SH3BGRL Gene

Name	SH3 domain binding glutamate-rich protein like
Description	Enables protein-RNA adaptor activity and ubiquitin-like ligase-substrate adaptor activity. Involved in positive regulation of cytoplasmic translational initiation and proteasome-mediated 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": "\nSH3BGRL has emerged as a context‐dependent regulator of tumor cell behavior. In v‑Rel–transformed fibroblasts, SH3BGRL expression is suppressed by direct binding of the v‑Rel oncogene to its promoter, and its co‑expression markedly reduces cell transformation. In acute myeloid leukemia (AML), diminished levels of SH3BGRL correlate with accelerated cell cycle progression, enhanced anti‑apoptotic responses, and therapy resistance, pointing to its tumor‐suppressive function in hematologic malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, in solid tumors such as breast cancer, SH3BGRL can adopt pro‑tumorigenic roles. In murine models, the adaptor protein functions as a robust activator of c‑Src; by binding to the kinase’s inactive, Tyr527‑phosphorylated form it promotes subsequent phosphorylation and downstream FAK, ERK, and AKT signaling, thereby fostering tumor cell invasion and metastasis. In clinical breast cancers, elevated SH3BGRL contributes to chemoresistance through enhanced autophagy—in part by associating with ribosomal subunits to upregulate the translation of PIK3C3 and stabilize ATG12—and further drives metastatic relapse by downregulating profilin 1, which leads to activation of AKT, NF‑κB, and WNT pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings underscore a dualistic nature of SH3BGRL—functioning as a tumor suppressor in certain hematologic contexts and as an oncogenic driver in select solid tumors—while also highlighting its potential utility as a diagnostic, prognostic, and therapeutic target. The divergent roles, including those influenced by point mutations that convert the human protein to a metastasis promoter, emphasize the importance of understanding SH3BGRL’s molecular context and post‑translational modifications when considering targeted cancer therapies.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S M Majid, A S Liss, M You, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The suppression of SH3BGRL is important for v-Rel-mediated transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209107"}], "href": "https://doi.org/10.1038/sj.onc.1209107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16186799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16186799"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Limei Xu, Mingming Zhang, Hui Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SH3BGRL as a novel prognostic biomarker is down-regulated in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Lymphoma (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/10428194.2017.1344843"}], "href": "https://doi.org/10.1080/10428194.2017.1344843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28679293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28679293"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaomin Chen, Fengqi Liu, Dade Rong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decitabine Enhances Acute Myeloid Leukemia Cell Apoptosis through SH3BGRL Upregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Agents Med Chem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1871520622666211228110630"}], "href": "https://doi.org/10.2174/1871520622666211228110630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34963436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34963436"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "H Wang, B Liu, A Q O Al-Aidaroos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual-faced SH3BGRL: oncogenic in mice, tumor suppressive in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.391"}], "href": "https://doi.org/10.1038/onc.2015.391"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26455318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26455318"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shaoyang Zhang, Xuemin Guo, Xiufeng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptor SH3BGRL promotes breast cancer metastasis through PFN1 degradation by translational STUB1 upregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-021-01970-8"}], "href": "https://doi.org/10.1038/s41388-021-01970-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34331014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34331014"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shaoyang Zhang, Xiufeng Liu, Saleh Abdulmomen Ali Mohammed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2021.2002108"}], "href": "https://doi.org/10.1080/15548627.2021.2002108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34870550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34870550"}]}]}]}
Synonyms	SH3BGR, HEL-S-115
Proteins	SH3L1_HUMAN
NCBI Gene ID	6451
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SH3BGRL has 8,467 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 114 datasets.

Click the + buttons to view associations for SH3BGRL from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SH3BGRL protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SH3BGRL 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 SH3BGRL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SH3BGRL 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 SH3BGRL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SH3BGRL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SH3BGRL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SH3BGRL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL 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 SH3BGRL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SH3BGRL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SH3BGRL gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SH3BGRL gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SH3BGRL 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 SH3BGRL gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SH3BGRL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SH3BGRL 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 SH3BGRL 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 SH3BGRL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SH3BGRL 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 SH3BGRL 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 SH3BGRL gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SH3BGRL 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 SH3BGRL from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SH3BGRL gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SH3BGRL gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.