lmmol · Proteins

A-type voltage-gated potassium channel KCND2

UniProt Q9NZV8 Organism Homo sapiens Gene KCND2, KIAA1044

Also known as: KCND2, KIAA1044

Function

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). 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 (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state).

Classification

Family (Pfam)
PF02214 BTB_2, PF11879 DUF3399, PF00520 Ion_trans, PF11601 Shal-type
InterPro
BTB/POZ_dom, Ion_trans_dom, K_chnl_volt-dep_Kv, K_chnl_volt-dep_Kv4, K_chnl_volt-dep_Kv4.2, K_chnl_volt-dep_Kv4_C, Shal-type_N, SKP1/BTB/POZ_sf, T1-type_BTB, VG_K_chnl, Volt_channel_dom_sf
Functional cluster
Protein Serine/Threonine Kinases

Experimental structures · PDB · 16

A predicted model is available from AlphaFold.

Gene Ontology · 27

Drugs targeting this protein · 6

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 29 cited papers

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