Protein: Potassium voltage-gated channel subfamily B member 1 (Delayed rectifier potassium channel 1) (DRK1) (Voltage-gated potassium channel subunit Kv2.1) (P15387)
Organism: Rattus norvegicus (Rat)
Function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain. Also plays a role in the regulation of exocytosis independently of its electrical function. 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. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes. Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells. Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion. Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (By similarity). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions. Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (By similarity). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner.
Subcellular location: Cell membrane {ECO:0000269|PubMed:10024359, ECO:0000269|PubMed:10414968, ECO:0000269|PubMed:10618149, ECO:0000269|PubMed:10719893, ECO:0000269|PubMed:12127166, ECO:0000269|PubMed:12403834, ECO:0000269|PubMed:12451110, ECO:0000269|PubMed:12560340, ECO:0000269|PubMed:12615930, ECO:0000269|PubMed:12621036, ECO:0000269|PubMed:12807875, ECO:0000269|PubMed:12832499, ECO:0000269|PubMed:12954870, ECO:0000269|PubMed:15195093, ECO:0000269|PubMed:15322114, ECO:0000269|PubMed:15855232, ECO:0000269|PubMed:16273079, ECO:0000269|PubMed:16319318, ECO:0000269|PubMed:16407566, ECO:0000269|PubMed:16988031, ECO:0000269|PubMed:17192433, ECO:0000269|PubMed:17301173, ECO:0000269|PubMed:17360683, ECO:0000269|PubMed:17379638, ECO:0000269|PubMed:17606996, ECO:0000269|PubMed:17965280, ECO:0000269|PubMed:18167541, ECO:0000269|PubMed:18463252, ECO:0000269|PubMed:18542995, ECO:0000269|PubMed:19014551, ECO:0000269|PubMed:19077057, ECO:0000269|PubMed:19219384, ECO:0000269|PubMed:19276663, ECO:0000269|PubMed:19690160, ECO:0000269|PubMed:20202934, ECO:0000269|PubMed:20484665, ECO:0000269|PubMed:21518833, ECO:0000269|PubMed:21712386, ECO:0000269|PubMed:22411134, ECO:0000269|PubMed:23878373, ECO:0000269|PubMed:24477962, ECO:0000269|PubMed:24569993, ECO:0000269|PubMed:24928958, ECO:0000269|PubMed:7623158, ECO:0000269|PubMed:8083226, ECO:0000269|PubMed:8463836, ECO:0000269|PubMed:8508921, ECO:0000269|PubMed:8670833, ECO:0000269|PubMed:8978827, ECO:0000269|PubMed:8980147, ECO:0000269|PubMed:9079713, ECO:0000269|PubMed:9305895, ECO:0000269|PubMed:9362476, ECO:0000269|PubMed:9522360, ECO:0000269|PubMed:9565597, ECO:0000269|PubMed:9616203, ECO:0000269|PubMed:9696692}. Perikaryon {ECO:0000269|PubMed:10024359, ECO:0000269|PubMed:10618149, ECO:0000269|PubMed:10719893, ECO:0000269|PubMed:12954870, ECO:0000269|PubMed:15195093, ECO:0000269|PubMed:16319318, ECO:0000269|PubMed:16407566, ECO:0000269|PubMed:16988031, ECO:0000269|PubMed:17379638, ECO:0000269|PubMed:17965280, ECO:0000269|PubMed:18463252, ECO:0000269|PubMed:19014551, ECO:0000269|PubMed:19077057, ECO:0000269|PubMed:1961744, ECO:0000269|PubMed:20202934, ECO:0000269|PubMed:21518833, ECO:0000269|PubMed:21712386, ECO:0000269|PubMed:22648171, ECO:0000269|PubMed:23878373, ECO:0000269|PubMed:24477962, ECO:0000269|PubMed:24569993, ECO:0000269|PubMed:7623158, ECO:0000269|PubMed:8463836, ECO:0000269|PubMed:8978827, ECO:0000269|PubMed:9522360}. Cell projection, dendrite {ECO:0000269|PubMed:10024359, ECO:0000269|PubMed:10618149, ECO:0000269|PubMed:10719893, ECO:0000269|PubMed:12954870, ECO:0000269|PubMed:15195093, ECO:0000269|PubMed:16319318, ECO:0000269|PubMed:16407566, ECO:0000269|PubMed:17379638, ECO:0000269|PubMed:17965280, ECO:0000269|PubMed:18463252, ECO:0000269|PubMed:19014551, ECO:0000269|PubMed:19077057, ECO:0000269|PubMed:20202934, ECO:0000269|PubMed:21518833, ECO:0000269|PubMed:21712386, ECO:0000269|PubMed:22648171, ECO:0000269|PubMed:23878373, ECO:0000269|PubMed:24477962, ECO:0000269|PubMed:24569993, ECO:0000269|PubMed:7623158, ECO:0000269|PubMed:8463836, ECO:0000269|PubMed:9522360}. Cell projection, axon {ECO:0000269|PubMed:19014551, ECO:0000269|PubMed:22648171, ECO:0000269|PubMed:24477962}. Postsynaptic cell membrane {ECO:0000269|PubMed:9522360}. Synapse {ECO:0000269|PubMed:9522360}. Synapse, synaptosome {ECO:0000269|PubMed:8508921}. Membrane {ECO:0000269|PubMed:8508921}; Multi-pass membrane protein. Lateral cell membrane {ECO:0000269|PubMed:8978827}. Cell membrane, sarcolemma {ECO:0000269|PubMed:17965280}. Note=Localizes to high-density somatodendritic clusters and non-clustered sites on the surface of neocortical and hippocampal pyramidal neurons in a cortical actin cytoskeleton-dependent manner (PubMed:10024359, PubMed:10719893, PubMed:15195093, PubMed:16319318, PubMed:16407566, PubMed:16988031, PubMed:17379638, PubMed:17606996, PubMed:18463252, PubMed:19014551, PubMed:1961744, PubMed:22648171, PubMed:23878373, PubMed:24477962, PubMed:24569993, PubMed:8978827, PubMed:9522360). Also localizes to high-density clusters in the axon initial segment (AIS), at ankyrin-G-deficient sites, on the surface of neocortical and hippocampal pyramidal neurons (PubMed:17379638, PubMed:19014551, PubMed:22648171, PubMed:24477962). KCNB1-containing AIS clusters localize either in close apposition to smooth endoplasmic reticulum cisternal organelles or with GABA-A receptor-containing synapses of hippocampal and cortical pyramidal neurons, respectively (PubMed:24477962). Localizes to high-density clusters on the cell surface of atrial and ventricular myocytes and at the lateral plasma membrane in epithelial cells (PubMed:17965280, PubMed:8978827). Localizes both to the axial and transverse tubules (T tubule) and sarcolemma in ventricular myocytes (PubMed:17965280). Associated with lipid raft domains (PubMed:15855232). In cortical neurons, apoptotic injuries induce de novo plasma membrane insertion in a SNARE-dependent manner causing an apoptotic potassium current surge (PubMed:16273079, PubMed:19077057). {ECO:0000250|UniProtKB:Q03717, ECO:0000250|UniProtKB:Q14721, ECO:0000269|PubMed:10024359, ECO:0000269|PubMed:10719893, ECO:0000269|PubMed:12615930, ECO:0000269|PubMed:12807875, ECO:0000269|PubMed:12954870, ECO:0000269|PubMed:15195093, ECO:0000269|PubMed:15855232, ECO:0000269|PubMed:16273079, ECO:0000269|PubMed:16319318, ECO:0000269|PubMed:16407566, ECO:0000269|PubMed:16988031, ECO:0000269|PubMed:17301173, ECO:0000269|PubMed:17379638, ECO:0000269|PubMed:17606996, ECO:0000269|PubMed:17965280, ECO:0000269|PubMed:18463252, ECO:0000269|PubMed:19014551, ECO:0000269|PubMed:19077057, ECO:0000269|PubMed:19219384, ECO:0000269|PubMed:1961744, ECO:0000269|PubMed:20202934, ECO:0000269|PubMed:21518833, ECO:0000269|PubMed:22648171, ECO:0000269|PubMed:23878373, ECO:0000269|PubMed:24477962, ECO:0000269|PubMed:24569993, ECO:0000269|PubMed:8508921, ECO:0000269|PubMed:8978827, ECO:0000269|PubMed:9522360}.
Sequence: MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKLRDCNTHDSLLQVCDDYSLEDNEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELDYWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREGEEFDNTCCAEKRKKLWDLLEKPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWFTMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFRIMRILRILKLARHSTGLQSLGFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIAGVLVIALPIPIIVNNFSEFYKEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGESIAKKDKVQDNHLSPNKWKWTKRALSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLEDMYSKMAKTQSQPILNTKEMAPQSKPPEELEMSSMPSPVAPLPARTEGVIDMRSMSSIDSFISCATDFPEATRFSHSPLASLSSKAGSSTAPEVGWRGALGASGGRLTETNPIPETSRSGFFVESPRSSMKTNNPLKLRALKVNFVEGDPTPLLPSLGLYHDPLRNRGGAAAAVAGLECASLLDKPVLSPESSIYTTASARTPPRSPEKHTAIAFNFEAGVHHYIDTDTDDEGQLLYSVDSSPPKSLHGSTSPKFSTGARTEKNHFESSPLPTSPKFLRPNCVYSSEGLTGKGPGAQEKCKLENHTPPDVHMLPGGGAHGSTRDQSI
InterPro domains: - IPR003973: Potassium channel, voltage dependent, Kv2 (family) [130-678]
- IPR028325: Voltage-gated potassium channel (family) [30-450]
- IPR027359: Voltage-dependent channel domain superfamily (homologous_superfamily) [161-313]
- IPR004350: Potassium channel, voltage dependent, Kv2.1 (family) [467-768]
- IPR003131: Potassium channel tetramerisation-type BTB domain (domain) [33-132]
- IPR000210: BTB/POZ domain (domain) [31-140]
- IPR011333: SKP1/BTB/POZ domain superfamily (homologous_superfamily) [23-152]
- IPR003968: Potassium channel, voltage dependent, Kv (family) [82-412]
- IPR005821: Ion transport domain (domain) [189-423]
Interaction partners: - Syntaxin-1A
- Vesicle-associated membrane protein-associated protein A
- Voltage-gated potassium channel subunit beta-1
- Voltage-gated potassium channel subunit beta-2
- Voltage-gated potassium channel subunit beta-3
- Ubiquitin-like protein FUBI
- FAU ubiquitin like and ribosomal protein S30 fusion like 2
- Delayed-rectifier potassium channel regulatory subunit KCNS1
- Vesicle-associated membrane protein-associated protein B
- Sodium channel protein type 2 subunit alpha
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:1901702 (salt transmembrane transporter activity), GO:0046983 (protein dimerization activity), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0044325 (transmembrane transporter binding), GO:0022803 (passive transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0005216 (monoatomic ion channel activity), GO:0015079 (potassium ion transmembrane transporter activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0015267 (channel activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0046982 (protein heterodimerization activity), GO:0005261 (monoatomic cation channel activity), GO:0022839 (monoatomic ion gated channel activity), GO:0005267 (potassium channel activity), GO:0022836 (gated channel activity), GO:0046873 (metal ion transmembrane transporter activity), GO:0022843 (voltage-gated monoatomic cation channel activity), GO:0005244 (voltage-gated monoatomic ion channel activity), GO:0005249 (voltage-gated potassium channel activity), GO:0022832 (voltage-gated channel activity), GO:0005251 (delayed rectifier potassium channel activity)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0051179 (localization), GO:0051234 (establishment of localization), GO:0051641 (cellular localization), GO:0055085 (transmembrane transport), GO:0033036 (macromolecule localization), GO:0070727 (cellular macromolecule localization), GO:0034220 (monoatomic ion transmembrane transport), GO:0051668 (localization within membrane), GO:0098660 (inorganic ion transmembrane transport), GO:0006810 (transport), GO:0098655 (monoatomic cation transmembrane transport), GO:0072657 (protein localization to membrane), GO:0098662 (inorganic cation transmembrane transport), GO:0008104 (protein localization), GO:0006811 (monoatomic ion transport), GO:0071805 (potassium ion transmembrane transport), GO:1990778 (protein localization to cell periphery), GO:0006812 (monoatomic cation transport), GO:0072659 (protein localization to plasma membrane), GO:0030001 (metal ion transport), GO:0006813 (potassium ion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0042995 (cell projection), GO:0016020 (membrane), GO:0044297 (cell body), GO:0044298 (cell body membrane), GO:0036477 (somatodendritic compartment), GO:0071944 (cell periphery), GO:0098796 (membrane protein complex), GO:1990351 (transporter complex), GO:0098797 (plasma membrane protein complex), GO:0043025 (neuronal cell body), GO:1902495 (transmembrane transporter complex), GO:0120025 (plasma membrane bounded cell projection), GO:0097447 (dendritic tree), GO:0032809 (neuronal cell body membrane), GO:0005886 (plasma membrane), GO:0043005 (neuron projection), GO:0034702 (ion channel complex), GO:0008076 (voltage-gated potassium channel complex), GO:0030425 (dendrite), GO:0034703 (cation channel complex), GO:0034705 (potassium channel complex)