SPSB1 Gene

Name	splA/ryanodine receptor domain and SOCS box containing 1
Description	Enables ubiquitin-like ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPSB1, a SPRY domain‐containing SOCS box protein, has emerged as a versatile E3 ubiquitin ligase adaptor implicated in regulating tumor recurrence. In breast cancer models, SPSB1 is spontaneously upregulated during mammary tumor recurrence and is both necessary and sufficient to promote recurrence by protecting cells from apoptosis induced by HER2/neu pathway inhibition or chemotherapy through the potentiation of c‐MET signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in tumor recurrence, SPSB1 functions as a key negative regulator within the transforming growth factor‑β (TGF‑β) signaling pathway. It exerts this effect by directly interacting with the TGF‑β type II receptor at the cell membrane via its Spry domain, thereby enhancing the receptor’s ubiquitination and degradation. The resultant reduction in receptor levels contributes to attenuated TGF‑β signaling, which in turn affects tumor cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSPSB1 also plays a crucial role in modulating alternative splicing in response to extracellular signals. Epidermal growth factor (EGF) signaling upregulates SPSB1, which then recruits Elongin B/C-Cullin complexes to conjugate lysine‑29–linked polyubiquitin chains onto the splicing regulator hnRNP A1. This post-translational modification of hnRNP A1 drives splicing changes—such as the upregulation of the Rac1b isoform—thereby promoting cell motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn ovarian cancer cells, SPSB1 contributes to enhanced cell proliferation and migration by targeting the cell cycle inhibitor p21. SPSB1 interacts directly with p21 to accelerate its ubiquitin-mediated proteasomal degradation, leading to reduced p21 levels, increased cell viability, and diminished apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, SPSB1 has been identified as a regulator of circadian rhythmicity. Along with its paralog SPSB4, SPSB1 interacts with the nuclear receptor RevErbα to facilitate its ubiquitination and degradation. This regulation of RevErbα stability contributes to the proper timing of the circadian clock, underlining a novel mechanism by which the ubiquitin proteasome system can influence circadian periodicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, SPSB1 is pivotal in dampening innate immune responses. It acts as a negative regulator of NF‑κB activation by associating with the transcription factor p65. Through this interaction, SPSB1 limits the inflammatory transcriptional program—without affecting other signaling pathways such as those driven by IRF‑3, AP‑1, or STATs—resulting in reduced cytokine production in response to various immune stimuli."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yi Feng, Tien-Chi Pan, Dhruv K Pant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPSB1 promotes breast cancer recurrence by potentiating c-MET signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-13-0548"}], "href": "https://doi.org/10.1158/2159-8290.CD-13-0548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24786206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24786206"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sheng Liu, Thao Nheu, Rodney Luwor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPSB1, a Novel Negative Regulator of the Transforming Growth Factor-β Signaling Pathway Targeting the Type II Receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.607184"}], "href": "https://doi.org/10.1074/jbc.M114.607184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26032413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26032413"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Feng Wang, Xing Fu, Peng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPSB1-mediated HnRNP A1 ubiquitylation regulates alternative splicing and cell migration in EGF signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2017.7"}], "href": "https://doi.org/10.1038/cr.2017.7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28084329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28084329"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marianne Burbage, Francesca Gasparrini, Shweta Aggarwal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.26556"}], "href": "https://doi.org/10.7554/eLife.26556"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29337666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29337666"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tsedey Mekbib, Ting-Chung Suen, Aisha Rollins-Hairston, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The E3 Ligases Spsb1 and Spsb4 Regulate RevErbα Degradation and Circadian Period."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Rhythms (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0748730419878036"}], "href": "https://doi.org/10.1177/0748730419878036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31607207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31607207"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Iliana Georgana, Carlos Maluquer de Motes "}, {"type": "b", "children": [{"type": "t", "text": "Cullin-5 Adaptor SPSB1 Controls NF-κB Activation Downstream of Multiple Signaling Pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2019.03121"}], "href": "https://doi.org/10.3389/fimmu.2019.03121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32038638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32038638"}]}]}]}
Synonyms	SSB-1
Proteins	SPSB1_HUMAN
NCBI Gene ID	80176
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SPSB1 has 7,427 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for SPSB1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SPSB1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SPSB1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPSB1 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 SPSB1 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 SPSB1 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 SPSB1 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 SPSB1 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 SPSB1 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 SPSB1 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 SPSB1 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 SPSB1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SPSB1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPSB1 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 SPSB1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SPSB1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPSB1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SPSB1 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 SPSB1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SPSB1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SPSB1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SPSB1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SPSB1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SPSB1 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 SPSB1 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 SPSB1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SPSB1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SPSB1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SPSB1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SPSB1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SPSB1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SPSB1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SPSB1 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 SPSB1 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 SPSB1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SPSB1 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 SPSB1 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 SPSB1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SPSB1 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 SPSB1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SPSB1 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 SPSB1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.