Details for: FBXL6

Gene ID: 26233

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: FBXL6

Ensembl ID: ENSG00000182325

Description: F-box and leucine rich repeat protein 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intestine goblet cell CL0019031
    CSI 3.75
    rCSI 3.33%
    PRS 97.78
  • cerebral cortex endothelial cell CL1001602
    CSI 2.8
    rCSI 4.85%
    PRS 96.91
  • colon epithelial cell CL0011108
    CSI 2.64
    rCSI 2.77%
    PRS 98.01
  • colonocyte CL1000347
    CSI 2.58
    rCSI 3.7%
    PRS 97.93
  • ependymal cell CL0000065
    CSI 2.2
    rCSI 4.47%
    PRS 91.79
  • endothelial cell of lymphatic vessel CL0002138
    CSI 1.86
    rCSI 3.68%
    PRS 98.15

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 [FBXL6](/details-gene/26233) (F-box and leucine rich repeat protein 6) is a protein-coding gene located on chromosome 8q24.3. Functionally, it is characterized as a component of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex, which targets specific proteins for proteasomal degradation ([Link](https://doi.org/10.1016/s0960-9822(00)80020-2)). This role in [proteolysis](/details-cell/GO:0006508) and protein turnover is critical for cellular regulation. Expression data indicates that [FBXL6](/details-gene/26233) is a significant gene in various epithelial and endothelial cell types, with particularly high significance in [intestine goblet cells](/details-cell/CL0019031), [colonocytes](/details-cell/CL1000347), and [cerebral cortex endothelial cells](/details-cell/CL1001602), suggesting a key role in the maintenance and function of mucosal barriers and vascular tissues. ## Cellular Roles and Expression Landscape The expression profile of [FBXL6](/details-gene/26233) highlights its importance in specific cellular contexts, primarily within epithelial and endothelial lineages. **Overall**, the gene shows its highest significance in the gastrointestinal tract, including [intestine goblet cells](/details-cell/CL0019031) (CSI: 3.75), [colon epithelial cells](/details-cell/CL0011108) (CSI: 2.64), and [colonocytes](/details-cell/CL1000347) (CSI: 2.58). This strong and specific expression pattern suggests a specialized function in regulating protein homeostasis in cells responsible for nutrient absorption, mucus secretion, and maintaining the intestinal barrier. Beyond the gut, [FBXL6](/details-gene/26233) is also a significant marker in vascular and neural-associated cells. Its high significance in [cerebral cortex endothelial cells](/details-cell/CL1001602) (CSI: 2.80) and [endothelial cells of lymphatic vessels](/details-cell/CL0002138) (CSI: 1.86) points towards a potential role in regulating vascular integrity, transport, or angiogenesis. Additionally, its expression in [ependymal cells](/details-cell/CL0000065) (CSI: 2.20), which line the ventricles of the brain, may indicate involvement in the maintenance of the cerebrospinal fluid barrier. The collective expression pattern points to a role for [FBXL6](/details-gene/26233) in the function of cellular barriers across different organ systems. ## Pathways and Molecular Function [FBXL6](/details-gene/26233) functions as a substrate-recognition component of an E3 ubiquitin ligase complex. Its molecular function is defined by [protein binding](/details-cell/GO:0005515) and [ubiquitin-protein transferase activity](/details-cell/GO:0004842), which are central to its role within the [Scf ubiquitin ligase complex](/details-cell/GO:0019005). This complex mediates the ubiquitination of target proteins, marking them for destruction by the proteasome. The primary biological process associated with [FBXL6](/details-gene/26233) is the [Scf-dependent proteasomal ubiquitin-dependent protein catabolic process](/details-cell/GO:0031146). This pathway is crucial for the timely degradation of regulatory proteins involved in cell cycle progression, signal transduction, and transcription. Given its high expression in metabolically active and high-turnover cells like intestinal epithelium and endothelium, the protein degradation pathway mediated by [FBXL6](/details-gene/26233) is likely essential for maintaining cellular homeostasis and responding to external stimuli in these dynamic tissue environments. The gene was initially identified as part of a large-scale characterization of human F-box proteins and full-length cDNAs ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)). ## Research Directions The specific substrates of [FBXL6](/details-gene/26233) are not yet well-defined, and understanding them is key to elucidating its precise biological roles. Based on its expression profile, several testable hypotheses can be proposed. 1. **Hypothesis 1:** In the intestine, [FBXL6](/details-gene/26233) may target proteins involved in mucus synthesis or secretion for degradation, thereby regulating the integrity and composition of the mucosal barrier. Dysregulation of [FBXL6](/details-gene/26233) in [intestine goblet cells](/details-cell/CL0019031) could contribute to the pathogenesis of inflammatory bowel disease (IBD) or colorectal cancer. 2. **Hypothesis 2:** Within the central nervous system, [FBXL6](/details-gene/26233) in [cerebral cortex endothelial cells](/details-cell/CL1001602) might regulate blood-brain barrier (BBB) permeability by controlling the turnover of tight junction proteins or transporters. Altered [FBXL6](/details-gene/26233) activity could impact BBB function in neurological disorders. **Experimental Approach:** To test the first hypothesis, a combination of *in vitro* and proteomic approaches could be employed. CRISPR-Cas9 could be used to knock out [FBXL6](/details-gene/26233) in human-derived intestinal organoids. The functional consequences could be assessed by measuring barrier integrity (e.g., FITC-dextran permeability assays) and quantifying mucus production via immunostaining for key mucins like MUC2. To identify its direct substrates, co-immunoprecipitation followed by mass spectrometry (IP-MS) could be performed in intestinal cell lines to pull down [FBXL6](/details-gene/26233)-associated proteins, revealing candidate targets for its ubiquitin ligase activity. **Therapeutic Potential:** As a component of an E3 ubiquitin ligase, [FBXL6](/details-gene/26233) is a potentially druggable target. E3 ligases are frequently implicated in cancer and inflammatory diseases by promoting the degradation of tumor suppressors or pro-inflammatory proteins. If [FBXL6](/details-gene/26233) is found to degrade a tumor suppressor in colon cancer, its **inhibition** could be a viable therapeutic strategy. Small molecule inhibitors designed to disrupt the interaction between the F-box protein and its substrate are an emerging class of therapeutics. However, its therapeutic utility is entirely dependent on the identification of its specific substrates and its role in disease pathology.

Genular Protein ID: 772748439

Symbol: FBXL6_HUMAN

Name: F-box and leucine-rich repeat protein 6

UniProtKB Accession Codes:

Q8N531 Q53G43 Q9H5W9 Q9UKC7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 4 GO 4 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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: 10531035

Title: Identification of a family of human F-box proteins.

PubMed ID: 10531035

DOI: 10.1016/s0960-9822(00)80020-2

Sequence Information:

  • Length: 539
  • Mass: 58558
  • Checksum: 8153184415203FB2
  • Sequence:
    • MAAPASRQVR RRARAAPRPR SAEDWWWDRL APRGSGYHLL QSDSMLLVLS EPGPARPRAQ 
RRASRRTPRQ PPRGPSAAAK PKAGLRSEAA AAPAPAPAPT PTPEEGPDAG WGDRIPLEIL 
VQIFGLLVAA DGPMPFLGRA ARVCRRWQEA ASQPALWHTV TLSSPLVGRP AKGGVKAEKK 
LLASLEWLMP NRFSQLQRLT LIHWKSQVHP VLKLVGECCP RLTFLKLSGC HGVTADALVM 
LAKACCQLHS LDLQHSMVES TAVVSFLEEA GSRMRKLWLT YSSQTTAILG ALLGSCCPQL 
QVLEVSTGIN RNSIPLQLPV EALQKGCPQL QVLRLLNLMW LPKPPGRGVA PGPGFPSLEE 
LCLASSTCNF VSNEVLGRLL HGSPNLRLLD LRGCARITPA GLQDLPCREL EQLHLGLYGT 
SDRLTLAKEG SPFLTQKWCH TLRELDLSGQ GFSEKDLEQA LAAFLSTPGG SHPALCSLNL 
RGTRVTPSTV SSVISGCPGL LYLNLESCRC LPRGLKRAYR GLEEVQWCLE QLLTSPSPS