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Protein

Cytochrome P450 2A4

Gene

Cyp2a4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

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

hemeBy similarity

Sites

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

GO - Molecular functioni

GO - Biological processi

  • response to stilbenoid Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_274299. Xenobiotics.
REACT_288150. Aflatoxin activation and detoxification.

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 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:88596. Cyp2a4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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

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.
GeneTreeiENSGT00760000118775.
HOGENOMiHOG000036992.
HOVERGENiHBG015789.
InParanoidiP15392.
KOiK07411.
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

        10         20         30         40         50
MLTSGLLLVA AVAFLSVLVL MSVWKQRKLS GKLPPGPTPL PFVGNFLQLN
60 70 80 90 100
TEQMYNSLMK ISQRYGPVFT IYLGSRRIVV LCGQETVKEA LVDQAEEFSG
110 120 130 140 150
RGEQATFDWL FKGYGIAFSS GERAKQLRRF SITTLRDFGV GKRGIEERIQ
160 170 180 190 200
EEAGFLIDSF RKTNGAFIDP TFYLSRTVSN VISSIVFGDR FDYEDKEFLS
210 220 230 240 250
LLRMMLGSLQ FTATSMGQVY EMFSSVMKHL PGPQQQAFKE LQGLEDFITK
260 270 280 290 300
KVEHNQRTLD PNSPRDFIDS FLIRMLEEKK NPNTEFYMKN LVLTTLNLFF
310 320 330 340 350
AGTETVSTTL RYGFLLLMKY PDIEAKVHEE IDRVIGRNRQ PKYEDRMKMP
360 370 380 390 400
YTEAVIHEIQ RFADLIPMGL ARRVTKDTKF RDFLLPKGTE VFPMLGSVLK
410 420 430 440 450
DPKFFSNPKD FNPKHFLDDK GQFKKSDAFV PFSIGKRYCF GEGLARMELF
460 470 480 490
LFLTNIMQNF HFKSTQEPQD IDVSPRLVGF VTIPPTYTMS FLSR
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

MINTiMINT-4080270.
STRINGi10090.ENSMUSP00000096254.

PTM databases

PhosphoSiteiP15392.

Proteomic databases

PaxDbiP15392.
PRIDEiP15392.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi13086.
MGIiMGI:88596. Cyp2a4.

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118775.
HOGENOMiHOG000036992.
HOVERGENiHBG015789.
InParanoidiP15392.
KOiK07411.
OrthoDBiEOG7RBZ85.
TreeFamiTF352043.

Enzyme and pathway databases

ReactomeiREACT_274299. Xenobiotics.
REACT_288150. Aflatoxin activation and detoxification.

Miscellaneous databases

NextBioi283050.
PROiP15392.
SOURCEiSearch...

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 116 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

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 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.