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P00185

- CP1A1_RAT

UniProt

P00185 - CP1A1_RAT

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Protein

Cytochrome P450 1A1

Gene

Cyp1a1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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
Binding sitei228 – 2281SubstrateBy similarity
Metal bindingi461 – 4611Iron (heme axial ligand)

GO - Molecular functioni

  1. aromatase activity Source: UniProtKB-EC
  2. catalytic activity Source: RGD
  3. demethylase activity Source: RGD
  4. enzyme binding Source: RGD
  5. flavonoid 3'-monooxygenase activity Source: RGD
  6. heme binding Source: InterPro
  7. iron ion binding Source: InterPro
  8. monooxygenase activity Source: RGD
  9. oxidoreductase activity Source: RGD
  10. oxidoreductase activity, acting on diphenols and related substances as donors Source: RGD
  11. steroid hydroxylase activity Source: RGD
  12. vitamin D 24-hydroxylase activity Source: Ensembl

GO - Biological processi

  1. 9-cis-retinoic acid biosynthetic process Source: RGD
  2. aging Source: RGD
  3. amine metabolic process Source: Ensembl
  4. camera-type eye development Source: RGD
  5. cell proliferation Source: RGD
  6. cellular response to organic cyclic compound Source: Ensembl
  7. coumarin metabolic process Source: RGD
  8. demethylation Source: GOC
  9. developmental process Source: RGD
  10. dibenzo-p-dioxin catabolic process Source: RGD
  11. dibenzo-p-dioxin metabolic process Source: RGD
  12. digestive tract development Source: RGD
  13. drug metabolic process Source: Ensembl
  14. embryo development ending in birth or egg hatching Source: RGD
  15. flavonoid metabolic process Source: RGD
  16. hepatocyte differentiation Source: RGD
  17. hydrogen peroxide biosynthetic process Source: Ensembl
  18. insecticide metabolic process Source: RGD
  19. liver development Source: RGD
  20. maternal process involved in parturition Source: RGD
  21. porphyrin-containing compound metabolic process Source: RGD
  22. positive regulation of G1/S transition of mitotic cell cycle Source: RGD
  23. response to antibiotic Source: RGD
  24. response to arsenic-containing substance Source: RGD
  25. response to drug Source: RGD
  26. response to food Source: RGD
  27. response to herbicide Source: RGD
  28. response to hyperoxia Source: RGD
  29. response to hypoxia Source: RGD
  30. response to immobilization stress Source: RGD
  31. response to iron(III) ion Source: RGD
  32. response to lipopolysaccharide Source: RGD
  33. response to nematode Source: RGD
  34. response to organic cyclic compound Source: RGD
  35. response to organic substance Source: RGD
  36. response to virus Source: RGD
  37. response to vitamin A Source: RGD
  38. response to wounding Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_196408. PPARA activates gene expression.
REACT_198836. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_198844. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
REACT_261605. Xenobiotics.
SABIO-RKP00185.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 1A1 (EC:1.14.14.1)
Short name:
CYP1A1
Alternative name(s):
CYPIA1
Cytochrome P450-C
Cytochrome P450MT2
Cleaved into the following 2 chains:
Gene namesi
Name:Cyp1a1
Synonyms:Cyp1a-1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 8

Organism-specific databases

RGDi2458. Cyp1a1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. endoplasmic reticulum Source: UniProtKB-KW
  3. intracellular membrane-bounded organelle Source: RGD
  4. membrane Source: UniProtKB-KW
  5. mitochondrion Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Microsome, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi32 – 332VT → AI: No proteolytic cleavage. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini2 – 524523Cytochrome P450 1A1PRO_0000003564Add
BLAST
Chaini5 – 524520Cytochrome P450MT2APRO_0000003565Add
BLAST
Chaini33 – 524492Cytochrome P450MT2BPRO_0000003566Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi71 – 711O-linked (GlcNAc)1 Publication

Post-translational modificationi

Two forms; MT2A (long form) and MT2B (short form); are produced by NH2-terminal proteolytic cleavage. This cleavage activates a cryptic mitochondrial targeting signal.

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP00185.
PRIDEiP00185.

Expressioni

Tissue specificityi

Liver.

Inductioni

By 3-methylcholanthrene (3MC) and beta-naphthoflavone (BNF).

Gene expression databases

GenevestigatoriP00185.

Interactioni

Protein-protein interaction databases

BioGridi246477. 2 interactions.
STRINGi10116.ENSRNOP00000026473.

Structurei

3D structure databases

ProteinModelPortaliP00185.
SMRiP00185. Positions 37-513.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni33 – 4412Mitochondrial targeting signalAdd
BLAST

Domaini

Contains a chimeric signal that facilitates targeting of the protein to both the endoplasmic reticulum and mitochondria. A 12 amino acid sequence between 33 and 44 functions as a putative mitochondrial-targeting signal. The removal of the first 4- or 32-amino acid residues from the intact protein positions the mitochondrial targeting signal for efficient binding to the mitochondrial import receptors. The membrane-free P4501A1 seems to be more sensitive to proteolysis.

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118992.
HOVERGENiHBG106944.
InParanoidiP00185.
KOiK07408.
OMAiKVITIVF.
OrthoDBiEOG7RBZ85.
PhylomeDBiP00185.
TreeFamiTF105095.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008066. Cyt_P450_E_grp-I_CYP1.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR01683. EP450ICYP1A.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P00185-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPSVYGFPAF TSATELLLAV TTFCLGFWVV RVTRTWVPKG LKSPPGPWGL
60 70 80 90 100
PFIGHVLTLG KNPHLSLTKL SQQYGDVLQI RIGSTPVVVL SGLNTIKQAL
110 120 130 140 150
VKQGDDFKGR PDLYSFTLIA NGQSMTFNPD SGPLWAARRR LAQNALKSFS
160 170 180 190 200
IASDPTLASS CYLEEHVSKE AEYLISKFQK LMAEVGHFDP FKYLVVSVAN
210 220 230 240 250
VICAICFGRR YDHDDQELLS IVNLSNEFGE VTGSGYPADF IPILRYLPNS
260 270 280 290 300
SLDAFKDLNK KFYSFMKKLI KEHYRTFEKG HIRDITDSLI EHCQDRRLDE
310 320 330 340 350
NANVQLSDDK VITIVFDLFG AGFDTITTAI SWSLMYLVTN PRIQRKIQEE
360 370 380 390 400
LDTVIGRDRQ PRLSDRPQLP YLEAFILETF RHSSFVPFTI PHSTIRDTSL
410 420 430 440 450
NGFYIPKGHC VFVNQWQVNH DQELWGDPNE FRPERFLTSS GTLDKHLSEK
460 470 480 490 500
VILFGLGKRK CIGETIGRLE VFLFLAILLQ QMEFNVSPGE KVDMTPAYGL
510 520
TLKHARCEHF QVQMRSSGPQ HLQA
Length:524
Mass (Da):59,393
Last modified:July 21, 1986 - v1
Checksum:iC766DF8044D598C5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti21 – 222TT → VV AA sequence (PubMed:3041969)Curated
Sequence conflicti53 – 531I → M in CAA25153. (PubMed:6324135)Curated
Sequence conflicti494 – 4941M → S in AAA41025. (PubMed:3838427)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02246 Genomic DNA. Translation: AAA41027.1.
X00469 mRNA. Translation: CAA25153.1.
M26129 Genomic DNA. Translation: AAA41025.1.
PIRiA00185. O4RTMC.
RefSeqiNP_036672.2. NM_012540.2.
XP_006243212.1. XM_006243150.2.
UniGeneiRn.10352.

Genome annotation databases

EnsembliENSRNOT00000026473; ENSRNOP00000026473; ENSRNOG00000019500.
GeneIDi24296.
KEGGirno:24296.
UCSCiRGD:2458. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02246 Genomic DNA. Translation: AAA41027.1 .
X00469 mRNA. Translation: CAA25153.1 .
M26129 Genomic DNA. Translation: AAA41025.1 .
PIRi A00185. O4RTMC.
RefSeqi NP_036672.2. NM_012540.2.
XP_006243212.1. XM_006243150.2.
UniGenei Rn.10352.

3D structure databases

ProteinModelPortali P00185.
SMRi P00185. Positions 37-513.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 246477. 2 interactions.
STRINGi 10116.ENSRNOP00000026473.

Chemistry

BindingDBi P00185.
ChEMBLi CHEMBL2922.

Proteomic databases

PaxDbi P00185.
PRIDEi P00185.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000026473 ; ENSRNOP00000026473 ; ENSRNOG00000019500 .
GeneIDi 24296.
KEGGi rno:24296.
UCSCi RGD:2458. rat.

Organism-specific databases

CTDi 1543.
RGDi 2458. Cyp1a1.

Phylogenomic databases

eggNOGi COG2124.
GeneTreei ENSGT00760000118992.
HOVERGENi HBG106944.
InParanoidi P00185.
KOi K07408.
OMAi KVITIVF.
OrthoDBi EOG7RBZ85.
PhylomeDBi P00185.
TreeFami TF105095.

Enzyme and pathway databases

Reactomei REACT_196408. PPARA activates gene expression.
REACT_198836. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_198844. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
REACT_261605. Xenobiotics.
SABIO-RK P00185.

Miscellaneous databases

NextBioi 602902.
PROi P00185.

Gene expression databases

Genevestigatori P00185.

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.
IPR008066. Cyt_P450_E_grp-I_CYP1.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PRINTSi PR00463. EP450I.
PR01683. EP450ICYP1A.
PR00385. P450.
SUPFAMi SSF48264. SSF48264. 1 hit.
PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Distinct organization of methylcholanthrene- and phenobarbital-inducible cytochrome P-450 genes in the rat."
    Sogawa K., Gotoh O., Kawajiri K., Fujii-Kuriyama Y.
    Proc. Natl. Acad. Sci. U.S.A. 81:5066-5070(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Nucleotide sequence of a full-length cDNA coding for 3-methylcholanthrene-induced rat liver cytochrome P-450MC."
    Yabusaki Y., Shimizu M., Murakami H., Nakamura K., Oeda K., Ohkawa H.
    Nucleic Acids Res. 12:2929-2938(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Amino-terminal sequence and structure of monoclonal antibody immunopurified cytochromes P-450."
    Cheng K.C., Park S.S., Krutzsch H.C., Grantham P.H., Gelboin H.V., Friedman F.K.
    Biochemistry 25:2397-2402(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-26.
  5. "Effect of nutritional imbalances on cytochrome P-450 isozymes in rat liver."
    Amelizad Z., Narbonne J.F., Wolf C.R., Robertson L.W., Oesch F.
    Biochem. Pharmacol. 37:3245-3249(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-22.
  6. "Identification and characterization of cytochrome P4501A1 amino acid residues interacting with a radiolabeled photoaffinity diazido-benzphetamine analogue."
    Cvrk T., Hodek P., Strobel H.W.
    Arch. Biochem. Biophys. 330:142-152(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE.
  7. "Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2."
    Addya S., Anandatheerthavarada H.K., Biswas G., Bhagwat S.V., Mullick J., Avadhani N.G.
    J. Cell Biol. 139:589-599(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 32-VAL-THR-33.
    Strain: Sprague-Dawley.
    Tissue: Liver.
  8. "Discovery and confirmation of O-GlcNAcylated proteins in rat liver mitochondria by combination of mass spectrometry and immunological methods."
    Cao W., Cao J., Huang J., Yao J., Yan G., Xu H., Yang P.
    PLoS ONE 8:E76399-E76399(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT SER-71.

Entry informationi

Entry nameiCP1A1_RAT
AccessioniPrimary (citable) accession number: P00185
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 26, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3