Reviewed, UniProtKB/Swiss-Prot P00185 (CP1A1_RAT)

Names and origin

Protein names

Recommended name:
    Cytochrome P450 1A1
      Short name=CYP1A1
    EC=1.14.14.1
Alternative name(s):
    CYPIA1
    P450-C
    P450MT2
Cleaved into the following 2 chains:
    1- Recommended name:
            Cytochrome P450MT2A
    2- Recommended name:
            Cytochrome P450MT2B

Gene names

Name:	Cyp1a1
Synonyms:	Cyp1a-1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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 sensible 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
PTM	Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	9-cis-retinoic acid biosynthetic process Inferred from direct assay. Source: RGD camera-type eye development Inferred from expression pattern. Source: RGD cell proliferation Inferred from expression pattern. Source: RGD coumarin metabolic process Inferred from direct assay. Source: RGD dibenzo-p-dioxin catabolic process Inferred from direct assay. Source: RGD embryonic development ending in birth or egg hatching Inferred from expression pattern. Source: RGD flavonoid metabolic process Inferred from direct assay. Source: RGD gut development Inferred from expression pattern. Source: RGD hepatocyte differentiation Inferred from expression pattern. Source: RGD insecticide metabolic process Inferred from direct assay. Source: RGD maternal process involved in parturition Inferred from expression pattern. Source: RGD oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW porphyrin metabolic process Inferred from direct assay. Source: RGD positive regulation of S phase of mitotic cell cycle Inferred from direct assay. Source: RGD response to antibiotic Inferred from expression pattern. Source: RGD response to arsenic Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to food Inferred from expression pattern. Source: RGD response to herbicide Inferred from expression pattern. Source: RGD response to hyperoxia Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to iron(III) ion Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to nematode Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD response to virus Inferred from expression pattern. Source: RGD response to vitamin A Inferred from expression pattern. Source: RGD response to wounding Inferred from expression pattern. Source: RGD
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from direct assay. Source: RGD mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aromatase activity Inferred from electronic annotation. Source: EC demethylase activity Inferred from direct assay. Source: RGD electron carrier activity Inferred from electronic annotation. Source: InterPro enzyme binding Inferred from direct assay. Source: RGD flavonoid 3'-monooxygenase activity Inferred from direct assay. Source: RGD heme binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on diphenols and related substances as donors Inferred from direct assay. Source: RGD steroid hydroxylase activity Inferred from direct assay. Source: RGD
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)
Amino acid modifications
	Modified residue	364	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	32 – 33	2	VT → AI: No proteolytic cleavage.
	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)
	P00185-1 [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: 6089174] [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: 6324135] [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: 3838427] [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: 3718958] [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: 3041969] [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: 8651689] [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: 9348277] [Abstract] Cited for: SUBCELLULAR LOCATION. Strain: Sprague-Dawley. Tissue: Liver.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Rn.10352
3D structure databases
HSSP	HSSP built from PDB template 1N6B based on UniProtKB P00179.
ModBase	Search...
Genome annotation databases
Ensembl	ENSRNOG00000019500. Rattus norvegicus. [Contig view]
GeneID	24296.
KEGG	rno:24296.
Organism-specific databases
RGD	2458. Cyp1a1.
Phylogenomic databases
HOVERGEN	P00185.
OMA	P00185. KEHYRTF.
Enzyme and pathway databases
BRENDA	1.14.14.1. 248.
Gene expression databases
ArrayExpress	P00185.
GermOnline	ENSRNOG00000019500. Rattus norvegicus.
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
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:	June 16, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)