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 27-MAR-2024, entry version 160. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 ChEMBL; CHEMBL1907985; -. DR PaxDb; 9986-ENSOCUP00000020892; -. DR Ensembl; ENSOCUT00000021366.1; ENSOCUP00000020892.1; ENSOCUG00000021501.3. 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; ANDAMYA; -. DR OrthoDB; 2900138at2759; -. 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 cell types or 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 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:SF374; CYTOCHROME P450 2C18; 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. 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 //