KIDINS220
Description
The KIDINS220 (kinase D interacting substrate 220) is a protein-coding gene located on chromosome 2.
KIDINS220, or Kinase D-interacting substrate of 220 kDa, is a scaffold protein encoded by the KIDINS220 gene in humans. It is a downstream target of neuronal signaling events initiated by neurotrophins and ephrins. It also plays roles in the immune system by interacting with B-cell and T-cell receptors. KIDINS220 is located on chromosome 2 and encodes a transmembrane protein preferentially expressed in the nervous system. It acts as a receptor for the CRKL-C3G complex, leading to Rap1-dependent sustained ERK activation. Mutations in KIDINS220 are associated with a syndrome characterized by spastic paraplegia, intellectual disability, nystagmus, and obesity.
KIDINS220 promotes sustained MAP kinase signaling initiated by neurotrophins through a Rap1-dependent mechanism. It acts as a docking site for the CRKL-C3G complex, leading to sustained ERK activation. KIDINS220 is involved in regulating postsynaptic signal transduction by localizing receptor tyrosine kinases like EPHA4. In collaboration with SNTA1, it enhances EPHA4-induced JAK/STAT activation. It plays a role in NGF-induced recruitment of RAPGEF2 to late endosomes, contributing to neurite outgrowth. KIDINS220 is implicated in neurotrophin- and ephrin-mediated neuronal outgrowth, axon guidance during neural development, and neuronal regeneration. Additionally, it modulates stress-induced apoptosis of melanoma cells by regulating the MEK/ERK signaling pathway.
KIDINS220 is also known as ARMS, SINO, VENARG.
Associated Diseases
- Spastic paraplegia, intellectual disability, nystagmus, and obesity
- Spastic paraplegia-intellectual disability-nystagmus-obesity syndrome
- Ventriculomegaly and arthrogryposis
