SSH2 Gene

HGNC Family	Phosphatases
Name	slingshot protein phosphatase 2
Description	This gene encodes a protein tyrosine phosphatase that plays a key role in the regulation of actin filaments. The encoded protein dephosphorylates and activates cofilin, which promotes actin filament depolymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSlingshot 2 (SSH2) is a key regulator of actin dynamics through its role in activating cofilin via dephosphorylation, which in turn modulates cell motility. In human keratinocytes, integrin α6β4 signaling through Rac1 and subsequent regulation by 14-3-3 proteins modulate SSH2 activity, ensuring proper cofilin function, actin reorganization, and the assembly of laminin‐332 tracks that dictate directional migration. In neutrophils, SSH2 functions as a crucial signaling effector downstream of G protein–coupled receptor (GPCR) activation via a PLC/PKC/PKD cascade, where it regulates cofilin phosphorylation and thereby coordinates the rapid cytoskeletal remodeling required for effective chemotaxis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of tumor biology, SSH2 has emerged as a potential therapeutic target. RNA interference studies have demonstrated that knockdown of SSH2 induces apoptotic cell death and cell cycle arrest specifically in FLCN-deficient cells, as observed in models of Birt–Hogg–Dubé syndrome, underscoring its relevance in cancer pathogenesis. Conversely, mutation analysis in microsatellite instable (MSI‐high) cancers suggests that while several dual‐specificity phosphatase genes contain repeat sequences, direct mutation of SSH2 is not a common event, hinting that its function is more likely deregulated via posttranslational or signaling network alterations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemically, SSH2 is regulated by an auto-inhibitory mechanism mediated by its N-terminal region. Structural studies reveal that binding to F-actin triggers significant conformational changes that relieve this auto-inhibition, thereby reactivating the phosphatase activity essential for cofilin dephosphorylation. This allosteric control ensures that SSH2’s enzymatic function is tightly coupled to the state of the actin cytoskeleton, enabling precise spatiotemporal regulation of filament turnover during cellular migration and dynamic remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristina Kligys, Jessica N Claiborne, Phillip J DeBiase, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707041200"}], "href": "https://doi.org/10.1074/jbc.M707041200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17848544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17848544"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xuehua Xu, Nidhi Gera, Hongyan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPCR-mediated PLCβγ/PKCβ/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E14-05-0982"}], "href": "https://doi.org/10.1091/mbc.E14-05-0982"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25568344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25568344"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sang Yong Song, Mi Ran Kang, Nam Jin Yoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "APMIS (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0463.2010.02612.x"}], "href": "https://doi.org/10.1111/j.1600-0463.2010.02612.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20477815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20477815"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "X Lu, U Boora, L Seabra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of Slingshot 2 (SSH2) serine phosphatase induces Caspase3 activation in human carcinoma cell lines with the loss of the Birt-Hogg-Dubé tumour suppressor gene (FLCN)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.27"}], "href": "https://doi.org/10.1038/onc.2013.27"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23416984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23416984"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Duxiao Yang, Peng Xiao, Qing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.004175"}], "href": "https://doi.org/10.1074/jbc.RA118.004175"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30154244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30154244"}]}]}]}
Synonyms	SSH-2, SSH-2L
Proteins	SSH2_HUMAN
NCBI Gene ID	85464
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SSH2 has 7,131 functional associations with biological entities spanning 9 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, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for SSH2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SSH2 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SSH2 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 SSH2 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 SSH2 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 SSH2 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 SSH2 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 SSH2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SSH2 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 SSH2 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 SSH2 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 SSH2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SSH2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SSH2 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 SSH2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SSH2 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 SSH2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SSH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SSH2 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 SSH2 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 SSH2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SSH2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SSH2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SSH2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SSH2 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 SSH2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SSH2 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 SSH2 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 SSH2 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 SSH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SSH2 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 SSH2 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 SSH2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SSH2 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 SSH2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SSH2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SSH2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SSH2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing SSH2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SSH2 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 SSH2 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 SSH2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.