Q9Z0V2 · KCND2_MOUSE
- ProteinA-type voltage-gated potassium channel KCND2
- GeneKcnd2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids630 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PubMed:10818150, PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518).
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 (PubMed:10818150, PubMed:17122039, PubMed:22815518).
Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (PubMed:22815518).
Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (PubMed:18045912).
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 (PubMed:10601491, PubMed:11909823, PubMed:23713033, PubMed:9734479).
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 (PubMed:22311982, PubMed:9734479).
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 (PubMed:11909823).
In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:11909823).
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 (PubMed:22311982).
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) (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 (PubMed:10818150, PubMed:17122039, PubMed:22815518).
Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (PubMed:22815518).
Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (PubMed:18045912).
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 (PubMed:10601491, PubMed:11909823, PubMed:23713033, PubMed:9734479).
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 (PubMed:22311982, PubMed:9734479).
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 (PubMed:11909823).
In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:11909823).
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 (PubMed:22311982).
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) (By similarity).
Miscellaneous
The transient neuronal A-type potassium current called I(SA) is triggered at membrane potentials that are below the threshold for action potentials. It inactivates rapidly and recovers rapidly from inactivation. It regulates the firing of action potentials and plays a role in synaptic integration and plasticity. Potassium channels containing KCND2 account for about 80% of the neuronal A-type potassium current. In contrast, the potassium channel responsible for the cardiac I(to) current differs between species; it is mediated by KCND2 in rodents. In human and other non-rodents KCND3 may play an equivalent role.
Is specifically and reversibly inhibited by the scorpion toxin Ts8 (AC P69940).
Catalytic activity
- K+(in) = K+(out)
Kinetics
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.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 105 | Zn2+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners; in chain A | ||||
Sequence: H | ||||||
Binding site | 111 | Zn2+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners; in chain B | ||||
Sequence: C | ||||||
Binding site | 132 | Zn2+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners; in chain A | ||||
Sequence: C | ||||||
Binding site | 133 | Zn2+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners; in chain A | ||||
Sequence: C | ||||||
Binding site | 370 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: T | ||||||
Binding site | 371 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: L | ||||||
Binding site | 372 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: G | ||||||
Binding site | 373 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: Y |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameA-type voltage-gated potassium channel KCND2
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z0V2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: In neurons, primarily detected on dendrites, dendritic spines and on the neuron cell body, but not on axons (PubMed:17122053, PubMed:22098631).
Localized preferentially at the dendrites of pyramidal cells in the hippocampus CA1 layer. Detected at GABAergic synapses (PubMed:16009497).
Detected at cell junctions that are distinct from synaptic cell contacts (By similarity).
Detected in lipid rafts (By similarity).
Detected primarily at the endoplasmic reticulum or Golgi when expressed by itself (By similarity).
Interaction with KCNIP1, KCNIP2, KCNIP3 or KCNIP4 promotes expression at the cell membrane (PubMed:22311982).
Interaction with DPP6 or DPP10 promotes expression at the cell membrane (By similarity).
Internalized from the cell membrane by clathrin-dependent endocytosis in response to activation of AMPA-selective glutamate receptors and PKA-mediated phosphorylation at Ser-552. Redistributed from dendritic spines to the main dendritic shaft in response to activation of AMPA-selective glutamate receptors and activation of PKA (By similarity).
Localized preferentially at the dendrites of pyramidal cells in the hippocampus CA1 layer. Detected at GABAergic synapses (PubMed:16009497).
Detected at cell junctions that are distinct from synaptic cell contacts (By similarity).
Detected in lipid rafts (By similarity).
Detected primarily at the endoplasmic reticulum or Golgi when expressed by itself (By similarity).
Interaction with KCNIP1, KCNIP2, KCNIP3 or KCNIP4 promotes expression at the cell membrane (PubMed:22311982).
Interaction with DPP6 or DPP10 promotes expression at the cell membrane (By similarity).
Internalized from the cell membrane by clathrin-dependent endocytosis in response to activation of AMPA-selective glutamate receptors and PKA-mediated phosphorylation at Ser-552. Redistributed from dendritic spines to the main dendritic shaft in response to activation of AMPA-selective glutamate receptors and activation of PKA (By similarity).
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-184 | Cytoplasmic | ||||
Sequence: MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLERYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAFFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDNTGESALPTMTARQRVWRAFENPHTSTMA | ||||||
Transmembrane | 185-206 | Helical; Name=Segment S1 | ||||
Sequence: LVFYYVTGFFIAVSVIANVVET | ||||||
Topological domain | 207-226 | Extracellular | ||||
Sequence: VPCGSSPGHIKELPCGERYA | ||||||
Transmembrane | 227-249 | Helical; Name=Segment S2 | ||||
Sequence: VAFFCLDTACVMIFTVEYLLRLA | ||||||
Topological domain | 250-256 | Cytoplasmic | ||||
Sequence: AAPSRYR | ||||||
Transmembrane | 257-281 | Helical; Name=Segment S3 | ||||
Sequence: FVRSVMSIIDVVAILPYYIGLVMTD | ||||||
Topological domain | 282-287 | Extracellular | ||||
Sequence: NEDVSG | ||||||
Transmembrane | 288-307 | Helical; Voltage-sensor; Name=Segment S4 | ||||
Sequence: AFVTLRVFRVFRIFKFSRHS | ||||||
Topological domain | 308-321 | Cytoplasmic | ||||
Sequence: QGLRILGYTLKSCA | ||||||
Transmembrane | 322-345 | Helical; Name=Segment S5 | ||||
Sequence: SELGFLLFSLTMAIIIFATVMFYA | ||||||
Topological domain | 346-357 | Extracellular | ||||
Sequence: EKGSSASKFTSI | ||||||
Intramembrane | 358-369 | Helical; Name=Pore helix | ||||
Sequence: PAAFWYTIVTMT | ||||||
Intramembrane | 370-377 | |||||
Sequence: TLGYGDMV | ||||||
Topological domain | 378-380 | Extracellular | ||||
Sequence: PKT | ||||||
Transmembrane | 381-403 | Helical; Name=Segment S6 | ||||
Sequence: IAGKIFGSICSLSGVLVIALPVP | ||||||
Topological domain | 404-630 | Cytoplasmic | ||||
Sequence: VIVSNFSRIYHQNQRADKRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEPAFISKSGSSFETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRIPNANVSGSHRGSVQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are viable, fertile and appear to be in good health (PubMed:16293790, PubMed:22738428).
The loss of KCND2 has only minor functional consequences, probably due to an increase of the activity of other potassium channels, even though there is no visible change of their expression levels (PubMed:20371829).
Mutant mice show no sign of heart dysfunction, but the fast component of the rapidly inactivating and rapidly recovering potassium current I(to) is lost in their ventricular myocytes (PubMed:16293790).
Instead, a slowly inactivating current is expressed that is not observed in wild-type (PubMed:16293790).
Electrocardiograms of mutant hearts display no significant differences relative to wild-type regarding their QT, PR, QRS and RR intervals (PubMed:16293790).
The neuronal A-type current is reduced by about 80% in brain cortex and hippocampus CA1 pyramidal neurons, by about 50% in suprachiasmatic nucleus neurons and by about 60% in dorsal horn neurons (PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518).
The dendritic A-type current is abolished in pyramidal neurons from the hippocampus CA1 layer (PubMed:17122039).
Concomitantly, the back-propagation of action potential in dendrites is increased (PubMed:17122039).
This may lower the treshold for neuronal long-term potentiation (LTP) (PubMed:17122039).
Loss of KCND2 does not influence the levels of KCND3 or KCNA4, but leads to reduced KCNIP1, KCNIP2 and KCNIP3 protein levels (PubMed:17122039, PubMed:18187474, PubMed:22612819).
Mutant mice show only minor differences in their behavior when compared to wild-type; they display hyperactivity to some, but not all, novel stimuli (PubMed:22738428).
Mutant mice show subtle spatial learning deficits (PubMed:20857488).
Mutant mice display shorter periods of locomotor activity that wild-type littermates, due to a corresponding change in the circadian rhythm of repetitive firing in suprachiasmatic nucleus neurons (PubMed:22815518).
Mutant mice display loss of spontaneous nociceptive behavior that is caused by the activation of GRM5 (PubMed:18045912).
The loss of KCND2 has only minor functional consequences, probably due to an increase of the activity of other potassium channels, even though there is no visible change of their expression levels (PubMed:20371829).
Mutant mice show no sign of heart dysfunction, but the fast component of the rapidly inactivating and rapidly recovering potassium current I(to) is lost in their ventricular myocytes (PubMed:16293790).
Instead, a slowly inactivating current is expressed that is not observed in wild-type (PubMed:16293790).
Electrocardiograms of mutant hearts display no significant differences relative to wild-type regarding their QT, PR, QRS and RR intervals (PubMed:16293790).
The neuronal A-type current is reduced by about 80% in brain cortex and hippocampus CA1 pyramidal neurons, by about 50% in suprachiasmatic nucleus neurons and by about 60% in dorsal horn neurons (PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518).
The dendritic A-type current is abolished in pyramidal neurons from the hippocampus CA1 layer (PubMed:17122039).
Concomitantly, the back-propagation of action potential in dendrites is increased (PubMed:17122039).
This may lower the treshold for neuronal long-term potentiation (LTP) (PubMed:17122039).
Loss of KCND2 does not influence the levels of KCND3 or KCNA4, but leads to reduced KCNIP1, KCNIP2 and KCNIP3 protein levels (PubMed:17122039, PubMed:18187474, PubMed:22612819).
Mutant mice show only minor differences in their behavior when compared to wild-type; they display hyperactivity to some, but not all, novel stimuli (PubMed:22738428).
Mutant mice show subtle spatial learning deficits (PubMed:20857488).
Mutant mice display shorter periods of locomotor activity that wild-type littermates, due to a corresponding change in the circadian rhythm of repetitive firing in suprachiasmatic nucleus neurons (PubMed:22815518).
Mutant mice display loss of spontaneous nociceptive behavior that is caused by the activation of GRM5 (PubMed:18045912).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 362 | Abolishes channel activity. Alters potassium channel kinetics in heart myocytes. Abolishes the fast component of I(to) in heart ventricle. | ||||
Sequence: W → F | ||||||
Mutagenesis | 602 | No effect on the regulation of neuronal A-type current in response to activation of metabotropic glutamate receptors. | ||||
Sequence: T → A | ||||||
Mutagenesis | 607 | No effect on the regulation of neuronal A-type current in response to activation of metabotropic glutamate receptors. | ||||
Sequence: T → A | ||||||
Mutagenesis | 616 | Abolishes regulation of neuronal A-type current in response to activation of metabotropic glutamate receptors. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 20 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000054065 | 1-630 | A-type voltage-gated potassium channel KCND2 | |||
Sequence: MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLERYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAFFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDNTGESALPTMTARQRVWRAFENPHTSTMALVFYYVTGFFIAVSVIANVVETVPCGSSPGHIKELPCGERYAVAFFCLDTACVMIFTVEYLLRLAAAPSRYRFVRSVMSIIDVVAILPYYIGLVMTDNEDVSGAFVTLRVFRVFRIFKFSRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPAAFWYTIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEPAFISKSGSSFETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRIPNANVSGSHRGSVQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL | ||||||
Modified residue | 38 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 438 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 548 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 552 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 572 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 575 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 602 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 607 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 616 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites. Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3. Phosphorylation at Ser-552 leads to KCND2 internalization (By similarity).
Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5 (PubMed:18045912).
Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (PubMed:18045912).
Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5 (PubMed:18045912).
Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (PubMed:18045912).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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).
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).
Gene expression databases
Interaction
Subunit
Homotetramer or heterotetramer with KCND3 or KCND1 (PubMed:11909823, PubMed:19713751, PubMed:20943905, PubMed:9734479).
Associates with the regulatory subunits KCNIP2, KCNIP3 and KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905).
Interacts with the regulatory subunit KCNIP1; this interaction mediates the capture of both the N- and C-terminus of KCND2, preventing N-type inactivation and stabilizing the S6 conformation, thereby accelerating closed state inactivation and recovery (By similarity).
In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751).
The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity).
Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity).
Interacts with DLG1 (By similarity).
Interacts with DLG4 (By similarity).
Interacts with NCS1/FREQ (PubMed:11606724).
Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity).
Interacts with FLNA and FLNC (By similarity).
Interacts with DPP10 (PubMed:22311982).
Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity).
Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery (PubMed:22311982).
Associates with the regulatory subunits KCNIP2, KCNIP3 and KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905).
Interacts with the regulatory subunit KCNIP1; this interaction mediates the capture of both the N- and C-terminus of KCND2, preventing N-type inactivation and stabilizing the S6 conformation, thereby accelerating closed state inactivation and recovery (By similarity).
In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751).
The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity).
Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity).
Interacts with DLG1 (By similarity).
Interacts with DLG4 (By similarity).
Interacts with NCS1/FREQ (PubMed:11606724).
Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity).
Interacts with FLNA and FLNC (By similarity).
Interacts with DPP10 (PubMed:22311982).
Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity).
Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery (PubMed:22311982).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Z0V2 | Kif17 Q99PW8 | 3 | EBI-959779, EBI-959754 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-20 | Interaction with KCNIP1, KCNIP2, and other family members | ||||
Sequence: AAGVAAWLPFARAAAIGWM | ||||||
Region | 71-90 | Interaction with KCNIP1 | ||||
Sequence: ERDFFYHPETQQYFFDRDPD | ||||||
Region | 308-321 | S4-S5 linker | ||||
Sequence: QGLRILGYTLKSCA | ||||||
Motif | 370-375 | Selectivity filter | ||||
Sequence: TLGYGD | ||||||
Region | 474-489 | Required for dendritic targeting | ||||
Sequence: FETQHHHLLHCLEKTT | ||||||
Region | 474-630 | Important for normal channel activation and inactivation, for interaction with KCNIP2, and probably other family members as well | ||||
Sequence: FETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRIPNANVSGSHRGSVQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL | ||||||
Region | 600-623 | Disordered | ||||
Sequence: IPTPPVTTPEGDDRPESPEYSGGN | ||||||
Motif | 627-630 | PDZ-binding | ||||
Sequence: VSAL |
Domain
The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (By similarity).
This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By similarity).
The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity).
The channel undergoes closed-state inactivation, where conformation changes lead to inactivation through an intermediate state involving breakdown of its 4-fold symmetry. that governs the distinct transient, fast-inactivating currents (By similarity).
This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By similarity).
The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity).
The channel undergoes closed-state inactivation, where conformation changes lead to inactivation through an intermediate state involving breakdown of its 4-fold symmetry. that governs the distinct transient, fast-inactivating currents (By similarity).
The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation. It is required for interaction with KCNIP2, and probably other family members as well.
Sequence similarities
Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length630
- Mass (Da)70,577
- Last updated1999-05-01 v1
- Checksum7FB94277429E7683
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 22 | in Ref. 2; BAA97986 | ||||
Sequence: V → A | ||||||
Sequence conflict | 516 | in Ref. 3; BAC41464 | ||||
Sequence: S → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF107780 EMBL· GenBank· DDBJ | AAD16972.1 EMBL· GenBank· DDBJ | mRNA | ||
AB045326 EMBL· GenBank· DDBJ | BAA97986.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AB093280 EMBL· GenBank· DDBJ | BAC41464.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK032268 EMBL· GenBank· DDBJ | BAC27787.1 EMBL· GenBank· DDBJ | mRNA | ||
AK032772 EMBL· GenBank· DDBJ | BAC28015.1 EMBL· GenBank· DDBJ | mRNA | ||
BC079667 EMBL· GenBank· DDBJ | AAH79667.1 EMBL· GenBank· DDBJ | mRNA |