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Reviewed, UniProtKB/Swiss-Prot P60174 (TPIS_HUMAN)

Last modified November 25, 2008. Version 63. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Triosephosphate isomerase
      Short name=TIM
    EC=5.3.1.1
Alternative name(s):
    Triose-phosphate isomerase
Gene names
Name: TPI1
Synonyms: TPI
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length249 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

D-glyceraldehyde 3-phosphate = glycerone phosphate.

Pathway

Carbohydrate biosynthesis; gluconeogenesis.

Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate from glycerone phosphate: step 1/1.

Subunit structure

Homodimer.

Involvement in disease

Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:190450]. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection.

Sequence similarities

Belongs to the triosephosphate isomerase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P60174-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P60174-2)

The sequence of this isoform differs from the canonical sequence as follows:
     180-249: QQAQEVHEKL...EFVDIINAKQ → PHPNCIFLYC...EGRRETILSL
Notes: No experimental confirmation available. Alternative splicing seems doubtful, since exon-intron junctions are not the consensus ones.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 249248Triosephosphate isomerase
PRO_0000090113

Sites

Active site961Electrophile
Active site1661Proton acceptor
Binding site121Substrate
Binding site141Substrate

Amino acid modifications

Modified residue211Phosphoserine
Modified residue1881N6-acetyllysine

Natural variations

Alternative sequence180 – 24970QQAQE…INAKQ → PHPNCIFLYCLYLHPVMVGT RPIPSPLTIMVGTKRHQGGF SLAERWKAWWDLLLGSLGPS EGRRETILSL in isoform 2.
VSP_011958
Natural variant421C → Y in TPI deficiency.
VAR_007534
Natural variant731G → A in TPI deficiency.
VAR_007535
Natural variant1051E → D in TPI deficiency; the enzyme becomes thermolabile.
VAR_007536
Natural variant1231G → R in Manchester; thermolabile.
VAR_007537
Natural variant1551V → M in TPI deficiency.
VAR_007538
Natural variant1711I → V in TPI deficiency.
VAR_007539
Natural variant2321V → M in TPI deficiency.
VAR_007540
Natural variant2411F → L in TPI deficiency; Hungary; thermolabile.
VAR_007541

Experimental info

Sequence conflict20 – 212QS → KN AA sequence Ref.1
Sequence conflict271G → S AA sequence Ref.1
Sequence conflict30 – 312NA → QG AA sequence Ref.1
Sequence conflict43 – 442AP → IG AA sequence Ref.1
Sequence conflict581P → Q AA sequence Ref.1
Sequence conflict1551V → A in AAH17917. Ref.7
Sequence conflict1671P → N AA sequence Ref.1
Sequence conflict2441I → L AA sequence Ref.1

Secondary structure

............................................... 249
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 73844175635F858E

FASTA24926,669
        10         20         30         40         50         60 
MAPSRKFFVG GNWKMNGRKQ SLGELIGTLN AAKVPADTEV VCAPPTAYID FARQKLDPKI 

        70         80         90        100        110        120 
AVAAQNCYKV TNGAFTGEIS PGMIKDCGAT WVVLGHSERR HVFGESDELI GQKVAHALAE 

       130        140        150        160        170        180 
GLGVIACIGE KLDEREAGIT EKVVFEQTKV IADNVKDWSK VVLAYEPVWA IGTGKTATPQ 

       190        200        210        220        230        240 
QAQEVHEKLR GWLKSNVSDA VAQSTRIIYG GSVTGATCKE LASQPDVDGF LVGGASLKPE 


FVDIINAKQ 

« Hide

Isoform 2 [UniParc].

Checksum: AC986AEA381D3536
Show »

24927,126

References

« Hide 'large scale' references
[1]"Primary structure of human triosephosphate isomerase."
Lu H.S., Yuan P.M., Gracy R.W.
J. Biol. Chem. 259:11958-11968(1984) [PubMed: 6434534] [Abstract]
Cited for: PROTEIN SEQUENCE (ISOFORM 1).
[2]"Human triosephosphate isomerase cDNA and protein structure. Studies of triosephosphate isomerase deficiency in man."
Maquat L.E., Chilcote R., Ryan P.M.
J. Biol. Chem. 260:3748-3753(1985) [PubMed: 2579079] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Characterization of the functional gene and several processed pseudogenes in the human triosephosphate isomerase gene family."
Brown J.R., Daar I.O., Krug J.R., Maquat L.E.
Mol. Cell. Biol. 5:1694-1706(1985) [PubMed: 4022011] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]Belgrader P., Boyer T., Daar I., Cheng J., Nesic D., Maquat L.E.
Submitted (DEC-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
Tissue: Liver.
[5]"A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13."
Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S., Malley T., Gibbs R.A.
Genome Res. 6:314-326(1996) [PubMed: 8723724] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination."
Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.
Genome Res. 7:268-280(1997) [PubMed: 9074930] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain, Kidney, Placenta, Prostate, Skeletal muscle, Skin and Uterus.
[8]"Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2."
Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J., Dorow D.S.
Electrophoresis 18:588-598(1997) [PubMed: 9150946] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-20.
Tissue: Mammary carcinoma.
[9]"A two-dimensional gel database of human colon carcinoma proteins."
Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.
Electrophoresis 18:605-613(1997) [PubMed: 9150948] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-20.
Tissue: Colon carcinoma.
[10]"Transcriptional regulatory sequences of the housekeeping gene for human triosephosphate isomerase."
Boyer T.G., Krug J.R., Maquat L.E.
J. Biol. Chem. 264:5177-5187(1989) [PubMed: 2925688] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-5.
[11]Lubec G., Vishwanath V.
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 34-53; 86-99; 114-131 AND 161-175, MASS SPECTROMETRY.
Tissue: Brain and Cajal-Retzius cell.
[12]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
Tissue: Epithelium.
[13]"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey."
Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.
Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-188, MASS SPECTROMETRY.
Tissue: Epithelium.
[14]"Phosphoproteomic analysis of the human pituitary."
Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.
Pituitary 9:109-120(2006) [PubMed: 16807684] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
Tissue: Pituitary.
[15]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
Tissue: Epithelium.
[16]"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction."
Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.
Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed: 17693683] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
[17]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
[18]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
[19]"Crystal structure of recombinant human triosephosphate isomerase at 2.8-A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme."
Mande S.C., Mainfroid V., Kalk K.H., Goraj K., Martial J.A., Hol W.G.J.
Protein Sci. 3:810-821(1994) [PubMed: 8061610] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, HOMODIMERIZATION.
[20]"Structure of a high-resolution crystal form of human triosephosphate isomerase: improvement of crystals using the gel-tube method."
Kinoshita T., Maruki R., Warizaya M., Nakajima H., Nishimura S.
Acta Crystallogr. F 61:346-349(2005) [PubMed: 16511037] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[21]"Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface."
Rodriguez-Almazan C., Arreola R., Rodriguez-Larrea D., Aguirre-Lopez B., de Gomez-Puyou M.T., Perez-Montfort R., Costas M., Gomez-Puyou A., Torres-Larios A.
J. Biol. Chem. 283:23254-23263(2008) [PubMed: 18562316] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF MUTANT ASP-105, SUBUNIT, CHARACTERIZATION OF VARIANT ASP-105.
[22]"Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme."
Daar I.O., Artymiuk P.J., Phillips D.C., Maquat L.E.
Proc. Natl. Acad. Sci. U.S.A. 83:7903-7907(1986) [PubMed: 2876430] [Abstract]
Cited for: VARIANT TPI DEFICIENCY ASP-105.
[23]"Relation between genetic defect, altered protein structure, and enzyme function in triose-phosphate isomerase (TPI) deficiency."
Neubauer B.A., Pekrun A., Eber S.W., Lakomek M., Schroeter W.
Eur. J. Pediatr. Suppl. 151:232-232(1992)
Cited for: VARIANTS TPI DEFICIENCY ASP-105 AND MET-232.
[24]"Human triosephosphate isomerase: substitution of Arg for Gly at position 122 in a thermolabile electromorph variant, TPI-Manchester."
Perry B.A., Mohrenweiser H.W.
Hum. Genet. 88:634-638(1992) [PubMed: 1339398] [Abstract]
Cited for: VARIANT MANCHESTER ARG-123.
[25]"Human triosephosphate isomerase deficiency resulting from mutation of Phe-240."
Chang M.-L., Artymiuk P.J., Wu X., Hollan S., Lammi A., Maquat L.E.
Am. J. Hum. Genet. 52:1260-1269(1993) [PubMed: 8503454] [Abstract]
Cited for: VARIANT TPI DEFICIENCY HUNGARY LEU-241.
[26]"Molecular analysis of a series of alleles in humans with reduced activity at the triosephosphate isomerase locus."
Watanabe M., Zingg B.C., Mohrenweiser H.W.
Am. J. Hum. Genet. 58:308-316(1996) [PubMed: 8571957] [Abstract]
Cited for: VARIANTS TPI DEFICIENCY ALA-73; ASP-105 AND MET-155.
[27]"Evidence for founder effect of the Glu104Asp substitution and identification of new mutations in triosephosphate isomerase deficiency."
Arya R., Lalloz M.R.A., Bellingham A.J., Layton D.M.
Hum. Mutat. 10:290-294(1997) [PubMed: 9338582] [Abstract]
Cited for: VARIANTS TPI DEFICIENCY TYR-42; ASP-105 AND VAL-171.
+Additional computationally mapped references.

Web resources

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