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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PEAK1
pseudopodium enriched atypical kinase 1
Chromosome 15 · 15q24.3
NCBI Gene: 79834Ensembl: ENSG00000173517.12HGNC: HGNC:29431UniProt: Q9H792
91PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ATP bindingfocal adhesion assemblyregulation of focal adhesion assemblyfocal adhesiontype 2 diabetes mellitusdiabetes mellitusneurodegenerative diseasediabetic eye disease
✦AI Summary

PEAK1 (pseudopodium enriched atypical kinase 1) is a catalytically inactive pseudokinase that functions as a critical scaffolding protein regulating cell adhesion, migration, and barrier function. In normal physiology, PEAK1 maintains intestinal tight junction integrity by interacting with ZO-1 and protecting it from autophagy-mediated degradation, with Src-mediated phosphorylation of Y724 promoting this stabilization 1. PEAK1 regulates cell migration through Src-mediated Y635 phosphorylation, which facilitates indirect binding to integrins via Tensin3 and enables convergence of integrin and growth factor signaling 2. In cancer, PEAK1 promotes oncogenic signaling through multiple mechanisms. It activates CAMK2 via PLCγ1/Ca2+ signaling in triple-negative breast cancer, with RA306 (CAMK2 inhibitor) showing therapeutic potential 3. PEAK1 upregulation correlates with poor prognosis across multiple cancer types, promoting epithelial-mesenchymal transition (EMT), invasion, and metastasis in breast, lung, and gastric cancers 4, 5, 6. In prostate cancer, PEAK1 mediates docetaxel resistance by promoting M2 macrophage polarization through HIF-1α/STAT3/NF-κB pathway activation 7. Emerging evidence suggests PEAK1 itself may be therapeutically targeted, as miRNA-enriched plant exosomes modulating PEAK1 expression alleviate colitis 8.

Sources cited
1
PEAK1 maintains tight junction integrity by protecting ZO-1 from autophagy-mediated degradation and is crucial for intestinal barrier homeostasis
PMID: 40707483
2
PEAK1 Y635 phosphorylation by Src regulates cell migration through association with Tensin3 and integrins in focal adhesions
PMID: 35687021
3
PEAK1 activates CAMK2 via PLCγ1/Ca2+ signaling in triple-negative breast cancer and CAMK2 inhibitor RA306 targets this pathway
PMID: 39984440
4
High PEAK1 expression in breast cancer correlates with invasion, metastasis, chemoresistance, and poor prognosis
PMID: 34554318
5
PEAK1 overexpression induces EMT and metastasis in lung cancer by activating ERK1/2 and JAK2 signaling
PMID: 30038287
6
PEAK1 promotes prostate cancer progression and docetaxel resistance by mediating M2 macrophage polarization through HIF-1α/STAT3/NF-κB pathway
PMID: 41495812
7
Loss of PEAK1 expression is associated with poor prognosis in gastric cancer and EMT activation
PMID: 25445115
8
Plant-derived miRNAs targeting PEAK1 alleviate colitis by modulating immunity and inflammation
PMID: 40994128
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.51Moderate
diabetes mellitusOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.42Moderate
diabetic eye diseaseOpen Targets
0.39Weak
uterine fibroidOpen Targets
0.32Weak
diabetic neuropathyOpen Targets
0.30Weak
diabetic retinopathyOpen Targets
0.30Weak
cervical carcinomaOpen Targets
0.28Weak
attention deficit hyperactivity disorderOpen Targets
0.26Weak
schizophreniaOpen Targets
0.26Weak
type 2 diabetes nephropathyOpen Targets
0.25Weak
response to antihypertensive drugOpen Targets
0.25Weak
poisoningOpen Targets
0.24Weak
metabolic syndromeOpen Targets
0.24Weak
heart failureOpen Targets
0.20Weak
Abnormality of refractionOpen Targets
0.18Weak
heart diseaseOpen Targets
0.14Weak
Abnormality of the skeletal systemOpen Targets
0.13Weak
exfoliation syndromeOpen Targets
0.12Weak
breast cancerOpen Targets
0.10Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SHC1Protein interaction97%SLKShared pathway20%NTN4Shared pathway20%PRAG1Shared pathway20%TSPAN11Shared pathway17%TMEM18Shared pathway17%
Tissue Expression6 tissues
Heart
100%
Lung
81%
Bone Marrow
59%
Brain
38%
Ovary
32%
Liver
15%
Gene Interaction Network
Click a node to explore
PEAK1SHC1SLKNTN4PRAG1TSPAN11TMEM18
PROTEIN STRUCTURE
Preparing viewer…
PDB6BHC · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.10Tolerant
Observed/Expected LoF0.42 [0.33–0.52]
RankingsWhere PEAK1 stands among ~20K protein-coding genes
  • #5,262of 20,598
    Most Researched91
  • #3,235of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedPEAK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PEAK1 maintains tight junctions in intestinal epithelial cells and resists colitis by inhibiting autophagy-mediated ZO-1 degradation.
PMID: 40707483
Nat Commun · 2025
1.00
2
Activation of CAMK2 by pseudokinase PEAK1 represents a targetable pathway in triple negative breast cancer.
PMID: 39984440
Nat Commun · 2025
0.90
3
MicroRNA-Enriched Plant-Derived Exosomes Alleviate Colitis by Modulating Systemic Immunity, Metabolic Homeostasis, and Gut Microbiota.
PMID: 40994128
Adv Sci (Weinh) · 2025
0.80
4
PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer.
PMID: 34554318
Clin Exp Med · 2022
0.70
5
PEAK1 Y635 phosphorylation regulates cell migration through association with Tensin3 and integrins.
PMID: 35687021
J Cell Biol · 2022
0.60