CP2C5_RABIT
ID CP2C5_RABIT Reviewed; 487 AA.
AC P00179; Q29511;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cytochrome P450 2C5;
DE EC=1.14.14.1;
DE AltName: Full=CYPIIC5;
DE AltName: Full=Cytochrome P450 1;
DE AltName: Full=Cytochrome P450IIC5;
DE AltName: Full=Progesterone 21-hydroxylase;
GN Name=CYP2C5;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3902818; DOI=10.1016/s0021-9258(17)38876-2;
RA Tukey R.H., Okino S., Barnes H.J., Griffin K.J., Johnson E.F.;
RT "Multiple gene-like sequences related to the rabbit hepatic progesterone
RT 21-hydroxylase cytochrome P-450 1.";
RL J. Biol. Chem. 260:13347-13354(1985).
RN [2]
RP SEQUENCE REVISION TO 252.
RA Tukey R.H.;
RL Submitted (FEB-1986) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=III/J; TISSUE=Liver;
RX PubMed=2387874; DOI=10.1016/s0021-9258(18)77353-5;
RA Pendurthi U.R., Lamb J.G., Nguyen N., Johnson E.F., Tukey R.H.;
RT "Characterization of the CYP2C5 gene in 21L III/J rabbits. Allelic
RT variation affects the expression of P450IIC5.";
RL J. Biol. Chem. 265:14662-14668(1990).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=10678174; DOI=10.1016/s1097-2765(00)80408-6;
RA Williams P.A., Cosme J., Sridhar V., Johnson E.F., McRee D.E.;
RT "Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations
RT for membrane binding and functional diversity.";
RL Mol. Cell 5:121-131(2000).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG.
RX PubMed=12767218; DOI=10.1021/bi0273922;
RA Wester M.R., Johnson E.F., Marques-Soares C., Dansette P.M., Mansuy D.,
RA Stout C.D.;
RT "Structure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 A
RT resolution: evidence for multiple substrate binding modes.";
RL Biochemistry 42:6370-6379(2003).
CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases.
CC In liver microsomes, this enzyme is involved in an NADPH-dependent
CC electron transport pathway. It oxidizes a variety of structurally
CC unrelated compounds, including steroids, fatty acids, and xenobiotics.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250}.
CC Microsome membrane {ECO:0000250}.
CC -!- INDUCTION: P450 can be induced to high levels in liver and other
CC tissues by various foreign compounds, including drugs, pesticides, and
CC carcinogens.
CC -!- MISCELLANEOUS: This protein differs from other forms of cytochrome P450
CC in that it catalyzes the 21-hydroxylation of progesterone, resulting in
CC the formation of deoxycorticosterone.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; M11299; AAA31209.1; -; mRNA.
DR EMBL; M55664; AAA63461.1; -; mRNA.
DR PIR; A00180; O4RBP4.
DR RefSeq; NP_001164397.1; NM_001170926.1.
DR PDB; 1DT6; X-ray; 3.00 A; A=22-487.
DR PDB; 1N6B; X-ray; 2.30 A; A=19-487.
DR PDB; 1NR6; X-ray; 2.10 A; A=19-487.
DR PDBsum; 1DT6; -.
DR PDBsum; 1N6B; -.
DR PDBsum; 1NR6; -.
DR AlphaFoldDB; P00179; -.
DR SMR; P00179; -.
DR STRING; 9986.ENSOCUP00000020892; -.
DR ChEMBL; CHEMBL1907985; -.
DR Ensembl; ENSOCUT00000021366; ENSOCUP00000020892; ENSOCUG00000021501.
DR GeneID; 100328549; -.
DR KEGG; ocu:100328549; -.
DR CTD; 100328549; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000154299; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; P00179; -.
DR OMA; YDSHRAT; -.
DR OrthoDB; 702827at2759; -.
DR TreeFam; TF352043; -.
DR SABIO-RK; P00179; -.
DR EvolutionaryTrace; P00179; -.
DR PRO; PR:P00179; -.
DR Proteomes; UP000001811; Chromosome 18.
DR Bgee; ENSOCUG00000021501; Expressed in liver and 6 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
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 3D-structure; Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding;
KW Microsome; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..487
FT /note="Cytochrome P450 2C5"
FT /id="PRO_0000051696"
FT BINDING 432
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 CONFLICT 97
FT /note="R -> T (in Ref. 1; AAA31209)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="Q -> E (in Ref. 1; AAA31209)"
FT /evidence="ECO:0000305"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 50..61
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 63..77
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 80..87
FT /evidence="ECO:0007829|PDB:1NR6"
FT TURN 88..94
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1N6B"
FT HELIX 103..107
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 117..130
FT /evidence="ECO:0007829|PDB:1NR6"
FT TURN 133..136
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 141..157
FT /evidence="ECO:0007829|PDB:1NR6"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 167..183
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 192..207
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 220..225
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 227..254
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 263..272
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:1DT6"
FT HELIX 281..312
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 314..327
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 336..341
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 343..356
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 388..392
FT /evidence="ECO:0007829|PDB:1NR6"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 406..409
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 412..415
FT /evidence="ECO:0007829|PDB:1DT6"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 435..452
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 453..459
FT /evidence="ECO:0007829|PDB:1NR6"
FT HELIX 461..463
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 472..476
FT /evidence="ECO:0007829|PDB:1NR6"
FT STRAND 482..486
FT /evidence="ECO:0007829|PDB:1NR6"
SQ SEQUENCE 487 AA; 55275 MW; ED67B2E255DF5EA0 CRC64;
MDPVVVLVLG LCCLLLLSIW KQNSGRGKLP PGPTPFPIIG NILQIDAKDI SKSLTKFSEC
YGPVFTVYLG MKPTVVLHGY EAVKEALVDL GEEFAGRGSV PILEKVSKGL GIAFSNAKTW
KEMRRFSLMT LRNFGMGKRS IEDRIQEEAR CLVEELRKTN ASPCDPTFIL GCAPCNVICS
VIFHNRFDYK DEEFLKLMES LNENVRILSS PWLQVYNNFP ALLDYFPGIH KTLLKNADYI
KNFIMEKVKE HQKLLDVNNP RDFIDCFLIK MEQENNLEFT LESLVIAVSD LFGAGTETTS
TTLRYSLLLL LKHPEVAARV QEEIERVIGR HRSPCMQDRS RMPYTDAVIH EIQRFIDLLP
TNLPHAVTRD VRFRNYFIPK GTDIITSLTS VLHDEKAFPN PKVFDPGHFL DESGNFKKSD
YFMPFSAGKR MCVGEGLARM ELFLFLTSIL QNFKLQSLVE PKDLDITAVV NGFVSVPPSY
QLCFIPI
