ERG5_YEAST
ID ERG5_YEAST Reviewed; 538 AA.
AC P54781; D6VZI9; E9P965;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=C-22 sterol desaturase ERG5 {ECO:0000303|PubMed:8635732};
DE EC=1.14.19.41 {ECO:0000269|PubMed:8543054, ECO:0000269|PubMed:8635732};
DE AltName: Full=Cytochrome P450 61 {ECO:0000303|PubMed:8543054};
DE AltName: Full=Ergosterol biosynthetic protein 5 {ECO:0000303|PubMed:8635732};
GN Name=ERG5 {ECO:0000303|PubMed:8635732};
GN Synonyms=CYP61 {ECO:0000303|PubMed:8543054}; OrderedLocusNames=YMR015C;
GN ORFNames=YM9711.02C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=8635732; DOI=10.1016/0378-1119(95)00770-9;
RA Skaggs B.A., Alexander J.F., Pierson C.A., Schweitzer K.S., Chun K.T.,
RA Koegel C., Barbuch R., Bard M.;
RT "Cloning and characterization of the Saccharomyces cerevisiae C-22 sterol
RT desaturase gene, encoding a second cytochrome P-450 involved in ergosterol
RT biosynthesis.";
RL Gene 169:105-109(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP PROTEIN SEQUENCE OF 32-42, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=DK2;
RX PubMed=8543054; DOI=10.1016/0014-5793(95)01342-3;
RA Kelly S.L., Lamb D.C., Corran A.J., Baldwin B.C., Parks L.W., Kelly D.E.;
RT "Purification and reconstitution of activity of Saccharomyces cerevisiae
RT P450 61, a sterol delta 22-desaturase.";
RL FEBS Lett. 377:217-220(1995).
RN [6]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [7]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-164 AND LYS-198, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=SUB592;
RX PubMed=12872131; DOI=10.1038/nbt849;
RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G.,
RA Roelofs J., Finley D., Gygi S.P.;
RT "A proteomics approach to understanding protein ubiquitination.";
RL Nat. Biotechnol. 21:921-926(2003).
RN [8]
RP FUNCTION, AND INTERACTION WITH ERG28.
RX PubMed=15995173; DOI=10.1194/jlr.m500153-jlr200;
RA Mo C., Bard M.;
RT "Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex.";
RL J. Lipid Res. 46:1991-1998(2005).
RN [9]
RP REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX PubMed=32679672; DOI=10.3390/genes11070795;
RA Jorda T., Puig S.;
RT "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL Genes (Basel) 11:0-0(2020).
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 (PubMed:8635732, PubMed:8543054). ERG5 converts 5-
CC dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming
CC the C-22(23) double bond in the sterol side chain (PubMed:8635732,
CC PubMed:8543054). The third module or late pathway involves the
CC ergosterol synthesis itself through consecutive reactions that mainly
CC occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene
CC synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate
CC moieties to form squalene, which is the precursor of all steroids.
CC Squalene synthase is crucial for balancing the incorporation of
CC 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 (PubMed:32679672). {ECO:0000269|PubMed:8543054,
CC ECO:0000269|PubMed:8635732, ECO:0000303|PubMed:32679672}.
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:0000269|PubMed:8543054, ECO:0000269|PubMed:8635732};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33468;
CC Evidence={ECO:0000269|PubMed:8543054, ECO:0000269|PubMed:8635732};
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:0000269|PubMed:8635732}.
CC -!- SUBUNIT: Interacts with ERG28. {ECO:0000269|PubMed:15995173}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- MISCELLANEOUS: Present with 24700 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; U34636; AAB06217.1; -; Genomic_DNA.
DR EMBL; Z49211; CAA89116.1; -; Genomic_DNA.
DR EMBL; AY723852; AAU09769.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA09913.1; -; Genomic_DNA.
DR PIR; S54015; S54015.
DR RefSeq; NP_013728.1; NM_001182511.1.
DR AlphaFoldDB; P54781; -.
DR SMR; P54781; -.
DR BioGRID; 35186; 247.
DR IntAct; P54781; 16.
DR MINT; P54781; -.
DR STRING; 4932.YMR015C; -.
DR iPTMnet; P54781; -.
DR MaxQB; P54781; -.
DR PaxDb; P54781; -.
DR PRIDE; P54781; -.
DR EnsemblFungi; YMR015C_mRNA; YMR015C; YMR015C.
DR GeneID; 855029; -.
DR KEGG; sce:YMR015C; -.
DR SGD; S000004617; ERG5.
DR VEuPathDB; FungiDB:YMR015C; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_023517_0_0_1; -.
DR InParanoid; P54781; -.
DR OMA; MVIPSFY; -.
DR BioCyc; MetaCyc:MON3O-232; -.
DR BioCyc; YEAST:MON3O-232; -.
DR BRENDA; 1.14.19.41; 984.
DR UniPathway; UPA00768; UER00763.
DR PRO; PR:P54781; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P54781; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
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:0000249; F:C-22 sterol desaturase activity; IDA:SGD.
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:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IDA:SGD.
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 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Metal-binding; NADP; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..538
FT /note="C-22 sterol desaturase ERG5"
FT /id="PRO_0000052050"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 476
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"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT CROSSLNK 198
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT CONFLICT 286
FT /note="I -> T (in Ref. 4; AAU09769)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 538 AA; 61334 MW; 2CE8DC6CE0315AC3 CRC64;
MSSVAENIIQ HATHNSTLHQ LAKDQPSVGV TTAFSILDTL KSMSYLKIFA TLICILLVWD
QVAYQIKKGS IAGPKFKFWP IIGPFLESLD PKFEEYKAKW ASGPLSCVSI FHKFVVIAST
RDLARKILQS SKFVKPCVVD VAVKILRPCN WVFLDGKAHT DYRKSLNGLF TKQALAQYLP
SLEQIMDKYM DKFVRLSKEN NYEPQVFFHE MREILCALSL NSFCGNYITE DQVRKIADDY
YLVTAALELV NFPIIIPYTK TWYGKKTADM AMKIFENCAQ MAKDHIAAGG KPVCVMDAWC
KLMHDAKNSN DDDSRIYHRE FTNKEISEAV FTFLFASQDA SSSLACWLFQ IVADRPDVLA
KIREEQLAVR NNDMSTELNL DLIEKMKYTN MVIKETLRYR PPVLMVPYVV KKNFPVSPNY
TAPKGAMLIP TLYPALHDPE VYENPDEFIP ERWVEGSKAS EAKKNWLVFG CGPHVCLGQT
YVMITFAALL GKFALYTDFH HTVTPLSEKI KVFATIFPKD DLLLTFKKRD PITGEVFE
