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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PAK5
p21 (RAC1) activated kinase 5
Chromosome 20 · 20p12.2
NCBI Gene: 57144Ensembl: ENSG00000101349.18HGNC: HGNC:15916UniProt: B0AZM9
79PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmmitochondrioncytosolnuclear membraneschizophreniaresponse to cranial radiation therapyinformation processing speedmathematical ability
✦AI Summary

PAK5 is a serine/threonine protein kinase that functions as a critical regulator of multiple cellular processes including cytoskeleton organization, cell migration, proliferation, and survival 1. PAK5 is activated by Cdc42 and Rac1 GTPases, leading to autophosphorylation and activation of downstream signaling cascades 2. The kinase promotes cell survival through anti-apoptotic mechanisms and regulates cytoskeletal dynamics by phosphorylating substrates such as MARK2 and CTNND1 2. PAK5 is significantly dysregulated across multiple cancer types including breast cancer, cervical cancer, renal carcinoma, and melanoma 1. In HER2-positive breast cancer, PAK5 promotes trastuzumab resistance by phosphorylating METTL14 to enhance m6A modification of MALAT1 lncRNA, thereby stabilizing nuclear HER2 accumulation 3. In cervical cancer, HPV E7-mediated upregulation of ALKBH5 enhances PAK5 expression through m6A demethylation, promoting malignant phenotypes 4. PAK5 also facilitates renal cell carcinoma metastasis by phosphorylating Slug to increase N-cadherin expression 5. Additionally, PAK5 regulates anaerobic glycolysis in endometriosis through PKM2 phosphorylation at Ser519 6. These findings establish PAK5 as a therapeutic target across multiple disease contexts.

Sources cited
1
PAK5 is highly expressed in multiple organs and dysregulated in various cancers including ovarian, cervical, melanoma, osteosarcoma, renal, and breast cancers, involved in proliferation, apoptosis, migration and invasion
PMID: 31805288
2
HPV E7 promotes ALKBH5 expression, which mediates m6A demethylation to enhance PAK5 expression, promoting cervical cancer progression
PMID: 37480971
3
PAK5 phosphorylates METTL14 to enhance m6A modification of MALAT1, stabilizing nuclear HER2 and promoting trastuzumab resistance in HER2-positive breast cancer
PMID: 40258843
4
PAK5 phosphorylates PKM2 at Ser519 to promote anaerobic glycolysis and cell proliferation and metastasis in endometriosis
PMID: 39331255
5
PAK5 functions as an oncogenic kinase downstream of Cdc42 and Rac with roles in cytoskeleton regulation, anti-apoptosis and proliferation
PMID: 24869804
6
PAK5 is regulated by PKD and EGF-stimulated phosphorylation of Ser99 and Ser288 for 14-3-3 binding, distinct from PAK4 and PAK6
PMID: 35969127
7
PAK5 is overexpressed in myelodysplastic syndrome and interacts with transcription regulators LMO2 and GATA1 in the nucleus
PMID: 36905268
8
PAK5 phosphorylates Slug at serine 87 to promote N-cadherin transactivation and epithelial-mesenchymal transition in renal cell carcinoma metastasis
PMID: 37437827
Disease Associationsⓘ20
schizophreniaOpen Targets
0.34Weak
information processing speedOpen Targets
0.32Weak
response to cranial radiation therapyOpen Targets
0.32Weak
mathematical abilityOpen Targets
0.31Weak
synovium disorderOpen Targets
0.31Weak
musculoskeletal system diseaseOpen Targets
0.30Weak
exostosisOpen Targets
0.25Weak
bipolar disorderOpen Targets
0.25Weak
Abnormality of the cardiovascular systemOpen Targets
0.23Weak
cervical carcinomaOpen Targets
0.22Weak
premature birthOpen Targets
0.22Weak
crush injuryOpen Targets
0.19Weak
ovarian neoplasmOpen Targets
0.19Weak
breast cancerOpen Targets
0.11Weak
osteosarcomaOpen Targets
0.10Suggestive
gliomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
melanomaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RAF1Protein interaction100%RAC2Protein interaction94%ARHGEF6Protein interaction94%CDC42Protein interaction93%LIMK1Protein interaction92%LIMK2Protein interaction92%
Tissue Expression6 tissues
Brain
100%
Liver
1%
Bone Marrow
1%
Lung
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
PAK5RAF1RAC2ARHGEF6CDC42LIMK1LIMK2
PROTEIN STRUCTURE
Preparing viewer…
PDB8C12 · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.33Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.21 [0.13–0.33]
RankingsWhere PAK5 stands among ~20K protein-coding genes
  • #6,015of 20,598
    Most Researched79
  • #1,374of 17,882
    Most Constrained (LOEUF)0.33 · top 10%
Genes detectedPAK5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human p21-activated kinase 5 (PAK5) expression and potential mechanisms in relevant cancers: Basic and clinical perspectives for molecular cancer therapeutics.
PMID: 31805288
Life Sci · 2020
1.00
2
HPV E7-drived ALKBH5 promotes cervical cancer progression by modulating m6A modification of PAK5.
PMID: 37480971
Pharmacol Res · 2023
0.90
3
PAK5 promotes the trastuzumab resistance by increasing HER2 nuclear accumulation in HER2-positive breast cancer.
PMID: 40258843
Cell Death Dis · 2025
0.80
4
PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis.
PMID: 39331255
Front Med · 2024
0.70
5
An oncogenic kinase: putting PAK5 forward.
PMID: 24869804
Expert Opin Ther Targets · 2014
0.60