CP51_TRYCC
ID CP51_TRYCC Reviewed; 481 AA.
AC Q7Z1V1; Q5I4E1; Q7Z1V0;
DT 24-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Sterol 14-alpha demethylase {ECO:0000303|PubMed:16321980, ECO:0000312|EMBL:AAW47718.1};
DE Short=Tc14DM {ECO:0000303|PubMed:14599667};
DE EC=1.14.14.154 {ECO:0000269|PubMed:16321980};
DE AltName: Full=Cytochrome P450 51 {ECO:0000250|UniProtKB:P0A512};
DE AltName: Full=Lanosterol 14-alpha demethylase {ECO:0000303|PubMed:14599667, ECO:0000312|EMBL:AAP33131.1};
GN Name=CYP51 {ECO:0000312|EMBL:AAW47718.1};
GN ORFNames=Tc00.1047053506297.260, Tc00.1047053510101.50;
OS Trypanosoma cruzi (strain CL Brener).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=353153;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP33131.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES 1 AND 2), AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=Tulahuen {ECO:0000312|EMBL:AAP33131.1};
RX PubMed=14599667; DOI=10.1016/j.molbiopara.2003.07.004;
RA Buckner F.S., Joubert B.M., Boyle S.M., Eastman R.T., Verlinde C.L.M.J.,
RA Matsuda S.P.T.;
RT "Cloning and analysis of Trypanosoma cruzi lanosterol 14alpha-
RT demethylase.";
RL Mol. Biochem. Parasitol. 132:75-81(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAW47718.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 1), FUNCTION, CATALYTIC ACTIVITY,
RP AND MUTAGENESIS OF ILE-105.
RX PubMed=16321980; DOI=10.1074/jbc.m510317200;
RA Lepesheva G.I., Zaitseva N.G., Nes W.D., Zhou W., Arase M., Liu J.,
RA Hill G.C., Waterman M.R.;
RT "CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B' helix
RT defines substrate preferences of sterol 14alpha-demethylase.";
RL J. Biol. Chem. 281:3577-3585(2006).
RN [3] {ECO:0000312|EMBL:EAN98359.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELES 1 AND 2).
RC STRAIN=CL Brener {ECO:0000312|EMBL:EAN98359.1};
RX PubMed=16020725; DOI=10.1126/science.1112631;
RA El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G.,
RA Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G.,
RA Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B.,
RA Anupama A., Arner E., Aslund L., Attipoe P., Bontempi E., Bringaud F.,
RA Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H.,
RA da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G.,
RA Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y.,
RA Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J.,
RA Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y.,
RA Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M.,
RA Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L.,
RA Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J.,
RA Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C.,
RA Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D.,
RA Andersson B.;
RT "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas
RT disease.";
RL Science 309:409-415(2005).
CC -!- FUNCTION: Catalyzes C14-demethylation of lanosterol which is critical
CC for ergosterol biosynthesis. It transforms lanosterol into 4,4'-
CC dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity). Favors C4
CC dimethylated substrates, the substrate preference order is 24-
CC methylenedihydrolanosterol > 24,25-dihydrolanosterol > lanosterol >
CC obtusifoliol > norlanosterol. {ECO:0000250|UniProtKB:P0A512,
CC ECO:0000269|PubMed:16321980}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC Evidence={ECO:0000269|PubMed:16321980};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P0A512};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 1/6. {ECO:0000250|UniProtKB:P0A512}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed in both the insect and mammalian life-
CC cycle stages. {ECO:0000269|PubMed:14599667}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
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DR EMBL; AY283022; AAP33131.1; -; Genomic_DNA.
DR EMBL; AY283023; AAP33132.1; -; Genomic_DNA.
DR EMBL; AY856083; AAW47718.1; -; Genomic_DNA.
DR EMBL; AAHK01000021; EAN99368.1; -; Genomic_DNA.
DR EMBL; AAHK01000058; EAN98359.1; -; Genomic_DNA.
DR RefSeq; XP_820210.1; XM_815117.1.
DR RefSeq; XP_821219.1; XM_816126.1.
DR PDB; 2WUZ; X-ray; 2.35 A; A/B=22-481.
DR PDB; 2WX2; X-ray; 2.27 A; A/B=22-481.
DR PDB; 3K1O; X-ray; 2.89 A; A=32-481.
DR PDB; 3KHM; X-ray; 2.85 A; A=32-481.
DR PDB; 3KSW; X-ray; 3.05 A; A=32-481.
DR PDB; 3ZG2; X-ray; 2.80 A; A=29-481.
DR PDB; 3ZG3; X-ray; 2.90 A; A=29-481.
DR PDB; 4BMM; X-ray; 2.84 A; A/B/C/D=32-481.
DR PDB; 4BY0; X-ray; 3.10 A; A/B=32-481.
DR PDB; 4C0C; X-ray; 2.04 A; A=32-481.
DR PDB; 4C27; X-ray; 1.95 A; A/B=29-481.
DR PDB; 4C28; X-ray; 2.03 A; A/B=29-481.
DR PDB; 4CK8; X-ray; 2.62 A; A/B=32-481.
DR PDB; 4CK9; X-ray; 2.74 A; A=32-481.
DR PDB; 4CKA; X-ray; 2.70 A; A=32-481.
DR PDB; 4COH; X-ray; 2.08 A; A/B=29-481.
DR PDB; 4H6O; X-ray; 2.80 A; A=29-481.
DR PDB; 4UQH; X-ray; 2.43 A; A=32-481.
DR PDB; 4UVR; X-ray; 2.48 A; A=32-481.
DR PDB; 5AJR; X-ray; 2.75 A; A=32-481.
DR PDB; 6FMO; X-ray; 3.18 A; A/B/C/D=1-481.
DR PDBsum; 2WUZ; -.
DR PDBsum; 2WX2; -.
DR PDBsum; 3K1O; -.
DR PDBsum; 3KHM; -.
DR PDBsum; 3KSW; -.
DR PDBsum; 3ZG2; -.
DR PDBsum; 3ZG3; -.
DR PDBsum; 4BMM; -.
DR PDBsum; 4BY0; -.
DR PDBsum; 4C0C; -.
DR PDBsum; 4C27; -.
DR PDBsum; 4C28; -.
DR PDBsum; 4CK8; -.
DR PDBsum; 4CK9; -.
DR PDBsum; 4CKA; -.
DR PDBsum; 4COH; -.
DR PDBsum; 4H6O; -.
DR PDBsum; 4UQH; -.
DR PDBsum; 4UVR; -.
DR PDBsum; 5AJR; -.
DR PDBsum; 6FMO; -.
DR AlphaFoldDB; Q7Z1V1; -.
DR SMR; Q7Z1V1; -.
DR STRING; 5693.XP_820210.1; -.
DR BindingDB; Q7Z1V1; -.
DR ChEMBL; CHEMBL1075110; -.
DR PaxDb; Q7Z1V1; -.
DR EnsemblProtists; EAN98359; EAN98359; Tc00.1047053506297.260.
DR EnsemblProtists; EAN99368; EAN99368; Tc00.1047053510101.50.
DR GeneID; 3552837; -.
DR GeneID; 3554116; -.
DR KEGG; tcr:506297.260; -.
DR KEGG; tcr:510101.50; -.
DR eggNOG; KOG0684; Eukaryota.
DR OrthoDB; 572303at2759; -.
DR BRENDA; 1.14.13.70; 6524.
DR BRENDA; 1.14.14.154; 6524.
DR UniPathway; UPA00770; UER00754.
DR EvolutionaryTrace; Q7Z1V1; -.
DR PRO; PR:Q7Z1V1; -.
DR Proteomes; UP000002296; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008398; F:sterol 14-demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..481
FT /note="Sterol 14-alpha demethylase"
FT /id="PRO_0000389527"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 422
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:P0A512"
FT VARIANT 62
FT /note="D -> E (in allele 2)"
FT /evidence="ECO:0000269|PubMed:14599667,
FT ECO:0000269|PubMed:16020725"
FT VARIANT 117
FT /note="A -> S (in allele 2)"
FT /evidence="ECO:0000269|PubMed:14599667,
FT ECO:0000269|PubMed:16020725"
FT VARIANT 160
FT /note="E -> K (in allele 2)"
FT /evidence="ECO:0000269|PubMed:14599667,
FT ECO:0000269|PubMed:16020725"
FT MUTAGEN 105
FT /note="I->F: Increases activity on norlanosterol and
FT obtusifoliol."
FT /evidence="ECO:0000269|PubMed:16321980"
FT CONFLICT 9
FT /note="A -> G (in Ref. 2; AAW47718 and 3; EAN98359)"
FT /evidence="ECO:0000305"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:2WUZ"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:2WX2"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 45..50
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 52..62
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 86..90
FT /evidence="ECO:0007829|PDB:4C27"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 107..110
FT /evidence="ECO:0007829|PDB:4C27"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:2WX2"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 120..132
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:4CK8"
FT HELIX 142..157
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 167..183
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 186..191
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 194..206
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 229..250
FT /evidence="ECO:0007829|PDB:4C27"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:3KSW"
FT HELIX 261..265
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:2WUZ"
FT HELIX 278..308
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 313..323
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:4CK9"
FT HELIX 332..337
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 340..352
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 359..365
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 384..387
FT /evidence="ECO:0007829|PDB:4C27"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 425..442
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 443..451
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:4C27"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:4C27"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:4C27"
SQ SEQUENCE 481 AA; 54683 MW; C83BA5243C959151 CRC64;
MFIEAIVLAL TALILYSVYS VKSFNTTRPT DPPVYPVTVP FLGHIVQFGK NPLEFMQRCK
RDLKSGVFTI SIGGQRVTIV GDPHEHSRFF SPRNEILSPR EVYTIMTPVF GEGVAYAAPY
PRMREQLNFL AEELTIAKFQ NFVPAIQHEV RKFMAENWKE DEGVINLLED CGAMIINTAC
QCLFGEDLRK RLNARHFAQL LSKMESSLIP AAVFMPWLLR LPLPQSARCR EARAELQKIL
GEIIVAREKE EASKDNNTSD LLGGLLKAVY RDGTRMSLHE VCGMIVAAMF AGQHTSTITT
SWSMLHLMHP KNKKWLDKLH KEIDEFPAQL NYDNVMDEMP FAERCVRESI RRDPPLLMVM
RMVKAEVKVG SYVVPKGDII ACSPLLSHHD EEAFPNPRLW DPERDEKVDG AFIGFGAGVH
KCIGQKFALL QVKTILATAF REYDFQLLRD EVPDPDYHTM VVGPTLNQCL VKYTRKKKLP
S
