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Protein

Cytochrome P450 1B1

Gene

Cyp1b1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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.6 Publications

Catalytic activityi

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

Cofactori

hemeBy similarity

Enzyme regulationi

Activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibited by 12-O-Tetradecanoylphorbol-13-acetate and PRKCB.1 Publication

Kineticsi

kcat is 0.04 min(-1) for retinol, 0.08 min(-1) for retinal, 1.24 min(-1) for 7,12-dimethyltetraphene, 0.13 min(-1) for arachidonic acid.

  1. KM=392.2 µM for retinol1 Publication
  2. KM=153.9 µM for retinal1 Publication
  3. KM=138.9 µM for 7,12-dimethyltetraphene1 Publication
  4. KM=500.0 µM for arachidonic acid1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi470 – 4701Iron (heme axial ligand)By similarity

    GO - Molecular functioni

    GO - Biological processi

    • angiogenesis Source: MGI
    • arachidonic acid metabolic process Source: UniProtKB
    • blood vessel morphogenesis Source: UniProtKB
    • cell adhesion Source: UniProtKB
    • cellular aromatic compound metabolic process Source: MGI
    • cellular response to hydrogen peroxide Source: UniProtKB
    • cellular response to organic cyclic compound Source: MGI
    • collagen fibril organization Source: UniProtKB
    • endothelial cell-cell adhesion Source: MGI
    • endothelial cell migration Source: UniProtKB
    • estrogen metabolic process Source: UniProtKB
    • intrinsic apoptotic signaling pathway in response to oxidative stress Source: UniProtKB
    • membrane lipid catabolic process Source: UniProtKB
    • negative regulation of cell adhesion mediated by integrin Source: UniProtKB
    • negative regulation of cell migration Source: UniProtKB
    • negative regulation of cell proliferation Source: UniProtKB
    • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    • nitric oxide biosynthetic process Source: UniProtKB
    • positive regulation of angiogenesis Source: UniProtKB
    • positive regulation of apoptotic process Source: UniProtKB
    • positive regulation of JAK-STAT cascade Source: UniProtKB
    • positive regulation of vascular endothelial growth factor production Source: UniProtKB
    • regulation of reactive oxygen species metabolic process Source: UniProtKB
    • response to toxic substance Source: MGI
    • retinal blood vessel morphogenesis Source: UniProtKB
    • retinal metabolic process Source: UniProtKB
    • retina vasculature development in camera-type eye Source: MGI
    • retinol metabolic process Source: UniProtKB
    • steroid metabolic process Source: UniProtKB
    • toxin metabolic process Source: MGI
    • trabecular meshwork development Source: UniProtKB
    • xenobiotic metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_281686. Endogenous sterols.
    REACT_295859. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    REACT_300263. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 1B1 (EC:1.14.14.1)
    Alternative name(s):
    CYPIB1
    Cytochrome P450CMEF
    Short name:
    Cytochrome P450EF
    Gene namesi
    Name:Cyp1b1
    Synonyms:Cyp1-b1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 17

    Organism-specific databases

    MGIiMGI:88590. Cyp1b1.

    Subcellular locationi

    GO - Cellular componenti

    • endoplasmic reticulum membrane Source: UniProtKB-SubCell
    • mitochondrion Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome, Mitochondrion

    Pathology & Biotechi

    Disruption phenotypei

    Severe ocular drainage structure abnormalities, significant elevated intraocular pressure.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 543543Cytochrome P450 1B1PRO_0000051661Add
    BLAST

    Proteomic databases

    MaxQBiQ64429.
    PaxDbiQ64429.
    PRIDEiQ64429.

    PTM databases

    PhosphoSiteiQ64429.

    Expressioni

    Tissue specificityi

    Constitutively expressed in retinal, heart and kidney pericytes cells.1 Publication

    Inductioni

    By polycyclic aromatic hydrocarbons (PAH) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).1 Publication

    Gene expression databases

    BgeeiQ64429.
    ExpressionAtlasiQ64429. baseline and differential.
    GenevestigatoriQ64429.

    Structurei

    3D structure databases

    ProteinModelPortaliQ64429.
    SMRiQ64429. Positions 68-530.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00760000118992.
    HOGENOMiHOG000036991.
    HOVERGENiHBG106944.
    InParanoidiQ64429.
    KOiK07410.
    OMAiNEPSKMS.
    OrthoDBiEOG7RBZ85.
    TreeFamiTF105095.

    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.

    Q64429-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MATSLSADSP QQLSSLSTQQ TTLLLLFSVL AAVHLGQWLL RQWQRKPWSS
    60 70 80 90 100
    PPGPFPWPLI GNAAAVGQAS HLYFARLARR YGDVFQIRLG SCPVVVLNGE
    110 120 130 140 150
    SAIHQALVQQ GSIFADRPPF ASFRVVSGGR SLAFGHYSEH WKTQRRSAYS
    160 170 180 190 200
    TMRAFSTRHP RSRGLLEGHA LAEARELVAV LVRRCAGGAF LDPTQPVIVA
    210 220 230 240 250
    VANVMSAVCF GCRYNHDDAE FLELLSHNEE FGRTVGAGSL VDVLPWLQLF
    260 270 280 290 300
    PNPVRTTFRK FEQLNRNFSN FVLDKFLRHR ESLVPGAAPR DMTDAFILSA
    310 320 330 340 350
    EKKASGAPGD DSSGLDLEDV PATITDIFGA SQDTLSTALL WLLILFTRYP
    360 370 380 390 400
    DVQARVQAEL DQVVGRDRLP CMSDQPNLPY VMAFLYESMR FSSFLPVTIP
    410 420 430 440 450
    HATTANTFVL GYYIPKNTVV FVNQWSVNHD PAKWPNPEDF DPARFLDKDG
    460 470 480 490 500
    FINKALASSV MIFSVGKRRC IGEELSKMLL FLFISILAHQ CNFKANQNES
    510 520 530 540
    SNMSFSYGLT IKPKSFRIHV SLRESMELLD NAVKKLQTEE GCK
    Length:543
    Mass (Da):60,537
    Last modified:July 27, 2011 - v3
    Checksum:i7C89B4312CB5BC4A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti195 – 1951Q → P in CAA55205 (PubMed:8195121).Curated
    Sequence conflicti307 – 3071A → D in CAA55205 (PubMed:8195121).Curated
    Sequence conflicti328 – 3281F → G in CAA55205 (PubMed:8195121).Curated
    Sequence conflicti457 – 4571A → T in CAA55205 (PubMed:8195121).Curated
    Sequence conflicti516 – 5161F → V in CAA55205 (PubMed:8195121).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U03283 mRNA. Translation: AAC52141.1.
    X78445 mRNA. Translation: CAA55205.1.
    AK137461 mRNA. Translation: BAE23362.1.
    CH466537 Genomic DNA. Translation: EDL38490.1.
    U02479 mRNA. Translation: AAC52131.1.
    CCDSiCCDS28986.1.
    PIRiA53790.
    RefSeqiNP_034124.1. NM_009994.1.
    UniGeneiMm.214016.

    Genome annotation databases

    EnsembliENSMUST00000024894; ENSMUSP00000024894; ENSMUSG00000024087.
    GeneIDi13078.
    KEGGimmu:13078.
    UCSCiuc008dqc.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U03283 mRNA. Translation: AAC52141.1.
    X78445 mRNA. Translation: CAA55205.1.
    AK137461 mRNA. Translation: BAE23362.1.
    CH466537 Genomic DNA. Translation: EDL38490.1.
    U02479 mRNA. Translation: AAC52131.1.
    CCDSiCCDS28986.1.
    PIRiA53790.
    RefSeqiNP_034124.1. NM_009994.1.
    UniGeneiMm.214016.

    3D structure databases

    ProteinModelPortaliQ64429.
    SMRiQ64429. Positions 68-530.
    ModBaseiSearch...
    MobiDBiSearch...

    PTM databases

    PhosphoSiteiQ64429.

    Proteomic databases

    MaxQBiQ64429.
    PaxDbiQ64429.
    PRIDEiQ64429.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000024894; ENSMUSP00000024894; ENSMUSG00000024087.
    GeneIDi13078.
    KEGGimmu:13078.
    UCSCiuc008dqc.1. mouse.

    Organism-specific databases

    CTDi1545.
    MGIiMGI:88590. Cyp1b1.

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00760000118992.
    HOGENOMiHOG000036991.
    HOVERGENiHBG106944.
    InParanoidiQ64429.
    KOiK07410.
    OMAiNEPSKMS.
    OrthoDBiEOG7RBZ85.
    TreeFamiTF105095.

    Enzyme and pathway databases

    ReactomeiREACT_281686. Endogenous sterols.
    REACT_295859. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    REACT_300263. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).

    Miscellaneous databases

    NextBioi283028.
    PROiQ64429.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ64429.
    ExpressionAtlasiQ64429. baseline and differential.
    GenevestigatoriQ64429.

    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]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "cDNA cloning, sequence analysis, and induction by aryl hydrocarbons of a murine cytochrome P450 gene, Cyp1b1."
      Shen Z., Liu J., Wells R.L., Elkind M.M.
      DNA Cell Biol. 13:763-769(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C3H.
    2. "Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P-450s. Cloning, sequence determination, and tissue expression."
      Savas U., Bhattacharyya K.K., Christou M., Alexander D.L., Jefcoate C.R.
      J. Biol. Chem. 269:14905-14911(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C3H.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Bone.
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Identification of a cytochrome P450 gene by reverse transcription-PCR using degenerate primers containing inosine."
      Shen Z., Wells R.L., Liu J., Elkind M.M.
      Proc. Natl. Acad. Sci. U.S.A. 90:11483-11487(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 361-466.
    6. "Regulation of cytochrome P4501B1 (CYP1B1) in mouse embryo fibroblast (C3H10T1/2) cells by protein kinase C (PKC)."
      Ikegwuonu F.I., Christou M., Jefcoate C.R.
      Biochem. Pharmacol. 57:619-630(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    7. "Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1."
      Choudhary D., Jansson I., Stoilov I., Sarfarazi M., Schenkman J.B.
      Drug Metab. Dispos. 32:840-847(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    8. "CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression."
      Tang Y., Scheef E.A., Wang S., Sorenson C.M., Marcus C.B., Jefcoate C.R., Sheibani N.
      Blood 113:744-754(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN VASCULAR DEVELOPMENT AND ANGIOGENESIS.
    9. "CYP1B1 and endothelial nitric oxide synthase combine to sustain proangiogenic functions of endothelial cells under hyperoxic stress."
      Tang Y., Scheef E.A., Gurel Z., Sorenson C.M., Jefcoate C.R., Sheibani N.
      Am. J. Physiol. 298:C665-C678(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ANGIOGENESIS.
    10. Cited for: SUBCELLULAR LOCATION.
    11. "Lack of Cyp1b1 promotes the proliferative and migratory phenotype of perivascular supporting cells."
      Palenski T.L., Sorenson C.M., Jefcoate C.R., Sheibani N.
      Lab. Invest. 93:646-662(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN VASCULAR HOMEOSTASIS, TISSUE SPECIFICITY, INDUCTION.
    12. "Cyp1b1 mediates periostin regulation of trabecular meshwork development by suppression of oxidative stress."
      Zhao Y., Wang S., Sorenson C.M., Teixeira L., Dubielzig R.R., Peters D.M., Conway S.J., Jefcoate C.R., Sheibani N.
      Mol. Cell. Biol. 33:4225-4240(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN TRABECULAR MESHWORK DEVELOPMENT, DISRUPTION PHENOTYPE.
    13. "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: FUNCTION IN ESTROGEN METABOLISM.

    Entry informationi

    Entry nameiCP1B1_MOUSE
    AccessioniPrimary (citable) accession number: Q64429
    Secondary accession number(s): Q3UVA8, Q60593, Q64461
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: July 27, 2011
    Last modified: May 27, 2015
    This is version 128 of the entry and version 3 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. 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.