You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NamePotassium voltage-gated channel subfamily B member 1
Synonyms
  • Delayed rectifier potassium channel 1
  • DRK1
  • h-DRK1
  • Voltage-gated potassium channel subunit Kv2.1
Gene NameKCNB1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008572|Potassium voltage-gated channel subfamily B member 1
MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKL
RDCNTHDSLLEVCDDYSLDDNEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELD
YWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREGEEFDNTCCAEKRKKLWDLLE
KPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWF
TMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFR
IMRILRILKLARHSTGLQSLGFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTK
FKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIAGVLVIALPIPIIVNNFSEFY
KEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGENMGKKDKVQD
NHLSPNKWKWTKRTLSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLEDMYNKMAKTQ
SQPILNTKESAAQSKPKEELEMESIPSPVAPLPTRTEGVIDMRSMSSIDSFISCATDFPE
ATRFSHSPLTSLPSKTGGSTAPEVGWRGALGASGGRFVEANPSPDASQHSSFFIESPKSS
MKTNNPLKLRALKVNFMEGDPSPLLPVLGMYHDPLRNRGSAAAAVAGLECATLLDKAVLS
PESSIYTTASAKTPPRSPEKHTAIAFNFEAGVHQYIDADTDDEGQLLYSVDSSPPKSLPG
STSPKFSTGTRSEKNHFESSPLPTSPKFLRQNCIYSTEALTGKGPSGQEKCKLENHISPD
VRVLPGGGAHGSTRDQSI
Number of residues858
Molecular Weight95876.615
Theoretical pINot Available
GO Classification
Functions
  • delayed rectifier potassium channel activity
  • protein heterodimerization activity
  • ion channel binding
  • outward rectifier potassium channel activity
  • ubiquitin-like protein binding
Processes
  • glucose homeostasis
  • energy reserve metabolic process
  • regulation of insulin secretion
  • positive regulation of protein targeting to membrane
  • cellular response to nutrient levels
  • cellular response to glucose stimulus
  • potassium ion transmembrane transport
  • positive regulation of norepinephrine secretion
  • action potential
  • protein targeting to plasma membrane
  • vesicle docking involved in exocytosis
  • regulation of action potential
  • protein homooligomerization
  • positive regulation of calcium ion-dependent exocytosis
  • positive regulation of catecholamine secretion
  • synaptic transmission
  • positive regulation of long term synaptic depression
  • negative regulation of insulin secretion
  • regulation of motor neuron apoptotic process
  • glutamate receptor signaling pathway
  • small molecule metabolic process
Components
  • dendrite membrane
  • dendrite
  • neuronal cell body membrane
  • perikaryon
  • lateral plasma membrane
  • sarcolemma
  • intracellular
  • postsynaptic membrane
  • plasma membrane
  • voltage-gated potassium channel complex
  • cell junction
  • axon
  • integral component of membrane
General FunctionUbiquitin-like protein binding
Specific FunctionVoltage-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).
Pfam Domain Function
Transmembrane Regions187-208 229-250 260-280 295-316 331-351 392-420
GenBank Protein IDNot Available
UniProtKB IDQ14721
UniProtKB Entry NameKCNB1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0017519|Potassium voltage-gated channel subfamily B member 1 (KCNB1)
ATGCCGGCGGGCATGACGAAGCATGGCTCCCGCTCCACCAGCTCGCTGCCGCCCGAGCCC
ATGGAGATCGTGCGCAGCAAGGCGTGCTCTCGGCGGGTCCGCCTCAACGTCGGGGGGCTG
GCGCACGAGGTACTCTGGCGTACCCTGGACCGCCTGCCCCGCACGCGGCTGGGCAAGCTC
CGCGACTGCAACACGCACGACTCGCTGCTCGAGGTGTGCGATGACTACAGCCTCGACGAC
AACGAGTACTTCTTTGACCGCCACCCGGGCGCCTTCACCTCCATCCTCAACTTCTACCGC
ACTGGGCGACTGCACATGATGGAGGAGATGTGCGCGCTCAGCTTCAGCCAAGAGCTCGAC
TACTGGGGCATCGACGAGATCTACCTGGAGTCCTGCTGCCAGGCCCGCTACCACCAGAAG
AAAGAGCAGATGAACGAGGAGCTCAAGCGTGAGGCCGAGACCCTACGGGAGCGGGAAGGC
GAGGAGTTCGATAACACGTGCTGCGCAGAGAAGAGGAAAAAACTCTGGGACCTACTGGAG
AAGCCCAATTCCTCTGTGGCTGCCAAGATCCTTGCCATAATTTCCATCATGTTCATCGTC
CTCTCCACCATTGCCCTGTCCCTCAACACGCTGCCTGAGCTACAGAGCCTCGATGAGTTC
GGCCAGTCCACAGACAACCCCCAGCTGGCCCACGTGGAGGCCGTGTGCATCGCATGGTTC
ACCATGGAGTACCTGCTGAGGTTCCTCTCCTCGCCCAAGAAGTGGAAGTTCTTCAAGGGC
CCACTCAATGCCATTGACTTGTTGGCCATTCTGCCATACTATGTCACCATTTTCCTCACC
GAATCCAACAAGAGCGTGCTGCAATTCCAGAATGTCCGCCGCGTGGTCCAGATCTTCCGC
ATCATGCGAATTCTCCGCATCCTTAAGCTTGCACGCCACTCCACTGGCCTCCAGTCTCTG
GGCTTCACTTTGCGGAGGAGCTACAATGAGTTGGGCTTGCTCATCCTCTTCCTTGCCATG
GGCATTATGATCTTCTCCAGCCTTGTCTTCTTTGCTGAGAAGGATGAGGACGACACCAAG
TTCAAAAGCATCCCAGCCTCTTTCTGGTGGGCCACCATCACCATGACTACTGTTGGGTAT
GGAGACATCTACCCCAAGACTCTCCTGGGGAAAATTGTTGGGGGACTCTGCTGCATTGCA
GGAGTCCTGGTGATTGCTCTTCCCATCCCCATCATCGTCAATAACTTCTCTGAGTTCTAT
AAGGAGCAGAAGAGACAGGAGAAAGCAATCAAACGGCGAGAGGCTCTGGAGAGAGCCAAG
AGGAATGGCAGCATCGTATCCATGAACATGAAGGATGCTTTTGCCCGGAGCATTGAGATG
ATGGACATTGTGGTTGAGAAAAATGGGGAGAATATGGGTAAGAAAGACAAAGTACAAGAT
AACCACTTGTCTCCTAACAAATGGAAATGGACAAAGAGGACACTGTCTGAAACCAGCTCA
AGTAAGTCCTTTGAAACCAAGGAACAGGGATCCCCTGAAAAAGCCAGATCGTCTTCTAGT
CCTCAGCACCTGAACGTTCAGCAGTTGGAAGACATGTACAATAAGATGGCCAAGACCCAA
TCCCAACCCATCCTCAATACCAAGGAGTCAGCAGCACAGAGCAAACCAAAGGAAGAACTT
GAAATGGAGAGTATCCCCAGCCCCGTAGCCCCTCTGCCCACTCGCACAGAAGGGGTCATT
GACATGCGAAGTATGTCAAGCATTGATAGTTTCATTAGCTGTGCCACAGACTTCCCTGAG
GCCACCAGATTCTCCCACAGCCCTTTGACATCACTCCCCAGCAAGACTGGGGGCAGCACA
GCCCCAGAAGTGGGCTGGCGGGGAGCTCTGGGTGCCAGTGGTGGTAGGTTTGTGGAGGCC
AACCCCAGCCCTGATGCCAGCCAGCACTCTAGTTTCTTCATCGAGAGCCCCAAGAGTTCC
ATGAAAACTAACAACCCTTTGAAGCTCCGAGCACTTAAAGTCAACTTCATGGAGGGTGAC
CCCAGTCCACTCCTCCCCGTTCTAGGGATGTACCATGACCCTCTCAGGAACCGGGGGAGT
GCTGCGGCTGCTGTCGCTGGACTGGAGTGTGCCACGCTTTTGGACAAGGCTGTGCTGAGC
CCAGAGTCCTCCATCTACACCACAGCAAGTGCTAAGACACCCCCCCGGTCTCCTGAGAAA
CACACAGCAATAGCGTTCAACTTTGAGGCGGGTGTCCACCAGTACATTGACGCAGACACA
GATGATGAGGGACAGCTGCTCTACAGTGTGGACTCCAGCCCCCCCAAAAGCCTCCCTGGG
AGCACCAGTCCGAAGTTCAGCACGGGGACAAGATCGGAGAAAAACCACTTTGAAAGCTCC
CCTTTACCCACCTCCCCTAAGTTCTTAAGGCAGAACTGTATTTACTCCACAGAAGCATTG
ACTGGAAAAGGCCCCAGTGGTCAGGAAAAGTGCAAACTTGAGAACCACATCTCCCCTGAC
GTCCGTGTGTTGCCAGGGGGAGGAGCCCATGGAAGCACACGAGATCAGAGCATCTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6231
Chromosome Location20
LocusNot Available
References
  1. Albrecht B, Lorra C, Stocker M, Pongs O: Cloning and characterization of a human delayed rectifier potassium channel gene. Receptors Channels. 1993;1(2):99-110. 8081723
  2. Ikeda SR, Soler F, Zuhlke RD, Joho RH, Lewis DL: Heterologous expression of the human potassium channel Kv2.1 in clonal mammalian cells by direct cytoplasmic microinjection of cRNA. Pflugers Arch. 1992 Nov;422(2):201-3. 1283219
  3. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  4. Shepard AR, Rae JL: Electrically silent potassium channel subunits from human lens epithelium. Am J Physiol. 1999 Sep;277(3 Pt 1):C412-24. 10484328
  5. Coetzee WA, Amarillo Y, Chiu J, Chow A, Lau D, McCormack T, Moreno H, Nadal MS, Ozaita A, Pountney D, Saganich M, Vega-Saenz de Miera E, Rudy B: Molecular diversity of K+ channels. Ann N Y Acad Sci. 1999 Apr 30;868:233-85. 10414301
  6. Sano Y, Mochizuki S, Miyake A, Kitada C, Inamura K, Yokoi H, Nozawa K, Matsushime H, Furuichi K: Molecular cloning and characterization of Kv6.3, a novel modulatory subunit for voltage-gated K(+) channel Kv2.1. FEBS Lett. 2002 Feb 13;512(1-3):230-4. 11852086
  7. MacDonald PE, Wang G, Tsuk S, Dodo C, Kang Y, Tang L, Wheeler MB, Cattral MS, Lakey JR, Salapatek AM, Lotan I, Gaisano HY: Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus. Mol Endocrinol. 2002 Nov;16(11):2452-61. 12403834
  8. Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ: Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7986-91. 12060745
  9. Shiau YS, Huang PT, Liou HH, Liaw YC, Shiau YY, Lou KL: Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels. Chem Res Toxicol. 2003 Oct;16(10):1217-25. 14565763
  10. Ju M, Stevens L, Leadbitter E, Wray D: The Roles of N- and C-terminal determinants in the activation of the Kv2.1 potassium channel. J Biol Chem. 2003 Apr 11;278(15):12769-78. Epub 2003 Jan 29. 12560340
  11. Yan L, Figueroa DJ, Austin CP, Liu Y, Bugianesi RM, Slaughter RS, Kaczorowski GJ, Kohler MG: Expression of voltage-gated potassium channels in human and rhesus pancreatic islets. Diabetes. 2004 Mar;53(3):597-607. 14988243
  12. Cox RH: Molecular determinants of voltage-gated potassium currents in vascular smooth muscle. Cell Biochem Biophys. 2005;42(2):167-95. 15858231
  13. Bocksteins E, Raes AL, Van de Vijver G, Bruyns T, Van Bogaert PP, Snyders DJ: Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in cultured small mouse DRG neurons. Am J Physiol Cell Physiol. 2009 Jun;296(6):C1271-8. doi: 10.1152/ajpcell.00088.2009. Epub 2009 Apr 8. 19357235
  14. Mederos Y Schnitzler M, Rinne S, Skrobek L, Renigunta V, Schlichthorl G, Derst C, Gudermann T, Daut J, Preisig-Muller R: Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4. J Biol Chem. 2009 Feb 13;284(7):4695-704. doi: 10.1074/jbc.M808786200. Epub 2008 Dec 11. 19074135
  15. Bocksteins E, Labro AJ, Mayeur E, Bruyns T, Timmermans JP, Adriaensen D, Snyders DJ: Conserved negative charges in the N-terminal tetramerization domain mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels. J Biol Chem. 2009 Nov 13;284(46):31625-34. doi: 10.1074/jbc.M109.039479. Epub 2009 Aug 28. 19717558
  16. Dai XQ, Kolic J, Marchi P, Sipione S, Macdonald PE: SUMOylation regulates Kv2.1 and modulates pancreatic beta-cell excitability. J Cell Sci. 2009 Mar 15;122(Pt 6):775-9. doi: 10.1242/jcs.036632. Epub 2009 Feb 17. 19223394
  17. Li XN, Herrington J, Petrov A, Ge L, Eiermann G, Xiong Y, Jensen MV, Hohmeier HE, Newgard CB, Garcia ML, Wagner M, Zhang BB, Thornberry NA, Howard AD, Kaczorowski GJ, Zhou YP: The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the regulation of insulin and somatostatin release from pancreatic islets. J Pharmacol Exp Ther. 2013 Feb;344(2):407-16. doi: 10.1124/jpet.112.199083. Epub 2012 Nov 16. 23161216
  18. King AN, Manning CF, Trimmer JS: A unique ion channel clustering domain on the axon initial segment of mammalian neurons. J Comp Neurol. 2014 Aug 1;522(11):2594-608. doi: 10.1002/cne.23551. 24477962
  19. Bocksteins E, Mayeur E, Van Tilborg A, Regnier G, Timmermans JP, Snyders DJ: The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits is determined by interactions between the N- and C-termini. PLoS One. 2014 Jun 5;9(6):e98960. doi: 10.1371/journal.pone.0098960. eCollection 2014. 24901643
  20. Torkamani A, Bersell K, Jorge BS, Bjork RL Jr, Friedman JR, Bloss CS, Cohen J, Gupta S, Naidu S, Vanoye CG, George AL Jr, Kearney JA: De novo KCNB1 mutations in epileptic encephalopathy. Ann Neurol. 2014 Oct;76(4):529-40. doi: 10.1002/ana.24263. Epub 2014 Sep 19. 25164438