MARK2 Protein (MAP/Microtubule Affinity-Regulating Kinase 2), also known as EMK1, is a serine/threonine protein kinase involved in microtubule dynamics, cell polarity, and tau phosphorylation. It plays critical roles in neuronal function and has been implicated in Alzheimer's disease and other neurodegenerative disorders.
| Attribute |
Value |
| Protein Name |
MAP/Microtubule Affinity-Regulating Kinase 2 (MARK2) |
| Gene |
MARK2 |
| UniProt ID |
Q9Y2R9 |
| Molecular Weight |
~80 kDa |
| Subcellular Localization |
Cytoplasm, Membrane, Cell junctions |
| Protein Family |
MARK/Par-1 kinase family |
| Associated Diseases |
Alzheimer's disease, Parkinson's disease, cancer |
MARK2 contains:
- N-terminal kinase domain (aa 1-272) — catalytic domain
- UBA domain (aa 352-395) — ubiquitin-associated
- Kinase-associated domain 1 (KA1) (aa 486-626) — membrane targeting
- C-terminal regulatory region
MARK2 phosphorylates microtubule-associated proteins (MAPs):
- Tau — at multiple sites (Ser262, Ser356, etc.)
- MAP2 — dendritic microtubule binding
- MAP4 — mitotic spindle regulation
Phosphorylation reduces MAP binding to microtubules, affecting:
- Microtubule stability
- Axonal transport
- Neuronal polarity
MARK2 is essential for:
- Establishment of neuronal polarity
- Dendrite specification
- Cell junction maintenance
- Epithelial polarity
- LKB1-AMPK-MARK axis — energy sensing
- Par3-Par6-aPKC complex — polarity establishment
- Wnt/β-catenin signaling
- MARK2 hyperphosphorylates tau
- Promotes tau aggregation and NFT formation
- Linked to synaptic dysfunction
- Alters axonal transport
- Involved in alpha-synuclein phosphorylation
- May affect dopaminergic neuron survival
- Connected to mitochondrial dysfunction
- Epilepsy — altered microtubule dynamics
- Autism — synaptic development abnormalities
MARK2 is a potential therapeutic target for:
- Tauopathies (AD, PSP, CBD)
- Neurodegenerative diseases with tau pathology
- Polarity disorders
- MARK kinases and tau phosphorylation in Alzheimer's disease
- MARK2 and neuronal polarity
- Microtubule regulation in neurodegeneration