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   02-SEP-2026, entry version 157.
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:18310029, PubMed:8125337). Erg4 catalyzes the last step
CC       of ergosterol biosynthesis by converting ergosta-5,7,22,24(28)-tetraen-
CC       3beta-ol into ergosterol (PubMed:18310029, PubMed:8125337). 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,
CC       ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28)
CC       sterol reductase erg4 to produce ergosterol (Probable)
CC       (PubMed:18310029). In the genus Schizosaccharomyces, a second route
CC       exists between lanosterol and fecosterol, via the methylation of
CC       lanosterol to eburicol by erg6, followed by C14-demethylation by
CC       erg11/cyp1 and C4-demethylation by the demethylation complex erg25-
CC       erg26-erg27 (Probable) (PubMed:8586261). {ECO:0000269|PubMed:18310029,
CC       ECO:0000269|PubMed:8125337, ECO:0000305|PubMed:18310029,
CC       ECO:0000305|PubMed:8586261}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ergosterol + NADP(+) = ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC         + NADPH + H(+); 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:18310029,
CC       PubMed:8125337). 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_001020170.3.
DR   AlphaFoldDB; P36209; -.
DR   SMR; P36209; -.
DR   BioGRID; 278234; 5.
DR   FunCoup; P36209; 46.
DR   STRING; 284812.P36209; -.
DR   iPTMnet; P36209; -.
DR   PaxDb; 284812-P36209; -.
DR   GeneID; 2541740; -.
DR   KEGG; spo:2541740; -.
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; QLPYFCN; -.
DR   PhylomeDB; P36209; -.
DR   UniPathway; UPA00768; -.
DR   PRO; PR:P36209; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000246; F:Delta24(24-1) sterol reductase activity; IMP:PomBase.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IMP:PomBase.
DR   FunFam; 1.20.120.1630:FF:000003; C-24(28) sterol reductase; 1.
DR   Gene3D; 1.20.120.1630; -; 1.
DR   InterPro; IPR001171; ERG24_DHCR-like.
DR   InterPro; IPR018083; Sterol_reductase_CS.
DR   PANTHER; PTHR21257; DELTA(14)-STEROL REDUCTASE; 1.
DR   PANTHER; PTHR21257:SF31; DELTA(24(24(1)))-STEROL REDUCTASE ERG4; 1.
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
//