Details for: ADAT1

Gene ID: 23536

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: ADAT1

Ensembl ID: ENSG00000065457

Description: adenosine deaminase tRNA specific 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 15.62
    rCSI 24.84%
    PRS 98.31
  • basal cell of epidermis CL0002187
    CSI 13.15
    rCSI 23.3%
    PRS 89.33
  • innate lymphoid cell CL0001065
    CSI 12.66
    rCSI 26.14%
    PRS 96.94
  • helper T cell CL0000912
    CSI 12.37
    rCSI 17.49%
    PRS 97.16
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 12.24
    rCSI 14.83%
    PRS 92.18
  • melanocyte of skin CL1000458
    CSI 11.38
    rCSI 15.52%
    PRS 90.87
  • mast cell CL0000097
    CSI 11.1
    rCSI 23.96%
    PRS 95.31
  • suprabasal keratinocyte CL4033013
    CSI 10.28
    rCSI 16.79%
    PRS 91.15
  • epithelial cell CL0000066
    CSI 5.67
    rCSI 8.72%
    PRS 96.38
  • pericyte CL0000669
    CSI 5.52
    rCSI 14.71%
    PRS 92.56
  • endothelial cell of vascular tree CL0002139
    CSI 5.44
    rCSI 29.75%
    PRS 98.12
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 4.72
    rCSI 4.3%
    PRS 99.74
  • regulatory T cell CL0000815
    CSI 4.17
    rCSI 4.84%
    PRS 96.11
  • multi-ciliated epithelial cell CL0005012
    CSI 4.03
    rCSI 4.02%
    PRS 98.32
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.99
    rCSI 2.79%
    PRS 99.77
  • erythrocyte CL0000232
    CSI 3.96
    rCSI 8.98%
    PRS 98.66
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.84
    rCSI 4.77%
    PRS 97.22
  • ependymal cell CL0000065
    CSI 3.53
    rCSI 7.17%
    PRS 95.59
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.29
    rCSI 2.53%
    PRS 99.73
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.19
    rCSI 5.63%
    PRS 97.59
  • peripheral nervous system neuron CL2000032
    CSI 3.03
    rCSI 4.12%
    PRS 98.64
  • club cell CL0000158
    CSI 3
    rCSI 4.4%
    PRS 99.37
  • cytotoxic T cell CL0000910
    CSI 2.37
    rCSI 13.59%
    PRS 97.47

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)

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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 [ADAT1](/details-gene/23536), or adenosine deaminase tRNA specific 1, is a protein-coding gene located on chromosome 16q23.1. It functions as a tRNA-specific adenosine deaminase, an essential enzyme in the post-transcriptional modification of transfer RNA ([Link](https://doi.org/10.1073/pnas.96.16.8895)). Its primary role involves converting adenosine to inosine at the wobble position (position 34) of specific tRNAs, a critical step in [tRNA processing](/details-go/GO:0008033) that expands the decoding capacity of the translational machinery. **Overall**, expression data indicates that [ADAT1](/details-gene/23536) is a significant gene in a diverse array of cell types, including structural cells like [chondrocytes](/details-cell/CL0000138) and [basal cells of the epidermis](/details-cell/CL0002187), as well as various immune cells such as [innate lymphoid cells](/details-cell/CL0001065) and [helper T cells](/details-cell/CL0000912). This broad but prominent expression pattern underscores its fundamental importance in cellular protein synthesis. ## Cellular Roles and Expression Landscape The expression profile of [ADAT1](/details-gene/23536) highlights its critical role in cells requiring high translational fidelity and efficiency. **Overall**, it exhibits the highest significance in [chondrocytes](/details-cell/CL0000138) (CSI: 15.62), suggesting a key function in maintaining the complex extracellular matrix produced by these cells. High significance is also observed in epithelial and skin-related cell types, including [basal cell of epidermis](/details-cell/CL0002187) (CSI: 13.15), [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 10.28), and [melanocyte of skin](/details-cell/CL1000458) (CSI: 11.38), which are all characterized by high rates of protein synthesis for structural integrity, pigmentation, and turnover. Concurrently, [ADAT1](/details-gene/23536) is a prominent gene within the immune system. It shows high significance in both the innate and adaptive compartments, including [innate lymphoid cells](/details-cell/CL0001065) (CSI: 12.66), [helper T cells](/details-cell/CL0000912) (CSI: 12.37), [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203) (CSI: 12.24), and [mast cells](/details-cell/CL0000097) (CSI: 11.10). This pattern is consistent with the need for rapid synthesis of cytokines, granzymes, and other effector proteins upon immune activation. The widespread, high expression across functionally distinct cell lineages suggests that [ADAT1](/details-gene/23536) is a vital housekeeping enzyme whose activity is particularly crucial for specialized, metabolically active cells. ## Pathways and Molecular Function The functional annotations for [ADAT1](/details-gene/23536) confirm its role as a specialized RNA-modifying enzyme. It is a key component of the [Metabolism of RNA](/details-pathway/R-HSA-8953854) and, more specifically, [tRNA processing](/details-pathway/R-HSA-72306). The gene's primary molecular function is its [tRNA-specific adenosine deaminase activity](/details-go/GO:0008251), particularly targeting adenosine at position 37 of the tRNA anticodon loop ([GO:0043829](https://www.ebi.ac.uk/QuickGO/term/GO:0043829)). This modification is crucial for accurate codon recognition during mRNA translation. The enzyme's ability to bind both RNA ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)) and metal ions ([GO:0046872](https://www.ebi.ac.uk/QuickGO/term/GO:0046872)) is integral to its catalytic activity. This fundamental role in ensuring translational accuracy aligns with its high expression in cells with demanding protein synthesis requirements, such as proliferating keratinocytes and activated lymphocytes. ## Research Directions The broad yet high expression of [ADAT1](/details-gene/23536) in key structural and immune cells provides a foundation for several testable hypotheses regarding its role in health and disease. 1. **Hypothesis 1:** Given its high significance in multiple T cell subsets ([helper T cell](/details-cell/CL0000912), [effector memory CD8-positive, alpha-beta T cell](/details-cell/CL0000913)), it is hypothesized that [ADAT1](/details-gene/23536)-mediated tRNA editing is indispensable for the rapid and massive production of effector cytokines and cytolytic molecules during an adaptive immune response. Defects in [ADAT1](/details-gene/23536) function may lead to proteotoxic stress and impaired T cell effector function. 2. **Hypothesis 2:** Based on its prominent expression in [basal cells](/details-cell/CL0002187) and [keratinocytes](/details-cell/CL4033013), it is hypothesized that [ADAT1](/details-gene/23536) is a critical regulator of skin homeostasis. Its loss could compromise the integrity of the epidermal barrier by disrupting the precise synthesis of structural proteins like keratins, potentially contributing to skin fragility disorders. **Proposed Experiment to Test Hypothesis 1:** To investigate the role of [ADAT1](/details-gene/23536) in T cell function, a conditional knockout mouse model using CD4-Cre to delete [ADAT1](/details-gene/23536) specifically in T lymphocytes could be generated. Naive CD4+ and CD8+ T cells isolated from these mice and wild-type controls would be activated *in vitro* using anti-CD3/CD28 stimulation. The functional consequences would be assessed by measuring proliferation (e.g., cell trace violet dilution via flow cytometry), cytokine secretion (e.g., IFN-γ, IL-2, TNF-α via multiplex assay), and metabolic reprogramming (e.g., via Seahorse assay). RNA-sequencing could then be used to determine if loss of [ADAT1](/details-gene/23536) leads to signatures of translational stress or the unfolded protein response. **Therapeutic Potential:** As an intracellular enzyme involved in the fundamental process of tRNA modification, [ADAT1](/details-gene/23536) is a challenging therapeutic target. Its broad expression in many healthy and essential cell types suggests that systemic inhibition would likely lead to significant off-target toxicity. Therefore, it is generally considered a poor candidate for drug development unless a specific cancer or disease state is discovered to have a unique and critical dependency on its activity, creating a potential therapeutic window.

Genular Protein ID: 4264632951

Symbol: ADAT1_HUMAN

Name: tRNA-specific adenosine deaminase 1

UniProtKB Accession Codes:

Q9BUB4 Q9NVB7 Q9UNG3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 15 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 5 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 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 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 Rhea 3 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10430867

Title: Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes.

PubMed ID: 10430867

DOI: 10.1073/pnas.96.16.8895

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 502
  • Mass: 55392
  • Checksum: 3664E4C50DA9DFE0
  • Sequence:
    • MWTADEIAQL CYEHYGIRLP KKGKPEPNHE WTLLAAVVKI QSPADKACDT PDKPVQVTKE 
VVSMGTGTKC IGQSKMRKNG DILNDSHAEV IARRSFQRYL LHQLQLAATL KEDSIFVPGT 
QKGVWKLRRD LIFVFFSSHT PCGDASIIPM LEFEDQPCCP VFRNWAHNSS VEASSNLEAP 
GNERKCEDPD SPVTKKMRLE PGTAAREVTN GAAHHQSFGK QKSGPISPGI HSCDLTVEGL 
ATVTRIAPGS AKVIDVYRTG AKCVPGEAGD SGKPGAAFHQ VGLLRVKPGR GDRTRSMSCS 
DKMARWNVLG CQGALLMHLL EEPIYLSAVV IGKCPYSQEA MQRALIGRCQ NVSALPKGFG 
VQELKILQSD LLFEQSRSAV QAKRADSPGR LVPCGAAISW SAVPEQPLDV TANGFPQGTT 
KKTIGSLQAR SQISKVELFR SFQKLLSRIA RDKWPHSLRV QKLDTYQEYK EAASSYQEAW 
STLRKQVFGS WIRNPPDYHQ FK