KCND2
entrez
3751
canonical
uniprot
Q9NZV8
canonical
ensembl
ENSG00000184408
resolver
ensp
ENSP00000333496
resolver
enst
ENST00000331113
resolver
genesymbol
KCND2
resolver
genesymbol_syn
KIAA1044
resolver
hgnc
HGNC:6238
resolver
uniprot
O95012
resolver
uniprot
O95021
resolver
uniprot
Q2TBD3
resolver
uniprot
Q9UBY7
resolver
uniprot
Q9UN98
resolver
uniprot
Q9UNH9
resolver
uniprot_entry
KCND2_HUMAN
resolver
uniprot_sec
O95012
resolver
uniprot_sec
O95021
resolver
uniprot_sec
Q2TBD3
resolver
uniprot_sec
Q9UBY7
resolver
uniprot_sec
Q9UN98
resolver
uniprot_sec
Q9UNH9
resolver
amino_acid_sequence
MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLERYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAFFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDTAGESALPTMTARQRVWRAFENPHTSTMALVFYYVTGFFIAVSVIANVVETVPCGSSPGHIKELPCGERYAVAFFCLDTACVMIFTVEYLLRLAAAPSRYRFVRSVMSIIDVVAILPYYIGLVMTDNEDVSGAFVTLRVFRVFRIFKFSRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPAAFWYTIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEQAFVSKSGSSFETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRIPNANVSGSHQGSIQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL
uniprot
proteins
disease_involvement
DISEASE: Note=KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. {ECO:0000269|PubMed:24501278}.; DISEASE: Note=A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. {ECO:0000269|PubMed:16934482}.
uniprot
proteins
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 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 (PubMed:10551270, PubMed:11507158, PubMed:14623880, PubMed:14695263, PubMed:14980201, PubMed:15454437, PubMed:16934482, PubMed:19171772, PubMed:24501278, PubMed:24811166, PubMed:34552243, PubMed:35597238). 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:14623880, PubMed:14980201, PubMed:15454437, 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). 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) (PubMed:35597238). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10551270, ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278, ECO:0000269|PubMed:24811166, ECO:0000269|PubMed:34552243, ECO:0000269|PubMed:35597238}.
uniprot
proteins
mass_dalton
70537
uniprot
proteins
mutagenesis
MUTAGEN 309; /note="G->A: Increases peak current amplitude and causes a negative shift in the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 311; /note="R->A: No effect on peak current amplitude, but causes a positive shift in the voltage-dependence of activation. May increase the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 312; /note="I->A: Increases peak current amplitude and causes a positive shift in the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 313; /note="L->A: Causes a positive shift in the voltage-dependence of activation. May decrease the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 314; /note="G->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 315; /note="Y->A: Increases peak current amplitude but has a minor effect on the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 316; /note="T->A: Increases peak current amplitude and causes a positive shift in the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 317; /note="L->A: Increases peak current amplitude and causes a positive shift in the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 318; /note="K->A: Increases peak current amplitude and causes a positive shift in the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 319; /note="S->A: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 320; /note="C->A: Increases peak current amplitude and causes a positive shift in the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 320; /note="C->S: Increases peak current amplitude and slows the onset of inactivation at low voltage, but has no effect on the voltage-dependence of activation."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 322; /note="S->A: Increases peak current amplitude and causes a positive shift in the voltage-dependence of activation. May increase the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 323; /note="E->A: Slightly increases peak current amplitude and causes a negative shift in the voltage-dependence of activation. May decrease the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 324; /note="L->A: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 327; /note="L->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 328; /note="L->A: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 329; /note="F->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 397; /note="V->A: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 398; /note="I->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 399; /note="A->V: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 401; /note="P->A: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 402..404; /note="VPV->IPI: Increases pak current amplitude and causes a positive shift in the voltage-dependence of activation and steady-state inactivation. May increase the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 403; /note="P->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 405; /note="I->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 406; /note="V->A: Loss of channel activity."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 407; /note="S->A: Increases peak current amplitude but has no effect on the voltage-dependence of activation. May increase the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 408; /note="N->A: Decreases peak current amplitude and causes a positive shift in the voltage-dependence of activation. May increase the affinity for the closed-inactivated state of the channel."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 409; /note="F->A: May impair protein folding."; /evidence="ECO:0000269|PubMed:19171772"; MUTAGEN 601..604; /note="PTPP->ATAA: Abolishes interaction with FLNC."; /evidence="ECO:0000269|PubMed:11102480
uniprot
proteins
post_translational_modification
PTM: 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 (By similarity). Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (By similarity). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2}.
uniprot
proteins
protein_family
D (Shal) (TC 1.A.1.2) subfamily
uniprot
proteins
protein_family
Kv4.2/KCND2 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10470851
uniprot
proteins
pubmed
10551270
uniprot
proteins
pubmed
10676964
uniprot
proteins
pubmed
10729221
uniprot
proteins
pubmed
11102480
uniprot
proteins
pubmed
11287421
uniprot
proteins
pubmed
11507158
uniprot
proteins
pubmed
11847232
uniprot
proteins
pubmed
12395204
uniprot
proteins
pubmed
12451113
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14623880
uniprot
proteins
pubmed
14695263
uniprot
proteins
pubmed
14980201
uniprot
proteins
pubmed
14980207
uniprot
proteins
pubmed
15358149
uniprot
proteins
pubmed
15454437
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15991246
uniprot
proteins
pubmed
16934482
uniprot
proteins
pubmed
17917103
uniprot
proteins
pubmed
18357523
uniprot
proteins
pubmed
19171772
uniprot
proteins
pubmed
19213956
uniprot
proteins
pubmed
24501278
uniprot
proteins
pubmed
24811166
uniprot
proteins
pubmed
34552243
uniprot
proteins
pubmed
35597238
uniprot
proteins
pubmed
9843794
uniprot
proteins
sequence_length
630
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278, ECO:0000269|PubMed:24811166}; Multi-pass membrane protein {ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:14980201, ECO:0000305}. Cell projection, dendrite {ECO:0000269|PubMed:11102480}. Synapse {ECO:0000250|UniProtKB:Q63881}. Perikaryon {ECO:0000250|UniProtKB:Q63881}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q63881}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q63881}. Cell junction {ECO:0000250|UniProtKB:Q63881}. Note=In neurons, primarily detected on dendrites, dendritic spines and on the neuron cell body, but not on axons. Localized preferentially at the dendrites of pyramidal cells in the hippocampus CA1 layer. Detected at GABAergic synapses. Detected at cell junctions that are distinct from synaptic cell contacts. Detected in lipid rafts. Detected primarily at the endoplasmic reticulum or Golgi when expressed by itself (PubMed:15454437). Interaction with KCNIP1, KCNIP2, KCNIP3 or KCNIP4 promotes expression at the cell membrane (PubMed:15454437, PubMed:24811166). 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). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:24811166}.
uniprot
proteins
transmembrane_region
TRANSMEM 185..206; /note="Helical; Name=Segment S1"; /evidence="ECO:0000269|PubMed:34552243, ECO:0007744|PDB:7F0J"; TRANSMEM 227..249; /note="Helical; Name=Segment S2"; /evidence="ECO:0000269|PubMed:34552243, ECO:0007744|PDB:7F0J"; TRANSMEM 257..281; /note="Helical; Name=Segment S3"; /evidence="ECO:0000269|PubMed:34552243, ECO:0007744|PDB:7F0J"; TRANSMEM 288..307; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000269|PubMed:34552243, ECO:0007744|PDB:7F0J"; TRANSMEM 322..345; /note="Helical; Name=Segment S5"; /evidence="ECO:0000269|PubMed:34552243, ECO:0007744|PDB:7F0J"; TRANSMEM 381..403; /note="Helical; Name=Segment S6"; /evidence="ECO:0000269|PubMed:34552243, ECO:0007744|PDB:7F0J
uniprot
proteins