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Reviewed, UniProtKB/Swiss-Prot P15392 (CP2A4_MOUSE)

Last modified July 22, 2008. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Cytochrome P450 2A4
    EC=1.14.14.1
Alternative name(s):
    CYPIIA4
    Testosterone 15-alpha-hydroxylase
    P450-15-alpha
    P450-IIA3.1
Gene names
Name: Cyp2a4
Synonyms: Cyp2a-4
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMus

Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at transcript level.

General annotation (Comments)

Function

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 activity

RH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O.

Cofactor

Heme group By similarity.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Tissue specificity

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

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.

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords

   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase

Gene Ontology (GO)

   Cellular componentmicrosome

Inferred from direct assay. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 494494Cytochrome P450 2A4

Sites

Metal binding4391Iron (heme axial ligand)

Experimental info

Sequence conflict2961L → Q in AAA40426 and AAA40429. Ref.2
Sequence conflict3061V → G in AAA40426 and AAA40429. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P15392-1 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: 69724BDE3195D75C

FASTA49456,595
        10         20         30         40         50         60 
MLTSGLLLVA AVAFLSVLVL MSVWKQRKLS GKLPPGPTPL PFVGNFLQLN TEQMYNSLMK 

        70         80         90        100        110        120 
ISQRYGPVFT IYLGSRRIVV LCGQEAVKEA LVDQAEEFSG RGEQATFDWL FKGYGIAFSS 

       130        140        150        160        170        180 
GERAKQLRSF SIATLRDFGV GKRGIEERIQ EEAGFLIDSF RKTNGAFIDP TFYLSRTVSN 

       190        200        210        220        230        240 
VISSIVFGDR FDYEDKEFLS LLRMMLGSLQ FTATSMGQVY EMFSSVMKHL PGPQQQAFKE 

       250        260        270        280        290        300 
LQGLEDFITK KVEHNQRTLD PNSPRDFIDS FLIRMLEEKK NPNTEFYMKN LVLTTLNLFF 

       310        320        330        340        350        360 
AGTETVSTTL RYGFLLLMKY PDIEAKVHEE IDRVIGRNRQ PKYEDRMKMP YTEAVIHEIQ 

       370        380        390        400        410        420 
RFADLIPMGL ARRVTKDTKF RDFLLPKGTE VFPMLGSVLK DPKFFSNPKD FNPKHFLDDK 

       430        440        450        460        470        480 
GQFKKSDAFV PFSIGKRYCF GEGLARMELF LFLTNIMQNF HFKSTQAPQD IDVSPRLVGF 

       490 
VTIPPTYTMS FLSR 

« Hide

References

[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: 2703500] [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: 3346244] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"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: 2733794] [Abstract]
Cited for: MUTAGENESIS.
[4]"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: 10490589] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

M26208 expand/collapse EMBL AC list , M25146, M25147, M26202, M26203, M26205, M26206, M26207 Genomic DNA. Translation: AAA37797.1.
J03549 mRNA. Translation: AAA40426.1.
M19319 mRNA. Translation: AAA40429.1.
PIRA33531.
UniGeneMm.154643
Mm.389848

3D structure databases

HSSPHSSP built from PDB template 1DT6 based on UniProtKB P00179.
SMRP15392. Positions 31-494.
ModBaseSearch...

Genome annotation databases

EnsemblENSMUSG00000074254. Mus musculus. [Contig view]

Organism-specific databases

MGIMGI:88596. Cyp2a4.

Phylogenomic databases

HOGENOMP15392.
HOVERGENP15392.

Gene expression databases

GermOnlineENSMUSG00000074254. Mus musculus.

Family and domain databases

InterProIPR001128. Cyt_P450.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
[Graphical view]
Gene3DG3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHERPTHR19383. Cyt_P450. 1 hit.
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProDomP15392.
[Graphical view] [Entries sharing at least one domain]
BLOCKSSearch...

Other Resources

SOURCESearch...
ProtoNetSearch...

Entry information

Entry nameCP2A4_MOUSE
AccessionPrimary (citable) accession number: P15392
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: July 22, 2008
This is version 69 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents