Details for: AGXT2

Gene ID: 64902

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: AGXT2

Ensembl ID: ENSG00000113492

Description: alanine--glyoxylate aminotransferase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • midzonal region hepatocyte CL0019028
    CSI 10.92
    rCSI 25.61%
    PRS 99.21
  • intestinal epithelial cell CL0002563
    CSI 7.51
    rCSI 7.85%
    PRS 99.52
  • epithelial cell of proximal tubule CL0002306
    CSI 6.2
    rCSI 15.13%
    PRS 98.73
  • periportal region hepatocyte CL0019026
    CSI 3.69
    rCSI 14.33%
    PRS 99.1
  • hepatocyte CL0000182
    CSI 3.5
    rCSI 6.26%
    PRS 99.12
  • parietal epithelial cell CL1000452
    CSI 3.03
    rCSI 8.08%
    PRS 99.41
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 2.1
    rCSI 16.73%
    PRS 99.31
  • podocyte CL0000653
    CSI 1.93
    rCSI 8.56%
    PRS 99.7

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [AGXT2](/details-gene/64902) encodes alanine--glyoxylate aminotransferase 2, a mitochondrial enzyme that plays a crucial role in amino acid metabolism. This protein is primarily involved in the catabolism of glyoxylate, glycine, and, notably, endogenous methylarginines such as asymmetric dimethylarginine (ADMA). By degrading ADMA, an inhibitor of nitric oxide synthase, [AGXT2](/details-gene/64902) positively regulates nitric oxide production, a key process in vascular health. Expression data indicates that [AGXT2](/details-gene/64902) is a highly significant gene in metabolic organs, with its highest expression and functional importance observed in liver cells, specifically [midzonal region hepatocytes](/details-cell/CL0019028), and in the [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney. Its function is clinically relevant, with links to cardiovascular disease via its role in regulating blood pressure ([Link](https://doi.org/10.1161/atvbaha.112.254078)). ## Cellular Roles and Expression Landscape The expression profile of [AGXT2](/details-gene/64902) highlights its specialized function in key metabolic and excretory tissues. **Overall**, the gene shows its highest significance in the liver and kidney. It is a top marker for [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 10.92), [periportal region hepatocytes](/details-cell/CL0019026) (CSI: 3.69), and [hepatocytes](/details-cell/CL0000182) in general (CSI: 3.50). This is consistent with the liver's central role in amino acid and nitrogen metabolism. Concurrently, [AGXT2](/details-gene/64902) is highly significant in multiple cell types within the kidney nephron, including [epithelial cells of the proximal tubule](/details-cell/CL0002306) (CSI: 6.20), [parietal epithelial cells](/details-cell/CL1000452) (CSI: 3.03), and [podocytes](/details-cell/CL0000653) (CSI: 1.93). Significant expression is also noted in [intestinal epithelial cells](/details-cell/CL0002563) (CSI: 7.51). This distinct expression pattern strongly suggests that [AGXT2](/details-gene/64902) functions as a specialized metabolic enzyme whose activity is concentrated in organs responsible for processing and clearing metabolic byproducts from the blood ([Link](https://doi.org/10.1016/j.atherosclerosissup.2019.08.041)). ## Pathways and Molecular Function The functional annotations for [AGXT2](/details-gene/64902) confirm its identity as a pyridoxal-phosphate-dependent aminotransferase operating within the [mitochondrial matrix](/details-go/GO:0005759). Its molecular function is defined by its transaminase activities, including [Alanine-glyoxylate transaminase activity](/details-go/GO:0008453) and [(R)-3-amino-2-methylpropionate-pyruvate transaminase activity](/details-go/GO:0047305). These activities place it within central metabolic pathways such as [Glyoxylate metabolism and glycine degradation](/details-pathway/R-HSA-389661) and the broader [Metabolism of amino acids and derivatives](/details-pathway/R-HSA-71291). Critically, [AGXT2](/details-gene/64902) participates in the [N(omega),n(omega)-dimethyl-l-arginine catabolic process](/details-go/GO:2001299). This process is directly linked to the [Positive regulation of nitric oxide biosynthetic process](/details-go/GO:0045429), as the substrate, ADMA, is a potent endogenous inhibitor of nitric oxide synthases. By degrading ADMA, [AGXT2](/details-gene/64902) helps maintain nitric oxide bioavailability, which is essential for endothelial function and blood pressure regulation ([Link](https://doi.org/10.1074/jbc.m109.091280)). This metabolic function is highly relevant in the vascularized liver and kidney, where its expression is highest. ## Research Directions The specific expression pattern and crucial metabolic function of [AGXT2](/details-gene/64902) suggest several avenues for future research, particularly concerning its role in metabolic and cardiovascular health. **Proposed Hypotheses:** 1. Given that functional polymorphisms in [AGXT2](/details-gene/64902) impact methylarginine metabolism ([Link](https://doi.org/10.1371/journal.pone.0088544)), it is hypothesized that individuals with loss-of-function variants in [AGXT2](/details-gene/64902) will exhibit elevated plasma ADMA levels, leading to endothelial dysfunction and a predisposition to hypertension and coronary heart disease ([Link](https://doi.org/10.5551/jat.23077)). 2. The high expression of [AGXT2](/details-gene/64902) in the [epithelial cell of the proximal tubule](/details-cell/CL0002306) suggests a role in renal detoxification. It is hypothesized that reduced [AGXT2](/details-gene/64902) activity could impair the kidney's ability to handle metabolic loads, potentially sensitizing the kidney to injury from conditions like diabetes or high-protein diets, which increase the flux of amino acids and their metabolites. **Experimental Approach:** To test the first hypothesis regarding the systemic impact of [AGXT2](/details-gene/64902) function, a conditional knockout mouse model could be generated with `Agxt2` specifically deleted in hepatocytes and renal proximal tubule cells. These mice and their wild-type littermates would be subjected to a normal and a high-protein diet. Key readouts would include: (1) quantification of plasma and tissue levels of ADMA and other methylarginines via mass spectrometry; (2) continuous blood pressure monitoring using telemetry; and (3) assessment of endothelial function via pressure myography of isolated arteries to measure endothelium-dependent vasodilation. A significant increase in ADMA and blood pressure, coupled with impaired vasodilation in knockout mice, would confirm the critical role of hepatic and renal [AGXT2](/details-gene/64902) in maintaining cardiovascular homeostasis. **Therapeutic Potential:** [AGXT2](/details-gene/64902) represents a promising therapeutic target for cardiovascular diseases associated with elevated ADMA and endothelial dysfunction. The therapeutic strategy would focus on **activation**, not inhibition. Development of small molecule activators that enhance the enzymatic activity of [AGXT2](/details-gene/64902) could provide a novel mechanism to lower systemic ADMA levels, thereby increasing nitric oxide bioavailability, improving endothelial function, and reducing blood pressure. As an intracellular enzyme, it is a suitable target for orally bioavailable small molecules.

Genular Protein ID: 2777064566

Symbol: AGT2_HUMAN

Name: Alanine--glyoxylate aminotransferase 2, mitochondrial

UniProtKB Accession Codes:

Q9BYV1 B7ZM47 E9PDL7 Q53FB4 Q53FY7 Q53G03 Q5W7Q1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 73 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 4 EC 4 EMBL 8 Ensembl 3 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 2 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 3 Rhea 21 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 20018850

Title: Human alanine-glyoxylate aminotransferase 2 lowers asymmetric dimethylarginine and protects from inhibition of nitric oxide production.

PubMed ID: 20018850

DOI: 10.1074/jbc.m109.091280

PubMed ID: 23023372

Title: Alanine-Glyoxylate aminotransferase-2 metabolizes endogenous methylarginines, regulates NO, and controls blood pressure.

PubMed ID: 23023372

DOI: 10.1161/atvbaha.112.254078

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 31818439

Title: Kidney and liver are the main organs of expression of a key metabolic enzyme alanine:glyoxylate aminotransferase 2 in humans.

PubMed ID: 31818439

DOI: 10.1016/j.atherosclerosissup.2019.08.041

PubMed ID: 24834905

Title: Association of the AGXT2 V140I polymorphism with risk for coronary heart disease in a Chinese population.

PubMed ID: 24834905

DOI: 10.5551/jat.23077

PubMed ID: 24586340

Title: Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have considerable impact on methylarginine and beta-aminoisobutyrate metabolism in healthy volunteers.

PubMed ID: 24586340

DOI: 10.1371/journal.pone.0088544

Sequence Information:

  • Length: 514
  • Mass: 57156
  • Checksum: CA562F84FF39B5AC
  • Sequence:
    • MTLIWRHLLR PLCLVTSAPR ILEMHPFLSL GTSRTSVTKL SLHTKPRMPP CDFMPERYQS 
LGYNRVLEIH KEHLSPVVTA YFQKPLLLHQ GHMEWLFDAE GSRYLDFFSG IVTVSVGHCH 
PKVNAVAQKQ LGRLWHTSTV FFHPPMHEYA EKLAALLPEP LKVIFLVNSG SEANELAMLM 
ARAHSNNIDI ISFRGAYHGC SPYTLGLTNV GTYKMELPGG TGCQPTMCPD VFRGPWGGSH 
CRDSPVQTIR KCSCAPDCCQ AKDQYIEQFK DTLSTSVAKS IAGFFAEPIQ GVNGVVQYPK 
GFLKEAFELV RARGGVCIAD EVQTGFGRLG SHFWGFQTHD VLPDIVTMAK GIGNGFPMAA 
VITTPEIAKS LAKCLQHFNT FGGNPMACAI GSAVLEVIKE ENLQENSQEV GTYMLLKFAK 
LRDEFEIVGD VRGKGLMIGI EMVQDKISCR PLPREEVNQI HEDCKHMGLL VGRGSIFSQT 
FRIAPSMCIT KPEVDFAVEV FRSALTQHME RRAK