CAMSAP3
Description
The CAMSAP3 (calmodulin regulated spectrin associated protein family member 3) is a protein-coding gene located on chromosome 19.
Calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) is a human protein encoded by the gene CAMSAP3. The protein is commonly referred to as Nezha. CAMSAP3 acts as a minus-end anchor of microtubules, and binds to them through its CKK domain. In epithelial cells, it anchors microtubules to the apical cortex, causing them to grow in an apical-to-basal direction. This gives the epithelial cells their rectangular shape. In early mouse embryogenesis, the interphase bridge linking sister cells is enriched with CAMSAP3.
CAMSAP3 is a key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19041755, PubMed:23169647). It recognizes growing microtubule minus-ends, decorates and stabilizes microtubule lattice formed by minus-end polymerization, and protects free minus-ends from depolymerization (PubMed:24486153). It also reduces the velocity of microtubule polymerization (PubMed:24486153). CAMSAP3 is required for the biogenesis and maintenance of zonula adherens by anchoring microtubule minus-ends to these junctions and recruiting the kinesin KIFC3 (PubMed:19041755). It is essential for orienting the apical-to-basal polarity of microtubules in epithelial cells by tethering non-centrosomal microtubules to the apical cortex (PubMed:27802168, PubMed:26715742). In early embryos lacking centrosomes, CAMSAP3 accumulates at microtubule bridges connecting cells, forming a non-centrosomal microtubule-organizing center that directs intracellular transport (By similarity). By interacting with MACF1 at the minus-ends of non-centrosomal microtubules, CAMSAP3 couples these microtubules to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). CAMSAP3 plays a key role in the generation of non-centrosomal microtubules by accumulating in the pericentrosomal region and cooperating with KATNA1 to release them from the centrosome (PubMed:28386021). Through the microtubule cytoskeleton, it regulates the organization of cellular organelles like the Golgi and early endosomes (PubMed:28089391). Interaction with AKAP9 is involved in translocation of Golgi vesicles in epithelial cells, where microtubules are mainly non-centrosomal (PubMed:28089391). CAMSAP3 plays an important role in motile cilia function by facilitating proper orientation of basal bodies and formation of central microtubule pairs (By similarity). {ECO:0000250|UniProtKB:Q80VC9, ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:26715742, ECO:0000269|PubMed:27693509, ECO:0000269|PubMed:27802168, ECO:0000269|PubMed:28089391, ECO:0000269|PubMed:28386021}
CAMSAP3 is also known as KIAA1543, NEZHA, PPP1R80.
Associated Diseases
- hemoglobin E-beta-thalassemia syndrome
- hemoglobin D disease
- cholesterol-ester transfer protein deficiency
- hypertriglyceridemia 2
- hemolytic anemia due to erythrocyte adenosine deaminase overproduction
- dominant beta-thalassemia
- galactokinase deficiency
- delta-beta-thalassemia
- pancreatic triacylglycerol lipase deficiency
- hemoglobin E disease
- IRIDA syndrome
- Rh deficiency syndrome
- hemoglobin C-beta-thalassemia syndrome
- alpha-thalassemia-myelodysplastic syndrome
- elliptocytosis 2
- homozygous familial hypercholesterolemia
- thyroid hormone metabolism, abnormal, 2
- sitosterolemia
- hemoglobin H disease
