ER24B_ASPFU
ID ER24B_ASPFU Reviewed; 518 AA.
AC Q4WJJ9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Delta(14)-sterol reductase erg24B {ECO:0000303|PubMed:33475797};
DE EC=1.3.1.- {ECO:0000269|PubMed:33475797};
DE AltName: Full=C-14 sterol reductase erg24B {ECO:0000303|PubMed:33475797};
DE AltName: Full=Ergosterol biosynthesis protein 24B {ECO:0000303|PubMed:33475797};
DE AltName: Full=Sterol C14-reductase erg24B {ECO:0000303|PubMed:33475797};
GN Name=erg24B {ECO:0000303|PubMed:33475797}; ORFNames=AFUA_1G05720;
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).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP AND PATHWAY.
RX PubMed=33475797; DOI=10.1007/s00253-021-11104-5;
RA Li Y., Dai M., Zhang Y., Lu L.;
RT "The sterol C-14 reductase Erg24 is responsible for ergosterol biosynthesis
RT and ion homeostasis in Aspergillus fumigatus.";
RL Appl. Microbiol. Biotechnol. 105:1253-1268(2021).
CC -!- FUNCTION: Delta(14)-sterol reductase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:33475797). Catalyzes the reduction of the C14=C15
CC double bond within 4,4,24-trimethyl ergosta-8,14,24(28)-trienolto
CC produce 4,4-dimethylfecosterol (PubMed:33475797). The third module or
CC 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:0000269|PubMed:33475797,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:18191972}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:16110826}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:33475797}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Results in decreased hyphal growth and virulence;
CC as well as to hypersensitivity to azole drugs (PubMed:33475797).
CC Deletion of both erg24A and erg24B affects ergosterol biosynthesis and
CC leads to the accumulation of the intermediate 4,4-dimethylcholesta-
CC 8,12,24-trienol (PubMed:33475797). {ECO:0000269|PubMed:33475797}.
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 ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; AAHF01000007; EAL88283.1; -; Genomic_DNA.
DR RefSeq; XP_750321.1; XM_745228.1.
DR STRING; 746128.CADAFUBP00000598; -.
DR EnsemblFungi; EAL88283; EAL88283; AFUA_1G05720.
DR GeneID; 3507579; -.
DR KEGG; afm:AFUA_1G05720; -.
DR eggNOG; KOG1435; Eukaryota.
DR HOGENOM; CLU_015631_0_3_1; -.
DR InParanoid; Q4WJJ9; -.
DR OMA; GWIILNC; -.
DR OrthoDB; 532774at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 1.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0050613; F:delta14-sterol reductase activity; IBA:GO_Central.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..518
FT /note="Delta(14)-sterol reductase erg24B"
FT /id="PRO_0000454123"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 382
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 386
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 409
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 414
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 421..422
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 490
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 494..498
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 505
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 518 AA; 58949 MW; 4CD08956635B7AF3 CRC64;
MKLRNTGQMA FRSPFSNLHV RRSSHKPSHP AFVRQNRSMH YYFRDALNIG AFGIIFGLPC
LLYAFTFFCN DISGCPAPSL LHPSTLSIDK LEQEVGWPED GIKALYDTQV TMWVLSYYLL
SLLMQVFLPG TEVEGTELAC GGRLKYKFNA FLSAVLILSG CAVGTYLYGT EFALWTFLWD
NYVQVITANL IICTAIAIFV YLRSFSVPAP GQLNPELRQL APGGHTGNVL YDFFIGRELN
PRIKLPIPFV GETARTIDIK VWCEMRPGLL GWIILDLSNI AHQYRTYGYI TDSIVLTTAF
QAFYVLDALY MEPALLTTMD VIMDGFGFML SFGDMVWVPF LYNFQTRYLS VYPSELGLSG
ILIVLAVTAA GYVIFRGANN QKNRFRTDPN DPRVKHLKYI ETKTGSKLLI SGWWGCARHI
NYLGDWIMSW SYCLPTGVAG YAIIESINPA SGEMQKQAVQ TPESRGWGMI FTYFYMIYFG
VLLLHRERRD EEKCKRKYGA DWNRYTSLVR SRIIPGIY
