Reviewed, UniProtKB/Swiss-Prot P04798 (CP1A1_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytochrome P450 1A1
    EC=1.14.14.1
Alternative name(s):
    CYPIA1
    P450-P1
    P450 form 6
    P450-C

Gene names

Name:

CYP1A1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	512 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
Cofactor	Heme group By similarity.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Tissue specificity	Lung, lymphocytes and placenta.
Induction	By 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	drug metabolic process Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from direct assay. Source: UniProtKB vitamin D metabolic process Inferred by curator. Source: UniProtKB
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from electronic annotation. Source: UniProtKB-KW
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 oxygen binding Traceable author statement. Source: ProtInc vitamin D 24-hydroxylase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 512	512	Cytochrome P450 1A1		PRO_0000051627
Sites
	Metal binding	457	1	Iron (heme axial ligand)
Amino acid modifications
	Modified residue	360	1	Phosphoserine Ref.9
Natural variations
	Natural variant	45	1	G → D: dbSNP rs4646422. Ref.5 Ref.15 Ref.16		VAR_023194
	Natural variant	66	1	M → V: dbSNP rs35035798.		VAR_033817
	Natural variant	78	1	I → T: dbSNP rs17861094. Ref.15 Ref.16		VAR_023195
	Natural variant	93	1	R → W: dbSNP rs2229150. Ref.15		VAR_024706
	Natural variant	173	1	T → R: dbSNP rs28399427. Ref.15		VAR_024707
	Natural variant	279	1	R → W: dbSNP rs34260157. Ref.12		VAR_009280
	Natural variant	286	1	I → T: dbSNP rs4987133.		VAR_020122
	Natural variant	331	1	M → I in allele CYP1A1*6. Ref.13		VAR_016937
	Natural variant	448	1	I → N in allele CYP1A1*8. Ref.14		VAR_016938
	Natural variant	461	1	T → N in allele CYP1A1*4. dbSNP rs1799814. Ref.15 Ref.16 Ref.11		VAR_008342
	Natural variant	462	1	I → V in allele CYP1A1*2B and allele CYP1A1*2C. dbSNP rs1048943. Ref.16 Ref.10		VAR_001243
	Natural variant	464	1	R → C in allele CYP1A1*9. Ref.14		VAR_016939
	Natural variant	464	1	R → S in allele CYP1A1*5. Ref.13		VAR_016940
	Natural variant	470	1	F → V: dbSNP rs36121583.		VAR_033818
	Natural variant	477	1	R → W in allele CYP1A1*10. Ref.14 Ref.17		VAR_016941
	Natural variant	482	1	V → M		VAR_024708
	Natural variant	492	1	P → R in allele CYP1A1*11. Ref.15 Ref.14		VAR_016942
Experimental info
	Sequence conflict	26	1	I → M in AAA52139. Ref.2
	Sequence conflict	235	1	D → E in AAA52139. Ref.2
	Sequence conflict	381	1	F → L in CAA26458. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P04798-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 3C62366044148EFD	FASTA	512	58,165
	10 20 30 40 50 60 MLFPISMSAT EFLLASVIFC LVFWVIRASR PQVPKGLKNP PGPWGWPLIG HMLTLGKNPH 70 80 90 100 110 120 LALSRMSQQY GDVLQIRIGS TPVVVLSGLD TIRQALVRQG DDFKGRPDLY TFTLISNGQS 130 140 150 160 170 180 MSFSPDSGPV WAARRRLAQN GLKSFSIASD PASSTSCYLE EHVSKEAEVL ISTLQELMAG 190 200 210 220 230 240 PGHFNPYRYV VVSVTNVICA ICFGRRYDHN HQELLSLVNL NNNFGEVVGS GNPADFIPIL 250 260 270 280 290 300 RYLPNPSLNA FKDLNEKFYS FMQKMVKEHY KTFEKGHIRD ITDSLIEHCQ EKQLDENANV 310 320 330 340 350 360 QLSDEKIINI VLDLFGAGFD TVTTAISWSL MYLVMNPRVQ RKIQEELDTV IGRSRRPRLS 370 380 390 400 410 420 DRSHLPYMEA FILETFRHSS FVPFTIPHST TRDTSLKGFY IPKGRCVFVN QWQINHDQKL 430 440 450 460 470 480 WVNPSEFLPE RFLTPDGAID KVLSEKVIIF GMGKRKCIGE TIARWEVFLF LAILLQRVEF 490 500 510 SVPLGVKVDM TPIYGLTMKH ACCEHFQMQL RS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human P1-450 gene sequence and correlation of mRNA with genetic differences in benzo[a]pyrene metabolism." Jaiswal A.K., Gonzales F.J., Nebert D.W. Nucleic Acids Res. 13:4503-4520(1985) [PubMed: 2989797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence." Jaiswal A.K., Gonzalez F.J., Nebert D.W. Science 228:80-83(1985) [PubMed: 3838385] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure and drug inducibility of the human cytochrome P-450c gene." Kawajiri K., Watanabe J., Gotoh O., Tagashira Y., Sogawa K., Fujii-Kuriyama Y. Eur. J. Biochem. 159:219-225(1986) [PubMed: 3019683] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation." Corchero J., Pimprale S., Kimura S., Gonzalez F.J. Pharmacogenetics 11:1-6(2001) [PubMed: 11207026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-45.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix.
[7]	"Identification of cytochrome P450 1A1 in human brain." Yun C.H., Park H.J., Kim S.J., Kim H.K. Biochem. Biophys. Res. Commun. 243:808-810(1998) [PubMed: 9500998] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 282-425. Tissue: Brain.
[8]	"Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6." Quattrochi L.C., Okino S.T., Pendurthi U.R., Tukey R.H. DNA 4:395-400(1985) [PubMed: 3000715] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 295-484.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene." Hayashi S., Watanabe J., Nakachi K., Kawajiri K. J. Biochem. 110:407-411(1991) [PubMed: 1722803] [Abstract] Cited for: VARIANT VAL-462.
[11]	"A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility." Cascorbi I., Brockmoller J., Roots I. Cancer Res. 56:4965-4969(1996) [PubMed: 8895751] [Abstract] Cited for: VARIANT ASN-461.
[12]	"Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms." Smart J., Daly A.K. Pharmacogenetics 10:11-24(2000) [PubMed: 10739168] [Abstract] Cited for: VARIANT TRP-279.
[13]	"Detection of known and two novel (M331I and R464S) missense mutations in the human CYP1A1 gene in a French Caucasian population." Chevalier D., Allorge D., Lo-Guidice J.-M., Cauffiez C., Lhermitte M., Lafitte J.-J., Broly F. Hum. Mutat. 17:355-355(2001) [PubMed: 11295847] [Abstract] Cited for: VARIANTS ILE-331 AND SER-464.
[14]	"Novel nonsynonymous polymorphisms of the CYP1A1 Gene in Japanese." Saito M., Egashira M., Kiyotani K., Fujieda M., Yamazaki H., Kiyohara C., Kunitoh H., Kamataki T. Drug Metab. Pharmacokinet. 18:218-222(2003) [PubMed: 15618738] [Abstract] Cited for: VARIANTS ASN-448; CYS-464; TRP-477 AND ARG-492.
[15]	"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population." Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P. Pharmacogenomics 5:895-931(2004) [PubMed: 15469410] [Abstract] Cited for: VARIANTS ASP-45; THR-78; TRP-93; ARG-173; ASN-461; MET-482 AND ARG-492.
[16]	"Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus." Jiang Z., Dalton T.P., Jin L., Wang B., Tsuneoka Y., Shertzer H.G., Deka R., Nebert D.W. Hum. Mutat. 25:196-206(2005) [PubMed: 15643613] [Abstract] Cited for: VARIANTS ASP-45; THR-78; ASN-461 AND VAL-462.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] TRP-477.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP1A1 alleles

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

CYP1A1 entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	X02612 Genomic DNA. Translation: CAA26458.1. K03191 mRNA. Translation: AAA52139.1. X04300 Genomic DNA. Translation: CAA27843.1. AF253322 Genomic DNA. Translation: AAK25727.1. AK223113 mRNA. Translation: BAD96833.1. BC023019 mRNA. Translation: AAH23019.1. M12079 mRNA. Translation: AAA52152.1. AF040259 mRNA. Translation: AAD10199.1.
IPI	IPI00218839.
PIR	O4HU6. A24797.
RefSeq	NP_000490.1.
UniGene	Hs.72912
3D structure databases
HSSP	HSSP built from PDB template 1DT6 based on UniProtKB P00179.
SMR	P04798. Positions 32-509.
ModBase	Search...
Protein-protein interaction databases
STRING	P04798.
PTM databases
PhosphoSite	P04798.
Proteomic databases
PRIDE	P04798.
Genome annotation databases
Ensembl	ENST00000268062; ENSP00000268062; ENSG00000140465; Homo sapiens. [Genome view] ENST00000379727; ENSP00000369050; ENSG00000140465; Homo sapiens. [Genome view] ENST00000395048; ENSP00000378488; ENSG00000140465; Homo sapiens. [Genome view] ENST00000395049; ENSP00000378489; ENSG00000140465; Homo sapiens. [Genome view]
GeneID	1543.
KEGG	hsa:1543.
UCSC	uc002ayp.2. human.
Organism-specific databases
CTD	1543.
GeneCards	GC15M072798.
H-InvDB	HIX0012410.
HGNC	HGNC:2595. CYP1A1.
HPA	CAB018654.
MIM	108330. gene.
PharmGKB	PA27092.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P04798.
HOVERGEN	P04798.
OMA	HNHQELL.
Enzyme and pathway databases
BRENDA	1.14.14.1. 247.
Reactome	REACT_13433. Biological oxidations. REACT_649. Phase 1 functionalization.
Gene expression databases
ArrayExpress	P04798.
Bgee	P04798.
CleanEx	HS_CYP1A1.
Genevestigator	P04798.
GermOnline	ENSG00000140465. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017973. Cyt_P450_C. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. IPR008066. Cyt_P450_E_grp-I_CYP1. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHER	PTHR19383. Cyt_P450. 1 hit. PTHR19383:SF63. Cyt_P450_E_grp-I_CYP1. 1 hit.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR01683. EP450ICYP1A. PR00385. P450.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB01169. Arsenic trioxide. DB00865. Benzphetamine. DB00290. Bleomycin. DB00356. Chlorzoxazone. DB00851. Dacarbazine. DB00970. Dactinomycin. DB00736. Esomeprazole. DB00655. Estrone. DB01095. Fluvastatin. DB00176. Fluvoxamine. DB01404. Ginseng. DB00889. Granisetron. DB01026. Ketoconazole. DB00170. Menadione. DB00466. Picrotoxin. DB01087. Primaquine. DB00908. Quinidine. DB00468. Quinine. DB00730. Thiabendazole.
NextBio	6387.
SOURCE	Search...

Entry information

Entry name

CP1A1_HUMAN

Accession

Primary (citable) accession number: P04798
Secondary accession number(s): Q53G18

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	April 1, 1988
Last modified:	November 3, 2009
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.