Protein Details: Potassium voltage-gated channel subfamily D member 2
Protein ID
ICDB_Pro_1728
Protein Name
Potassium voltage-gated channel subfamily D member 2
Gene Name
Kcnd2; Kiaa1044; MNCb-7013
Organism
Mus musculus (Mouse)
Length
630 amino acids
AlphaFoldDB
AF-Q9Z0V2-F1-model_v4.pdb
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes; primarily in the brain; but also in rodent heart. Mediates the major part of the dendritic A-type current I(SA) in brain neurons . This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability; prolongs the latency before the first spike in a series of action potentials; regulates the frequency of repetitive action potential firing; shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites . Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons; which regulates the circadian rhythm of locomotor activity. Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5. Mediates the transient outward current I(to) in rodent heart left ventricle apex cells; but not in human heart; where this current is mediated by another family member . Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane . Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo; membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1; KCNIP2; KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation; shifts the threshold for channel activation to more negative voltage values; shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (By similarity). Likewise; interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity
Sequence
PDB Structures
Ligand Binding
Binding Site
105;132;133
Disease
Location
Detected in hippocampus; thalamus; medial habenular nucleus; striatum; amygdala; brain cortex and cerebellum (PubMed:11040264; PubMed:17122039; PubMed:18187474; PubMed:20371829; PubMed:22612819). Detected in hippocampus CA1 and CA3 layer; in stratum oriens; stratum radiatum and stratum lacunosum-moleculare and in dentate gyrus (PubMed:16009497; PubMed:22098631). Detected in dorsal horn neurons; colocalizes with GRM5 (PubMed:18045912). C-terminally phosphorylated forms are detected in the stratum radiatum and in basilar dendrites in stratum oriens in hippocampus CA1 and on cell bodies in hippocampus CA3 layers; with lower levels in stratum lacunosum-moleculare (PubMed:11040264). In contrast; N-terminally phosphorylated forms are detected in stratum lacunosum moleculare in the hippocampus CA1 layer (PubMed:11040264). Both C-terminally and N-terminally phosphorylated forms are observed on cell bodies and neuronal processes in the amygdala (PubMed:11040264). C-terminally phosphorylated forms are detected in the dentate gyrus molecular layer; while N-terminally phosphorylated forms are detected in the hilus of the dentate gyrus (PubMed:11040264). Both N-terminally and C-terminally phosphorylated forms are detected in the somatosensory cortex (PubMed:11040264). C-terminally phosphorylated forms are detected in the cerebellum granular layers (PubMed:11040264). Detected in heart ventricle myocytes (at protein level) (PubMed:11909823; PubMed:16293790; PubMed:23713033; PubMed:9734479). Detected in brain and heart (PubMed:16293790).
DOI ID
10.1093/dnares/9.5.179; 10.1126/science.1112014; 10.1101/gr.2596504; 10.1161/01.res.83.5.560; 10.1111/j.1469-7793.1999.00587.x; 10.1523/jneurosci.20-11-04145.2000; 10.1101/lm.35300; 10.1073/pnas.221168498; 10.1161/01.res.0000012664.05949.e0; 10.1161/01.res.0000196559.63223.aa; 10.1016/j.neuroscience.2005.04.065; 10.1523/jneurosci.2667-06.2006; 10.1523/jneurosci.2599-06.2006; 10.1523/jneurosci.0269-07.2007; 10.1007/s12035-007-8001-0; 10.1113/jphysiol.2007.146597; 10.1007/s11064-008-9650-8; 10.4161/chan.3.4.9553; 10.1016/j.cell.2010.12.001; 10.1523/jneurosci.5890-09.2010; 10.1523/jneurosci.2487-10.2010; 10.1002/hipo.20877; 10.1186/2045-5380-2-5; 10.1111/j.1528-1167.2012.03485.x; 10.1111/j.1460-9568.2011.07907.x; 10.1074/jbc.m111.324574; 10.1523/jneurosci.0174-12.2012; 10.1113/jphysiol.2013.255836
RefSeq
NP_062671.1