ID   ERG24_SCHPO             Reviewed;         424 AA.
AC   Q09195;
DT   11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 148.
DE   RecName: Full=Delta(14)-sterol reductase erg24 {ECO:0000303|PubMed:7698661};
DE            EC=1.3.1.70 {ECO:0000250|UniProtKB:P32462};
DE   AltName: Full=C-14 sterol reductase erg24 {ECO:0000303|PubMed:7698661};
DE   AltName: Full=Ergosterol biosynthetic protein 24 {ECO:0000250|UniProtKB:P32462};
DE   AltName: Full=Sterol C14-reductase erg24 {ECO:0000250|UniProtKB:P32462};
GN   Name=erg24 {ECO:0000303|PubMed:7698661}; ORFNames=SPBC16G5.18;
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 [MRNA].
RC   STRAIN=SP66;
RX   PubMed=7698661; DOI=10.1016/0378-1119(94)00902-5;
RA   Smith S.;
RT   "Cloning and sequence analysis of an ERG24 homolog from Schizosaccharomyces
RT   pombe.";
RL   Gene 155:139-140(1995).
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.
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   [4]
RP   FUNCTION.
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: Delta(14)-sterol reductase; part of the third module of
CC       ergosterol biosynthesis pathway that includes by the late steps of the
CC       pathway (By similarity). Erg24 reduces the C14=C15 double bond of 4,4-
CC       dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-
CC       cholesta-8,24-dienol (By similarity). The third module or late pathway
CC       involves the ergosterol synthesis itself through consecutive reactions
CC       that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly,
CC       the squalene synthase erg9 catalyzes the condensation of 2 farnesyl
CC       pyrophosphate moieties to form squalene, which is the precursor of all
CC       steroids. Secondly, squalene is converted into lanosterol by the
CC       consecutive action of the squalene epoxidase erg1 and the lanosterol
CC       synthase erg7. The lanosterol 14-alpha-demethylase erg11/cyp1 catalyzes
CC       C14-demethylation of lanosterol to produce 4,4'-dimethyl
CC       cholesta-8,14,24-triene-3-beta-ol. In the next steps, a complex process
CC       involving various demethylation, reduction and desaturation reactions
CC       catalyzed by the C-14 reductase erg24 and the C-4 demethylation complex
CC       erg25-erg26-erg27 leads to the production of zymosterol. Erg28 likely
CC       functions in the C-4 demethylation complex reaction by tethering erg26
CC       and Erg27 to the endoplasmic reticulum or to facilitate interaction
CC       between these proteins. Then, the sterol 24-C-methyltransferase erg6
CC       catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of
CC       zymosterol to form fecosterol. The C-8 sterol isomerase erg2 catalyzes
CC       the reaction which results in unsaturation at C-7 in the B ring of
CC       sterols and thus converts fecosterol to episterol. The sterol-C5-
CC       desaturases erg31 and erg32 then catalyze 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:18310029) (Probable). In the genus
CC       Schizosaccharomyces, a second route exists between lanosterol and
CC       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:0000250|UniProtKB:P32462, ECO:0000305|PubMed:18310029,
CC       ECO:0000305|PubMed:8586261}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC         4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC         Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC         ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC         Evidence={ECO:0000250|UniProtKB:P32462};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18563;
CC         Evidence={ECO:0000250|UniProtKB:P32462};
CC   -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC       lanosterol: step 2/6. {ECO:0000250|UniProtKB:P32462}.
CC   -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC       {ECO:0000250|UniProtKB:P32462}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC       Multi-pass membrane protein {ECO:0000255}.
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; L36039; AAA74121.1; -; mRNA.
DR   EMBL; CU329671; CAA19037.1; -; Genomic_DNA.
DR   PIR; JC4057; JC4057.
DR   RefSeq; NP_596767.1; NM_001023787.2.
DR   AlphaFoldDB; Q09195; -.
DR   SMR; Q09195; -.
DR   BioGRID; 276650; 3.
DR   STRING; 284812.Q09195; -.
DR   MaxQB; Q09195; -.
DR   PaxDb; 4896-SPBC16G5-18-1; -.
DR   EnsemblFungi; SPBC16G5.18.1; SPBC16G5.18.1:pep; SPBC16G5.18.
DR   GeneID; 2540113; -.
DR   KEGG; spo:SPBC16G5.18; -.
DR   PomBase; SPBC16G5.18; erg24.
DR   VEuPathDB; FungiDB:SPBC16G5.18; -.
DR   eggNOG; KOG1435; Eukaryota.
DR   HOGENOM; CLU_015631_0_3_1; -.
DR   InParanoid; Q09195; -.
DR   OMA; DINVWCE; -.
DR   PhylomeDB; Q09195; -.
DR   Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR   Reactome; R-SPO-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR   Reactome; R-SPO-9013405; RHOD GTPase cycle.
DR   UniPathway; UPA00768; -.
DR   UniPathway; UPA00770; UER00755.
DR   PRO; PR:Q09195; -.
DR   Proteomes; UP000002485; Chromosome II.
DR   GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:PomBase.
DR   GO; GO:0050613; F:delta14-sterol reductase activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
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:SF52; DELTA(14)-STEROL REDUCTASE LBR; 1.
DR   Pfam; PF01222; ERG4_ERG24; 1.
DR   PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR   PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE   2: Evidence at transcript level;
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..424
FT                   /note="Delta(14)-sterol reductase erg24"
FT                   /id="PRO_0000207493"
FT   TRANSMEM        19..39
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        370..390
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         317
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         321
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         344
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         349
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         356..357
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         396
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         400..404
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
FT   BINDING         411
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:G4SW86"
SQ   SEQUENCE   424 AA;  48560 MW;  1D3CE704F1E5EF5B CRC64;
     MAKGAVKKEK FEYEFFGPIG ALGVTVLTTV VSFGSFYICN EEGCPAKFSK ISHIFKKTPL
     FDQKSLILYL LWFSTLTLLW KCTNGKWAKG TPIDDKGTRL LYKINGFNSA CLILGVVCTS
     IYLLGASCME FIWDNFLQLM FAAYVFSVVL CTFCYVQSFF GKQQLAKGGT SGNILFDWFI
     GRSLNPRIGN FDIKCFCELR PGLILWVVFD IAFACHQYLV LGGRITDSMV LVIIFHTWYV
     LDSLINESAV LTTMDITTDG FGYMLSFGDL VWVPFLYSLQ ARYLAFHPVD LGLVKTLAIL
     CLQFLGYYIF RGANGQKNRF RSNPNDPKLK HLKFIQTKRG TKLLTSGWWG MARHINYFGD
     WIMAWAWCLP AGFGSPIPYF YVAYFGVLLV HRNARDDHKC RVKYGEDWEK YCKAVKYRII
     PYVY
//