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 27-MAR-2024, entry version 188. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9606-ENSP00000333534; -. DR PeptideAtlas; P24903; -. DR ProteomicsDB; 54239; -. [P24903-1] DR Antibodypedia; 30699; 141 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 AGR; HGNC:2632; -. 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; WPVDIFP; -. DR OrthoDB; 2900138at2759; -. 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 1153 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 75 other cell types or tissues. DR ExpressionAtlas; P24903; baseline and differential. 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:0019373; P:epoxygenase P450 pathway; IBA:GO_Central. DR GO; GO:1901170; P:naphthalene catabolic process; IDA:UniProtKB. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central. DR CDD; cd20669; Cyp2F; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24300:SF275; CYTOCHROME P450 2F1; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01957; EP450ICYP2F. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P24903; HS. 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 //