PRPC_EMENI
ID PRPC_EMENI Reviewed; 460 AA.
AC Q9TEM3; C8V1D7; Q5AYI0;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=2-methylcitrate synthase, mitochondrial {ECO:0000305};
DE Short=Methylcitrate synthase {ECO:0000303|PubMed:10712680};
DE EC=2.3.3.5 {ECO:0000269|PubMed:10712680};
DE AltName: Full=(2S,3S)-2-methylcitrate synthase {ECO:0000250|UniProtKB:P31660};
DE AltName: Full=Citrate synthase 2;
DE EC=2.3.3.16 {ECO:0000269|PubMed:10712680};
DE Flags: Precursor;
GN Name=mcsA {ECO:0000303|PubMed:10712680}; ORFNames=AN6650;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 25-58, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND
RP DISRUPTION PHENOTYPE.
RC TISSUE=Mycelium {ECO:0000269|PubMed:10712680};
RX PubMed=10712680; DOI=10.1046/j.1365-2958.2000.01737.x;
RA Brock M., Fischer R., Linder D., Buckel W.;
RT "Methylcitrate synthase from Aspergillus nidulans: implications for
RT propionate as an antifungal agent.";
RL Mol. Microbiol. 35:961-973(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15265042; DOI=10.1111/j.1432-1033.2004.04255.x;
RA Brock M., Buckel W.;
RT "On the mechanism of action of the antifungal agent propionate.";
RL Eur. J. Biochem. 271:3227-3241(2004).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15514053; DOI=10.1534/genetics.104.027540;
RA Zhang Y.Q., Brock M., Keller N.P.;
RT "Connection of propionyl-CoA metabolism to polyketide biosynthesis in
RT Aspergillus nidulans.";
RL Genetics 168:785-794(2004).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=15066039; DOI=10.1111/j.1365-2958.2004.03994.x;
RA Zhang Y.Q., Keller N.P.;
RT "Blockage of methylcitrate cycle inhibits polyketide production in
RT Aspergillus nidulans.";
RL Mol. Microbiol. 52:541-550(2004).
RN [7]
RP INDUCTION.
RX PubMed=17107606; DOI=10.1186/gb-2006-7-11-r108;
RA David H., Hofmann G., Oliveira A.P., Jarmer H., Nielsen J.;
RT "Metabolic network driven analysis of genome-wide transcription data from
RT Aspergillus nidulans.";
RL Genome Biol. 7:R108.1-R108.16(2006).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18331473; DOI=10.1111/j.1365-2958.2008.06180.x;
RA Fleck C.B., Brock M.;
RT "Characterization of an acyl-CoA: carboxylate CoA-transferase from
RT Aspergillus nidulans involved in propionyl-CoA detoxification.";
RL Mol. Microbiol. 68:642-656(2008).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=20173036; DOI=10.1128/ec.00373-09;
RA Murray S.L., Hynes M.J.;
RT "Metabolic and developmental effects resulting from deletion of the citA
RT gene encoding citrate synthase in Aspergillus nidulans.";
RL Eukaryot. Cell 9:656-666(2010).
CC -!- FUNCTION: Catalyzes the synthesis of (2S,3S)-2-methylcitrate from
CC propionyl-CoA and oxaloacetate and also from acetyl-CoA and
CC oxaloacetate with a greater efficiency. Also has citrate synthase
CC activity and can substitute for the loss of citA activity.
CC {ECO:0000269|PubMed:10712680, ECO:0000269|PubMed:15066039,
CC ECO:0000269|PubMed:15265042, ECO:0000269|PubMed:15514053,
CC ECO:0000269|PubMed:18331473, ECO:0000269|PubMed:20173036}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + oxaloacetate + propanoyl-CoA = (2S,3S)-2-methylcitrate +
CC CoA + H(+); Xref=Rhea:RHEA:23780, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57392, ChEBI:CHEBI:58853; EC=2.3.3.5;
CC Evidence={ECO:0000269|PubMed:10712680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + H2O + oxaloacetate = citrate + CoA + H(+);
CC Xref=Rhea:RHEA:16845, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288; EC=2.3.3.16;
CC Evidence={ECO:0000269|PubMed:10712680};
CC -!- ACTIVITY REGULATION: Partially inhibited by ATP.
CC {ECO:0000269|PubMed:10712680}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.7 uM for propionyl-CoA (in the presence of 1 mM oxaloacetate)
CC {ECO:0000269|PubMed:10712680};
CC KM=2.5 uM for acetyl-CoA (in the presence of 1 mM oxaloacetate)
CC {ECO:0000269|PubMed:10712680};
CC KM=0.63 uM for oxaloacetate (in the presence of 100 mM propionyl-CoA)
CC {ECO:0000269|PubMed:10712680};
CC pH dependence:
CC Optimum pH is 8.5-9.5. {ECO:0000269|PubMed:10712680};
CC Temperature dependence:
CC Optimum temperature is 45-52 degrees Celsius.
CC {ECO:0000269|PubMed:10712680};
CC -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:10712680}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC -!- INDUCTION: Expression is highly induced by propionate. Also induced by
CC ethanol. Transcription is subject to CreA-mediated carbon repression.
CC {ECO:0000269|PubMed:15066039, ECO:0000269|PubMed:17107606,
CC ECO:0000269|PubMed:20173036}.
CC -!- DISRUPTION PHENOTYPE: Blocks propionyl-CoA utilization, as well as
CC growth on propionate. Impairs production of several polyketides such as
CC sterigmatocystin. {ECO:0000269|PubMed:10712680,
CC ECO:0000269|PubMed:15066039, ECO:0000269|PubMed:15265042,
CC ECO:0000269|PubMed:15514053, ECO:0000269|PubMed:18331473,
CC ECO:0000269|PubMed:20173036}.
CC -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR EMBL; AJ249117; CAB53336.1; -; Genomic_DNA.
DR EMBL; AACD01000110; EAA58179.1; -; Genomic_DNA.
DR EMBL; BN001301; CBF71174.1; -; Genomic_DNA.
DR RefSeq; XP_664254.1; XM_659162.1.
DR AlphaFoldDB; Q9TEM3; -.
DR SMR; Q9TEM3; -.
DR STRING; 162425.CADANIAP00007433; -.
DR PRIDE; Q9TEM3; -.
DR EnsemblFungi; CBF71174; CBF71174; ANIA_06650.
DR EnsemblFungi; EAA58179; EAA58179; AN6650.2.
DR GeneID; 2870401; -.
DR KEGG; ani:AN6650.2; -.
DR VEuPathDB; FungiDB:AN6650; -.
DR eggNOG; KOG2617; Eukaryota.
DR HOGENOM; CLU_022049_2_1_1; -.
DR InParanoid; Q9TEM3; -.
DR OMA; AEYWEPT; -.
DR OrthoDB; 1131452at2759; -.
DR BRENDA; 2.3.3.16; 517.
DR UniPathway; UPA00946; -.
DR Proteomes; UP000000560; Chromosome I.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0050440; F:2-methylcitrate synthase activity; IDA:UniProtKB.
DR GO; GO:0004108; F:citrate (Si)-synthase activity; IDA:AspGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; IBA:GO_Central.
DR GO; GO:0019629; P:propionate catabolic process, 2-methylcitrate cycle; IEA:EnsemblFungi.
DR GO; GO:0019679; P:propionate metabolic process, methylcitrate cycle; IDA:UniProtKB.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IMP:AspGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 1.10.580.10; -; 1.
DR InterPro; IPR016142; Citrate_synth-like_lrg_a-sub.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase.
DR InterPro; IPR019810; Citrate_synthase_AS.
DR InterPro; IPR036969; Citrate_synthase_sf.
DR PANTHER; PTHR11739; PTHR11739; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR PRINTS; PR00143; CITRTSNTHASE.
DR SUPFAM; SSF48256; SSF48256; 1.
DR PROSITE; PS00480; CITRATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Mitochondrion; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:10712680"
FT CHAIN 25..460
FT /note="2-methylcitrate synthase, mitochondrial"
FT /id="PRO_0000005469"
FT ACT_SITE 300
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT ACT_SITE 346
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT ACT_SITE 403
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT BINDING 264
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT BINDING 340..344
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT BINDING 355
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT BINDING 429
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT CONFLICT 42
FT /note="R -> K (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 460 AA; 50580 MW; 205CFD6F28321227 CRC64;
MALPLRTARH ASRLAQTIGR RGYATAEPDL KSALKAVIPA KRELLAEVKK QGDEVIGEVK
VSNVIGGMRG LKSMLWEGSV LDADEGIRFH GKTIKDCQKE LPKGPTGTEM LPEAMFWLLL
TGEVPSTSQV RAFSKQLAEE SHLPDHILDL AKSFPKHMHP MTQISIITAA LNTESKFAKL
YEKGINKADY WEPTFDDAIS LLAKIPRVAA LVFRPNEIDV VGRQKLDPAQ DWSYNFAELL
GKGGANNADF HDLLRLYLAL HGDHEGGNVS AHATHLVGSA LSDPFLSYSA GLLGLAGPLH
GLAAQEVLRW ILAMQEKIGT KFTDEDVRAY LWDTLKSGRV VPGYGHGVLR KPDPRFQALM
DFAATRKDVL ANPVFQLVKK NSEIAPGVLT EHGKTKNPHP NVDAASGVLF YHYGFQQPLY
YTVTFGVSRA LGPLVQLIWD RALGLPIERP KSINLLGLKK
