ER24A_ASPFU
ID ER24A_ASPFU Reviewed; 498 AA.
AC Q4WKA5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Delta(14)-sterol reductase erg24A {ECO:0000303|PubMed:33475797};
DE EC=1.3.1.- {ECO:0000269|PubMed:33475797};
DE AltName: Full=C-14 sterol reductase erg24A {ECO:0000303|PubMed:33475797};
DE AltName: Full=Ergosterol biosynthesis protein 24A {ECO:0000303|PubMed:33475797};
DE AltName: Full=Sterol C14-reductase erg24A {ECO:0000303|PubMed:33475797};
GN Name=erg24A {ECO:0000303|PubMed:33475797}; ORFNames=AFUA_1G03150;
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}.
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; AAHF01000007; EAL88027.1; -; Genomic_DNA.
DR RefSeq; XP_750065.1; XM_744972.1.
DR STRING; 746128.CADAFUBP00000349; -.
DR EnsemblFungi; EAL88027; EAL88027; AFUA_1G03150.
DR GeneID; 3507893; -.
DR KEGG; afm:AFUA_1G03150; -.
DR VEuPathDB; FungiDB:Afu1g03150; -.
DR eggNOG; KOG1435; Eukaryota.
DR HOGENOM; CLU_015631_0_3_1; -.
DR InParanoid; Q4WKA5; -.
DR OMA; SYWRVDT; -.
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..498
FT /note="Delta(14)-sterol reductase erg24A"
FT /id="PRO_0000454122"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..464
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 363
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 367
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 395
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 402..403
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 470
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 474..478
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 485
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 498 AA; 56389 MW; EFC884FD51A1F379 CRC64;
MAPRKDFEDK ATVPIQPVPG KRGYEFGGPL GAFVFIFGLS TLIYCLTFLC NDVSGCPVPS
LLNPSTLSLD KLKEEAGWPQ EGLKAFFDVR VTVWVLSYYV LSLVLYVFLP GEVVEGTELA
CKGRLRYKFN ALPSAILILG GLALGTYMHG ADFVVWTFLW DNYVQIITAN LIICVVLAIF
VYARSFSIPA PGQPNPELRE LAPGGHSGNA LYDFFIGREL NPRVQLPIPF VDEASRTIDI
NVWCEMRPGL LGWIILNLSN IARQYRTYGY ITNSIVLSTV FQTFYVLDAL YMEPAVLTTM
DVIMDGFGYM LSFGHLVWVP FIYNIQTRYL AVFPLELRLR EILLILAVTG AGYAIFRGAN
NQKNRFRRDP SDPRMMHIKY IQTSSGSKLM ISGWWGLARH INYLGDWLMS WSYSLPTGIA
GYTIIESINS SGDMQKQAIQ TPEVRGWGMI FTYFFLVYFG ALLIHREGRD EEKCKSKYGT
DWERYTSIVR SRIIPGIY
