Maleylacetoacetate isomerase (GSTZ1)
The protein contains 216 amino acids for an estimated molecular weight of 24212 Da.
Bifunctional enzyme showing minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with T-butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
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.
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The reference OMIM entry for this protein is 603758
Glutathione s-transferase, zeta-1; gstz1
Glutathione s-transferase z1
Maleylacetoacetate isomerase; maai
DESCRIPTION
The zeta class glutathione transferases catalyze the isomerization of maleylacetoacetate (MAAI; EC 5.2.1.2) to fumarylacetoacetate (FAA), and the biotransformation of dichloroacetic acid to glyoxylate (Blackburn et al., 2001). The conversion of maleylacetoacetate to fumarylacetoacetate is the fifth step in the phenylalanine/phenylacetate degradation pathway. Deficiencies in other steps of this pathway cause metabolic diseases, including type I tyrosinemia (276700) and phenylketonuria (261600) (Fernandez-Canon and Penalva, 1998). For background information on glutathione S-transferases, see 138350.CLONING
Fernandez-Canon and Penalva (1998) noted that Aspergillus nidulans was used previously as a fungal model for human phenylalanine catabolism. These authors isolated the Aspergillus maiA gene and found that it encodes MAAI. By searching EST databases for sequences related to maiA, they identified several cDNAs encoding the human MAAI homolog. The predicted 216-amino acid human protein shares 45% identity with Aspergillus maiA. By sequence alignment and phylogenetic analysis, Board et al. (1997) identified a novel subgroup of GST-like proteins from human, C. elegans, and carnation, which they designated GST-zeta. Human GSTZ1-1 was 38% and 49% identical to the carnation and C. elegans proteins, respectively. The authors found that recombinant human GSTZ1-1 was a dimer composed of 24.2-kD subunits. Western blot analysis indicated that GSTZ1-1 was most abundant in liver, with lower levels detected in skeletal muscle and brain. Blackburn et al. (1998) noted that the GSTZ1 and MAAI genes are identical.GENE FUNCTION
Fernandez-Canon and Penalva (1998) found that recombinant human MAAI protein showed strong MAAI activity, as evidenced by its ability to complement an Aspergillus extract deficient for the enzyme. Board et al. (1997) found that human GSTZ1-1 exhibited limited activity with known GST substrates.GENE STRUCTURE
The GSTZ1 gene contains 9 exons and spans approximately 11 kb (Blackburn et al., 1998).MAPPING
By fluorescence in situ hybridization, Blackburn et al. (1998) mapped the GSTZ1 gene to 14q24.3. These authors stated that an STS corresponding to the GSTZ1 gene (TMAP WI-12309) was mapped to the same region by analysis of radiation hybrids.MOLECULAR GENETICS
By analysis of an EST database, Blackburn et al. (2001) identified a novel allele of the GSTZ1 gene, which they termed GSTZ1d. In European Australians, GSTZ1d has a frequency of 0.16. Like GSTZ1b-1b and GSTZ1c-1c, the novel isoform has low activity with dichloroacetic acid compared with GSTZ1a-1a. The low activity appeared to be due to a high sensitivity to substrate inhibition. The GSTZ1a-1a allele had a notably lower catalytic efficiency of MAAI activity compared to the others.PHENOTYPE
- Putative MAAI Deficiency Fernandez-Canon and Penalva (1998) stated that a patient with a putative MAAI deficiency was reported by Berger et al. (1988) in an abstract. The patient was a male with a very severe disorder that was clinically indistinguishable from type I tyrosinemia and was therefore called tyrosinemia type Ib. MAAI enzymatic activity was undetectable in liver and skin fibroblasts of the proband; it was low in both parents, suggesting autosomal recessive inheritance. One of the authors of the abstract (Matalon, 1999) stated that the patient, as well as a second case of the same disorder, h ... More on the omim web site
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 603758 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).