Protein Details: Potassium voltage-gated channel subfamily D member 2
Protein ID
ICDB_Pro_1057
Protein Name
Potassium voltage-gated channel subfamily D member 2
Gene Name
Kcnd2
Organism
Rattus norvegicus (Rat)
Length
630 amino acids
AlphaFoldDB
AF-Q63881-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 (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). 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 . Likewise; interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity
Sequence
Ligand Binding
Binding Site
105;132;133
Disease
Location
Detected in brain cortex; hippocampus; dentate gyrus; thalamus and cerebellum (PubMed:16123112). Detected in neurons from the primary visual cortex (PubMed:16207878). Detected in the supraoptic nucleus in hypothalamus; in hippocampus and the habenular nucleus of the thalamus (PubMed:9070739). Detected in the bed nucleus of the stria terminalis (PubMed:24037673). Detected in dendritic fields in the hippocampus CA1 layer; in stratum radiatum; stratum oriens; stratum lacunosum-moleculare and stratum pyramidale (PubMed:10676964; PubMed:22098631). Detected in dendritic fields in the hippocampus CA3 layer and in dentate gyrus (PubMed:10676964). Detected in the cerebellum granule cell layer; where it localizes at synapses (PubMed:10676964; PubMed:11102480; PubMed:15736227). Detected in the main olfactory bulb; especially in the granule cell layer and the external plexiform layer; but also the mitral layer (PubMed:18371079). Detected in heart atrium and ventricle (PubMed:10860776). Detected in heart left ventricle (at protein level) (PubMed:24793047). Highly expressed in heart and throughout the brain; with similar levels in cortex and hypothalamus; and much higher levels in hippocampus; dentate gyrus and the habenular nucleus of the thalamus. Detected in brain; and at lower levels in heart atrium and ventricle (PubMed:1705709). Detected in neurons from the bed nucleus of the stria terminalis (PubMed:24037673). Detected in aorta; cardiac and smooth muscle.
DOI ID
10.1016/0896-6273(91)90299-f; 10.1073/pnas.88.5.1798; 10.1016/0014-5793(91)81420-d; 10.1016/s0008-6363(96)00221-0; 10.1016/s0306-4522(96)00561-1; 10.1074/jbc.275.8.5337; 10.1006/jmcc.2000.1172; 10.1046/j.1471-4159.2000.0752277.x; 10.1523/jneurosci.20-23-08736.2000; 10.1038/35000592; 10.1523/jneurosci.22-23-10123.2002; 10.1074/jbc.m200897200; 10.1074/jbc.m109412200; 10.1073/pnas.022509299; 10.1074/jbc.m306142200; 10.1038/nn1020; 10.1016/s0896-6273(02)01185-6; 10.1074/jbc.m304268200; 10.1074/jbc.m304675200; 10.1074/jbc.m409721200; 10.1523/jneurosci.0776-04.2004; 10.1016/s0896-6273(04)00049-2; 10.1007/s00424-004-1328-8; 10.1385/cbb:42:2:167; 10.1074/jbc.m410613200; 10.1002/cne.20443; 10.1523/jneurosci.2858-05.2005; 10.1113/jphysiol.2005.087858; 10.1074/jbc.m604843200; 10.1111/j.1471-4159.2006.04185.x; 10.1007/s12035-007-8001-0; 10.1016/j.neuron.2007.05.026; 10.1111/j.1460-9568.2008.06141.x; 10.1523/jneurosci.1951-08.2008; 10.1113/jphysiol.2007.150540; 10.1007/s11064-008-9650-8; 10.1021/bi802316m; 10.4161/chan.3.6.10216; 10.1161/circresaha.108.191007; 10.1523/jneurosci.4767-08.2009; 10.4161/chan.4.3.11479; 10.1016/j.mcn.2009.12.005; 10.1111/j.1460-9568.2011.07907.x; 10.1038/ncomms1871; 10.3389/fncel.2014.00329; 10.1002/cne.23435; 10.1074/jbc.m114.563452; 10.1007/s00424-014-1521-3; 10.1371/journal.pone.0084086; 10.1016/j.toxicon.2016.06.014; 10.1073/pnas.1432840100; 10.1016/s0896-6273(04)00045-5
RefSeq
NP_113918.2