ERG28_CANAL
ID ERG28_CANAL Reviewed; 138 AA.
AC Q5AD51;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Ergosterol biosynthetic protein 28 {ECO:0000250|UniProtKB:P40030};
GN Name=ERG28 {ECO:0000250|UniProtKB:P40030}; OrderedLocusNames=orf19.2016;
GN ORFNames=CAALFM_C201090CA;
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).
CC -!- FUNCTION: Part of the third module of ergosterol biosynthesis pathway
CC that includes the late steps of the pathway (By similarity). ERG28 has
CC a role as a scaffold to help anchor the catalytic components of the C-4
CC demethylation complex ERG25, ERG26 and ERG27 to the endoplasmic
CC reticulum (By similarity). 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:0000250|UniProtKB:P40030, ECO:0000305}.
CC -!- SUBUNIT: Heterotetramer of ERG25, ERG26, ERG27 and ERG28. ERG28 acts as
CC a scaffold to tether ERG27 and other 4,4-demethylation-related enzymes,
CC forming a demethylation enzyme complex, in the endoplasmic reticulum.
CC Interacts with ERG25, ERG26 and ERG27. Also interacts with ERG1, ERG3,
CC ERG5, ERG6 and ERG11. {ECO:0000250|UniProtKB:P40030}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P40030}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P40030}.
CC -!- SIMILARITY: Belongs to the ERG28 family. {ECO:0000305}.
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DR EMBL; CP017624; AOW27158.1; -; Genomic_DNA.
DR RefSeq; XP_719465.1; XM_714372.2.
DR AlphaFoldDB; Q5AD51; -.
DR STRING; 237561.Q5AD51; -.
DR EnsemblFungi; KHC81185; KHC81185; W5Q_01556.
DR EnsemblFungi; KHC88676; KHC88676; I503_01550.
DR GeneID; 3638833; -.
DR KEGG; cal:CAALFM_C201090CA; -.
DR CGD; CAL0000184284; ERG28.
DR VEuPathDB; FungiDB:C2_01090C_A; -.
DR eggNOG; KOG3455; Eukaryota.
DR HOGENOM; CLU_114589_0_0_1; -.
DR InParanoid; Q5AD51; -.
DR OMA; SEWLIFG; -.
DR OrthoDB; 1590576at2759; -.
DR Proteomes; UP000000559; Chromosome 2.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR005352; Erg28.
DR PANTHER; PTHR15451; PTHR15451; 1.
DR Pfam; PF03694; Erg28; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..138
FT /note="Ergosterol biosynthetic protein 28"
FT /id="PRO_0000454177"
FT TRANSMEM 17..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 138 AA; 16033 MW; F168F6ADECC3CAFA CRC64;
MLGYFESILP YTNGGKLPYW LLFISVVSIF NSVQTYQNIN LTKRVYEKNP NQVSPLSART
FGTWTLITSI VRFYGAYYLQ NKQIYELTQF TFAIAAWHFL SEWLYFGTCK LGKGLSGPLI
VSSVSLVWMY LQKDFYVN
