Details for: TRIM23

Gene ID: 373

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: TRIM23

Ensembl ID: ENSG00000113595

Description: tripartite motif containing 23

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 8.17
    rCSI 17.38%
    PRS 76.37
  • lung ciliated cell CL1000271
    CSI 4.61
    rCSI 5.34%
    PRS 75.04
  • multi-ciliated epithelial cell CL0005012
    CSI 4.43
    rCSI 4.42%
    PRS 76.47
  • pro-B cell CL0000826
    CSI 4.32
    rCSI 3.58%
    PRS 84.48
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.16
    rCSI 9.33%
    PRS 66.03
  • double negative thymocyte CL0002489
    CSI 3.91
    rCSI 2.72%
    PRS 92.58
  • pancreatic A cell CL0000171
    CSI 3.67
    rCSI 3.84%
    PRS 85.4
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 3.66
    rCSI 3.73%
    PRS 90.83
  • interneuron CL0000099
    CSI 3.63
    rCSI 7.29%
    PRS 73.33
  • cardiac endothelial cell CL0010008
    CSI 3.3
    rCSI 13.31%
    PRS 82.44
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.1
    rCSI 5.63%
    PRS 74.23
  • mature B cell CL0000785
    CSI 2.97
    rCSI 2.58%
    PRS 90.72
  • vascular leptomeningeal cell CL4023051
    CSI 2.94
    rCSI 5.16%
    PRS 76.72
  • cerebral cortex neuron CL0010012
    CSI 2.87
    rCSI 11.69%
    PRS 74.29
  • melanocyte CL0000148
    CSI 2.7
    rCSI 2%
    PRS 76.43
  • stem cell CL0000034
    CSI 2.6
    rCSI 2.51%
    PRS 76.43
  • ciliated epithelial cell CL0000067
    CSI 2.5
    rCSI 2.2%
    PRS 72.08
  • neural crest cell CL0011012
    CSI 2.49
    rCSI 1.97%
    PRS 72.09
  • cerebellar granule cell CL0001031
    CSI 2.35
    rCSI 3.45%
    PRS 75.55
  • Mueller cell CL0000636
    CSI 2.29
    rCSI 5.23%
    PRS 74.2
  • erythrocyte CL0000232
    CSI 2.28
    rCSI 5.18%
    PRS 82.6
  • peripheral nervous system neuron CL2000032
    CSI 2.25
    rCSI 3.06%
    PRS 74.36
  • rod bipolar cell CL0000751
    CSI 2.22
    rCSI 3.99%
    PRS 76.04
  • enteric smooth muscle cell CL0002504
    CSI 2.19
    rCSI 3.12%
    PRS 83.16
  • cerebral cortex endothelial cell CL1001602
    CSI 2.1
    rCSI 3.64%
    PRS 74.56
  • ependymal cell CL0000065
    CSI 2.04
    rCSI 4.13%
    PRS 61.51
  • hepatic stellate cell CL0000632
    CSI 2.03
    rCSI 7.6%
    PRS 75.33
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.96
    rCSI 2.34%
    PRS 65.28
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.83
    rCSI 5.4%
    PRS 83.15
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.72
    rCSI 2.76%
    PRS 66.56
  • amacrine cell CL0000561
    CSI 1.7
    rCSI 4.93%
    PRS 72.19
  • retina horizontal cell CL0000745
    CSI 1.69
    rCSI 2.58%
    PRS 79.2
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.65
    rCSI 5.94%
    PRS 63.06
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.57
    rCSI 1.96%
    PRS 63.06
  • blood vessel smooth muscle cell CL0019018
    CSI 1.5
    rCSI 12.21%
    PRS 77.16
  • direct pathway medium spiny neuron CL4023026
    CSI 1.49
    rCSI 35.74%
    PRS 63.14
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.48
    rCSI 1.91%
    PRS 66.33
  • chondrocyte CL0000138
    CSI 1.47
    rCSI 2.34%
    PRS 75.91
  • cardiac muscle cell CL0000746
    CSI 1.46
    rCSI 2.09%
    PRS 72.66
  • GABAergic amacrine cell CL4030027
    CSI 1.43
    rCSI 4.89%
    PRS 68.61
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.38
    rCSI 33.32%
    PRS 63.71
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.34
    rCSI 4.2%
    PRS 66.84
  • inhibitory interneuron CL0000498
    CSI 1.32
    rCSI 3.04%
    PRS 70.77
  • retinal bipolar neuron CL0000748
    CSI 1.31
    rCSI 2.45%
    PRS 71.27
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.3
    rCSI 4.29%
    PRS 68.46
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.25
    rCSI 3.17%
    PRS 73.31
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.23
    rCSI 2.99%
    PRS 63.11
  • glial cell CL0000125
    CSI 1.15
    rCSI 4.37%
    PRS 73.79
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.15
    rCSI 1.93%
    PRS 65.17
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 1.04
    rCSI 4.74%
    PRS 95.18
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.03
    rCSI 1.82%
    PRS 64.68
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.02
    rCSI 2.44%
    PRS 69.52
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 0.97
    rCSI 2.11%
    PRS 69.97
  • retinal ganglion cell CL0000740
    CSI 0.9
    rCSI 1.99%
    PRS 68.79
  • retinal cone cell CL0000573
    CSI 0.89
    rCSI 1.44%
    PRS 72.97
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.83
    rCSI 2.58%
    PRS 69.12
  • podocyte CL0000653
    CSI 0.76
    rCSI 3.38%
    PRS 83.02
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.75
    rCSI 2.17%
    PRS 81.83
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.72
    rCSI 4.25%
    PRS 65.72
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.6
    rCSI 2.25%
    PRS 65.72
  • central nervous system neuron CL2000029
    CSI 0.46
    rCSI 3.38%
    PRS 70.37
  • medium spiny neuron CL1001474
    CSI 0.38
    rCSI 3.28%
    PRS 70.89

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 [TRIM23](/details-gene/373), also known as ADP-ribosylation factor domain protein 1 (ARD1), is a protein-coding gene located on chromosome 5q12.3. It belongs to the tripartite motif (TRIM) family of proteins, characterized by their conserved RING finger, B-box, and coiled-coil domains. [TRIM23](/details-gene/373) is a multifunctional enzyme that uniquely combines the E3 ubiquitin ligase activity typical of TRIM proteins with a C-terminal ADP-ribosylation factor (ARF) domain that confers GTPase activity [Link](https://doi.org/10.1016/s0021-9258(18)52945-8). Functionally, it is implicated in a range of core cellular processes including the [innate immune response](/details-go/GO:0045087), [positive regulation of autophagy](/details-go/GO:0010508), and [vesicle-mediated transport](/details-go/GO:0016192). Expression data reveals its highest significance in [progenitor cell](/details-cell/CL0011026), with broad and notable expression across developing lymphocytes, specialized epithelial cells, and various neural cell types, underscoring its fundamental role in cellular maintenance and stress response. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [TRIM23](/details-gene/373) suggests a widespread but functionally specific role across multiple tissues. Its highest significance is observed in [progenitor cell](/details-cell/CL0011026) (CSI: 8.17), which may indicate a crucial function in maintaining cellular plasticity, proteostasis, or developmental processes. The gene's role extends prominently into several key biological systems: * **Immune System:** [TRIM23](/details-gene/373) shows significant expression in various stages of lymphocyte development, including in [pro-B cell](/details-cell/CL0000826) (CSI: 4.32), [double negative thymocyte](/details-cell/CL0002489) (CSI: 3.91), and [double-positive, alpha-beta thymocyte](/details-cell/CL0000809) (CSI: 3.66). This is consistent with its established role in innate immunity and antiviral responses. * **Specialized Epithelia:** High significance in [lung ciliated cell](/details-cell/CL1000271) (CSI: 4.61) and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 4.43) suggests a specialized function in tissues that form a barrier to the external environment, possibly related to pathogen clearance or mucociliary transport. * **Nervous System:** The gene is also broadly significant across diverse neural cell types, including [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 4.16), [interneuron](/details-cell/CL0000099) (CSI: 3.63), and [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) (CSI: 3.10), pointing towards a role in neuronal homeostasis or development. This widespread expression pattern in functionally diverse cells like [pancreatic A cell](/details-cell/CL0000171) and [cardiac endothelial cell](/details-cell/CL0010008) highlights its involvement in fundamental cellular machinery, likely related to protein quality control and intracellular trafficking. ## Pathways and Molecular Function [TRIM23](/details-gene/373) is a bifunctional protein that integrates ubiquitination with GTPase-regulated vesicle transport. Its molecular functions are primarily driven by its two key domains. The N-terminal TRIM motif confers [ubiquitin protein ligase activity](/details-go/GO:0061630), enabling it to tag substrate proteins for degradation or signaling, a function confirmed experimentally [Link](https://doi.org/10.1073/pnas.0409800102). The C-terminal ARF domain provides [GTPase activity](/details-go/GO:0003924) and is involved in regulating membrane trafficking. This unique combination of activities positions [TRIM23](/details-gene/373) at the crossroads of several critical cellular pathways: * **Innate Immunity and Autophagy:** [TRIM23](/details-gene/373) plays a direct role in antiviral defense. It has been shown to mediate virus-induced autophagy through the activation of the kinase TBK1 [Link](https://doi.org/10.1038/s41564-017-0017-2). It also acts as a cofactor in the regulation of the NF-kappaB pathway during human cytomegalovirus infection, linking it to inflammatory signaling [Link](https://doi.org/10.1128/jvi.02072-08). * **Intracellular Transport:** Consistent with its ARF domain, [TRIM23](/details-gene/373) is localized to the [Golgi membrane](/details-go/GO:0000139) and [lysosomal membrane](/details-go/GO:0005765) [Link](https://doi.org/10.1073/pnas.95.15.8613). This places it in a prime position to regulate [vesicle-mediated transport](/details-go/GO:0016192) between these organelles, a process essential for protein sorting, secretion, and degradation. Its functions are supported by its ability to bind zinc ions ([zinc ion binding](/details-go/GO:0008270)), essential for the structural integrity of the RING finger domain, and engage in [protein binding](/details-go/GO:0005515) to interact with substrates and regulatory partners. ## Research Directions The broad yet significant expression pattern of [TRIM23](/details-gene/373) raises important questions about its cell-type-specific functions and regulatory mechanisms. Future research could explore how its dual enzymatic activities are coordinated to control distinct biological outcomes in different cellular contexts. **Testable Hypotheses:** 1. Given its exceptionally high CSI in [progenitor cell](/details-cell/CL0011026) and its role in autophagy and proteostasis, the E3 ligase activity of [TRIM23](/details-gene/373) may be essential for clearing aggregated or obsolete proteins during lineage commitment, and its loss could impair differentiation potential. 2. Based on its high expression in [lung ciliated cell](/details-cell/CL1000271) and its known role in antiviral autophagy [Link](https://doi.org/10.1038/s41564-017-0017-2), [TRIM23](/details-gene/373) likely functions as a key sensor or effector in the innate immune defense of the respiratory tract, mediating the capture and autophagic degradation of inhaled viral pathogens. **Proposed Experimental Approach:** To test the first hypothesis regarding its role in progenitor cells, a CRISPR-Cas9-mediated knockout of [TRIM23](/details-gene/373) could be generated in human induced pluripotent stem cells (iPSCs). These knockout iPSCs and isogenic wild-type controls would be differentiated towards neural and hematopoietic lineages. The efficiency of differentiation would be quantified by flow cytometry for lineage-specific markers (e.g., CD34 for hematopoietic progenitors, PAX6 for neural progenitors). In parallel, proteomic analysis (e.g., mass spectrometry of the ubiquitinated proteome) and cell imaging for protein aggregates would be used to determine if the loss of [TRIM23](/details-gene/373) leads to defects in proteostasis that correlate with impaired differentiation. **Therapeutic Potential:** As an E3 ubiquitin ligase, [TRIM23](/details-gene/373) belongs to a druggable class of enzymes. Its roles in autophagy, immunity, and NF-kappaB signaling make it a potential target for diseases involving these pathways, such as cancer, viral infections, and inflammatory disorders. Inhibition of [TRIM23](/details-gene/373) could be explored as a strategy to disrupt autophagy in cancer cells that depend on this process for survival. Conversely, targeted activation of its autophagic function could be beneficial in neurodegenerative diseases characterized by toxic protein accumulation. However, its broad expression pattern poses a significant challenge, suggesting that therapeutic interventions would likely require cell-type-specific delivery systems or the development of highly selective small molecule modulators to avoid off-target toxicity.

Genular Protein ID: 2813304776

Symbol: TRI23_HUMAN

Name: E3 ubiquitin-protein ligase TRIM23

UniProtKB Accession Codes:

P36406 Q9BZY4 Q9BZY5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 4 CORUM 1 CTD 1 ChEBI 3 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 5 Ensembl 3 ExpressionAtlas 1 GO 18 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRINTS 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 4 SIGNOR 1 SMART 6 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8473324

Title: ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP-ribosylation factor domain.

PubMed ID: 8473324

DOI: 10.1016/s0021-9258(18)52945-8

PubMed ID: 11331580

Title: The tripartite motif family identifies cell compartments.

PubMed ID: 11331580

DOI: 10.1093/emboj/20.9.2140

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: 9671726

Title: Localization of ADP-ribosylation factor domain protein 1 (ARD1) in lysosomes and Golgi apparatus.

PubMed ID: 9671726

DOI: 10.1073/pnas.95.15.8613

PubMed ID: 10748148

Title: Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1).

PubMed ID: 10748148

DOI: 10.1074/jbc.m909642199

PubMed ID: 15684077

Title: E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1).

PubMed ID: 15684077

DOI: 10.1073/pnas.0409800102

PubMed ID: 19176615

Title: Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus.

PubMed ID: 19176615

DOI: 10.1128/jvi.02072-08

PubMed ID: 28871090

Title: TRIM23 mediates virus-induced autophagy via activation of TBK1.

PubMed ID: 28871090

DOI: 10.1038/s41564-017-0017-2

PubMed ID: 28681414

Title: Structure and catalytic activation of the TRIM23 RING E3 ubiquitin ligase.

PubMed ID: 28681414

DOI: 10.1002/prot.25348

Sequence Information:

  • Length: 574
  • Mass: 64067
  • Checksum: CB85923B29BF0320
  • Sequence:
    • MATLVVNKLG AGVDSGRQGS RGTAVVKVLE CGVCEDVFSL QGDKVPRLLL CGHTVCHDCL 
TRLPLHGRAI RCPFDRQVTD LGDSGVWGLK KNFALLELLE RLQNGPIGQY GAAEESIGIS 
GESIIRCDED EAHLASVYCT VCATHLCSEC SQVTHSTKTL AKHRRVPLAD KPHEKTMCSQ 
HQVHAIEFVC LEEGCQTSPL MCCVCKEYGK HQGHKHSVLE PEANQIRASI LDMAHCIRTF 
TEEISDYSRK LVGIVQHIEG GEQIVEDGIG MAHTEHVPGT AENARSCIRA YFYDLHETLC 
RQEEMALSVV DAHVREKLIW LRQQQEDMTI LLSEVSAACL HCEKTLQQDD CRVVLAKQEI 
TRLLETLQKQ QQQFTEVADH IQLDASIPVT FTKDNRVHIG PKMEIRVVTL GLDGAGKTTI 
LFKLKQDEFM QPIPTIGFNV ETVEYKNLKF TIWDVGGKHK LRPLWKHYYL NTQAVVFVVD 
SSHRDRISEA HSELAKLLTE KELRDALLLI FANKQDVAGA LSVEEITELL SLHKLCCGRS 
WYIQGCDARS GMGLYEGLDW LSRQLVAAGV LDVA