ERG24_CANAL
ID ERG24_CANAL Reviewed; 448 AA.
AC A0A1D8PIC7;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Delta(14)-sterol reductase ERG24 {ECO:0000303|PubMed:11897574};
DE EC=1.3.1.70 {ECO:0000305|PubMed:11897574};
DE AltName: Full=C-14 sterol reductase ERG24 {ECO:0000303|PubMed:11897574};
DE AltName: Full=Sterol C14-reductase ERG24 {ECO:0000303|PubMed:11897574};
GN Name=ERG24 {ECO:0000303|PubMed:11897574}; OrderedLocusNames=orf19.1598;
GN ORFNames=CAALFM_C209400CA;
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, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=11897574; DOI=10.1128/aac.46.4.947-957.2002;
RA Jia N., Arthington-Skaggs B., Lee W., Pierson C.A., Lees N.D., Eckstein J.,
RA Barbuch R., Bard M.;
RT "Candida albicans sterol C-14 reductase, encoded by the ERG24 gene, as a
RT potential antifungal target site.";
RL Antimicrob. Agents Chemother. 46:947-957(2002).
CC -!- FUNCTION: C-14 sterol reductase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (PubMed:11897574). ERG24 reduces the C14=C15 double bond of 4,4-
CC dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-cholesta-
CC 8,24-dienol (PubMed:11897574). 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:0000269|PubMed:11897574, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC Evidence={ECO:0000305|PubMed:11897574};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18562;
CC Evidence={ECO:0000305|PubMed:11897574};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 2/6. {ECO:0000305|PubMed:11897574}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of ignosterol (ergosta-
CC 8,14-dienol), and of a new sterol, ergosta-8,14,22-trienol
CC (PubMed:11897574). Results in slow growth and significant increased
CC sensitivity to an allylamine antifungal and to selected cellular
CC inhibitors including cycloheximide, cerulenin, fluphenazine, and
CC brefeldin A (PubMed:11897574). Slightly increases resistance to azoles
CC (PubMed:11897574). Significantly reduces pathogenicity in a mouse model
CC system and fails to produce germ tubes upon incubation in human serum
CC (PubMed:11897574). {ECO:0000269|PubMed:11897574}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; CP017624; AOW27923.1; -; Genomic_DNA.
DR RefSeq; XP_710679.2; XM_705587.2.
DR AlphaFoldDB; A0A1D8PIC7; -.
DR SMR; A0A1D8PIC7; -.
DR STRING; 237561.A0A1D8PIC7; -.
DR GeneID; 3647716; -.
DR KEGG; cal:CAALFM_C209400CA; -.
DR CGD; CAL0000185086; ERG24.
DR VEuPathDB; FungiDB:C2_09400C_A; -.
DR eggNOG; KOG1435; Eukaryota.
DR OrthoDB; 532774at2759; -.
DR UniPathway; UPA00770; UER00755.
DR Proteomes; UP000000559; Chromosome 2.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0050613; F:delta14-sterol reductase activity; IGI:CGD.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IGI:CGD.
DR GO; GO:0036180; P:filamentous growth of a population of unicellular organisms in response to biotic stimulus; IMP:CGD.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..448
FT /note="Delta(14)-sterol reductase ERG24"
FT /id="PRO_0000454174"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..414
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 345
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 349
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 368
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 373
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 380..381
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 420
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 424..428
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 435
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
SQ SEQUENCE 448 AA; 51492 MW; D3072F9BEE9547F6 CRC64;
MKSSKLNPVT THKEFNGISG ALGITIGLPT LTVLFYLLCN QTYSIHGINV DFAKIKSQLP
ITQDELWQLV FDKTCWSAYL AWFFILVILD YLLPGKSLNG VKLRDGTVLN YKINGLSMSS
LLIVLLLARL FQSNSDSSLE YYLPELQFIY DNQLQLIIIC FLFSFMLAVF VYIISFIPLA
KPNGIGTKER ILSINGNTGN PFYDWFIGRE LNPRIGSWDI KLFCELRPGM LLWLLINLSC
LHYQYHNLGY VTDSMIVVNL LQAFYIFDGV LNEEGCLTMI DITTDGFGFM LSFGDLAWVP
WTYSLQARYL SIKGNEVNLG WTLSLLIVGL QALGFYIFRS ANKQKSDFRQ GKLPHLKSIQ
TKTGSKLLVE GWWGLSQHIN YLGDWLIGLS WCLPTGFQTP LTYFYVIYFA SLLIHRQVRD
EMKCRAKYGE DWEKYEKLVP YKIIPYVY
