RPS6KA4
Ribosomal Protein S6 Kinase A4 (MSK2) – A Key Regulator of Transcription and Chromatin Remodeling
Gene Information Card
| Symbol | RPS6KA4 |
|---|---|
| Full Name | ribosomal protein S6 kinase A4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 8986 ncbi.nlm.nih.gov/gene/8986 |
| Ensembl ID | ENSG00000162367 |
| UniProt ID | O75676 |
| OMIM ID | 603606 |
| HGNC ID | 10433 |
| Aliases | MSK2, RSK-B, S6K-alpha-4 |
Description
RPS6KA4 (ribosomal protein S6 kinase A4) encodes MSK2 (mitogen- and stress-activated protein kinase 2), a serine/threonine kinase that acts downstream of ERK and p38 MAPK pathways. MSK2 phosphorylates transcription factors (e.g., CREB, ATF1) and histone H3, thereby regulating gene expression in response to growth factors, stress, and inflammatory signals. It plays roles in cell proliferation, survival, and chromatin remodeling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Dysregulated MSK2 activity alters transcription of oncogenes and tumor suppressors; mutations and copy number changes observed in multiple tumor types. | COSMIC; literature |
| Inflammatory disorders | MSK2 modulates NF-κB and AP-1 signaling; implicated in chronic inflammation. | UniProt; PubMed |
| Neurodevelopmental conditions | Rare variants in RPS6KA4 associated with intellectual disability and autism spectrum disorder. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 8.5 | Low |
| Kidney | 11.3 | Medium |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical cancer cell line |
| A549 | 13.2 | Lung cancer cell line |
| HEK293 | 16.1 | Embryonic kidney cell line |
| K562 | 11.8 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Unknown; predicted damaging |
| c.1426G>A (p.Glu476Lys) | Missense | <0.01% | Unknown; predicted benign |
| c.1885_1887del (p.Lys629del) | In-frame deletion | <0.01% | Unknown; may affect kinase domain |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in major databases.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
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)
• Signaling by NTRK1 (Reactome: R-HSA-187037)
• Signaling by ERBB2 (Reactome: R-HSA-1226099)
• CREB phosphorylation through the activation of Ras (Reactome: R-HSA-442742)
Protein Summary
MSK2 (UniProt O75676) is a 772-amino-acid serine/threonine kinase with two kinase domains (N-terminal and C-terminal). It is activated by phosphorylation via ERK1/2 or p38 MAPK. Once active, MSK2 phosphorylates CREB at Ser133, ATF1 at Ser63, and histone H3 at Ser10, promoting transcriptional activation. It also phosphorylates NF-κB p65 and STAT3, linking it to inflammatory and survival pathways. MSK2 is widely expressed, with highest levels in testis and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPS6KA4 Knockout HEK293 Cell Line | EDJ-KQ752 | Human | 8986 | Details Get a Quote |
| RPS6KA4 Knockout HeLa Cell Line | EDJ-KQ18243 | Human | 8986 | Details Get a Quote |
| RPS6KA4 Knockout A-549 Cell Line | EDJ-KQ19410 | Human | 8986 | Details Get a Quote |
| RPS6KA4 Knockout HCT 116 Cell Line | EDJ-KQ19411 | Human | 8986 | Details Get a Quote |
