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Q64678

- CP1B1_RAT

UniProt

Q64678 - CP1B1_RAT

Protein

Cytochrome P450 1B1

Gene

Cyp1b1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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

    GO - Biological processi

    1. adrenal gland development Source: RGD
    2. arachidonic acid metabolic process Source: UniProtKB
    3. benzene-containing compound metabolic process Source: RGD
    4. blood vessel morphogenesis Source: UniProtKB
    5. cell adhesion Source: UniProtKB
    6. cellular aromatic compound metabolic process Source: RGD
    7. cellular response to cAMP Source: RGD
    8. cellular response to cortisol stimulus Source: RGD
    9. cellular response to hydrogen peroxide Source: UniProtKB
    10. cellular response to luteinizing hormone stimulus Source: RGD
    11. cellular response to progesterone stimulus Source: RGD
    12. cellular response to tumor necrosis factor Source: RGD
    13. collagen fibril organization Source: UniProtKB
    14. DNA modification Source: RGD
    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 cell adhesion mediated by integrin Source: UniProtKB
    23. negative regulation of cell migration Source: UniProtKB
    24. negative regulation of cell proliferation Source: UniProtKB
    25. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    26. nitric oxide biosynthetic process Source: UniProtKB
    27. positive regulation of angiogenesis Source: UniProtKB
    28. positive regulation of apoptotic process Source: RGD
    29. positive regulation of DNA biosynthetic process Source: RGD
    30. positive regulation of gene expression involved in extracellular matrix organization Source: UniProtKB
    31. positive regulation of JAK-STAT cascade 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

    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

    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 1B1PRO_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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    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

    « Hide

    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...
    MobiDBi 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: October 1, 2014
    This is version 111 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