ERG26_CANAL
ID ERG26_CANAL Reviewed; 350 AA.
AC Q5A1B0; Q96W98;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26, decarboxylating {ECO:0000303|PubMed:12702354};
DE EC=1.1.1.170 {ECO:0000269|PubMed:12702354};
DE AltName: Full=C-3 sterol dehydrogenase ERG26 {ECO:0000303|PubMed:12702354};
DE AltName: Full=C-4 decarboxylase ERG26 {ECO:0000303|PubMed:12702354};
GN Name=ERG26 {ECO:0000303|PubMed:12702354}; OrderedLocusNames=orf19.2909;
GN ORFNames=CAALFM_C406270CA;
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, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=12702354; DOI=10.1111/j.1567-1364.2001.tb00020.x;
RA Aaron K.E., Pierson C.A., Lees N.D., Bard M.;
RT "The Candida albicans ERG26 gene encoding the C-3 sterol dehydrogenase (C-4
RT decarboxylase) is essential for growth.";
RL FEMS Yeast Res. 1:93-101(2001).
RN [5]
RP INDUCTION.
RX PubMed=15917516; DOI=10.1128/aac.49.6.2226-2236.2005;
RA Liu T.T., Lee R.E., Barker K.S., Lee R.E., Wei L., Homayouni R.,
RA Rogers P.D.;
RT "Genome-wide expression profiling of the response to azole, polyene,
RT echinocandin, and pyrimidine antifungal agents in Candida albicans.";
RL Antimicrob. Agents Chemother. 49:2226-2236(2005).
RN [6]
RP INDUCTION.
RX PubMed=22265407; DOI=10.1016/j.cell.2011.10.048;
RA Nobile C.J., Fox E.P., Nett J.E., Sorrells T.R., Mitrovich Q.M.,
RA Hernday A.D., Tuch B.B., Andes D.R., Johnson A.D.;
RT "A recently evolved transcriptional network controls biofilm development in
RT Candida albicans.";
RL Cell 148:126-138(2012).
CC -!- FUNCTION: Sterol-4-alpha-carboxylate 3-dehydrogenase; part of the third
CC module of ergosterol biosynthesis pathway that includes the late steps
CC of the pathway (PubMed:12702354). ERG26 is a catalytic component of the
CC C-4 demethylation complex that catalyzes the oxidative decarboxylation
CC that results in a reduction of the 3-beta-hydroxy group at the C-3
CC carbon to an oxo group (PubMed:12702354). The third module or late
CC pathway involves the ergosterol synthesis itself through consecutive
CC reactions that mainly occur in the endoplasmic reticulum (ER) membrane.
CC Firstly, the squalene synthase ERG9 catalyzes the condensation of 2
CC farnesyl pyrophosphate moieties to form squalene, which is the
CC precursor of all steroids. Squalene synthase is crucial for balancing
CC the incorporation of farnesyl diphosphate (FPP) into sterol and
CC nonsterol isoprene synthesis. Secondly, the squalene epoxidase ERG1
CC catalyzes the stereospecific oxidation of squalene to (S)-2,3-
CC epoxysqualene, which is considered to be a rate-limiting enzyme in
CC steroid biosynthesis. Then, the lanosterol synthase ERG7 catalyzes the
CC cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that
CC forms the sterol core. In the next steps, lanosterol is transformed to
CC zymosterol through a complex process involving various demethylation,
CC reduction and desaturation reactions. The lanosterol 14-alpha-
CC demethylase ERG11 (also known as CYP51) catalyzes C14-demethylation of
CC lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol,
CC which is critical for ergosterol biosynthesis. The C-14 reductase ERG24
CC reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-
CC trienol to produce 4,4-dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-
CC cholesta-8,24-dienol is substrate of the C-4 demethylation complex
CC ERG25-ERG26-ERG27 in which ERG25 catalyzes the three-step
CC monooxygenation required for the demethylation of 4,4-dimethyl and
CC 4alpha-methylsterols, ERG26 catalyzes the oxidative decarboxylation
CC that results in a reduction of the 3-beta-hydroxy group at the C-3
CC carbon to an oxo group, and ERG27 is responsible for the reduction of
CC the keto group on the C-3. ERG28 has a role as a scaffold to help
CC anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and ERG29
CC regulates the activity of the iron-containing C4-methylsterol oxidase
CC ERG25. Then, the sterol 24-C-methyltransferase ERG6 catalyzes the
CC methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to
CC form fecosterol. The C-8 sterol isomerase ERG2 catalyzes the reaction
CC which results in unsaturation at C-7 in the B ring of sterols and thus
CC converts fecosterol to episterol. The sterol-C5-desaturase ERG3 then
CC catalyzes the introduction of a C-5 double bond in the B ring to
CC produce 5-dehydroepisterol. The C-22 sterol desaturase ERG5 further
CC converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC by forming the C-22(23) double bond in the sterol side chain. Finally,
CC ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28)
CC sterol reductase ERG4 to produce ergosterol (Probable).
CC {ECO:0000269|PubMed:12702354, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3-
CC dehydro-4-methylzymosterol + CO2 + NADPH; Xref=Rhea:RHEA:33447,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:50593, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64925; EC=1.1.1.170;
CC Evidence={ECO:0000269|PubMed:12702354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33448;
CC Evidence={ECO:0000269|PubMed:12702354};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 4/6. {ECO:0000269|PubMed:12702354}.
CC -!- SUBUNIT: Heterotetramer of ERG25, ERG26, ERG27 and ERG28 (By
CC similarity). ERG28 acts as a scaffold to tether ERG27 and other 4,4-
CC demethylation-related enzymes, forming a demethylation enzyme complex,
CC in the endoplasmic reticulum (By similarity).
CC {ECO:0000250|UniProtKB:P53199}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P53199}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P53199}.
CC -!- INDUCTION: Expression is repressed by amphotericin B and caspofungin
CC (PubMed:15917516). Expression is also repressed during biofilm
CC formation (PubMed:22265407). {ECO:0000269|PubMed:15917516,
CC ECO:0000269|PubMed:22265407}.
CC -!- DISRUPTION PHENOTYPE: Impairs growth. {ECO:0000269|PubMed:12702354}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; CP017626; AOW29353.1; -; Genomic_DNA.
DR RefSeq; XP_715564.1; XM_710471.1.
DR AlphaFoldDB; Q5A1B0; -.
DR SMR; Q5A1B0; -.
DR STRING; 237561.Q5A1B0; -.
DR EnsemblFungi; KHC76700; KHC76700; W5Q_03916.
DR EnsemblFungi; KHC86253; KHC86253; I503_03941.
DR GeneID; 3642803; -.
DR KEGG; cal:CAALFM_C406270CA; -.
DR CGD; CAL0000199131; ERG26.
DR VEuPathDB; FungiDB:C4_06270C_A; -.
DR eggNOG; KOG1430; Eukaryota.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; Q5A1B0; -.
DR OMA; WGPGDTQ; -.
DR OrthoDB; 930591at2759; -.
DR BRENDA; 1.1.1.170; 1096.
DR UniPathway; UPA00770; UER00757.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
DR GO; GO:0000252; F:C-3 sterol dehydrogenase (C-4 sterol decarboxylase) activity; IGI:CGD.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IGI:CGD.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT CHAIN 1..350
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26,
FT decarboxylating"
FT /id="PRO_0000454175"
FT ACT_SITE 156
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 12..18
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 63..64
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 85..87
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 125
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 152
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A0A059TC02"
FT BINDING 152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 156
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 179..182
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
SQ SEQUENCE 350 AA; 39184 MW; A18DABB1A1EA4636 CRC64;
MSESLQSVLI IGGSGFLGLH LIEQFYRHCP NVAITVFDVR PLPEKLSKYF TFDPSKIQFF
KGDLTSDKDV SDAINQSKCD VIVHSASPMH GLPQEIYEKV NVQGTKNLLS VAQKLHVKAL
VYTSSAGVIF NGQDVINADE TWPYPEVHMD GYNETKAAAE EAVMKANDND QLRTVCLRPA
GIFGPGDRQL VPGLRASAKL GQSKYQLGDN NNLFDWTYVG NVADAHVLAA QKILDKSTRD
DISGQTFFIT NDSPTYFWTL ARTVWKNDGY IDKYYIKLPY PVALTLGYIS EFVAKNILKK
EPGITPFRVK VVCAIRYHNI AKAKKLLGYK PEVDLETGIN YTLDWMNEDL
