RPS6KA5
Ribosomal Protein S6 Kinase A5 (MSK1) – A Key Regulator of Chromatin Remodeling and Transcriptional Activation
Gene Information Card
| Symbol | RPS6KA5 |
|---|---|
| Full Name | Ribosomal Protein S6 Kinase A5 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q31.1 |
| NCBI Gene ID | 9252 ncbi.nlm.nih.gov/gene/9252 |
| Ensembl ID | ENSG00000100784 |
| UniProt ID | O75582 |
| OMIM ID | 603607 |
| HGNC ID | 10432 |
| Aliases | MSK1, S6K-alpha-5, RSK-like protein |
Description
RPS6KA5 encodes the mitogen- and stress-activated protein kinase 1 (MSK1), a serine/threonine kinase that acts downstream of ERK and p38 MAPK pathways. MSK1 phosphorylates histone H3 and transcription factors such as CREB and ATF1, thereby regulating chromatin remodeling and immediate early gene expression in response to growth factors, stress, and inflammatory signals.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Dysregulated MSK1 activity alters chromatin accessibility and gene expression, promoting proliferation and metastasis | COSMIC; multiple studies |
| Inflammatory disorders | MSK1-mediated CREB activation modulates cytokine production | PubMed; reviewed in OMIM |
| Neurodevelopmental disorders | Rare variants in RPS6KA5 associated with intellectual disability | ClinVar; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 4.1 | Low |
| Lung | 9.7 | Low |
| Spleen | 15.2 | Medium |
| Testis | 18.6 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Moderate expression |
| HeLa | 11.8 | Moderate expression |
| K562 | 9.5 | Low expression |
| A549 | 13.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1492C>T (p.Arg498Trp) | Missense | <0.01% | Likely loss of function; reported in ClinVar |
| c.214G>A (p.Gly72Arg) | Missense | <0.01% | Uncertain significance; COSMIC |
| c.1021_1023del (p.Lys341del) | In-frame deletion | <0.01% | Unknown effect; COSMIC |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the kinase domain (e.g., p.Arg498Trp) reduce catalytic activity, impairing histone H3 phosphorylation and CREB activation.
Gain of Function (GOF)
Not well documented; some cancer-associated variants may increase kinase activity but evidence is limited.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• ErbB signaling pathway (KEGG: hsa04012)
• Neurotrophin signaling pathway (KEGG: hsa04722)
• Signaling by MSK1 (Reactome: R-HSA-198753)
Protein Summary
MSK1 is a 802-amino acid protein with two kinase domains (N-terminal and C-terminal) and a linker region. It is activated by dual phosphorylation by ERK1/2 or p38 MAPK. Once active, MSK1 phosphorylates histone H3 at Ser10 and Ser28, facilitating chromatin decondensation, and phosphorylates transcription factors CREB at Ser133 and ATF1 at Ser63, driving expression of immediate early genes such as c-Fos and JunB. MSK1 also phosphorylates the NF-κB subunit p65, modulating inflammatory responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPS6KA5 Knockout HEK293 Cell Line | EDJ-KQ753 | Human | 9252 | Details Get a Quote |
| RPS6KA5 Knockout A-549 Cell Line | EDJ-KQ19413 | Human | 9252 | Details Get a Quote |
| RPS6KA5 Knockout HCT 116 Cell Line | EDJ-KQ19414 | Human | 9252 | Details Get a Quote |
| RPS6KA5 Knockout HeLa Cell Line | EDJ-KQ19415 | Human | 9252 | Details Get a Quote |
