ID   ERG6_SCHPO              Reviewed;         378 AA.
AC   O14321; P78782;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 152.
DE   RecName: Full=Sterol 24-C-methyltransferase erg6 {ECO:0000303|PubMed:18310029};
DE            Short=SCMT {ECO:0000305};
DE            Short=SMT {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000305|PubMed:18310029};
DE            EC=2.1.1.41 {ECO:0000305|PubMed:8586261};
DE   AltName: Full=Delta(24)-sterol C-methyltransferase erg6 {ECO:0000305};
DE   AltName: Full=Ergosterol biosynthesis protein 6 {ECO:0000303|PubMed:18310029};
GN   Name=erg6 {ECO:0000303|PubMed:18310029}; ORFNames=SPBC16E9.05;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 55-378.
RC   STRAIN=PR745;
RX   PubMed=9501991; DOI=10.1093/dnares/4.6.363;
RA   Yoshioka S., Kato K., Nakai K., Okayama H., Nojima H.;
RT   "Identification of open reading frames in Schizosaccharomyces pombe
RT   cDNAs.";
RL   DNA Res. 4:363-369(1997).
RN   [3]
RP   SEQUENCE REVISION TO 55-63.
RA   Yoshioka S., Kato K., Nakai K., Okayama H., Nojima H.;
RL   Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
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   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=16823372; DOI=10.1038/nbt1222;
RA   Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA   Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA   Yoshida M.;
RT   "ORFeome cloning and global analysis of protein localization in the fission
RT   yeast Schizosaccharomyces pombe.";
RL   Nat. Biotechnol. 24:841-847(2006).
RN   [6]
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   [7]
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: Sterol 24-C-methyltransferase; part of the third module of
CC       ergosterol biosynthesis pathway that includes by the late steps of the
CC       pathway (PubMed:18310029). Erg6 catalyzes the methyl transfer from S-
CC       adenosyl-methionine to the C-24 of zymosterol to form fecosterol
CC       (PubMed:18310029). 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:0000269|PubMed:18310029, ECO:0000305|PubMed:18310029,
CC       ECO:0000305|PubMed:8586261}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-adenosyl-L-methionine + zymosterol = fecosterol + H(+) + S-
CC         adenosyl-L-homocysteine; Xref=Rhea:RHEA:21128, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17038, ChEBI:CHEBI:18252, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789; EC=2.1.1.41;
CC         Evidence={ECO:0000305|PubMed:18310029};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21129;
CC         Evidence={ECO:0000305|PubMed:18310029};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=lanosterol + S-adenosyl-L-methionine = eburicol + H(+) + S-
CC         adenosyl-L-homocysteine; Xref=Rhea:RHEA:52652, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16521, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:70315; Evidence={ECO:0000305|PubMed:8586261};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52653;
CC         Evidence={ECO:0000305|PubMed:8586261};
CC   -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC       {ECO:0000269|PubMed:18310029}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16823372}.
CC       Endoplasmic reticulum {ECO:0000305|PubMed:16823372}.
CC   -!- INDUCTION: Expression is anaerobically up-regulated via the sterol
CC       regulatory element binding protein sre1. {ECO:0000269|PubMed:16537923}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of ergosterol and leads
CC       to abnormal cellular morphology (PubMed:18310029). Leads to
CC       susceptibility to cycloheximide and to staurosporine, but does not
CC       affect tolerance to nystatin and to amphotericin B (PubMed:18310029).
CC       {ECO:0000269|PubMed:18310029}.
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 class I-like SAM-binding methyltransferase
CC       superfamily. Erg6/SMT family. {ECO:0000255|PROSITE-ProRule:PRU01022}.
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DR   EMBL; CU329671; CAB16897.1; -; Genomic_DNA.
DR   EMBL; D89131; BAA13793.2; -; mRNA.
DR   PIR; T39579; T39579.
DR   PIR; T42375; T42375.
DR   RefSeq; NP_595787.1; NM_001021688.2.
DR   AlphaFoldDB; O14321; -.
DR   SMR; O14321; -.
DR   STRING; 284812.O14321; -.
DR   iPTMnet; O14321; -.
DR   MaxQB; O14321; -.
DR   PaxDb; 4896-SPBC16E9-05-1; -.
DR   EnsemblFungi; SPBC16E9.05.1; SPBC16E9.05.1:pep; SPBC16E9.05.
DR   GeneID; 2539602; -.
DR   KEGG; spo:SPBC16E9.05; -.
DR   PomBase; SPBC16E9.05; erg6.
DR   VEuPathDB; FungiDB:SPBC16E9.05; -.
DR   eggNOG; KOG1269; Eukaryota.
DR   HOGENOM; CLU_039068_5_3_1; -.
DR   InParanoid; O14321; -.
DR   OMA; AFNKAMH; -.
DR   PhylomeDB; O14321; -.
DR   UniPathway; UPA00768; -.
DR   PRO; PR:O14321; -.
DR   Proteomes; UP000002485; Chromosome II.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; HDA:PomBase.
DR   GO; GO:0003838; F:sterol 24-C-methyltransferase activity; IBA:GO_Central.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IMP:PomBase.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   CDD; cd02440; AdoMet_MTases; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR013216; Methyltransf_11.
DR   InterPro; IPR030384; MeTrfase_SMT.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR013705; Sterol_MeTrfase_C.
DR   PANTHER; PTHR44068:SF1; HYPOTHETICAL LOC100005854; 1.
DR   PANTHER; PTHR44068; ZGC:194242; 1.
DR   Pfam; PF08241; Methyltransf_11; 1.
DR   Pfam; PF08498; Sterol_MT_C; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   PROSITE; PS51685; SAM_MT_ERG6_SMT; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism;
KW   Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transferase.
FT   CHAIN           1..378
FT                   /note="Sterol 24-C-methyltransferase erg6"
FT                   /id="PRO_0000124797"
SQ   SEQUENCE   378 AA;  42867 MW;  FA4D3D82A1CE03D6 CRC64;
     MSSTALLPPN TDQVLSRRLH GKAAEKKTGL AAIASKDVDE QSRKLQEYFE FWDRNHENES
     EEDRARRIDG YKSVVNSYYD LATDLYEYGW SQSFHFSRFY KGEAFAQSIA RHEHYLAYRM
     GIKPGSRVLD VGCGVGGPAR EITEFTGCNL VGLNNNDYQI SRCNNYAVKR NLDKKQVFVK
     GDFMHMPFED NTFDYVYAIE ATVHAPSLEG VYGEIFRVLK PGGVFGVYEW VMSDDYDSSI
     PKHREIAYNI EVGDGIPQMV RKCDAVEAIK KVGFNLLEED DLTDHDNPDL PWYYPLTGDI
     TKCQNIWDVF TVFRTSRLGK LVTRYSVQFL EKIGVAAKGT SKVGDTLAIA QKGLIEGGET
     HLFTPMFLMI AKKPETDA
//