ERG5_ASPFU
ID ERG5_ASPFU Reviewed; 521 AA.
AC Q4WK25;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=C-22 sterol desaturase erg5 {ECO:0000303|PubMed:16110826};
DE EC=1.14.19.41 {ECO:0000250|UniProtKB:P54781};
DE AltName: Full=Cytochrome P450 monooxygenase erg5 {ECO:0000305};
DE AltName: Full=Ergosterol biosynthesis protein 5 {ECO:0000303|PubMed:16110826};
GN Name=erg5 {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_1G03950;
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.
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: C-22 sterol desaturase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:16110826) (Probable). Erg5 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 (By similarity). The third module
CC 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:0000250|UniProtKB:P54781,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:18191972}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-dehydroepisterol + H(+) + NADPH + O2 = ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol + 2 H2O + NADP(+);
CC Xref=Rhea:RHEA:33467, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:18249, ChEBI:CHEBI:52972,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.19.41;
CC Evidence={ECO:0000250|UniProtKB:P54781};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33468;
CC Evidence={ECO:0000250|UniProtKB:P54781};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000303|PubMed:16110826}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}.
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 cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AAHF01000007; EAL88107.1; -; Genomic_DNA.
DR RefSeq; XP_750145.1; XM_745052.1.
DR STRING; 746128.CADAFUBP00000428; -.
DR EnsemblFungi; EAL88107; EAL88107; AFUA_1G03950.
DR GeneID; 3507982; -.
DR KEGG; afm:AFUA_1G03950; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_023517_0_0_1; -.
DR InParanoid; Q4WK25; -.
DR OMA; MVIPSFY; -.
DR OrthoDB; 574756at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 1.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000249; F:C-22 sterol desaturase activity; IEA:EnsemblFungi.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IEA:EnsemblFungi.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..521
FT /note="C-22 sterol desaturase erg5"
FT /id="PRO_0000454130"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 521 AA; 59042 MW; 61EF2BF23A53A3EE CRC64;
MANVNGSFVS PSADATISPQ LFYNVDSLSA VLNGFTFWKA LATLFFAAVI YDQLRYFYLK
GSLVGPTFKL PFMGPFLQSV NPKFHEYKAK WDSGELSCVS VFHKFVVIAS TRDMSRKIFN
SPAYVKPCVV DIAHKLLGPD NWVFLDGKEH VEFRKGLNGL FTRSALSSYL PVMEECYNKY
YKYFLEKSKA NDYKPEPWMP EFRELMCAVS CRTFVGHYMT DAAIKKIADD YYMITAALEL
VNFPFILPFT KAWYGKKASD MVLEEFSNCA AKSKAHMAAG GEITCIMDAW VKAQQDSAKY
NEKIAKGLPV EDSEKPSHLL REFTDYEIAQ TVFTLLFASQ DATSAACTWL FQLVADRPDV
LEKIREENLR VRNGNINAPL TMDLLDEMKY TRAVVRETLR YRPPVIMVPY LVKKDFPITD
SITVSKGSMI IPSVWPATHD PEAYPNPDSF DPDRWITGDA EKQAKNFLVF GTGPHYCLGQ
TYAQLNLIAM IGKASLEMDW EHAPTPKSED IKVFATIFPE V
