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Kv1.4

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Target not currently curated in GtoImmuPdb

Target id: 541

Nomenclature: Kv1.4

Family: Voltage-gated potassium channels (Kv)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 653 11p14.1 KCNA4 potassium voltage-gated channel subfamily A member 4 23,41
Mouse 6 1 654 2 56.12 cM Kcna4 potassium voltage-gated channel, shaker-related subfamily, member 4 41
Rat 6 1 655 3q33 Kcna4 potassium voltage-gated channel subfamily A member 4 40
Previous and Unofficial Names Click here for help
HK1 | hPCN2 | MK4 | RCK4 | RHK1 | RK4 | RK8 | KCNA4L | KCHAN | potassium voltage-gated channel subfamily A member 4 | RK3 | potassium channel, voltage gated shaker related subfamily A, member 4 | potassium voltage-gated channel
Database Links Click here for help
Alphafold P22459 (Hs), Q61423 (Mm), P15385 (Rn)
CATH/Gene3D 1.20.5.600
ChEMBL Target CHEMBL4205 (Hs), CHEMBL5583 (Rn)
DrugBank Target P22459 (Hs)
Ensembl Gene ENSG00000182255 (Hs), ENSMUSG00000042604 (Mm), ENSRNOG00000004918 (Rn)
Entrez Gene 3739 (Hs), 16492 (Mm), 25469 (Rn)
Human Protein Atlas ENSG00000182255 (Hs)
KEGG Gene hsa:3739 (Hs), mmu:16492 (Mm), rno:25469 (Rn)
OMIM 176266 (Hs)
Pharos P22459 (Hs)
RefSeq Nucleotide NM_002233 (Hs), NM_021275 (Mm), NM_012971 (Rn)
RefSeq Protein NP_002224 (Hs), NP_067250 (Mm), NP_037103 (Rn)
UniProtKB P22459 (Hs), Q61423 (Mm), P15385 (Rn)
Wikipedia KCNA4 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Kv1.1 4-5,27
Kv1.2 4-5,27,32
Auxiliary Subunits
Name References
KVβ1 4,26-27
Kvβ2 4,26-27
Other Associated Proteins
Name References
KChAP 17
α-actinin-2 6
σ-receptor 2
SAP97 16,38
PSD-95 15,39
Calmodulin-dependent kinase II 30
Lgi1 31
synaptotagmin 1 42
Functional Characteristics Click here for help
KA
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  K+ > Na+
References:  24
Species:  Rat
Rank order:  K+ [5.0 pS]
References:  35
Species:  Human
Macroscopic current rectification:  Ik, A-Type current, fast-inactivating
References:  24
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -34.0 - 24 Xenopus laevis oocyte Human
Inactivation  -62.0 47.0 24
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -22.0 3.0 35 Xenopus laevis oocyte Rat
Inactivation  -74.0 - 35

Download all structure-activity data for this target as a CSV file go icon to follow link

Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
CP-339818 Small molecule or natural product Click here for species-specific activity table Mm - 6.5 pIC50 - - 20
⤷ pIC50 6.5 [20]
nicardipine Small molecule or natural product Approved drug Rn - 6.1 pIC50 - - 10
⤷ pIC50 6.1 [10]
quinidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Rn - 3.7 pIC50 - - 43
⤷ pIC50 3.7 [43]
fampridine Small molecule or natural product Approved drug Click here for species-specific activity table Rn - 1.9 pIC50 - - 35
⤷ pIC50 1.9 (IC50 1.25x10-2 M) [35]
View species-specific channel blocker tables
Tissue Distribution Click here for help
Heart
Species:  Human
Technique:  Northern Blot
References:  37
Insulinoma and islet
Species:  Human
Technique:  Northern Blot
References:  22
Skeletal muscle, arterial smooth muscle, retina
Species:  Rat
Technique:  Northern Blot and immunohistochemistry
References:  12,19,34
Dorsal root ganglia, small diameter cells
Species:  Rat
Technique:  Immunohistochemistry
References:  25
Brain (olfactory bulb, corpus striatum > hippocampus, superior and inferior colliculus > cerebral cortex, midbrain basal ganglia > pons/medulla)
Species:  Rat
Technique:  Northern Blot, in situ hybridisation and immunohistochemistry
References:  3,24,27,32-33
Pancreatic islet
Species:  Rat
Technique:  RT-PCR
References:  18,36
Heart
Species:  Rat
Technique:  Northern Blot
References:  29,40
Functional Assays Click here for help
Two electrode voltage clamp
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  Rapidly inactivated
References:  24
Molecular clone and voltage clamp
Species:  Rat
Tissue:  Xenopus laevis oocytes
Response measured:  A-type current
References:  35
Physiological Functions Click here for help
Potential mediators of repolarisation.
Species:  Rat
Tissue:  Pancreatic islet.
References:  18,36
After hypolarisation or early repolarisation.
Species:  Rat
Tissue:  Brain, heart.
References:  7,28,35
Potential mediators of repolarisation.
Species:  Human
Tissue:  Heart, pancreatic islet.
References:  21,28
Ito,s
Species:  Mouse
Tissue:  Heart
References:  9
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna4tm1Lndn Kcna4tm1Lndn/Kcna4tm1Lndn
involves: 129S4/SvJae * C57BL/6		 MGI:96661  MP:0002064 seizures PMID: 9547391 
Gene Expression and Pathophysiology Click here for help
KV1.4 mRNA expression increases in AΒ25-35-treated rat hippocampus.
Tissue or cell type:  Rat brain.
Pathophysiology:  Spatial memory deficit.
Species:  Rat
Technique:  In vivo
References:  21
KV1.4 expression decreased after myocardial infarction.
Tissue or cell type:  Rat heart.
Pathophysiology:  Decrease after MI.
Species:  Rat
Technique:  In vivo
References:  8,11,14
Biologically Significant Variant Comments
A total of 187 SNPs have been identified in human KCNA4. for more information see the entry on GeneCards.
General Comments
The inactivating Kv1.4 can coassemble with and confer inactivation to heteromutlimers containing non-activating Kv1 family members. Prominently expressed on axons of brain neurons, and in small diameter DRG neurons.

Intronless coding region.

Mouse Kv1.4 mRNA contains an internal ribosome entry site in its 5-noncoding region and may be translated by cap-independent mechanisms [1,13].

References

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1. Albrecht B, Weber K, Pongs O. (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Recept Channels, 3 (3): 213-20. [PMID:8821794]

2. Aydar E, Palmer CP, Klyachko VA, Jackson MB. (2002) The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron, 34 (3): 399-410. [PMID:11988171]

3. Beckh S, Pongs O. (1990) Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J, 9 (3): 777-82. [PMID:2311579]

4. Bildl W, Haupt A, Müller CS, Biniossek ML, Thumfart JO, Hüber B, Fakler B, Schulte U. (2012) Extending the dynamic range of label-free mass spectrometric quantification of affinity purifications. Mol Cell Proteomics, 11 (2): M111.007955. [PMID:22067099]

5. Coleman SK, Newcombe J, Pryke J, Dolly JO. (1999) Subunit composition of Kv1 channels in human CNS. J Neurochem, 73 (2): 849-58. [PMID:10428084]

6. Cukovic D, Lu GW, Wible B, Steele DF, Fedida D. (2001) A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of alpha-actinin-2. FEBS Lett, 498 (1): 87-92. [PMID:11389904]

7. Geiger JR, Jonas P. (2000) Dynamic control of presynaptic Ca(2+) inflow by fast-inactivating K(+) channels in hippocampal mossy fiber boutons. Neuron, 28 (3): 927-39. [PMID:11163277]

8. Gidh-Jain M, Huang B, Jain P, el-Sherif N. (1996) Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. Circ Res, 79 (4): 669-75. [PMID:8831490]

9. Guo W, Xu H, London B, Nerbonne JM. (1999) Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes. J Physiol (Lond.), 521 Pt 3: 587-99. [PMID:10601491]

10. Hatano N, Ohya S, Muraki K, Giles W, Imaizumi Y. (2003) Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells. Br J Pharmacol, 139 (3): 533-44. [PMID:12788813]

11. Huang B, Qin D, El-Sherif N. (2001) Spatial alterations of Kv channels expression and K(+) currents in post-MI remodeled rat heart. Cardiovasc Res, 52 (2): 246-54. [PMID:11684072]

12. Höltje M, Brunk I, Grosse J, Beyer E, Veh RW, Bergmann M, Grosse G, Ahnert-Hilger G. (2007) Differential distribution of voltage-gated potassium channels Kv 1.1-Kv1.6 in the rat retina during development. J Neurosci Res, 85 (1): 19-33. [PMID:17075900]

13. Jang GM, Leong LE, Hoang LT, Wang PH, Gutman GA, Semler BL. (2004) Structurally distinct elements mediate internal ribosome entry within the 5'-noncoding region of a voltage-gated potassium channel mRNA. J Biol Chem, 279 (46): 47419-30. [PMID:15339906]

14. Kaprielian R, Wickenden AD, Kassiri Z, Parker TG, Liu PP, Backx PH. (1999) Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction. J Physiol (Lond.), 517 ( Pt 1): 229-45. [PMID:10226162]

15. Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M. (1995) Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature, 378 (6552): 85-8. [PMID:7477295]

16. Kim E, Sheng M. (1996) Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology, 35 (7): 993-1000. [PMID:8938729]

17. Kuryshev YA, Wible BA, Gudz TI, Ramirez AN, Brown AM. (2001) KChAP/Kvbeta1.2 interactions and their effects on cardiac Kv channel expression. Am J Physiol, Cell Physiol, 281 (1): C290-9. [PMID:11401852]

18. MacDonald PE, Ha XF, Wang J, Smukler SR, Sun AM, Gaisano HY, Salapatek AM, Backx PH, Wheeler MB. (2001) Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol Endocrinol, 15 (8): 1423-35. [PMID:11463864]

19. Matsubara H, Liman ER, Hess P, Koren G. (1991) Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles. J Biol Chem, 266 (20): 13324-8. [PMID:1712780]

20. Nguyen A, Kath JC, Hanson DC, Biggers MS, Canniff PC, Donovan CB, Mather RJ, Bruns MJ, Rauer H, Aiyar J et al.. (1996) Novel nonpeptide agents potently block the C-type inactivated conformation of Kv1.3 and suppress T cell activation. Mol Pharmacol, 50 (6): 1672-9. [PMID:8967992]

21. Pan Y, Xu X, Tong X, Wang X. (2004) Messenger RNA and protein expression analysis of voltage-gated potassium channels in the brain of Abeta(25-35)-treated rats. J Neurosci Res, 77 (1): 94-9. [PMID:15197742]

22. Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, Steiner DF. (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc Natl Acad Sci USA, 88 (1): 53-7. [PMID:1986382]

23. Philipson LH, Schaefer K, LaMendola J, Bell GI, Steiner DF. (1990) Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4. Nucleic Acids Res, 18 (23): 7160. [PMID:2263489]

24. Po S, Snyders DJ, Baker R, Tamkun MM, Bennett PB. (1992) Functional expression of an inactivating potassium channel cloned from human heart. Circ Res, 71 (3): 732-6. [PMID:1499114]

25. Rasband MN, Park EW, Vanderah TW, Lai J, Porreca F, Trimmer JS. (2001) Distinct potassium channels on pain-sensing neurons. Proc Natl Acad Sci USA, 98 (23): 13373-8. [PMID:11698689]

26. Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN, Dolly JO, Pongs O. (1994) Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit. Nature, 369 (6478): 289-94. [PMID:8183366]

27. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, Trimmer JS. (1997) Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes. J Neurosci, 17 (21): 8246-58. [PMID:9334400]

28. Roberds SL, Knoth KM, Po S, Blair TA, Bennett PB, Hartshorne RP, Snyders DJ, Tamkun MM. (1993) Molecular biology of the voltage-gated potassium channels of the cardiovascular system. J Cardiovasc Electrophysiol, 4 (1): 68-80. [PMID:8287238]

29. Roberds SL, Tamkun MM. (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc Natl Acad Sci USA, 88 (5): 1798-802. [PMID:1705709]

30. Roeper J, Lorra C, Pongs O. (1997) Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase. J Neurosci, 17 (10): 3379-91. [PMID:9133364]

31. Schulte U, Thumfart JO, Klöcker N, Sailer CA, Bildl W, Biniossek M, Dehn D, Deller T, Eble S, Abbass K et al.. (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron, 49 (5): 697-706. [PMID:16504945]

32. Sheng M, Liao YJ, Jan YN, Jan LY. (1993) Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. Nature, 365 (6441): 72-5. [PMID:8361540]

33. Sheng M, Tsaur ML, Jan YN, Jan LY. (1992) Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron, 9 (2): 271-84. [PMID:1497894]

34. Standen NB, Quayle JM. (1998) K+ channel modulation in arterial smooth muscle. Acta Physiol Scand, 164 (4): 549-57. [PMID:9887977]

35. Stühmer W, Ruppersberg JP, Schröter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O. (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J, 8 (11): 3235-44. [PMID:2555158]

36. Su J, Yu H, Lenka N, Hescheler J, Ullrich S. (2001) The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1. Pflugers Arch, 442 (1): 49-56. [PMID:11374068]

37. Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, Glover DM. (1991) Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J, 5 (3): 331-7. [PMID:2001794]

38. Tiffany AM, Manganas LN, Kim E, Hsueh YP, Sheng M, Trimmer JS. (2000) PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering. J Cell Biol, 148 (1): 147-58. [PMID:10629225]

39. Topinka JR, Bredt DS. (1998) N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron, 20 (1): 125-34. [PMID:9459448]

40. Tseng-Crank JC, Tseng GN, Schwartz A, Tanouye MA. (1990) Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac library. FEBS Lett, 268 (1): 63-8. [PMID:2384173]

41. Wymore RS, Korenberg JR, Kinoshita KD, Aiyar J, Coyne C, Chen XN, Hustad CM, Copeland NG, Gutman GA, Jenkins NA et al.. (1994) Genomic organization, nucleotide sequence, biophysical properties, and localization of the voltage-gated K+ channel gene KCNA4/Kv1.4 to mouse chromosome 2/human 11p14 and mapping of KCNC1/Kv3.1 to mouse 7/human 11p14.3-p15.2 and KCNA1/Kv1.1 to human 12p13. Genomics, 20 (2): 191-202. [PMID:8020965]

42. Xie C, Su H, Guo T, Yan Y, Peng X, Cao R, Wang Y, Chen P, Wang X, Liang S. (2014) Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus. Mol Brain, 7: 4. [PMID:24423395]

43. Yamagishi T, Ishii K, Taira N. (1995) Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels, KV1.2 and KV1.4. Eur J Pharmacol, 281 (2): 151-9. [PMID:7589202]

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