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P24903

- CP2F1_HUMAN

UniProt

P24903 - CP2F1_HUMAN

Protein

Cytochrome P450 2F1

Gene

CYP2F1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (22 Sep 2009)
      Previous versions | rss
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    Functioni

    May be involved in the metabolism of various pneumotoxicants including naphthalene. Is able to dealkylate ethoxycoumarin, propoxycoumarin, and pentoxyresorufin but possesses no activity toward ethoxyresorufin and only trace dearylation activity toward benzyloxyresorufin. Bioactivates 3-methylindole (3MI) by dehydrogenation to the putative electrophile 3-methylene-indolenine.1 Publication

    Catalytic activityi

    RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.3 Publications

    Cofactori

    Heme group.By similarity

    Kineticsi

    1. KM=0.018 mM for 3-methylindole2 Publications

    Vmax=51.2 pmol/min/mg enzyme toward ethoxy-coumarin2 Publications

    Vmax=24.3 pmol/min/mg enzyme toward propoxy-coumarin2 Publications

    Vmax=22 pmol/min/mg enzyme toward pentoxy-resorufin2 Publications

    Vmax=2.29 pmol/min/mg enzyme toward benzyloxy-resorufin2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi436 – 4361Iron (heme axial ligand)By similarity

    GO - Molecular functioni

    1. aromatase activity Source: UniProtKB-EC
    2. heme binding Source: InterPro
    3. iron ion binding Source: InterPro
    4. monooxygenase activity Source: ProtInc
    5. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen Source: InterPro
    6. 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
    7. oxygen binding Source: ProtInc

    GO - Biological processi

    1. naphthalene metabolic process Source: UniProtKB
    2. response to toxic substance Source: Ensembl
    3. small molecule metabolic process Source: Reactome
    4. trichloroethylene metabolic process Source: Ensembl
    5. xenobiotic metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_13814. Fatty acids.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 2F1 (EC:1.14.14.1)
    Alternative name(s):
    CYPIIF1
    Gene namesi
    Name:CYP2F1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:2632. CYP2F1.

    Subcellular locationi

    Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein 1 Publication. Microsome membrane 1 Publication; Peripheral membrane protein 1 Publication

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. intracellular membrane-bounded organelle Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27109.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 491491Cytochrome P450 2F1PRO_0000051759Add
    BLAST

    Proteomic databases

    PaxDbiP24903.
    PRIDEiP24903.

    PTM databases

    PhosphoSiteiP24903.

    Expressioni

    Tissue specificityi

    Expressed in lung. Rarely detected in liver and placenta.2 Publications

    Gene expression databases

    BgeeiP24903.
    CleanExiHS_CYP2F1.
    GenevestigatoriP24903.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000333534.

    Structurei

    3D structure databases

    ProteinModelPortaliP24903.
    SMRiP24903. Positions 27-491.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    HOVERGENiHBG015789.
    InParanoidiP24903.
    KOiK07416.
    OMAiLRHAFLV.
    OrthoDBiEOG7RBZ85.
    PhylomeDBiP24903.
    TreeFamiTF352043.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR020469. Cyt_P450_CYP2_fam.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01957. EP450ICYP2F.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P24903-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDSISTAILL LLLALVCLLL TLSSRDKGKL PPGPRPLSIL GNLLLLCSQD    50
    MLTSLTKLSK EYGSMYTVHL GPRRVVVLSG YQAVKEALVD QGEEFSGRGD 100
    YPAFFNFTKG NGIAFSSGDR WKVLRQFSIQ ILRNFGMGKR SIEERILEEG 150
    SFLLAELRKT EGEPFDPTFV LSRSVSNIIC SVLFGSRFDY DDERLLTIIR 200
    LINDNFQIMS SPWGELYDIF PSLLDWVPGP HQRIFQNFKC LRDLIAHSVH 250
    DHQASLDPRS PRDFIQCFLT KMAEEKEDPL SHFHMDTLLM TTHNLLFGGT 300
    KTVSTTLHHA FLALMKYPKV QARVQEEIDL VVGRARLPAL KDRAAMPYTD 350
    AVIHEVQRFA DIIPMNLPHR VTRDTAFRGF LIPKGTDVIT LLNTVHYDPS 400
    QFLTPQEFNP EHFLDANQSF KKSPAFMPFS AGRRLCLGES LARMELFLYL 450
    TAILQSFSLQ PLGAPEDIDL TPLSSGLGNL PRPFQLCLRP R 491
    Length:491
    Mass (Da):55,501
    Last modified:September 22, 2009 - v2
    Checksum:iD8022271FC0B6D06
    GO
    Isoform 2 (identifier: P24903-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         303-320: VSTTLHHAFLALMKYPKV → PACRRRSTSWWDARGCRR
         321-491: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:320
    Mass (Da):36,410
    Checksum:i19FA98DD0E534DBB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti156 – 1572EL → DV in AAA52156. (PubMed:1974816)Curated
    Sequence conflicti219 – 2191I → ILDPR in AAA52156. (PubMed:1974816)Curated
    Sequence conflicti219 – 2191I → ILDPR in AAL69652. (PubMed:11827709)Curated
    Sequence conflicti256 – 2594Missing in AAA52156. (PubMed:1974816)Curated
    Sequence conflicti440 – 4401S → L in AAA52156. (PubMed:1974816)Curated

    Polymorphismi

    Eight non disease-associated alleles are known: CYP2F1*1, CYP2F1*2A, CYP2F1*2B, CYP2F1*3, CYP2F1*4, CYP2F1*5A, CYP2F1*5B and CYP2F1*6. The sequence shown corresponds to allele CYP2F1*1.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti38 – 381S → P in allele CYP2F1*4.
    Corresponds to variant rs58285195 [ dbSNP | Ensembl ].
    VAR_058863
    Natural varianti98 – 981R → P in allele CYP2F1*6.
    Corresponds to variant rs57670668 [ dbSNP | Ensembl ].
    VAR_058864
    Natural varianti218 – 2181D → N in allele CYP2F1*3 and in allele CYP2F1*4.
    Corresponds to variant rs80319612 [ dbSNP | Ensembl ].
    VAR_058865
    Natural varianti266 – 2661Q → H in allele CYP2F1*3. 1 Publication
    VAR_058866
    Natural varianti391 – 3911L → P in allele CYP2F1*5A and in allele CYP2F1*5B.
    Corresponds to variant rs144315434 [ dbSNP | Ensembl ].
    VAR_058867
    Natural varianti490 – 4901P → L in allele CYP2F1*3.
    Corresponds to variant rs7246981 [ dbSNP | Ensembl ].
    VAR_058868

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei303 – 32018VSTTL…KYPKV → PACRRRSTSWWDARGCRR in isoform 2. 1 PublicationVSP_055575Add
    BLAST
    Alternative sequencei321 – 491171Missing in isoform 2. 1 PublicationVSP_055576Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02906 mRNA. Translation: AAA52156.1.
    AF372573
    , AF372570, AF372571, AF372572 Genomic DNA. Translation: AAL69652.1.
    EF122241 Genomic DNA. Translation: ABO41976.1.
    EF122242 Genomic DNA. Translation: ABO41977.1.
    EF122243 Genomic DNA. Translation: ABO41978.1.
    EF122244 Genomic DNA. Translation: ABO41979.1.
    EF122245 Genomic DNA. Translation: ABO41980.1.
    AC008962 Genomic DNA. No translation available.
    BC109056 mRNA. Translation: AAI09057.1.
    CCDSiCCDS12572.1.
    PIRiA36036.
    B36036.
    RefSeqiNP_000765.2. NM_000774.3.
    UniGeneiHs.558318.

    Genome annotation databases

    EnsembliENST00000331105; ENSP00000333534; ENSG00000197446. [P24903-1]
    ENST00000532164; ENSP00000471416; ENSG00000197446. [P24903-2]
    GeneIDi1572.
    KEGGihsa:1572.
    UCSCiuc002opu.1. human.

    Polymorphism databases

    DMDMi259016202.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP2F1 alleles

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02906 mRNA. Translation: AAA52156.1 .
    AF372573
    , AF372570 , AF372571 , AF372572 Genomic DNA. Translation: AAL69652.1 .
    EF122241 Genomic DNA. Translation: ABO41976.1 .
    EF122242 Genomic DNA. Translation: ABO41977.1 .
    EF122243 Genomic DNA. Translation: ABO41978.1 .
    EF122244 Genomic DNA. Translation: ABO41979.1 .
    EF122245 Genomic DNA. Translation: ABO41980.1 .
    AC008962 Genomic DNA. No translation available.
    BC109056 mRNA. Translation: AAI09057.1 .
    CCDSi CCDS12572.1.
    PIRi A36036.
    B36036.
    RefSeqi NP_000765.2. NM_000774.3.
    UniGenei Hs.558318.

    3D structure databases

    ProteinModelPortali P24903.
    SMRi P24903. Positions 27-491.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000333534.

    PTM databases

    PhosphoSitei P24903.

    Polymorphism databases

    DMDMi 259016202.

    Proteomic databases

    PaxDbi P24903.
    PRIDEi P24903.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000331105 ; ENSP00000333534 ; ENSG00000197446 . [P24903-1 ]
    ENST00000532164 ; ENSP00000471416 ; ENSG00000197446 . [P24903-2 ]
    GeneIDi 1572.
    KEGGi hsa:1572.
    UCSCi uc002opu.1. human.

    Organism-specific databases

    CTDi 1572.
    GeneCardsi GC19P041620.
    H-InvDB HIX0202929.
    HGNCi HGNC:2632. CYP2F1.
    MIMi 124070. gene.
    neXtProti NX_P24903.
    PharmGKBi PA27109.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOVERGENi HBG015789.
    InParanoidi P24903.
    KOi K07416.
    OMAi LRHAFLV.
    OrthoDBi EOG7RBZ85.
    PhylomeDBi P24903.
    TreeFami TF352043.

    Enzyme and pathway databases

    Reactomei REACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_13814. Fatty acids.

    Miscellaneous databases

    GeneWikii CYP2F1.
    GenomeRNAii 1572.
    NextBioi 6465.
    PROi P24903.
    SOURCEi Search...

    Gene expression databases

    Bgeei P24903.
    CleanExi HS_CYP2F1.
    Genevestigatori P24903.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR020469. Cyt_P450_CYP2_fam.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR01957. EP450ICYP2F.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The human CYP2F gene subfamily: identification of a cDNA encoding a new cytochrome P450, cDNA-directed expression, and chromosome mapping."
      Nhamburo P.T., Kimura S., McBride O.W., Kozak C.A., Gelboin H.V., Gonzalez F.J.
      Biochemistry 29:5491-5499(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
      Tissue: Lung.
    2. "Identification and cross-species comparisons of CYP2F subfamily genes in mammals."
      Chen N., Whitehead S.E., Caillat A.W., Gavit K., Isphording D.R., Kovacevic D., McCreary M.B., Hoffman S.M.G.
      Mutat. Res. 499:155-161(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-266.
    3. "Molecular analysis of the CYP2F1 gene: identification of a frequent non-functional allelic variant."
      Tournel G., Cauffiez C., Billaut-Laden I., Allorge D., Chevalier D., Bonnifet F., Mensier E., Lafitte J.-J., Lhermitte M., Broly F., Lo-Guidice J.-M.
      Mutat. Res. 617:79-89(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES CYP2F1*1; CYP2F1*2A; CYP2F1*2B; CYP2F1*3; CYP2F1*4; CYP2F1*5A; CYP2F1*5B AND CYP2F1*6).
    4. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    6. "Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta."
      Hakkola J., Pasanen M., Hukkanen J., Pelkonen O., Maeenpaeae J., Edwards R.J., Boobis A.R., Raunio H.
      Biochem. Pharmacol. 51:403-411(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    7. "Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes: correlation of 3-methyleneindolenine formation and protein-binding."
      Thornton-Manning J., Appleton M.L., Gonzalez F.J., Yost G.S.
      J. Pharmacol. Exp. Ther. 276:21-29(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY.
    8. "Specific dehydrogenation of 3-methylindole and epoxidation of naphthalene by recombinant human CYP2F1 expressed in lymphoblastoid cells."
      Lanza D.L., Code E., Crespi C.L., Gonzalez F.J., Yost G.S.
      Drug Metab. Dispos. 27:798-803(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiCP2F1_HUMAN
    AccessioniPrimary (citable) accession number: P24903
    Secondary accession number(s): A7KAU6
    , A7KAU7, A7KAU8, A7KAU9, A7KAV0, Q32MN5, Q8WWJ2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 1992
    Last sequence update: September 22, 2009
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3