TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


1.A.1.16.2
The intermediate conductance, Ca2+-activated K+ channel, Kcnn4, SK4, Sk4, Smik, Ik1 hIK1, IKCa or KCa3.1, also called the Gardos channel, of 543 aas and 6 TMSs. It is inhibited by 1 μM arachidonate which binds in the pore (Hamilton et al., 2003)). Nucleoside diphosphate kinase B (NDPK-B) activates KCa3.1 via histidine phosphorylation, resulting in receptor-stimulated Ca2+ flux and T cell activation (Di et al., 2010). It regulates endothelial vascular function (Sonkusare et al., 2012).  Tissue-specific expression of splice variants of the orthologous rat KCNN4 protein have been reported (Barmeyer et al. 2010).  Residues involved in gating have been identified (Garneau et al. 2014). It is also present in the inner mitochondrial membrane where increases of mitochondrial matrix [Ca2+] cause mtKCa3.1 opening, thus linking inner membrane K+ permeability and transmembrane potential to Ca2+ signalling (De Marchi et al. 2009). KCa3.1 (IKCa) channels are expressed in CA1 hippocampal pyramidal cells and contribute to the slow afterhyperpolarization that regulates spike accommodation (Turner et al. 2016). SK channel activators can compensate for age-related changes of the autorhythmic functions of the cerebellum (Karelina et al. 2017). The activation mechanism has been revealed by the cryoEM structure of the SK4-calmodulin complex (Lee and MacKinnon 2018).  It is responsible for hyperpolarization in some tumor cells (Lazzari-Dean et al. 2019). Mutations are linked to dehydrated hereditary stomatocytosis (xerocytosis) (Andolfo et al. 2015). This channel is present in mitochondria (Parrasia et al. 2019). KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways (Xu et al. 2021). KCa3.1 channels in human microglia link extracellular ATP-evoked Ca2+ transients to changes in membrane conductance with an inflammation-dependent mechanism, and suggests that during brain inflammation, the KCa3.1-mediated microglial response to purinergic signaling may be reduced (Palomba et al. 2021).  

Accession Number:O15554
Protein Name:hIK1 aka KCNN4 aka KCA4
Length:427
Molecular Weight:47696.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

RefSeq: NP_002241.1   
Entrez Gene ID: 3783   
Pfam: PF02888    PF07885    PF03530   
OMIM: 602754  gene
KEGG: hsa:3783   

Gene Ontology

GO:0008076 C:voltage-gated potassium channel complex
GO:0015269 F:calcium-activated potassium channel activity
GO:0005516 F:calmodulin binding
GO:0006952 P:defense response
GO:0006813 P:potassium ion transport

References (9)

[1] “hSK4, a member of a novel subfamily of calcium-activated potassium channels.”  Joiner W.J.et.al.   9380751
[2] “A human intermediate conductance calcium-activated potassium channel.”  Ishii T.M.et.al.   9326665
[3] “A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes.”  Logsdon N.J.et.al.   9407042
[4] “Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia.”  Ghanshani S.et.al.   9693050
[5] “Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences.”  Ghanshani S.et.al.   10961988
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1.”  Fanger C.M.et.al.   10026195
[8] “Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1.”  Wulff H.et.al.   11425865
[9] “The phosphatidylinositol 3-phosphate phosphatase myotubularin-related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1.”  Srivastava S.et.al.   15831468
Structure:
6CNM   6CNN   6CNO   6D42     

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MGGDLVLGLG ALRRRKRLLE QEKSLAGWAL VLAGTGIGLM VLHAEMLWFG GCSWALYLFL 
61:	VKCTISISTF LLLCLIVAFH AKEVQLFMTD NGLRDWRVAL TGRQAAQIVL ELVVCGLHPA 
121:	PVRGPPCVQD LGAPLTSPQP WPGFLGQGEA LLSLAMLLRL YLVPRAVLLR SGVLLNASYR 
181:	SIGALNQVRF RHWFVAKLYM NTHPGRLLLG LTLGLWLTTA WVLSVAERQA VNATGHLSDT 
241:	LWLIPITFLT IGYGDVVPGT MWGKIVCLCT GVMGVCCTAL LVAVVARKLE FNKAEKHVHN 
301:	FMMDIQYTKE MKESAARVLQ EAWMFYKHTR RKESHAARRH QRKLLAAINA FRQVRLKHRK 
361:	LREQVNSMVD ISKMHMILYD LQQNLSSSHR ALEKQIDTLA GKLDALTELL STALGPRQLP 
421:	EPSQQSK