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Q64678

- CP1B1_RAT

UniProt

Q64678 - CP1B1_RAT

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Protein
Cytochrome P450 1B1
Gene
Cyp1b1
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, 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.1 Publication

Catalytic activityi

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

Cofactori

Heme group By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei395 – 3951Major determinant of CYP1B1 17beta-estradiol hydroxylation regiospecificity
Metal bindingi470 – 4701Iron (heme axial ligand) By similarity

GO - Molecular functioni

  1. aromatase activity Source: UniProtKB-EC
  2. heme binding Source: UniProtKB
  3. iron ion binding Source: InterPro
  4. monooxygenase activity Source: UniProtKB
  5. oxidoreductase activity Source: RGD
Complete GO annotation...

GO - Biological processi

  1. DNA modification Source: RGD
  2. adrenal gland development Source: RGD
  3. arachidonic acid metabolic process Source: UniProtKB
  4. benzene-containing compound metabolic process Source: RGD
  5. blood vessel morphogenesis Source: UniProtKB
  6. cell adhesion Source: UniProtKB
  7. cellular aromatic compound metabolic process Source: RGD
  8. cellular response to cAMP Source: RGD
  9. cellular response to cortisol stimulus Source: RGD
  10. cellular response to hydrogen peroxide Source: UniProtKB
  11. cellular response to luteinizing hormone stimulus Source: RGD
  12. cellular response to progesterone stimulus Source: RGD
  13. cellular response to tumor necrosis factor Source: RGD
  14. collagen fibril organization Source: UniProtKB
  15. endothelial cell migration Source: UniProtKB
  16. estrogen metabolic process Source: RGD
  17. estrous cycle phase Source: RGD
  18. ganglion development Source: RGD
  19. intrinsic apoptotic signaling pathway in response to oxidative stress Source: UniProtKB
  20. male gonad development Source: RGD
  21. membrane lipid catabolic process Source: UniProtKB
  22. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  23. negative regulation of cell adhesion mediated by integrin Source: UniProtKB
  24. negative regulation of cell migration Source: UniProtKB
  25. negative regulation of cell proliferation Source: UniProtKB
  26. nitric oxide biosynthetic process Source: UniProtKB
  27. positive regulation of DNA biosynthetic process Source: RGD
  28. positive regulation of JAK-STAT cascade Source: UniProtKB
  29. positive regulation of angiogenesis Source: UniProtKB
  30. positive regulation of apoptotic process Source: RGD
  31. positive regulation of gene expression involved in extracellular matrix organization Source: UniProtKB
  32. positive regulation of reactive oxygen species metabolic process Source: RGD
  33. positive regulation of smooth muscle cell migration Source: RGD
  34. positive regulation of translation Source: RGD
  35. positive regulation vascular endothelial growth factor production Source: UniProtKB
  36. regulation of reactive oxygen species metabolic process Source: UniProtKB
  37. response to arsenic-containing substance Source: RGD
  38. response to dexamethasone Source: RGD
  39. response to estradiol Source: RGD
  40. response to follicle-stimulating hormone Source: RGD
  41. response to indole-3-methanol Source: RGD
  42. response to nutrient Source: RGD
  43. response to organic cyclic compound Source: RGD
  44. response to organic substance Source: RGD
  45. response to steroid hormone Source: RGD
  46. response to toxic substance Source: RGD
  47. retinal blood vessel morphogenesis Source: UniProtKB
  48. retinal metabolic process Source: UniProtKB
  49. retinol metabolic process Source: UniProtKB
  50. steroid metabolic process Source: UniProtKB
  51. trabecular meshwork development Source: UniProtKB
  52. xenobiotic metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_198836. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_198844. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 1B1 (EC:1.14.14.1)
Alternative name(s):
CYPIB1
Cytochrome P450RAP
Gene namesi
Name:Cyp1b1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2460. Cyp1b1.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi395 – 3951L → V: Shifts the 4OH E2:2OH E2 hydroxylation ratio from 0.38 to 1.8. Has the 4OH-hydroxylation specificity of the human enzyme. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 543543Cytochrome P450 1B1
PRO_0000051662Add
BLAST

Expressioni

Inductioni

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).3 Publications

Gene expression databases

GenevestigatoriQ64678.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000058711.

Structurei

3D structure databases

ProteinModelPortaliQ64678.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.

Phylogenomic databases

eggNOGiNOG266486.
HOGENOMiHOG000036991.
HOVERGENiHBG106944.
InParanoidiQ64678.
KOiK07410.
PhylomeDBiQ64678.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q64678-1 [UniParc]FASTAAdd to Basket

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MATSLSADSP QQLSSLSTQQ TILLLLVSVL AIVHLGQWLL RQWRRKPWSS    50
PPGPFPWPLI GNAASVGRAS HLYFARLARR YGDVFQIRLG SCPVVVLNGE 100
SAIHQALVQQ GGVFADRPPF ASFRVVSGGR SLAFGHYSER WKERRRAAYG 150
TMRAFSTRHP RSRGLLEGHA LGEARELVAV LVRRCAGGAC LDPTQPIIVA 200
VANVMSAVCF GCRYNHDDAE FLELLSHNEE FGRTVGAGSL VDVMPWLQLF 250
PNPVRTIFRE FEQINRNFSN FVLDKFLRHR ESLVPGAAPR DMMDAFILSA 300
EKKATGDPGD SPSGLDLEDV PATITDIFGA SQDTLSTALL WLLILFTRYP 350
DVQARVQAEL DQVVGRDRLP CMSDQPNLPY VMAFLYESMR FTSFLPVTLP 400
HATTANTFVL GYYIPKNTVV FVNQWSVNHD PAKWSNPEDF DPARFLDKDG 450
FINKALASSV MIFSVGKRRC IGEELSKTLL FLFISILAHQ CNFKANQNEP 500
SNMSFSYGLS IKPKSFKIHV SLRESMKLLD SAVEKLQAEE ACQ 543
Length:543
Mass (Da):60,557
Last modified:November 1, 1996 - v1
Checksum:i8D144B0000D5F095
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X83867 mRNA. Translation: CAA58748.1.
U09540 mRNA. Translation: AAA79864.1.
PIRiI48130.
RefSeqiNP_037072.1. NM_012940.2.
UniGeneiRn.10125.

Genome annotation databases

GeneIDi25426.
KEGGirno:25426.
UCSCiRGD:2460. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X83867 mRNA. Translation: CAA58748.1 .
U09540 mRNA. Translation: AAA79864.1 .
PIRi I48130.
RefSeqi NP_037072.1. NM_012940.2.
UniGenei Rn.10125.

3D structure databases

ProteinModelPortali Q64678.
ModBasei Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000058711.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25426.
KEGGi rno:25426.
UCSCi RGD:2460. rat.

Organism-specific databases

CTDi 1545.
RGDi 2460. Cyp1b1.

Phylogenomic databases

eggNOGi NOG266486.
HOGENOMi HOG000036991.
HOVERGENi HBG106944.
InParanoidi Q64678.
KOi K07410.
PhylomeDBi Q64678.

Enzyme and pathway databases

Reactomei REACT_198836. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_198844. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).

Miscellaneous databases

NextBioi 606603.
PROi Q64678.

Gene expression databases

Genevestigatori Q64678.

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.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PRINTSi PR00463. EP450I.
PR00385. P450.
SUPFAMi SSF48264. SSF48264. 1 hit.
PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiCP1B1_RAT
AccessioniPrimary (citable) accession number: Q64678
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: September 3, 2014
This is version 110 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

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