CP2F1_HUMAN
ID CP2F1_HUMAN Reviewed; 491 AA.
AC P24903; A7KAU6; A7KAU7; A7KAU8; A7KAU9; A7KAV0; Q32MN5; Q8WWJ2;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Cytochrome P450 2F1;
DE EC=1.14.14.1 {ECO:0000269|PubMed:10383923, ECO:0000269|PubMed:1974816, ECO:0000269|PubMed:8558432};
DE AltName: Full=CYPIIF1;
GN Name=CYP2F1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=1974816; DOI=10.1021/bi00475a012;
RA Nhamburo P.T., Kimura S., McBride O.W., Kozak C.A., Gelboin H.V.,
RA Gonzalez F.J.;
RT "The human CYP2F gene subfamily: identification of a cDNA encoding a new
RT cytochrome P450, cDNA-directed expression, and chromosome mapping.";
RL Biochemistry 29:5491-5499(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-266.
RX PubMed=11827709; DOI=10.1016/s0027-5107(01)00274-3;
RA Chen N., Whitehead S.E., Caillat A.W., Gavit K., Isphording D.R.,
RA Kovacevic D., McCreary M.B., Hoffman S.M.G.;
RT "Identification and cross-species comparisons of CYP2F subfamily genes in
RT mammals.";
RL Mutat. Res. 499:155-161(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES CYP2F1*1; CYP2F1*2A; CYP2F1*2B;
RP CYP2F1*3; CYP2F1*4; CYP2F1*5A; CYP2F1*5B AND CYP2F1*6).
RX PubMed=17327131; DOI=10.1016/j.mrfmmm.2007.01.007;
RA Tournel G., Cauffiez C., Billaut-Laden I., Allorge D., Chevalier D.,
RA Bonnifet F., Mensier E., Lafitte J.-J., Lhermitte M., Broly F.,
RA Lo-Guidice J.-M.;
RT "Molecular analysis of the CYP2F1 gene: identification of a frequent non-
RT functional allelic variant.";
RL Mutat. Res. 617:79-89(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=8619884; DOI=10.1016/0006-2952(95)02184-1;
RA Hakkola J., Pasanen M., Hukkanen J., Pelkonen O., Maeenpaeae J.,
RA Edwards R.J., Boobis A.R., Raunio H.;
RT "Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-
RT term placenta.";
RL Biochem. Pharmacol. 51:403-411(1996).
RN [7]
RP CATALYTIC ACTIVITY.
RX PubMed=8558432;
RA Thornton-Manning J., Appleton M.L., Gonzalez F.J., Yost G.S.;
RT "Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes:
RT correlation of 3-methyleneindolenine formation and protein-binding.";
RL J. Pharmacol. Exp. Ther. 276:21-29(1996).
RN [8]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10383923;
RA Lanza D.L., Code E., Crespi C.L., Gonzalez F.J., Yost G.S.;
RT "Specific dehydrogenation of 3-methylindole and epoxidation of naphthalene
RT by recombinant human CYP2F1 expressed in lymphoblastoid cells.";
RL Drug Metab. Dispos. 27:798-803(1999).
CC -!- FUNCTION: May be involved in the metabolism of various pneumotoxicants
CC including naphthalene. Is able to dealkylate ethoxycoumarin,
CC propoxycoumarin, and pentoxyresorufin but possesses no activity toward
CC ethoxyresorufin and only trace dearylation activity toward
CC benzyloxyresorufin. Bioactivates 3-methylindole (3MI) by
CC dehydrogenation to the putative electrophile 3-methylene-indolenine.
CC {ECO:0000269|PubMed:1974816}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:10383923, ECO:0000269|PubMed:1974816,
CC ECO:0000269|PubMed:8558432};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.018 mM for 3-methylindole {ECO:0000269|PubMed:10383923,
CC ECO:0000269|PubMed:1974816};
CC Vmax=51.2 pmol/min/mg enzyme toward ethoxy-coumarin
CC {ECO:0000269|PubMed:10383923, ECO:0000269|PubMed:1974816};
CC Vmax=24.3 pmol/min/mg enzyme toward propoxy-coumarin
CC {ECO:0000269|PubMed:10383923, ECO:0000269|PubMed:1974816};
CC Vmax=22 pmol/min/mg enzyme toward pentoxy-resorufin
CC {ECO:0000269|PubMed:10383923, ECO:0000269|PubMed:1974816};
CC Vmax=2.29 pmol/min/mg enzyme toward benzyloxy-resorufin
CC {ECO:0000269|PubMed:10383923, ECO:0000269|PubMed:1974816};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:10383923}; Peripheral membrane protein
CC {ECO:0000305|PubMed:10383923}. Microsome membrane
CC {ECO:0000269|PubMed:10383923}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10383923}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P24903-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P24903-2; Sequence=VSP_055575, VSP_055576;
CC -!- TISSUE SPECIFICITY: Expressed in lung. Rarely detected in liver and
CC placenta. {ECO:0000269|PubMed:1974816, ECO:0000269|PubMed:8619884}.
CC -!- POLYMORPHISM: Eight non disease-associated alleles are known: CYP2F1*1,
CC CYP2F1*2A, CYP2F1*2B, CYP2F1*3, CYP2F1*4, CYP2F1*5A, CYP2F1*5B and
CC CYP2F1*6. The sequence shown corresponds to allele CYP2F1*1.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP2F1 alleles;
CC URL="https://www.pharmvar.org/gene/CYP2F1";
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DR EMBL; J02906; AAA52156.1; -; mRNA.
DR EMBL; AF372573; AAL69652.1; -; Genomic_DNA.
DR EMBL; AF372570; AAL69652.1; JOINED; Genomic_DNA.
DR EMBL; AF372571; AAL69652.1; JOINED; Genomic_DNA.
DR EMBL; AF372572; AAL69652.1; JOINED; Genomic_DNA.
DR EMBL; EF122241; ABO41976.1; -; Genomic_DNA.
DR EMBL; EF122242; ABO41977.1; -; Genomic_DNA.
DR EMBL; EF122243; ABO41978.1; -; Genomic_DNA.
DR EMBL; EF122244; ABO41979.1; -; Genomic_DNA.
DR EMBL; EF122245; ABO41980.1; -; Genomic_DNA.
DR EMBL; AC008962; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109056; AAI09057.1; -; mRNA.
DR CCDS; CCDS12572.1; -. [P24903-1]
DR PIR; A36036; A36036.
DR PIR; B36036; B36036.
DR RefSeq; NP_000765.2; NM_000774.4. [P24903-1]
DR AlphaFoldDB; P24903; -.
DR SMR; P24903; -.
DR IntAct; P24903; 1.
DR MINT; P24903; -.
DR STRING; 9606.ENSP00000333534; -.
DR BindingDB; P24903; -.
DR ChEMBL; CHEMBL4523986; -.
DR iPTMnet; P24903; -.
DR PhosphoSitePlus; P24903; -.
DR BioMuta; CYP2F1; -.
DR DMDM; 259016202; -.
DR jPOST; P24903; -.
DR MassIVE; P24903; -.
DR PaxDb; P24903; -.
DR PeptideAtlas; P24903; -.
DR PRIDE; P24903; -.
DR ProteomicsDB; 54239; -. [P24903-1]
DR ProteomicsDB; 61607; -.
DR Antibodypedia; 30699; 119 antibodies from 26 providers.
DR DNASU; 1572; -.
DR Ensembl; ENST00000331105.7; ENSP00000333534.2; ENSG00000197446.9. [P24903-1]
DR Ensembl; ENST00000532164.2; ENSP00000471416.1; ENSG00000197446.9. [P24903-2]
DR GeneID; 1572; -.
DR KEGG; hsa:1572; -.
DR MANE-Select; ENST00000331105.7; ENSP00000333534.2; NM_000774.5; NP_000765.2.
DR UCSC; uc002opu.2; human. [P24903-1]
DR CTD; 1572; -.
DR DisGeNET; 1572; -.
DR GeneCards; CYP2F1; -.
DR HGNC; HGNC:2632; CYP2F1.
DR HPA; ENSG00000197446; Tissue enhanced (lung, salivary gland, testis).
DR MIM; 124070; gene.
DR neXtProt; NX_P24903; -.
DR OpenTargets; ENSG00000197446; -.
DR PharmGKB; PA27109; -.
DR VEuPathDB; HostDB:ENSG00000197446; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000162522; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P24903; -.
DR OMA; NTVHHDP; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P24903; -.
DR TreeFam; TF352043; -.
DR PathwayCommons; P24903; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211981; Xenobiotics.
DR Reactome; R-HSA-211999; CYP2E1 reactions.
DR SABIO-RK; P24903; -.
DR SignaLink; P24903; -.
DR BioGRID-ORCS; 1572; 10 hits in 1073 CRISPR screens.
DR GeneWiki; CYP2F1; -.
DR GenomeRNAi; 1572; -.
DR Pharos; P24903; Tbio.
DR PRO; PR:P24903; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P24903; protein.
DR Bgee; ENSG00000197446; Expressed in olfactory segment of nasal mucosa and 74 other tissues.
DR ExpressionAtlas; P24903; baseline and differential.
DR Genevisible; P24903; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; TAS:Reactome.
DR GO; GO:0016712; F: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; IDA:UniProtKB.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:1901170; P:naphthalene catabolic process; IDA:UniProtKB.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR020469; Cyt_P450_CYP2_fam.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01957; EP450ICYP2F.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..491
FT /note="Cytochrome P450 2F1"
FT /id="PRO_0000051759"
FT BINDING 436
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
FT VAR_SEQ 303..320
FT /note="VSTTLHHAFLALMKYPKV -> PACRRRSTSWWDARGCRR (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055575"
FT VAR_SEQ 321..491
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055576"
FT VARIANT 38
FT /note="S -> P (in allele CYP2F1*4; dbSNP:rs58285195)"
FT /id="VAR_058863"
FT VARIANT 98
FT /note="R -> P (in allele CYP2F1*6; dbSNP:rs57670668)"
FT /id="VAR_058864"
FT VARIANT 218
FT /note="D -> N (in allele CYP2F1*3 and in allele CYP2F1*4;
FT dbSNP:rs305974)"
FT /id="VAR_058865"
FT VARIANT 266
FT /note="Q -> H (in allele CYP2F1*3; dbSNP:rs75405062)"
FT /evidence="ECO:0000269|PubMed:11827709"
FT /id="VAR_058866"
FT VARIANT 391
FT /note="L -> P (in allele CYP2F1*5A and in allele CYP2F1*5B;
FT dbSNP:rs144315434)"
FT /id="VAR_058867"
FT VARIANT 490
FT /note="P -> L (in allele CYP2F1*3; dbSNP:rs7246981)"
FT /id="VAR_058868"
FT CONFLICT 156..157
FT /note="EL -> DV (in Ref. 1; AAA52156)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="I -> ILDPR (in Ref. 1; AAA52156 and 2; AAL69652)"
FT /evidence="ECO:0000305"
FT CONFLICT 256..259
FT /note="Missing (in Ref. 1; AAA52156)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="S -> L (in Ref. 1; AAA52156)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 491 AA; 55501 MW; D8022271FC0B6D06 CRC64;
MDSISTAILL LLLALVCLLL TLSSRDKGKL PPGPRPLSIL GNLLLLCSQD MLTSLTKLSK
EYGSMYTVHL GPRRVVVLSG YQAVKEALVD QGEEFSGRGD YPAFFNFTKG NGIAFSSGDR
WKVLRQFSIQ ILRNFGMGKR SIEERILEEG SFLLAELRKT EGEPFDPTFV LSRSVSNIIC
SVLFGSRFDY DDERLLTIIR LINDNFQIMS SPWGELYDIF PSLLDWVPGP HQRIFQNFKC
LRDLIAHSVH DHQASLDPRS PRDFIQCFLT KMAEEKEDPL SHFHMDTLLM TTHNLLFGGT
KTVSTTLHHA FLALMKYPKV QARVQEEIDL VVGRARLPAL KDRAAMPYTD AVIHEVQRFA
DIIPMNLPHR VTRDTAFRGF LIPKGTDVIT LLNTVHYDPS QFLTPQEFNP EHFLDANQSF
KKSPAFMPFS AGRRLCLGES LARMELFLYL TAILQSFSLQ PLGAPEDIDL TPLSSGLGNL
PRPFQLCLRP R
