Details for: SHISA3

Gene ID: 152573

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: SHISA3

Ensembl ID: ENSG00000178343

Description: shisa family member 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 8.08
    rCSI 7.46%
    PRS 99.26
  • mesodermal cell CL0000222
    CSI 7.86
    rCSI 9.43%
    PRS 99.25
  • myofibroblast cell CL0000186
    CSI 7.45
    rCSI 10.32%
    PRS 98.16
  • mesenchymal cell CL0008019
    CSI 4.15
    rCSI 10.53%
    PRS 98.3
  • podocyte CL0000653
    CSI 1.56
    rCSI 6.93%
    PRS 98.63
  • stromal cell CL0000499
    CSI 1.48
    rCSI 4.16%
    PRS 98.09
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.16
    rCSI 12.26%
    PRS 97.43
  • mesenchymal stem cell CL0000134
    CSI 0.79
    rCSI 8.66%
    PRS 99.17

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.

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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 [SHISA3](/details-gene/152573) (shisa family member 3) is a protein-coding gene located on chromosome 4p13. It encodes a protein that localizes to the [endoplasmic reticulum membrane](/details-cell/GO:0005789) and is implicated in [protein binding](/details-cell/GO:0005515) and the [negative regulation of canonical wnt signaling pathway](/details-cell/GO:0090090). Expression data from the **Overall** context indicates that [SHISA3](/details-gene/152573) is a significant gene in cells of both myeloid and mesenchymal lineages, with its highest significance observed in [myeloid leukocyte](/details-cell/CL0000766), [mesodermal cell](/details-cell/CL0000222), and [myofibroblast cell](/details-cell/CL0000186). This expression pattern, combined with its known function, suggests a potential role in modulating immune cell development and tissue remodeling processes like fibrosis through the Wnt signaling cascade. The characterization of this gene was advanced by large-scale cDNA projects such as the Mammalian Gene Collection [Link](https://doi.org/10.1101/gr.2596504). ## Cellular Roles and Expression Landscape In the **Overall** biological context, [SHISA3](/details-gene/152573) expression is most significant in cell populations associated with immunity and structural tissue, suggesting a dual role in these systems. The highest significance score is found in [myeloid leukocyte](/details-cell/CL0000766) (CSI: 8.08), indicating a prominent role within this broad class of immune cells. Its significance extends to several cell types of the mesenchymal lineage, including [mesodermal cell](/details-cell/CL0000222) (CSI: 7.86), [myofibroblast cell](/details-cell/CL0000186) (CSI: 7.45), [mesenchymal cell](/details-cell/CL0008019) (CSI: 4.15), and [mesenchymal stem cell](/details-cell/CL0000134) (CSI: 0.79). This pattern suggests that [SHISA3](/details-gene/152573) may be involved in fundamental processes common to these cells, such as differentiation, activation, or maintenance of lineage identity. Additionally, notable expression is observed in specialized cells like the renal [podocyte](/details-cell/CL0000653) (CSI: 1.56) and [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849) (CSI: 1.16), hinting at specific functions within the kidney. The collective expression profile points towards [SHISA3](/details-gene/152573) being a key regulator in cell fate decisions and functional modulation within myeloid and mesenchymal compartments. ## Pathways and Molecular Function The functional annotations for [SHISA3](/details-gene/152573) provide a clear molecular basis for its cellular roles. It is classified as a component of the [endoplasmic reticulum membrane](/details-cell/GO:0005789), where it is involved in [protein binding](/details-cell/GO:0005515). The most salient annotated biological process is the [negative regulation of canonical wnt signaling pathway](/details-cell/GO:0090090). The Wnt pathway is a critical signaling cascade that governs cell proliferation, differentiation, and fate determination in numerous tissues. The role of [SHISA3](/details-gene/152573) as an inhibitor of this pathway is highly consistent with its expression profile. For instance, its high significance in [myeloid leukocyte](/details-cell/CL0000766) suggests it may act as a brake on Wnt-driven proliferation or differentiation during hematopoiesis. Similarly, its expression in [mesenchymal stem cell](/details-cell/CL0000134) and [myofibroblast cell](/details-cell/CL0000186) indicates a potential role in controlling cell fate choices and fibrotic processes, which are often dysregulated by aberrant Wnt signaling. ## Research Directions The specific expression pattern of [SHISA3](/details-gene/152573) and its function as a Wnt signaling inhibitor present several avenues for future research, particularly concerning its role in tissue fibrosis and immune regulation. **Proposed Testable Hypotheses:** 1. **[SHISA3](/details-gene/152573) acts as an anti-fibrotic factor by suppressing Wnt-mediated activation of myofibroblasts.** The high expression in [myofibroblast cell](/details-cell/CL0000186) suggests [SHISA3](/details-gene/152573) may function to restrain their pro-fibrotic activities. Downregulation of [SHISA3](/details-gene/152573) in response to tissue injury could be a key step that permits myofibroblast activation and extracellular matrix deposition, contributing to pathological fibrosis. 2. **[SHISA3](/details-gene/152573) modulates myeloid cell differentiation and inflammatory responses.** Given its high significance in [myeloid leukocyte](/details-cell/CL0000766), [SHISA3](/details-gene/152573) could be a critical checkpoint in myelopoiesis. Its loss may skew differentiation towards a pro-inflammatory myeloid phenotype by disinhibiting the Wnt pathway, potentially impacting the progression of inflammatory diseases. **Suggested Experimental Approach:** To test the hypothesis that [SHISA3](/details-gene/152573) is an anti-fibrotic factor (Hypothesis 1), an *in vitro* study could be performed. Primary human fibroblasts (e.g., from lung or kidney) would be cultured and transduced with shRNA or a CRISPR-Cas9 system to achieve stable knockdown or knockout of [SHISA3](/details-gene/152573). Control and [SHISA3](/details-gene/152573)-deficient cells would then be treated with a pro-fibrotic stimulus, such as TGF-β. The impact would be assessed by measuring key endpoints: * **Myofibroblast differentiation:** Quantify expression of alpha-smooth muscle actin (α-SMA) and collagen type I (COL1A1) via qPCR and Western blotting. * **Wnt pathway activity:** Measure the activation of the canonical Wnt pathway using a TCF/LEF luciferase reporter assay. An enhanced pro-fibrotic response and increased Wnt signaling in [SHISA3](/details-gene/152573)-deficient cells would strongly support its role as an endogenous inhibitor of fibrosis. **Therapeutic Potential:** If [SHISA3](/details-gene/152573) is confirmed to be an endogenous anti-fibrotic factor, it represents an attractive therapeutic target. The therapeutic strategy would focus on **activation** or augmentation of its function rather than inhibition. For diseases characterized by excessive fibrosis, such as idiopathic pulmonary fibrosis (IPF) or chronic kidney disease, developing strategies to increase [SHISA3](/details-gene/152573) expression or activity could be beneficial. As it is a membrane protein, this could be challenging with small molecules, but approaches like gene therapy or administration of recombinant protein mimetics could be explored to restore this natural brake on the fibrotic process.

Genular Protein ID: 1249525086

Symbol: SHSA3_HUMAN

Name: Protein shisa-3 homolog

UniProtKB Accession Codes:

A0PJX4 A0PJX3 Q96EQ5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 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 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 238
  • Mass: 25832
  • Checksum: 8469E3758F61D22C
  • Sequence:
    • MRALLALCLL LGWLRWGPAG AQQSGEYCHG WVDVQGNYHE GFQCPEDFDT LDATICCGSC 
ALRYCCAAAD ARLEQGGCTN DRRELEHPGI TAQPVYVPFL IVGSIFIAFI ILGSVVAIYC 
CTCLRPKEPS QQPIRFSLRS YQTETLPMIL TSTSPRAPSR QSSTATSSSS TGGSIRRFSF 
ARAEPGCLVP SPPPPYTTSH SIHLAQPSGF LVSPQYFAYP LQQEPPLPGK SCPDFSSS