SH3RF1 Gene

HGNC Family	Zinc fingers
Name	SH3 domain containing ring finger 1
Description	This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rho GTPase Rac. Via the RING-finger, the encoded protein has been shown to function as an ubiquitin-protein ligase involved in protein sorting at the trans-Golgi network. The encoded protein may also act as a scaffold for the c-Jun N-terminal kinase signaling pathway, facilitating the formation of a functional signaling module. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSH3RF1, also known as POSH (Plenty of SH3 domains), is a multi‐functional scaffold protein endowed with E3 ubiquitin ligase activity that modulates diverse intracellular signaling pathways. Initial studies identified SH3RF1 as a Rac effector that assembles a signaling complex leading to the coordinated activation of the JNK MAP kinase cascade, nuclear translocation of NF‑κB, and induction of apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, SH3RF1 serves as a molecular hub that interacts with regulatory factors such as Akt2 and MLK3; disruption of its binding to Akt2 enhances MLK3 association and JNK activation, pointing to a role in fine‐tuning stress‐responsive signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \nMoreover, SH3RF1’s ubiquitin ligase activity is critical in other cellular contexts. In the setting of HIV‑1 biogenesis, SH3RF1 is essential for the proper targeting of viral Gag to the plasma membrane, where its RING finger–dependent ubiquitination activity is required for efficient virus release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its functionality extends further through interactions with intracellular trafficking mediators; for example, SH3RF1 has been shown to bind ALIX, an adaptor protein pivotal for vesicle budding and protein sorting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n \nIn control of plasma membrane protein composition, SH3RF1 can enhance the ubiquitination of specific targets such as the ROMK potassium channel, thereby promoting their internalization and turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In parallel, studies in Drosophila and human rheumatoid arthritis synovial fibroblasts reveal that higher levels of SH3RF1/POSH correlate with resistance to apoptosis, implicating it as a pro‐survival factor under certain stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n \nFinally, a yeast two-hybrid screening approach identified SH3RF1 as the most frequently recovered binding partner for the cytoplasmic tail of FAT1 cadherin, and functional studies demonstrated that SH3RF1 acts as a negative post-translational regulator of FAT1 by reducing its cell surface expression upon ubiquitination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N Tapon, K Nagata, N Lamarche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/17.5.1395"}], "href": "https://doi.org/10.1093/emboj/17.5.1395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9482736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9482736"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Claudia Figueroa, Samantha Tarras, Jennifer Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307357200"}], "href": "https://doi.org/10.1074/jbc.M307357200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14504284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14504284"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Iris Alroy, Shmuel Tuvia, Tsvika Greener, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0408717102"}], "href": "https://doi.org/10.1073/pnas.0408717102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15659549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15659549"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jörg Votteler, Elena Iavnilovitch, Orit Fingrut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2091-10-12"}], "href": "https://doi.org/10.1186/1471-2091-10-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19393081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19393081"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Manabu Tsuda, Reimi Kawaida, Kyoko Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POSH promotes cell survival in Drosophila and in human RASF cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2010.10.048"}], "href": "https://doi.org/10.1016/j.febslet.2010.10.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20974134"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20974134"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xinshi Wang, Xin Tian, Yong Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POSH participates in epileptogenesis by increasing the surface expression of the NMDA receptor: a promising therapeutic target for epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Expert Opin Ther Targets (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/14728222.2017.1394456"}], "href": "https://doi.org/10.1080/14728222.2017.1394456"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29057721"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29057721"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hao Chen, Juan Zhou, Lin Jiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Assessing the role of SH3RF1 and SH3RF2 polymorphisms in susceptibility to tuberculosis: A case-control study in the Han Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microb Pathog (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.micpath.2020.104567"}], "href": "https://doi.org/10.1016/j.micpath.2020.104567"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33129950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33129950"}]}]}]}
Synonyms	POSH, RNF142, SH3MD2
Proteins	SH3R1_HUMAN
NCBI Gene ID	57630
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SH3RF1 has 6,497 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 115 datasets.

Click the + buttons to view associations for SH3RF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SH3RF1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SH3RF1 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 SH3RF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SH3RF1 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 SH3RF1 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 SH3RF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SH3RF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SH3RF1 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 SH3RF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing SH3RF1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SH3RF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SH3RF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SH3RF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SH3RF1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SH3RF1 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 SH3RF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 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 SH3RF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SH3RF1 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 SH3RF1 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 SH3RF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SH3RF1 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 SH3RF1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SH3RF1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SH3RF1 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 SH3RF1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SH3RF1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.