ERG25_SCHPO
ID ERG25_SCHPO Reviewed; 300 AA.
AC Q9UUH4;
DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 129.
DE RecName: Full=C-4 methylsterol oxidase erg25 {ECO:0000303|PubMed:15797383};
DE EC=1.14.18.- {ECO:0000250|UniProtKB:P53045};
DE AltName: Full=Ergosterol biosynthetic protein 25 {ECO:0000250|UniProtKB:P53045};
DE AltName: Full=Sterol-C4-methyl oxidase erg25 {ECO:0000250|UniProtKB:P53045};
DE Short=SMO {ECO:0000250|UniProtKB:P53045};
GN Name=erg25 {ECO:0000303|PubMed:15797383}; ORFNames=SPAC630.08c;
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 [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 [2]
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 [3]
RP IDENTIFICATION, AND INDUCTION.
RX PubMed=15797383; DOI=10.1016/j.cell.2005.01.012;
RA Hughes A.L., Todd B.L., Espenshade P.J.;
RT "SREBP pathway responds to sterols and functions as an oxygen sensor in
RT fission yeast.";
RL Cell 120:831-842(2005).
RN [4]
RP INDUCTION.
RX PubMed=16537923; DOI=10.1128/mcb.26.7.2817-2831.2006;
RA Todd B.L., Stewart E.V., Burg J.S., Hughes A.L., Espenshade P.J.;
RT "Sterol regulatory element binding protein is a principal regulator of
RT anaerobic gene expression in fission yeast.";
RL Mol. Cell. Biol. 26:2817-2831(2006).
RN [5]
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: C-4 methylsterol oxidase; part of the third module of
CC ergosterol biosynthesis pathway that includes by the late steps of the
CC pathway (PubMed:15797383). Erg25 is a catalytic component of the C-4
CC demethylation complex that catalyzes the three-step monooxygenation
CC required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols
CC (By similarity). 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 Secondly, squalene is converted into lanosterol by the consecutive
CC action of the squalene epoxidase erg1 and the lanosterol synthase erg7.
CC The lanosterol 14-alpha-demethylase erg11/cyp1 catalyzes C14-
CC demethylation of lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-
CC triene-3-beta-ol. In the next steps, a complex process involving
CC various demethylation, reduction and desaturation reactions catalyzed
CC by the C-14 reductase erg24 and the C-4 demethylation complex erg25-
CC 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:P53045, ECO:0000269|PubMed:15797383,
CC ECO:0000305|PubMed:18310029, ECO:0000305|PubMed:8586261}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4beta-methylzymosterol-4alpha-
CC carboxylate + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:55244, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:64925; Evidence={ECO:0000250|UniProtKB:P53045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55245;
CC Evidence={ECO:0000250|UniProtKB:P53045};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methylzymosterol + 6 Fe(II)-[cytochrome b5] + 5 H(+) +
CC 3 O2 = 4alpha-carboxyzymosterol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:47056, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:1949, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:143575; Evidence={ECO:0000250|UniProtKB:P53045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47057;
CC Evidence={ECO:0000250|UniProtKB:P53045};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P53045};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 3/6. {ECO:0000250|UniProtKB:P53045}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000250|UniProtKB:P53045}.
CC -!- SUBUNIT: Heterotetramer of erg25, erg26, erg27 and erg28 (By
CC similarity). Erg28 acts as a scaffold to tether erg27 and other 4,4-
CC demethylation-related enzymes, forming a demethylation enzyme complex,
CC in the endoplasmic reticulum (By similarity).
CC {ECO:0000250|UniProtKB:P53045}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P53045}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Expression is highly up-regulated under low oxygen and low
CC sterol conditions in a sre1- and scp1-dependent manner.
CC {ECO:0000269|PubMed:15797383, ECO:0000269|PubMed:16537923}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding. {ECO:0000250|UniProtKB:P53045}.
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 sterol desaturase family.
CC {ECO:0000250|UniProtKB:P53045}.
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DR EMBL; CU329670; CAB52730.1; -; Genomic_DNA.
DR PIR; T38986; T38986.
DR RefSeq; NP_592903.1; NM_001018303.2.
DR AlphaFoldDB; Q9UUH4; -.
DR STRING; 4896.SPAC630.08c.1; -.
DR MaxQB; Q9UUH4; -.
DR PaxDb; Q9UUH4; -.
DR EnsemblFungi; SPAC630.08c.1; SPAC630.08c.1:pep; SPAC630.08c.
DR GeneID; 2543373; -.
DR KEGG; spo:SPAC630.08c; -.
DR PomBase; SPAC630.08c; erg25.
DR VEuPathDB; FungiDB:SPAC630.08c; -.
DR eggNOG; KOG0873; Eukaryota.
DR HOGENOM; CLU_047036_5_0_1; -.
DR InParanoid; Q9UUH4; -.
DR OMA; EIMFYYA; -.
DR PhylomeDB; Q9UUH4; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR Reactome; R-SPO-192105; Synthesis of bile acids and bile salts.
DR UniPathway; UPA00768; -.
DR UniPathway; UPA00770; UER00756.
DR PRO; PR:Q9UUH4; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:PomBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0000254; F:C-4 methylsterol oxidase activity; ISS:PomBase.
DR GO; GO:0005506; F:iron ion binding; ISM:PomBase.
DR GO; GO:0016491; F:oxidoreductase activity; 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; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; NAD; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..300
FT /note="C-4 methylsterol oxidase erg25"
FT /id="PRO_0000117038"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 140..276
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 154..158
FT /note="Histidine box-1"
FT MOTIF 167..171
FT /note="Histidine box-2"
FT MOTIF 251..257
FT /note="Histidine box-3"
SQ SEQUENCE 300 AA; 35803 MW; AA8C2603D35DF331 CRC64;
MNTTSEVIVG TGFQAIRQQL AQMHPELNFV EQLWLAYYKW FDNDVVATGL MSFLLHELIY
FGRCIPWMII DAMPYFRRWK IQPKKVPTLA EQWECTRLVL LSHFTVELPQ IWLFDPMCAT
FGLSTSVPFP PVTKMIWQIT LFFFLEDTWH YWAHRLFHYG IFYRFIHKVH HRYSAPFGLS
AEYAHPLEII LLGAGTVFVP LMWCYFTHDL HLVTMYIWIT LRLFQAVDSH AGYDFPWSLN
KFLPIWAGAD HHDYHHMAFK DNFSSSFRWW DAVLKTDQNY HQFKARRLAA KYEAESKKAK
