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Protein

Cytochrome P450 2D4

Gene

Cyp2d4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Catalytic activityi

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

Cofactori

hemeBy similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi446 – 4461Iron (heme axial ligand)By similarity

GO - Molecular functioni

  1. arachidonic acid epoxygenase activity Source: GO_Central
  2. arachidonic acid monooxygenase activity Source: RGD
  3. aromatase activity Source: UniProtKB-EC
  4. heme binding Source: GO_Central
  5. iron ion binding Source: InterPro
  6. monooxygenase activity Source: RGD
  7. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Source: GO_Central
  8. oxygen binding Source: GO_Central
  9. steroid 21-monooxygenase activity Source: RGD
  10. steroid hydroxylase activity Source: GO_Central

GO - Biological processi

  1. arachidonic acid metabolic process Source: RGD
  2. dopamine biosynthetic process Source: RGD
  3. dopamine metabolic process Source: RGD
  4. drug metabolic process Source: RGD
  5. exogenous drug catabolic process Source: GO_Central
  6. female pregnancy Source: RGD
  7. oxidation-reduction process Source: GO_Central
  8. response to organic substance Source: RGD
  9. xenobiotic metabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

SABIO-RKP13108.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 2D4 (EC:1.14.14.1)
Alternative name(s):
CYPIID4
Cytochrome P450-CMF3
Cytochrome P450-DB4
Debrisoquine 4-hydroxylase
Gene namesi
Name:Cyp2d4
Synonyms:Cyp2d-4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620640. Cyp2d4.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  3. intracellular membrane-bounded organelle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 500500Cytochrome P450 2D4PRO_0000051730Add
BLAST

Proteomic databases

PaxDbiP13108.
PRIDEiP13108.

Expressioni

Inductioni

P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.

Gene expression databases

GenevestigatoriP13108.

Interactioni

Structurei

3D structure databases

ProteinModelPortaliP13108.
SMRiP13108. Positions 37-500.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiCOG2124.
HOGENOMiHOG000036991.
HOVERGENiHBG015789.
InParanoidiP13108.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR01686. EP450ICYP2D.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P13108-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRMPTGSELW PIAIFTIIFL LLVDLMHRRQ RWTSRYPPGP VPWPVLGNLL
60 70 80 90 100
QIDFQNMPAG FQKLRCRFGD LFSLQLAFES VVVLNGLPAL REALVKYSED
110 120 130 140 150
TADRPPLHFN DQSGFGPRSQ GVVLARYGPA WRQQRRFSVS TFRHFGLGKK
160 170 180 190 200
SLEQWVTEEA RCLCAAFADH SGFPFSPNTL LDKAVCNVIA SLLFACRFEY
210 220 230 240 250
NDPRFIRLLD LLKDTLEEES GFLPMLLNVF PMLLHIPGLL GKVFSGKKAF
260 270 280 290 300
VAMLDELLTE HKVTWDPAQP PRDLTDAFLA EVEKAKGNPE SSFNDENLRV
310 320 330 340 350
VVADLFMAGM VTTSTTLTWA LLFMILHPDV QCRVQQEIDE VIGQVRRPEM
360 370 380 390 400
ADQARMPFTN AVIHEVQRFA DILPLGVPHK TSRDIEVQGF LIPKGTTLIT
410 420 430 440 450
NLSSVLKDET VWEKPLRFHP EHFLDAQGNF VKHEAFMPFS AGRRACLGEP
460 470 480 490 500
LARMELFLFF TCLLQRFSFS VPTGQPRPSD YGIFGALTTP RPYQLCASPR
Length:500
Mass (Da):56,698
Last modified:March 1, 1992 - v2
Checksum:i505D29B2C0BB1F7E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti473 – 4731T → A in BAA23125 (PubMed:9434752).Curated
Sequence conflicti480 – 4801D → N in BAA23125 (PubMed:9434752).Curated
Sequence conflicti483 – 4831I → V in BAA23125 (PubMed:9434752).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52029 Genomic DNA. Translation: CAA36271.1.
AB008425 mRNA. Translation: BAA23125.1.
M22331 mRNA. Translation: AAA41052.1.
PIRiS16873. D31579.
UniGeneiRn.26060.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52029 Genomic DNA. Translation: CAA36271.1.
AB008425 mRNA. Translation: BAA23125.1.
M22331 mRNA. Translation: AAA41052.1.
PIRiS16873. D31579.
UniGeneiRn.26060.

3D structure databases

ProteinModelPortaliP13108.
SMRiP13108. Positions 37-500.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiP13108.
ChEMBLiCHEMBL2304403.

Proteomic databases

PaxDbiP13108.
PRIDEiP13108.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi620640. Cyp2d4.

Phylogenomic databases

eggNOGiCOG2124.
HOGENOMiHOG000036991.
HOVERGENiHBG015789.
InParanoidiP13108.

Enzyme and pathway databases

SABIO-RKP13108.

Gene expression databases

GenevestigatoriP13108.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR01686. EP450ICYP2D.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The rat P450 IID subfamily: complete sequences of four closely linked genes and evidence that gene conversions maintained sequence homogeneity at the heme-binding region of the cytochrome P450 active site."
    Matsunaga E., Umeno M., Gonzalez F.J.
    J. Mol. Evol. 30:155-169(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. "Expression of four rat CYP2D isoforms in Saccharomyces cerevisiae and their catalytic specificity."
    Wan J., Imaoka S., Chow T., Hiroi T., Yabusaki Y., Funae Y.
    Arch. Biochem. Biophys. 348:383-390(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "Four species of cDNAs for cytochrome P450 isozymes immunorelated to P450C-M/F encode for members of P450IID subfamily, increasing the number of members within the subfamily."
    Ishida N., Tawaragi Y., Inuzuka C., Sugita O., Kubota I., Nakazato H., Noguchi T., Sassa S.
    Biochem. Biophys. Res. Commun. 156:681-688(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 177-500.

Entry informationi

Entry nameiCP2D4_RAT
AccessioniPrimary (citable) accession number: P13108
Secondary accession number(s): O35107
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: March 1, 1992
Last modified: February 4, 2015
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.