Potassium voltage-gated channel subfamily D member 2

Details

Name
Potassium voltage-gated channel subfamily D member 2
Synonyms
  • KIAA1044
  • Voltage-gated potassium channel subunit Kv4.2
Gene Name
KCND2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006933|Potassium voltage-gated channel subfamily D member 2
MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLE
RYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELA
FFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDTAGESALPTMTARQRVWRAFENPHT
STMALVFYYVTGFFIAVSVIANVVETVPCGSSPGHIKELPCGERYAVAFFCLDTACVMIF
TVEYLLRLAAAPSRYRFVRSVMSIIDVVAILPYYIGLVMTDNEDVSGAFVTLRVFRVFRI
FKFSRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPAA
FWYTIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRAD
KRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEQAFVSKSGSSFETQHHH
LLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRI
PNANVSGSHQGSIQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISI
PTPPVTTPEGDDRPESPEYSGGNIVRVSAL
Number of residues
630
Molecular Weight
70535.825
Theoretical pI
8.03
GO Classification
Functions
A-type (transient outward) potassium channel activity / metal ion binding / voltage-gated potassium channel activity
Processes
action potential / cellular response to hypoxia / locomotor rhythm / neuronal action potential / potassium ion transmembrane transport / protein homooligomerization / sensory perception of pain / synaptic transmission
Components
cell junction / dendritic spine / integral component of plasma membrane / intrinsic component of plasma membrane / neuronal cell body membrane / perikaryon / plasma membrane / plasma membrane raft / postsynaptic membrane / voltage-gated potassium channel complex
General Function
Voltage-gated potassium channel activity
Specific 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 rhytm 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:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). 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:15454437, PubMed:14623880, PubMed:14980201, 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).
Pfam Domain Function
Transmembrane Regions
183-204 229-250 262-279 287-306 322-343 385-413
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019444|Potassium voltage-gated channel subfamily D member 2 (KCND2)
ATGGCGGCGGGGGTGGCAGCGTGGCTGCCTTTTGCAAGGGCAGCGGCTATCGGGTGGATG
CCTGTGGCCTCGGGGCCTATGCCGGCTCCCCCGAGGCAGGAGAGGAAAAGGACCCAAGAT
GCTCTCATTGTGCTGAATGTGAGTGGCACCCGCTTCCAGACGTGGCAGGACACCCTGGAA
CGTTACCCAGACACTCTACTGGGCAGTTCTGAGAGGGACTTTTTCTACCACCCAGAAACT
CAGCAGTATTTCTTTGACCGTGACCCAGACATCTTCCGCCACATCCTGAATTTCTACCGC
ACTGGGAAGCTCCACTATCCTCGCCACGAGTGCATCTCTGCTTACGATGAAGAACTGGCC
TTCTTTGGCCTCATCCCGGAAATCATCGGCGACTGCTGTTATGAGGAGTACAAGGATCGC
AGGCGAGAGAACGCCGAGCGCCTGCAGGACGACGCGGATACCGACACCGCTGGGGAGAGC
GCCTTGCCCACCATGACTGCAAGGCAGAGGGTCTGGAGGGCCTTCGAGAACCCCCACACC
AGCACGATGGCCCTGGTGTTCTACTATGTCACGGGGTTTTTCATTGCCGTCTCTGTCATC
GCGAATGTGGTGGAAACAGTGCCGTGCGGATCAAGCCCAGGTCACATTAAAGAACTGCCC
TGTGGAGAGCGGTATGCTGTGGCCTTCTTCTGCTTGGACACGGCCTGCGTCATGATCTTC
ACAGTTGAGTATTTGCTTCGCCTGGCTGCAGCGCCTAGTCGTTACCGTTTTGTGCGTAGT
GTCATGAGTATCATCGACGTGGTGGCCATCCTGCCTTATTACATTGGGCTGGTGATGACA
GACAATGAGGACGTCAGCGGAGCCTTTGTCACACTCCGAGTCTTCCGGGTCTTCAGGATC
TTTAAGTTTTCCCGCCACTCTCAAGGCCTGCGCATCCTGGGGTACACACTGAAGAGTTGT
GCCTCAGAATTGGGCTTCTTGCTTTTCTCGCTCACCATGGCTATCATCATCTTCGCTACA
GTTATGTTCTACGCAGAGAAGGGGTCTTCGGCTAGCAAGTTCACCAGCATCCCTGCAGCC
TTCTGGTATACCATCGTCACCATGACAACACTAGGGTATGGTGACATGGTGCCAAAAACC
ATAGCAGGGAAGATTTTTGGTTCTATCTGTTCGCTGAGTGGGGTCTTGGTCATTGCTCTA
CCTGTTCCGGTGATTGTATCCAACTTCAGTCGCATCTACCACCAGAATCAACGAGCAGAC
AAACGAAGGGCACAAAAGAAAGCTAGACTGGCCAGGATCCGGGCAGCCAAAAGCGGAAGC
GCAAATGCTTACATGCAGAGCAAACGGAATGGTTTACTCAGTAATCAGCTGCAGTCCTCA
GAGGATGAGCAGGCTTTTGTTAGCAAATCCGGCTCCAGCTTTGAAACCCAGCACCACCAC
CTGCTTCACTGCCTGGAAAAAACCACGAATCACGAGTTTGTGGACGAACAAGTCTTTGAA
GAAAGCTGCATGGAAGTTGCAACTGTTAATCGTCCTTCAAGTCACAGTCCTTCACTGTCT
TCACAACAAGGAGTCACCAGCACCTGCTGTTCACGACGACACAAAAAAACTTTTCGCATC
CCAAATGCCAATGTATCAGGAAGCCATCAAGGTAGTATACAAGAACTCAGCACGATTCAG
ATCAGATGTGTGGAGAGAACACCTCTGTCTAACAGCCGATCCAGTTTAAATGCCAAAATG
GAAGAGTGTGTTAAACTAAACTGTGAACAACCTTATGTGACTACAGCAATAATAAGCATC
CCAACACCTCCAGTAACCACACCAGAAGGAGACGATAGGCCAGAATCCCCTGAGTACTCA
GGAGGAAATATTGTCAGAGTTTCTGCTTTGTAA
Chromosome Location
7
Locus
7q31
External Identifiers
ResourceLink
UniProtKB IDQ9NZV8
UniProtKB Entry NameKCND2_HUMAN
GenBank Protein ID4530478
GenBank Gene IDAF121104
HGNC IDHGNC:6238
General References
  1. Kong W, Po S, Yamagishi T, Ashen MD, Stetten G, Tomaselli GF: Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing. Am J Physiol. 1998 Dec;275(6 Pt 2):H1963-70. [PubMed:9843794]
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  3. Zhu XR, Wulf A, Schwarz M, Isbrandt D, Pongs O: Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Receptors Channels. 1999;6(5):387-400. [PubMed:10551270]
  4. Isbrandt D, Leicher T, Waldschutz R, Zhu X, Luhmann U, Michel U, Sauter K, Pongs O: Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA). Genomics. 2000 Mar 1;64(2):144-54. [PubMed:10729221]
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  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Petrecca K, Miller DM, Shrier A: Localization and enhanced current density of the Kv4.2 potassium channel by interaction with the actin-binding protein filamin. J Neurosci. 2000 Dec 1;20(23):8736-44. [PubMed:11102480]
  8. An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ: Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000 Feb 3;403(6769):553-6. [PubMed:10676964]
  9. Bahring R, Dannenberg J, Peters HC, Leicher T, Pongs O, Isbrandt D: Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating. J Biol Chem. 2001 Jun 29;276(26):23888-94. Epub 2001 Apr 3. [PubMed:11287421]
  10. Bahring R, Boland LM, Varghese A, Gebauer M, Pongs O: Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels. J Physiol. 2001 Aug 15;535(Pt 1):65-81. [PubMed:11507158]
  11. Bertaso F, Sharpe CC, Hendry BM, James AF: Expression of voltage-gated K+ channels in human atrium. Basic Res Cardiol. 2002 Nov;97(6):424-33. [PubMed:12395204]
  12. Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N, Imaizumi Y, Tomita T, Iwatsubo T: Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4. J Biol Chem. 2002 Apr 26;277(17):14965-75. Epub 2002 Feb 14. [PubMed:11847232]
  13. Schrader LA, Anderson AE, Mayne A, Pfaffinger PJ, Sweatt JD: PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex. J Neurosci. 2002 Dec 1;22(23):10123-33. [PubMed:12451113]
  14. Gebauer M, Isbrandt D, Sauter K, Callsen B, Nolting A, Pongs O, Bahring R: N-type inactivation features of Kv4.2 channel gating. Biophys J. 2004 Jan;86(1 Pt 1):210-23. [PubMed:14695263]
  15. Jerng HH, Qian Y, Pfaffinger PJ: Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10). Biophys J. 2004 Oct;87(4):2380-96. [PubMed:15454437]
  16. Lin YL, Chen CY, Cheng CP, Chang LS: Protein-protein interactions of KChIP proteins and Kv4.2. Biochem Biophys Res Commun. 2004 Aug 27;321(3):606-10. [PubMed:15358149]
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  20. Barghaan J, Bahring R: Dynamic coupling of voltage sensor and gate involved in closed-state inactivation of kv4.2 channels. J Gen Physiol. 2009 Feb;133(2):205-24. doi: 10.1085/jgp.200810073. [PubMed:19171772]
  21. Kitazawa M, Kubo Y, Nakajo K: The stoichiometry and biophysical properties of the Kv4 potassium channel complex with K+ channel-interacting protein (KChIP) subunits are variable, depending on the relative expression level. J Biol Chem. 2014 Jun 20;289(25):17597-609. doi: 10.1074/jbc.M114.563452. Epub 2014 May 8. [PubMed:24811166]
  22. Kim LA, Furst J, Gutierrez D, Butler MH, Xu S, Goldstein SA, Grigorieff N: Three-dimensional structure of I(to); Kv4.2-KChIP2 ion channels by electron microscopy at 21 Angstrom resolution. Neuron. 2004 Feb 19;41(4):513-9. [PubMed:14980201]
  23. Kim LA, Furst J, Butler MH, Xu S, Grigorieff N, Goldstein SA: Ito channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2. J Biol Chem. 2004 Feb 13;279(7):5549-54. Epub 2003 Nov 17. [PubMed:14623880]
  24. Kunz L, Ramsch R, Krieger A, Young KA, Dissen GA, Stouffer RL, Ojeda SR, Mayerhofer A: Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the human ovary. J Cell Physiol. 2006 Jan;206(1):167-74. [PubMed:15991246]
  25. Scannevin RH, Wang K, Jow F, Megules J, Kopsco DC, Edris W, Carroll KC, Lu Q, Xu W, Xu Z, Katz AH, Olland S, Lin L, Taylor M, Stahl M, Malakian K, Somers W, Mosyak L, Bowlby MR, Chanda P, Rhodes KJ: Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1. Neuron. 2004 Feb 19;41(4):587-98. [PubMed:14980207]
  26. El-Haou S, Balse E, Neyroud N, Dilanian G, Gavillet B, Abriel H, Coulombe A, Jeromin A, Hatem SN: Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes. Circ Res. 2009 Mar 27;104(6):758-69. doi: 10.1161/CIRCRESAHA.108.191007. Epub 2009 Feb 12. [PubMed:19213956]
  27. Lee H, Lin MC, Kornblum HI, Papazian DM, Nelson SF: Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum Mol Genet. 2014 Jul 1;23(13):3481-9. doi: 10.1093/hmg/ddu056. Epub 2014 Feb 5. [PubMed:24501278]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00458ImipramineapprovednoinhibitorDetails
DB00280DisopyramideapprovedunknowninhibitorDetails
DB06637DalfampridineapprovedyesantagonistDetails