07411.
    OMAi EAVIHEM.
    OrthoDBi EOG7RBZ85.
    TreeFami TF352043.

    Miscellaneous databases

    ChiTaRSi Cyp2a4. mouse.
    NextBioi 283050.
    PROi P15392.
    SOURCEi Search...

    Gene expression databases

    Genevestigatori P15392.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR01684. EP450ICYP2A.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The structure and characterization of type I P-450(15) alpha gene as major steroid 15 alpha-hydroxylase and its comparison with type II P-450(15) alpha gene."
      Lindberg R., Burkhart B., Ichikawa T., Negishi M.
      J. Biol. Chem. 264:6465-6471(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Liver.
    2. "Reciprocal regulation of sex-dependent expression of testosterone 15 alpha-hydroxylase (P-450(15 alpha)) in liver and kidney of male mice by androgen. Evidence for a single gene."
      Squires E.J., Negishi M.
      J. Biol. Chem. 263:4166-4171(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Kidney.
    5. "Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue."
      Lindberg R., Negishi M.
      Nature 339:632-634(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS.
    6. "Circadian expression of the steroid 15 alpha-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP."
      Lavery D.J., Lopez-Molina L., Margueron R., Fleury-Olela F., Conquet F., Schibler U., Bonfils C.
      Mol. Cell. Biol. 19:6488-6499(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiCP2A4_MOUSE
    AccessioniPrimary (citable) accession number: P15392
    Secondary accession number(s): Q91XG2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: October 3, 2012
    Last modified: October 1, 2014
    This is version 111 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    There are only 11 differences between the sequence of testosterone 15-alpha-hydroxylase and that of coumarin 7-hydroxylase. By site-directed mutagenesis it has been shown that modification of position 209 is sufficient to convert the specificity of the two forms of the enzyme.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3