ERG5_CANAL
ID ERG5_CANAL Reviewed; 517 AA.
AC G1UB11;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=C-22 sterol desaturase ERG5 {ECO:0000303|PubMed:20547793};
DE EC=1.14.19.41 {ECO:0000250|UniProtKB:P54781};
DE AltName: Full=Cytochrome P450 61 {ECO:0000303|PubMed:20547793};
DE AltName: Full=Ergosterol biosynthetic protein 5 {ECO:0000303|PubMed:20547793};
GN Name=ERG5 {ECO:0000303|PubMed:20547793};
GN Synonyms=CYP61 {ECO:0000303|PubMed:20547793}; OrderedLocusNames=orf19.5178;
GN ORFNames=CAALFM_C702840CA;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=20547793; DOI=10.1128/aac.00303-10;
RA Martel C.M., Parker J.E., Bader O., Weig M., Gross U., Warrilow A.G.,
RA Kelly D.E., Kelly S.L.;
RT "A clinical isolate of Candida albicans with mutations in ERG11 (encoding
RT sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross
RT resistant to azoles and amphotericin B.";
RL Antimicrob. Agents Chemother. 54:3578-3583(2010).
CC -!- FUNCTION: C-22 sterol desaturase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (Probable). ERG5 converts 5-dehydroepisterol into ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in
CC the sterol side chain (By similarity). The third module or late pathway
CC involves the ergosterol synthesis itself through consecutive reactions
CC that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly,
CC the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl
CC pyrophosphate moieties to form squalene, which is the precursor of all
CC steroids. Squalene synthase is crucial for balancing the incorporation
CC of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene
CC synthesis. Secondly, the squalene epoxidase ERG1 catalyzes the
CC stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, which is
CC considered to be a rate-limiting enzyme in steroid biosynthesis. Then,
CC the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3
CC oxidosqualene to lanosterol, a reaction that forms the sterol core. In
CC the next steps, lanosterol is transformed to zymosterol through a
CC complex process involving various demethylation, reduction and
CC desaturation reactions. The lanosterol 14-alpha-demethylase ERG11 (also
CC known as CYP51) catalyzes C14-demethylation of lanosterol to produce
CC 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol, which is critical for
CC ergosterol biosynthesis. The C-14 reductase ERG24 reduces the C14=C15
CC double bond of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-
CC dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-cholesta-8,24-dienol is
CC substrate of the C-4 demethylation complex ERG25-ERG26-ERG27 in which
CC ERG25 catalyzes the three-step monooxygenation required for the
CC demethylation of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes
CC the oxidative decarboxylation that results in a reduction of the 3-
CC beta-hydroxy group at the C-3 carbon to an oxo group, and ERG27 is
CC responsible for the reduction of the keto group on the C-3. ERG28 has a
CC role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the
CC endoplasmic reticulum and ERG29 regulates the activity of the iron-
CC containing C4-methylsterol oxidase ERG25. Then, the sterol 24-C-
CC methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl-
CC methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol
CC isomerase ERG2 catalyzes the reaction which results in unsaturation at
CC C-7 in the B ring of sterols and thus converts fecosterol to episterol.
CC The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5
CC double bond in the B ring to produce 5-dehydroepisterol. The C-22
CC sterol desaturase ERG5 further converts 5-dehydroepisterol into
CC ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double
CC bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen-
CC 3beta-ol is substrate of the C-24(28) sterol reductase ERG4 to produce
CC ergosterol (Probable). {ECO:0000250|UniProtKB:P54781, ECO:0000305,
CC ECO:0000305|PubMed:20547793}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-dehydroepisterol + H(+) + NADPH + O2 = ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol + 2 H2O + NADP(+);
CC Xref=Rhea:RHEA:33467, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:18249, ChEBI:CHEBI:52972,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.19.41;
CC Evidence={ECO:0000250|UniProtKB:P54781};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33468;
CC Evidence={ECO:0000250|UniProtKB:P54781};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from
CC zymosterol: step 4/5. {ECO:0000305|PubMed:20547793}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CP017629; AOW30631.1; -; Genomic_DNA.
DR RefSeq; XP_717000.1; XM_711907.1.
DR AlphaFoldDB; G1UB11; -.
DR SMR; G1UB11; -.
DR STRING; 237561.G1UB11; -.
DR PRIDE; G1UB11; -.
DR EnsemblFungi; KHC71957; KHC71957; W5Q_05316.
DR EnsemblFungi; KHC79814; KHC79814; I503_05280.
DR GeneID; 3641400; -.
DR KEGG; cal:CAALFM_C702840CA; -.
DR CGD; CAL0000198637; ERG5.
DR VEuPathDB; FungiDB:C7_02840C_A; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_023517_0_0_1; -.
DR InParanoid; G1UB11; -.
DR OMA; MVIPSFY; -.
DR OrthoDB; 574756at2759; -.
DR UniPathway; UPA00768; UER00763.
DR Proteomes; UP000000559; Chromosome 7.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:CGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0000249; F:C-22 sterol desaturase activity; ISS:CGD.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IMP:CGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; ISS:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0036180; P:filamentous growth of a population of unicellular organisms in response to biotic stimulus; IMP:CGD.
DR GO; GO:0036170; P:filamentous growth of a population of unicellular organisms in response to starvation; IMP:CGD.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
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 SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..517
FT /note="C-22 sterol desaturase ERG5"
FT /id="PRO_0000454179"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 458
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:P04798"
SQ SEQUENCE 517 AA; 59652 MW; 76F7F9AF94DBEC19 CRC64;
MNSTEVDNLP FQQQLTSFVE LAVAKATGSP ITTLFTIIFL ILSYDQLSYQ INKGSIAGPR
FKFYPIIGPF LESLDPKFEE YKAKWDSGEL SCVSIFHKFV VIASSRDLAR KILSSPKYVK
PCVVDVAIKI LRPTNWVFLD GKQHTDYRRS LNGLFSSKAL EIYIPVQEKY MDIYLERFCK
YDGPREFFPE FRELLCALSL RTFCGDYITE DQIALVADNY YRVTAALELV NFPIIIPYTK
TWYGKKIADD TMKIFENCAA MAKKHINENN GTPKCVMDEW IHLMKEAREK HSEDPDSKLL
VREFSNREIS EAIFTFLFAS QDASSSLACW LFQIVADRPD IVAKIREEQL RVRNNNPDVR
LSLDLINEMT YTNNVVKESL RYRPPVLMVP YVVKKSFPVT ESYTAPKGAM IIPTLYPALH
DPEVYDEPDS FIPERWENAS GDMYKRNWLV FGTGPHVCLG KNYVLMLFTG MLGKFVMNSD
MIHHKTDLSE EIKVFATIFP KDDLILEWKK RDPLKSL
