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   24-JAN-2024, entry version 160.
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,
GN   ECO:0000312|MGI:MGI:2385878};
GN   Synonyms=Cyp2c-70 {ECO:0000250|UniProtKB:P19225}, Cyp2c22
GN   {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
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51448, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:36234,
CC         ChEBI:CHEBI:57618, 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; 10090-ENSMUSP00000060584; -.
DR   PeptideAtlas; Q91W64; -.
DR   ProteomicsDB; 285258; -.
DR   DNASU; 226105; -.
DR   Ensembl; ENSMUST00000051846.13; ENSMUSP00000060584.7; ENSMUSG00000060613.11.
DR   GeneID; 226105; -.
DR   KEGG; mmu:226105; -.
DR   UCSC; uc008hkj.2; mouse.
DR   AGR; MGI:2385878; -.
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; SYELCFI; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; Q91W64; -.
DR   TreeFam; TF352043; -.
DR   BioGRID-ORCS; 226105; 5 hits in 75 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 cell types or tissues.
DR   ExpressionAtlas; Q91W64; baseline and differential.
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:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR   CDD; cd20665; CYP2C-like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR24300:SF200; CYTOCHROME P450 2C70; 1.
DR   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   Genevisible; Q91W64; MM.
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
//