ERG3A_ASPFU
ID ERG3A_ASPFU Reviewed; 352 AA.
AC Q4WDL3; Q2VWQ6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Delta(7)-sterol 5(6)-desaturas erg3A {ECO:0000303|PubMed:16110826};
DE EC=1.14.19.- {ECO:0000305|PubMed:16110826};
DE AltName: Full=C-5 sterol desaturase erg3A {ECO:0000303|PubMed:16110826};
DE AltName: Full=Ergosterol Delta(5,6) desaturase erg3A {ECO:0000305};
DE AltName: Full=Ergosterol biosynthesis protein 3A {ECO:0000303|PubMed:16436696};
DE AltName: Full=Sterol-C5-desaturase erg3A {ECO:0000305};
GN Name=erg3A {ECO:0000303|PubMed:16436696}; ORFNames=AFUA_6G05140;
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, AND FUNCTION.
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.
RX PubMed=16436696; DOI=10.1128/aac.50.2.453-460.2006;
RA Alcazar-Fuoli L., Mellado E., Garcia-Effron G., Buitrago M.J., Lopez J.F.,
RA Grimalt J.O., Cuenca-Estrella J.M., Rodriguez-Tudela J.L.;
RT "Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in
RT sterol biosynthesis and antifungal drug susceptibility.";
RL Antimicrob. Agents Chemother. 50:453-460(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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: Delta(7)-sterol 5(6)-desaturase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:16436696, PubMed:18191972). Erg3A is a minor delta(7)-
CC sterol 5(6)-desaturase within the ergosterol pathway, erg3B being the
CC major one (PubMed:16436696, PubMed:18191972). The third module or late
CC pathway involves the ergosterol synthesis itself through consecutive
CC reactions that mainly occur in the endoplasmic reticulum (ER) membrane.
CC Firstly, the squalene synthase erg9 catalyzes the condensation of 2
CC farnesyl pyrophosphate moieties to form squalene, which is the
CC precursor of all steroids. Squalene synthase is crucial for balancing
CC the incorporation of farnesyl diphosphate (FPP) into sterol and
CC nonsterol isoprene synthesis. Secondly, squalene is converted into
CC lanosterol by the consecutive action of the squalene epoxidase erg1 and
CC the lanosterol synthase erg7. Then, the delta(24)-sterol C-
CC methyltransferase erg6 methylates lanosterol at C-24 to produce
CC eburicol. Eburicol is the substrate of the sterol 14-alpha demethylase
CC encoded by cyp51A and cyp51B, to yield 4,4,24-trimethyl ergosta-
CC 8,14,24(28)-trienol. The C-14 reductase erg24 then reduces the C14=C15
CC double bond which leads to 4,4-dimethylfecosterol. A sequence of
CC further demethylations at C-4, involving the C-4 demethylation complex
CC containing the C-4 methylsterol oxidases erg25A or erg25B, the sterol-
CC 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:16436696,
CC ECO:0000269|PubMed:18191972, ECO:0000305|PubMed:16110826,
CC ECO:0000305|PubMed:18191972}.
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P53045};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
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 -!- DISRUPTION PHENOTYPE: Does not affect the susceptibility to
CC amphotericin B, itraconazole, fluconazole, voriconazole, and
CC ketoconazole. {ECO:0000269|PubMed:16436696}.
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 sterol desaturase family. {ECO:0000305}.
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DR EMBL; AAHF01000012; EAL85525.1; -; Genomic_DNA.
DR RefSeq; XP_747563.1; XM_742470.1.
DR STRING; 746128.CADAFUBP00009051; -.
DR EnsemblFungi; EAL85525; EAL85525; AFUA_6G05140.
DR GeneID; 3505076; -.
DR KEGG; afm:AFUA_6G05140; -.
DR VEuPathDB; FungiDB:Afu6g05140; -.
DR eggNOG; KOG0872; Eukaryota.
DR HOGENOM; CLU_047036_3_0_1; -.
DR InParanoid; Q4WDL3; -.
DR OMA; IFPLQKM; -.
DR OrthoDB; 1249774at2759; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0000248; F:C-5 sterol desaturase activity; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0044255; P:cellular lipid metabolic process; IEA:UniProt.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..352
FT /note="Delta(7)-sterol 5(6)-desaturas erg3A"
FT /id="PRO_0000454124"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 174..299
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 188..192
FT /note="Histidine box-1"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT MOTIF 201..205
FT /note="Histidine box-2"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT MOTIF 276..280
FT /note="Histidine box-3"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 352 AA; 41243 MW; 966C0D555EAC5126 CRC64;
MDIVLEIWDT FIGDRVYSAL LPLSLSSTVS LPGLTNAANS SLSLFGASKP FVYEPATQLF
RLEPSKYAYL SAWPRNNIYR QFLSFFLIVW IFGIIVYFIS ATLSYIFIWD KTTVKHPKFL
KNQIPMEIAQ TMRSMPVMSL LTAPFLVAEV RGYAKLYDSV DEEPFPYYSI LQFPLFIAFT
DFCIYWIHRG LHHPLIYKSL HKPHHKWIMP SPFASHAFHP LDGWSQSVPY HVFPFIFPLQ
KLAYVFLFGF INLWTVMIHD GEYVANSPII NGAACHTMHH LYFNYNYGQF TTLWDRLGGS
YRKPNEELFR RETKMDEAEW KRQTKEMETI LKTVEGEDDR KYLSQEEAKK DL
