HOSM_YEAST
ID HOSM_YEAST Reviewed; 440 AA.
AC Q12122; D6VRL8; E9P8Z7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Homocitrate synthase, mitochondrial;
DE Short=HCS;
DE EC=2.3.3.14 {ECO:0000250|UniProtKB:O87198};
DE Flags: Precursor;
GN Name=LYS21; OrderedLocusNames=YDL131W; ORFNames=D2195;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8972577;
RX DOI=10.1002/(sici)1097-0061(199612)12:15<1549::aid-yea42>3.0.co;2-s;
RA Woelfl S., Haneman V., Saluz H.P.;
RT "Analysis of a 26,756 bp segment from the left arm of yeast chromosome
RT IV.";
RL Yeast 12:1549-1554(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-410, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
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 {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 21900 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
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; X96876; CAA65629.1; -; Genomic_DNA.
DR EMBL; Z74179; CAA98700.1; -; Genomic_DNA.
DR EMBL; AY692941; AAT92960.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11728.1; -; Genomic_DNA.
DR PIR; S67674; S67674.
DR RefSeq; NP_010151.1; NM_001180190.1.
DR AlphaFoldDB; Q12122; -.
DR SMR; Q12122; -.
DR BioGRID; 31931; 68.
DR DIP; DIP-4634N; -.
DR IntAct; Q12122; 15.
DR MINT; Q12122; -.
DR STRING; 4932.YDL131W; -.
DR iPTMnet; Q12122; -.
DR MaxQB; Q12122; -.
DR PaxDb; Q12122; -.
DR PRIDE; Q12122; -.
DR EnsemblFungi; YDL131W_mRNA; YDL131W; YDL131W.
DR GeneID; 851425; -.
DR KEGG; sce:YDL131W; -.
DR SGD; S000002289; LYS21.
DR VEuPathDB; FungiDB:YDL131W; -.
DR eggNOG; KOG2367; Eukaryota.
DR GeneTree; ENSGT00940000176819; -.
DR HOGENOM; CLU_022158_2_2_1; -.
DR InParanoid; Q12122; -.
DR OMA; NTMRMLV; -.
DR BioCyc; MetaCyc:YDL131W-MON; -.
DR BioCyc; YEAST:YDL131W-MON; -.
DR BRENDA; 2.3.3.14; 984.
DR SABIO-RK; Q12122; -.
DR UniPathway; UPA00033; UER00028.
DR PRO; PR:Q12122; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; Q12122; protein.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0004410; F:homocitrate synthase activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IMP:SGD.
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; Phosphoprotein; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..440
FT /note="Homocitrate synthase, mitochondrial"
FT /id="PRO_0000001051"
FT DOMAIN 37..290
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 323
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 45
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 46
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 105
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 165
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 199
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 226
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 228
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT MOD_RES 399
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48570"
FT MOD_RES 410
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CONFLICT 199
FT /note="T -> A (in Ref. 4; AAT92960)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 440 AA; 48594 MW; 6B01827D998FD9AD CRC64;
MSENNEFQSV TESTTAPTTS NPYGPNPADY LSNVKNFQLI DSTLREGEQF ANAFFDTEKK
IEIARALDDF GVDYIELTSP VASEQSRKDC EAICKLGLKA KILTHIRCHM DDARVAVETG
VDGVDVVIGT SKFLRQYSHG KDMNYIAKSA VEVIEFVKSK GIEIRFSSED SFRSDLVDLL
NIYKTVDKIG VNRVGIADTV GCANPRQVYE LIRTLKSVVS CDIECHFHND TGCAIANAYT
ALEGGARLID VSVLGIGERN GITPLGGLMA RMIVAAPDYV RSKYKLHKIR DIENLVADAV
EVNIPFNNPI TGFCAFTHKA GIHAKAILAN PSTYEILDPH DFGMKRYIHF ANRLTGWNAI
KSRVDQLNLN LTDDQIKEVT AKIKKLGDVR PLNIDDVDSI IKDFHAELST PLLKPVNKGT
DDDNIDISNG HVSKKAKVTK
