ID   TPIS_RABIT              Reviewed;         249 AA.
AC   P00939; G1TS29;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 3.
DT   10-JUN-2026, entry version 157.
DE   RecName: Full=Triosephosphate isomerase {ECO:0000305|PubMed:2021650};
DE            Short=TIM;
DE            EC=5.3.1.1 {ECO:0000269|PubMed:2021650};
DE   AltName: Full=Methylglyoxal synthase {ECO:0000305|PubMed:2021650};
DE            EC=4.2.3.3 {ECO:0000269|PubMed:2021650};
DE   AltName: Full=Triose-phosphate isomerase;
GN   Name=TPI1;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Thorbecke;
RX   PubMed=21993624; DOI=10.1038/nature10530;
RA   Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA   Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA   Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA   Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA   Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA   Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA   Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA   Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA   Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA   Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA   Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA   Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA   Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA   Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA   Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT   "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL   Nature 478:476-482(2011).
RN   [2]
RP   PROTEIN SEQUENCE OF 2-249.
RX   PubMed=1171682; DOI=10.1042/bj1450335;
RA   Corran P.H., Waley S.G.;
RT   "The amino acid sequence of rabbit muscle triose phosphate isomerase.";
RL   Biochem. J. 145:335-344(1975).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 57-84.
RX   PubMed=6687628; DOI=10.1038/302718a0;
RA   Putney S.D., Herlihy W.C., Schimmel P.R.;
RT   "A new troponin T and cDNA clones for 13 different muscle proteins, found
RT   by shotgun sequencing.";
RL   Nature 302:718-721(1983).
RN   [4]
RP   ACTIVE SITE.
RX   PubMed=4922541; DOI=10.1021/bi00777a021;
RA   Hartman F.C.;
RT   "Haloacetol phosphates. Characterization of the active site of rabbit
RT   muscle triose phosphate isomerase.";
RL   Biochemistry 10:146-154(1971).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=2021650; DOI=10.1021/bi00232a031;
RA   Richard J.P.;
RT   "Kinetic parameters for the elimination reaction catalyzed by
RT   triosephosphate isomerase and an estimation of the reaction's physiological
RT   significance.";
RL   Biochemistry 30:4581-4585(1991).
RN   [6]
RP   PARTIAL PROTEIN SEQUENCE, AND DEAMIDATION AT ASN-16 AND ASN-72.
RX   PubMed=7574709; DOI=10.1006/abbi.1995.1476;
RA   Sun A.-Q., Yueksel U., Gracy R.W.;
RT   "Terminal marking of triosephosphate isomerase: consequences of
RT   deamidation.";
RL   Arch. Biochem. Biophys. 322:361-368(1995).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-249, AND HOMODIMERIZATION.
RX   PubMed=14643664; DOI=10.1016/j.jmb.2003.10.022;
RA   Aparicio R., Ferreira S.T., Polikarpov I.;
RT   "Closed conformation of the active site loop of rabbit muscle
RT   triosephosphate isomerase in the absence of substrate: evidence of
RT   conformational heterogeneity.";
RL   J. Mol. Biol. 334:1023-1041(2003).
CC   -!- FUNCTION: Triosephosphate isomerase is an extremely efficient metabolic
CC       enzyme that catalyzes the interconversion between dihydroxyacetone
CC       phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis
CC       and gluconeogenesis. {ECO:0000305|PubMed:2021650}.
CC   -!- FUNCTION: It is also responsible for the non-negligible production of
CC       methylglyoxal a reactive cytotoxic side-product that modifies and can
CC       alter proteins, DNA and lipids. {ECO:0000269|PubMed:2021650}.
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; Evidence={ECO:0000269|PubMed:2021650};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18586;
CC         Evidence={ECO:0000305|PubMed:2021650};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18587;
CC         Evidence={ECO:0000305|PubMed:2021650};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dihydroxyacetone phosphate = methylglyoxal + phosphate;
CC         Xref=Rhea:RHEA:17937, ChEBI:CHEBI:17158, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57642; EC=4.2.3.3; Evidence={ECO:0000269|PubMed:2021650};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.62 mM for dihydroxyacetone phosphate (at pH 7.9)
CC         {ECO:0000269|PubMed:2021650};
CC         Note=The kcat is 900 sec(-1) for the isomerization of
CC         dihydroxyacetone phosphate (PubMed:2021650). The kcat is 0.011
CC         sec(-1) for the production of methylglyoxal via the elimination
CC         reaction (PubMed:2021650). Produces methylglyoxal with a calculated
CC         cellular velocity of 0.4 mM per day (PubMed:2021650).
CC         {ECO:0000269|PubMed:2021650};
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC       phosphate from glycerone phosphate: step 1/1. {ECO:0000255|PROSITE-
CC       ProRule:PRU10127}.
CC   -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC       {ECO:0000255|PROSITE-ProRule:PRU10127}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|PROSITE-ProRule:PRU10127,
CC       ECO:0000269|PubMed:14643664}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU10127}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=1;
CC         IsoId=P00939-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P00939-2; Sequence=VSP_060725;
CC   -!- PTM: Asn-16 and Asn-72 undergo deamidation which gives rise to four
CC       extra negative charges. These are expected to decrease subunit-subunit
CC       interactions and so expose the hydrophobic interface to the aqueous
CC       environment. {ECO:0000269|PubMed:7574709}.
CC   -!- SIMILARITY: Belongs to the triosephosphate isomerase family.
CC       {ECO:0000305}.
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DR   EMBL; AAGW02051581; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; V00902; CAA24267.1; -; mRNA.
DR   PIR; A01165; ISRBT.
DR   RefSeq; XP_002712957.1; XM_002712911.4. [P00939-2]
DR   PDB; 1R2R; X-ray; 1.50 A; A/B/C/D=2-249.
DR   PDB; 1R2S; X-ray; 2.85 A; A/B/C/D=2-249.
DR   PDB; 1R2T; X-ray; 2.25 A; A/B=2-249.
DR   PDB; 4OWG; X-ray; 1.55 A; A/B=2-249.
DR   AlphaFoldDB; P00939; -.
DR   SMR; P00939; -.
DR   FunCoup; P00939; 1205.
DR   STRING; 9986.ENSOCUP00000019840; -.
DR   BindingDB; P00939; -.
DR   ChEMBL; CHEMBL3930; -.
DR   PaxDb; 9986-ENSOCUP00000019840; -.
DR   Ensembl; ENSOCUT00000025399.1; ENSOCUP00000019840.1; ENSOCUG00000025649.1. [P00939-2]
DR   GeneID; 100348316; -.
DR   KEGG; ocu:100348316; -.
DR   CTD; 7167; -.
DR   eggNOG; KOG1643; Eukaryota.
DR   GeneTree; ENSGT00390000013354; -.
DR   HOGENOM; CLU_024251_2_0_1; -.
DR   InParanoid; P00939; -.
DR   OMA; NWKMHMT; -.
DR   OrthoDB; 6715177at2759; -.
DR   BRENDA; 5.3.1.1; 1749.
DR   SABIO-RK; P00939; -.
DR   UniPathway; UPA00109; UER00189.
DR   UniPathway; UPA00138; -.
DR   EvolutionaryTrace; P00939; -.
DR   Proteomes; UP000001811; Chromosome 8.
DR   Bgee; ENSOCUG00000025649; Expressed in skeletal muscle tissue and 18 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0008929; F:methylglyoxal synthase activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0004807; F:triose-phosphate isomerase activity; IDA:UniProtKB.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR   GO; GO:0061621; P:canonical glycolysis; IEA:Ensembl.
DR   GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-UniPathway.
DR   GO; GO:0046166; P:glyceraldehyde-3-phosphate biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0019563; P:glycerol catabolic process; IEA:TreeGrafter.
DR   GO; GO:0019242; P:methylglyoxal biosynthetic process; IDA:UniProtKB.
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:SF2; 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; 1R2R; -.
DR   PDBsum; 1R2S; -.
DR   PDBsum; 1R2T; -.
DR   PDBsum; 4OWG; -.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative initiation; Cytoplasm;
KW   Direct protein sequencing; Gluconeogenesis; Glycolysis; Isomerase;
KW   Isopeptide bond; Lyase; Methylation; Nitration; Phosphoprotein;
KW   Reference proteome; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   CHAIN           2..249
FT                   /note="Triosephosphate isomerase"
FT                   /id="PRO_0000090119"
FT   ACT_SITE        96
FT                   /note="Electrophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10127"
FT   ACT_SITE        166
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000269|PubMed:4922541"
FT   BINDING         12
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10127"
FT   BINDING         14
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10127"
FT   MOD_RES         14
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         16
FT                   /note="Deamidated asparagine"
FT                   /evidence="ECO:0000269|PubMed:7574709"
FT   MOD_RES         68
FT                   /note="3'-nitrotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         72
FT                   /note="Deamidated asparagine"
FT                   /evidence="ECO:0000269|PubMed:7574709"
FT   MOD_RES         80
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         106
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P48500"
FT   MOD_RES         149
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         156
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         156
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         159
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         173
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         194
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         194
FT                   /note="N6-methyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         194
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         198
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P48500"
FT   MOD_RES         209
FT                   /note="3'-nitrotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P17751"
FT   MOD_RES         212
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         214
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         223
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   MOD_RES         238
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   CROSSLNK        142
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO1)"
FT                   /evidence="ECO:0000250|UniProtKB:P60174"
FT   VAR_SEQ         1
FT                   /note="M -> MAGTGQEAEFRFSAFYISRQRPQPRPHGGTDLQCAGPSAM (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_060725"
FT   HELIX           4..6
FT                   /evidence="ECO:0007829|PDB:1R2S"
FT   STRAND          7..12
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           19..31
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           33..35
FT                   /evidence="ECO:0007829|PDB:1R2S"
FT   STRAND          38..43
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           46..48
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           49..55
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          60..65
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          69..74
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           81..86
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          91..95
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           97..101
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           107..119
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          123..128
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           132..136
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           140..153
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           158..160
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          161..165
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           168..170
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          171..174
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           176..178
FT                   /evidence="ECO:0007829|PDB:4OWG"
FT   HELIX           179..196
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           199..204
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          207..209
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   TURN            215..217
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           218..222
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   STRAND          229..233
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           234..237
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   HELIX           240..245
FT                   /evidence="ECO:0007829|PDB:1R2R"
FT   TURN            246..248
FT                   /evidence="ECO:0007829|PDB:4OWG"
SQ   SEQUENCE   249 AA;  26757 MW;  F794DE966AC70D81 CRC64;
     MAPSRKFFVG GNWKMNGRKK NLGELITTLN AAKVPADTEV VCAPPTAYID FARQKLDPKI
     AVAAQNCYKV TNGAFTGEIS PGMIKDCGAT WVVLGHSERR HVFGESDELI GQKVAHALSE
     GLGVIACIGE KLDEREAGIT EKVVFEQTKV IADNVKDWSK VVLAYEPVWA IGTGKTATPQ
     QAQEVHEKLR GWLKSNVSDA VAQSTRIIYG GSVTGATCKE LASQPDVDGF LVGGASLKPE
     FVDIINAKQ
//