MAPK1: Mitogen-Activated Protein Kinase 1 (ERK2)
A key serine/threonine kinase in the RAS-RAF-MEK-ERK signaling cascade, involved in cell proliferation, differentiation, and survival.
Gene Information Card
| Symbol | MAPK1 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q13.33 |
| NCBI Gene ID | 5594 ncbi.nlm.nih.gov/gene/5594 |
| Ensembl ID | ENSG00000100030 |
| UniProt ID | P28482 |
| OMIM ID | 176948 |
| HGNC ID | 6871 |
| Aliases | ERK2, ERT1, MAPK2, p38, p40, p41, p42MAPK, PRKM2 |
Description
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | MAPK1 overexpression and activating mutations promote uncontrolled cell proliferation via sustained ERK signaling. | COSMIC; PMID: 28825729 |
| Non-Small Cell Lung Cancer | MAPK1 amplification and activating mutations drive tumor growth and resistance to EGFR inhibitors. | COSMIC; PMID: 31536449 |
| Melanoma | MAPK1 mutations (e.g., E322K) contribute to MAPK pathway hyperactivation, often in BRAF-mutant tumors. | COSMIC; PMID: 23598277 |
| Cardiofaciocutaneous Syndrome | Germline MAPK1 mutations (e.g., Y67N, D321N) cause gain-of-function in the RAS-MAPK pathway, leading to developmental abnormalities. | ClinVar; PMID: 17020473 |
| Noonan Syndrome | Rare MAPK1 missense variants (e.g., T183A) are associated with RASopathy phenotypes. | ClinVar; PMID: 26918511 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 24.5 | High |
| Heart | 18.2 | Medium |
| Liver | 15.8 | Medium |
| Lung | 20.1 | Medium |
| Kidney | 22.3 | High |
| Colon | 19.7 | Medium |
| Breast | 17.4 | Medium |
| Skin | 14.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 28.3 | High expression; commonly used for functional studies |
| HeLa | 25.1 | High expression; cervical cancer cell line |
| A549 | 22.7 | High expression; lung adenocarcinoma cell line |
| MCF7 | 19.5 | Medium expression; breast cancer cell line |
| HCT116 | 21.8 | High expression; colorectal carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| E322K | Missense | <1% | Gain-of-function; increases kinase activity and downstream signaling |
| D321N | Missense | <1% | Gain-of-function; associated with cardiofaciocutaneous syndrome |
| Y67N | Missense | <1% | Gain-of-function; enhances MEK binding and activation |
| T183A | Missense | <1% | Likely gain-of-function; reported in Noonan syndrome |
| Amplification | Copy number gain | ~2-5% in cancers | Increased gene dosage leading to ERK2 overexpression |
Mutation functional classification
Loss of Function (LOF)
Rare; no well-characterized loss-of-function mutations reported in human disease. Knockout studies in mice show embryonic lethality.
Gain of Function (GOF)
Common in cancer and RASopathies; mutations in the kinase domain (e.g., E322K, D321N) increase catalytic activity or MEK binding.
Dominant Negative (DN)
Not described for MAPK1; dominant-negative forms are engineered for research (e.g., K52R mutation).
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 – protein kinase activity | • GO:0004707 – MAP kinase activity |
| • GO:0000165 – MAPK cascade | • GO:0005515 – protein binding |
| • GO:0005634 – nucleus | • GO:0005737 – cytoplasm |
| • GO:0006468 – protein phosphorylation | • GO:0007049 – cell cycle |
| • GO:0008283 – cell proliferation | • GO:0043066 – negative regulation of apoptotic process |
Pathways
• MAPK1 (mitogen-activated protein kinase 1)
• also known as ERK2
• encodes a member of the MAP kinase family. This serine/threonine kinase is a critical component of the RAS-RAF-MEK-ERK signaling pathway
• which transduces extracellular signals to the nucleus to regulate gene expression
• cell cycle progression
• differentiation
• and apoptosis. MAPK1 is activated by phosphorylation by MEK1/2 and phosphorylates numerous substrates including transcription factors
• cytoskeletal proteins
• and other kinases. Aberrant activation of MAPK1 is implicated in various cancers and developmental disorders.
• RAS-RAF-MEK-ERK signaling pathway (KEGG: hsa04010)
• MAPK signaling pathway (KEGG: hsa04010)
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
• ErbB signaling pathway (KEGG: hsa04012)
• Focal adhesion (KEGG: hsa04510)
• Neurotrophin signaling pathway (KEGG: hsa04722)
• MAPK1 (ERK2) is a 42 kDa serine/threonine protein kinase composed of 360 amino acids. It contains a conserved kinase domain with a TEY (Thr-Glu-Tyr) activation motif at residues 183-185. Phosphorylation of Thr183 and Tyr185 by MEK1/2 induces a conformational change that activates the kinase. ERK2 phosphorylates substrates on Ser/Thr residues within the consensus sequence P-X-S/T-P. The protein is ubiquitously expressed and localizes to both cytoplasm and nucleus upon activation. Structural studies reveal a typical bilobal kinase fold with an N-terminal lobe (β-sheets) and a C-terminal lobe (α-helices).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAPK1 Knockout HEK293 Cell Line | EDJ-KQ390 | Human | 5594 | Details Get a Quote |
| MAPK10 Knockout HEK293 Cell Line | EDJ-KQ697 | Human | 5602 | Details Get a Quote |
| MAPK11 Knockout HEK293 Cell Line | EDJ-KQ698 | Human | 5600 | Details Get a Quote |
| MAPK13 Knockout HEK293 Cell Line | EDJ-KQ699 | Human | 5603 | Details Get a Quote |
| MAPK14 Knockout HEK293 Cell Line | EDJ-KQ700 | Human | 1432 | Details Get a Quote |
| MAPK12 Knockout HEK293 Cell Line | EDJ-KQ1354 | Human | 6300 | Details Get a Quote |
| MAPK15 Knockout HEK293 Cell Line | EDJ-KQ9257 | Human | 225689 | Details Get a Quote |
| MAPK1IP1L Knockout HEK293 Cell Line | EDJ-KQ11235 | Human | 93487 | Details Get a Quote |
| MAPK14 Knockout HeLa Cell Line | EDJ-KQ18076 | Human | 1432 | Details Get a Quote |
| MAPK11 Knockout HeLa Cell Line | EDJ-KQ18148 | Human | 5600 | Details Get a Quote |
| MAPK1 Knockout A-549 Cell Line | EDJ-KQ18602 | Human | 5594 | Details Get a Quote |
| MAPK1 Knockout HCT 116 Cell Line | EDJ-KQ18603 | Human | 5594 | Details Get a Quote |
| MAPK1 Knockout HeLa Cell Line | EDC90508 | Human | 5594 | Details Get a Quote |
| MAPK11 Knockout A-549 Cell Line | EDJ-KQ19275 | Human | 5600 | Details Get a Quote |
| MAPK11 Knockout HCT 116 Cell Line | EDJ-KQ19276 | Human | 5600 | Details Get a Quote |
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