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Protein

Bifunctional cytochrome P450/NADPH--P450 reductase 2

Gene

cypB

Organism
Bacillus subtilis (strain 168)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a fatty acid monooxygenase. Catalyzes hydroxylation of a range of medium to long-chain fatty acids, with a preference for long-chain unsaturated and branched-chain fatty acids over saturated fatty acids. Hydroxylation of myristic acid occurs mainly at the omega-2 and omega-3 positions, in approximately equal proportions. Also displays a NADPH-dependent reductase activity in the C-terminal domain, which allows electron transfer from NADPH to the heme iron of the cytochrome P450 N-terminal domain.2 Publications

Catalytic activityi

RH + [reduced NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.2 Publications
NADPH + n oxidized hemoprotein = NADP+ + n reduced hemoprotein.2 Publications

Cofactori

Protein has several cofactor binding sites:

Kineticsi

kcat is 104 min(-1) for lauric acid hydroxylation. kcat is 5556 min(-1) for myristic acid hydroxylation. kcat is 676 min(-1) for palmitic acid hydroxylation. kcat is 374 min(-1) for stearic acid hydroxylation. kcat is 794 min(-1) for phytanic acid hydroxylation. kcat is 3845 min(-1) for 15-methylpalmitic acid hydroxylation. kcat is 1690 min(-1) for arachidonic acid hydroxylation. kcat is 3520 min(-1) for the reduction of cytochrome c. kcat is 37050 min(-1) for the reduction of ferricyanide.1 Publication

  1. KM=165 µM for lauric acid1 Publication
  2. KM=542 µM for myristic acid1 Publication
  3. KM=337 µM for palmitic acid1 Publication
  4. KM=68.5 µM for stearic acid1 Publication
  5. KM=28.7 µM for phytanic acid1 Publication
  6. KM=68.3 µM for 15-methylpalmitic acid1 Publication
  7. KM=79 µM for arachidonic acid1 Publication
  8. KM=5.1 µM for NADPH1 Publication
  9. KM=2.43 mM for NADH1 Publication
  10. KM=10.9 µM for cytochrome c (in the reductase assay)1 Publication
  11. KM=285 µM for ferricyanide (in the reductase assay)1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi403 – 4031Iron (heme axial ligand)By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi492 – 4965FMNPROSITE-ProRule annotation
    Nucleotide bindingi570 – 60233FMNPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    • aromatase activity Source: UniProtKB-EC
    • fatty acid binding Source: UniProtKB
    • flavin adenine dinucleotide binding Source: UniProtKB
    • FMN binding Source: UniProtKB
    • heme binding Source: UniProtKB
    • iron ion binding Source: InterPro
    • NADPH-hemoprotein reductase activity Source: UniProtKB
    • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Source: UniProtKB

    GO - Biological processi

    • fatty acid oxidation Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Biological processi

    Electron transport, Transport

    Keywords - Ligandi

    FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciBSUB:BSU27160-MONOMER.
    SABIO-RKO08336.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional cytochrome P450/NADPH--P450 reductase 2Curated
    Alternative name(s):
    CYP102A31 Publication
    Fatty acid hydroxylase CypBCurated
    Flavocytochrome P450 102A3Curated
    Including the following 2 domains:
    Cytochrome P450 102A3Curated (EC:1.14.14.12 Publications)
    NADPH--cytochrome P450 reductase (EC:1.6.2.42 Publications)
    Gene namesi
    Name:cypBImported
    Synonyms:cyp102A32 Publications, yrhJ2 Publications
    Ordered Locus Names:BSU27160
    OrganismiBacillus subtilis (strain 168)
    Taxonomic identifieri224308 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesBacillaceaeBacillus
    ProteomesiUP000001570 Componenti: Chromosome

    Organism-specific databases

    GenoListiBSU27160. [Micado]

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi89 – 891F → V: Hydroxylates shorter substrates with higher conversion rates than wild-type, and in contrast to wild-type, is also able to convert medium-chain alkanes and aromatic compounds; when associated with Q-190. 1 Publication
    Mutagenesisi190 – 1901S → Q: Hydroxylates shorter substrates with higher conversion rates than wild-type, and in contrast to wild-type, is also able to convert medium-chain alkanes and aromatic compounds; when associated with V-89. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10541054Bifunctional cytochrome P450/NADPH--P450 reductase 2PRO_0000052207Add
    BLAST

    Proteomic databases

    PaxDbiO08336.

    Expressioni

    Inductioni

    Negatively regulated by the transcriptional repressor FatR (PubMed:11574077) (PubMed:11734890). Is induced by fatty acids such as oleate, linoleate and phytanate, that bind and displace the FatR repressor (PubMed:11734890). Is also induced by palmitate, likely via another mechanism (PubMed:11574077).2 Publications

    Interactioni

    Protein-protein interaction databases

    STRINGi224308.Bsubs1_010100014841.

    Structurei

    3D structure databases

    ProteinModelPortaliO08336.
    SMRiO08336. Positions 29-455, 478-1052.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini486 – 625140Flavodoxin-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini663 – 896234FAD-binding FR-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 475475Cytochrome P4501 PublicationAdd
    BLAST
    Regioni476 – 1053578NADPH--P450 reductase1 PublicationAdd
    BLAST

    Sequence similaritiesi

    In the N-terminal section; belongs to the cytochrome P450 family.Curated
    Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
    Contains 1 flavodoxin-like domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiENOG4107EER. Bacteria.
    COG0369. LUCA.
    HOGENOMiHOG000093545.
    InParanoidiO08336.
    KOiK14338.
    OMAiEDYPACE.
    OrthoDBiEOG63Z73K.
    PhylomeDBiO08336.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    1.20.990.10. 1 hit.
    3.40.50.360. 1 hit.
    InterProiIPR023206. Bifunctional_P450_P450_red.
    IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR003097. FAD-binding_1.
    IPR017927. Fd_Rdtase_FAD-bd.
    IPR001094. Flavdoxin-like.
    IPR008254. Flavodoxin/NO_synth.
    IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
    IPR029039. Flavoprotein-like_dom.
    IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF00667. FAD_binding_1. 1 hit.
    PF00258. Flavodoxin_1. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    PF00067. p450. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000209. Bifunctional_P450_P450R. 1 hit.
    PRINTSiPR00369. FLAVODOXIN.
    PR00371. FPNCR.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    SSF52218. SSF52218. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    PS51384. FAD_FR. 1 hit.
    PS50902. FLAVODOXIN_LIKE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O08336-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKQASAIPQP KTYGPLKNLP HLEKEQLSQS LWRIADELGP IFRFDFPGVS
    60 70 80 90 100
    SVFVSGHNLV AEVCDEKRFD KNLGKGLQKV REFGGDGLFT SWTHEPNWQK
    110 120 130 140 150
    AHRILLPSFS QKAMKGYHSM MLDIATQLIQ KWSRLNPNEE IDVADDMTRL
    160 170 180 190 200
    TLDTIGLCGF NYRFNSFYRD SQHPFITSML RALKEAMNQS KRLGLQDKMM
    210 220 230 240 250
    VKTKLQFQKD IEVMNSLVDR MIAERKANPD ENIKDLLSLM LYAKDPVTGE
    260 270 280 290 300
    TLDDENIRYQ IITFLIAGHE TTSGLLSFAI YCLLTHPEKL KKAQEEADRV
    310 320 330 340 350
    LTDDTPEYKQ IQQLKYIRMV LNETLRLYPT APAFSLYAKE DTVLGGEYPI
    360 370 380 390 400
    SKGQPVTVLI PKLHRDQNAW GPDAEDFRPE RFEDPSSIPH HAYKPFGNGQ
    410 420 430 440 450
    RACIGMQFAL QEATMVLGLV LKHFELINHT GYELKIKEAL TIKPDDFKIT
    460 470 480 490 500
    VKPRKTAAIN VQRKEQADIK AETKPKETKP KHGTPLLVLF GSNLGTAEGI
    510 520 530 540 550
    AGELAAQGRQ MGFTAETAPL DDYIGKLPEE GAVVIVTASY NGAPPDNAAG
    560 570 580 590 600
    FVEWLKELEE GQLKGVSYAV FGCGNRSWAS TYQRIPRLID DMMKAKGASR
    610 620 630 640 650
    LTAIGEGDAA DDFESHRESW ENRFWKETMD AFDINEIAQK EDRPSLSITF
    660 670 680 690 700
    LSEATETPVA KAYGAFEGIV LENRELQTAA STRSTRHIEL EIPAGKTYKE
    710 720 730 740 750
    GDHIGILPKN SRELVQRVLS RFGLQSNHVI KVSGSAHMAH LPMDRPIKVV
    760 770 780 790 800
    DLLSSYVELQ EPASRLQLRE LASYTVCPPH QKELEQLVSD DGIYKEQVLA
    810 820 830 840 850
    KRLTMLDFLE DYPACEMPFE RFLALLPSLK PRYYSISSSP KVHANIVSMT
    860 870 880 890 900
    VGVVKASAWS GRGEYRGVAS NYLAELNTGD AAACFIRTPQ SGFQMPNDPE
    910 920 930 940 950
    TPMIMVGPGT GIAPFRGFIQ ARSVLKKEGS TLGEALLYFG CRRPDHDDLY
    960 970 980 990 1000
    REELDQAEQD GLVTIRRCYS RVENEPKGYV QHLLKQDTQK LMTLIEKGAH
    1010 1020 1030 1040 1050
    IYVCGDGSQM APDVERTLRL AYEAEKAASQ EESAVWLQKL QDQRRYVKDV

    WTGM
    Length:1,054
    Mass (Da):118,676
    Last modified:July 1, 1997 - v1
    Checksum:i705F8E27866CA110
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U93874 Genomic DNA. Translation: AAB80867.1.
    AL009126 Genomic DNA. Translation: CAB14658.1.
    PIRiA69975.
    RefSeqiNP_390594.1. NC_000964.3.
    WP_003246174.1. NZ_JNCM01000036.1.

    Genome annotation databases

    EnsemblBacteriaiCAB14658; CAB14658; BSU27160.
    GeneIDi937585.
    KEGGibsu:BSU27160.
    PATRICi18977286. VBIBacSub10457_2832.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U93874 Genomic DNA. Translation: AAB80867.1.
    AL009126 Genomic DNA. Translation: CAB14658.1.
    PIRiA69975.
    RefSeqiNP_390594.1. NC_000964.3.
    WP_003246174.1. NZ_JNCM01000036.1.

    3D structure databases

    ProteinModelPortaliO08336.
    SMRiO08336. Positions 29-455, 478-1052.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi224308.Bsubs1_010100014841.

    Proteomic databases

    PaxDbiO08336.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCAB14658; CAB14658; BSU27160.
    GeneIDi937585.
    KEGGibsu:BSU27160.
    PATRICi18977286. VBIBacSub10457_2832.

    Organism-specific databases

    GenoListiBSU27160. [Micado]

    Phylogenomic databases

    eggNOGiENOG4107EER. Bacteria.
    COG0369. LUCA.
    HOGENOMiHOG000093545.
    InParanoidiO08336.
    KOiK14338.
    OMAiEDYPACE.
    OrthoDBiEOG63Z73K.
    PhylomeDBiO08336.

    Enzyme and pathway databases

    BioCyciBSUB:BSU27160-MONOMER.
    SABIO-RKO08336.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    1.20.990.10. 1 hit.
    3.40.50.360. 1 hit.
    InterProiIPR023206. Bifunctional_P450_P450_red.
    IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR003097. FAD-binding_1.
    IPR017927. Fd_Rdtase_FAD-bd.
    IPR001094. Flavdoxin-like.
    IPR008254. Flavodoxin/NO_synth.
    IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
    IPR029039. Flavoprotein-like_dom.
    IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF00667. FAD_binding_1. 1 hit.
    PF00258. Flavodoxin_1. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    PF00067. p450. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000209. Bifunctional_P450_P450R. 1 hit.
    PRINTSiPR00369. FLAVODOXIN.
    PR00371. FPNCR.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    SSF52218. SSF52218. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    PS51384. FAD_FR. 1 hit.
    PS50902. FLAVODOXIN_LIKE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Sequence of the Bacillus subtilis genome region in the vicinity of the lev operon reveals two new extracytoplasmic function RNA polymerase sigma factors SigV and SigZ."
      Sorokin A., Bolotin A., Purnelle B., Hilbert H., Lauber J., Duesterhoeft A., Ehrlich S.D.
      Microbiology 143:2939-2943(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 168.
    2. "The complete genome sequence of the Gram-positive bacterium Bacillus subtilis."
      Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V., Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R., Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S., Bruschi C.V.
      , Caldwell B., Capuano V., Carter N.M., Choi S.-K., Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F., Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D., Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M., Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P., Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K., Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S., Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y., Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G., Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J., Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C., Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S., Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B., Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S., Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M., Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y., Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J., Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A., Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M., Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S., Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E., Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K., Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E., Yoshikawa H., Danchin A.
      Nature 390:249-256(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: 168.
    3. "Transcriptional regulation of the Bacillus subtilis bscR-CYP102A3 operon by the BscR repressor and differential induction of cytochrome CYP102A3 expression by oleic acid and palmitate."
      Lee T.-R., Hsu H.-P., Shaw G.-C.
      J. Biochem. 130:569-574(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    4. "Fatty-acid-displaced transcriptional repressor, a conserved regulator of cytochrome P450 102 transcription in Bacillus species."
      Gustafsson M.C., Palmer C.N., Wolf C.R., von Wachenfeldt C.
      Arch. Microbiol. 176:459-464(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
      Strain: 168 / 1A1.
    5. "Expression, purification, and characterization of Bacillus subtilis cytochromes P450 CYP102A2 and CYP102A3: flavocytochrome homologues of P450 BM3 from Bacillus megaterium."
      Gustafsson M.C., Roitel O., Marshall K.R., Noble M.A., Chapman S.K., Pessegueiro A., Fulco A.J., Cheesman M.R., von Wachenfeldt C., Munro A.W.
      Biochemistry 43:5474-5487(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
      Strain: 168 / 1A1.
    6. "Substrate specificity of native and mutated cytochrome P450 (CYP102A3) from Bacillus subtilis."
      Lentz O., Urlacher V., Schmid R.D.
      J. Biotechnol. 108:41-49(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, MUTAGENESIS OF PHE-89 AND SER-190.
      Strain: 168 / ATCC 33234 / DSM 402 / NCIMB 10106.
    7. "Altering the regioselectivity of cytochrome P450 CYP102A3 of Bacillus subtilis by using a new versatile assay system."
      Lentz O., Feenstra A., Habicher T., Hauer B., Schmid R.D., Urlacher V.B.
      ChemBioChem 7:345-350(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN ENGINEERING.
      Strain: 168 / ATCC 33234 / DSM 402 / NCIMB 10106.

    Entry informationi

    Entry nameiCYPB_BACSU
    AccessioniPrimary (citable) accession number: O08336
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: July 1, 1997
    Last modified: January 20, 2016
    This is version 128 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Bacillus subtilis
      Bacillus subtilis (strain 168): entries, gene names and cross-references to SubtiList
    2. SIMILARITY comments
      Index of protein domains and families

    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 one 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.