HOSM_PENRW
ID HOSM_PENRW Reviewed; 474 AA.
AC O94225; B6HST1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Homocitrate synthase, mitochondrial;
DE Short=HCS;
DE EC=2.3.3.14 {ECO:0000250|UniProtKB:O87198};
DE Flags: Precursor;
GN Name=lys1; ORFNames=Pc22g13190;
OS Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS 54-1255) (Penicillium chrysogenum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC Penicillium chrysogenum species complex.
OX NCBI_TaxID=500485;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9889317; DOI=10.1016/s0378-1119(98)00551-4;
RA Banuelos O., Casqueiro J., Fierro F., Hijarrubia M.J., Gutierrez S.,
RA Martin J.F.;
RT "Characterization and lysine control of expression of the lys1 gene of
RT Penicillium chrysogenum encoding homocitrate synthase.";
RL Gene 226:51-59(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX PubMed=18820685; DOI=10.1038/nbt.1498;
RA van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA Bovenberg R.A.L.;
RT "Genome sequencing and analysis of the filamentous fungus Penicillium
RT chrysogenum.";
RL Nat. Biotechnol. 26:1161-1168(2008).
RN [3]
RP CHARACTERIZATION.
RX PubMed=2115771; DOI=10.1042/bj2690247;
RA Jaklitsch W.M., Kubicek C.P.;
RT "Homocitrate synthase from Penicillium chrysogenum. Localization,
RT purification of the cytosolic isoenzyme, and sensitivity to lysine.";
RL Biochem. J. 269:247-253(1990).
CC -!- FUNCTION: Catalyzes the aldol-type condensation of 2-oxoglutarate with
CC acetyl-CoA to yield homocitrate. Carries out the first step of the
CC alpha-aminoadipate (AAA) lysine biosynthesis pathway.
CC {ECO:0000250|UniProtKB:O87198}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + acetyl-CoA + H2O = (2R)-homocitrate + CoA +
CC H(+); Xref=Rhea:RHEA:12929, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58884; EC=2.3.3.14;
CC Evidence={ECO:0000250|UniProtKB:O87198};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12930;
CC Evidence={ECO:0000250|UniProtKB:O87198};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O87198};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O87198};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 1/5.
CC {ECO:0000250|UniProtKB:O87198}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. Homocitrate synthase LYS20/LYS21 subfamily. {ECO:0000305}.
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DR EMBL; AJ223630; CAA11503.1; -; Genomic_DNA.
DR EMBL; AM920437; CAP98607.1; -; Genomic_DNA.
DR RefSeq; XP_002565245.1; XM_002565199.1.
DR AlphaFoldDB; O94225; -.
DR SMR; O94225; -.
DR STRING; 1108849.XP_002565245.1; -.
DR PRIDE; O94225; -.
DR EnsemblFungi; CAP98607; CAP98607; PCH_Pc22g13190.
DR GeneID; 8310823; -.
DR KEGG; pcs:Pc22g13190; -.
DR VEuPathDB; FungiDB:PCH_Pc22g13190; -.
DR eggNOG; KOG2367; Eukaryota.
DR HOGENOM; CLU_022158_2_2_1; -.
DR OMA; NTMRMLV; -.
DR OrthoDB; 928619at2759; -.
DR UniPathway; UPA00033; UER00028.
DR Proteomes; UP000000724; Contig Pc00c22.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0004410; F:homocitrate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_02222; Homocitr_synth_fung_arch; 1.
DR InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR011872; Homocitrate_synth_fun/arc.
DR InterPro; IPR000891; PYR_CT.
DR Pfam; PF00682; HMGL-like; 1.
DR TIGRFAMs; TIGR02146; LysS_fung_arch; 1.
DR PROSITE; PS00815; AIPM_HOMOCIT_SYNTH_1; 1.
DR PROSITE; PS00816; AIPM_HOMOCIT_SYNTH_2; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Lysine biosynthesis; Magnesium; Manganese;
KW Metal-binding; Mitochondrion; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..474
FT /note="Homocitrate synthase, mitochondrial"
FT /id="PRO_0000001048"
FT DOMAIN 67..320
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT ACT_SITE 353
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 75
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 135
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 195
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 229
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 256
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 258
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
SQ SEQUENCE 474 AA; 51985 MW; 84CBFAF169702AAC CRC64;
MVLLPPSLPV CQLKVTAPEF PSNFYLDGDH SGFVGIETRQ NPHPSASRNP YGHDAGVTDF
LSNVSRFQII ESTLREGEQF ANAFFDTAKK IEIAKALDDF GVDYIELTSP CASEQSRADC
EAICKLGLKA KILTHIRCHM DDARIAVETG VDGVDVVIGT SSYLREHSHG KDMTYIKNAA
IEVIEFVKSK GIEIRFSSED SFRSDLVDLL SIYSAVDKVG VNRVGIADTV GCASPRQVYE
LVRVLRGVVG CDIETHFHND TGCAIANAFC ALEAGATHID TSVLGIGERN GITPLGGLMA
RMMVADREYV KSKYKLEKLK EIEDLVAEAV EVNIPFNNYI TGFCAFTHKA GIHAKAILNN
PSTYEIINPA DFGMSRYVHF ASRLTGWNAI KSRAQQLKLE MTDTQYKECT AKIKAMADIR
PIAVDDADSI IRAYHRNLKS GENKPLLDLT AEEQAAFAAK EKELLEAQAA GLPV
