Details for: FBXL22

Gene ID: 283807

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: FBXL22

Ensembl ID: ENSG00000197361

Description: F-box and leucine rich repeat protein 22

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • myoepithelial cell CL0000185
    CSI 2.99
    rCSI 7.56%
    PRS 99.87
  • enteric smooth muscle cell CL0002504
    CSI 2.95
    rCSI 4.21%
    PRS 99.81
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.19
    rCSI 7.41%
    PRS 98.78
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.16
    rCSI 3.37%
    PRS 99.6

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

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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 [FBXL22](/details-gene/283807) is a protein-coding gene that encodes F-box and leucine-rich repeat protein 22, a component of the Skp1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Functionally, it is involved in [protein ubiquitination](/details-go/GO:0016567) and the subsequent [proteasome-mediated ubiquitin-dependent protein catabolic process](/details-go/GO:0043161). Expression data from the **Overall** context indicates that [FBXL22](/details-gene/283807) is a gene of high significance in various contractile cell lineages, including [myoepithelial cell](/details-cell/CL0000185), [enteric smooth muscle cell](/details-cell/CL0002504), and [regular ventricular cardiac myocyte](/details-cell/CL0002131). This expression pattern, combined with its established role in protein turnover, suggests a crucial function in maintaining protein homeostasis and structural integrity in muscle tissues. ## Cellular Roles and Expression Landscape The expression profile of [FBXL22](/details-gene/283807) highlights its specialized role in cells characterized by contractile machinery. **Overall**, it demonstrates high significance in [myoepithelial cell](/details-cell/CL0000185) (CSI: 2.99), [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 2.95), [regular ventricular cardiac myocyte](/details-cell/CL0002131) (CSI: 1.19), and [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 1.16). This consistent enrichment across cardiac muscle, smooth muscle, and myoepithelial cells strongly suggests a conserved function in the maintenance of the contractile apparatus. Research has confirmed that [FBXL22](/details-gene/283807) is a cardiac-enriched F-box protein essential for regulating the turnover of sarcomeric proteins and maintaining contractile function in vivo [Link](https://doi.org/10.1161/circresaha.112.271007). The specificity of its expression suggests that its primary biological impact is focused on muscle physiology. ## Pathways and Molecular Function The functional annotations for [FBXL22](/details-gene/283807) are highly consistent with a role in cellular protein quality control. As a key component of an E3 ubiquitin ligase complex, it possesses [ubiquitin protein ligase activity](/details-go/GO:0061630) and participates in the broader [metabolism of proteins](/details-pathway/R-HSA-392499). Its involvement in [antigen processing: ubiquitination & proteasome degradation](/details-pathway/R-HSA-983168) further underscores its role in the controlled degradation of intracellular proteins, a process fundamental to both immune surveillance and general cellular housekeeping. Crucially, the localization of the protein to the [Z disc](/details-go/GO:0030018), a critical structural component of the muscle sarcomere, directly links its molecular function to its cellular expression pattern. This cellular component annotation provides a mechanistic basis for its high significance in [regular ventricular cardiac myocyte](/details-cell/CL0002131) and other contractile cells. It suggests that [FBXL22](/details-gene/283807) specifically targets proteins within the sarcomere for ubiquitination, thereby playing a direct role in maintaining the structural and functional integrity of the muscle contraction unit [Link](https://doi.org/10.1161/circresaha.112.271007). ## Research Directions Given its established role in cardiac muscle, further investigation should focus on its function in other contractile tissues and its potential involvement in pathology. **Proposed Hypotheses:** 1. Dysregulation of [FBXL22](/details-gene/283807) activity contributes to the pathogenesis of specific inherited or acquired cardiomyopathies by disrupting the precise balance of sarcomeric protein turnover, leading to contractile dysfunction. 2. In smooth muscle, [FBXL22](/details-gene/283807) regulates the turnover of key proteins involved in calcium sensitization or actin-myosin cross-bridging, and its altered expression or function could be a contributing factor in diseases of vascular tone (e.g., hypertension) or gastrointestinal motility. **Experimental Approach:** To test the second hypothesis, a smooth muscle-specific conditional knockout of *Fbxl22* in a mouse model could be generated. These mice could then be phenotyped for abnormalities in blood pressure using tail-cuff plethysmography and for altered gut motility using a carmine red transit time assay. To identify the specific substrates of [FBXL22](/details-gene/283807) in this context, proteomic analysis (e.g., mass spectrometry) comparing protein ubiquitination profiles in aortic or intestinal smooth muscle tissue from knockout versus wild-type mice would be performed. This would reveal the downstream targets of [FBXL22](/details-gene/283807) and provide mechanistic insight into its role in smooth muscle physiology. **Therapeutic Potential:** [FBXL22](/details-gene/283807) represents a potential therapeutic target for muscle-related disorders. As loss of its function is known to be detrimental to cardiac contractility, therapeutic strategies for conditions like heart failure might focus on *enhancing* or *stabilizing* [FBXL22](/details-gene/283807) activity to improve protein quality control. Conversely, if its hyperactivity is implicated in a pathology characterized by excessive degradation of essential structural proteins, developing specific small-molecule inhibitors would be a viable strategy. Its relative specificity to muscle lineages makes it an attractive target, potentially minimizing off-target effects in other tissues.

Genular Protein ID: 2252256003

Symbol: FXL22_HUMAN

Name: F-box and leucine-rich protein 22

UniProtKB Accession Codes:

Q6P050

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 15520277

Title: Systematic analysis and nomenclature of mammalian F-box proteins.

PubMed ID: 15520277

DOI: 10.1101/gad.1255304

PubMed ID: 22972877

Title: F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that regulates sarcomeric protein turnover and is essential for maintenance of contractile function in vivo.

PubMed ID: 22972877

DOI: 10.1161/circresaha.112.271007

Sequence Information:

  • Length: 247
  • Mass: 27269
  • Checksum: 9966D98688B8FF26
  • Sequence:
    • MWPLLTMHIT QLNRECLLHL FSFLDKDSRK SLARTCSQLH DVFEDPALWS LLHFRSLTEL 
QKDNFLLGPA LRSLSICWHS SRVQVCSIED WLKSAFQRSI CSRHESLVND FLLRVCDRLS 
AVRSPRRREA PAPSSGTPIA VGPKSPRWGG PDHSEFADLR SGVTGARAAA RRGLGSLRAE 
RPSETPPAPG VSWGPPPPGA PVVISVKQEE GKQGRTGRRS HRAAPPCGFA RTRVCPPTFP 
GADAFPQ