P04798 (CP1A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 1A1
EC=1.14.14.1

Alternative name(s):
CYPIA1
Cytochrome P450 form 6
Cytochrome P450-C
Cytochrome P450-P1

Gene names

Name:

CYP1A1

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	512 AA.
Sequence status	Complete.
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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	9-cis-retinoic acid biosynthetic process Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara amine metabolic process Inferred from electronic annotation. Source: Compara camera-type eye development Inferred from electronic annotation. Source: Compara cell proliferation Inferred from electronic annotation. Source: Compara cellular lipid metabolic process Traceable author statement. Source: Reactome coumarin metabolic process Inferred from electronic annotation. Source: Compara dibenzo-p-dioxin catabolic process Inferred from electronic annotation. Source: Compara digestive tract development Inferred from electronic annotation. Source: Compara drug metabolic process Inferred from direct assay PubMed 19219744. Source: BHF-UCL embryo development ending in birth or egg hatching Inferred from electronic annotation. Source: Compara flavonoid metabolic process Inferred from electronic annotation. Source: Compara hepatocyte differentiation Inferred from electronic annotation. Source: Compara hydrogen peroxide biosynthetic process Inferred from electronic annotation. Source: Compara insecticide metabolic process Inferred from electronic annotation. Source: Compara maternal process involved in parturition Inferred from electronic annotation. Source: Compara porphyrin-containing compound metabolic process Inferred from electronic annotation. Source: Compara positive regulation of S phase of mitotic cell cycle Inferred from electronic annotation. Source: Compara response to antibiotic Inferred from electronic annotation. Source: Compara response to arsenic-containing substance Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to food Inferred from electronic annotation. Source: Compara response to herbicide Inferred from electronic annotation. Source: Compara response to hyperoxia Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to iron(III) ion Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to nematode Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara response to virus Inferred from electronic annotation. Source: Compara response to vitamin A Inferred from electronic annotation. Source: Compara response to wounding Inferred from electronic annotation. Source: Compara vitamin D metabolic process Inferred by curator PubMed 15546903. Source: BHF-UCL xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	aromatase activity Inferred from electronic annotation. Source: EC demethylase activity Inferred from electronic annotation. Source: Compara electron carrier activity Inferred from electronic annotation. Source: InterPro flavonoid 3'-monooxygenase activity Inferred from electronic annotation. Source: Compara heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on diphenols and related substances as donors Inferred from electronic annotation. Source: Compara oxygen binding Traceable author statement PubMed 1691986. Source: ProtInc steroid hydroxylase activity Inferred from electronic annotation. Source: Compara vitamin D 24-hydroxylase activity Inferred from direct assay PubMed 15546903. Source: BHF-UCL
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)
Natural variations
	Natural variant	45	1	G → D. Ref.5 Ref.14 Ref.15 Corresponds to variant rs4646422 [ dbSNP | Ensembl ].		VAR_023194
	Natural variant	66	1	M → V. Corresponds to variant rs35035798 [ dbSNP | Ensembl ].		VAR_033817
	Natural variant	78	1	I → T. Ref.14 Ref.15 Corresponds to variant rs17861094 [ dbSNP | Ensembl ].		VAR_023195
	Natural variant	93	1	R → W. Ref.14 Corresponds to variant rs2229150 [ dbSNP | Ensembl ].		VAR_024706
	Natural variant	173	1	T → R. Ref.14 Corresponds to variant rs28399427 [ dbSNP | Ensembl ].		VAR_024707
	Natural variant	279	1	R → W. Ref.11 Corresponds to variant rs34260157 [ dbSNP | Ensembl ].		VAR_009280
	Natural variant	286	1	I → T. Corresponds to variant rs4987133 [ dbSNP | Ensembl ].		VAR_020122
	Natural variant	331	1	M → I in allele CYP1A1*6. Ref.12 Corresponds to variant rs56313657 [ dbSNP | Ensembl ].		VAR_016937
	Natural variant	448	1	I → N in allele CYP1A1*8. Ref.13		VAR_016938
	Natural variant	461	1	T → N in allele CYP1A1*4. Ref.10 Ref.14 Ref.15 Corresponds to variant rs1799814 [ dbSNP | Ensembl ].		VAR_008342
	Natural variant	462	1	I → V in allele CYP1A1*2B and allele CYP1A1*2C. Ref.9 Ref.15 Corresponds to variant rs1048943 [ dbSNP | Ensembl ].		VAR_001243
	Natural variant	464	1	R → C in allele CYP1A1*9. Ref.13		VAR_016939
	Natural variant	464	1	R → S in allele CYP1A1*5. Ref.12 Corresponds to variant rs41279188 [ dbSNP | Ensembl ].		VAR_016940
	Natural variant	470	1	F → V. Corresponds to variant rs36121583 [ dbSNP | Ensembl ].		VAR_033818
	Natural variant	477	1	R → W in allele CYP1A1*10. Ref.13 Ref.16 Corresponds to variant rs56240201 [ dbSNP | Ensembl ].		VAR_016941
	Natural variant	482	1	V → M. Ref.14 Corresponds to variant rs28399429 [ dbSNP | Ensembl ].		VAR_024708
	Natural variant	492	1	P → R in allele CYP1A1*11. Ref.13 Ref.14 Corresponds to variant rs28399430 [ dbSNP | Ensembl ].		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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 295-484.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANT VAL-462.
[10]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ASN-461.
[11]	"Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms." Smart J., Daly A.K. Pharmacogenetics 10:11-24(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-279.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-331 AND SER-464.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ASN-448; CYS-464; TRP-477 AND ARG-492.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-45; THR-78; TRP-93; ARG-173; ASN-461; MET-482 AND ARG-492.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-45; THR-78; ASN-461 AND VAL-462.
[16]	"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] [Europe PMC] [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

EMBL
GenBank
DDBJ

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. NM_000499.3.

UniGene

Hs.72912.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4I8V	X-ray	2.60	A/B/C/D	35-512	[»]

ProteinModelPortal

P04798.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000369050.

PTM databases

PhosphoSite

P04798.

Polymorphism databases

DMDM

117139.

Proteomic databases

PaxDb

P04798.

PRIDE

P04798.

Protocols and materials databases

DNASU

1543.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379727; ENSP00000369050; ENSG00000140465.
ENST00000395048; ENSP00000378488; ENSG00000140465.
ENST00000567032; ENSP00000456585; ENSG00000140465.

GeneID

1543.

KEGG

hsa:1543.

UCSC

uc002ayp.4. human.

Organism-specific databases

CTD

1543.

GeneCards

GC15M075011.

HGNC

HGNC:2595. CYP1A1.

HPA

CAB018654.

MIM

108330. gene.

neXtProt

NX_P04798.

PharmGKB

PA27092.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000036991.

HOVERGEN

HBG106944.

InParanoid

P04798.

KO

K07408.

OMA

HLPYMEA.

OrthoDB

EOG4WSW9D.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P04798.

Gene expression databases

ArrayExpress

P04798.

Bgee

P04798.

CleanEx

HS_CYP1A1.

Genevestigator

P04798.

GermOnline

ENSG00000140465. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008066. Cyt_P450_E_grp-I_CYP1.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR01683. EP450ICYP1A.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P04798.

ChEMBL

CHEMBL2231.

ChiTaRS

CYP1A1. human.

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.

GenomeRNAi

1543.

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:	May 1, 2013
This is version 155 of the entry and version 1 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.