Names & Taxonomy

Uniprot ID:
Q9NZV8
Entry Name:
KCND2_HUMAN
Status:
reviewed
Protein Names:
Potassium voltage-gated channel subfamily D member 2 (Voltage-gated potassium channel subunit Kv4.2)
Gene Names:
KCND2 KIAA1044
Gene Names Primary:
KCND2
Organism:
Homo sapiens (Human)

Structure

Length:
630
Sequence:
MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLERYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAFFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDTAGESALPTMTARQRVWRAFENPHTSTMALVFYYVTGFFIAVSVIANVVETVPCGSSPGHIKELPCGERYAVAFFCLDTACVMIFTVEYLLRLAAAPSRYRFVRSVMSIIDVVAILPYYIGLVMTDNEDVSGAFVTLRVFRVFRIFKFSRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPAAFWYTIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEQAFVSKSGSSFETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRIPNANVSGSHQGSIQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane
Intramembrane:
INTRAMEM 358 369 Helical; Name=Pore helix.

Function

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 rhytm 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 (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). 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 (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: Note=Homotetrameric channels activate rapidly, i.e within a few msec. After that, they inactivate rapidly, i.e within about 50-100 msec. The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system and the presence or absence of ancillary subunits. Homotetrameric channels have a unitary conductance of about 4 pS when expressed in a heterologous system. For the activation of homotetrameric channels expressed in xenopus oocytes, the voltage at half-maximal amplitude is about -10 mV. The time constant for inactivation is about 20 msec. For inactivation, the voltage at half-maximal amplitude is -62 mV. The time constant for recovery after inactivation is about 70 msec.
Cross Reference Drug Bank:
DB00321 DB06637 DB00280 DB00458
Gene Ontology Go:
cell junction
dendritic spine
integral component of plasma membrane
intrinsic component of plasma membrane
neuronal cell body membrane
perikaryon
plasma membrane
plasma membrane raft
postsynaptic membrane
voltage-gated potassium channel complex
A-type (transient outward) potassium channel activity
metal ion binding
voltage-gated potassium channel activity
action potential
cardiac conduction
cellular response to hypoxia
locomotor rhythm
neuronal action potential
potassium ion transmembrane transport
protein homooligomerization
sensory perception of pain
synaptic transmission
Gene Ontology Biological Process:
action potential
cardiac conduction
cellular response to hypoxia
locomotor rhythm
neuronal action potential
potassium ion transmembrane transport
protein homooligomerization
sensory perception of pain
synaptic transmission
Gene Ontology Molecular Function:
A-type (transient outward) potassium channel activity
metal ion binding
voltage-gated potassium channel activity
Gene Ontology Cellular Component:
cell junction
dendritic spine
integral component of plasma membrane
intrinsic component of plasma membrane
neuronal cell body membrane
perikaryon
plasma membrane
plasma membrane raft
postsynaptic membrane
voltage-gated potassium channel complex
Keywords:
Autism
Autism spectrum disorder
Cell junction
Cell membrane
Cell projection
Complete proteome
Disease mutation
Epilepsy
Ion channel
Ion transport
Membrane
Metal-binding
Phosphoprotein
Postsynaptic cell membrane
Potassium
Potassium channel
Potassium transport
Reference proteome
Synapse
Transmembrane
Transmembrane helix
Transport
Voltage-gated channel
Zinc
Interacts With:
Q9NZI2; Q9NS61; Q9NS61-3

Publication

PubMed ID:
9843794 10470851 10551270 10729221 12853948 15489334 11102480 10676964 11287421 11507158 12395204 11847232 12451113 14695263 15454437 15358149 16934482 17917103 18357523 19171772 24811166 14980201 14623880 15991246 14980207 19213956 24501278