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Protein

Cytochrome P450 2A4

Gene

Cyp2a4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 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.

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.

Catalytic activityi

RH + [reduced NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.

Cofactori

hemeBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi439Iron (heme axial ligand)1

GO - Molecular functioni

GO - Biological processi

  • epoxygenase P450 pathway Source: GO_Central
  • response to stilbenoid Source: UniProtKB

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-211981. Xenobiotics.
R-MMU-5423646. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:88596. Cyp2a4.

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000516661 – 494Cytochrome P450 2A4Add BLAST494

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei131PhosphoserineBy similarity1
Modified residuei379N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP15392.
PeptideAtlasiP15392.
PRIDEiP15392.

PTM databases

iPTMnetiP15392.
PhosphoSitePlusiP15392.

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

BgeeiENSMUSG00000074254.
GenevisibleiP15392. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-4080270.
STRINGi10090.ENSMUSP00000096254.

Structurei

3D structure databases

ProteinModelPortaliP15392.
SMRiP15392.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiKOG0156. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00880000137861.
HOGENOMiHOG000036992.
HOVERGENiHBG015789.
InParanoidiP15392.
KOiK07411.
OMAiVGSRCRY.
OrthoDBiEOG091G0BT8.
TreeFamiTF352043.

Family and domain databases

InterProiView protein in InterPro
IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
PfamiView protein in Pfam
PF00067. p450. 1 hit.
PRINTSiPR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiView protein in PROSITE
PS00086. CYTOCHROME_P450. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti86T → A in AAA37797 (PubMed:2703500).Curated1
Sequence conflicti86T → A in AAA40426 (PubMed:3346244).Curated1
Sequence conflicti86T → A in AAA40429 (PubMed:3346244).Curated1
Sequence conflicti129R → S in AAA37797 (PubMed:2703500).Curated1
Sequence conflicti129R → S in AAA40426 (PubMed:3346244).Curated1
Sequence conflicti129R → S in AAA40429 (PubMed:3346244).Curated1
Sequence conflicti133T → A in AAA37797 (PubMed:2703500).Curated1
Sequence conflicti133T → A in AAA40426 (PubMed:3346244).Curated1
Sequence conflicti133T → A in AAA40429 (PubMed:3346244).Curated1
Sequence conflicti296L → Q in AAA40426 (PubMed:3346244).Curated1
Sequence conflicti296L → Q in AAA40429 (PubMed:3346244).Curated1
Sequence conflicti306V → G in AAA40426 (PubMed:3346244).Curated1
Sequence conflicti306V → G in AAA40429 (PubMed:3346244).Curated1
Sequence conflicti467E → A in AAA37797 (PubMed:2703500).Curated1
Sequence conflicti467E → A in AAA40426 (PubMed:3346244).Curated1
Sequence conflicti467E → A in AAA40429 (PubMed:3346244).Curated1

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.

Similar proteinsi

Entry informationi

Entry nameiCP2A4_MOUSE
AccessioniPrimary (citable) accession number: P15392
Secondary accession number(s): Q91XG2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: October 3, 2012
Last modified: August 30, 2017
This is version 135 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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