Aspartate aminotransferase, cytoplasmic (GOT1)
The protein contains 413 amino acids for an estimated molecular weight of 46248 Da.
Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. (updated: April 1, 2015)
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.
- 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.
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Biological Process
2-oxoglutarate metabolic process
Aspartate biosynthetic process
Aspartate catabolic process
Aspartate family amino acid metabolic process
Aspartate metabolic process
Carbohydrate metabolic process
Cellular amino acid biosynthetic process
Cellular nitrogen compound metabolic process
Cellular response to insulin stimulus
Cellular response to mechanical stimulus
Fatty acid homeostasis
Gluconeogenesis
Glucose metabolic process
Glutamate catabolic process to 2-oxoglutarate
Glutamate catabolic process to aspartate
Glutamate metabolic process
Glycerol biosynthetic process
L-methionine salvage from methylthioadenosine
Negative regulation of collagen biosynthetic process
Negative regulation of cytosolic calcium ion concentration
Negative regulation of mitochondrial depolarization
Notch signaling pathway
Oxaloacetate metabolic process
Pathogenesis
Polyamine metabolic process
Positive regulation of transforming growth factor beta receptor signaling pathway
Response to cadmium ion
Response to carbohydrate
Response to glucocorticoid
Response to immobilization stress
Response to transition metal nanoparticle
Small molecule metabolic process
Sulfur amino acid metabolic process
Transdifferentiation
Cellular Component
Axon terminus
Cytoplasm
Cytosol
Extracellular exosome
Lysosome
Nucleoplasm
Nucleus
Obsolete cell
The reference OMIM entry for this protein is 138180
Glutamate oxaloacetate transaminase, soluble; got1
Aspartate aminotransferase, cytosolic
DESCRIPTION
Glutamate oxaloacetate transaminase (EC 2.6.1.1) is a ubiquitous pyridoxal phosphate-dependent enzyme which exists in both mitochondrial (138150) and cytosolic forms. The enzyme plays an important role in amino acid metabolism and in the urea and tricarboxylic acid cycles. The 2 isoenzymes are homodimeric. In liver about 80% of the enzyme activity is mitochondrial in origin, whereas in serum the enzyme activity is largely cytosolic. Although the mitochondrial and soluble forms of GOT are coded by different chromosomes (according to a rule that has few exceptions; McKusick, 1986), the 2 show close homology in amino acid sequence and were presumably derived from a common ancestral gene (Ford et al., 1980; Doonan et al., 1984). See ASTQTL1 (614419) for information on a quantitative trait locus influencing the serum level of cytosolic glutamate oxaloacetate transaminase.CLONING
Pol et al. (1988) cloned cDNAs corresponding to human liver cytosolic and mitochondrial aspartate aminotransferase mRNAs.GENE STRUCTURE
Wang et al. (1999) determined the genomic structure of the GOT1 gene. The gene contains 9 exons and all of its intron/exon junctions follow the GT-AG rule.GENE FUNCTION
Son et al. (2013) reported the identification of a noncanonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC; see 260350) cells that is required for tumor growth. Whereas most cells use glutamate dehydrogenase (GLUD1; 138130) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, Son et al. (2013) established that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS (190070), the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway.MAPPING
By analysis of mouse-human somatic cell hybrids, Creagan et al. (1973) concluded that the structural locus for cytoplasmic glutamate oxaloacetate transaminase is on chromosome 10. Spritz et al. (1979) studied soluble GOT activity in fibroblasts of 2 persons with duplications of the long arm of chromosome 10. Since the 2 differed by only half a band, the authors concluded that the structural locus is on band 10q24. Junien et al. (1982) assigned GOT1 and PGAMA (172250) to 10q26.1 (or 10q25.3) by dosage studies. Pol et al. (1989) used human liver cytosolic and mitochondrial aspartate aminotransferase cDNA probes to locate the GOT1 gene in the region 10q24.1-q25.1 by in situ hybridization. Wang et al. (1999) located the GOT1 gene within the critical region for the urofacial syndrome (236730), between markers D10S198 and D10S2 ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 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 138180 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed