ID   TPIS_YEAST              Reviewed;         248 AA.
AC   P00942; D6VS37;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   02-SEP-2026, entry version 235.
DE   RecName: Full=Triosephosphate isomerase;
DE            Short=TIM;
DE            EC=5.3.1.1;
DE   AltName: Full=Triose-phosphate isomerase;
GN   Name=TPI1; OrderedLocusNames=YDR050C; ORFNames=YD9609.05C;
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].
RX   PubMed=6759603;
RA   Alber T., Kawasaki G.;
RT   "Nucleotide sequence of the triose phosphate isomerase gene of
RT   Saccharomyces cerevisiae.";
RL   J. Mol. Appl. Genet. 1:419-434(1982).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169867; DOI=10.1038/387s075;
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   PROTEIN SEQUENCE OF 2-15.
RX   PubMed=7005233; DOI=10.1016/s0021-9258(19)69972-2;
RA   Alber T., Hartman F.C., Johnson R.M., Petsko G.A., Tsernoglou D.;
RT   "Crystallization of yeast triose phosphate isomerase from polyethylene
RT   glycol.";
RL   J. Biol. Chem. 256:1356-1361(1981).
RN   [6]
RP   PROTEIN SEQUENCE OF 56-84 AND 90-101.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7895733; DOI=10.1002/elps.11501501210;
RA   Garrels J.I., Futcher B., Kobayashi R., Latter G.I., Schwender B.,
RA   Volpe T., Warner J.R., McLaughlin C.S.;
RT   "Protein identifications for a Saccharomyces cerevisiae protein database.";
RL   Electrophoresis 15:1466-1486(1994).
RN   [7]
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   [8]
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   [9]
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71 AND SER-215, AND
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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-4; SER-71 AND SER-215, AND
RP   IDENTIFICATION BY 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).
RN   [12]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-223, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22106047; DOI=10.1002/pmic.201100166;
RA   Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT   "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL   Proteomics 12:236-240(2012).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX   PubMed=2204417; DOI=10.1021/bi00480a009;
RA   Lolis E., Alber T.C., Davenport R.C., Rose D., Hartman F.C., Petsko G.A.;
RT   "Structure of yeast triosephosphate isomerase at 1.9-A resolution.";
RL   Biochemistry 29:6609-6618(1990).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF COMPLEX WITH 2-P-GLYCOLATE.
RX   PubMed=2204418; DOI=10.1021/bi00480a010;
RA   Lolis E., Petsko G.A.;
RT   "Crystallographic analysis of the complex between triosephosphate isomerase
RT   and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis.";
RL   Biochemistry 29:6619-6625(1990).
RN   [15]
RP   COMPARISON OF X-RAY STRUCTURES.
RX   PubMed=1569570; DOI=10.1016/0022-2836(92)90473-w;
RA   Wierenga R.K., Noble M.E.M., Davenport R.C.;
RT   "Comparison of the refined crystal structures of liganded and unliganded
RT   chicken, yeast and trypanosomal triosephosphate isomerase.";
RL   J. Mol. Biol. 224:1115-1126(1992).
RN   [16]
RP   REVIEW.
RX   PubMed=3331346; DOI=10.1101/sqb.1987.052.01.069;
RA   Alber T.C., Davenport R.C., Giammona D.A., Lolis E., Petsko G.A., Ringe D.;
RT   "Crystallography and site-directed mutagenesis of yeast triosephosphate
RT   isomerase: what can we learn about catalysis from a 'simple' enzyme?";
RL   Cold Spring Harb. Symp. Quant. Biol. 52:603-613(1987).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, AND
RP   HOMODIMERIZATION.
RX   PubMed=12509510; DOI=10.1073/pnas.0233793100;
RA   Jogl G., Rozovsky S., McDermott A.E., Tong L.;
RT   "Optimal alignment for enzymatic proton transfer: structure of the
RT   Michaelis complex of triosephosphate isomerase at 1.2-A resolution.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:50-55(2003).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glyceraldehyde 3-phosphate = dihydroxyacetone phosphate;
CC         Xref=Rhea:RHEA:18585, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776;
CC         EC=5.3.1.1;
CC   -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC       phosphate from glycerone phosphate: step 1/1.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12509510}.
CC   -!- MISCELLANEOUS: Present with 207000 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the triosephosphate isomerase family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; J01366; AAA88757.1; -; Genomic_DNA.
DR   EMBL; Z49209; CAA89080.1; -; Genomic_DNA.
DR   EMBL; AY557654; AAS55980.1; -; Genomic_DNA.
DR   EMBL; BK006938; DAA11897.1; -; Genomic_DNA.
DR   PIR; A01168; ISBYT.
DR   RefSeq; NP_010335.1; NM_001180358.1.
DR   PDB; 1I45; X-ray; 1.80 A; A/B=2-248.
DR   PDB; 1NEY; X-ray; 1.20 A; A/B=2-248.
DR   PDB; 1NF0; X-ray; 1.60 A; A/B=2-248.
DR   PDB; 1YPI; X-ray; 1.90 A; A/B=2-248.
DR   PDB; 2YPI; X-ray; 2.50 A; A/B=2-248.
DR   PDB; 3YPI; X-ray; 2.80 A; A/B=2-248.
DR   PDB; 4FF7; X-ray; 1.86 A; A/B=1-248.
DR   PDB; 7TIM; X-ray; 1.90 A; A/B=2-248.
DR   AlphaFoldDB; P00942; -.
DR   BMRB; P00942; -.
DR   MDRepo; P00942; -.
DR   PCDDB; P00942; -.
DR   SMR; P00942; -.
DR   BioGRID; 32104; 232.
DR   DIP; DIP-6671N; -.
DR   FunCoup; P00942; 920.
DR   IntAct; P00942; 76.
DR   MINT; P00942; -.
DR   STRING; 4932.YDR050C; -.
DR   iPTMnet; P00942; -.
DR   PaxDb; 4932-YDR050C; -.
DR   PeptideAtlas; P00942; -.
DR   TopDownProteomics; P00942; -.
DR   EnsemblFungi; YDR050C_mRNA; YDR050C; YDR050C.
DR   GeneID; 851620; -.
DR   KEGG; sce:YDR050C; -.
DR   AGR; SGD:S000002457; -.
DR   SGD; S000002457; TPI1.
DR   VEuPathDB; FungiDB:YDR050C; -.
DR   eggNOG; KOG1643; Eukaryota.
DR   HOGENOM; CLU_024251_2_0_1; -.
DR   InParanoid; P00942; -.
DR   OMA; NWKMHMT; -.
DR   OrthoDB; 6715177at2759; -.
DR   BioCyc; YEAST:YDR050C-MONOMER; -.
DR   BRENDA; 5.3.1.1; 984.
DR   Reactome; R-SCE-70171; Glycolysis.
DR   Reactome; R-SCE-70263; Gluconeogenesis.
DR   SABIO-RK; P00942; -.
DR   UniPathway; UPA00109; UER00189.
DR   UniPathway; UPA00138; -.
DR   BioGRID-ORCS; 851620; 0 hits in 10 CRISPR screens.
DR   CD-CODE; E03F929F; Stress granule.
DR   EvolutionaryTrace; P00942; -.
DR   PRO; PR:P00942; -.
DR   Proteomes; UP000002311; Chromosome IV.
DR   RNAct; P00942; protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR   GO; GO:0005886; C:plasma membrane; HDA:SGD.
DR   GO; GO:0004807; F:triose-phosphate isomerase activity; IDA:SGD.
DR   GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central.
DR   GO; GO:0006096; P:glycolytic process; IMP:SGD.
DR   CDD; cd00311; TIM; 1.
DR   FunFam; 3.20.20.70:FF:000025; Triosephosphate isomerase; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   HAMAP; MF_00147_B; TIM_B; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR035990; TIM_sf.
DR   InterPro; IPR022896; TrioseP_Isoase_bac/euk.
DR   InterPro; IPR000652; Triosephosphate_isomerase.
DR   InterPro; IPR020861; Triosephosphate_isomerase_AS.
DR   NCBIfam; TIGR00419; tim; 1.
DR   PANTHER; PTHR21139; TRIOSEPHOSPHATE ISOMERASE; 1.
DR   PANTHER; PTHR21139:SF41; TRIOSEPHOSPHATE ISOMERASE; 1.
DR   Pfam; PF00121; TIM; 1.
DR   SUPFAM; SSF51351; Triosephosphate isomerase (TIM); 1.
DR   PROSITE; PS00171; TIM_1; 1.
DR   PROSITE; PS51440; TIM_2; 1.
DR   PDBsum; 1I45; -.
DR   PDBsum; 1NEY; -.
DR   PDBsum; 1NF0; -.
DR   PDBsum; 1YPI; -.
DR   PDBsum; 2YPI; -.
DR   PDBsum; 3YPI; -.
DR   PDBsum; 4FF7; -.
DR   PDBsum; 7TIM; -.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Gluconeogenesis; Glycolysis;
KW   Isomerase; Isopeptide bond; Phosphoprotein; Reference proteome;
KW   Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:7005233"
FT   CHAIN           2..248
FT                   /note="Triosephosphate isomerase"
FT                   /id="PRO_0000090169"
FT   ACT_SITE        95
FT                   /note="Electrophile"
FT   ACT_SITE        165
FT                   /note="Proton acceptor"
FT   BINDING         10
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:12509510"
FT   BINDING         12
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:12509510"
FT   MOD_RES         4
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         71
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   MOD_RES         215
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   CROSSLNK        223
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   STRAND          5..10
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           17..29
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          36..41
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           44..46
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           47..53
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          59..64
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          68..73
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           80..85
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          90..94
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           96..100
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           106..118
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          122..127
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           131..135
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           139..153
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          160..164
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           167..169
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   TURN            170..172
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           175..177
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           178..196
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           198..203
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          206..211
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   TURN            214..216
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           217..220
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   STRAND          228..232
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           233..236
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   HELIX           239..244
FT                   /evidence="ECO:0007829|PDB:1NEY"
FT   TURN            245..247
FT                   /evidence="ECO:0007829|PDB:1NEY"
SQ   SEQUENCE   248 AA;  26795 MW;  8429251C4DF51F86 CRC64;
     MARTFFVGGN FKLNGSKQSI KEIVERLNTA SIPENVEVVI CPPATYLDYS VSLVKKPQVT
     VGAQNAYLKA SGAFTGENSV DQIKDVGAKW VILGHSERRS YFHEDDKFIA DKTKFALGQG
     VGVILCIGET LEEKKAGKTL DVVERQLNAV LEEVKDWTNV VVAYEPVWAI GTGLAATPED
     AQDIHASIRK FLASKLGDKA ASELRILYGG SANGSNAVTF KDKADVDGFL VGGASLKPEF
     VDIINSRN
//