ERG26_ASPFU
ID ERG26_ASPFU Reviewed; 412 AA.
AC Q4X017;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase erg26, decarboxylating {ECO:0000250|UniProtKB:P53199};
DE EC=1.1.1.- {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=C-3 sterol dehydrogenase erg26 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=C-4 decarboxylase erg26 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=Ergosterol biosynthetic protein 26 {ECO:0000250|UniProtKB:P53199};
GN Name=erg26 {ECO:0000250|UniProtKB:P53199}; ORFNames=AFUA_2G15030;
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 FUNCTION.
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).
CC -!- FUNCTION: Sterol-C4-methyl oxidase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (By similarity). Erg26 is a catalytic component of the C-4
CC demethylation complex that catalyzes the conversion of 4,4-
CC dimethylfecosterol into fecosterol via 4-methylfecosterol (By
CC similarity). The third module or late pathway involves the ergosterol
CC synthesis itself through consecutive reactions that mainly occur in the
CC endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase
CC erg9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to
CC form squalene, which is the precursor of all steroids. Squalene
CC synthase is crucial for balancing the incorporation of farnesyl
CC diphosphate (FPP) into sterol and nonsterol isoprene synthesis.
CC Secondly, squalene is converted into lanosterol by the consecutive
CC action of the squalene epoxidase erg1 and the lanosterol synthase erg7.
CC Then, the delta(24)-sterol C-methyltransferase erg6 methylates
CC lanosterol at C-24 to produce eburicol. Eburicol is the substrate of
CC the sterol 14-alpha demethylase encoded by cyp51A and cyp51B, to yield
CC 4,4,24-trimethyl ergosta-8,14,24(28)-trienol. The C-14 reductase erg24
CC then reduces the C14=C15 double bond which leads to 4,4-
CC dimethylfecosterol. A sequence of further demethylations at C-4,
CC involving the C-4 demethylation complex containing the C-4 methylsterol
CC oxidases erg25A or erg25B, the sterol-4-alpha-carboxylate 3-
CC dehydrogenase erg26 and the 3-keto-steroid reductase erg27, leads to
CC the production of fecosterol via 4-methylfecosterol. The C-8 sterol
CC isomerase erg2 then catalyzes the reaction which results in
CC unsaturation at C-7 in the B ring of sterols and thus converts
CC fecosterol to episterol. The sterol-C5-desaturase erg3B then catalyzes
CC the introduction of a C-5 double bond in the B ring to produce 5-
CC dehydroepisterol. The 2 other sterol-C5-desaturases, erg3A and erg3C,
CC seem to be less important in ergosterol biosynthesis. The C-22 sterol
CC desaturase erg5 further converts 5-dehydroepisterol into ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in
CC the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC is substrate of the C-24(28) sterol reductases erg4A and erg4B to
CC produce ergosterol. Possible alternative sterol biosynthetic pathways
CC might exist from fecosterol to ergosterol, depending on the activities
CC of the erg3 isoforms (PubMed:18191972) (Probable).
CC {ECO:0000250|UniProtKB:P53199, ECO:0000305|PubMed:18191972}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000250|UniProtKB:P53199}.
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:P53199}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P53199}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P53199}.
CC -!- MISCELLANEOUS: In Aspergillus, the biosynthesis pathway of the sterol
CC precursors leading to the prevalent sterol ergosterol differs from
CC yeast. The ring system 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 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL93798.1; -; Genomic_DNA.
DR RefSeq; XP_755836.1; XM_750743.1.
DR STRING; 746128.CADAFUBP00003006; -.
DR EnsemblFungi; EAL93798; EAL93798; AFUA_2G15030.
DR GeneID; 3512963; -.
DR KEGG; afm:AFUA_2G15030; -.
DR VEuPathDB; FungiDB:Afu2g15030; -.
DR eggNOG; KOG1430; Eukaryota.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; Q4X017; -.
DR OMA; AYEAFGY; -.
DR OrthoDB; 930591at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
DR GO; GO:0000252; F:C-3 sterol dehydrogenase (C-4 sterol decarboxylase) activity; IBA:GO_Central.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis.
FT CHAIN 1..412
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase erg26,
FT decarboxylating"
FT /id="PRO_0000454370"
FT ACT_SITE 192
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 17..23
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 89..90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 111..113
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 188
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A0A059TC02"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 192
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 217..220
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
SQ SEQUENCE 412 AA; 45669 MW; 46DEDF703C5EEBF6 CRC64;
MPQKRPTLEL GSVLVVGGCG FLGWHIVDQL LNFPSETDAS VALPKPEGDS RFDNPRLADR
YPRCVAKVSV LDLRTANNRL PGAQYYDGDI TSEESLLAIF RKVKPDVVIH TATANVLEGN
KELLRKVNVD GTKTLLEVAG GDRGDWGGKC KAFVYTSSAS VLHDTQSDLK NVNEDWPLIR
GKLQLEYYSD TKAEAEEIVL KYNRASPSSM VTCALRPAGI YGEKDTTFTF KVLEHAAKAS
PTVLRMQLGD NNNLFDFTYV GNVAYSHLLA AYRLLATQTR YESGQSGPLD HEKVDGEAFN
ITNDSPVYFW DITRAAWALA GKVVEPNQVW QLSEDLLGPV GAVLETVFGL IGKTPRLTRR
IVRYSCMTRY YSCEKAKYRL GYSPIVSVPE GLSRAVGYVL ARERLESEKK GL
