CaMKII

Calcium/calmodulin dependent protein kinase II association domain
Crystal structure of calcium/calmodulin-dependent protein kinase
Identifiers
Symbol	CaMKII_AD
Pfam	PF08332
Pfam clan	CL0051
InterPro	IPR013543
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Ca2+
/calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is regulated by the Ca2+
/calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for Ca2+
homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation.

Misregulation of CaMKII is linked to Alzheimer’s disease, Angelman syndrome, and heart arrhythmia.

There are two types of CaM kinase:

CaMKII accounts for 1–2% of all proteins in the brain, and has 28 different isoforms. The isoforms derive from the alpha, beta, gamma, and delta genes.

All of the isoforms of CaMKII have: a catalytic domain, an autoinhibitory domain, a variable segment, and a self-association domain.

The catalytic domain has several binding sites for ATP and other substrate anchor proteins. It is responsible for the transfer of phosphate from ATP to Ser or Thr residues in substrates. The autoinhibitory domain features a pseudosubstrate site, which binds to the catalytic domain and blocks its ability to phosphorylate proteins.

The structural feature that governs this autoinhibition is the Threonine 286 residue. Phosphorylation of this site will permanently activate the CaMKII enzyme. Once the Threonine 286 residue has been phosphorylated, the inhibitory domain is blocked from the pseudosubstrate site. This effectively blocks autoinhibition, allowing for permanent activation of the CaMKII enzyme. This enables CamKII to be active, even in the absence of calcium and calmodulin.