GRIK2

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability.

Full Name

Glutamate Ionotropic Receptor Kainate Type Subunit 2

Function

Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (PubMed:28180184).

Modulates cell surface expression of NETO2 (By similarity).

Independent of its ionotropic glutamate receptor activity, acts as a thermoreceptor conferring sensitivity to cold temperatures (PubMed:31474366).

Functions in dorsal root ganglion neurons (By similarity).

Biological Process

Chemical synaptic transmission Source: ProtInc
Detection of cold stimulus involved in thermoception Source: UniProtKB
Glutamate receptor signaling pathway Source: ProtInc
Modulation of chemical synaptic transmission Source: UniProtKB
Positive regulation of synaptic transmission Source: UniProtKB
Regulation of short-term neuronal synaptic plasticity Source: UniProtKB
Synaptic transmission, glutamatergic Source: GO_Central

Cellular Location

Cell membrane; Postsynaptic cell membrane

Involvement in disease

Mental retardation, autosomal recessive 6 (MRT6):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. In contrast to syndromic or specific mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic mental retardation. MRT6 patients display mild to severe mental retardation and psychomotor development delay in early childhood. Patients do not have neurologic problems, congenital malformations, or facial dysmorphism. Body height, weight, and head circumference are normal.

Topology

Extracellular: 32-561
Helical: 562-582
Cytoplasmic: 583-635
Helical: 636-656
Extracellular: 657-819
Helical: 820-840
Cytoplasmic: 841-908

PTM

Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1 (By similarity).
Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome (By similarity).
Phosphorylated by PKC at Ser-868 upon agonist activation, this directly enhance sumoylation.