P10613 (CP51_CANAL) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lanosterol 14-alpha demethylase
EC=1.14.13.70

Alternative name(s):
CYPLI
Cytochrome P450 51
Cytochrome P450-14DM
Cytochrome P450-LIA1
Sterol 14-alpha demethylase

Gene names

Name:	ERG11
Synonyms:	CYP51, ERG16
ORF Names:	CaO19.922

Organism

Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)

Taxonomic identifier

237561 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › mitosporic Saccharomycetales › Candida

Protein attributes

Sequence length	528 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Catalytic activity	Obtusifoliol + 3 O2 + 3 NADPH = 4-alpha-methyl-5-alpha-ergosta-8,14,24(28)-trien-3-beta-ol + formate + 3 NADP+ + 4 H2O.
Cofactor	Heme group By similarity.
Pathway	Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6.
Subcellular location	Membrane Potential.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Membrane
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Gene Ontology (GO)
Biological process	cellular response to drug Inferred from mutant phenotype. Source: CGD ergosterol biosynthetic process Inferred from genetic interaction. Source: CGD membrane raft polarization Inferred from mutant phenotype. Source: CGD
Cellular component	integral to membrane Inferred from direct assay. Source: CGD membrane fraction Inferred from direct assay. Source: CGD plasma membrane Inferred from direct assay. Source: CGD
Molecular function	drug binding Inferred from direct assay. Source: CGD electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro sterol 14-demethylase activity Inferred from direct assay. Source: CGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 528	528	Lanosterol 14-alpha demethylase		PRO_0000052003
Sites
	Metal binding	470	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	105	1	F → L in fluconazole-resistant isolates.
	Natural variant	266	1	E → D in strain: fluconazole-resistant isolates.
	Natural variant	287	1	K → R in strain: fluconazole-resistant isolates.
	Natural variant	450	1	G → E in strain: fluconazole-resistant isolates.
	Natural variant	464	1	G → S in strain: fluconazole-resistant isolates.
	Natural variant	467	1	R → K in strain: Isolate 13; azole-resistant. Ref.4
	Natural variant	488	1	V → I in strain: fluconazole-resistant isolates.
Experimental info
	Sequence conflict	19	1	V → D in AAB08099. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P10613 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 026948CEE4AF1B88	FASTA	528	60,675
	10 20 30 40 50 60 MAIVETVIDG INYFLSLSVT QQISILLGVP FVYNLVWQYL YSLRKDRAPL VFYWIPWFGS 70 80 90 100 110 120 AASYGQQPYE FFESCRQKYG DVFSFMLLGK IMTVYLGPKG HEFVFNAKLS DVSAEDAYKH 130 140 150 160 170 180 LTTPVFGKGV IYDCPNSRLM EQKKFAKFAL TTDSFKRYVP KIREEILNYF VTDESFKLKE 190 200 210 220 230 240 KTHGVANVMK TQPEITIFTA SRSLFGDEMR RIFDRSFAQL YSDLDKGFTP INFVFPNLPL 250 260 270 280 290 300 PHYWRRDAAQ KKISATYMKE IKSRRERGDI DPNRDLIDSL LIHSTYKDGV KMTDQEIANL 310 320 330 340 350 360 LIGILMGGQH TSASTSAWFL LHLGEKPHLQ DVIYQEVVEL LKEKGGDLND LTYEDLQKLP 370 380 390 400 410 420 SVNNTIKETL RMHMPLHSIF RKVTNPLRIP ETNYIVPKGH YVLVSPGYAH TSERYFDNPE 430 440 450 460 470 480 DFDPTRWDTA AAKANSVSFN SSDEVDYGFG KVSKGVSSPY LPFGGGRHRC IGEQFAYVQL 490 500 510 520 GTILTTFVYN LRWTIDGYKV PDPDYSSMVV LPTEPAEIIW EKRETCMF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of cytochrome P450 L1A1 (lanosterol 14 alpha-demethylase) from Candida albicans." Lai M.H., Kirsch D.R. Nucleic Acids Res. 17:804-804(1989) [PubMed: 2644625] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: SC5314 / ATCC MYA-2876.
[2]	"ERG11 mutations in oral strains of Candida albicans isolated in Sardinia." Orru G., Ciusa M.L., Pilia F., Taccori F., Cosentino S., Pisano M.B., Meloni M., Fadda M.E. Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: CA100, CA11, CA36 and CA95.
[3]	"The diploid genome sequence of Candida albicans." Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B., Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W., Scherer S. Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004) [PubMed: 15123810] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: SC5314 / ATCC MYA-2876.
[4]	"The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14-alpha demethylase in Candida albicans." White T.C. Antimicrob. Agents Chemother. 41:1488-1494(1997) [PubMed: 9210671] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-48 AND 467-528, VARIANT LYS-467. Strain: SS.
[5]	"Modeling cytochrome P450 14-alpha demethylase (Candida albicans) from P450cam." Boscott P.E., Grant G.H. J. Mol. Graph. 12:185-192(1994) [PubMed: 7819160] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[6]	"Molecular analysis of cyp51 from fluconazole-resistant Candida albicans strains." Loffler J., Kelly S.L., Hebart H., Schumacher U., Lass-Florl C., Einsele H. FEMS Microbiol. Lett. 151:263-268(1997) [PubMed: 9228762] [Abstract] Cited for: VARIANTS FLUCONAZOLE-RESISTANT.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X13296 Genomic DNA. Translation: CAA31658.1. EU819548 Genomic DNA. Translation: ACF34636.1. EU819551 Genomic DNA. Translation: ACF34639.1. FJ002303 Genomic DNA. Translation: ACH91036.1. FJ403378 Genomic DNA. Translation: ACJ23064.1. AACQ01000063 Genomic DNA. Translation: EAK97774.1. U67192 Genomic DNA. Translation: AAB08099.1. U67193 Genomic DNA. Translation: AAB08100.1.
PIR	O4CK51. S02713.
RefSeq	XP_716761.1. XM_711668.1.
3D structure databases
ProteinModelPortal	P10613.
ModBase	Search...
Protein-protein interaction databases
STRING	P10613.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	3641571.
KEGG	cal:CaO19.922.
Organism-specific databases
CGD	CAL0003627. ERG11.
Phylogenomic databases
PhylomeDB	P10613.
Enzyme and pathway databases
BRENDA	1.14.13.70. 1096.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002403. Cyt_P450_E_grp-IV. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
KO	K05917.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00465. EP450IV. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00646. Nystatin.

Entry information

Entry name

CP51_CANAL

Accession

Primary (citable) accession number: P10613
Secondary accession number(s): Q5A524, Q92208

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program