SPSB3 Gene

Name splA/ryanodine receptor domain and SOCS box containing 3
Description Enables ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including negative regulation of cGAS/STING signaling pathway; negative regulation of epithelial to mesenchymal transition; and protein K48-linked ubiquitination. Part of Cul5-RING ubiquitin ligase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPSB3 acts as a substrate recognition component of E3 ubiquitin ligase complexes that promote targeted protein degradation. In one study, SPSB3 was shown to bind and mediate the polyubiquitination of the zinc-finger transcription factor SNAIL following its phosphorylation by GSK‑3β. This ubiquitin‐dependent degradation of SNAIL impairs the epithelial–mesenchymal transition (EMT), thereby inhibiting cancer cell stemness, motility, and ultimately tumor metastasis. Low levels of SPSB3 were linked to increased nodal metastasis, while high SPSB3 expression correlated with better overall prognosis in various cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn a separate investigation, SPSB3 was identified as the substrate receptor for the cullin‑RING ligase 5 (CRL5) complex that targets nuclear cyclic GMP‑AMP synthase (cGAS) for ubiquitination and proteasomal degradation. A conserved Asn–Asn (NN) motif at the cGAS C terminus was found to be critical for this interaction. The SPSB3‑mediated turnover of nuclear cGAS serves as a regulatory mechanism to prevent undue activation of innate immune responses by genomic DNA, thereby modulating type I interferon signalling and bolstering cell resistance to DNA virus infections."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these studies highlight the multifaceted role of SPSB3 in maintaining cellular homeostasis through precise protein turnover. By targeting SNAIL, SPSB3 acts as a suppressor of EMT and cancer metastasis, while its regulation of nuclear cGAS underlines its importance in modulating innate immune responses. These findings not only offer mechanistic insights into SPSB3 function but also underscore its potential as a therapeutic target in cancer and antiviral strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Y Liu, H Zhou, R Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPSB3 targets SNAIL for degradation in GSK-3β phosphorylation-dependent manner and regulates metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2017.370"}], "href": "https://doi.org/10.1038/onc.2017.370"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29059170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29059170"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pengbiao Xu, Ying Liu, Chong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-024-07112-w"}], "href": "https://doi.org/10.1038/s41586-024-07112-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38418882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38418882"}]}]}]}
Synonyms SSB3, C16ORF31
Proteins SPSB3_HUMAN
NCBI Gene ID 90864
API
Download Associations
Predicted Functions View SPSB3's ARCHS4 Predicted Functions.
Co-expressed Genes View SPSB3's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View SPSB3's ARCHS4 Predicted Functions.

Functional Associations

SPSB3 has 5,675 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 98 datasets.

Click the + buttons to view associations for SPSB3 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of SPSB3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of SPSB3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of SPSB3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of SPSB3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of SPSB3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of SPSB3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of SPSB3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of SPSB3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPSB3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of SPSB3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of SPSB3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CM4AI U2OS Cell Map Protein Localization Assemblies assemblies containing SPSB3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of SPSB3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing SPSB3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing SPSB3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing SPSB3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with SPSB3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with SPSB3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of SPSB3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with SPSB3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with SPSB3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with SPSB3 gene/protein from the curated CTD Gene-Disease Associations dataset.
DeepCoverMOA Drug Mechanisms of Action small molecule perturbations with high or low expression of SPSB3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by SPSB3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with SPSB3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with SPSB3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with SPSB3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with SPSB3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at SPSB3 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPSB3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of SPSB3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing SPSB3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with SPSB3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of SPSB3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing SPSB3 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of SPSB3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of SPSB3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of SPSB3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of SPSB3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of SPSB3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of SPSB3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving SPSB3 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving SPSB3 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving SPSB3 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2023 cellular components containing SPSB3 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing SPSB3 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by SPSB3 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by SPSB3 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of SPSB3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of SPSB3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with SPSB3 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of SPSB3 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of SPSB3 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of SPSB3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of SPSB3 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with SPSB3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for SPSB3 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of SPSB3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of SPSB3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of SPSB3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of SPSB3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of SPSB3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with SPSB3 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of SPSB3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of SPSB3 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of SPSB3 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of SPSB3 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain SPSB3 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of SPSB3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of SPSB3 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing SPSB3 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for SPSB3 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of SPSB3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of SPSB3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
Reactome Pathways 2024 pathways involving SPSB3 protein from the Reactome Pathways 2024 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of SPSB3 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of SPSB3 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of SPSB3 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of SPSB3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of SPSB3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at SPSB3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of SPSB3 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of SPSB3 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of SPSB3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of SPSB3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of SPSB3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of SPSB3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of SPSB3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of SPSB3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with SPSB3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with SPSB3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.