KCNN4
entrez
3783
canonical
uniprot
O15554
canonical
ensembl
ENSG00000104783
resolver
ensp
ENSP00000496939
resolver
ensp
ENSP00000523003
resolver
ensp
ENSP00000649830
resolver
enst
ENST00000648319
resolver
genesymbol
KCNN4
resolver
genesymbol_syn
IK1
resolver
genesymbol_syn
IKCA1
resolver
genesymbol_syn
KCA4
resolver
genesymbol_syn
SK4
resolver
hgnc
HGNC:6293
resolver
uniprot
Q53XR4
resolver
uniprot_entry
KCNN4_HUMAN
resolver
uniprot_sec
Q53XR4
resolver
activity_regulation
ACTIVITY REGULATION: The channel is inhibited by clotrimazole and charybdotoxin but is insensitive to apamin. {ECO:0000269|PubMed:10961988, ECO:0000269|PubMed:11425865, ECO:0000269|PubMed:17157250, ECO:0000269|PubMed:18796614, ECO:0000269|PubMed:9326665, ECO:0000269|PubMed:9407042}.
uniprot
proteins
amino_acid_sequence
MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFLVKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPAPVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYRSIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDTLWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRKLREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLPEPSQQSK
uniprot
proteins
disease_involvement
DISEASE: Dehydrated hereditary stomatocytosis 2 (DHS2) [MIM:616689]: An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. Affected individuals typically manifest mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. {ECO:0000269|PubMed:26148990, ECO:0000269|PubMed:26178367, ECO:0000269|PubMed:26198474}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Intermediate conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calcium allowing its opening (PubMed:10026195, PubMed:10961988, PubMed:11425865, PubMed:15831468, PubMed:17157250, PubMed:18796614, PubMed:26148990, PubMed:9326665, PubMed:9380751, PubMed:9407042). The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of about 25 picosiemens (PubMed:9326665, PubMed:9380751, PubMed:9407042). Also presents an inwardly rectifying current, thus reducing its already small outward conductance of potassium ions, which is particularly the case when the membrane potential displays positive values, above + 20 mV (PubMed:9326665, PubMed:9380751, PubMed:9407042). Controls calcium influx during vascular contractility by being responsible of membrane hyperpolarization induced by vasoactive factors in proliferative vascular smooth muscle cell types (By similarity). Following calcium influx, the consecutive activation of KCNN4 channel leads to a hyperpolarization of the cell membrane potential and hence an increase of the electrical driving force for further calcium influx promoting sustained calcium entry in response to stimulation with chemotactic peptides (PubMed:26418693). Required for maximal calcium influx and proliferation during the reactivation of naive T-cells (PubMed:17157250, PubMed:18796614). Plays a role in the late stages of EGF-induced macropinocytosis through activation by PI(3)P (PubMed:24591580). {ECO:0000250|UniProtKB:Q9QYW1, ECO:0000269|PubMed:10026195, ECO:0000269|PubMed:10961988, ECO:0000269|PubMed:11425865, ECO:0000269|PubMed:15831468, ECO:0000269|PubMed:17157250, ECO:0000269|PubMed:18796614, ECO:0000269|PubMed:24591580, ECO:0000269|PubMed:26148990, ECO:0000269|PubMed:26418693, ECO:0000269|PubMed:9326665, ECO:0000269|PubMed:9380751, ECO:0000269|PubMed:9407042}.
uniprot
proteins
mass_dalton
47696
uniprot
proteins
mutagenesis
MUTAGEN 250; /note="T->S: Loss of sensitivity to triarylmethanes."; /evidence="ECO:0000269|PubMed:11425865"; MUTAGEN 275; /note="V->A: Loss of sensitivity to triarylmethanes."; /evidence="ECO:0000269|PubMed:11425865
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at His-358 by NDKB activates the intermediate conductance calcium-activated potassium channel activity, and conversely its dephosphorylation by PHPT1 inhibits this activity. {ECO:0000269|PubMed:17157250, ECO:0000269|PubMed:18796614}.
uniprot
proteins
protein_family
KCa3.1/KCNN4 subfamily
uniprot
proteins
protein_family
Potassium channel KCNN family
uniprot
proteins
pubmed
10026195
uniprot
proteins
pubmed
10961988
uniprot
proteins
pubmed
11425865
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15831468
uniprot
proteins
pubmed
17157250
uniprot
proteins
pubmed
18796614
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24591580
uniprot
proteins
pubmed
26148990
uniprot
proteins
pubmed
26178367
uniprot
proteins
pubmed
26198474
uniprot
proteins
pubmed
26418693
uniprot
proteins
pubmed
29724949
uniprot
proteins
pubmed
29953543
uniprot
proteins
pubmed
9326665
uniprot
proteins
pubmed
9380751
uniprot
proteins
pubmed
9407042
uniprot
proteins
pubmed
9693050
uniprot
proteins
sequence_length
427
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15831468, ECO:0000269|PubMed:24591580, ECO:0000269|PubMed:26148990}; Multi-pass membrane protein {ECO:0000255}. Cell projection, ruffle membrane {ECO:0000269|PubMed:24591580}. Note=Targeted to membrane ruffles after EGF stimulation. {ECO:0000269|PubMed:24591580}.
uniprot
proteins
transmembrane_region
TRANSMEM 29..49; /note="Helical; Name=Segment S1"; /evidence="ECO:0000255"; TRANSMEM 59..79; /note="Helical; Name=Segment S2"; /evidence="ECO:0000255"; TRANSMEM 108..128; /note="Helical; Name=Segment S3"; /evidence="ECO:0000255"; TRANSMEM 143..163; /note="Helical; Name=Segment S4"; /evidence="ECO:0000255"; TRANSMEM 207..227; /note="Helical; Name=Segment S5"; /evidence="ECO:0000255"; TRANSMEM 265..285; /note="Helical; Name=Segment S6"; /evidence="ECO:0000255
uniprot
proteins