ERG27_CANAL
ID ERG27_CANAL Reviewed; 346 AA.
AC Q5A888;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=3-keto-steroid reductase ERG27 {ECO:0000303|PubMed:15552648};
DE EC=1.1.1.270 {ECO:0000269|PubMed:15552648};
GN Name=ERG27 {ECO:0000303|PubMed:15552648};
GN OrderedLocusNames=CAALFM_CR01140CA, orf19.3240;
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, INDUCTION, AND PATHWAY.
RX PubMed=15552648; DOI=10.1080/1369378032000141471;
RA Pierson C.A., Jia N., Mo C., Lees N.D., Sturm A.M., Eckstein J.,
RA Barbuct R., Bard M.;
RT "Isolation, characterization, and regulation of the Candida albicans ERG27
RT gene encoding the sterol 3-keto reductase.";
RL Med. Mycol. 42:461-473(2004).
CC -!- FUNCTION: 3-keto-steroid reductase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:15552648). ERG27 is a catalytic component of the C-4
CC demethylation complex that catalyzes the reduction of the keto group on
CC the C-3 (PubMed:15552648). The third module or late pathway involves
CC the ergosterol synthesis itself through consecutive reactions that
CC mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the
CC 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:15552648, ECO:0000305}.
CC -!- FUNCTION: Facilitates the association of ERG7 with lipid particles
CC preventing its digestion in the endoplasmic reticulum and the lipid
CC particles. {ECO:0000250|UniProtKB:Q12452}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-dehydro-4alpha-methylzymosterol + H(+) + NADPH = 4alpha-
CC methylzymosterol + NADP(+); Xref=Rhea:RHEA:36379, ChEBI:CHEBI:1949,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:136486; EC=1.1.1.270;
CC Evidence={ECO:0000269|PubMed:15552648};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36380;
CC Evidence={ECO:0000269|PubMed:15552648};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 5/6. {ECO:0000269|PubMed:15552648}.
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. Interacts with ERG25 and ERG28. Also
CC interacts with ERG7, but only in lipid particles (By similarity).
CC {ECO:0000250|UniProtKB:Q12452}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q12452}; Single-pass membrane protein
CC {ECO:0000255}. Lipid droplet {ECO:0000250|UniProtKB:Q12452}.
CC -!- INDUCTION: Expression is increased by itraconazole (which targets the
CC lanosterol demethylase CYP51/ERG11) and by zaragozic acid A (which
CC targets the squalene synthase ERG9). {ECO:0000269|PubMed:15552648}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete loss of both 3-keto reductase
CC and oxidosqualene cyclase (performed by ERG7) activities, compromising
CC all sterol synthesis. {ECO:0000269|PubMed:15552648}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. ERG27 subfamily. {ECO:0000305}.
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DR EMBL; CP017630; AOW30876.1; -; Genomic_DNA.
DR RefSeq; XP_717931.1; XM_712838.1.
DR AlphaFoldDB; Q5A888; -.
DR SMR; Q5A888; -.
DR STRING; 237561.Q5A888; -.
DR EnsemblFungi; KHC71091; KHC71091; W5Q_05573.
DR EnsemblFungi; KHC79701; KHC79701; I503_05536.
DR GeneID; 3640432; -.
DR KEGG; cal:CAALFM_CR01140CA; -.
DR CGD; CAL0000174882; ERG27.
DR VEuPathDB; FungiDB:CR_01140C_A; -.
DR eggNOG; KOG1478; Eukaryota.
DR HOGENOM; CLU_029944_1_0_1; -.
DR InParanoid; Q5A888; -.
DR OMA; ASYEGSK; -.
DR OrthoDB; 1413827at2759; -.
DR UniPathway; UPA00770; UER00758.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IMP:CGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IGI:CGD.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid droplet;
KW Lipid metabolism; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..346
FT /note="3-keto-steroid reductase ERG27"
FT /id="PRO_0000454176"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 205
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
FT BINDING 47..83
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 346 AA; 38981 MW; 040CB9783ACAECEE CRC64;
MSLLKDSTVA VITGTSSNLG FNIAVRLLEG LPDNKEITLV VTSRTLPKVK EVISDIKKYI
VAKIPTKVNK VEFDYLLVDF TDMVSILSAY YELNKRYKHI DYLFINAAQG VYGGIDWTGA
VLEVLQSPIE AVTNPTYKLQ KVGVESGDKL GLVFQANVFG PYYFIHRIKH LLENGGKIVW
VSSLMSSPKY LSFNDLQLLR SPASYEGSKR LVDLMHFGTY NKLEREHGIK QYLVHPGIFT
SFSFFQYLNV FTYYGMLFLF YLARFLGSPY HNISGYIAAN APVAAALGQT KQNCKTASAC
TRSGKEYLLE EEIDSTGSDD VVSYLDTLTK EWDEKLKDQI VNTRQP
