Names & Taxonomy
- Uniprot ID:
- Q14721
- Entry Name:
- KCNB1_HUMAN
- Status:
- reviewed
- Protein Names:
- Potassium voltage-gated channel subfamily B member 1 (Delayed rectifier potassium channel 1) (DRK1) (h-DRK1) (Voltage-gated potassium channel subunit Kv2.1)
- Gene Names:
- KCNB1
- Gene Names Primary:
- KCNB1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 858
- Sequence:
- MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKLRDCNTHDSLLEVCDDYSLDDNEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELDYWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREGEEFDNTCCAEKRKKLWDLLEKPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWFTMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFRIMRILRILKLARHSTGLQSLGFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIAGVLVIALPIPIIVNNFSEFYKEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGENMGKKDKVQDNHLSPNKWKWTKRTLSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLEDMYNKMAKTQSQPILNTKESAAQSKPKEELEMESIPSPVAPLPTRTEGVIDMRSMSSIDSFISCATDFPEATRFSHSPLTSLPSKTGGSTAPEVGWRGALGASGGRFVEANPSPDASQHSSFFIESPKSSMKTNNPLKLRALKVNFMEGDPSPLLPVLGMYHDPLRNRGSAAAAVAGLECATLLDKAVLSPESSIYTTASAKTPPRSPEKHTAIAFNFEAGVHQYIDADTDDEGQLLYSVDSSPPKSLPGSTSPKFSTGTRSEKNHFESSPLPTSPKFLRQNCIYSTEALTGKGPSGQEKCKLENHISPDVRVLPGGGAHGSTRDQSI
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
- Intramembrane:
- INTRAMEM 365 376 Helical; Name=Pore helix.
Function
- 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 (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). 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 (PubMed:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340, PubMed:19074135, PubMed:19717558, PubMed:24901643). 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 (By similarity). 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 (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). 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 (By similarity). 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 (By similarity). 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 (PubMed:23161216). 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. 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 (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). 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 (By similarity).
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: Note=Homotetrameric channels expressed in xenopus oocytes or in mammalian non-neuronal cells display delayed-rectifier voltage-dependent potassium currents which are activated during membrane depolarization, i.e within a risetime of about 20 msec (PubMed:8081723, PubMed:1283219). After that, inactivate very slowly, i.e within more than 5 sec (PubMed:8081723, PubMed:1283219). Their activation requires low threshold potentials of about -20 to -30 mV, with a midpoint activation at about 10 mV. For inactivation, the voltage at half-maximal amplitude is about -20 mV (PubMed:11852086). The time constant for recovery after inactivation is about 1.6 sec. Channels have an unitary conductance of about 8 pS (PubMed:10484328). The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, the presence or absence of ancillary subunits and post-translational modifications.
- Enzyme Regulation:
- ENZYME REGULATION: Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (PubMed:14565763). Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata (PubMed:14565763). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) (PubMed:8081723, PubMed:1283219). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).
- Cross Reference Drug Bank:
- DB06637
- Gene Ontology Go:
- axon
cell junction
dendrite
intracellular
lateral plasma membrane
neuronal cell body membrane
perikaryon
plasma membrane
postsynaptic membrane
sarcolemma
voltage-gated potassium channel complex
delayed rectifier potassium channel activity
ion channel binding
protein heterodimerization activity
ubiquitin-like protein binding
action potential
cellular response to glucose stimulus
cellular response to nutrient levels
energy reserve metabolic process
glucose homeostasis
glutamate receptor signaling pathway
negative regulation of insulin secretion
positive regulation of calcium ion-dependent exocytosis
positive regulation of catecholamine secretion
positive regulation of long term synaptic depression
positive regulation of norepinephrine secretion
positive regulation of protein targeting to membrane
potassium ion transmembrane transport
protein homooligomerization
protein targeting to plasma membrane
regulation of action potential
regulation of insulin secretion
regulation of motor neuron apoptotic process
small molecule metabolic process
synaptic transmission
vesicle docking involved in exocytosis - Gene Ontology Biological Process:
- action potential
cellular response to glucose stimulus
cellular response to nutrient levels
energy reserve metabolic process
glucose homeostasis
glutamate receptor signaling pathway
negative regulation of insulin secretion
positive regulation of calcium ion-dependent exocytosis
positive regulation of catecholamine secretion
positive regulation of long term synaptic depression
positive regulation of norepinephrine secretion
positive regulation of protein targeting to membrane
potassium ion transmembrane transport
protein homooligomerization
protein targeting to plasma membrane
regulation of action potential
regulation of insulin secretion
regulation of motor neuron apoptotic process
small molecule metabolic process
synaptic transmission
vesicle docking involved in exocytosis - Gene Ontology Molecular Function:
- delayed rectifier potassium channel activity
ion channel binding
protein heterodimerization activity
ubiquitin-like protein binding - Gene Ontology Cellular Component:
- axon
cell junction
dendrite
intracellular
lateral plasma membrane
neuronal cell body membrane
perikaryon
plasma membrane
postsynaptic membrane
sarcolemma
voltage-gated potassium channel complex - Keywords:
- Cell junction
Cell membrane
Cell projection
Complete proteome
Disease mutation
Epilepsy
Exocytosis
Ion channel
Ion transport
Isopeptide bond
Membrane
Phosphoprotein
Polymorphism
Postsynaptic cell membrane
Potassium
Potassium channel
Potassium transport
Reference proteome
Synapse
Synaptosome
Transmembrane
Transmembrane helix
Transport
Ubl conjugation
Voltage-gated channel