TPIS_RABIT
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 03-AUG-2022, entry version 143.
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 -!- 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 sec(-
CC 1) for the production of methylglyoxal via the elimination reaction
CC (PubMed:2021650). Produces methylglyoxal with a calculated cellular
CC 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_002712911.2. [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 PDBsum; 1R2R; -.
DR PDBsum; 1R2S; -.
DR PDBsum; 1R2T; -.
DR PDBsum; 4OWG; -.
DR AlphaFoldDB; P00939; -.
DR SMR; P00939; -.
DR STRING; 9986.ENSOCUP00000019840; -.
DR ChEMBL; CHEMBL3930; -.
DR Ensembl; ENSOCUT00000025399; ENSOCUP00000019840; ENSOCUG00000025649. [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; QEVCGAI; -.
DR OrthoDB; 1272577at2759; -.
DR TreeFam; TF300829; -.
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 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:0019242; P:methylglyoxal biosynthetic process; IDA:UniProtKB.
DR CDD; cd00311; TIM; 1.
DR Gene3D; 3.20.20.70; -; 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 PANTHER; PTHR21139; PTHR21139; 1.
DR Pfam; PF00121; TIM; 1.
DR SUPFAM; SSF51351; SSF51351; 1.
DR TIGRFAMs; TIGR00419; tim; 1.
DR PROSITE; PS00171; TIM_1; 1.
DR PROSITE; PS51440; TIM_2; 1.
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 STRAND 7..12
FT /evidence="ECO:0007829|PDB:1R2R"
FT HELIX 19..31
FT /evidence="ECO:0007829|PDB:1R2R"
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 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
