P24903 (CP2F1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 2F1
EC=1.14.14.1

Alternative name(s):
CYPIIF1

Gene names

Name:

CYP2F1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	491 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O. Ref.1 Ref.5 Ref.6
Cofactor	Heme group By similarity.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein Probable. Microsome membrane; Peripheral membrane protein Ref.6.
Tissue specificity	Expressed in lung. Rarely detected in liver and placenta. Ref.1 Ref.4
Polymorphism	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.
Sequence similarities	Belongs to the cytochrome P450 family.
Biophysicochemical properties	Kinetic parameters: KM=0.018 mM for 3-methylindole Ref.1 Ref.6 Vmax=51.2 pmol/min/mg enzyme toward ethoxy-coumarin Vmax=24.3 pmol/min/mg enzyme toward propoxy-coumarin Vmax=22 pmol/min/mg enzyme toward pentoxy-resorufin Vmax=2.29 pmol/min/mg enzyme toward benzyloxy-resorufin

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	naphthalene metabolic process Inferred from direct assay Ref.6. Source: UniProtKB response to toxin Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome trichloroethylene metabolic process Inferred from electronic annotation. Source: Compara xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro 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 Inferred from direct assay Ref.6. Source: UniProtKB oxygen binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 491	491	Cytochrome P450 2F1		PRO_0000051759
Sites
	Metal binding	436	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	38	1	S → P in allele CYP2F1*4. Corresponds to variant rs58285195 [ dbSNP | Ensembl ].		VAR_058863
	Natural variant	98	1	R → P in allele CYP2F1*6. Corresponds to variant rs57670668 [ dbSNP | Ensembl ].		VAR_058864
	Natural variant	218	1	D → N in allele CYP2F1*3 and in allele CYP2F1*4.		VAR_058865
	Natural variant	266	1	Q → H in allele CYP2F1*3. Ref.2		VAR_058866
	Natural variant	391	1	L → P in allele CYP2F1*5A and in allele CYP2F1*5B.		VAR_058867
	Natural variant	490	1	P → L in allele CYP2F1*3. Corresponds to variant rs7246981 [ dbSNP | Ensembl ].		VAR_058868
Experimental info
	Sequence conflict	156 – 157	2	EL → DV in AAA52156. Ref.1
	Sequence conflict	219	1	I → ILDPR in AAA52156. Ref.1
	Sequence conflict	219	1	I → ILDPR in AAL69652. Ref.2
	Sequence conflict	256 – 259	4	Missing in AAA52156. Ref.1
	Sequence conflict	440	1	S → L in AAA52156. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P24903 [UniParc]. Last modified September 22, 2009. Version 2. Checksum: D8022271FC0B6D06	FASTA	491	55,501
	10 20 30 40 50 60 MDSISTAILL LLLALVCLLL TLSSRDKGKL PPGPRPLSIL GNLLLLCSQD MLTSLTKLSK 70 80 90 100 110 120 EYGSMYTVHL GPRRVVVLSG YQAVKEALVD QGEEFSGRGD YPAFFNFTKG NGIAFSSGDR 130 140 150 160 170 180 WKVLRQFSIQ ILRNFGMGKR SIEERILEEG SFLLAELRKT EGEPFDPTFV LSRSVSNIIC 190 200 210 220 230 240 SVLFGSRFDY DDERLLTIIR LINDNFQIMS SPWGELYDIF PSLLDWVPGP HQRIFQNFKC 250 260 270 280 290 300 LRDLIAHSVH DHQASLDPRS PRDFIQCFLT KMAEEKEDPL SHFHMDTLLM TTHNLLFGGT 310 320 330 340 350 360 KTVSTTLHHA FLALMKYPKV QARVQEEIDL VVGRARLPAL KDRAAMPYTD AVIHEVQRFA 370 380 390 400 410 420 DIIPMNLPHR VTRDTAFRGF LIPKGTDVIT LLNTVHYDPS QFLTPQEFNP EHFLDANQSF 430 440 450 460 470 480 KKSPAFMPFS AGRRLCLGES LARMELFLYL TAILQSFSLQ PLGAPEDIDL TPLSSGLGNL 490 PRPFQLCLRP R

References

[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], 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]	"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.
[5]	"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.
[6]	"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.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2F1 alleles

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00103355.
PIR	A36036. B36036.
RefSeq	NP_000765.2. NM_000774.3.
UniGene	Hs.558318.
3D structure databases
ProteinModelPortal	P24903.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000333534.
PTM databases
PhosphoSite	P24903.
Polymorphism databases
DMDM	259016202.
Proteomic databases
PaxDb	P24903.
PRIDE	P24903.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000331105; ENSP00000333534; ENSG00000197446.
GeneID	1572.
KEGG	hsa:1572.
UCSC	uc002opu.1. human.
Organism-specific databases
CTD	1572.
GeneCards	GC19P041620.
H-InvDB	HIX0202929.
HGNC	HGNC:2632. CYP2F1.
MIM	124070. gene.
neXtProt	NX_P24903.
PharmGKB	PA27109.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOVERGEN	HBG015789.
InParanoid	P24903.
KO	K07416.
OMA	DYPVFFN.
OrthoDB	EOG4MKNG9.
PhylomeDB	P24903.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P24903.
Bgee	P24903.
CleanEx	HS_CYP2F1.
Genevestigator	P24903.
GermOnline	ENSG00000197446. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 1 hit.
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR020469. Cyt_P450_CYP2_fam. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR01957. EP450ICYP2F. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1572.
NextBio	6465.
SOURCE	Search...

Entry information

Entry name

CP2F1_HUMAN

Accession

Primary (citable) accession number: P24903
Secondary accession number(s): A7KAU6 , A7KAU7, A7KAU8, A7KAU9, A7KAV0, Q8WWJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	September 22, 2009
Last modified:	May 1, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.