Details for: RNF113A

Gene ID: 7737

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: RNF113A

Ensembl ID: ENSG00000125352

Description: ring finger protein 113A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • bronchus fibroblast of lung CL2000093
    CSI 19.67
    rCSI 15.98%
    PRS 53.96
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 6.68
    rCSI 5.08%
    PRS 66.07
  • mature alpha-beta T cell CL0000791
    CSI 4.92
    rCSI 17.82%
    PRS 73.3
  • unswitched memory B cell CL0000970
    CSI 4.62
    rCSI 3.88%
    PRS 71.39
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 4.42
    rCSI 2.95%
    PRS 76.16
  • activated type II NK T cell CL0000931
    CSI 4.36
    rCSI 4.91%
    PRS 69.99
  • rod bipolar cell CL0000751
    CSI 4.22
    rCSI 7.59%
    PRS 46.74
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 3.63
    rCSI 2.91%
    PRS 74.81
  • immature B cell CL0000816
    CSI 2.98
    rCSI 2.21%
    PRS 67.56
  • hematopoietic stem cell CL0000037
    CSI 2.85
    rCSI 1.89%
    PRS 57.15
  • plasmablast CL0000980
    CSI 2.8
    rCSI 2.2%
    PRS 60.36
  • naive T cell CL0000898
    CSI 2.79
    rCSI 1.94%
    PRS 67.81
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.72
    rCSI 2.35%
    PRS 58.2
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.71
    rCSI 1.95%
    PRS 67.53
  • double negative thymocyte CL0002489
    CSI 2.69
    rCSI 1.87%
    PRS 63.76
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 2.68
    rCSI 3.65%
    PRS 79.41
  • mature T cell CL0002419
    CSI 2.63
    rCSI 2.04%
    PRS 71.45
  • ON-bipolar cell CL0000749
    CSI 2.55
    rCSI 3.79%
    PRS 55.82
  • epithelial cell of lung CL0000082
    CSI 2.54
    rCSI 2.11%
    PRS 52.38
  • CD4-positive helper T cell CL0000492
    CSI 2.48
    rCSI 1.87%
    PRS 67.25
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2.46
    rCSI 2.27%
    PRS 73.77
  • precursor B cell CL0000817
    CSI 2.38
    rCSI 2.09%
    PRS 63.84
  • pulmonary ionocyte CL0017000
    CSI 2.37
    rCSI 2.88%
    PRS 61.39
  • perivascular cell CL4033054
    CSI 2.32
    rCSI 3.18%
    PRS 59.05
  • neural crest cell CL0011012
    CSI 2.31
    rCSI 1.82%
    PRS 40.66
  • mesodermal cell CL0000222
    CSI 2.3
    rCSI 2.75%
    PRS 51.68
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.26
    rCSI 2.22%
    PRS 69.52
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.23
    rCSI 1.56%
    PRS 56.15
  • pro-B cell CL0000826
    CSI 2.17
    rCSI 1.8%
    PRS 55.24
  • myeloid leukocyte CL0000766
    CSI 2.16
    rCSI 2%
    PRS 54.68
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.13
    rCSI 6.3%
    PRS 57.32
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 2.04
    rCSI 2.44%
    PRS 73.72
  • T follicular helper cell CL0002038
    CSI 2.03
    rCSI 1.52%
    PRS 68.99
  • class switched memory B cell CL0000972
    CSI 1.99
    rCSI 1.49%
    PRS 71.34
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.99
    rCSI 3.4%
    PRS 73.07
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.98
    rCSI 3.94%
    PRS 71.94
  • stem cell CL0000034
    CSI 1.94
    rCSI 1.87%
    PRS 44.09
  • duct epithelial cell CL0000068
    CSI 1.93
    rCSI 2.82%
    PRS 57.23
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.92
    rCSI 5.51%
    PRS 72.87
  • dendritic cell, human CL0001056
    CSI 1.87
    rCSI 2.87%
    PRS 61.76
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.87
    rCSI 1.44%
    PRS 53.1
  • group 3 innate lymphoid cell CL0001071
    CSI 1.84
    rCSI 1.38%
    PRS 58.16
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.81
    rCSI 2.49%
    PRS 73.82
  • early lymphoid progenitor CL0000936
    CSI 1.77
    rCSI 1.55%
    PRS 58.91
  • ciliated epithelial cell CL0000067
    CSI 1.76
    rCSI 1.55%
    PRS 41.96
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.76
    rCSI 2.26%
    PRS 51.29
  • lung ciliated cell CL1000271
    CSI 1.74
    rCSI 2.01%
    PRS 43.46
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 1.71
    rCSI 1.74%
    PRS 67.13
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 1.66
    rCSI 2.58%
    PRS 79.37
  • club cell CL0000158
    CSI 1.63
    rCSI 2.39%
    PRS 51.1
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.61
    rCSI 1.45%
    PRS 50.37
  • T-helper 17 cell CL0000899
    CSI 1.57
    rCSI 1.25%
    PRS 75.77
  • common dendritic progenitor CL0001029
    CSI 1.42
    rCSI 1.79%
    PRS 63.93
  • common myeloid progenitor CL0000049
    CSI 1.34
    rCSI 1.08%
    PRS 54.75
  • peripheral nervous system neuron CL2000032
    CSI 1.27
    rCSI 1.74%
    PRS 46.16
  • type B pancreatic cell CL0000169
    CSI 1.24
    rCSI 2.75%
    PRS 51.3
  • promyelocyte CL0000836
    CSI 1.17
    rCSI 1.69%
    PRS 63.36
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.06
    rCSI 5.3%
    PRS 65.81
  • mature B cell CL0000785
    CSI 0.97
    rCSI 0.85%
    PRS 64.15
  • late pro-B cell CL0002048
    CSI 0.95
    rCSI 2.37%
    PRS 81.18
  • large pre-B-II cell CL0000957
    CSI 0.82
    rCSI 2.35%
    PRS 67.18
  • Cajal-Retzius cell CL0000695
    CSI 0.55
    rCSI 4.32%
    PRS 67.46
  • retinal cone cell CL0000573
    CSI 0.49
    rCSI 0.79%
    PRS 43.6
  • follicular B cell CL0000843
    CSI 0.46
    rCSI 1.68%
    PRS 82.85
  • helper T cell CL0000912
    CSI 0.4
    rCSI 0.56%
    PRS 60.36
  • erythroid progenitor cell CL0000038
    CSI 0.38
    rCSI 2.18%
    PRS 64
  • cytotoxic T cell CL0000910
    CSI 0.25
    rCSI 1.44%
    PRS 64.22

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 [RNF113A](/details-gene/7737) is a protein-coding gene located on the X chromosome that encodes Ring Finger Protein 113A, an E3 ubiquitin-protein ligase. Functionally, it is implicated in several fundamental cellular processes, including [mRNA splicing, via spliceosome](/details-go/GO:0000398), [protein ubiquitination](/details-go/GO:0016567), and [DNA repair](/details-go/GO:0006281). **Overall**, expression data reveals its most prominent significance in [bronchus fibroblast of lung](/details-cell/CL2000093), suggesting a key role in this mesenchymal cell type. It also shows notable expression across a wide range of immune cells, including [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) and various B cell and T cell progenitors. Clinically, mutations in [RNF113A](/details-gene/7737) are associated with X-linked developmental disorders, including trichothiodystrophy ([300951](https://omim.org/entry/300951)) and digital-facial-genital syndrome ([300953](https://omim.org/entry/300953)). ## Cellular Roles and Expression Landscape The expression profile of [RNF113A](/details-gene/7737) indicates a broad but distinct functional landscape. Its highest significance score (**CSI: 19.67**) is observed in [bronchus fibroblast of lung](/details-cell/CL2000093), pointing towards a potentially critical role in the structural integrity or signaling functions of pulmonary connective tissue. Beyond this, [RNF113A](/details-gene/7737) is significantly expressed across the hematopoietic system. It appears to be a key factor in both the innate and adaptive immune systems. High significance is noted in cytotoxic lymphocytes like [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) and [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939), as well as in various stages of lymphocyte development and memory, including [mature alpha-beta T cell](/details-cell/CL0000791), [unswitched memory B cell](/details-cell/CL0000970), and [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810). The gene's expression in early progenitors, such as [hematopoietic stem cell](/details-cell/CL0000037) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557), suggests its involvement in lineage commitment and the maintenance of immune cell populations. Additionally, its expression in [rod bipolar cell](/details-cell/CL0000751) suggests a specialized function within the retina, extending its relevance beyond structural and immune contexts. ## Pathways and Molecular Function Functionally, [RNF113A](/details-gene/7737) operates as an E3 ubiquitin ligase, mediating the attachment of ubiquitin to substrate proteins ([GO:0016567](/details-go/GO:0016567)). This activity is central to its diverse biological roles. A primary function is its integral role in RNA processing, where it is a component of the [U2-type spliceosomal complex](/details-go/GO:0005684) involved in the [mRNA splicing](/details-reactome/R-HSA-72172) pathway. This is consistent with its localization to the [nucleus](/details-go/GO:0005634) and specifically to [nuclear speck](/details-go/GO:0016607)s, which are key sites for spliceosome component assembly. The importance of RNF113A in the dynamic regulation of the spliceosome has been noted in proteomics studies [Link](https://doi.org/10.1016/j.molcel.2011.12.034). In addition to RNA metabolism, [RNF113A](/details-gene/7737) is annotated in [DNA repair](/details-go/GO:0006281), where its ubiquitin ligase activity may be required for signaling DNA damage or recruiting repair factors. Furthermore, its role in the [negative regulation of chemokine-mediated signaling pathway](/details-go/GO:0070100) directly connects its molecular function to its expression pattern in immune cells, suggesting it acts as a modulator of immune cell trafficking and activation. ## Research Directions The widespread yet specific expression pattern of [RNF113A](/details-gene/7737), combined with its fundamental roles in ubiquitination and splicing, opens several avenues for future research. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [bronchus fibroblast of lung](/details-cell/CL2000093) and its role in RNA splicing, [RNF113A](/details-gene/7737) may regulate fibroblast activation and extracellular matrix deposition by controlling the alternative splicing of key profibrotic genes (e.g., collagen, fibronectin). Its dysregulation could be a contributing factor in pulmonary fibrosis. 2. Based on its function in negatively regulating chemokine signaling and its expression in cytotoxic lymphocytes, [RNF113A](/details-gene/7737) may act as a crucial checkpoint to prevent excessive immune cell activation and tissue damage. It could achieve this by ubiquitinating and promoting the degradation of chemokine receptors or downstream signaling adaptors. **Key Experiment:** To test the second hypothesis, one could use CRISPR-Cas9 to knock out [RNF113A](/details-gene/7737) in primary human [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050)s. A comparative study between knockout and wild-type T cells could then be performed. The key readouts would include: * A transwell migration assay to assess chemotactic responses to specific chemokines (e.g., CXCL9, CXCL10). An increased migration rate in knockout cells would support a role as a negative regulator. * Immunoprecipitation of the relevant chemokine receptor (e.g., CXCR3) followed by western blotting for ubiquitin to determine if RNF113A directly mediates its ubiquitination upon ligand binding. * Phosphoproteomic analysis post-chemokine stimulation to map downstream signaling changes resulting from [RNF113A](/details-gene/7737) loss. **Therapeutic Potential:** The critical role of [RNF113A](/details-gene/7737) in normal development, as evidenced by its association with X-linked syndromes ([300951](https://omim.org/entry/300951)), suggests that systemic inhibition may be associated with high toxicity. However, its specific functions present opportunities for targeted therapeutic intervention. As a negative regulator of immune signaling, selective **inhibition** of RNF113A could be explored as a strategy to enhance T-cell infiltration and activity in the tumor microenvironment, potentially synergizing with existing immunotherapies. Conversely, if its role in fibroblasts is protective against fibrosis, strategies aimed at **activation** or stabilization of RNF113A function could be beneficial in treating fibrotic lung diseases. Due to its intracellular and nuclear localization, any therapeutic approach would likely rely on small molecule modulators rather than biologics.

Genular Protein ID: 1038231579

Symbol: R113A_HUMAN

Name: E3 ubiquitin-protein ligase RNF113A

UniProtKB Accession Codes:

O15541 B2RBR7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 EMDB 6 Ensembl 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9224902

Title: Identification of a new member (ZNF183) of the Ring finger gene family in Xq24-25.

PubMed ID: 9224902

DOI: 10.1016/s0378-1119(97)00108-x

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 17487921

Title: Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line.

PubMed ID: 17487921

DOI: 10.1002/elps.200600782

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 22365833

Title: Dynamic protein-protein interaction wiring of the human spliceosome.

PubMed ID: 22365833

DOI: 10.1016/j.molcel.2011.12.034

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 25612912

Title: A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A.

PubMed ID: 25612912

DOI: 10.1136/jmedgenet-2014-102418

PubMed ID: 28978524

Title: RING finger protein 113A regulates C-X-C chemokine receptor type 4 stability and signaling.

PubMed ID: 28978524

DOI: 10.1152/ajpcell.00193.2017

PubMed ID: 29144457

Title: A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair.

PubMed ID: 29144457

DOI: 10.1038/nature24484

PubMed ID: 29361316

Title: Structure and Conformational Dynamics of the Human Spliceosomal Bact Complex.

PubMed ID: 29361316

DOI: 10.1016/j.cell.2018.01.010

PubMed ID: 29360106

Title: Structure of the human activated spliceosome in three conformational states.

PubMed ID: 29360106

DOI: 10.1038/cr.2018.14

PubMed ID: 33509932

Title: Structure of the activated human minor spliceosome.

PubMed ID: 33509932

DOI: 10.1126/science.abg0879

Sequence Information:

  • Length: 343
  • Mass: 38787
  • Checksum: F76E28037A6FF78B
  • Sequence:
    • MAEQLSPGKA VDQVCTFLFK KPGRKGAAGR RKRPACDPEP GESGSSSDEG CTVVRPEKKR 
VTHNPMIQKT RDSGKQKAAY GDLSSEEEEE NEPESLGVVY KSTRSAKPVG PEDMGATAVY 
ELDTEKERDA QAIFERSQKI QEELRGKEDD KIYRGINNYQ KYMKPKDTSM GNASSGMVRK 
GPIRAPEHLR ATVRWDYQPD ICKDYKETGF CGFGDSCKFL HDRSDYKHGW QIERELDEGR 
YGVYEDENYE VGSDDEEIPF KCFICRQSFQ NPVVTKCRHY FCESCALQHF RTTPRCYVCD 
QQTNGVFNPA KELIAKLEKH RATGEGGASD LPEDPDEDAI PIT