CP270_MOUSE
ID CP270_MOUSE Reviewed; 489 AA.
AC Q91W64; Q5GLY9; Q80VW0; Q8R120; Q8VC00;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Cytochrome P450 2C70;
DE EC=1.14.14.- {ECO:0000269|PubMed:27638959};
DE AltName: Full=CYPIIC70;
DE Flags: Precursor;
GN Name=Cyp2c70 {ECO:0000303|PubMed:27638959, ECO:0000312|MGI:MGI:2385878};
GN Synonyms=Cyp2c-70 {ECO:0000250|UniProtKB:P19225},
GN Cyp2c22 {ECO:0000250|UniProtKB:P19225};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Zhao Y., Wang H., Goldstein J.A., Zeldin D.C.;
RT "Molecular cloning, expression, and characterization of four novel mouse
RT cytochrome P450 (CYP) genes (CYP2C65, CYP2C66, CYP2C53 and CYP2C70).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=27638959; DOI=10.1194/jlr.m071183;
RA Takahashi S., Fukami T., Masuo Y., Brocker C.N., Xie C., Krausz K.W.,
RA Wolf C.R., Henderson C.J., Gonzalez F.J.;
RT "Cyp2c70 is responsible for the species difference in bile acid metabolism
RT between mice and humans.";
RL J. Lipid Res. 57:2130-2137(2016).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in muricholic acid
CC (MCA) synthesis (PubMed:27638959). Hydroxylates at the 6-beta position
CC two major bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic
CC acid (UDCA) to form alpha-MCA and beta-MCA, respectively
CC (PubMed:27638959). May regulate NR1H4/farnesoid X receptor signaling,
CC as taurine-conjugated MCAs are antagonists of NR1H4. Mechanistically,
CC uses molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein
CC reductase) (PubMed:27638959). {ECO:0000269|PubMed:27638959}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + O2 + reduced [NADPH--hemoprotein
CC reductase] = alpha-muricholate + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:51448, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:36234, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:134116;
CC Evidence={ECO:0000269|PubMed:27638959};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51449;
CC Evidence={ECO:0000305|PubMed:27638959};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + ursodeoxycholate
CC = beta-muricholate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:51452, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78604,
CC ChEBI:CHEBI:134119; Evidence={ECO:0000269|PubMed:27638959};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51453;
CC Evidence={ECO:0000305|PubMed:27638959};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P33261};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in liver. {ECO:0000269|PubMed:27638959}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH25822.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY227736; AAP55509.1; -; mRNA.
DR EMBL; BC016494; AAH16494.1; -; mRNA.
DR EMBL; BC022151; AAH22151.1; -; mRNA.
DR EMBL; BC023894; AAH23894.2; -; mRNA.
DR EMBL; BC025822; AAH25822.1; ALT_INIT; mRNA.
DR EMBL; BC034831; AAH34831.1; -; mRNA.
DR CCDS; CCDS37976.1; -.
DR RefSeq; NP_663474.2; NM_145499.2.
DR AlphaFoldDB; Q91W64; -.
DR SMR; Q91W64; -.
DR STRING; 10090.ENSMUSP00000060584; -.
DR SwissLipids; SLP:000001666; -.
DR iPTMnet; Q91W64; -.
DR PhosphoSitePlus; Q91W64; -.
DR SwissPalm; Q91W64; -.
DR jPOST; Q91W64; -.
DR MaxQB; Q91W64; -.
DR PaxDb; Q91W64; -.
DR PeptideAtlas; Q91W64; -.
DR PRIDE; Q91W64; -.
DR ProteomicsDB; 285258; -.
DR DNASU; 226105; -.
DR Ensembl; ENSMUST00000051846; ENSMUSP00000060584; ENSMUSG00000060613.
DR GeneID; 226105; -.
DR KEGG; mmu:226105; -.
DR UCSC; uc008hkj.2; mouse.
DR CTD; 226105; -.
DR MGI; MGI:2385878; Cyp2c70.
DR VEuPathDB; HostDB:ENSMUSG00000060613; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000162654; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; Q91W64; -.
DR OMA; TSGRPTM; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q91W64; -.
DR TreeFam; TF352043; -.
DR BioGRID-ORCS; 226105; 4 hits in 70 CRISPR screens.
DR ChiTaRS; Cyp2c70; mouse.
DR PRO; PR:Q91W64; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q91W64; protein.
DR Bgee; ENSMUSG00000060613; Expressed in left lobe of liver and 50 other tissues.
DR ExpressionAtlas; Q91W64; baseline and differential.
DR Genevisible; Q91W64; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F: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; IBA:GO_Central.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..489
FT /note="Cytochrome P450 2C70"
FT /evidence="ECO:0000255"
FT /id="PRO_0000051726"
FT BINDING 434
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P33261"
FT CONFLICT 46
FT /note="D -> Y (in Ref. 1; AAP55509 and 2; AAH16494)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="V -> A (in Ref. 1; AAP55509)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 489 AA; 56020 MW; 90973D9B05964B1B CRC64;
MALFIFLGIW LSCFLFLFLW NQHRGRGKLP PGPTPLPIVG NILQVDVKNI SKSMGMLAKK
YGPVFTVYLG MKPTVVLHGY KAMKEALIDQ GDEFSDKTDS SLLSRTSQGL GIVFSNGETW
KQTRRFSLMV LRSMGMGKKT IEDRIQEEIL YMLDALRKTN GSPCDPSFLL ACVPCNVIST
VIFQHRFDYN DQTFQDFMEN FHRKIEILAS PWSQLCSAYP ILYYLPGIHN RFLKDVTQQK
KFILEEINRH QKSLDLSNPQ DFIDYFLIKM EKEKHNQKSE FTMDNLVVSI GDLFGAGTET
TSSTVKYGLL LLLKYPEVTA KIQEEIAHVI GRHRRPTMQD RNHMPYTDAV LHEIQRYIDF
VPIPSPRKTT QDVEFRGYHI PKGTSVMACL TSVLNDDKEF PNPEKFDPGH FLDEKGNFKK
SDYFVAFSAG RRACIGEGLA RMEMFLILTN ILQHFTLKPL VKPEDIDTKP VQTGLLHVPP
PFELCFIPV
