ID   CP270_RAT               Reviewed;         489 AA.
AC   P19225;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 1.
DT   24-JAN-2024, entry version 164.
DE   RecName: Full=Cytochrome P450 2C70;
DE            EC=1.14.14.- {ECO:0000250|UniProtKB:Q91W64};
DE   AltName: Full=CYPIIC70;
DE   AltName: Full=Cytochrome P-450Md;
DE   AltName: Full=Cytochrome P450 P49;
DE   Flags: Precursor;
GN   Name=Cyp2c70 {ECO:0000312|RGD:620368};
GN   Synonyms=Cyp2c-70, Cyp2c22, P450md;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=2395662; DOI=10.1093/nar/18.16.4934;
RA   Nagata K., Sasamura H., Miyata M., Shimada M., Yamazoe Y., Kato R.;
RT   "cDNA and deduced amino acid sequences of a male dominant P-450Md mRNA in
RT   rats.";
RL   Nucleic Acids Res. 18:4934-4934(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=2263625; DOI=10.1073/pnas.87.24.9746;
RA   Emi Y., Chijiiwa C., Omura T.;
RT   "A different cytochrome P450 form is induced in primary cultures of rat
RT   hepatocytes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:9746-9750(1990).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase involved in muricholic acid
CC       (MCA) synthesis. Hydroxylates at the 6-beta position two major bile
CC       acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) to
CC       form alpha-MCA and beta-MCA, respectively. May regulate NR1H4/farnesoid
CC       X receptor signaling, as taurine-conjugated MCAs are antagonists of
CC       NR1H4. Mechanistically, uses molecular oxygen inserting one oxygen atom
CC       into a substrate, and reducing the second into a water molecule, with
CC       two electrons provided by NADPH via cytochrome P450 reductase (CPR;
CC       NADPH-ferrihemoprotein reductase). {ECO:0000250|UniProtKB:Q91W64}.
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:0000250|UniProtKB:Q91W64};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51449;
CC         Evidence={ECO:0000250|UniProtKB:Q91W64};
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:0000250|UniProtKB:Q91W64};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51453;
CC         Evidence={ECO:0000250|UniProtKB:Q91W64};
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   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; X53477; CAA37570.1; -; mRNA.
DR   EMBL; M58041; AAA40950.1; -; mRNA.
DR   PIR; S11160; A39257.
DR   RefSeq; NP_612521.1; NM_138512.1.
DR   AlphaFoldDB; P19225; -.
DR   SMR; P19225; -.
DR   IntAct; P19225; 4.
DR   STRING; 10116.ENSRNOP00000051607; -.
DR   iPTMnet; P19225; -.
DR   PhosphoSitePlus; P19225; -.
DR   PaxDb; 10116-ENSRNOP00000051607; -.
DR   Ensembl; ENSRNOT00000054724.3; ENSRNOP00000051607.2; ENSRNOG00000021924.5.
DR   Ensembl; ENSRNOT00055050001; ENSRNOP00055041169; ENSRNOG00055028865.
DR   Ensembl; ENSRNOT00060042148; ENSRNOP00060034950; ENSRNOG00060024351.
DR   Ensembl; ENSRNOT00065052030; ENSRNOP00065042828; ENSRNOG00065030141.
DR   GeneID; 171518; -.
DR   KEGG; rno:171518; -.
DR   UCSC; RGD:620368; rat.
DR   AGR; RGD:620368; -.
DR   CTD; 171518; -.
DR   RGD; 620368; Cyp2c22.
DR   eggNOG; KOG0156; Eukaryota.
DR   GeneTree; ENSGT00940000162654; -.
DR   HOGENOM; CLU_001570_22_3_1; -.
DR   InParanoid; P19225; -.
DR   OMA; SYELCFI; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; P19225; -.
DR   TreeFam; TF352043; -.
DR   PRO; PR:P19225; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000021924; Expressed in liver and 14 other cell types or tissues.
DR   ExpressionAtlas; P19225; 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:0004497; F:monooxygenase activity; TAS:RGD.
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; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
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; PR01686; EP450ICYP2D.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   Genevisible; P19225; RN.
PE   2: Evidence at transcript 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_0000051727"
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        50
FT                   /note="I -> M (in Ref. 2; AAA40950)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        177
FT                   /note="V -> L (in Ref. 2; AAA40950)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        456
FT                   /note="T -> I (in Ref. 2; AAA40950)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        478
FT                   /note="V -> L (in Ref. 2; AAA40950)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        483
FT                   /note="E -> Q (in Ref. 2; AAA40950)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   489 AA;  56157 MW;  E4C5B082AB81CB4D CRC64;
     MALFIFLGIW LSCLVFLFLW NQHHVRRKLP PGPTPLPIFG NILQVGVKNI SKSMCMLAKE
     YGPVFTMYLG MKPTVVLYGY EVLKEALIDR GEEFSDKMHS SMLSKVSQGL GIVFSNGEIW
     KQTRRFSLMV LRSMGMGKRT IENRIQEEVV YLLEALRKTN GSPCDPSFLL ACVPCNVISS
     VIFQHRFDYS DEKFQKFIEN FHTKIEILAS PWAQLCSAYP VLYYLPGIHN KFLKDVTEQK
     KFILMEINRH RASLNLSNPQ DFIDYFLIKM EKEKHNEKSE FTMDNLIVTI GDLFGAGTET
     TSSTIKYGLL LLLKYPEVTA KIQEEITRVI GRHRRPCMQD RNHMPYTDAV LHEIQRYIDF
     VPIPLPRKTT QDVEFRGYHI PKGTSVMACL TSALHDDKEF PNPEKFDPGH FLDEKGNFKK
     SDYFMAFSAG RRACIGEGLA RMEMFLILTS ILQHFTLKPL VNPEDIDTTP VQPGLLSVPP
     PFELCFIPV
//