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Q64678 (CP1B1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 1B1

EC=1.14.14.1
Alternative name(s):
CYPIB1
Cytochrome P450RAP
Gene names
Name:Cyp1b1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length543 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression. Ref.6

Catalytic activity

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

Cofactor

Heme group By similarity.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. Mitochondrion By similarity.

Induction

By polycyclic aromatic hydrocarbons (PAH), beta-naphthoflavone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Up-regulated by diesel exhaust particles (DEP). Decreased by estradiol (at protein level). Ref.3 Ref.4 Ref.5

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
Mitochondrion
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA modification

Inferred from mutant phenotype PubMed 24025706. Source: RGD

adrenal gland development

Inferred from expression pattern PubMed 10098502. Source: RGD

angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

benzene-containing compound metabolic process

Inferred from direct assay PubMed 9806168. Source: RGD

blood vessel morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cellular aromatic compound metabolic process

Inferred from direct assay Ref.1. Source: RGD

cellular response to cAMP

Inferred from expression pattern PubMed 21389345. Source: RGD

cellular response to cortisol stimulus

Inferred from expression pattern PubMed 8674863. Source: RGD

cellular response to luteinizing hormone stimulus

Inferred from expression pattern PubMed 21389345. Source: RGD

cellular response to progesterone stimulus

Inferred from expression pattern PubMed 8674863. Source: RGD

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 10403529. Source: RGD

estrogen metabolic process

Inferred from direct assay Ref.6. Source: RGD

estrous cycle phase

Inferred from expression pattern PubMed 12223220. Source: RGD

ganglion development

Inferred from expression pattern PubMed 17687037. Source: RGD

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from sequence or structural similarity. Source: UniProtKB

male gonad development

Inferred from expression pattern PubMed 19074971. Source: RGD

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell adhesion mediated by integrin

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of DNA biosynthetic process

Inferred from mutant phenotype PubMed 20439821. Source: RGD

positive regulation of JAK-STAT cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from expression pattern PubMed 18336843. Source: RGD

positive regulation of gene expression involved in extracellular matrix organization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype PubMed 20439821. Source: RGD

positive regulation of smooth muscle cell migration

Inferred from mutant phenotype PubMed 20439821. Source: RGD

positive regulation of translation

Inferred from mutant phenotype PubMed 20439821. Source: RGD

positive regulation vascular endothelial growth factor production

Inferred from sequence or structural similarity. Source: UniProtKB

response to arsenic-containing substance

Inferred from expression pattern PubMed 23999541. Source: RGD

response to dexamethasone

Inferred from expression pattern PubMed 9804617. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 19074971. Source: RGD

response to follicle-stimulating hormone

Inferred from expression pattern PubMed 19074971. Source: RGD

response to indole-3-methanol

Inferred from expression pattern PubMed 11719698. Source: RGD

response to nutrient

Inferred from expression pattern PubMed 11739881. Source: RGD

response to organic cyclic compound

Inferred from expression pattern Ref.1. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 16901605. Source: RGD

response to steroid hormone

Inferred from expression pattern PubMed 12704664. Source: RGD

response to toxic substance

Inferred from expression pattern Ref.2. Source: RGD

steroid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

xenobiotic metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

intracellular membrane-bounded organelle

Inferred from direct assay Ref.1. Source: RGD

nucleus

Inferred from direct assay PubMed 12051558. Source: RGD

   Molecular_functionaromatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

heme binding

Inferred from sequence or structural similarity. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

monooxygenase activity

Inferred from direct assay. Source: RGD

oxidoreductase activity

Inferred from direct assay PubMed 16893557. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 543543Cytochrome P450 1B1
PRO_0000051662

Sites

Metal binding4701Iron (heme axial ligand) By similarity
Site3951Major determinant of CYP1B1 17beta-estradiol hydroxylation regiospecificity

Experimental info

Mutagenesis3951L → V: Shifts the 4OH E2:2OH E2 hydroxylation ratio from 0.38 to 1.8. Has the 4OH-hydroxylation specificity of the human enzyme. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Q64678 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 8D144B0000D5F095

FASTA54360,557
        10         20         30         40         50         60 
MATSLSADSP QQLSSLSTQQ TILLLLVSVL AIVHLGQWLL RQWRRKPWSS PPGPFPWPLI 

        70         80         90        100        110        120 
GNAASVGRAS HLYFARLARR YGDVFQIRLG SCPVVVLNGE SAIHQALVQQ GGVFADRPPF 

       130        140        150        160        170        180 
ASFRVVSGGR SLAFGHYSER WKERRRAAYG TMRAFSTRHP RSRGLLEGHA LGEARELVAV 

       190        200        210        220        230        240 
LVRRCAGGAC LDPTQPIIVA VANVMSAVCF GCRYNHDDAE FLELLSHNEE FGRTVGAGSL 

       250        260        270        280        290        300 
VDVMPWLQLF PNPVRTIFRE FEQINRNFSN FVLDKFLRHR ESLVPGAAPR DMMDAFILSA 

       310        320        330        340        350        360 
EKKATGDPGD SPSGLDLEDV PATITDIFGA SQDTLSTALL WLLILFTRYP DVQARVQAEL 

       370        380        390        400        410        420 
DQVVGRDRLP CMSDQPNLPY VMAFLYESMR FTSFLPVTLP HATTANTFVL GYYIPKNTVV 

       430        440        450        460        470        480 
FVNQWSVNHD PAKWSNPEDF DPARFLDKDG FINKALASSV MIFSVGKRRC IGEELSKTLL 

       490        500        510        520        530        540 
FLFISILAHQ CNFKANQNEP SNMSFSYGLS IKPKSFKIHV SLRESMKLLD SAVEKLQAEE 


ACQ 

« Hide

References

[1]"Identification of a rat adrenal cytochrome P450 active in polycyclic hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue-specific pattern of hormonal and aryl hydrocarbon receptor-linked regulation."
Bhattacharyya K.K., Brake P.B., Eltom S.E., Otto S.A., Jefcoate C.R.
J. Biol. Chem. 270:11595-11602(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Strain: Sprague-Dawley.
[2]"Rat CYP1B1: an adrenal cytochrome P450 that exhibits sex-dependent expression in livers and kidneys of TCDD-treated animals."
Walker N.J., Gastel J.A., Costa L.T., Clark G.C., Lucier G.W., Sutter T.R.
Carcinogenesis 16:1319-1327(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Liver.
[3]"Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels."
Jacob A., Hartz A.M., Potin S., Coumoul X., Yousif S., Scherrmann J.M., Bauer B., Decleves X.
Fluids Barriers CNS 8:23-23(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[4]"Estradiol-mediated suppression of CYP1B1 expression in mouse MA-10 Leydig cells is independent of protein kinase A and estrogen receptor."
Deb S., Tai J.K., Leung G.S., Chang T.K., Bandiera S.M.
Mol. Cell. Biochem. 358:387-395(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[5]"The effect of aryl hydrocarbon receptor ligands on the expression of polymerase (DNA directed) kappa (Polkappa), polymerase RNA II (DNA directed) polypeptide A (PolR2a), CYP1B1 and CYP1A1 genes in rat liver."
Brauze D., Rawluszko A.A.
Environ. Toxicol. Pharmacol. 34:819-825(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[6]"Specificity determinants of CYP1B1 estradiol hydroxylation."
Nishida C.R., Everett S., Ortiz de Montellano P.R.
Mol. Pharmacol. 84:451-458(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-395, FUNCTION IN ESTROGEN METABOLISM.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X83867 mRNA. Translation: CAA58748.1.
U09540 mRNA. Translation: AAA79864.1.
PIRI48130.
RefSeqNP_037072.1. NM_012940.2.
UniGeneRn.10125.

3D structure databases

ProteinModelPortalQ64678.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000058711.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25426.
KEGGrno:25426.
UCSCRGD:2460. rat.

Organism-specific databases

CTD1545.
RGD2460. Cyp1b1.

Phylogenomic databases

eggNOGNOG266486.
HOGENOMHOG000036991.
HOVERGENHBG106944.
InParanoidQ64678.
KOK07410.
PhylomeDBQ64678.

Gene expression databases

GenevestigatorQ64678.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio606603.
PROQ64678.

Entry information

Entry nameCP1B1_RAT
AccessionPrimary (citable) accession number: Q64678
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families