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P24903

- CP2F1_HUMAN

UniProt

P24903 - CP2F1_HUMAN

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Protein

Cytochrome P450 2F1

Gene

CYP2F1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Source: UniProtKB
  6. 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
Complete GO annotation...

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.
SABIO-RKP24903.

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
Complete GO annotation...

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.
ExpressionAtlasiP24903. baseline.
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.
GeneTreeiENSGT00760000118775.
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

        10         20         30         40         50
MDSISTAILL LLLALVCLLL TLSSRDKGKL PPGPRPLSIL GNLLLLCSQD
60 70 80 90 100
MLTSLTKLSK EYGSMYTVHL GPRRVVVLSG YQAVKEALVD QGEEFSGRGD
110 120 130 140 150
YPAFFNFTKG NGIAFSSGDR WKVLRQFSIQ ILRNFGMGKR SIEERILEEG
160 170 180 190 200
SFLLAELRKT EGEPFDPTFV LSRSVSNIIC SVLFGSRFDY DDERLLTIIR
210 220 230 240 250
LINDNFQIMS SPWGELYDIF PSLLDWVPGP HQRIFQNFKC LRDLIAHSVH
260 270 280 290 300
DHQASLDPRS PRDFIQCFLT KMAEEKEDPL SHFHMDTLLM TTHNLLFGGT
310 320 330 340 350
KTVSTTLHHA FLALMKYPKV QARVQEEIDL VVGRARLPAL KDRAAMPYTD
360 370 380 390 400
AVIHEVQRFA DIIPMNLPHR VTRDTAFRGF LIPKGTDVIT LLNTVHYDPS
410 420 430 440 450
QFLTPQEFNP EHFLDANQSF KKSPAFMPFS AGRRLCLGES LARMELFLYL
460 470 480 490
TAILQSFSLQ PLGAPEDIDL TPLSSGLGNL PRPFQLCLRP R
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. [P24903-1]
PIRiA36036.
B36036.
RefSeqiNP_000765.2. NM_000774.3. [P24903-1]
UniGeneiHs.558318.

Genome annotation databases

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

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. [P24903-1 ]
PIRi A36036.
B36036.
RefSeqi NP_000765.2. NM_000774.3. [P24903-1 ]
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. [P24903-1 ]

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.
GeneTreei ENSGT00760000118775.
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.
SABIO-RK P24903.

Miscellaneous databases

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

Gene expression databases

Bgeei P24903.
CleanExi HS_CYP2F1.
ExpressionAtlasi P24903. baseline.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 125 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