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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SH3BGRL
SH3 domain binding glutamate rich protein like
Chromosome X · Xq21.1
NCBI Gene: 6451Ensembl: ENSG00000131171.14HGNC: HGNC:10823UniProt: O75368
41PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-RNA adaptor activityubiquitin-like ligase-substrate adaptor activityproteasome-mediated ubiquitin-dependent protein catabolic processpositive regulation of cytoplasmic translational initiationAlzheimer diseaseParkinson diseaseneurodegenerative diseasemultiple sclerosis
✦AI Summary

SH3BGRL (SH3 domain binding glutamate rich protein like) functions as a multifunctional adapter protein with tumor suppressor activities in various cancers. The protein bridges proteins together or proteins with mRNAs and may function as a ubiquitin ligase-substrate adapter 1. SH3BGRL associates with translating cytoplasmic ribosomes, promoting specific mRNA expression through ribosomal protein interactions 12. In breast cancer, SH3BGRL promotes metastasis by enhancing STUB1 translation, leading to PFN1 degradation and activation of AKT, NF-kB, and WNT signaling pathways 1. Conversely, SH3BGRL exhibits tumor suppressor functions in hematologic malignancies, being downregulated in 62.37% of acute myeloid leukemia (AML) cases with poor prognosis 3. In AML, SH3BGRL expression correlates with positive therapeutic response and sensitizes cells to chemotherapy by promoting apoptosis 34. The protein is also suppressed by EZH2-mediated epigenetic mechanisms in lung cancer, where its overexpression inhibits cancer stem cell self-renewal and tumor progression 5. SH3BGRL expression patterns vary during zebrafish development, suggesting roles in neural system development and intestinal homeostasis 6. These findings indicate SH3BGRL has context-dependent oncogenic or tumor suppressor functions across different cancer types.

Sources cited
1
SH3BGRL functions as adapter protein bridging proteins/mRNAs, associates with ribosomes, and promotes breast cancer metastasis through PFN1 degradation
PMID: 34331014
2
SH3BGRL binds ribosomal subunits and enhances PIK3C3 translation efficiency
PMID: 34870550
3
SH3BGRL is downregulated in 62.37% of AML cases with poor prognosis and acts as tumor suppressor
PMID: 28679293
4
SH3BGRL expression correlates with positive therapeutic response in AML and sensitizes cells to chemotherapy
PMID: 34963436
5
EZH2 epigenetically suppresses SH3BGRL in lung cancer, where it inhibits cancer stem cell self-renewal
PMID: 33631674
6
SH3BGRL expression patterns in zebrafish development suggest roles in neural system and intestinal homeostasis
PMID: 27233781
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.32Weak
Parkinson diseaseOpen Targets
0.32Weak
lysosomal storage diseaseOpen Targets
0.32Weak
multiple sclerosisOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.32Weak
Abnormality of refractionOpen Targets
0.22Weak
neoplasmOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.10Suggestive
liver cancerOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
breast neoplasmOpen Targets
0.04Suggestive
liver and intrahepatic bile duct neoplasmOpen Targets
0.04Suggestive
Neoplasm of the liverOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.02Suggestive
posterior cortical atrophyOpen Targets
0.02Suggestive
juvenile dermatomyositisOpen Targets
0.01Suggestive
Duchenne muscular dystrophyOpen Targets
0.01Suggestive
Abnormal sperm morphologyOpen Targets
0.01Suggestive
lung carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KBTBD13Shared pathway100%LRRC75AShared pathway100%KLHL30Shared pathway100%KLHL38Shared pathway100%KLHL10Shared pathway100%KLHL35Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
43%
Ovary
35%
Lung
35%
Heart
29%
Liver
10%
Gene Interaction Network
Click a node to explore
SH3BGRLKBTBD13LRRC75AKLHL30KLHL38KLHL10KLHL35
PROTEIN STRUCTURE
Preparing viewer…
PDB1U6T · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.35LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.72 [0.41–1.35]
RankingsWhere SH3BGRL stands among ~20K protein-coding genes
  • #10,085of 20,598
    Most Researched41
  • #14,084of 17,882
    Most Constrained (LOEUF)1.35
Genes detectedSH3BGRL
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PMID: 39465506
Biomol Biomed · 2025
1.00
2
Expression patterns of SH3BGR family members in zebrafish development.
PMID: 27233781
Dev Genes Evol · 2016
0.90
3
Adaptor SH3BGRL promotes breast cancer metastasis through PFN1 degradation by translational STUB1 upregulation.
PMID: 34331014
Oncogene · 2021
0.80
4
Decitabine Enhances Acute Myeloid Leukemia Cell Apoptosis through SH3BGRL Upregulation.
PMID: 34963436
Anticancer Agents Med Chem · 2022
0.70
5
Expression, purification and crystallization of a human protein SH3BGRL at atomic resolution.
PMID: 16511048
Acta Crystallogr Sect F Struct Biol Cryst Commun · 2005
0.60