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
- Functionscalcium-activated potassium channel activity / calmodulin binding / Intermediate conductance calcium-activated potassium channel activity / protein phosphatase bindingProcessescalcium 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 transmissionComponentsapical 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
Resource Link UniProtKB ID O15554 UniProtKB Entry Name KCNN4_HUMAN GenBank Protein ID 2584866 GenBank Gene ID AF000972 GenAtlas ID KCNN4 HGNC ID HGNC:6293 - General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB01159 Halothane approved, vet_approved unknown inhibitor Details DB00257 Clotrimazole approved, vet_approved yes inhibitor Details DB00468 Quinine approved unknown inhibitor Details DB00721 Procaine approved, investigational, vet_approved unknown blocker Details DB09089 Trimebutine approved yes inhibitor Details DB01110 Miconazole approved, investigational, vet_approved unknown inhibitor Details DB00867 Ritodrine approved, investigational yes activator Details DB01054 Nitrendipine approved, investigational unknown inhibitor Details DB02587 Colforsin experimental, investigational unknown activator Details