Details for: ASB5

Gene ID: 140458

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: ASB5

Ensembl ID: ENSG00000164122

Description: ankyrin repeat and SOCS box containing 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • fast muscle cell CL0000190
    CSI 6.22
    rCSI 24.32%
    PRS 97.6
  • ependymal cell CL0000065
    CSI 3.31
    rCSI 6.72%
    PRS 96.83
  • skeletal muscle satellite stem cell CL0008011
    CSI 1.88
    rCSI 8.39%
    PRS 99.92
  • slow muscle cell CL0000189
    CSI 1.56
    rCSI 20.75%
    PRS 96.9
  • cell of skeletal muscle CL0000188
    CSI 0.95
    rCSI 10.28%
    PRS 98.35

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 Ankyrin repeat and SOCS box containing 5 ([ASB5](/details-gene/140458)) is a protein-coding gene located on chromosome 4q34.2. As a member of the ASB family, it contains a SOCS box domain, suggesting it functions as a component of an E3 ubiquitin ligase complex. Functional annotations strongly link [ASB5](/details-gene/140458) to protein ubiquitination, catabolism, and pathways of the adaptive immune system, particularly MHC class I antigen processing and presentation. **Overall**, expression analysis reveals its highest significance and abundance not in immune cells, but predominantly in muscle lineage cells, including [fast muscle cell](/details-cell/CL0000190) and [skeletal muscle satellite stem cell](/details-cell/CL0008011), suggesting a specialized role in muscle physiology. ## Cellular Roles and Expression Landscape The expression profile of [ASB5](/details-gene/140458) highlights its primary role within the musculoskeletal system. - **Overall Context:** Analysis across diverse human tissues indicates that [ASB5](/details-gene/140458) is a gene of particularly high significance in muscle cells. It is most prominent in [fast muscle cell](/details-cell/CL0000190) (CSI: 6.22), which is responsible for rapid, powerful contractions. Its significance is also high in [skeletal muscle satellite stem cell](/details-cell/CL0008011) (CSI: 1.88) and [slow muscle cell](/details-cell/CL0000189) (CSI: 1.56), indicating a potential role in both muscle maintenance, regeneration, and function. - **Other Cell Types:** Notably, [ASB5](/details-gene/140458) also shows significant expression in [ependymal cell](/details-cell/CL0000065) (CSI: 3.31), a type of glial cell lining the ventricles of the brain. This suggests a secondary, though less characterized, function outside of the muscle system. ## Pathways and Molecular Function [ASB5](/details-gene/140458) is annotated as a cytosolic protein ([GO:0005829](https://www.ebi.ac.uk/QuickGO/term/GO:0005829)) involved in intracellular signaling and protein turnover. Its SOCS box domain implicates it in forming an E3 ubiquitin ligase complex, which targets substrate proteins for proteasomal degradation. This is consistent with its annotated involvement in [protein ubiquitination](/ontology-term/GO0016567) and the [positive regulation of protein catabolic process](/ontology-term/GO0045732). A striking feature of its functional profile is its strong association with immune system pathways. Reactome analysis places [ASB5](/details-gene/140458) in the [Adaptive immune system](/pathway/R-HSA-1280218) pathway, specifically in processes related to [Class i mhc mediated antigen processing & presentation](/pathway/R-HSA-983169) and [Antigen processing: ubiquitination & proteasome degradation](/pathway/R-HSA-983168). This suggests that while highly expressed in muscle, its function may be to facilitate the processing of endogenous proteins for surveillance by the immune system, a critical process for detecting viral infections or cellular transformation within muscle tissue. Its role also extends to broader protein metabolism ([R-HSA-392499](https://reactome.org/content/detail/R-HSA-392499)) and modification ([R-HSA-597592](https://reactome.org/content/detail/R-HSA-597592)). ## Research Directions The juxtaposition of [ASB5](/details-gene/140458)'s immune-related functional annotations with its muscle-specific expression profile presents several intriguing avenues for future research. **Proposed Hypotheses:** 1. [ASB5](/details-gene/140458) functions as a key regulator of protein turnover specific to muscle homeostasis and atrophy. It may target specific contractile or structural proteins for degradation, playing a critical role in muscle remodeling in response to exercise, injury, or disease states like sarcopenia. 2. In muscle cells, [ASB5](/details-gene/140458) is a specialized component of the antigen-presenting machinery, facilitating the ubiquitination and degradation of endogenous or pathogen-derived proteins for loading onto MHC class I molecules. This role may become particularly important during inflammatory myopathies or viral infections of muscle tissue. **Suggested Experimental Approach:** To test the hypothesis that [ASB5](/details-gene/140458) is involved in antigen presentation in muscle, the following experiment could be performed: - A stable knockout of [ASB5](/details-gene/140458) could be generated in a murine myoblast cell line (e.g., C2C12) using CRISPR-Cas9. - These knockout cells and wild-type controls would be differentiated into myotubes and then treated with interferon-gamma (IFN-γ) to upregulate the antigen presentation machinery. - Following stimulation, MHC class I molecules would be immuno-precipitated from both cell types, and the bound peptide repertoire would be analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). - A significant alteration in the diversity or abundance of presented peptides in the [ASB5](/details-gene/140458) knockout cells would provide direct evidence for its role in the muscle immunopeptidome. **Therapeutic Potential:** As a component of an E3 ligase, [ASB5](/details-gene/140458) is a potentially druggable target. - **Inhibition:** If [ASB5](/details-gene/140458) is validated as a key driver of muscle protein degradation, its inhibition could represent a novel therapeutic strategy to combat muscle wasting (atrophy) associated with aging, cancer cachexia, or prolonged disuse. Small molecule inhibitors targeting the substrate-binding ankyrin repeats or the SOCS box interaction domain could be developed. - **Modulation:** In the context of autoimmune diseases like polymyositis, where aberrant antigen presentation by muscle cells is implicated, modulating [ASB5](/details-gene/140458) activity could potentially alter the presentation of autoantigens and dampen the autoimmune response. However, given its high expression in healthy muscle, any therapeutic approach would need to carefully consider potential on-target toxicities.

Genular Protein ID: 1179585641

Symbol: ASB5_HUMAN

Name: Ankyrin repeat and SOCS box protein 5

UniProtKB Accession Codes:

Q8WWX0 Q8N7B5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 4 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 3 SMART 2 SMR 1 STRING 1 SUPFAM 2 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 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: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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

Sequence Information:

  • Length: 329
  • Mass: 36341
  • Checksum: 966B823CED8A8B71
  • Sequence:
    • MSVLEENRPF AQQLSNVYFT ILSLFCFKLF VKISLAILSH FYIVKGNRKE AARIAAEFYG 
VTQGQGSWAD RSPLHEAASQ GRLLALRTLL SQGYNVNAVT LDHVTPLHEA CLGDHVACAR 
TLLEAGANVN AITIDGVTPL FNACSQGSPS CAELLLEYGA KAQLESCLPS PTHEAASKGH 
HECLDILISW GIDVDQEIPH LGTPLYVACM SQQFHCIWKL LYAGADVQKG KYWDTPLHAA 
AQQSSTEIVN LLLEFGADIN AKNTELLRPI DVATSSSMVE RILLQHEATP SSLYQLCRLC 
IRSYIGKPRL HLIPQLQLPT LLKNFLQYR