ERG7A_ASPFU
ID ERG7A_ASPFU Reviewed; 751 AA.
AC Q4WES9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Lanosterol synthase erg7A {ECO:0000303|PubMed:16110826};
DE EC=5.4.99.7 {ECO:0000250|UniProtKB:P38604};
DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase erg7A {ECO:0000250|UniProtKB:P38604};
DE AltName: Full=Ergosterol biosynthesis protein 7A {ECO:0000303|PubMed:16110826};
DE AltName: Full=Oxidosqualene--lanosterol cyclase erg7A {ECO:0000250|UniProtKB:P38604};
DE Short=OSC {ECO:0000250|UniProtKB:P38604};
GN Name=erg7A {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_5G04080;
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: Lanosterol synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway (By
CC similarity). ERG7A and ERG7B catalyze the cyclization of (S)-2,3
CC oxidosqualene to lanosterol, a reaction that forms the sterol core (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:16110826, PubMed:18191972) (Probable).
CC {ECO:0000250|UniProtKB:P38604, ECO:0000305|PubMed:16110826,
CC ECO:0000305|PubMed:18191972}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3-epoxysqualene = lanosterol; Xref=Rhea:RHEA:14621,
CC ChEBI:CHEBI:15441, ChEBI:CHEBI:16521; EC=5.4.99.7;
CC Evidence={ECO:0000250|UniProtKB:P38604};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14622;
CC Evidence={ECO:0000250|UniProtKB:P38604};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:16110826}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000250|UniProtKB:P38604}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P38604};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P38604}.
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 terpene cyclase/mutase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AAHF01000011; EAL85898.1; -; Genomic_DNA.
DR RefSeq; XP_747936.1; XM_742843.1.
DR STRING; 746128.CADAFUBP00005148; -.
DR EnsemblFungi; EAL85898; EAL85898; AFUA_5G04080.
DR GeneID; 3505512; -.
DR KEGG; afm:AFUA_5G04080; -.
DR eggNOG; KOG0497; Eukaryota.
DR HOGENOM; CLU_009074_2_1_1; -.
DR InParanoid; Q4WES9; -.
DR OMA; CWARQTI; -.
DR OrthoDB; 365003at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 5.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR GO; GO:0000250; F:lanosterol synthase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro.
DR CDD; cd02892; SQCY_1; 1.
DR InterPro; IPR032696; SQ_cyclase_C.
DR InterPro; IPR032697; SQ_cyclase_N.
DR InterPro; IPR018333; Squalene_cyclase.
DR InterPro; IPR002365; Terpene_synthase_CS.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR PANTHER; PTHR11764; PTHR11764; 1.
DR Pfam; PF13243; SQHop_cyclase_C; 1.
DR Pfam; PF13249; SQHop_cyclase_N; 1.
DR SFLD; SFLDG01016; Prenyltransferase_Like_2; 1.
DR SUPFAM; SSF48239; SSF48239; 2.
DR TIGRFAMs; TIGR01787; squalene_cyclas; 1.
DR PROSITE; PS01074; TERPENE_SYNTHASES; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Isomerase; Lipid biosynthesis; Lipid droplet;
KW Lipid metabolism; Membrane; Reference proteome; Repeat;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism.
FT CHAIN 1..751
FT /note="Lanosterol synthase erg7A"
FT /id="PRO_0000454118"
FT REPEAT 147..189
FT /note="PFTB 1"
FT /evidence="ECO:0000255"
FT REPEAT 508..553
FT /note="PFTB 2"
FT /evidence="ECO:0000255"
FT REPEAT 585..625
FT /note="PFTB 3"
FT /evidence="ECO:0000255"
FT REPEAT 634..675
FT /note="PFTB 4"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 481
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
SQ SEQUENCE 751 AA; 86808 MW; 3E5ED9412046B02B CRC64;
MTGGPIASWR TAAQGHLTPD ENGDLKTDYS RWRLLDDRGR QTWHYLESDE ENEKWPQSVA
DKHFLGLPTV TPLAPAATNR MFAIHELPEL PKAKTPLQCA ENGLEFFSKL QLPPGNWACE
YGGPMFLLPG LIITYYVTNT PIPPEYATEI KRYLFARQHP EDGGWGLHIE AHSSVFGTCM
NYVALRLIGV SEDDPRMIKA RGLLHKFGGA IYGPHWAKFW LSVLGVMEWE CVNPVPPELW
LLPDWVPFTP WRWWIHIRQV FLPMSYLWSK KFTHPLDPLT KQLRQELYTQ PYDSISFANH
RNSIHAADNY YPKTWLLNLI NQLLVSVWNP YFRIPALVKR AEEWTWELIR MEDENTDYAG
LGPVSNPMNM VACYLHDGPD SYSVRRHRER LNDYMWMKNE GMLMNGTNGV QVWDTAFITQ
AIVVAGFADD PKWRPMLTKA LEFLEDHQLR ENVPDQEKCY RQHRKGAWPF SNKTQGYTVS
DCTAEGLRST IQLQEMHNYP RLISVERLKD SVDCLLLMQN PSGGFTEYET TRGSEKLEWL
NAAEVFGGIM IGYDYPECTT ASVTALSLFS RFYPDYRADE IKAAKDKAVK YIKRVQRPDG
SWYGSWGICF TYAAMFALES LASVGETYET SEYARRGCEF LLSKQKEDGG WGESYLSSEK
HVYVQHEKSQ VVQTAWACLA LMEAEYPHKE PLQKAMKLLM SRQQPNGEWL QESIEGVFNQ
SCMISYPNYK FYWPIRALGL YSRKFGNEEL M
