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 24-JAN-2024, entry version 121. 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 CC [NADPH--hemoprotein reductase] = a Delta(14) steroid + formate + 4 CC H(+) + 4 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}. 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; 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; 353153.Q7Z1V1; -. DR BindingDB; Q7Z1V1; -. DR ChEMBL; CHEMBL1075110; -. DR PaxDb; 353153-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 InParanoid; Q7Z1V1; -. DR OrthoDB; 5474434at2759; -. 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:0016020; C:membrane; IEA:UniProtKB-SubCell. 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 CDD; cd11042; CYP51-like; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24304:SF2; 24-HYDROXYCHOLESTEROL 7-ALPHA-HYDROXYLASE; 1. DR PANTHER; PTHR24304; CYTOCHROME P450 FAMILY 7; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00465; EP450IV. 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; 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 //