PAK1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the PAK1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PAK1 |
|---|---|
| Full Name | p21 (RAC1) activated kinase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 11q13.5-q14.2 |
| NCBI Gene ID | 5058 ncbi.nlm.nih.gov/gene/5058 |
| Ensembl ID | ENSG00000149269 |
| UniProt ID | Q13153 |
| OMIM ID | 602590 |
| HGNC ID | 8590 |
| Aliases | PAKalpha, CDC42/RAC1 effector kinase 1 |
Description
PAK1 encodes a serine/threonine protein kinase that acts as an effector of the small GTPases CDC42 and RAC1. It plays a critical role in various cellular processes including cytoskeletal reorganization, cell motility, apoptosis, and proliferation. PAK1 is implicated in multiple cancers and other diseases, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression and hyperactivation of PAK1 promote tumorigenesis via enhanced cell survival, proliferation, and invasion. | COSMIC, ClinVar, literature |
| Intellectual Disability | Mutations in PAK1 have been associated with neurodevelopmental disorders, affecting neuronal migration and synaptic function. | ClinVar, OMIM |
| Cardiac Hypertrophy | PAK1 activation contributes to pathological cardiac remodeling through signaling pathways that regulate cell growth. | Literature, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.2 | Medium |
| Lung | 12.5 | Low |
| Breast | 15.3 | Medium |
| Colon | 10.1 | Low |
| Kidney | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 20.5 | High expression |
| MCF7 | 18.2 | High expression |
| A549 | 14.7 | Medium expression |
| HEK293 | 12.3 | Medium expression |
| HepG2 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.R193Q | Missense | 0.5% | Potential gain-of-function, increased kinase activity |
| p.A204T | Missense | 0.2% | Unknown effect, possibly neutral |
| p.E329K | Missense | 0.1% | Loss-of-function, reduced kinase activity |
| p.R357W | Missense | 0.3% | Gain-of-function, enhanced signaling |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish PAK1 kinase activity, leading to impaired cytoskeletal dynamics and cell migration.
Gain of Function (GOF)
Mutations that increase PAK1 kinase activity, promoting oncogenic signaling and cell proliferation.
Dominant Negative (DN)
Mutations that produce a truncated or inactive PAK1 protein that interferes with the function of the wild-type protein, often seen in experimental models.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity | • ATP binding |
| • signal transduction | • cell migration |
| • cytoskeleton organization | • apoptotic process |
| • cell proliferation | • response to stress |
Pathways
• RAC1/CDC42 signaling
• MAPK signaling
• PI3K-Akt signaling
• Regulation of actin cytoskeleton
• Focal adhesion
Protein Summary
The PAK1 protein is a 545-amino acid serine/threonine kinase with an N-terminal regulatory domain containing a p21-binding domain (PBD) and an autoinhibitory domain, and a C-terminal kinase domain. Upon binding to activated RAC1 or CDC42, PAK1 undergoes a conformational change that relieves autoinhibition, leading to its activation. PAK1 phosphorylates multiple substrates involved in cytoskeletal dynamics, cell survival, and gene expression. Its dysregulation is linked to cancer progression and other diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAK1 Knockout HEK293 Cell Line | EDJ-KQ721 | Human | 5058 | Details Get a Quote |
| PAK1 Knockout A-549 Cell Line | EDJ-KQ19341 | Human | 5058 | Details Get a Quote |
| PAK1 Knockout HCT 116 Cell Line | EDJ-KQ19342 | Human | 5058 | Details Get a Quote |
| PAK1 Knockout HeLa Cell Line | EDJ-KQ19343 | Human | 5058 | Details Get a Quote |
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