ERG6_ASPFU
ID ERG6_ASPFU Reviewed; 377 AA.
AC Q4W9V1;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Sterol 24-C-methyltransferase erg6 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:28224386};
DE AltName: Full=Delta(24)-sterol C-methyltransferase erg6 {ECO:0000303|PubMed:28224386};
DE Short=24-SMT {ECO:0000303|PubMed:28224386};
DE AltName: Full=Ergosterol biosynthesis protein 6 {ECO:0000303|PubMed:16372009};
DE AltName: Full=S-adenosyl-L-methionine:sterol C-24 methyl transferase erg6 {ECO:0000305};
DE Short=SAM:SMT;
GN Name=erg6 {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_4G03630;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP IDENTIFICATION, FUNCTION, AND PATHWAY.
RX PubMed=16110826; DOI=10.1080/13693780400029114;
RA Ferreira M.E., Colombo A.L., Paulsen I., Ren Q., Wortman J., Huang J.,
RA Goldman M.H., Goldman G.H.;
RT "The ergosterol biosynthesis pathway, transporter genes, and azole
RT resistance in Aspergillus fumigatus.";
RL Med. Mycol. 43:S313-S319(2005).
RN [3]
RP FUNCTION, AND PATHWAY.
RX PubMed=18191972; DOI=10.1016/j.steroids.2007.11.005;
RA Alcazar-Fuoli L., Mellado E., Garcia-Effron G., Lopez J.F., Grimalt J.O.,
RA Cuenca-Estrella J.M., Rodriguez-Tudela J.L.;
RT "Ergosterol biosynthesis pathway in Aspergillus fumigatus.";
RL Steroids 73:339-347(2008).
RN [4]
RP FUNCTION, INDUCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=28224386; DOI=10.1007/s11274-017-2214-9;
RA Jahanshiri Z., Shams-Ghahfarokhi M., Asghari-Paskiabi F., Saghiri R.,
RA Razzaghi-Abyaneh M.;
RT "alpha-Bisabolol inhibits Aspergillus fumigatus Af239 growth via affecting
RT microsomal delta24-sterol methyltransferase as a crucial enzyme in
RT ergosterol biosynthesis pathway.";
RL World J. Microbiol. Biotechnol. 33:55-55(2017).
CC -!- FUNCTION: Sterol 24-C-methyltransferase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:18191972, PubMed:28224386). Methylates lanosterol at C-
CC 24 to produce eburicol (PubMed:18191972, PubMed:28224386). 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. Squalene synthase is crucial
CC for balancing the incorporation of farnesyl diphosphate (FPP) into
CC sterol and nonsterol isoprene synthesis. Secondly, squalene is
CC converted into lanosterol by the consecutive action of the squalene
CC epoxidase erg1 and the lanosterol synthase erg7. Then, the delta(24)-
CC sterol C-methyltransferase erg6 methylates lanosterol at C-24 to
CC produce eburicol. Eburicol is the substrate of the sterol 14-alpha
CC demethylase encoded by cyp51A and cyp51B, to yield 4,4,24-trimethyl
CC ergosta-8,14,24(28)-trienol. The C-14 reductase erg24 then reduces the
CC C14=C15 double bond which leads to 4,4-dimethylfecosterol. A sequence
CC of further demethylations at C-4, involving the C-4 demethylation
CC complex containing the C-4 methylsterol oxidases erg25A or erg25B, the
CC sterol-4-alpha-carboxylate 3-dehydrogenase erg26 and the 3-keto-steroid
CC reductase erg27, leads to the production of fecosterol via 4-
CC methylfecosterol. The C-8 sterol isomerase erg2 then catalyzes the
CC reaction which results in unsaturation at C-7 in the B ring of sterols
CC and thus converts fecosterol to episterol. The sterol-C5-desaturase
CC erg3B then catalyzes the introduction of a C-5 double bond in the B
CC ring to produce 5-dehydroepisterol. The 2 other sterol-C5-desaturases,
CC erg3A and erg3C, seem to be less important in ergosterol biosynthesis.
CC The C-22 sterol desaturase erg5 further converts 5-dehydroepisterol
CC into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23)
CC double bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-
CC tetraen-3beta-ol is substrate of the C-24(28) sterol reductases erg4A
CC and erg4B to produce ergosterol. Possible alternative sterol
CC biosynthetic pathways might exist from fecosterol to ergosterol,
CC depending on the activities of the erg3 isoforms (PubMed:16110826,
CC PubMed:18191972) (Probable). {ECO:0000269|PubMed:18191972,
CC ECO:0000269|PubMed:28224386, ECO:0000305|PubMed:16110826,
CC ECO:0000305|PubMed:18191972}.
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:0000269|PubMed:28224386};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52653;
CC Evidence={ECO:0000269|PubMed:28224386};
CC -!- ACTIVITY REGULATION: Specific and total activity is decreased in
CC presence of alpha-bisabolol. {ECO:0000269|PubMed:28224386}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:18191972}.
CC -!- SUBCELLULAR LOCATION: Microsome {ECO:0000250|UniProtKB:P32352}.
CC Mitochondrion {ECO:0000250|UniProtKB:P32352}.
CC -!- INDUCTION: Expression is significantly suppressed in the presence of
CC alpha-bisabolol. {ECO:0000269|PubMed:28224386}.
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.
CC {ECO:0000305|PubMed:18191972}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Erg6/SMT family. {ECO:0000305}.
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DR EMBL; AAHF01000016; EAL84512.1; -; Genomic_DNA.
DR RefSeq; XP_746550.1; XM_741457.1.
DR AlphaFoldDB; Q4W9V1; -.
DR SMR; Q4W9V1; -.
DR STRING; 746128.CADAFUBP00009660; -.
DR EnsemblFungi; EAL84512; EAL84512; AFUA_4G03630.
DR GeneID; 3504016; -.
DR KEGG; afm:AFUA_4G03630; -.
DR VEuPathDB; FungiDB:Afu4g03630; -.
DR eggNOG; KOG1269; Eukaryota.
DR HOGENOM; CLU_039068_5_3_1; -.
DR InParanoid; Q4W9V1; -.
DR OMA; ISNMCKV; -.
DR OrthoDB; 661953at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005811; C:lipid droplet; IEA:EnsemblFungi.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IEA:EnsemblFungi.
DR GO; GO:0003838; F:sterol 24-C-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.150; -; 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 Pfam; PF08241; Methyltransf_11; 1.
DR Pfam; PF08498; Sterol_MT_C; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51685; SAM_MT_ERG6_SMT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism;
KW Methyltransferase; Microsome; Mitochondrion; Reference proteome;
KW S-adenosyl-L-methionine; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..377
FT /note="Sterol 24-C-methyltransferase erg6"
FT /id="PRO_0000442289"
SQ SEQUENCE 377 AA; 42571 MW; 74396ADEEA766FA8 CRC64;
MAPVALEQEN HLRDAEFNRA MHGKSAQFRG GFAALRGKDS AAQKAAVDEY FKHWDNKPAE
DETEETRAAR RAEYATLTRH YYNLATDLYE YGWGTSFHFC RFAQGEPFYQ AIARHEHYLA
HQMGIKEGMK VLDVGCGVGG PAREIVKFTD ANVVGLNNND YQIERATRYA EREGLSHKLS
FVKGDFMQMK FPDNSFDAVY AIEATVHAPD LEGVYKEIFR VLKPGGVFGV YEWLMTDAYD
NDNPEHRRIR LGIELGDGIS NMVKVSEGLT AFKNAGFELL HNEDLADRPD AIPWYYPLAG
SFKHMTSPWD FFTIARMTWW GRGIAHRFCG AMETIGLFPK GTQKTADSLA IAGDCLVAGG
EKKLFTPMYL MVGRKPE
