PAK4
p21 (RAC1) Activated Kinase 4
Gene Information Card
| Symbol | PAK4 |
|---|---|
| Full Name | p21 (RAC1) Activated Kinase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 10298 ncbi.nlm.nih.gov/gene/10298 |
| Ensembl ID | ENSG00000130669 |
| UniProt ID | O96013 |
| OMIM ID | 605451 |
| HGNC ID | 8591 |
| Aliases | PAK-4, KIAA1142 |
Description
PAK4 (p21 (RAC1) Activated Kinase 4) is a member of the PAK family of serine/threonine kinases. It is activated by binding to active GTP-bound forms of RAC1 and CDC42. PAK4 plays a role in cytoskeletal remodeling, cell motility, and survival signaling. It is frequently overexpressed or mutated in various cancers and is implicated in developmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic Cancer | PAK4 overexpression promotes tumor growth and metastasis via activation of downstream signaling pathways (e.g., ERK, AKT). | NCBI Gene, COSMIC |
| Colorectal Cancer | PAK4 amplification and activating mutations contribute to cell proliferation and invasion. | COSMIC, ClinVar |
| Breast Cancer | PAK4 overexpression correlates with poor prognosis and promotes epithelial-mesenchymal transition. | NCBI Gene, OMIM |
| Prostate Cancer | PAK4 upregulation enhances androgen receptor signaling and tumor progression. | NCBI Gene |
| Lung Cancer | PAK4 mutations and overexpression are associated with increased cell migration and resistance to therapy. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Pancreas | 12.8 | Medium |
| Brain | 10.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer cell line |
| A549 | 14.2 | Lung cancer cell line |
| MCF7 | 11.3 | Breast cancer cell line |
| HEK293 | 9.8 | Embryonic kidney cell line |
| HCT116 | 16.1 | Colorectal cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu329Lys | Missense | <1% | Alters kinase activity; potential gain-of-function |
| p.Arg359Trp | Missense | <1% | Unknown functional effect |
| p.Val361Met | Missense | <1% | Reported in COSMIC; functional impact unclear |
| p.Leu467Phe | Missense | <1% | Located in kinase domain; may affect substrate binding |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in PAK4.
Gain of Function (GOF)
p.Glu329Lys is suspected to increase kinase activity based on structural modeling.
Dominant Negative (DN)
No dominant-negative mutations described in PAK4.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • Rac GTPase binding |
| • Cdc42 GTPase binding | • cytoskeleton organization |
| • cell migration | • apoptotic process |
| • positive regulation of cell proliferation |
Pathways
• RAC1/PAK signaling
• Regulation of actin cytoskeleton
• MAPK signaling pathway
• Focal adhesion
• ErbB signaling pathway
Protein Summary
PAK4 is a 591-amino acid serine/threonine kinase with an N-terminal regulatory domain containing a p21-binding domain (PBD) and a C-terminal kinase domain. It is activated by binding to RAC1 or CDC42, leading to autophosphorylation and subsequent phosphorylation of downstream targets such as LIMK1, BAD, and MYH9. PAK4 regulates cytoskeletal dynamics, cell adhesion, and survival. Its overexpression and mutation are linked to oncogenesis and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAK4 Knockout HEK293 Cell Line | EDJ-KQ683 | Human | 10298 | Details Get a Quote |
| PAK4 Knockout A-549 Cell Line | EDJ-KQ20590 | Human | 10298 | Details Get a Quote |
| PAK4 Knockout HCT 116 Cell Line | EDJ-KQ20592 | Human | 10298 | Details Get a Quote |
| PAK4 Knockout HeLa Cell Line | EDJ-KQ20593 | Human | 10298 | Details Get a Quote |
