ER10A_ASPFU
ID ER10A_ASPFU Reviewed; 433 AA.
AC Q4WLA8;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Acetyl-CoA acetyltransferase erg10A, mitochondrial {ECO:0000303|PubMed:32005728};
DE EC=2.3.1.9 {ECO:0000269|PubMed:32005728};
DE AltName: Full=Acetoacetyl-CoA thiolase erg10A {ECO:0000303|PubMed:32005728};
DE AltName: Full=Ergosterol biosynthesis protein 10A {ECO:0000303|PubMed:32005728};
DE Flags: Precursor;
GN Name=erg10A {ECO:0000303|PubMed:32005728}; ORFNames=AFUA_6G14200;
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, DISRUPTION PHENOTYPE, BIOTECHNOLOGY, AND PATHWAY.
RX PubMed=32005728; DOI=10.1128/aem.02986-19;
RA Zhang Y., Wei W., Fan J., Jin C., Lu L., Fang W.;
RT "Characterization of Aspergillus fumigatus mitochondrial acetyl-CoA
RT acetyltransferase as an antifungal target.";
RL Appl. Environ. Microbiol. 0:0-0(2020).
CC -!- FUNCTION: Mitochondrial acetyl-CoA acetyltransferase that catalyzes
CC both the formation and degradation of acetoacetyl-CoA
CC (PubMed:32005728). Has no overlapping function with erg10B and seems
CC not to be involved in ergosterol biosynthesis (PubMed:32005728). Plays
CC an important role in growth, morphogenesis and maintaining
CC mitochondrial function including the response to oxidative stresses
CC (PubMed:32005728). {ECO:0000269|PubMed:32005728}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036,
CC ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.9;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10020,
CC ECO:0000269|PubMed:32005728};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC Evidence={ECO:0000269|PubMed:32005728};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038;
CC Evidence={ECO:0000269|PubMed:32005728};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:Q4WCL5};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=26 uM for CoA {ECO:0000269|PubMed:32005728};
CC KM=43 uM for acetoacetyl-CoA {ECO:0000269|PubMed:32005728};
CC KM=232 uM for acetyl-CoA {ECO:0000269|PubMed:32005728};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 1/3.
CC {ECO:0000269|PubMed:32005728}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P41338}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:32005728}.
CC -!- DISRUPTION PHENOTYPE: Leads to lethality.
CC {ECO:0000269|PubMed:32005728}.
CC -!- BIOTECHNOLOGY: Mitochondrial erg10A is essential for A.fumigatus cell
CC viability and might be a potential drug target to feed the antifungal
CC drug development pipeline. {ECO:0000305|PubMed:32005728}.
CC -!- MISCELLANEOUS: Even though it is not involved in catalysis directly,
CC the Cl(-) anion stabilizes the catalytic site via both direct and
CC water-mediated hydrogen bonds to catalytic residues and residues
CC adjacent. {ECO:0000250|UniProtKB:Q4WCL5}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000006; EAL89256.1; -; Genomic_DNA.
DR RefSeq; XP_751294.1; XM_746201.1.
DR SMR; Q4WLA8; -.
DR STRING; 746128.CADAFUBP00000055; -.
DR EnsemblFungi; EAL89256; EAL89256; AFUA_6G14200.
DR GeneID; 3508611; -.
DR KEGG; afm:AFUA_6G14200; -.
DR VEuPathDB; FungiDB:Afu6g14200; -.
DR eggNOG; KOG1390; Eukaryota.
DR HOGENOM; CLU_031026_0_1_1; -.
DR InParanoid; Q4WLA8; -.
DR OMA; TNVCCTT; -.
DR OrthoDB; 1011220at2759; -.
DR UniPathway; UPA00058; UER00101.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR CDD; cd00751; thiolase; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR020615; Thiolase_acyl_enz_int_AS.
DR InterPro; IPR020610; Thiolase_AS.
DR InterPro; IPR020617; Thiolase_C.
DR InterPro; IPR020616; Thiolase_N.
DR Pfam; PF02803; Thiolase_C; 1.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1.
DR PROSITE; PS00098; THIOLASE_1; 1.
DR PROSITE; PS00099; THIOLASE_3; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Metal-binding; Mitochondrion; Potassium;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 35..433
FT /note="Acetyl-CoA acetyltransferase erg10A, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000454144"
FT ACT_SITE 124
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 387
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT ACT_SITE 415
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT BINDING 219
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 229
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:B0XMC1"
FT BINDING 262
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 280
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 284
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 416
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
SQ SEQUENCE 433 AA; 45710 MW; 4D5B4C442DAAABA0 CRC64;
MAIQTTTGLA ARLVAKRATF PASRRNFSAS RSALKEIQEA YILSGARTPT AKFNGSFVSV
SAPELGAVAI KSAVSKSGVP VEKITDVYMG NVLQGAVGQA PARQASMFAG LSPTVESMTV
NKVCASGLKA VALAAQNIQL GLAEAQVAGG MENMSRVPYY LPRSTQLPPF GEIKLQDGLI
QDGLWDVYNQ FHMGICAEKT AKKYEISREE QDQYAIQSYQ RAQAAWKENK FAEEIAPVTV
KGKKGETVVE RDEGYENLRI DKMATLKPAF LRDGTGTVTA GNASTMNDGA SALVLGSKAI
AREFAQGNRA LARIVSTADA AIDPVDFPVA PAKAVPIALE RAGITKDQVA VWEFNEAFAA
VIKANEKILG LQNARVNPLG GAISLGHALG SSGSRILVTL LHQLQPGEYG VAAICNGGGA
ATAMVVQKLD RVD
