ERG4_SCHPO
ID ERG4_SCHPO Reviewed; 453 AA.
AC P36209; O13891;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Delta(24(24(1)))-sterol reductase {ECO:0000303|PubMed:8125337};
DE EC=1.3.1.71 {ECO:0000305|PubMed:8125337};
DE AltName: Full=C-24(28) sterol reductase {ECO:0000303|PubMed:8125337};
DE AltName: Full=Staurosporine-supersensitivity protein 1 {ECO:0000303|PubMed:1320960};
DE AltName: Full=Sterol Delta(24(28))-reductase {ECO:0000303|PubMed:8125337};
GN Name=sts1 {ECO:0000303|PubMed:1320960}; ORFNames=SPAC20G4.07c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RX PubMed=1320960; DOI=10.1091/mbc.3.3.263;
RA Shimanuki M., Goebl M., Yanagida M., Toda T.;
RT "Fission yeast sts1+ gene encodes a protein similar to the chicken lamin B
RT receptor and is implicated in pleiotropic drug-sensitivity, divalent
RT cation-sensitivity, and osmoregulation.";
RL Mol. Biol. Cell 3:263-273(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8125337; DOI=10.1016/0378-1119(94)90728-5;
RA Lai M.H., Bard M., Pierson C.A., Alexander J.F., Goebl M., Carter G.T.,
RA Kirsch D.R.;
RT "The identification of a gene family in the Saccharomyces cerevisiae
RT ergosterol biosynthesis pathway.";
RL Gene 140:41-49(1994).
RN [4]
RP FUNCTION.
RX PubMed=8586261; DOI=10.1111/j.1574-6968.1995.tb07929.x;
RA Harmouch N., Coulon J., Bonaly R.;
RT "Identification of 24-methylene-24,25-dihydrolanosterol as a precursor of
RT ergosterol in the yeasts Schizosaccharomyces pombe and Schizosaccharomyces
RT octosporus.";
RL FEMS Microbiol. Lett. 134:147-152(1995).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=18310029; DOI=10.1099/mic.0.2007/011155-0;
RA Iwaki T., Iefuji H., Hiraga Y., Hosomi A., Morita T., Giga-Hama Y.,
RA Takegawa K.;
RT "Multiple functions of ergosterol in the fission yeast Schizosaccharomyces
RT pombe.";
RL Microbiology 154:830-841(2008).
CC -!- FUNCTION: C-24(28) sterol reductase; part of the third module of
CC ergosterol biosynthesis pathway that includes by the late steps of the
CC pathway (PubMed:8125337, PubMed:18310029). Erg4 catalyzes the last step
CC of ergosterol biosynthesis by converting ergosta-5,7,22,24(28)-tetraen-
CC 3beta-ol into ergosterol (PubMed:8125337, PubMed:18310029). The third
CC module or late pathway involves the ergosterol synthesis itself through
CC consecutive reactions that mainly occur in the endoplasmic reticulum
CC (ER) membrane. Firstly, the squalene synthase erg9 catalyzes the
CC condensation of 2 farnesyl pyrophosphate moieties to form squalene,
CC which is the precursor of all steroids. Secondly, squalene is converted
CC into lanosterol by the consecutive action of the squalene epoxidase
CC erg1 and the lanosterol synthase erg7. The lanosterol 14-alpha-
CC demethylase erg11/cyp1 catalyzes C14-demethylation of lanosterol to
CC produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. In the next
CC steps, a complex process involving various demethylation, reduction and
CC desaturation reactions catalyzed by the C-14 reductase erg24 and the C-
CC 4 demethylation complex erg25-erg26-erg27 leads to the production of
CC zymosterol. Erg28 likely functions in the C-4 demethylation complex
CC reaction by tethering erg26 and Erg27 to the endoplasmic reticulum or
CC to facilitate interaction between these proteins. Then, the sterol 24-
CC C-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-desaturases erg31 and erg32 then catalyze the
CC introduction of a C-5 double bond in the B ring to produce 5-
CC dehydroepisterol. The C-22 sterol desaturase erg5 further 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. Finally, ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28) sterol
CC reductase erg4 to produce ergosterol (PubMed:18310029) (Probable). In
CC the genus Schizosaccharomyces, a second route exists between lanosterol
CC and fecosterol, via the methylation of lanosterol to eburicol by erg6,
CC followed by C14-demethylation by erg11/cyp1 and C4-demethylation by the
CC demethylation complex erg25-erg26-erg27 (PubMed:8586261) (Probable).
CC {ECO:0000269|PubMed:18310029, ECO:0000269|PubMed:8125337,
CC ECO:0000305|PubMed:18310029, ECO:0000305|PubMed:8586261}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ergosterol + NADP(+) = ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC + H(+) + NADPH; Xref=Rhea:RHEA:18501, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16933, ChEBI:CHEBI:18249, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.71;
CC Evidence={ECO:0000305|PubMed:8125337};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18503;
CC Evidence={ECO:0000305|PubMed:8125337};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000269|PubMed:18310029}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ergosterol and
CC accumulates ergosta-5,7,22,24(28)-tetraenol (PubMed:8125337,
CC PubMed:18310029). Leads to susceptibility to cycloheximide and to
CC staurosporine, but does not affect tolerance to nystatin and to
CC amphotericin B (PubMed:18310029). Leads to cold-sensitivity, a
CC supersensitivity to divalent cations and several unrelated drugs
CC including staurosporine, caffeine, chloramphenicol, sorbitol, and SDS
CC (PubMed:1320960, PubMed:18310029). Does not lead to a sensitivity to
CC nystatin, amphotericin B, thiabendazole or hydroxyurea (PubMed:1320960,
CC PubMed:18310029). {ECO:0000269|PubMed:1320960,
CC ECO:0000269|PubMed:18310029, ECO:0000269|PubMed:8125337}.
CC -!- MISCELLANEOUS: In Aspergillus, the biosynthesis pathway of the sterol
CC precursors leading to the prevalent sterol ergosterol differs from
CC yeast. The ringsystem of lanosterol in S.cerevisiae is firstly
CC demethylised in three enzymatic steps leading to the intermediate
CC zymosterol and secondly a methyl group is added to zymosterol by the
CC sterol 24-C-methyltransferase to form fecosterol. In Aspergillus,
CC lanosterol is firstly transmethylated by the sterol 24-C-
CC methyltransferase leading to the intermediate eburicol and secondly
CC demethylated in three steps to form fecosterol. In the genus
CC Schizosaccharomyces, 2 routes exist from lanosterol to erposterol: the
CC classical one via zymosterol and the second one via the formation of
CC eburicol followed by demethylation. {ECO:0000269|PubMed:8586261}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; X63549; CAA45113.1; -; Genomic_DNA.
DR EMBL; CU329670; CAB11256.1; -; Genomic_DNA.
DR PIR; A43765; A43765.
DR RefSeq; NP_594742.1; NM_001020170.2.
DR AlphaFoldDB; P36209; -.
DR SMR; P36209; -.
DR BioGRID; 278234; 5.
DR STRING; 4896.SPAC20G4.07c.1; -.
DR MaxQB; P36209; -.
DR PaxDb; P36209; -.
DR EnsemblFungi; SPAC20G4.07c.1; SPAC20G4.07c.1:pep; SPAC20G4.07c.
DR GeneID; 2541740; -.
DR KEGG; spo:SPAC20G4.07c; -.
DR PomBase; SPAC20G4.07c; sts1.
DR VEuPathDB; FungiDB:SPAC20G4.07c; -.
DR eggNOG; KOG1435; Eukaryota.
DR HOGENOM; CLU_015631_3_1_1; -.
DR InParanoid; P36209; -.
DR OMA; KQLPYFC; -.
DR PhylomeDB; P36209; -.
DR UniPathway; UPA00768; -.
DR PRO; PR:P36209; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0000246; F:delta24(24-1) sterol reductase activity; IMP:PomBase.
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; IMP:PomBase.
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..453
FT /note="Delta(24(24(1)))-sterol reductase"
FT /id="PRO_0000207492"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 333
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 337
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 385..386
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 425
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 429..433
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 440
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT CONFLICT 412
FT /note="C -> S (in Ref. 1; CAA45113)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 453 AA; 52546 MW; 4740B6EE3BBD27CF CRC64;
MKSTVKKSAP REFGGAKGAL AIMTGFPCLM YYLWACSKFN DSQFIKPESF TIAGFQNFFR
TLGHYIYVGA YPTRYAFLVF WSFCIVQAVM YLTLPGVRTQ GLPLKHRNNE RLPYLCNAIW
SFYTTIVILA VLHVTHVFPI TTFIDMFGPL MSVAIITAFV CTFVLYTGTL LFGDRLFDKP
HRLSGNPIYD AFMGACLNPR LGKLLDFKMF FEVRIPWFIL FFISVGAAVR QYETYGTVSP
QVLFVCLGHY LYANACSKGE QLIVPTWDMA YEKFGFMLIF WNMAGVPFTY SHCTLYLFSH
DPSVYNWSTQ YTTGIYVLLL CCYYIFDTCN GQKNHFRNQI YGTEVHRKTF PQLPWLIIKN
PTFIRCANGG TLLTSGWYRY ARKIHYTADF FQSLSWALIT GFQSPLPYFY PCFFFVVLVH
RVSRDIKKCK AKYGADFDEY CRICPYLFIP YIF
