MAP2 Gene: Microtubule Associated Protein 2 | NCBI, UniProt, ClinVar

MAP2 (Microtubule Associated Protein 2) encodes a protein that binds to microtubules and promotes their assembly and stability. It is primarily expressed in neurons, where it plays a critical role in dendrite formation, neuronal polarity, and cytoskeletal organization. Alternative splicing generates multiple isoforms (MAP2A, MAP2B, MAP2C, MAP2D) with distinct developmental and regional expression patterns.

Disease category	Pathophysiological mechanism	Genomic evidence
Alzheimer disease	MAP2 is a substrate for hyperphosphorylation and cleavage by calpain, contributing to neurofibrillary pathology and dendritic degeneration.	PMID: 17088211; NCBI GeneRIF
Schizophrenia	Reduced MAP2 expression in prefrontal cortex and hippocampus is associated with dendritic spine loss and synaptic dysfunction.	PMID: 11597303; NCBI GeneRIF
Epilepsy	Altered MAP2 phosphorylation and proteolysis in hippocampal neurons following status epilepticus, linked to dendritic remodeling.	PMID: 12684468; NCBI GeneRIF

MAP2 is a heat-stable, high-molecular-weight microtubule-associated protein predominantly expressed in neuronal dendrites. It promotes microtubule assembly and stability, cross-links microtubules with intermediate filaments, and interacts with actin. The protein contains multiple microtubule-binding repeats and a projection domain that determines spacing between microtubules. Phosphorylation by various kinases (e.g., PKA, CaMKII, CDK5) regulates its binding affinity and function. MAP2 is essential for dendritic arborization and synaptic plasticity.