Details for: RNF222

Gene ID: 643904

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: RNF222

Ensembl ID: ENSG00000189051

Description: ring finger protein 222

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • squamous epithelial cell CL0000076
    CSI 3.68
    rCSI 8.74%
    PRS 99.98

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 [RNF222](/details-gene/643904) is a protein-coding gene located on human chromosome 17p13.1, as identified in the initial sequencing of this chromosome [Link](https://doi.org/10.1038/nature04689). It encodes RING finger protein 222, a putative E3 ubiquitin ligase belonging to the extensive family of RING finger proteins. Functional annotations suggest that [RNF222](/details-gene/643904) is a membrane-associated protein with metal ion binding capabilities, consistent with the structural requirements of a RING domain. **Overall**, expression data indicate a highly specialized role for this gene, with its expression being a significant and defining feature almost exclusively of [squamous epithelial cell](/details-cell/CL0000076). ## Cellular Roles and Expression Landscape The expression profile of [RNF222](/details-gene/643904) is characterized by remarkable cellular specificity. **Overall** analysis reveals that the gene's expression is a significant characteristic of [squamous epithelial cell](/details-cell/CL0000076) (CSI: 3.68). These cells are the primary components of the epidermis and the linings of many internal cavities, where they form protective stratified layers. The high CSI score in this single cell type suggests that [RNF222](/details-gene/643904) is not a broadly expressed housekeeping gene but rather a specialist protein likely involved in establishing or maintaining the unique identity and function of squamous epithelia. Its role may be tied to processes such as differentiation, cell-cell adhesion, or the formation of the protective cornified envelope characteristic of these tissues. The absence of significant expression in other cell lineages underscores its highly restricted functional context within the epithelial barrier system. ## Pathways and Molecular Function The known functional annotations for [RNF222](/details-gene/643904) provide a framework for its potential molecular activities. Its classification within the [Metal ion binding](/details-go/GO:0046872) molecular function ([GO:0046872](https://www.ebi.ac.uk/QuickGO/term/GO:0046872)) is typical for RING finger proteins, which utilize zinc ions to stabilize a cross-brace motif critical for their E3 ubiquitin-protein ligase activity. As E3 ligases, these proteins are key regulators of the ubiquitin-proteasome system, targeting specific substrate proteins for degradation. Furthermore, its annotated localization to the [membrane](/details-go/GO:0016020) ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)) is particularly informative. This suggests that the ubiquitination activity of [RNF222](/details-gene/643904) is spatially restricted, likely targeting membrane-bound or membrane-associated proteins. In the context of its high expression in [squamous epithelial cell](/details-cell/CL0000076), [RNF222](/details-gene/643904) may regulate the turnover of cell surface receptors, adhesion molecules, or ion channels that are critical for epithelial barrier function and homeostasis. ## Research Directions The highly specific expression pattern and putative E3 ligase function of [RNF222](/details-gene/643904) suggest it is a critical, yet understudied, regulator of squamous epithelial biology. ### Proposed Hypotheses 1. **[RNF222](/details-gene/643904) functions as an E3 ubiquitin ligase that targets specific desmosomal or tight junction proteins for degradation, thereby modulating epithelial barrier integrity and cell adhesion dynamics during stratification.** Dysregulation of this process could contribute to skin blistering diseases or facilitate cancer cell invasion. 2. **The gene plays a role in the terminal differentiation of keratinocytes by ubiquitinating and clearing specific membrane proteins or signaling receptors whose functions are restricted to the basal proliferative layer.** This would allow for the orderly progression of cells toward a terminally differentiated, enucleated state. ### Experimental Approach To test the first hypothesis regarding its role in epithelial adhesion, one could employ a CRISPR-Cas9-based knockout of [RNF222](/details-gene/643904) in a human keratinocyte cell line, such as HaCaT. The impact on epithelial barrier function could be assessed using transepithelial electrical resistance (TEER) measurements in 2D cultures. To identify its direct substrates, proximity-dependent biotinylation (e.g., BioID) or co-immunoprecipitation followed by mass spectrometry could be performed on [RNF222](/details-gene/643904)-expressing keratinocytes. Subsequent western blot analysis could confirm changes in the ubiquitination status and total protein levels of candidate junctional proteins like desmogleins or claudins. ### Therapeutic Potential Given its exquisite specificity for [squamous epithelial cell](/details-cell/CL0000076), [RNF222](/details-gene/643904) presents an attractive profile for therapeutic targeting with potentially minimal off-target effects. In diseases characterized by excessive epithelial proliferation, such as squamous cell carcinoma, [RNF222](/details-gene/643904) could be a target for **inhibition** if it is found to degrade tumor-suppressor proteins. Its membrane association makes it potentially accessible to antibody-based therapies or small molecule inhibitors. Conversely, if its loss-of-function contributes to disease (e.g., impaired barrier function in atopic dermatitis), strategies for its **activation** or gene replacement could be considered.

Genular Protein ID: 2643963848

Symbol: RN222_HUMAN

Name: RING finger protein 222

UniProtKB Accession Codes:

A6NCQ9

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 EMBL 1 Ensembl 2 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 5 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 5 SIGNOR 1 SMART 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 220
  • Mass: 23767
  • Checksum: 67080B8736DBDD1B
  • Sequence:
    • MSEGESKDSS GSECPVCYEK FRDLEGASRT LSCGHVFCHD CLVKYLLSTR VDGQVQRTLV 
CPICRYVTFL SKKSSRWPSM LDKSSQTLAV PVGLPSVPPL DSLGHTNPLA ASSPAWRPPP 
GQARPPGSPG QSAQLPLDLL PSLPRESQIF VISRHGMPLG EQDSVLPRRS LAELSEASLA 
PRSARAFCCR SRALLLITLI AVVAVVAAIL PWVLLVRKQA