ERG24_SCHPO
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 03-AUG-2022, entry version 141.
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-cholesta-
CC 8,24-dienol (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. 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 cholesta-
CC 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=left-to-right; Xref=Rhea:RHEA:18562;
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; 4896.SPBC16G5.18.1; -.
DR MaxQB; Q09195; -.
DR PaxDb; Q09195; -.
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; IKTWCEV; -.
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-9013106; RHOC GTPase cycle.
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:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0050613; F:delta14-sterol reductase activity; ISS:PomBase.
DR GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
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; ISS: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 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
