P00185 (CP1A1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 1A1
Short name=CYP1A1
EC=1.14.14.1

Alternative name(s):
CYPIA1
Cytochrome P450-C
Cytochrome P450MT2

Cleaved into the following 2 chains:

1. Cytochrome P450MT2A
2. Cytochrome P450MT2B

Gene names

Name:	Cyp1a1
Synonyms:	Cyp1a-1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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	Cytochrome P450 1A1: Cytoplasm Ref.7. Cytochrome P450MT2A: Endoplasmic reticulum membrane. Mitochondrion membrane. Microsome membrane Ref.7. Cytochrome P450MT2B: Endoplasmic reticulum. Mitochondrion Ref.7.
Tissue specificity	Liver.
Induction	By 3-methylcholanthrene (3MC) and beta-naphthoflavone (BNF).
Domain	Contains a chimeric signal that facilitates targeting of the protein to both the endoplasmic reticulum and mitochondria. A 12 amino acid sequence between 33 and 44 functions as a putative mitochondrial-targeting signal. The removal of the first 4- or 32-amino acid residues from the intact protein positions the mitochondrial targeting signal for efficient binding to the mitochondrial import receptors. The membrane-free P4501A1 seems to be more sensitive to proteolysis.
Post-translational modification	Two forms; MT2A (long form) and MT2B (short form); are produced by NH2-terminal proteolytic cleavage. This cleavage activates a cryptic mitochondrial targeting signal.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Microsome Mitochondrion
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	9-cis-retinoic acid biosynthetic process Inferred from direct assay PubMed 8765131. Source: RGD aging Inferred from expression pattern PubMed 21769602. Source: RGD amine metabolic process Inferred from electronic annotation. Source: Compara camera-type eye development Inferred from expression pattern PubMed 15967433. Source: RGD cell proliferation Inferred from expression pattern PubMed 17560764. Source: RGD coumarin metabolic process Inferred from direct assay PubMed 11780761. Source: RGD dibenzo-p-dioxin catabolic process Inferred from direct assay PubMed 15812643. Source: RGD digestive tract development Inferred from expression pattern PubMed 12162855. Source: RGD drug metabolic process Inferred from electronic annotation. Source: Compara embryo development ending in birth or egg hatching Inferred from expression pattern PubMed 16225763. Source: RGD flavonoid metabolic process Inferred from direct assay PubMed 18057719. Source: RGD hepatocyte differentiation Inferred from expression pattern PubMed 17574236. Source: RGD hydrogen peroxide biosynthetic process Inferred from electronic annotation. Source: Compara insecticide metabolic process Inferred from direct assay PubMed 16169030. Source: RGD maternal process involved in parturition Inferred from expression pattern PubMed 16226747. Source: RGD porphyrin-containing compound metabolic process Inferred from direct assay PubMed 12907239. Source: RGD positive regulation of S phase of mitotic cell cycle Inferred from direct assay PubMed 14742689. Source: RGD response to antibiotic Inferred from expression pattern PubMed 10037757. Source: RGD response to arsenic-containing substance Inferred from expression pattern PubMed 10329507. Source: RGD response to drug Inferred from expression pattern PubMed 19122336. Source: RGD response to food Inferred from expression pattern PubMed 15740081PubMed 17673347. Source: RGD response to herbicide Inferred from expression pattern PubMed 12907239. Source: RGD response to hyperoxia Inferred from expression pattern PubMed 16497785. Source: RGD response to hypoxia Inferred from expression pattern PubMed 11589108. Source: RGD response to iron(III) ion Inferred from expression pattern PubMed 15211619. Source: RGD response to lipopolysaccharide Inferred from expression pattern PubMed 18308837. Source: RGD response to nematode Inferred from expression pattern PubMed 12621079. Source: RGD response to organic cyclic compound Inferred from expression pattern PubMed 10413312PubMed 10640292PubMed 10772642PubMed 16937917PubMed 18678235PubMed 18827444PubMed 18978342PubMed 19373505. Source: RGD response to virus Inferred from expression pattern PubMed 15061698. Source: RGD response to vitamin A Inferred from expression pattern PubMed 10381141. Source: RGD response to wounding Inferred from expression pattern PubMed 14723344. Source: RGD
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay Ref.7. Source: RGD
Molecular_function	aromatase activity Inferred from electronic annotation. Source: EC demethylase activity Inferred from direct assay PubMed 10915793PubMed 11370669. Source: RGD electron carrier activity Inferred from electronic annotation. Source: InterPro enzyme binding Inferred from direct assay PubMed 10891369. Source: RGD flavonoid 3'-monooxygenase activity Inferred from direct assay PubMed 18057719. Source: RGD 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 direct assay PubMed 12054491. Source: RGD steroid hydroxylase activity Inferred from direct assay PubMed 11370669. Source: RGD vitamin D 24-hydroxylase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	2 – 524	523	Cytochrome P450 1A1		PRO_0000003564
	Chain	5 – 524	520	Cytochrome P450MT2A		PRO_0000003565
	Chain	33 – 524	492	Cytochrome P450MT2B		PRO_0000003566
Regions
	Region	33 – 44	12	Mitochondrial targeting signal
Sites
	Metal binding	461	1	Iron (heme axial ligand)
Experimental info
	Mutagenesis	32 – 33	2	VT → AI: No proteolytic cleavage. Ref.7
	Sequence conflict	21 – 22	2	TT → VV AA sequence Ref.5
	Sequence conflict	53	1	I → M in CAA25153. Ref.2
	Sequence conflict	494	1	M → S in AAA41025. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P00185 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: C766DF8044D598C5	FASTA	524	59,393
	10 20 30 40 50 60 MPSVYGFPAF TSATELLLAV TTFCLGFWVV RVTRTWVPKG LKSPPGPWGL PFIGHVLTLG 70 80 90 100 110 120 KNPHLSLTKL SQQYGDVLQI RIGSTPVVVL SGLNTIKQAL VKQGDDFKGR PDLYSFTLIA 130 140 150 160 170 180 NGQSMTFNPD SGPLWAARRR LAQNALKSFS IASDPTLASS CYLEEHVSKE AEYLISKFQK 190 200 210 220 230 240 LMAEVGHFDP FKYLVVSVAN VICAICFGRR YDHDDQELLS IVNLSNEFGE VTGSGYPADF 250 260 270 280 290 300 IPILRYLPNS SLDAFKDLNK KFYSFMKKLI KEHYRTFEKG HIRDITDSLI EHCQDRRLDE 310 320 330 340 350 360 NANVQLSDDK VITIVFDLFG AGFDTITTAI SWSLMYLVTN PRIQRKIQEE LDTVIGRDRQ 370 380 390 400 410 420 PRLSDRPQLP YLEAFILETF RHSSFVPFTI PHSTIRDTSL NGFYIPKGHC VFVNQWQVNH 430 440 450 460 470 480 DQELWGDPNE FRPERFLTSS GTLDKHLSEK VILFGLGKRK CIGETIGRLE VFLFLAILLQ 490 500 510 520 QMEFNVSPGE KVDMTPAYGL TLKHARCEHF QVQMRSSGPQ HLQA

References

[1]	"Distinct organization of methylcholanthrene- and phenobarbital-inducible cytochrome P-450 genes in the rat." Sogawa K., Gotoh O., Kawajiri K., Fujii-Kuriyama Y. Proc. Natl. Acad. Sci. U.S.A. 81:5066-5070(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Nucleotide sequence of a full-length cDNA coding for 3-methylcholanthrene-induced rat liver cytochrome P-450MC." Yabusaki Y., Shimizu M., Murakami H., Nakamura K., Oeda K., Ohkawa H. Nucleic Acids Res. 12:2929-2938(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Gene structure and nucleotide sequence for rat cytochrome P-450c." Hines R.N., Levy J.B., Conrad R.D., Iversen P.L., Shen M.-L., Renli A.M., Bresnick E. Arch. Biochem. Biophys. 237:465-476(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Amino-terminal sequence and structure of monoclonal antibody immunopurified cytochromes P-450." Cheng K.C., Park S.S., Krutzsch H.C., Grantham P.H., Gelboin H.V., Friedman F.K. Biochemistry 25:2397-2402(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-26.
[5]	"Effect of nutritional imbalances on cytochrome P-450 isozymes in rat liver." Amelizad Z., Narbonne J.F., Wolf C.R., Robertson L.W., Oesch F. Biochem. Pharmacol. 37:3245-3249(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-22.
[6]	"Identification and characterization of cytochrome P4501A1 amino acid residues interacting with a radiolabeled photoaffinity diazido-benzphetamine analogue." Cvrk T., Hodek P., Strobel H.W. Arch. Biochem. Biophys. 330:142-152(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[7]	"Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2." Addya S., Anandatheerthavarada H.K., Biswas G., Bhagwat S.V., Mullick J., Avadhani N.G. J. Cell Biol. 139:589-599(1997) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 32-VAL-THR-33. Strain: Sprague-Dawley. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	K02246 Genomic DNA. Translation: AAA41027.1. X00469 mRNA. Translation: CAA25153.1. M26129 Genomic DNA. Translation: AAA41025.1.
IPI	IPI00206995.
PIR	O4RTMC. A00185.
RefSeq	NP_036672.2. NM_012540.2.
UniGene	Rn.10352.
3D structure databases
ProteinModelPortal	P00185.
SMR	P00185. Positions 37-513.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000026473.
Proteomic databases
PaxDb	P00185.
PRIDE	P00185.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000026473; ENSRNOP00000026473; ENSRNOG00000019500.
GeneID	24296.
KEGG	rno:24296.
UCSC	RGD:2458. rat.
Organism-specific databases
CTD	1543.
RGD	2458. Cyp1a1.
Phylogenomic databases
eggNOG	COG2124.
GeneTree	ENSGT00680000099714.
HOVERGEN	HBG106944.
InParanoid	P00185.
KO	K07408.
OMA	FDSENIQ.
OrthoDB	EOG4WSW9D.
Enzyme and pathway databases
SABIO-RK	P00185.
Gene expression databases
Genevestigator	P00185.
GermOnline	ENSRNOG00000019500. Rattus norvegicus.
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
ChEMBL	CHEMBL2922.
NextBio	602902.

Entry information

Entry name

CP1A1_RAT

Accession

Primary (citable) accession number: P00185

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program