Full text data of TPI1
TPI1
(TPI)
[Confidence: high (present in two of the MS resources)]
Triosephosphate isomerase; TIM; 5.3.1.1 (Triose-phosphate isomerase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Triosephosphate isomerase; TIM; 5.3.1.1 (Triose-phosphate isomerase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00465028
IPI00465028 Triosephosphate isomerase metabolic pathways, D-glyceraldehyde 3-phosphate = glycerone phosphate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00465028 Triosephosphate isomerase metabolic pathways, D-glyceraldehyde 3-phosphate = glycerone phosphate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P60174
ID TPIS_HUMAN Reviewed; 286 AA.
AC P60174; B7Z5D8; D3DUS9; P00938; Q6FHP9; Q6IS07; Q8WWD0; Q96AG5;
read moreDT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 3.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=Triosephosphate isomerase;
DE Short=TIM;
DE EC=5.3.1.1;
DE AltName: Full=Triose-phosphate isomerase;
GN Name=TPI1; Synonyms=TPI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2579079;
RA Maquat L.E., Chilcote R., Ryan P.M.;
RT "Human triosephosphate isomerase cDNA and protein structure. Studies
RT of triosephosphate isomerase deficiency in man.";
RL J. Biol. Chem. 260:3748-3753(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=4022011;
RA Brown J.R., Daar I.O., Krug J.R., Maquat L.E.;
RT "Characterization of the functional gene and several processed
RT pseudogenes in the human triosephosphate isomerase gene family.";
RL Mol. Cell. Biol. 5:1694-1706(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8723724;
RA Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA Malley T., Gibbs R.A.;
RT "A gene-rich cluster between the CD4 and triosephosphate isomerase
RT genes at human chromosome 12p13.";
RL Genome Res. 6:314-326(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074930;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 27-286 (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42.
RX PubMed=2925688;
RA Boyer T.G., Krug J.R., Maquat L.E.;
RT "Transcriptional regulatory sequences of the housekeeping gene for
RT human triosephosphate isomerase.";
RL J. Biol. Chem. 264:5177-5187(1989).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 26-286 (ISOFORM 1).
RC TISSUE=Brain, Kidney, Placenta, Prostate, Skeletal muscle, Skin, and
RC Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 38-286 (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 39-286.
RX PubMed=6434534;
RA Lu H.S., Yuan P.M., Gracy R.W.;
RT "Primary structure of human triosephosphate isomerase.";
RL J. Biol. Chem. 259:11958-11968(1984).
RN [12]
RP PROTEIN SEQUENCE OF 39-57.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E.,
RA Simpson R.J., Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed
RT lineage kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [13]
RP PROTEIN SEQUENCE OF 39-57.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [14]
RP PROTEIN SEQUENCE OF 43-51; 56-90; 97-168; 180-193; 198-212 AND
RP 232-256, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17693683; DOI=10.1074/mcp.M700120-MCP200;
RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S.,
RA Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.;
RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling
RT network: indicating the involvement of ribonucleoside-diphosphate
RT reductase M2 subunit phosphorylation at residue serine 20 in canonical
RT Wnt signal transduction.";
RL Mol. Cell. Proteomics 6:1952-1967(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58 AND SER-117, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-51; LYS-231 AND LYS-275, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 39-286 IN COMPLEX WITH
RP SUBSTRATE ANALOG, AND HOMODIMERIZATION.
RX PubMed=8061610;
RA Mande S.C., Mainfroid V., Kalk K.H., Goraj K., Martial J.A.,
RA Hol W.G.J.;
RT "Crystal structure of recombinant human triosephosphate isomerase at
RT 2.8-A resolution. Triosephosphate isomerase-related human genetic
RT disorders and comparison with the trypanosomal enzyme.";
RL Protein Sci. 3:810-821(1994).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 39-286.
RX PubMed=16511037; DOI=10.1107/S1744309105008341;
RA Kinoshita T., Maruki R., Warizaya M., Nakajima H., Nishimura S.;
RT "Structure of a high-resolution crystal form of human triosephosphate
RT isomerase: improvement of crystals using the gel-tube method.";
RL Acta Crystallogr. F 61:346-349(2005).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 39-289 OF MUTANT ASP-142,
RP SUBUNIT, AND CHARACTERIZATION OF VARIANT ASP-142.
RX PubMed=18562316; DOI=10.1074/jbc.M802145200;
RA Rodriguez-Almazan C., Arreola R., Rodriguez-Larrea D.,
RA Aguirre-Lopez B., de Gomez-Puyou M.T., Perez-Montfort R., Costas M.,
RA Gomez-Puyou A., Torres-Larios A.;
RT "Structural basis of human triosephosphate isomerase deficiency:
RT mutation E104D is related to alterations of a conserved water network
RT at the dimer interface.";
RL J. Biol. Chem. 283:23254-23263(2008).
RN [30]
RP VARIANT TPI DEFICIENCY ASP-142.
RX PubMed=2876430; DOI=10.1073/pnas.83.20.7903;
RA Daar I.O., Artymiuk P.J., Phillips D.C., Maquat L.E.;
RT "Human triose-phosphate isomerase deficiency: a single amino acid
RT substitution results in a thermolabile enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7903-7907(1986).
RN [31]
RP VARIANTS TPI DEFICIENCY ASP-142 AND MET-269.
RA Neubauer B.A., Pekrun A., Eber S.W., Lakomek M., Schroeter W.;
RT "Relation between genetic defect, altered protein structure, and
RT enzyme function in triose-phosphate isomerase (TPI) deficiency.";
RL Eur. J. Pediatr. Suppl. 151:232-232(1992).
RN [32]
RP VARIANT MANCHESTER ARG-160.
RX PubMed=1339398; DOI=10.1007/BF02265287;
RA Perry B.A., Mohrenweiser H.W.;
RT "Human triosephosphate isomerase: substitution of Arg for Gly at
RT position 122 in a thermolabile electromorph variant, TPI-Manchester.";
RL Hum. Genet. 88:634-638(1992).
RN [33]
RP VARIANT TPI DEFICIENCY HUNGARY LEU-278.
RX PubMed=8503454;
RA Chang M.-L., Artymiuk P.J., Wu X., Hollan S., Lammi A., Maquat L.E.;
RT "Human triosephosphate isomerase deficiency resulting from mutation of
RT Phe-240.";
RL Am. J. Hum. Genet. 52:1260-1269(1993).
RN [34]
RP VARIANTS TPI DEFICIENCY ALA-110; ASP-142 AND MET-192.
RX PubMed=8571957;
RA Watanabe M., Zingg B.C., Mohrenweiser H.W.;
RT "Molecular analysis of a series of alleles in humans with reduced
RT activity at the triosephosphate isomerase locus.";
RL Am. J. Hum. Genet. 58:308-316(1996).
RN [35]
RP VARIANTS TPI DEFICIENCY TYR-79; ASP-142 AND VAL-208.
RX PubMed=9338582;
RX DOI=10.1002/(SICI)1098-1004(1997)10:4<290::AID-HUMU4>3.3.CO;2-F;
RA Arya R., Lalloz M.R.A., Bellingham A.J., Layton D.M.;
RT "Evidence for founder effect of the Glu104Asp substitution and
RT identification of new mutations in triosephosphate isomerase
RT deficiency.";
RL Hum. Mutat. 10:290-294(1997).
CC -!- CATALYTIC ACTIVITY: D-glyceraldehyde 3-phosphate = glycerone
CC phosphate.
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate from glycerone phosphate: step 1/1.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC P12004:PCNA; NbExp=2; IntAct=EBI-717475, EBI-358311;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P60174-3; Sequence=Displayed;
CC Name=2;
CC IsoId=P60174-1; Sequence=VSP_041895;
CC Name=4;
CC IsoId=P60174-4; Sequence=VSP_045310;
CC Note=Produced by alternative splicing;
CC -!- PTM: The initiator methionine for isoform 2 is removed.
CC -!- DISEASE: Triosephosphate isomerase deficiency (TPI deficiency)
CC [MIM:190450]: Autosomal recessive disorder. It is the most severe
CC clinical disorder of glycolysis. It is associated with neonatal
CC jaundice, chronic hemolytic anemia, progressive neuromuscular
CC dysfunction, cardiomyopathy and increased susceptibility to
CC infection. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the triosephosphate isomerase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB51316.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAB59511.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH07086.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH07812.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH09329.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH11611.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH15100.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH17917.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH70129.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH70129.1; Type=Miscellaneous discrepancy; Note=Sequence differs at the C-terminus;
CC Sequence=AAN86636.1; Type=Frameshift; Positions=23;
CC Sequence=BAG36090.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAA49379.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Triosephosphate isomerase
CC entry;
CC URL="http://en.wikipedia.org/wiki/Triosephosphate_isomerase";
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DR EMBL; M10036; AAB59511.1; ALT_INIT; mRNA.
DR EMBL; X69723; CAA49379.1; ALT_INIT; Genomic_DNA.
DR EMBL; AK298809; BAH12874.1; -; mRNA.
DR EMBL; U47924; AAB51316.1; ALT_INIT; Genomic_DNA.
DR EMBL; CH471116; EAW88722.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88723.1; -; Genomic_DNA.
DR EMBL; J04603; AAN86636.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BC007086; AAH07086.1; ALT_INIT; mRNA.
DR EMBL; BC007812; AAH07812.1; ALT_INIT; mRNA.
DR EMBL; BC009329; AAH09329.1; ALT_INIT; mRNA.
DR EMBL; BC011611; AAH11611.1; ALT_INIT; mRNA.
DR EMBL; BC015100; AAH15100.1; ALT_INIT; mRNA.
DR EMBL; BC017165; AAH17165.1; -; mRNA.
DR EMBL; BC017917; AAH17917.1; ALT_INIT; mRNA.
DR EMBL; BC070129; AAH70129.1; ALT_SEQ; mRNA.
DR EMBL; AK313282; BAG36090.1; ALT_INIT; mRNA.
DR EMBL; CR541702; CAG46503.1; -; mRNA.
DR PIR; S29743; ISHUT.
DR RefSeq; NP_000356.1; NM_000365.5.
DR RefSeq; NP_001152759.1; NM_001159287.1.
DR RefSeq; NP_001244955.1; NM_001258026.1.
DR UniGene; Hs.524219; -.
DR PDB; 1HTI; X-ray; 2.80 A; A/B=39-286.
DR PDB; 1WYI; X-ray; 2.20 A; A/B=39-286.
DR PDB; 2IAM; X-ray; 2.80 A; P=60-74.
DR PDB; 2IAN; X-ray; 2.80 A; C/H/M/R=60-74.
DR PDB; 2JK2; X-ray; 1.70 A; A/B=39-286.
DR PDB; 2VOM; X-ray; 1.85 A; A/B/C/D=39-286.
DR PDB; 4BR1; X-ray; 1.90 A; A/B=41-286.
DR PDB; 4E41; X-ray; 2.60 A; C/H=60-74.
DR PDBsum; 1HTI; -.
DR PDBsum; 1WYI; -.
DR PDBsum; 2IAM; -.
DR PDBsum; 2IAN; -.
DR PDBsum; 2JK2; -.
DR PDBsum; 2VOM; -.
DR PDBsum; 4BR1; -.
DR PDBsum; 4E41; -.
DR ProteinModelPortal; P60174; -.
DR SMR; P60174; 41-286.
DR IntAct; P60174; 14.
DR MINT; MINT-1384176; -.
DR STRING; 9606.ENSP00000379933; -.
DR BindingDB; P60174; -.
DR ChEMBL; CHEMBL4880; -.
DR PhosphoSite; P60174; -.
DR DMDM; 39932641; -.
DR DOSAC-COBS-2DPAGE; P60174; -.
DR REPRODUCTION-2DPAGE; IPI00797687; -.
DR REPRODUCTION-2DPAGE; P60174; -.
DR SWISS-2DPAGE; P60174; -.
DR UCD-2DPAGE; P00938; -.
DR UCD-2DPAGE; P60174; -.
DR PaxDb; P60174; -.
DR PRIDE; P60174; -.
DR DNASU; 7167; -.
DR Ensembl; ENST00000229270; ENSP00000229270; ENSG00000111669.
DR Ensembl; ENST00000396705; ENSP00000379933; ENSG00000111669.
DR Ensembl; ENST00000488464; ENSP00000475620; ENSG00000111669.
DR Ensembl; ENST00000535434; ENSP00000443599; ENSG00000111669.
DR Ensembl; ENST00000595390; ENSP00000469350; ENSG00000268548.
DR Ensembl; ENST00000598287; ENSP00000469966; ENSG00000268548.
DR Ensembl; ENST00000599583; ENSP00000476032; ENSG00000268548.
DR Ensembl; ENST00000601074; ENSP00000469782; ENSG00000268548.
DR GeneID; 7167; -.
DR KEGG; hsa:7167; -.
DR UCSC; uc001qrk.4; human.
DR CTD; 7167; -.
DR GeneCards; GC12P007112; -.
DR HGNC; HGNC:12009; TPI1.
DR HPA; CAB004675; -.
DR MIM; 190450; gene+phenotype.
DR neXtProt; NX_P60174; -.
DR Orphanet; 868; Triose phosphate-isomerase deficiency.
DR PharmGKB; PA36689; -.
DR eggNOG; COG0149; -.
DR HOGENOM; HOG000226413; -.
DR HOVERGEN; HBG002599; -.
DR InParanoid; P60174; -.
DR KO; K01803; -.
DR OMA; LYISGQW; -.
DR OrthoDB; EOG76DTT8; -.
DR BioCyc; MetaCyc:HS03441-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P60174; -.
DR UniPathway; UPA00109; UER00189.
DR UniPathway; UPA00138; -.
DR ChiTaRS; TPI1; human.
DR EvolutionaryTrace; P60174; -.
DR GeneWiki; TPI1; -.
DR GenomeRNAi; 7167; -.
DR NextBio; 28066; -.
DR PRO; PR:P60174; -.
DR Bgee; P60174; -.
DR CleanEx; HS_TPI1; -.
DR Genevestigator; P60174; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004807; F:triose-phosphate isomerase activity; NAS:UniProtKB.
DR GO; GO:0009790; P:embryo development; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0019682; P:glyceraldehyde-3-phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0006096; P:glycolysis; TAS:Reactome.
DR GO; GO:0006098; P:pentose-phosphate shunt; IEA:UniProtKB-KW.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
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 promoter usage;
KW Alternative splicing; Complete proteome; Direct protein sequencing;
KW Disease mutation; Gluconeogenesis; Glycolysis; Isomerase; Nitration;
KW Pentose shunt; Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 286 Triosephosphate isomerase.
FT /FTId=PRO_0000090113.
FT ACT_SITE 133 133 Electrophile.
FT ACT_SITE 203 203 Proton acceptor.
FT BINDING 49 49 Substrate.
FT BINDING 51 51 Substrate.
FT MOD_RES 51 51 N6-acetyllysine.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 105 105 Nitrated tyrosine (By similarity).
FT MOD_RES 117 117 Phosphoserine.
FT MOD_RES 231 231 N6-acetyllysine.
FT MOD_RES 246 246 Nitrated tyrosine (By similarity).
FT MOD_RES 249 249 Phosphoserine (By similarity).
FT MOD_RES 275 275 N6-acetyllysine.
FT VAR_SEQ 1 119 Missing (in isoform 4).
FT /FTId=VSP_045310.
FT VAR_SEQ 1 37 Missing (in isoform 2).
FT /FTId=VSP_041895.
FT VARIANT 79 79 C -> Y (in TPI deficiency).
FT /FTId=VAR_007534.
FT VARIANT 110 110 G -> A (in TPI deficiency).
FT /FTId=VAR_007535.
FT VARIANT 142 142 E -> D (in TPI deficiency; the enzyme
FT becomes thermolabile).
FT /FTId=VAR_007536.
FT VARIANT 160 160 G -> R (in Manchester; thermolabile).
FT /FTId=VAR_007537.
FT VARIANT 192 192 V -> M (in TPI deficiency;
FT dbSNP:rs188138723).
FT /FTId=VAR_007538.
FT VARIANT 208 208 I -> V (in TPI deficiency).
FT /FTId=VAR_007539.
FT VARIANT 269 269 V -> M (in TPI deficiency).
FT /FTId=VAR_007540.
FT VARIANT 278 278 F -> L (in TPI deficiency; Hungary;
FT thermolabile).
FT /FTId=VAR_007541.
FT CONFLICT 23 26 RLRA -> TAR (in Ref. 1; AAB59511).
FT CONFLICT 36 36 Missing (in Ref. 1; AAB59511 and 6;
FT AAN86636).
FT CONFLICT 57 58 QS -> KN (in Ref. 11; AA sequence).
FT CONFLICT 64 64 G -> S (in Ref. 11; AA sequence).
FT CONFLICT 67 68 NA -> QG (in Ref. 11; AA sequence).
FT CONFLICT 80 81 AP -> IG (in Ref. 11; AA sequence).
FT CONFLICT 95 95 P -> Q (in Ref. 11; AA sequence).
FT CONFLICT 192 192 V -> A (in Ref. 9; AAH17917).
FT CONFLICT 204 204 P -> N (in Ref. 11; AA sequence).
FT CONFLICT 281 281 I -> L (in Ref. 11; AA sequence).
FT STRAND 44 49
FT HELIX 56 68
FT STRAND 75 80
FT HELIX 83 85
FT HELIX 86 92
FT STRAND 97 102
FT STRAND 106 111
FT HELIX 118 123
FT STRAND 128 132
FT HELIX 134 138
FT HELIX 144 156
FT STRAND 160 165
FT HELIX 169 173
FT HELIX 177 190
FT HELIX 195 197
FT STRAND 198 202
FT HELIX 205 207
FT STRAND 208 211
FT HELIX 216 231
FT HELIX 236 241
FT STRAND 244 246
FT TURN 252 254
FT HELIX 255 259
FT STRAND 266 270
FT HELIX 271 274
FT HELIX 277 282
FT TURN 283 285
SQ SEQUENCE 286 AA; 30791 MW; E6C2157706AE97F8 CRC64;
MAEDGEEAEF HFAALYISGQ WPRLRADTDL QRLGSSAMAP SRKFFVGGNW KMNGRKQSLG
ELIGTLNAAK VPADTEVVCA PPTAYIDFAR QKLDPKIAVA AQNCYKVTNG AFTGEISPGM
IKDCGATWVV LGHSERRHVF GESDELIGQK VAHALAEGLG VIACIGEKLD EREAGITEKV
VFEQTKVIAD NVKDWSKVVL AYEPVWAIGT GKTATPQQAQ EVHEKLRGWL KSNVSDAVAQ
STRIIYGGSV TGATCKELAS QPDVDGFLVG GASLKPEFVD IINAKQ
//
ID TPIS_HUMAN Reviewed; 286 AA.
AC P60174; B7Z5D8; D3DUS9; P00938; Q6FHP9; Q6IS07; Q8WWD0; Q96AG5;
read moreDT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 3.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=Triosephosphate isomerase;
DE Short=TIM;
DE EC=5.3.1.1;
DE AltName: Full=Triose-phosphate isomerase;
GN Name=TPI1; Synonyms=TPI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2579079;
RA Maquat L.E., Chilcote R., Ryan P.M.;
RT "Human triosephosphate isomerase cDNA and protein structure. Studies
RT of triosephosphate isomerase deficiency in man.";
RL J. Biol. Chem. 260:3748-3753(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=4022011;
RA Brown J.R., Daar I.O., Krug J.R., Maquat L.E.;
RT "Characterization of the functional gene and several processed
RT pseudogenes in the human triosephosphate isomerase gene family.";
RL Mol. Cell. Biol. 5:1694-1706(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8723724;
RA Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA Malley T., Gibbs R.A.;
RT "A gene-rich cluster between the CD4 and triosephosphate isomerase
RT genes at human chromosome 12p13.";
RL Genome Res. 6:314-326(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074930;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 27-286 (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42.
RX PubMed=2925688;
RA Boyer T.G., Krug J.R., Maquat L.E.;
RT "Transcriptional regulatory sequences of the housekeeping gene for
RT human triosephosphate isomerase.";
RL J. Biol. Chem. 264:5177-5187(1989).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 26-286 (ISOFORM 1).
RC TISSUE=Brain, Kidney, Placenta, Prostate, Skeletal muscle, Skin, and
RC Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 38-286 (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 39-286.
RX PubMed=6434534;
RA Lu H.S., Yuan P.M., Gracy R.W.;
RT "Primary structure of human triosephosphate isomerase.";
RL J. Biol. Chem. 259:11958-11968(1984).
RN [12]
RP PROTEIN SEQUENCE OF 39-57.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E.,
RA Simpson R.J., Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed
RT lineage kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [13]
RP PROTEIN SEQUENCE OF 39-57.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [14]
RP PROTEIN SEQUENCE OF 43-51; 56-90; 97-168; 180-193; 198-212 AND
RP 232-256, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17693683; DOI=10.1074/mcp.M700120-MCP200;
RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S.,
RA Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.;
RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling
RT network: indicating the involvement of ribonucleoside-diphosphate
RT reductase M2 subunit phosphorylation at residue serine 20 in canonical
RT Wnt signal transduction.";
RL Mol. Cell. Proteomics 6:1952-1967(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58 AND SER-117, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-51; LYS-231 AND LYS-275, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 39-286 IN COMPLEX WITH
RP SUBSTRATE ANALOG, AND HOMODIMERIZATION.
RX PubMed=8061610;
RA Mande S.C., Mainfroid V., Kalk K.H., Goraj K., Martial J.A.,
RA Hol W.G.J.;
RT "Crystal structure of recombinant human triosephosphate isomerase at
RT 2.8-A resolution. Triosephosphate isomerase-related human genetic
RT disorders and comparison with the trypanosomal enzyme.";
RL Protein Sci. 3:810-821(1994).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 39-286.
RX PubMed=16511037; DOI=10.1107/S1744309105008341;
RA Kinoshita T., Maruki R., Warizaya M., Nakajima H., Nishimura S.;
RT "Structure of a high-resolution crystal form of human triosephosphate
RT isomerase: improvement of crystals using the gel-tube method.";
RL Acta Crystallogr. F 61:346-349(2005).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 39-289 OF MUTANT ASP-142,
RP SUBUNIT, AND CHARACTERIZATION OF VARIANT ASP-142.
RX PubMed=18562316; DOI=10.1074/jbc.M802145200;
RA Rodriguez-Almazan C., Arreola R., Rodriguez-Larrea D.,
RA Aguirre-Lopez B., de Gomez-Puyou M.T., Perez-Montfort R., Costas M.,
RA Gomez-Puyou A., Torres-Larios A.;
RT "Structural basis of human triosephosphate isomerase deficiency:
RT mutation E104D is related to alterations of a conserved water network
RT at the dimer interface.";
RL J. Biol. Chem. 283:23254-23263(2008).
RN [30]
RP VARIANT TPI DEFICIENCY ASP-142.
RX PubMed=2876430; DOI=10.1073/pnas.83.20.7903;
RA Daar I.O., Artymiuk P.J., Phillips D.C., Maquat L.E.;
RT "Human triose-phosphate isomerase deficiency: a single amino acid
RT substitution results in a thermolabile enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7903-7907(1986).
RN [31]
RP VARIANTS TPI DEFICIENCY ASP-142 AND MET-269.
RA Neubauer B.A., Pekrun A., Eber S.W., Lakomek M., Schroeter W.;
RT "Relation between genetic defect, altered protein structure, and
RT enzyme function in triose-phosphate isomerase (TPI) deficiency.";
RL Eur. J. Pediatr. Suppl. 151:232-232(1992).
RN [32]
RP VARIANT MANCHESTER ARG-160.
RX PubMed=1339398; DOI=10.1007/BF02265287;
RA Perry B.A., Mohrenweiser H.W.;
RT "Human triosephosphate isomerase: substitution of Arg for Gly at
RT position 122 in a thermolabile electromorph variant, TPI-Manchester.";
RL Hum. Genet. 88:634-638(1992).
RN [33]
RP VARIANT TPI DEFICIENCY HUNGARY LEU-278.
RX PubMed=8503454;
RA Chang M.-L., Artymiuk P.J., Wu X., Hollan S., Lammi A., Maquat L.E.;
RT "Human triosephosphate isomerase deficiency resulting from mutation of
RT Phe-240.";
RL Am. J. Hum. Genet. 52:1260-1269(1993).
RN [34]
RP VARIANTS TPI DEFICIENCY ALA-110; ASP-142 AND MET-192.
RX PubMed=8571957;
RA Watanabe M., Zingg B.C., Mohrenweiser H.W.;
RT "Molecular analysis of a series of alleles in humans with reduced
RT activity at the triosephosphate isomerase locus.";
RL Am. J. Hum. Genet. 58:308-316(1996).
RN [35]
RP VARIANTS TPI DEFICIENCY TYR-79; ASP-142 AND VAL-208.
RX PubMed=9338582;
RX DOI=10.1002/(SICI)1098-1004(1997)10:4<290::AID-HUMU4>3.3.CO;2-F;
RA Arya R., Lalloz M.R.A., Bellingham A.J., Layton D.M.;
RT "Evidence for founder effect of the Glu104Asp substitution and
RT identification of new mutations in triosephosphate isomerase
RT deficiency.";
RL Hum. Mutat. 10:290-294(1997).
CC -!- CATALYTIC ACTIVITY: D-glyceraldehyde 3-phosphate = glycerone
CC phosphate.
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate from glycerone phosphate: step 1/1.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC P12004:PCNA; NbExp=2; IntAct=EBI-717475, EBI-358311;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P60174-3; Sequence=Displayed;
CC Name=2;
CC IsoId=P60174-1; Sequence=VSP_041895;
CC Name=4;
CC IsoId=P60174-4; Sequence=VSP_045310;
CC Note=Produced by alternative splicing;
CC -!- PTM: The initiator methionine for isoform 2 is removed.
CC -!- DISEASE: Triosephosphate isomerase deficiency (TPI deficiency)
CC [MIM:190450]: Autosomal recessive disorder. It is the most severe
CC clinical disorder of glycolysis. It is associated with neonatal
CC jaundice, chronic hemolytic anemia, progressive neuromuscular
CC dysfunction, cardiomyopathy and increased susceptibility to
CC infection. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the triosephosphate isomerase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB51316.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAB59511.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH07086.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH07812.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH09329.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH11611.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH15100.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH17917.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH70129.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH70129.1; Type=Miscellaneous discrepancy; Note=Sequence differs at the C-terminus;
CC Sequence=AAN86636.1; Type=Frameshift; Positions=23;
CC Sequence=BAG36090.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAA49379.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Triosephosphate isomerase
CC entry;
CC URL="http://en.wikipedia.org/wiki/Triosephosphate_isomerase";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M10036; AAB59511.1; ALT_INIT; mRNA.
DR EMBL; X69723; CAA49379.1; ALT_INIT; Genomic_DNA.
DR EMBL; AK298809; BAH12874.1; -; mRNA.
DR EMBL; U47924; AAB51316.1; ALT_INIT; Genomic_DNA.
DR EMBL; CH471116; EAW88722.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88723.1; -; Genomic_DNA.
DR EMBL; J04603; AAN86636.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BC007086; AAH07086.1; ALT_INIT; mRNA.
DR EMBL; BC007812; AAH07812.1; ALT_INIT; mRNA.
DR EMBL; BC009329; AAH09329.1; ALT_INIT; mRNA.
DR EMBL; BC011611; AAH11611.1; ALT_INIT; mRNA.
DR EMBL; BC015100; AAH15100.1; ALT_INIT; mRNA.
DR EMBL; BC017165; AAH17165.1; -; mRNA.
DR EMBL; BC017917; AAH17917.1; ALT_INIT; mRNA.
DR EMBL; BC070129; AAH70129.1; ALT_SEQ; mRNA.
DR EMBL; AK313282; BAG36090.1; ALT_INIT; mRNA.
DR EMBL; CR541702; CAG46503.1; -; mRNA.
DR PIR; S29743; ISHUT.
DR RefSeq; NP_000356.1; NM_000365.5.
DR RefSeq; NP_001152759.1; NM_001159287.1.
DR RefSeq; NP_001244955.1; NM_001258026.1.
DR UniGene; Hs.524219; -.
DR PDB; 1HTI; X-ray; 2.80 A; A/B=39-286.
DR PDB; 1WYI; X-ray; 2.20 A; A/B=39-286.
DR PDB; 2IAM; X-ray; 2.80 A; P=60-74.
DR PDB; 2IAN; X-ray; 2.80 A; C/H/M/R=60-74.
DR PDB; 2JK2; X-ray; 1.70 A; A/B=39-286.
DR PDB; 2VOM; X-ray; 1.85 A; A/B/C/D=39-286.
DR PDB; 4BR1; X-ray; 1.90 A; A/B=41-286.
DR PDB; 4E41; X-ray; 2.60 A; C/H=60-74.
DR PDBsum; 1HTI; -.
DR PDBsum; 1WYI; -.
DR PDBsum; 2IAM; -.
DR PDBsum; 2IAN; -.
DR PDBsum; 2JK2; -.
DR PDBsum; 2VOM; -.
DR PDBsum; 4BR1; -.
DR PDBsum; 4E41; -.
DR ProteinModelPortal; P60174; -.
DR SMR; P60174; 41-286.
DR IntAct; P60174; 14.
DR MINT; MINT-1384176; -.
DR STRING; 9606.ENSP00000379933; -.
DR BindingDB; P60174; -.
DR ChEMBL; CHEMBL4880; -.
DR PhosphoSite; P60174; -.
DR DMDM; 39932641; -.
DR DOSAC-COBS-2DPAGE; P60174; -.
DR REPRODUCTION-2DPAGE; IPI00797687; -.
DR REPRODUCTION-2DPAGE; P60174; -.
DR SWISS-2DPAGE; P60174; -.
DR UCD-2DPAGE; P00938; -.
DR UCD-2DPAGE; P60174; -.
DR PaxDb; P60174; -.
DR PRIDE; P60174; -.
DR DNASU; 7167; -.
DR Ensembl; ENST00000229270; ENSP00000229270; ENSG00000111669.
DR Ensembl; ENST00000396705; ENSP00000379933; ENSG00000111669.
DR Ensembl; ENST00000488464; ENSP00000475620; ENSG00000111669.
DR Ensembl; ENST00000535434; ENSP00000443599; ENSG00000111669.
DR Ensembl; ENST00000595390; ENSP00000469350; ENSG00000268548.
DR Ensembl; ENST00000598287; ENSP00000469966; ENSG00000268548.
DR Ensembl; ENST00000599583; ENSP00000476032; ENSG00000268548.
DR Ensembl; ENST00000601074; ENSP00000469782; ENSG00000268548.
DR GeneID; 7167; -.
DR KEGG; hsa:7167; -.
DR UCSC; uc001qrk.4; human.
DR CTD; 7167; -.
DR GeneCards; GC12P007112; -.
DR HGNC; HGNC:12009; TPI1.
DR HPA; CAB004675; -.
DR MIM; 190450; gene+phenotype.
DR neXtProt; NX_P60174; -.
DR Orphanet; 868; Triose phosphate-isomerase deficiency.
DR PharmGKB; PA36689; -.
DR eggNOG; COG0149; -.
DR HOGENOM; HOG000226413; -.
DR HOVERGEN; HBG002599; -.
DR InParanoid; P60174; -.
DR KO; K01803; -.
DR OMA; LYISGQW; -.
DR OrthoDB; EOG76DTT8; -.
DR BioCyc; MetaCyc:HS03441-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P60174; -.
DR UniPathway; UPA00109; UER00189.
DR UniPathway; UPA00138; -.
DR ChiTaRS; TPI1; human.
DR EvolutionaryTrace; P60174; -.
DR GeneWiki; TPI1; -.
DR GenomeRNAi; 7167; -.
DR NextBio; 28066; -.
DR PRO; PR:P60174; -.
DR Bgee; P60174; -.
DR CleanEx; HS_TPI1; -.
DR Genevestigator; P60174; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004807; F:triose-phosphate isomerase activity; NAS:UniProtKB.
DR GO; GO:0009790; P:embryo development; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0019682; P:glyceraldehyde-3-phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0006096; P:glycolysis; TAS:Reactome.
DR GO; GO:0006098; P:pentose-phosphate shunt; IEA:UniProtKB-KW.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
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 promoter usage;
KW Alternative splicing; Complete proteome; Direct protein sequencing;
KW Disease mutation; Gluconeogenesis; Glycolysis; Isomerase; Nitration;
KW Pentose shunt; Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 286 Triosephosphate isomerase.
FT /FTId=PRO_0000090113.
FT ACT_SITE 133 133 Electrophile.
FT ACT_SITE 203 203 Proton acceptor.
FT BINDING 49 49 Substrate.
FT BINDING 51 51 Substrate.
FT MOD_RES 51 51 N6-acetyllysine.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 105 105 Nitrated tyrosine (By similarity).
FT MOD_RES 117 117 Phosphoserine.
FT MOD_RES 231 231 N6-acetyllysine.
FT MOD_RES 246 246 Nitrated tyrosine (By similarity).
FT MOD_RES 249 249 Phosphoserine (By similarity).
FT MOD_RES 275 275 N6-acetyllysine.
FT VAR_SEQ 1 119 Missing (in isoform 4).
FT /FTId=VSP_045310.
FT VAR_SEQ 1 37 Missing (in isoform 2).
FT /FTId=VSP_041895.
FT VARIANT 79 79 C -> Y (in TPI deficiency).
FT /FTId=VAR_007534.
FT VARIANT 110 110 G -> A (in TPI deficiency).
FT /FTId=VAR_007535.
FT VARIANT 142 142 E -> D (in TPI deficiency; the enzyme
FT becomes thermolabile).
FT /FTId=VAR_007536.
FT VARIANT 160 160 G -> R (in Manchester; thermolabile).
FT /FTId=VAR_007537.
FT VARIANT 192 192 V -> M (in TPI deficiency;
FT dbSNP:rs188138723).
FT /FTId=VAR_007538.
FT VARIANT 208 208 I -> V (in TPI deficiency).
FT /FTId=VAR_007539.
FT VARIANT 269 269 V -> M (in TPI deficiency).
FT /FTId=VAR_007540.
FT VARIANT 278 278 F -> L (in TPI deficiency; Hungary;
FT thermolabile).
FT /FTId=VAR_007541.
FT CONFLICT 23 26 RLRA -> TAR (in Ref. 1; AAB59511).
FT CONFLICT 36 36 Missing (in Ref. 1; AAB59511 and 6;
FT AAN86636).
FT CONFLICT 57 58 QS -> KN (in Ref. 11; AA sequence).
FT CONFLICT 64 64 G -> S (in Ref. 11; AA sequence).
FT CONFLICT 67 68 NA -> QG (in Ref. 11; AA sequence).
FT CONFLICT 80 81 AP -> IG (in Ref. 11; AA sequence).
FT CONFLICT 95 95 P -> Q (in Ref. 11; AA sequence).
FT CONFLICT 192 192 V -> A (in Ref. 9; AAH17917).
FT CONFLICT 204 204 P -> N (in Ref. 11; AA sequence).
FT CONFLICT 281 281 I -> L (in Ref. 11; AA sequence).
FT STRAND 44 49
FT HELIX 56 68
FT STRAND 75 80
FT HELIX 83 85
FT HELIX 86 92
FT STRAND 97 102
FT STRAND 106 111
FT HELIX 118 123
FT STRAND 128 132
FT HELIX 134 138
FT HELIX 144 156
FT STRAND 160 165
FT HELIX 169 173
FT HELIX 177 190
FT HELIX 195 197
FT STRAND 198 202
FT HELIX 205 207
FT STRAND 208 211
FT HELIX 216 231
FT HELIX 236 241
FT STRAND 244 246
FT TURN 252 254
FT HELIX 255 259
FT STRAND 266 270
FT HELIX 271 274
FT HELIX 277 282
FT TURN 283 285
SQ SEQUENCE 286 AA; 30791 MW; E6C2157706AE97F8 CRC64;
MAEDGEEAEF HFAALYISGQ WPRLRADTDL QRLGSSAMAP SRKFFVGGNW KMNGRKQSLG
ELIGTLNAAK VPADTEVVCA PPTAYIDFAR QKLDPKIAVA AQNCYKVTNG AFTGEISPGM
IKDCGATWVV LGHSERRHVF GESDELIGQK VAHALAEGLG VIACIGEKLD EREAGITEKV
VFEQTKVIAD NVKDWSKVVL AYEPVWAIGT GKTATPQQAQ EVHEKLRGWL KSNVSDAVAQ
STRIIYGGSV TGATCKELAS QPDVDGFLVG GASLKPEFVD IINAKQ
//
MIM
190450
*RECORD*
*FIELD* NO
190450
*FIELD* TI
*190450 TRIOSEPHOSPHATE ISOMERASE 1; TPI1
;;TPI
*FIELD* TX
DESCRIPTION
Triosephosphate isomerase (TPI; EC 5.3.1.1) catalyzes the
read moreinterconversion of dihydroxyacetone phosphate (DHAP) and
glyceraldehyde-3-phosphate (summary by Ationu et al., 1999).
CLONING
Electrophoretic variants of triosephosphate isomerase were identified by
the Galton Laboratory group (Hopkinson and Harris, 1971).
Brown et al. (1985) isolated the functional gene and 3 intronless
pseudogenes for human TPI from a recombinant DNA library. The
pseudogenes share a high degree of homology with the functional gene but
contain mutations that preclude synthesis of active TPI enzyme. Sequence
divergence indicated origin of the pseudogenes about 18 million years
ago. Brown et al. (1985) concluded that the human TPI gene family has
only 1 functional gene.
Yuan et al. (1979), on the basis of structural analysis, concluded that
the TPI-A and TPI-B isozymes are products of distinct structural loci.
Decker and Mohrenweiser (1981) presented evidence that triosephosphate
isomerase isozymes are the expression of a single structural locus. (The
existence of 2 TPI loci, both probably coded by chromosome 12, had been
suggested to explain the observed isozyme patterns.) They identified a
rare electrophoretic variant and found that the variant phenotype was
expressed in the TPI-B isozyme of both red cells and circulating
lymphocytes and was also expressed in the TPI-A isozyme of
mitogen-stimulated lymphoblasts.
GENE FUNCTION
TPI is a dimeric enzyme of identical subunits that is characterized by a
high constitutive level of activity in all tissues. It is involved in
both glycolysis and gluconeogenesis, catalyzing the interconversion of
DHAP and glyceraldehyde-3-phosphate. TPI is one of the most efficient
enzymes known, enhancing proton transfer by a factor of 10(10), and is
the least rate-limiting step in glycolysis (summary by Watanabe et al.,
1996).
GENE STRUCTURE
Brown et al. (1985) found that the functional TPI1 gene spans 3.5 kb and
is split into 7 exons.
MAPPING
From study of 3 patients with different deletions of chromosome 12,
Rethore et al. (1976, 1977) concluded that the GAPD locus (138400) is on
the distal part of 12p, between 12p12.2 and 12pter, and that the LDHB
locus (150100) is on the middle third between 12p12.1 and 12p12.2. The
results for TPI were like those for GAPD, suggesting the same distal
localization.
Law and Kao (1978) summarized data suggesting the order
12pter--TPI--GAPD--SHMT (SHMT2; 138450) on chromosome 12. SHMT lies on
the proximal part of 12q between the centromere and PEPB (169900).
Brown et al. (1985) confirmed that the functional TPI gene is on
chromosome 12 whereas the pseudogenes are on other chromosomes.
Asakawa and Iida (1985) also found support for a single TPI locus. GPI
(172400) and PEPD (613230), which are on chromosome 19 in man, are on
chromosome 9 of the Chinese hamster, and TPI, which is on chromosome 12
of man, is on Chinese hamster chromosome 8 (Siciliano et al., 1983).
OTHER FEATURES
TPI was 1 of 4 representative 'ancient' proteins used by Stoltzfus et
al. (1994) to test the exon theory of genes. Spliceosomal introns are
present in the nuclear protein-coding genes of most eukaryotic
organisms, but they have not been detected in several eukaryotic protist
phyla or in eubacteria, archaebacteria, and organelles. Two major
theories had emerged in the continuing debate on the origin of these
introns. The exon theory of genes (sometimes called the introns-early
view) proposed that exons are the descendants of ancient mini-genes and
introns are the descendants of the spaces between them; genes large
enough to encode contemporary proteins were first assembled from sets of
exons; the machinery of splicing originated in an ancient RNA world; and
introns were lost completely from both kingdoms of bacteria as well as
several protist groups. In contrast, the insertional theory of intron
origin (also known as the introns-late view) holds that split genes
arise from uninterrupted genes by insertion of introns; genes large
enough to encode contemporary proteins first arose (presumably from
smaller genes) without the participation of introns; the machinery of
spliceosomal splicing arose from fragmented self-splicing introns; and
spliceosomal introns were never present in the ancestors of those
organisms that now lack them. The analysis performed by Stoltzfus et al.
(1994) on TPI, the globins, pyruvate kinase, and alcohol dehydrogenase
demonstrated no significant correspondence between exons and units of
protein structure, suggesting that the putative correspondence does not
exist and that the exon theory of genes is untenable.
The chicken-and-egg question of which came first--exons or introns--was
studied, using TPI as a model, also by Kwiatowski et al. (1995) and
Logsdon et al. (1995). Each group looked at the positions of introns in
homologous TPI genes from a number of phylogenetically diverse species.
Both groups concluded that introns were gained comparatively recently in
eukaryotic evolution by insertion into preexisting genes.
MOLECULAR GENETICS
Eber et al. (1979) identified 5 persons heterozygous for a TPI null
allele.
Maquat et al. (1985) concluded that the genetic basis of TPI deficiency
is heterogeneous: normal levels of TPI mRNA were found in 1 homozygote
and about 40% of normal in another. The rare homozygous deficient
persons usually have 3 to 10% of normal enzyme activity.
Daar et al. (1986) and Pekrun et al. (1995) identified homoygosity for a
glu104-to-asp (E104D; 190450.0001) mutation in the TPI1 gene in patients
with triosephosphate deficiency. Arya et al. (1997) found that among 7
unrelated Northern European kindreds with clinical TPI deficiency, the
glu104-to-asp mutation accounted for 11 of 14 (79%) mutant alleles.
Haplotype analysis supported a founder effect.
Studies by Boyer et al. (1989) and Boyer and Maquat (1990) identified
several sequences in the 5-prime region that appear to be required for
maintenance of normal levels of gene expression. These include a CAP
proximal element (CPE) spanning nucleotides -6 and -12. The -5A-G and
-8G-A substitutions identified by Watanabe et al. (1996) are located
within the CPE region. The observation that all 7 affected individuals
shared the same variant CPE allele, an allele that does not exist at
higher frequency in the general African American population, suggested
to the authors a common origin for this TPI-deficiency allele; how the
allele frequency is maintained at such a high level was unclear.
Watanabe et al. (1996) undertook the molecular characterization of the
variant alleles from 7 African American and 3 Caucasian individuals from
the unrelated group identified in the frequency studies. In Caucasians
they found 3 amino acid substitutions, all in residues that are not
directly involved in the enzyme's active site but are highly conserved
through evolutionary time, suggesting important roles for these residues
in maintenance of subunit structure and conformation. One of the amino
acid substitutions, glu104-to-asp (190450.0001), had been previously
identified in cases of hemolytic anemia due to TPI deficiency. The
variant allele in the 7 African American individuals had nucleotide
changes at positions -8 and -5 on the 5-prime side of the
transcription-initiation site.
In a study of 424 African American subjects and 75 white subjects,
Schneider et al. (1998) found that the -5 (592A-G), -8 (382G-A), and -24
(573T-G) variants in the triosephosphate isomerase gene occurred
frequently (41%) in the African American subjects but did not occur in
whites. These data suggested that this set of polymorphisms may be one
of the higher-incidence molecular markers of African lineage. Although
the variant substitutions (occurring in 3 haplotypes: -5 alone, -5 -8,
and -5 -8 -24) were associated with moderate reduction in enzyme
activity, severe deficiency heterozygotes could not be identified with
certainty, and none of the haplotypes was restricted to subjects with
marked reduction of enzyme activity. Three subjects were homozygous for
the -5 -8 haplotype, a finding inconsistent with the putative role of
this haplotype as the cause of a null variant incompatible with life in
homozygotes, as had been suggested in the past for the rarity of
homozygotes with TPI deficiency in African Americans. Despite these
findings, Schneider et al. (1998) admitted the possibility that the -5
-8 or -5 -8 -24 haplotypes may in some instances contribute to compound
heterozygosity and clinical TPI deficiency.
ANIMAL MODEL
Gnerer et al. (2006) identified a recessive hypomorphic mutation in
Drosophila, which they called 'wasted away' (wstd), that causes
progressive motor impairment, vacuolar neuropathology, and severely
reduced life span. They found that wstd was caused by a mutation in the
Tpi1 gene. The mutation did not result in a significant deficit in ATP,
and the authors suggested that the lack of TPI1 activity may cause the
accumulation of toxic metabolites upstream of the enzymatic block.
HISTORY
From studies in the cri-du-chat syndrome (123450), Sparkes et al. (1969)
suggested that the TPI locus is on the short arm of chromosome 5. Others
failed to confirm this (Brock and Singer, 1970). Cell hybridization
studies indicated that the TPI locus is on chromosome 12.
*FIELD* AV
.0001
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, GLU104ASP
In 2 unrelated patients with TPI deficiency (615512), Daar et al. (1986)
found a guanine-to-cytosine transversion in the codon for amino acid
104, resulting in a structurally altered protein in which a glutamate
residue was replaced by an aspartate residue. The importance of
glutamate-104 to enzyme structure and function was indicated by its
conservation in the TPI protein of all species characterized to date.
The glutamate-to-aspartate substitution resulted in a thermolabile
enzyme. The same mutation was identified in an Australian family by
Chang et al. (1993). The alteration of codon 104 was from GAG to GAC.
Pekrun et al. (1995) found this same mutation in a family with severe
TPI deficiency. The 1-year-old index patient suffered from hemolytic
anemia, neuromuscular impairment, and recurrent pneumonia, with the
necessity of intermittent mechanical ventilation. TPI activity in red
cells was reduced to about 20% of normal. Heat stability of the enzyme
was strongly reduced; concentration of the physiologic substrate,
dihydroxyacetone phosphate, was increased 20-fold due to the metabolic
block. During a second pregnancy, examination of a cord blood sample
obtained in the nineteenth gestational week showed that the infant was
homozygous normal. An unaffected, healthy newborn was delivered. The
parents were consanguineous and of Turkish origin.
Arya et al. (1997) found that among 7 unrelated Northern European
kindreds with clinical TPI deficiency, the glu104-to-asp mutation
accounted for 11 (79%) of 14 mutant alleles. In 3 families, molecular
analysis revealed compound heterozygosity for glu104 to asp and novel
missense mutations (see 190450.0004 and 190450.0005). The origin of the
glu104-to-asp mutation was defined by haplotype analysis using a novel
G/A polymorphism at nucleotide 2898 of the TPI gene. Cosegregation of
the low frequency 2898A allele with the G-to-C base change at nucleotide
315, responsible for the glu104-to-asp amino acid substitution,
supported a single origin for that mutation, i.e., founder effect.
.0002
TRIOSEPHOSPHATE ISOMERASE MANCHESTER
TPI-MANCHESTER
TPI1, GLY122ARG
In a screening of more than 3,400 persons in an Ann Arbor, Michigan,
population, Perry and Mohrenweiser (1992) found only 1 example of a TPI
electromorph variant. Denaturing gradient gel electrophoresis of
polymerase chain reaction (PCR)-amplified DNA products and subsequent
direct sequencing identified a G-to-A transition causing a replacement
of gly122 with arg in this electrophoretic mobility variant of TPI which
was referred to as TPI-Manchester. The substitution was at the amino
terminus or solvent interaction end of the fifth beta sheet of the
alpha/beta barrel structure. TPI-Manchester was found to be thermolabile
but the stability of the variant enzyme was not sensitive to other
denaturants.
.0003
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI-HUNGARY
TPI1, PHE240LEU
In a Hungarian family, Chang et al. (1993) found that the proband with
TPI deficiency (615512), who had chronic nonspherocytic hemolytic anemia
but no neuromuscular disabilities, was a genetic compound. One of the
mutations was a missense mutation within codon 240 that changed TTC
(phe) to CTC (leu) and created a thermolabile protein. The substitution
occurred in a phylogenetically conserved amino acid and affected enzyme
activity by disrupting intersubunit contacts or substrate binding, as
deduced from enzyme structural studies. The nature of the other mutation
was not identified (see 190450.0006), but it had the effect of reducing
the abundance of TPI mRNA 10- to 20-fold. The same family was also
reported by Hollan et al. (1993) who gave clinical details on the
13-year-old boy with congenital hemolytic anemia and hyperkinetic
torsion dyskinesia associated with severe TPI deficiency, and on his
brother, a 23-year-old amateur wrestler, who also had congenital
hemolytic anemia but no neurologic symptoms. The latter was the proband
in the study of Chang et al. (1993), which demonstrated compound
heterozygosity. (Hollan et al. (1993) incorrectly referred to the
brothers as being double heterozygotes.) Both had less than 10% TPI
activity and a greatly increased dihydroxyacetone phosphate (DHAP) level
in their red blood cells. Their TPI had a slow electrophoretic mobility
and was heat unstable. Both parents and a third brother were healthy
heterozygotes. The older brother represented a unique phenotype since
all published homozygotes had severe neurologic alterations from infancy
or early childhood except 1 infant who died at 11 months, probably too
young for neurologic symptoms to be noted. Furthermore, in contrast to
the 2 affected Hungarian brothers, all but 1 homozygote had died before
the age of 6 years.
.0004
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, CYS41TYR
In 2 families with triosephosphate isomerase deficiency (615512), Arya
et al. (1997) found compound heterozygosity for the common glu104-to-asp
mutation (190450.0001) and a previously unknown missense mutation, cys41
to tyr, due to a TGT-to-TAT transition.
.0005
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, ILE170VAL
In a family with triosephosphate isomerase deficiency (615512), Arya et
al. (1997) found that affected individuals showed compound
heterozygosity for the common glu104-to-asp substitution (190450.0001)
and a novel ile170-to-val missense mutation.
.0006
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, GLU145TER
In a Hungarian family with severe TPI deficiency (615512) originally
described by Chang et al. (1993), Orosz et al. (2001) analyzed 2
germline-identical but phenotypically different brothers who were
compound heterozygotes for the F240L mutation (190450.0003) and a
glu145-to-ter (E145X) mutation. The kinetic, thermodynamic, and
associative properties of the recombinant human wildtype and F240L
mutant enzymes were compared with those of TPIs in normal and deficient
erythrocyte hemolysates. The specific activity of the recombinant mutant
enzyme relative to the wildtype was much higher (30%) than expected from
the activity (3%) measured in hemolysates. Comparative studies of the
hemolysate from a British patient with glu104-to-asp (190450.0001)
homozygosity (Ationu et al., 1999) and the platelet lysates from the
Hungarian family suggested that the microcompartmentation of TPI is not
unique for the hemolysates from the Hungarian TPI-deficient brothers.
*FIELD* SA
Asakawa et al. (1984); Bellingham and Lestas (1990); Bellingham et
al. (1989); Clay et al. (1982); Hendrickson et al. (1973); Herbschleb-Voogt
et al. (1978); Peters et al. (1973); Rudiger et al. (1970); Vives-Corrons
et al. (1978); Zanella et al. (1985)
*FIELD* RF
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Evidence for founder effect of the glu104-to-asp substitution and
identification of new mutations in triosephosphate isomerase deficiency. Hum.
Mutat. 10: 290-294, 1997.
2. Asakawa, J.; Iida, S.: Origin of human triosephosphate isomerase
isozymes: further evidence for the single structural locus hypothesis
with Japanese variants. Hum. Genet. 71: 22-26, 1985.
3. Asakawa, J.; Satoh, C.; Takahashi, N.; Fujita, M.; Kaneko, J.;
Goriki, K.; Hazama, R.; Kageoka, T.: Electrophoretic variants of
blood proteins in Japanese: III. Triosephosphate isomerase. Hum.
Genet. 68: 185-188, 1984.
4. Ationu, A.; Humphries, A.; Lalloz, M. R. A.; Arya, R.; Wild, B.;
Warrilow, J.; Morgan, J.; Bellingham, A. J.; Layton, D. M.: Reversal
of metabolic block in glycolysis by enzyme replacement in triosephosphate
isomerase-deficient cells. Blood 94: 3193-3198, 1999.
5. Ationu, A.; Humphries, A.; Wild, B.; Carr, T.; Will, A.; Arya,
R.; Layton, D. M.: Towards enzyme-replacement treatment in triosephosphate
isomerase deficiency. Lancet 353: 1155-1156, 1999.
6. Bellingham, A. J.; Lestas, A. N.: Prenatal diagnosis of triose
phosphate isomerase deficiency. (Letter) Lancet 335: 230 only, 1990.
7. Bellingham, A. J.; Lestas, A. N.; Williams, L. H. P.; Nicolaides,
K. H.: Prenatal diagnosis of a red-cell enzymopathy: triose phosphate
isomerase deficiency. Lancet 334: 419-421, 1989. Note: Originally
Volume II.
8. Boyer, T. G.; Krug, J. R.; Maquat, L. E.: Transcriptional regulatory
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9. Boyer, T. G.; Maquat, L. E.: Minimal sequence and factor requirements
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10. Brock, D. J. H.; Singer, J. D.: Red cell triosephosphate isomerase
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II.
11. Brown, J. R.; Daar, I. O.; Krug, J. R.; Maquat, L. E.: Characterization
of the functional gene and several processed pseudogenes in the human
triosephosphate isomerase gene family. Molec. Cell. Biol. 5: 1694-1706,
1985.
12. Chang, M.-L.; Artymiuk, P. J.; Wu, X.; Hollan, S.; Lammi, A.;
Maquat, L. E.: Human triosephosphate isomerase deficiency resulting
from mutation of phe-240. Am. J. Hum. Genet. 52: 1260-1269, 1993.
13. Clay, S. A.; Shore, N. A.; Landing, B. H.: Triosephosphate isomerase
deficiency: a case report with neuropathological findings. Am. J.
Dis. Child. 136: 800-802, 1982.
14. Daar, I. O.; Artymiuk, P. J.; Phillips, D. C.; Maquat, L. E.:
Human triose-phosphate isomerase deficiency: a single amino acid substitution
results in a thermolabile enzyme. Proc. Nat. Acad. Sci. 83: 7903-7907,
1986.
15. Decker, R. S.; Mohrenweiser, H. W.: Origin of the triosephosphate
isomerase isozymes in humans: genetic evidence for the expression
of a single structural locus. Hum. Genet. 33: 683-691, 1981.
16. Eber, S. W.; Dunnwald, M.; Belohradsky, B. H.; Bidlingmaier, F.;
Schievelbein, H.; Weinmann, H. M.; Krietsch, W. K. G.: Hereditary
deficiency of triosephosphate isomerase in four unrelated families. Europ.
J. Clin. Invest. 9: 195-202, 1979.
17. Gnerer, J. P.; Kreber, R. A.; Ganetzky, B.: wasted away, a Drosophila
mutation in triosephosphate isomerase, causes paralysis, neurodegeneration,
and early death. Proc. Nat. Acad. Sci. 103: 14987-14993, 2006.
18. Hendrickson, R. J.; Snapka, R. M.; Sawyer, T. H.; Gracy, R. W.
: Studies on human triosephosphate isomerase. II. Characterization
of the enzyme from patients with the cri du chat syndrome. Am. J.
Hum. Genet. 25: 433-438, 1973.
19. Herbschleb-Voogt, E.; Monteba-van Heuvel, M.; Wijnen, L. M. M.;
Westerveld, A.; Pearson, P. L.; Meera Khan, P.: Chromosomal assignment
and regional localization of CS, ENO-2, GAPDH, LDH-B, PEPB, and TPI
in man-rodent cell hybrids. Cytogenet. Cell Genet. 22: 482-486,
1978.
20. Hollan, S.; Fujii, H.; Hirono, A.; Hirono, K.; Karro, H.; Miwa,
S.; Harsanyi, V.; Gyodi, E.; Inselt-Kovacs, M.: Hereditary triosephosphate
isomerase (TPI) deficiency: two severely affected brothers one with
and one without neurological symptoms. Hum. Genet. 92: 486-490,
1993.
21. Hopkinson, D. A.; Harris, H.: Recent work on isozymes in man. Ann.
Rev. Genet. 5: 5-32, 1971.
22. Kwiatowski, J.; Krawczyk, M.; Kornacki, M.; Bailey, K.; Ayala,
F. J.: Evidence against the exon theory of genes derived from the
triose-phosphate isomerase gene. Proc. Nat. Acad. Sci. 92: 8503-8506,
1995.
23. Law, M. L.; Kao, F.-T.: Induced segregation of human syntenic
genes by 5-bromodeoxyuridine plus near-visible light. Somat. Cell
Genet. 4: 465-476, 1978.
24. Logsdon, J. M., Jr.; Tyshenko, M. G.; Dixon, C.; D.-Jafari, J.;
Walker, V. K.; Palmer, J. D.: Seven newly discovered intron positions
in the triose-phosphate isomerase gene: evidence for the introns-late
theory. Proc. Nat. Acad. Sci. 92: 8507-8511, 1995.
25. Maquat, L. E.; Chilcote, R.; Ryan, P. M.: Human triosephosphate
isomerase cDNA and protein structure: studies of triosephosphate isomerase
deficiency in man. J. Biol. Chem. 260: 3748-3753, 1985.
26. Orosz, F.; Olah, J.; Alvarez, M.; Keseru, G. M.; Szabo, B.; Wagner,
G.; Kovari, Z.; Horanyi, M.; Baroti, K.; Martial, J. A.; Hollan, S.;
Ovadi, J.: Distinct behavior of mutant triosephosphate isomerase
in hemolysate and in isolated form: molecular basis of enzyme deficiency. Blood 98:
3106-3112, 2001.
27. Pekrun, A.; Neubauer, B. A.; Eber, S. W.; Lakomek, M.; Seidel,
H.; Schroter, W.: Triosephosphate isomerase deficiency: biochemical
and molecular genetic analysis for prenatal diagnosis. Clin. Genet. 47:
175-179, 1995.
28. Perry, B. A.; Mohrenweiser, H. W.: Human triosephosphate isomerase:
substitution of arg for gly at position 122 in a thermolabile electromorph
variant, TPI-Manchester. Hum. Genet. 88: 634-638, 1992.
29. Peters, J.; Hopkinson, D. A.; Harris, H.: Genetic and non-genetic
variations of triose phosphate isomerase isozymes in human tissues. Ann.
Hum. Genet. 36: 297-312, 1973.
30. Rethore, M.-O.; Junien, C.; Malpuech, G.; Baccichetti, C.; Tenconi,
R.; Kaplan, J.-C.; de Romeuf, J.; Lejeune, J.: Localisation du gene
de la glyceraldehyde 3-phosphate deshydrogenase (G3PD) sur le segment
distal du bras court du chromosome 12. Ann. Genet. 19: 140-142,
1976.
31. Rethore, M.-O.; Kaplan, J.-C.; Junien, C.; Lejeune, J.: 12pter-12p12.2:
Possible assignment of human triosephosphate isomerase. Hum. Genet. 36:
235-237, 1977.
32. Rudiger, H. W.; Passarge, E.; Hirth, L.; Goedde, H. W.; Blume,
K. G.; Lohr, G. W.; Benohr, H. C.; Waller, H. D.: Triosephosphate
isomerase gene not localized on the short arm of chromosome 5 in man.
(Letter) Nature 228: 1320-1321, 1970.
33. Schneider, A.; Forman, L.; Westwood, B.; Yim, C.; Lin, J.; Singh,
S.; Beutler, E.: The relationship of the -5, -8, and -24 variant
alleles in African Americans to triosephosphate isomerase (TPI) enzyme
activity and to TPI deficiency. Blood 92: 2959-2962, 1998.
34. Siciliano, M. J.; Stallings, R. L.; Adair, G. M.; Humphrey, R.
M.; Siciliano, J.: Provisional assignment of TPI, GPI, and PEPD to
Chinese hamster autosomes 8 and 9: a cytogenetic basis for functional
haploidy of an autosomal linkage group in CHO cells. Cytogenet. Cell
Genet. 35: 15-20, 1983.
35. Sparkes, R. S.; Carrel, R. E.; Paglia, D. E.: Probable localization
of a triosephosphate isomerase gene to the short arm of number 5 human
chromosome. Nature 224: 367-398, 1969.
36. Stoltzfus, A.; Spencer, D. F.; Zuker, M.; Logsdon, J. M., Jr.;
Doolittle, W. F.: Testing the exon theory of genes: the evidence
from protein structure. Science 265: 202-207, 1994.
37. Vives-Corrons, J.-L.; Rubinson-Skala, H.; Mateo, M.; Estella,
J.; Feliu, E.; Dreyfus, J.-C.: Triosephosphate isomerase deficiency
with hemolytic anemia and severe neuromuscular disease: familial and
biochemical studies of a case found in Spain. Hum. Genet. 42: 171-180,
1978.
38. Watanabe, M.; Zingg, B. C.; Mohrenweiser, H. W.: Molecular analysis
of a series of alleles in humans with reduced activity at the triosephosphate
isomerase locus. Am. J. Hum. Genet. 58: 308-316, 1996.
39. Yuan, P. M.; Dewan, R. N.; Zaun, M.; Thompson, R. E.; Gracy, R.
W.: Isolation and characterization of triosephosphate isomerase isozymes
from human placenta. Arch. Biochem. Biophys. 198: 42-52, 1979.
40. Zanella, A.; Mariani, M.; Colombo, M. B.; Borgna-Pignatti, C.;
De Stefano, P.; Morgese, G.; Sirchia, G.: Triosephosphate isomerase
deficiency: 2 new cases. Scand. J. Haemat. 34: 417-424, 1985.
*FIELD* CN
Patricia A. Hartz - updated: 12/1/2006
Victor A. McKusick - updated: 2/26/2002
Victor A. McKusick - updated: 5/13/1999
Victor A. McKusick - updated: 11/30/1998
Victor A. McKusick - updated: 10/14/1997
Alan F. Scott - updated: 11/7/1995
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 11/07/2013
alopez: 11/7/2013
terry: 2/9/2009
wwang: 6/6/2007
wwang: 12/1/2006
wwang: 9/7/2006
mgross: 3/17/2004
mgross: 3/6/2002
terry: 2/26/2002
mgross: 5/19/1999
mgross: 5/17/1999
terry: 5/13/1999
carol: 12/2/1998
terry: 11/30/1998
dkim: 9/11/1998
jenny: 10/24/1997
jenny: 10/21/1997
terry: 10/14/1997
terry: 7/8/1997
jenny: 6/5/1997
mark: 2/23/1996
terry: 2/19/1996
mark: 11/7/1995
mark: 6/27/1995
mimadm: 6/7/1995
terry: 10/27/1994
carol: 4/14/1994
carol: 7/13/1993
*RECORD*
*FIELD* NO
190450
*FIELD* TI
*190450 TRIOSEPHOSPHATE ISOMERASE 1; TPI1
;;TPI
*FIELD* TX
DESCRIPTION
Triosephosphate isomerase (TPI; EC 5.3.1.1) catalyzes the
read moreinterconversion of dihydroxyacetone phosphate (DHAP) and
glyceraldehyde-3-phosphate (summary by Ationu et al., 1999).
CLONING
Electrophoretic variants of triosephosphate isomerase were identified by
the Galton Laboratory group (Hopkinson and Harris, 1971).
Brown et al. (1985) isolated the functional gene and 3 intronless
pseudogenes for human TPI from a recombinant DNA library. The
pseudogenes share a high degree of homology with the functional gene but
contain mutations that preclude synthesis of active TPI enzyme. Sequence
divergence indicated origin of the pseudogenes about 18 million years
ago. Brown et al. (1985) concluded that the human TPI gene family has
only 1 functional gene.
Yuan et al. (1979), on the basis of structural analysis, concluded that
the TPI-A and TPI-B isozymes are products of distinct structural loci.
Decker and Mohrenweiser (1981) presented evidence that triosephosphate
isomerase isozymes are the expression of a single structural locus. (The
existence of 2 TPI loci, both probably coded by chromosome 12, had been
suggested to explain the observed isozyme patterns.) They identified a
rare electrophoretic variant and found that the variant phenotype was
expressed in the TPI-B isozyme of both red cells and circulating
lymphocytes and was also expressed in the TPI-A isozyme of
mitogen-stimulated lymphoblasts.
GENE FUNCTION
TPI is a dimeric enzyme of identical subunits that is characterized by a
high constitutive level of activity in all tissues. It is involved in
both glycolysis and gluconeogenesis, catalyzing the interconversion of
DHAP and glyceraldehyde-3-phosphate. TPI is one of the most efficient
enzymes known, enhancing proton transfer by a factor of 10(10), and is
the least rate-limiting step in glycolysis (summary by Watanabe et al.,
1996).
GENE STRUCTURE
Brown et al. (1985) found that the functional TPI1 gene spans 3.5 kb and
is split into 7 exons.
MAPPING
From study of 3 patients with different deletions of chromosome 12,
Rethore et al. (1976, 1977) concluded that the GAPD locus (138400) is on
the distal part of 12p, between 12p12.2 and 12pter, and that the LDHB
locus (150100) is on the middle third between 12p12.1 and 12p12.2. The
results for TPI were like those for GAPD, suggesting the same distal
localization.
Law and Kao (1978) summarized data suggesting the order
12pter--TPI--GAPD--SHMT (SHMT2; 138450) on chromosome 12. SHMT lies on
the proximal part of 12q between the centromere and PEPB (169900).
Brown et al. (1985) confirmed that the functional TPI gene is on
chromosome 12 whereas the pseudogenes are on other chromosomes.
Asakawa and Iida (1985) also found support for a single TPI locus. GPI
(172400) and PEPD (613230), which are on chromosome 19 in man, are on
chromosome 9 of the Chinese hamster, and TPI, which is on chromosome 12
of man, is on Chinese hamster chromosome 8 (Siciliano et al., 1983).
OTHER FEATURES
TPI was 1 of 4 representative 'ancient' proteins used by Stoltzfus et
al. (1994) to test the exon theory of genes. Spliceosomal introns are
present in the nuclear protein-coding genes of most eukaryotic
organisms, but they have not been detected in several eukaryotic protist
phyla or in eubacteria, archaebacteria, and organelles. Two major
theories had emerged in the continuing debate on the origin of these
introns. The exon theory of genes (sometimes called the introns-early
view) proposed that exons are the descendants of ancient mini-genes and
introns are the descendants of the spaces between them; genes large
enough to encode contemporary proteins were first assembled from sets of
exons; the machinery of splicing originated in an ancient RNA world; and
introns were lost completely from both kingdoms of bacteria as well as
several protist groups. In contrast, the insertional theory of intron
origin (also known as the introns-late view) holds that split genes
arise from uninterrupted genes by insertion of introns; genes large
enough to encode contemporary proteins first arose (presumably from
smaller genes) without the participation of introns; the machinery of
spliceosomal splicing arose from fragmented self-splicing introns; and
spliceosomal introns were never present in the ancestors of those
organisms that now lack them. The analysis performed by Stoltzfus et al.
(1994) on TPI, the globins, pyruvate kinase, and alcohol dehydrogenase
demonstrated no significant correspondence between exons and units of
protein structure, suggesting that the putative correspondence does not
exist and that the exon theory of genes is untenable.
The chicken-and-egg question of which came first--exons or introns--was
studied, using TPI as a model, also by Kwiatowski et al. (1995) and
Logsdon et al. (1995). Each group looked at the positions of introns in
homologous TPI genes from a number of phylogenetically diverse species.
Both groups concluded that introns were gained comparatively recently in
eukaryotic evolution by insertion into preexisting genes.
MOLECULAR GENETICS
Eber et al. (1979) identified 5 persons heterozygous for a TPI null
allele.
Maquat et al. (1985) concluded that the genetic basis of TPI deficiency
is heterogeneous: normal levels of TPI mRNA were found in 1 homozygote
and about 40% of normal in another. The rare homozygous deficient
persons usually have 3 to 10% of normal enzyme activity.
Daar et al. (1986) and Pekrun et al. (1995) identified homoygosity for a
glu104-to-asp (E104D; 190450.0001) mutation in the TPI1 gene in patients
with triosephosphate deficiency. Arya et al. (1997) found that among 7
unrelated Northern European kindreds with clinical TPI deficiency, the
glu104-to-asp mutation accounted for 11 of 14 (79%) mutant alleles.
Haplotype analysis supported a founder effect.
Studies by Boyer et al. (1989) and Boyer and Maquat (1990) identified
several sequences in the 5-prime region that appear to be required for
maintenance of normal levels of gene expression. These include a CAP
proximal element (CPE) spanning nucleotides -6 and -12. The -5A-G and
-8G-A substitutions identified by Watanabe et al. (1996) are located
within the CPE region. The observation that all 7 affected individuals
shared the same variant CPE allele, an allele that does not exist at
higher frequency in the general African American population, suggested
to the authors a common origin for this TPI-deficiency allele; how the
allele frequency is maintained at such a high level was unclear.
Watanabe et al. (1996) undertook the molecular characterization of the
variant alleles from 7 African American and 3 Caucasian individuals from
the unrelated group identified in the frequency studies. In Caucasians
they found 3 amino acid substitutions, all in residues that are not
directly involved in the enzyme's active site but are highly conserved
through evolutionary time, suggesting important roles for these residues
in maintenance of subunit structure and conformation. One of the amino
acid substitutions, glu104-to-asp (190450.0001), had been previously
identified in cases of hemolytic anemia due to TPI deficiency. The
variant allele in the 7 African American individuals had nucleotide
changes at positions -8 and -5 on the 5-prime side of the
transcription-initiation site.
In a study of 424 African American subjects and 75 white subjects,
Schneider et al. (1998) found that the -5 (592A-G), -8 (382G-A), and -24
(573T-G) variants in the triosephosphate isomerase gene occurred
frequently (41%) in the African American subjects but did not occur in
whites. These data suggested that this set of polymorphisms may be one
of the higher-incidence molecular markers of African lineage. Although
the variant substitutions (occurring in 3 haplotypes: -5 alone, -5 -8,
and -5 -8 -24) were associated with moderate reduction in enzyme
activity, severe deficiency heterozygotes could not be identified with
certainty, and none of the haplotypes was restricted to subjects with
marked reduction of enzyme activity. Three subjects were homozygous for
the -5 -8 haplotype, a finding inconsistent with the putative role of
this haplotype as the cause of a null variant incompatible with life in
homozygotes, as had been suggested in the past for the rarity of
homozygotes with TPI deficiency in African Americans. Despite these
findings, Schneider et al. (1998) admitted the possibility that the -5
-8 or -5 -8 -24 haplotypes may in some instances contribute to compound
heterozygosity and clinical TPI deficiency.
ANIMAL MODEL
Gnerer et al. (2006) identified a recessive hypomorphic mutation in
Drosophila, which they called 'wasted away' (wstd), that causes
progressive motor impairment, vacuolar neuropathology, and severely
reduced life span. They found that wstd was caused by a mutation in the
Tpi1 gene. The mutation did not result in a significant deficit in ATP,
and the authors suggested that the lack of TPI1 activity may cause the
accumulation of toxic metabolites upstream of the enzymatic block.
HISTORY
From studies in the cri-du-chat syndrome (123450), Sparkes et al. (1969)
suggested that the TPI locus is on the short arm of chromosome 5. Others
failed to confirm this (Brock and Singer, 1970). Cell hybridization
studies indicated that the TPI locus is on chromosome 12.
*FIELD* AV
.0001
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, GLU104ASP
In 2 unrelated patients with TPI deficiency (615512), Daar et al. (1986)
found a guanine-to-cytosine transversion in the codon for amino acid
104, resulting in a structurally altered protein in which a glutamate
residue was replaced by an aspartate residue. The importance of
glutamate-104 to enzyme structure and function was indicated by its
conservation in the TPI protein of all species characterized to date.
The glutamate-to-aspartate substitution resulted in a thermolabile
enzyme. The same mutation was identified in an Australian family by
Chang et al. (1993). The alteration of codon 104 was from GAG to GAC.
Pekrun et al. (1995) found this same mutation in a family with severe
TPI deficiency. The 1-year-old index patient suffered from hemolytic
anemia, neuromuscular impairment, and recurrent pneumonia, with the
necessity of intermittent mechanical ventilation. TPI activity in red
cells was reduced to about 20% of normal. Heat stability of the enzyme
was strongly reduced; concentration of the physiologic substrate,
dihydroxyacetone phosphate, was increased 20-fold due to the metabolic
block. During a second pregnancy, examination of a cord blood sample
obtained in the nineteenth gestational week showed that the infant was
homozygous normal. An unaffected, healthy newborn was delivered. The
parents were consanguineous and of Turkish origin.
Arya et al. (1997) found that among 7 unrelated Northern European
kindreds with clinical TPI deficiency, the glu104-to-asp mutation
accounted for 11 (79%) of 14 mutant alleles. In 3 families, molecular
analysis revealed compound heterozygosity for glu104 to asp and novel
missense mutations (see 190450.0004 and 190450.0005). The origin of the
glu104-to-asp mutation was defined by haplotype analysis using a novel
G/A polymorphism at nucleotide 2898 of the TPI gene. Cosegregation of
the low frequency 2898A allele with the G-to-C base change at nucleotide
315, responsible for the glu104-to-asp amino acid substitution,
supported a single origin for that mutation, i.e., founder effect.
.0002
TRIOSEPHOSPHATE ISOMERASE MANCHESTER
TPI-MANCHESTER
TPI1, GLY122ARG
In a screening of more than 3,400 persons in an Ann Arbor, Michigan,
population, Perry and Mohrenweiser (1992) found only 1 example of a TPI
electromorph variant. Denaturing gradient gel electrophoresis of
polymerase chain reaction (PCR)-amplified DNA products and subsequent
direct sequencing identified a G-to-A transition causing a replacement
of gly122 with arg in this electrophoretic mobility variant of TPI which
was referred to as TPI-Manchester. The substitution was at the amino
terminus or solvent interaction end of the fifth beta sheet of the
alpha/beta barrel structure. TPI-Manchester was found to be thermolabile
but the stability of the variant enzyme was not sensitive to other
denaturants.
.0003
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI-HUNGARY
TPI1, PHE240LEU
In a Hungarian family, Chang et al. (1993) found that the proband with
TPI deficiency (615512), who had chronic nonspherocytic hemolytic anemia
but no neuromuscular disabilities, was a genetic compound. One of the
mutations was a missense mutation within codon 240 that changed TTC
(phe) to CTC (leu) and created a thermolabile protein. The substitution
occurred in a phylogenetically conserved amino acid and affected enzyme
activity by disrupting intersubunit contacts or substrate binding, as
deduced from enzyme structural studies. The nature of the other mutation
was not identified (see 190450.0006), but it had the effect of reducing
the abundance of TPI mRNA 10- to 20-fold. The same family was also
reported by Hollan et al. (1993) who gave clinical details on the
13-year-old boy with congenital hemolytic anemia and hyperkinetic
torsion dyskinesia associated with severe TPI deficiency, and on his
brother, a 23-year-old amateur wrestler, who also had congenital
hemolytic anemia but no neurologic symptoms. The latter was the proband
in the study of Chang et al. (1993), which demonstrated compound
heterozygosity. (Hollan et al. (1993) incorrectly referred to the
brothers as being double heterozygotes.) Both had less than 10% TPI
activity and a greatly increased dihydroxyacetone phosphate (DHAP) level
in their red blood cells. Their TPI had a slow electrophoretic mobility
and was heat unstable. Both parents and a third brother were healthy
heterozygotes. The older brother represented a unique phenotype since
all published homozygotes had severe neurologic alterations from infancy
or early childhood except 1 infant who died at 11 months, probably too
young for neurologic symptoms to be noted. Furthermore, in contrast to
the 2 affected Hungarian brothers, all but 1 homozygote had died before
the age of 6 years.
.0004
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, CYS41TYR
In 2 families with triosephosphate isomerase deficiency (615512), Arya
et al. (1997) found compound heterozygosity for the common glu104-to-asp
mutation (190450.0001) and a previously unknown missense mutation, cys41
to tyr, due to a TGT-to-TAT transition.
.0005
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, ILE170VAL
In a family with triosephosphate isomerase deficiency (615512), Arya et
al. (1997) found that affected individuals showed compound
heterozygosity for the common glu104-to-asp substitution (190450.0001)
and a novel ile170-to-val missense mutation.
.0006
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
TPI1, GLU145TER
In a Hungarian family with severe TPI deficiency (615512) originally
described by Chang et al. (1993), Orosz et al. (2001) analyzed 2
germline-identical but phenotypically different brothers who were
compound heterozygotes for the F240L mutation (190450.0003) and a
glu145-to-ter (E145X) mutation. The kinetic, thermodynamic, and
associative properties of the recombinant human wildtype and F240L
mutant enzymes were compared with those of TPIs in normal and deficient
erythrocyte hemolysates. The specific activity of the recombinant mutant
enzyme relative to the wildtype was much higher (30%) than expected from
the activity (3%) measured in hemolysates. Comparative studies of the
hemolysate from a British patient with glu104-to-asp (190450.0001)
homozygosity (Ationu et al., 1999) and the platelet lysates from the
Hungarian family suggested that the microcompartmentation of TPI is not
unique for the hemolysates from the Hungarian TPI-deficient brothers.
*FIELD* SA
Asakawa et al. (1984); Bellingham and Lestas (1990); Bellingham et
al. (1989); Clay et al. (1982); Hendrickson et al. (1973); Herbschleb-Voogt
et al. (1978); Peters et al. (1973); Rudiger et al. (1970); Vives-Corrons
et al. (1978); Zanella et al. (1985)
*FIELD* RF
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*FIELD* CN
Patricia A. Hartz - updated: 12/1/2006
Victor A. McKusick - updated: 2/26/2002
Victor A. McKusick - updated: 5/13/1999
Victor A. McKusick - updated: 11/30/1998
Victor A. McKusick - updated: 10/14/1997
Alan F. Scott - updated: 11/7/1995
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 11/07/2013
alopez: 11/7/2013
terry: 2/9/2009
wwang: 6/6/2007
wwang: 12/1/2006
wwang: 9/7/2006
mgross: 3/17/2004
mgross: 3/6/2002
terry: 2/26/2002
mgross: 5/19/1999
mgross: 5/17/1999
terry: 5/13/1999
carol: 12/2/1998
terry: 11/30/1998
dkim: 9/11/1998
jenny: 10/24/1997
jenny: 10/21/1997
terry: 10/14/1997
terry: 7/8/1997
jenny: 6/5/1997
mark: 2/23/1996
terry: 2/19/1996
mark: 11/7/1995
mark: 6/27/1995
mimadm: 6/7/1995
terry: 10/27/1994
carol: 4/14/1994
carol: 7/13/1993