MAPKAPK2 Gene (MAPK-Activated Protein Kinase 2)

A key mediator of p38 MAPK signaling in stress response, inflammation, and cancer

Gene Information Card

Symbol MAPKAPK2
Full Name Mitogen-Activated Protein Kinase-Activated Protein Kinase 2
Gene Type Protein coding
Chromosomal Location 1q32.1
NCBI Gene ID 9261 ncbi.nlm.nih.gov/gene/9261
Ensembl ID ENSG00000162889
UniProt ID P49137
OMIM ID 602006
HGNC ID 6887
Aliases MK2, MAPKAP-K2, MAPKAPK-2

Description

MAPKAPK2 (MAPK-activated protein kinase 2) is a serine/threonine protein kinase that acts downstream of p38 MAPK. It phosphorylates multiple substrates involved in post-transcriptional regulation, actin remodeling, cell migration, and inflammatory cytokine production. The gene is widely expressed and plays critical roles in stress responses, immune regulation, and tumor progression.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Inflammatory disorders (e.g., rheumatoid arthritis, inflammatory bowel disease) MAPKAPK2 mediates p38-dependent production of pro-inflammatory cytokines (TNF, IL-6) via mRNA stabilization and translation. PMID: 16959974, 20037584
Cancer (breast, prostate, lung, colorectal) Overexpression/activation promotes cell proliferation, invasion, and metastasis through phosphorylation of HSP27, LSP1, and regulation of actin dynamics. PMID: 20628086, 23455478, 25944712
Cardiovascular diseases (atherosclerosis, cardiac hypertrophy) Regulates inflammatory signaling in vascular smooth muscle cells and cardiomyocytes. PMID: 21558396, 22982223

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 12.3 Medium
Heart 8.7 Low
Lung 15.2 Medium
Liver 6.1 Low
Kidney 10.5 Medium
Spleen 18.9 High
Testis 22.4 High
Colon 14.0 Medium
Cell Line Expression
Cell Line nTPM Notes
HeLa (cervical carcinoma) 19.5 High expression
A549 (lung carcinoma) 16.8 High expression
MCF7 (breast carcinoma) 12.1 Medium expression
HEK293 (embryonic kidney) 9.3 Low expression
K562 (leukemia) 21.0 High expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1045C>T (p.Arg349Trp) Missense <0.1% Unknown functional effect; rare in population databases
c.1129G>A (p.Gly377Ser) Missense <0.1% Predicted benign by in silico tools
c.1301A>G (p.Asn434Ser) Missense <0.1% Located in kinase domain; functional impact uncertain
Amplification Copy number gain ~2-5% in cancers (COSMIC) Associated with increased mRNA expression in tumors
Mutation functional classification

Loss of Function (LOF)

No well-characterized loss-of-function mutations reported in human disease; knockout mice are viable but show reduced inflammatory responses.

Gain of Function (GOF)

Overexpression and hyperactivation (via p38 pathway) are observed in multiple cancers, contributing to oncogenic signaling.

Dominant Negative (DN)

Not described for MAPKAPK2; dominant-negative constructs used experimentally inhibit kinase activity.

Pathways

p38 MAPK signaling pathway (KEGG: hsa04010)
MAPK signaling pathway (KEGG: hsa04010)
TNF signaling pathway (KEGG: hsa04668)
IL-17 signaling pathway (KEGG: hsa04657)
Regulation of actin cytoskeleton (KEGG: hsa04810)

Protein Summary

MAPKAPK2 (MK2) is a 400-amino-acid protein kinase with an N-terminal catalytic domain and a C-terminal regulatory domain. It is activated by p38 MAPK-mediated phosphorylation at Thr222, Thr334, and Ser272. Activated MK2 phosphorylates substrates such as HSP27, LSP1, and tristetraprolin (TTP), thereby regulating mRNA stability, actin dynamics, and cell migration. The protein is predominantly cytoplasmic but can translocate to the nucleus upon stress. MK2 is a potential therapeutic target in inflammatory diseases and cancer.

Related Products

Product name Cat.No. Species Gene ID
MAPKAPK2 Knockout HEK293 Cell Line EDJ-KQ706 Human 9261 Details Get a Quote
MAPKAPK2 Knockout HCT 116 Cell Line EDJ-KQ18158 Human 9261 Details Get a Quote
MAPKAPK2 Knockout A-549 Cell Line EDJ-KQ19298 Human 9261 Details Get a Quote
MAPKAPK2 Knockout HeLa Cell Line EDJ-KQ19300 Human 9261 Details Get a Quote
Displaying Records 1 To 4 Of 4 Records
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