Kcnd2
entrez
65180
canonical
uniprot
Q63881
canonical
ensembl
ENSRNOG00000067416
resolver
ensp
ENSRNOP00000095226
resolver
enst
ENSRNOT00000112178
resolver
genesymbol
Kcnd2
resolver
uniprot
A0A8I6GL23
resolver
uniprot
Q00090
resolver
uniprot
Q99249
resolver
uniprot_entry
A0A8I6GL23_RAT
resolver
uniprot_entry
KCND2_RAT
resolver
uniprot_sec
Q00090
resolver
uniprot_sec
Q99249
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by 5 mM 4-aminopyridine (4-AP) (PubMed:1722463, PubMed:1840649, PubMed:9093524). Not inhibited by dendrotoxins and by tetraethylammonium (TEA) (PubMed:1722463). Inhibited by 10 mM flecainide and 20 mM quinidine (PubMed:9093524). Inhibited by the heteropodatoxins HpTx(1), HpTx(2), and HpTx(3) (PubMed:9058605). {ECO:0000269|PubMed:1722463, ECO:0000269|PubMed:1840649, ECO:0000269|PubMed:9058605, ECO:0000269|PubMed:9093524}.
uniprot
proteins
amino_acid_sequence
MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLERYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAFFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDNTGESALPTMTARQRVWRAFENPHTSTMALVFYYVTGFFIAVSVIANVVETVPCGSSPGHIKELPCGERYAVAFFCLDTACVMIFTVEYLLRLAAAPSRYRFVRSVMSIIDVVAILPYYIGLVMTDNEDVSGAFVTLRVFRVFRIFKFSRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPAAFWYTIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEPAFVSKSGSSFETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKSFRIPNANVSGSHRGSVQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL
uniprot
proteins
function
FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart (PubMed:10676964, PubMed:12592409, PubMed:12754210, PubMed:14980206, PubMed:16123112, PubMed:16207878, PubMed:1722463, PubMed:1840649, PubMed:19279261, PubMed:25352783, PubMed:9058605, PubMed:9093524). Mediates the major part of the dendritic A-type current I(SA) in brain neurons (PubMed:16207878, PubMed:17026528). 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 (PubMed:9058605, PubMed:9093524). 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:10676964, PubMed:12451113, PubMed:12592409, PubMed:12754210, PubMed:14980206, PubMed:15452711, PubMed:16207878, PubMed:16820361, PubMed:1722463, PubMed:1840649, PubMed:25352783, PubMed:9093524). 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:25352783). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:12451113, PubMed:16123112). 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:12451113, PubMed:14980206, PubMed:15452711, PubMed:16123112, PubMed:16820361, PubMed:20045463). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:15671030, PubMed:16123112, PubMed:19279261, PubMed:19441798, PubMed:19901547). 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). {ECO:0000250|UniProtKB:Q9NZV8, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11847232, ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:12592409, ECO:0000269|PubMed:12754210, ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:15452711, ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:16123112, ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:16820361, ECO:0000269|PubMed:17026528, ECO:0000269|PubMed:1722463, ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:1840649, ECO:0000269|PubMed:19279261, ECO:0000269|PubMed:19441798, ECO:0000269|PubMed:19901547, ECO:0000269|PubMed:24404150, ECO:0000269|PubMed:25352783, ECO:0000269|PubMed:9058605, ECO:0000269|PubMed:9093524, ECO:0000305}.
uniprot
proteins
mass_dalton
70549
uniprot
proteins
mutagenesis
MUTAGEN 7..11; /note="Missing: Greatly reduces interaction with KCNIP1."; /evidence="ECO:0000269|PubMed:14980207"; MUTAGEN 8; /note="W->A: Abolishes interaction with KCNP1; when associated with A-11."; /evidence="ECO:0000269|PubMed:14980206"; MUTAGEN 11; /note="F->A: Abolishes interaction with KCNP1; when associated with A-8."; /evidence="ECO:0000269|PubMed:14980206"; MUTAGEN 66; /note="L->R: Abolishes expression."; /evidence="ECO:0000269|PubMed:12835418"; MUTAGEN 71; /note="E->K: Abolishes interaction with KCNIP1."; /evidence="ECO:0000269|PubMed:14980207"; MUTAGEN 73; /note="D->M: Abolishes interaction with KCNIP1."; /evidence="ECO:0000269|PubMed:14980207"; MUTAGEN 74; /note="F->R: Abolishes interaction with KCNIP1."; /evidence="ECO:0000269|PubMed:14980207"; MUTAGEN 79; /note="E->L,R: Abolishes interaction with KCNIP1."; /evidence="ECO:0000269|PubMed:14980207"; MUTAGEN 93; /note="R->A: Greatly reduces expression and changes multimerization."; /evidence="ECO:0000269|PubMed:12835418"; MUTAGEN 105; /note="H->A: Abolishes tetramerization and assembly of a functional channel."; /evidence="ECO:0000269|PubMed:12754210"; MUTAGEN 111; /note="C->A: Abolishes tetramerization and assembly of a functional channel; when associated with A-105; A-132 and A-133."; /evidence="ECO:0000269|PubMed:12754210"; MUTAGEN 132; /note="C->A: Abolishes tetramerization and assembly of a functional channel; when associated with A-105; A-111 and A-133."; /evidence="ECO:0000269|PubMed:12754210"; MUTAGEN 133; /note="C->A: Abolishes tetramerization and assembly of a functional channel; when associated with A-105; A-111 and A-132."; /evidence="ECO:0000269|PubMed:12754210"; MUTAGEN 481..482; /note="Missing: Loss of dendritic targeted expression."; /evidence="ECO:0000269|PubMed:12592409"; MUTAGEN 552; /note="S->A: Abolishes PKA-mediated modulation of cell surface expression and channel activity."; /evidence="ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:18650329"; MUTAGEN 627..630; /note="Missing: Abolishes interaction with DLG4."; /evidence="ECO:0000269|PubMed:11923279, ECO:0000269|PubMed:14559911
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites (PubMed:24404150). Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552 (PubMed:19441798). Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3 (PubMed:12451113). Phosphorylation at Ser-552 leads to KCND2 internalization (PubMed:17582333). 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:Q9Z0V2, ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:19441798, ECO:0000269|PubMed:24404150}.
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
10676964
uniprot
proteins
pubmed
10681507
uniprot
proteins
pubmed
10860776
uniprot
proteins
pubmed
11080179
uniprot
proteins
pubmed
11102480
uniprot
proteins
pubmed
11805342
uniprot
proteins
pubmed
11847232
uniprot
proteins
pubmed
11923279
uniprot
proteins
pubmed
12451113
uniprot
proteins
pubmed
12575952
uniprot
proteins
pubmed
12592409
uniprot
proteins
pubmed
12754210
uniprot
proteins
pubmed
12829703
uniprot
proteins
pubmed
12835418
uniprot
proteins
pubmed
14559911
uniprot
proteins
pubmed
14980206
uniprot
proteins
pubmed
14980207
uniprot
proteins
pubmed
15356203
uniprot
proteins
pubmed
15452711
uniprot
proteins
pubmed
15485870
uniprot
proteins
pubmed
15671030
uniprot
proteins
pubmed
15736227
uniprot
proteins
pubmed
15858231
uniprot
proteins
pubmed
16123112
uniprot
proteins
pubmed
16207878
uniprot
proteins
pubmed
16820361
uniprot
proteins
pubmed
17026528
uniprot
proteins
pubmed
1705709
uniprot
proteins
pubmed
1722463
uniprot
proteins
pubmed
17582333
uniprot
proteins
pubmed
17917103
uniprot
proteins
pubmed
18276729
uniprot
proteins
pubmed
18357523
uniprot
proteins
pubmed
18371079
uniprot
proteins
pubmed
1840649
uniprot
proteins
pubmed
18650329
uniprot
proteins
pubmed
19213956
uniprot
proteins
pubmed
19279261
uniprot
proteins
pubmed
19441798
uniprot
proteins
pubmed
19901547
uniprot
proteins
pubmed
20045463
uniprot
proteins
pubmed
20224290
uniprot
proteins
pubmed
22098631
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
24037673
uniprot
proteins
pubmed
24404150
uniprot
proteins
pubmed
24793047
uniprot
proteins
pubmed
24811166
uniprot
proteins
pubmed
25352783
uniprot
proteins
pubmed
27346450
uniprot
proteins
pubmed
9058605
uniprot
proteins
pubmed
9070739
uniprot
proteins
pubmed
9093524
uniprot
proteins
sequence_length
630
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:10860776, ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:11847232, ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:12592409, ECO:0000269|PubMed:12754210, ECO:0000269|PubMed:12829703, ECO:0000269|PubMed:14559911, ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:15452711, ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:15671030, ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:16123112, ECO:0000269|PubMed:16820361, ECO:0000269|PubMed:1722463, ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18371079, ECO:0000269|PubMed:1840649, ECO:0000269|PubMed:18650329, ECO:0000269|PubMed:20045463, ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24793047, ECO:0000269|PubMed:25352783, ECO:0000269|PubMed:9070739, ECO:0000269|PubMed:9093524}; Multi-pass membrane protein {ECO:0000305}. Cell projection, dendrite {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:12592409, ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18371079, ECO:0000269|PubMed:20224290, ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24037673, ECO:0000269|PubMed:24404150, ECO:0000269|PubMed:9070739}. Synapse {ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:9070739}. Perikaryon {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:18371079, ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:9070739}. Postsynaptic cell membrane {ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:9070739}. Cell projection, dendritic spine {ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18650329, ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24037673, ECO:0000269|PubMed:9070739}. Cell membrane, sarcolemma {ECO:0000269|PubMed:10860776}. Cell junction {ECO:0000269|PubMed:18371079}. Membrane, caveola {ECO:0000269|PubMed:20224290}. Note=In neurons, primarily detected on dendrites, dendritic spines and on the neuron cell body, but not on axons (PubMed:16207878, PubMed:17582333, PubMed:22098631, PubMed:9070739). Localized preferentially at the dendrites of pyramidal cells in the hippocampus CA1 layer (PubMed:22098631). Detected at GABAergic synapses (By similarity). Detected at cell junctions that are distinct from synaptic cell contacts (PubMed:18371079). Detected in lipid rafts (PubMed:14559911, PubMed:20224290, PubMed:24793047). Detected primarily at the endoplasmic reticulum or Golgi when expressed by itself (PubMed:12754210, PubMed:12829703, PubMed:14980206, PubMed:16820361, PubMed:19441798). Interaction with KCNIP1, KCNIP2, KCNIP3 or KCNIP4 promotes expression at the cell membrane (PubMed:12829703, PubMed:14980206, PubMed:15485870, PubMed:20045463). Interaction with DPP6 or DPP10 promotes expression at the cell membrane (PubMed:19441798). 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 (PubMed:17582333, PubMed:18650329). Redistributed from dendritic spines to the main dendritic shaft in response to activation of AMPA-selective glutamate receptors and activation of PKA (PubMed:17582333, PubMed:18650329). {ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:12754210, ECO:0000269|PubMed:14559911, ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:16820361, ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18650329, ECO:0000269|PubMed:19441798, ECO:0000269|PubMed:20045463, ECO:0000269|PubMed:20224290, ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24793047, ECO:0000269|PubMed:9070739, ECO:0000305}.
uniprot
proteins
transmembrane_region
TRANSMEM 185..206; /note="Helical; Name=Segment S1"; /evidence="ECO:0000250|UniProtKB:Q9NZV8"; TRANSMEM 227..249; /note="Helical; Name=Segment S2"; /evidence="ECO:0000250|UniProtKB:Q9NZV8"; TRANSMEM 257..281; /note="Helical; Name=Segment S3"; /evidence="ECO:0000250|UniProtKB:Q9NZV8"; TRANSMEM 288..307; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000250|UniProtKB:Q9NZV8"; TRANSMEM 322..345; /note="Helical; Name=Segment S5"; /evidence="ECO:0000250|UniProtKB:Q9NZV8"; TRANSMEM 381..403; /note="Helical; Name=Segment S6"; /evidence="ECO:0000250|UniProtKB:Q9NZV8
uniprot
proteins