CP270_RAT
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 03-AUG-2022, entry version 157.
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}; 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 [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: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; P19225; -.
DR PRIDE; P19225; -.
DR Ensembl; ENSRNOT00000054724; ENSRNOP00000051607; ENSRNOG00000021924.
DR GeneID; 171518; -.
DR KEGG; rno:171518; -.
DR UCSC; RGD:620368; rat.
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; IRESPNR; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P19225; -.
DR TreeFam; TF352043; -.
DR PRO; PR:P19225; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000021924; Expressed in liver and 14 other tissues.
DR ExpressionAtlas; P19225; baseline and differential.
DR Genevisible; P19225; RN.
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: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; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01686; EP450ICYP2D.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
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
