GOT2 (Glutamic-Oxaloacetic Transaminase 2): Gene, Function, and Clinical Significance
A comprehensive overview of the GOT2 gene, encoding mitochondrial aspartate aminotransferase, including its genomic context, expression, disease associations, and mutation landscape.
Gene Information Card
| Symbol | GOT2 |
|---|---|
| Full Name | Glutamic-Oxaloacetic Transaminase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q21 |
| NCBI Gene ID | 2806 ncbi.nlm.nih.gov/gene/2806 |
| Ensembl ID | ENSG00000125166 |
| UniProt ID | P00505 |
| OMIM ID | 138150 |
| HGNC ID | 4433 |
| Aliases | KAT4, mitAAT, Aspartate aminotransferase 2, Glutamate oxaloacetate transaminase 2 |
Description
GOT2 encodes the mitochondrial aspartate aminotransferase, a pyridoxal phosphate-dependent enzyme that catalyzes the reversible transamination between aspartate and alpha-ketoglutarate to form oxaloacetate and glutamate. This enzyme plays a critical role in amino acid metabolism, the malate-aspartate shuttle for transferring reducing equivalents across the mitochondrial membrane, and in gluconeogenesis. GOT2 is also involved in the regulation of mitochondrial function and has been implicated in various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | GOT2 overexpression promotes tumor growth and metastasis by enhancing the malate-aspartate shuttle and supporting biosynthesis of amino acids and nucleotides. | COSMIC; multiple studies (e.g., PMID: 29784789) |
| Mitochondrial diseases | Mutations in GOT2 can impair mitochondrial aspartate transport and energy metabolism, leading to neurological and muscular symptoms. | ClinVar; OMIM |
| Diabetes | GOT2 activity influences insulin secretion and glucose metabolism; altered expression may contribute to beta-cell dysfunction. | NCBI; literature (e.g., PMID: 23451046) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Heart | High | High |
| Skeletal Muscle | High | High |
| Kidney | Medium | Medium |
| Brain | Medium | Medium |
| Pancreas | Medium | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Liver cancer cell line |
| K562 | Medium | Leukemia cell line |
| A549 | Medium | Lung carcinoma cell line |
| MCF7 | Low | Breast cancer cell line |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100A>G (p.Thr34Ala) | Missense | Rare | May affect enzyme activity; reported in ClinVar |
| c.589C>T (p.Arg197Trp) | Missense | Rare | Associated with mitochondrial dysfunction; ClinVar |
| c.1045G>A (p.Gly349Ser) | Missense | Rare | Potential impact on protein stability; ClinVar |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GOT2 are rare and may lead to reduced enzyme activity, impairing the malate-aspartate shuttle and mitochondrial metabolism, potentially contributing to neurological disorders.
Gain of Function (GOF)
Gain-of-function alterations, such as gene amplification or overexpression, have been observed in cancers, enhancing metabolic reprogramming and tumor progression.
Dominant Negative (DN)
No clear dominant-negative mutations have been reported for GOT2; most pathogenic variants are recessive or haploinsufficient.
View complete mutation data:
Gene Ontology (GO)
Pathways
• Malate-aspartate shuttle
• Alanine
• aspartate and glutamate metabolism
• Cysteine and methionine metabolism
• Arginine biosynthesis
Protein Summary
GOT2 is a 430-amino acid protein localized to the mitochondrial matrix. It forms homodimers and requires pyridoxal phosphate as a cofactor. The enzyme catalyzes the reversible transamination of aspartate and alpha-ketoglutarate to oxaloacetate and glutamate, playing a central role in the malate-aspartate shuttle, which transfers reducing equivalents from the cytosol into mitochondria. GOT2 also participates in gluconeogenesis and amino acid metabolism. Its expression is ubiquitous but highest in tissues with high metabolic demand such as liver, heart, and skeletal muscle. Post-translational modifications, including acetylation, regulate its activity. GOT2 has been implicated in cancer metabolism, where it supports tumor growth by facilitating NAD+ regeneration and providing precursors for nucleotide synthesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GOT2 Knockout HEK293 Cell Line | EDJ-KQ1967 | Human | 2806 | Details Get a Quote |
| GOT2 Knockout HCT 116 Cell Line | EDJ-KQ21936 | Human | 2806 | Details Get a Quote |
| GOT2 Knockout HeLa Cell Line | EDJ-KQ21937 | Human | 2806 | Details Get a Quote |
| GOT2 Knockout A-549 Cell Line | EDJ-KQ20640 | Human | 2806 | Details Get a Quote |
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