Intermediate conductance calcium-activated potassium channel protein 4

Details

Name
Intermediate conductance calcium-activated potassium channel protein 4
Synonyms
  • IK1
  • IKCA1
  • KCa3.1
  • KCA4
  • Putative Gardos channel
  • SK4
Gene Name
KCNN4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016086|Intermediate conductance calcium-activated potassium channel protein 4
MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFL
VKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPA
PVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYR
SIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDT
LWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHN
FMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRK
LREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLP
EPSQQSK
Number of residues
427
Molecular Weight
47695.12
Theoretical pI
10.39
GO Classification
Functions
calcium-activated potassium channel activity / calmodulin binding / Intermediate conductance calcium-activated potassium channel activity / protein phosphatase binding
Processes
calcium ion transport / cell volume homeostasis / defense response / immune system process / phospholipid translocation / positive regulation of protein secretion / positive regulation of T cell receptor signaling pathway / potassium ion export / potassium ion transmembrane transport / potassium ion transport / saliva secretion / stabilization of membrane potential / synaptic transmission
Components
apical plasma membrane / basolateral plasma membrane / membrane raft / neuronal cell body / plasma membrane / voltage-gated potassium channel complex
General Function
Protein phosphatase binding
Specific Function
Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).
Pfam Domain Function
Transmembrane Regions
29-49 59-79 108-128 143-163 207-227 265-285
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0016087|Intermediate conductance calcium-activated potassium channel protein 4 (KCNN4)
ATGGGCGGGGATCTGGTGCTTGGCCTGGGGGCCTTGAGACGCCGAAAGCGCTTGCTGGAG
CAGGAGAAGTCTCTGGCCGGCTGGGCACTGGTGCTGGCAGGAACTGGCATTGGACTCATG
GTGCTGCATGCAGAGATGCTGTGGTTCGGGGGGTGCTCGTGGGCGCTCTACCTGTTCCTG
GTTAAATGCACGATCAGCATTTCCACCTTCTTACTCCTCTGCCTCATCGTGGCCTTTCAT
GCCAAAGAGGTCCAGCTGTTCATGACCGACAACGGGCTGCGGGACTGGCGCGTGGCGCTG
ACCGGGCGGCAGGCGGCGCAGATCGTGCTGGAGCTGGTGGTGTGTGGGCTGCACCCGGCG
CCCGTGCGGGGCCCGCCGTGCGTGCAGGATTTAGGGGCGCCGCTGACCTCCCCGCAGCCC
TGGCCGGGATTCCTGGGCCAAGGGGAAGCGCTGCTGTCCCTGGCCATGCTGCTGCGTCTC
TACCTGGTGCCCCGCGCCGTGCTCCTGCGCAGCGGCGTCCTGCTCAACGCTTCCTACCGC
AGCATCGGCGCTCTCAATCAAGTCCGCTTCCGCCACTGGTTCGTGGCCAAGCTTTACATG
AACACGCACCCTGGCCGCCTGCTGCTCGGCCTCACGCTTGGCCTCTGGCTGACCACCGCC
TGGGTGCTGTCCGTGGCCGAGAGGCAGGCTGTTAATGCCACTGGGCACCTTTCAGACACA
CTTTGGCTGATCCCCATCACATTCCTGACCATCGGCTATGGTGACGTGGTGCCGGGCACC
ATGTGGGGCAAGATCGTCTGCCTGTGCACTGGAGTCATGGGTGTCTGCTGCACAGCCCTG
CTGGTGGCCGTGGTGGCCCGGAAGCTGGAGTTTAACAAGGCAGAGAAGCACGTGCACAAC
TTCATGATGGATATCCAGTATACCAAAGAGATGAAGGAGTCCGCTGCCCGAGTGCTACAA
GAAGCCTGGATGTTCTACAAACATACTCGCAGGAAGGAGTCTCATGCTGCCCGCAGGCAT
CAGCGCAAGCTGCTGGCCGCCATCAACGCGTTCCGCCAGGTGCGGCTGAAACACCGGAAG
CTCCGGGAACAAGTGAACTCCATGGTGGACATCTCCAAGATGCACATGATCCTGTATGAC
CTGCAGCAGAATCTGAGCAGCTCACACCGGGCCCTGGAGAAACAGATTGACACGCTGGCG
GGGAAGCTGGATGCCCTGACTGAGCTGCTTAGCACTGCCCTGGGGCCGAGGCAGCTTCCA
GAACCCAGCCAGCAGTCCAAGTAG
Chromosome Location
19
Locus
19q13.2
External Identifiers
ResourceLink
UniProtKB IDO15554
UniProtKB Entry NameKCNN4_HUMAN
GenBank Protein ID2584866
GenBank Gene IDAF000972
GenAtlas IDKCNN4
HGNC IDHGNC:6293
General References
  1. Joiner WJ, Wang LY, Tang MD, Kaczmarek LK: hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):11013-8. [PubMed:9380751]
  2. Ishii TM, Silvia C, Hirschberg B, Bond CT, Adelman JP, Maylie J: A human intermediate conductance calcium-activated potassium channel. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11651-6. [PubMed:9326665]
  3. Logsdon NJ, Kang J, Togo JA, Christian EP, Aiyar J: A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J Biol Chem. 1997 Dec 26;272(52):32723-6. [PubMed:9407042]
  4. Ghanshani S, Coleman M, Gustavsson P, Wu AC, Gargus JJ, Gutman GA, Dahl N, Mohrenweiser H, Chandy KG: Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia. Genomics. 1998 Jul 1;51(1):160-1. [PubMed:9693050]
  5. Ghanshani S, Wulff H, Miller MJ, Rohm H, Neben A, Gutman GA, Cahalan MD, Chandy KG: Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences. J Biol Chem. 2000 Nov 24;275(47):37137-49. [PubMed:10961988]
  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. Fanger CM, Ghanshani S, Logsdon NJ, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, Aiyar J: Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J Biol Chem. 1999 Feb 26;274(9):5746-54. [PubMed:10026195]
  8. Wulff H, Gutman GA, Cahalan MD, Chandy KG: Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1. J Biol Chem. 2001 Aug 24;276(34):32040-5. Epub 2001 Jun 25. [PubMed:11425865]
  9. Srivastava S, Li Z, Lin L, Liu G, Ko K, Coetzee WA, Skolnik EY: The phosphatidylinositol 3-phosphate phosphatase myotubularin- related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1. Mol Cell Biol. 2005 May;25(9):3630-8. [PubMed:15831468]
  10. Srivastava S, Li Z, Ko K, Choudhury P, Albaqumi M, Johnson AK, Yan Y, Backer JM, Unutmaz D, Coetzee WA, Skolnik EY: Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Mol Cell. 2006 Dec 8;24(5):665-75. [PubMed:17157250]
  11. Srivastava S, Zhdanova O, Di L, Li Z, Albaqumi M, Wulff H, Skolnik EY: Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14442-6. doi: 10.1073/pnas.0803678105. Epub 2008 Sep 16. [PubMed:18796614]
  12. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [PubMed:22814378]
  13. Andolfo I, Russo R, Manna F, Shmukler BE, Gambale A, Vitiello G, De Rosa G, Brugnara C, Alper SL, Snyder LM, Iolascon A: Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis). Am J Hematol. 2015 Oct;90(10):921-6. doi: 10.1002/ajh.24117. [PubMed:26178367]
  14. Rapetti-Mauss R, Lacoste C, Picard V, Guitton C, Lombard E, Loosveld M, Nivaggioni V, Dasilva N, Salgado D, Desvignes JP, Beroud C, Viout P, Bernard M, Soriani O, Vinti H, Lacroze V, Feneant-Thibault M, Thuret I, Guizouarn H, Badens C: A mutation in the Gardos channel is associated with hereditary xerocytosis. Blood. 2015 Sep 10;126(11):1273-80. doi: 10.1182/blood-2015-04-642496. Epub 2015 Jul 6. [PubMed:26148990]
  15. Glogowska E, Lezon-Geyda K, Maksimova Y, Schulz VP, Gallagher PG: Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood. 2015 Sep 10;126(11):1281-4. doi: 10.1182/blood-2015-07-657957. Epub 2015 Jul 21. [PubMed:26198474]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01159Halothaneapproved, vet_approvedunknowninhibitorDetails
DB00257Clotrimazoleapproved, vet_approvedyesinhibitorDetails
DB00468QuinineapprovedunknowninhibitorDetails
DB00228Enfluraneapproved, investigational, vet_approvedunknowninhibitorDetails
DB01110Miconazoleapproved, investigational, vet_approvedunknowninhibitorDetails
DB00721Procaineapproved, investigational, vet_approvedunknownbinderDetails
DB09089TrimebutineapprovedyesinhibitorDetails