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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SBK2
SH3 domain binding kinase family member 2
Chromosome 19 · 19q13.42
NCBI Gene: 646643Ensembl: ENSG00000187550.10HGNC: HGNC:34416UniProt: P0C263
5PubMed Papers
15Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
MAP kinase kinase activityMAPK cascadeprotein kinase activityprotein serine/threonine kinase activityneurodegenerative diseaseplasma fibronectin deficiencyHereditary persistence of alpha-fetoproteincongenital lethal erythroderma
✦AI Summary

SBK2 (SH3 domain binding kinase family member 2) is a serine/threonine protein kinase with dual roles in inflammation and cardiac development. In the immune system, SBK2 functions as a critical negative regulator of atherosclerosis by phosphorylating NLRP3 inflammasome at Ser161, triggering Tollip-dependent autophagic degradation and subsequent inflammasome inactivation 1. This phosphorylation event represents the sole known kinase-driven mechanism for selective NLRP3 clearance, suppressing pro-inflammatory IL-1β/IL-18 secretion. In cardiac tissue, SBK2 is atrium-enriched and localized to sarcomere A-bands, where it maintains sarcomeric organization and integrity during cardiomyocyte differentiation 2. SBK2 knockdown causes loss of sarcomeric structure and decreased sarcomeric gene expression in neonatal and adult cardiomyocytes. Therapeutically, SBK2 is being investigated as a tumor imaging target; the SBK2 peptide specifically recognizes PTPmu-derived biomarkers on glioblastoma cells, enabling fluorescence and MRI-guided surgical resection 34. Additionally, SBK2 methylation patterns in cord blood show associations with immune pathway regulation following prenatal pet exposure 5. These findings identify SBK2 as a potential therapeutic target for atherosclerosis management and cardiac disease.

Sources cited
1
SBK2 phosphorylates NLRP3 at Ser161 to trigger inflammasome inactivation and suppress atherosclerosis; SBK2 is the sole known kinase mediating selective NLRP3 autophagic degradation
PMID: 41684124
2
SBK2 is atrium-enriched, localized to sarcomere A-bands, and required for sarcomeric organization and cardiomyocyte differentiation
PMID: 35587025
3
SBK2 peptide targets PTPmu biomarker on glioblastoma cells for fluorescence image-guided surgery
PMID: 36695968
4
SBK2-Tris-(Gd-DOTA)3 molecular imaging probe specifically labels glioma tumors via PTPmu targeting for MRI applications
PMID: 23730413
5
SBK2 methylation patterns in cord blood are associated with immune pathway regulation including IL-18, Toll signaling, and complement
PMID: 34642452
Disease Associationsⓘ15
neurodegenerative diseaseOpen Targets
0.42Moderate
plasma fibronectin deficiencyOpen Targets
0.07Suggestive
Hereditary persistence of alpha-fetoproteinOpen Targets
0.04Suggestive
congenital lethal erythrodermaOpen Targets
0.04Suggestive
Congenital deficiency in alpha-fetoproteinOpen Targets
0.03Suggestive
atherosclerosisOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
multiple sclerosisOpen Targets
0.01Suggestive
gliomaOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
muscular atrophyOpen Targets
0.00Suggestive
glioblastomaOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RCE1Shared pathway100%PBKShared pathway50%PTPN7Shared pathway50%MAP4K5Shared pathway50%MAP3K19Shared pathway50%MAP3K21Shared pathway50%
Tissue Expression6 tissues
Heart
100%
Brain
8%
Liver
0%
Lung
0%
Ovary
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SBK2RCE1PBKPTPN7MAP4K5MAP3K19MAP3K21
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P0C263
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.77LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.23 [0.85–1.77]
RankingsWhere SBK2 stands among ~20K protein-coding genes
  • #18,483of 20,598
    Most Researched5
  • #16,423of 17,882
    Most Constrained (LOEUF)1.77
Genes detectedSBK2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Comparison of Near-Infrared Imaging Agents Targeting the PTPmu Tumor Biomarker.
PMID: 36695968
Mol Imaging Biol · 2023
1.00
2
Pet ownership in pregnancy and methylation pattern in cord blood.
PMID: 34642452
Genes Immun · 2021
0.90
3
Molecular Magnetic Resonance Imaging of Tumors with a PTPµ Targeted Contrast Agent.
PMID: 23730413
Transl Oncol · 2013
0.80
4
Macrophage SBK2 suppresses inflammation and atherosclerosis by NLRP3 phosphorylation.
PMID: 41684124
Eur Heart J · 2026
0.70
5
Molecular Imaging of Tumors Using a Quantitative T 1 Mapping Technique via Magnetic Resonance Imaging.
PMID: 26435847
Diagnostics (Basel) · 2015
0.60