Details for: ATP23

Gene ID: 91419

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: ATP23

Ensembl ID: ENSG00000166896

Description: ATP23 metallopeptidase and ATP synthase assembly factor homolog

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pro-B cell CL0000826
    CSI 3.64
    rCSI 3.02%
    PRS 99.52
  • epithelial cell CL0000066
    CSI 3.16
    rCSI 4.86%
    PRS 96.96

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

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 [ATP23](/details-gene/91419) is a protein-coding gene located on chromosome 12q14.1 that encodes a homolog of the mitochondrial inner membrane protease and ATP synthase assembly factor. The protein exhibits a notable dual functionality, participating in both mitochondrial bioenergetics and nuclear DNA repair. Its primary functions include the assembly of the mitochondrial ATP synthase complex and a role in double-strand break repair via the nonhomologous end joining (NHEJ) pathway. **Overall**, expression data indicates that [ATP23](/details-gene/91419) is a significant gene in developing immune cells, particularly [pro-B cells](/details-cell/CL0000826), as well as in [epithelial cells](/details-cell/CL0000066), suggesting its importance in contexts requiring robust DNA maintenance and high metabolic activity. ## Cellular Roles and Expression Landscape The expression profile of [ATP23](/details-gene/91419) highlights its importance in specific cellular contexts characterized by high rates of proliferation, DNA rearrangement, or metabolic demand. **Overall**, the gene shows its most significant expression in [pro-B cells](/details-cell/CL0000826) (CSI: 3.64). This is consistent with its role in the NHEJ pathway, as V(D)J recombination, a critical process for generating antibody diversity in developing lymphocytes, creates programmed DNA double-strand breaks that must be repaired by this mechanism. Its high expression suggests [ATP23](/details-gene/91419) is a key component of the machinery ensuring genomic integrity during B-cell maturation. The gene also demonstrates significant expression in [epithelial cells](/details-cell/CL0000066) (CSI: 3.16). These cells form barrier tissues that are often exposed to environmental stressors and genotoxic agents, necessitating efficient DNA repair mechanisms. Furthermore, their high metabolic activity requires proper mitochondrial function for energy production, aligning with the dual roles of [ATP23](/details-gene/91419) in both mitochondrial ATP synthase assembly and DNA repair. ## Pathways and Molecular Function Functional annotation reveals that [ATP23](/details-gene/91419) operates in two distinct subcellular compartments and biological pathways. In the mitochondrion, [ATP23](/details-gene/91419) is integral to energy metabolism. It is involved in [mitochondrial protein processing](/details-go/GO:0034982) and the assembly of the [mitochondrial proton-transporting ATP synthase complex](/details-go/GO:0033615). This role is supported by its predicted [metalloendopeptidase activity](/details-go/GO:0004222) and its localization to the [mitochondrion](/details-go/GO:0005739). In the nucleus, [ATP23](/details-gene/91419) is a key participant in genome maintenance through its role in [double-strand break repair via nonhomologous end joining](/details-go/GO:0006303). This function is substantiated by its annotated [DNA-dependent protein kinase activity](/details-go/GO:0004677) and its identification as a component of the [DNA-dependent protein kinase-DNA ligase 4 complex](/details-go/GO:0005958). Research has further identified it as a Ku70-binding protein, directly linking it to the core machinery of the NHEJ pathway ([Link](https://doi.org/10.1093/nar/27.10.2165)). The protein's ability to bind [metal ions](/details-go/GO:0046872) and engage in [protein binding](/details-go/GO:0005515) underpins its enzymatic and structural roles in both of these critical cellular processes. ## Research Directions The dual localization and function of [ATP23](/details-gene/91419) in both mitochondrial bioenergetics and nuclear DNA repair present intriguing questions about its regulation and its specific roles in cellular health and disease. **Proposed Hypotheses:** 1. The subcellular trafficking of [ATP23](/details-gene/91419) between the mitochondrion and the nucleus is a regulated process that shifts in response to cellular state. For example, in response to genotoxic stress, a greater proportion of [ATP23](/details-gene/91419) may be directed to the nucleus to support DNA repair, potentially impacting mitochondrial function. 2. In developing B-lymphocytes, [ATP23](/details-gene/91419) is indispensable for the repair of DNA breaks generated during V(D)J recombination. Its functional loss in this context would lead to a developmental block at the [pro-B cell](/details-cell/CL0000826) stage due to the accumulation of unresolved DNA damage and subsequent apoptosis. **Experimental Approach:** To test the second hypothesis regarding its role in B-cell development, a conditional knockout mouse model could be employed. Specifically, deleting [ATP23](/details-gene/91419) in the B-cell lineage using a CD19-Cre driver would allow for targeted investigation. Flow cytometric analysis of bone marrow and spleen from these mice would be expected to reveal a significant reduction or absence of mature B-cells and an accumulation of cells at the [pro-B cell](/details-cell/CL0000826) stage. This cellular phenotype should be accompanied by increased staining for DNA damage markers (e.g., γH2AX foci) and apoptosis (e.g., Annexin V) within the B-cell precursor population. **Therapeutic Potential:** Given its critical function in the NHEJ DNA repair pathway, [ATP23](/details-gene/91419) emerges as a plausible target for cancer therapy. Inhibition of [ATP23](/details-gene/91419) could act as a sensitizing agent, enhancing the efficacy of DNA-damaging treatments such as radiotherapy or certain chemotherapies, particularly in tumors reliant on NHEJ for survival. A therapeutic strategy involving inhibition would be pursued, though it would require careful assessment to mitigate potential toxicity arising from the disruption of its essential mitochondrial functions in healthy tissues.

Genular Protein ID: 2966482302

Symbol: ATP23_HUMAN

Name: Mitochondrial inner membrane protease ATP23 homolog

UniProtKB Accession Codes:

Q9Y6H3 Q1RLM4 Q96E81

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 12 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 4 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10219089

Title: Isolation of Ku70-binding proteins (KUBs).

PubMed ID: 10219089

DOI: 10.1093/nar/27.10.2165

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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

Sequence Information:

  • Length: 246
  • Mass: 28081
  • Checksum: A9541CBEA299A35F
  • Sequence:
    • MAGAPDERRR GPAAGEQLQQ QHVSCQVFPE RLAQGNPQQG FFSSFFTSNQ KCQLRLLKTL 
ETNPYVKLLL DAMKHSGCAV NKDRHFSCED CNGNVSGGFD ASTSQIVLCQ NNIHNQAHMN 
RVVTHELIHA FDHCRAHVDW FTNIRHLACS EVRAANLSGD CSLVNEIFRL HFGLKQHHQT 
CVRDRATLSI LAVRNISKEV AKKAVDEVFE SCFNDHEPFG RIPHNKTYAR YAHRDFENRD 
RYYSNI