ER10B_ASPFU
ID ER10B_ASPFU Reviewed; 398 AA.
AC Q4WCL5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Acetyl-CoA acetyltransferase erg10B, cytosolic {ECO:0000303|Ref.6};
DE EC=2.3.1.9 {ECO:0000269|Ref.6};
DE AltName: Full=Acetoacetyl-CoA thiolase erg10B {ECO:0000303|Ref.6};
DE Short=ACAT {ECO:0000303|Ref.6};
DE AltName: Full=Cytosolic thiolase erg10B {ECO:0000303|Ref.6};
DE Short=CT {ECO:0000303|Ref.6};
DE AltName: Full=Ergosterol biosynthesis protein 10B {ECO:0000303|PubMed:17352532};
GN Name=erg10B {ECO:0000303|PubMed:32005728};
GN Synonyms=erg10 {ECO:0000303|PubMed:17352532}; ORFNames=AFUA_8G04000;
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, AND FUNCTION.
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 DISRUPTION PHENOTYPE.
RX PubMed=17352532; DOI=10.1371/journal.ppat.0030024;
RA Hu W., Sillaots S., Lemieux S., Davison J., Kauffman S., Breton A.,
RA Linteau A., Xin C., Bowman J., Becker J., Jiang B., Roemer T.;
RT "Essential gene identification and drug target prioritization in
RT Aspergillus fumigatus.";
RL PLoS Pathog. 3:e24-e24(2007).
RN [4]
RP FUNCTION.
RX PubMed=22106303; DOI=10.1073/pnas.1106399108;
RA Yasmin S., Alcazar-Fuoli L., Gruendlinger M., Puempel T., Cairns T.,
RA Blatzer M., Lopez J.F., Grimalt J.O., Bignell E., Haas H.;
RT "Mevalonate governs interdependency of ergosterol and siderophore
RT biosyntheses in the fungal pathogen Aspergillus fumigatus.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E497-E504(2012).
RN [5]
RP IDENTIFICATION.
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).
RN [6] {ECO:0007744|PDB:6AQP, ECO:0007744|PDB:6ARE, ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG, ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR, ECO:0007744|PDB:6ART}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND ACTIVITY REGULATION.
RX DOI=10.1021/acscatal.7b02873;
RA Marshall A.C., Bond C.S., Bruning J.B.;
RT "Structure of Aspergillus fumigatus cytosolic thiolase: trapped tetrahedral
RT reaction intermediates and activation by monovalent cations.";
RL ACS Catal. 8:1973-1989(2018).
CC -!- FUNCTION: Acetyl-CoA acetyltransferase; part of the first module of
CC ergosterol biosynthesis pathway that includes the early steps of the
CC pathway, conserved across all eukaryotes, and which results in the
CC formation of mevalonate from acetyl-coenzyme A (acetyl-CoA) (Ref.6).
CC Erg10B catalyzes the formation of acetoacetyl-CoA from acetyl-CoA
CC (Ref.6). The first module starts with the action of the cytosolic
CC acetyl-CoA acetyltransferase erg10B that catalyzes the formation of
CC acetoacetyl-CoA. The hydroxymethylglutaryl-CoA synthases erg13A and
CC erg13B then condense acetyl-CoA with acetoacetyl-CoA to form HMG-CoA.
CC The rate-limiting step of the early module is the reduction to
CC mevalonate by the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
CC reductases hmg1 and hmg2. Mevalonate is also a precursor for the
CC extracellular siderophore triacetylfusarinine C (TAFC)
CC (PubMed:16110826, PubMed:22106303) (Probable). {ECO:0000269|Ref.6,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:22106303}.
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, ECO:0000269|Ref.6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC Evidence={ECO:0000269|Ref.6};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000269|Ref.6};
CC -!- ACTIVITY REGULATION: Activity is increased by monovalent cations such
CC as K(+), Rb(+) or Cs(+). {ECO:0000269|Ref.6}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=42 uM for acetoacetyl-CoA (in law salt conditions)
CC {ECO:0000269|Ref.6};
CC KM=8 uM for acetoacetyl-CoA (in the presence of 100 mM NaCl)
CC {ECO:0000269|Ref.6};
CC KM=8 uM for acetoacetyl-CoA (in the presence of 100 mM KCl)
CC {ECO:0000269|Ref.6};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 1/3.
CC {ECO:0000269|Ref.6}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|Ref.6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:32005728}.
CC -!- DISRUPTION PHENOTYPE: Leads to lethality. {ECO:0000269|PubMed:17352532,
CC ECO:0000269|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:0000269|Ref.6}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000013; EAL85169.1; -; Genomic_DNA.
DR RefSeq; XP_747207.1; XM_742114.1.
DR PDB; 6AQP; X-ray; 1.80 A; A/B/C/D=1-398.
DR PDB; 6ARE; X-ray; 1.75 A; A/B/C/D=1-398.
DR PDB; 6ARF; X-ray; 1.70 A; A/B/C/D=1-398.
DR PDB; 6ARG; X-ray; 1.78 A; A/B/C/D=1-398.
DR PDB; 6ARL; X-ray; 1.90 A; A/B/C/D=1-398.
DR PDB; 6ARR; X-ray; 1.82 A; A/B/C/D=1-398.
DR PDB; 6ART; X-ray; 2.25 A; A/B/C/D=1-398.
DR PDBsum; 6AQP; -.
DR PDBsum; 6ARE; -.
DR PDBsum; 6ARF; -.
DR PDBsum; 6ARG; -.
DR PDBsum; 6ARL; -.
DR PDBsum; 6ARR; -.
DR PDBsum; 6ART; -.
DR SMR; Q4WCL5; -.
DR STRING; 746128.CADAFUBP00008134; -.
DR SwissPalm; Q4WCL5; -.
DR EnsemblFungi; EAL85169; EAL85169; AFUA_8G04000.
DR GeneID; 3504871; -.
DR KEGG; afm:AFUA_8G04000; -.
DR eggNOG; KOG1390; Eukaryota.
DR HOGENOM; CLU_031026_0_1_1; -.
DR InParanoid; Q4WCL5; -.
DR OMA; ICPSIAI; -.
DR OrthoDB; 1011220at2759; -.
DR UniPathway; UPA00058; UER00101.
DR PHI-base; PHI:2529; -.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
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:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
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; IPR020617; Thiolase_C.
DR InterPro; IPR020613; Thiolase_CS.
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; PS00737; THIOLASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Lipid biosynthesis;
KW Lipid metabolism; Metal-binding; Potassium; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..398
FT /note="Acetyl-CoA acetyltransferase erg10B, cytosolic"
FT /id="PRO_0000454146"
FT ACT_SITE 92
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT ACT_SITE 384
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT BINDING 187
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6AQP,
FT ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG,
FT ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR,
FT ECO:0007744|PDB:6ART"
FT BINDING 229
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6ARE"
FT BINDING 232
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6ARE"
FT BINDING 249
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6AQP,
FT ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG,
FT ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR,
FT ECO:0007744|PDB:6ART"
FT BINDING 250
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6AQP,
FT ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG,
FT ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR,
FT ECO:0007744|PDB:6ART"
FT BINDING 252
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6AQP,
FT ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG,
FT ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR,
FT ECO:0007744|PDB:6ART"
FT BINDING 253
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6ARE"
FT BINDING 350
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6AQP,
FT ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG,
FT ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR,
FT ECO:0007744|PDB:6ART"
FT BINDING 385
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PDB:6AQP,
FT ECO:0007744|PDB:6ARF, ECO:0007744|PDB:6ARG,
FT ECO:0007744|PDB:6ARL, ECO:0007744|PDB:6ARR,
FT ECO:0007744|PDB:6ART"
FT HELIX 1..3
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 7..14
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 23..26
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 29..42
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:6ARE"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 94..107
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 112..121
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 146..150
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 161..172
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 176..195
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 196..202
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 230..235
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:6ARE"
FT STRAND 256..266
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 267..272
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 278..288
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 298..309
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 317..321
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 326..336
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:6ARF"
FT HELIX 356..373
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 377..385
FT /evidence="ECO:0007829|PDB:6ARF"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:6ARF"
FT STRAND 389..397
FT /evidence="ECO:0007829|PDB:6ARF"
SQ SEQUENCE 398 AA; 40909 MW; 648C2196D8C00BC8 CRC64;
MSSLPAVYIV SSARTPVGSF LGSLSSLTAP QLGAHAIKAA LAKVDGLKPS DVQEVFFGNV
ISANVGQNPA RQCALGAGLE ESTICTTVNK VCASGLKAII LGAQTIMTGN ADVVVAGGTE
SMSNAPHYLP NLRTGAKYGH QSLVDGIMKD GLTDAGKQEL MGLQAEECAQ DHGFSREQQD
EYAIRTYEKA QAAQKAGLFD EEIAPIQLPG FRGKPDVTVT QDEEPKNLNP EKLRAIKPAF
IPGSGTVTAP NSSPLNDGAA AVVLVSEAKL KELNLKPVAK ILGWGDAAQQ PSKFTTAPAL
AIPKALKHAG VGQDAIDAFE INEAFSVVAL ANMKLLGIPE EKVNLHGGAV AIGHPIGASG
ARILTTLLGV LKAKKGKLGC AGICNGGGGA SALVVELL
