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.

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 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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