ERG2_ASPFU
ID ERG2_ASPFU Reviewed; 239 AA.
AC Q4WJU9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=C-8 sterol isomerase erg2 {ECO:0000303|PubMed:16110826};
DE EC=5.-.-.- {ECO:0000250|UniProtKB:P32352};
DE AltName: Full=Delta-8--delta-7 sterol isomerase erg2 {ECO:0000303|PubMed:16110826};
DE AltName: Full=Ergosterol biosynthesis protein 2 {ECO:0000303|PubMed:16110826};
GN Name=erg2 {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_1G04720;
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-8 sterol isomerase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (PubMed:16110826) (Probable). Erg2 catalyzes the reaction which results
CC in unsaturation at C-7 in the B ring of sterols and thus converts
CC fecosterol to episterol (By similarity). 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:0000250|UniProtKB:P32352,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:18191972}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fecosterol = episterol; Xref=Rhea:RHEA:33435,
CC ChEBI:CHEBI:17038, ChEBI:CHEBI:23929;
CC Evidence={ECO:0000250|UniProtKB:P32352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33436;
CC Evidence={ECO:0000250|UniProtKB:P32352};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|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 ERG2 family. {ECO:0000305}.
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DR EMBL; AAHF01000007; EAL88183.1; -; Genomic_DNA.
DR RefSeq; XP_750221.1; XM_745128.1.
DR STRING; 746128.CADAFUBP00000500; -.
DR EnsemblFungi; EAL88183; EAL88183; AFUA_1G04720.
DR GeneID; 3508000; -.
DR KEGG; afm:AFUA_1G04720; -.
DR VEuPathDB; FungiDB:Afu1g04720; -.
DR eggNOG; KOG4143; Eukaryota.
DR HOGENOM; CLU_085469_0_0_1; -.
DR InParanoid; Q4WJU9; -.
DR OMA; LWATTRI; -.
DR OrthoDB; 1285317at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 1.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006716; ERG2_sigma1_rcpt-like.
DR PANTHER; PTHR10868; PTHR10868; 1.
DR Pfam; PF04622; ERG2_Sigma1R; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Glycoprotein; Isomerase; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..239
FT /note="C-8 sterol isomerase erg2"
FT /id="PRO_0000454129"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 239 AA; 27032 MW; 41C482B810B57438 CRC64;
MPSKSSSPQS NSTRKNSCGC CCFSVRKFGF LAVFVAIFAA LYSYLDARLE QFYIFNPEHL
HDLSQRAIQA HGNDTRAMVD FIVAELDQKI PGNHLNKNEE WIFNNAGGAM GAMYIIHASI
TEYLIIFGTA IGTEGHTGRH TADDYFNILQ GTQVAFVPGT FEPEVYPPGT VHHLRRGEVK
QYKMEQSCFA LEYARGWIPP MLFFGYADTF TSTLDFPTLW ATTRVTGREM ITNLLRRKF
