Triosephosphate isomerase (TPI1)
The protein contains 286 amino acids for an estimated molecular weight of 30791 Da.
Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis.', 'It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids. (updated: Jan. 16, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
Biological Process
Canonical glycolysis
Carbohydrate metabolic process
Gluconeogenesis
Glucose metabolic process
Glyceraldehyde-3-phosphate biosynthetic process
Glycerol catabolic process
Glycolytic process
Methylglyoxal biosynthetic process
Multicellular organism development
Pathogenesis
Pentose-phosphate shunt
Small molecule metabolic process
The reference OMIM entry for this protein is 190450
Triosephosphate isomerase 1; tpi1
Tpi
DESCRIPTION
The TPI1 gene encodes triosephosphate isomerase (TPI; EC 5.3.1.1), a homodimeric enzyme that catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate during glycolysis and gluconeogenesis (summary by Chang et al., 1993).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) concluded on the basis of structural analysis 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 contains 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).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 (TPID; 615512) 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) a ... More on the omim web site
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 190450 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed