Intermediate conductance calcium-activated potassium channel protein 4

UniProt O15554 Organism Homo sapiens Gene IK1, IKCA1, KCA4, KCNN4, SK4

Also known as: IK1, IKCA1, KCA4, KCNN4, SK4

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. 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. 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. 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. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. Plays a role in the late stages of EGF-induced macropinocytosis through activation by PI(3)P.

Classification

Family (Pfam): PF02888 CaMBD, PF07885 Ion_trans_2, PF03530 SK_channel
InterPro: CaM-bd_dom, CaM-bd_dom_sf, K_chnl_Ca-activ_SK, K_chnl_dom
Functional cluster: Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 11

6CNM EM 3.40A
6CNN EM 3.50A
6CNO EM 4.70A
6D42 X-ray 1.75A
9ED1 EM 3.50A
9O48 EM 3.10A
9O51 EM 3.40A
9O52 EM 3.18A
9O53 EM 3.30A
9O5O EM 3.10A
9OA8 EM 3.59A

A predicted model is available from AlphaFold.

Gene Ontology · 24

Disease associations

dehydrated hereditary stomatocytosis 2 MONDO:0014737

Drugs targeting this protein · 2

CHLORZOXAZONE opener
SENICAPOC blocker

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Small conductance calcium-activated potassium channel protein 1 1 shared papers
Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR6 2 shared papers
Nucleoside diphosphate kinase B 1 shared papers
Calmodulin-1 1 shared papers
Inositol polyphosphate 4-phosphatase type II 1 shared papers
Myotubularin-related protein 9 1 shared papers
Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR6 1 shared papers
Myotubularin-related protein 9 1 shared papers

Literature · 19 cited papers

Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1. PLoS ONE · 2018
Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures. Science · 2018
KCa3.1-Dependent Hyperpolarization Enhances Intracellular Ca2+ Signaling Induced by fMLF in Differentiated U937 Cells. PLoS ONE · 2015
Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood · 2015
Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis). Am. J. Hematol. · 2015
A mutation in the Gardos channel is associated with hereditary xerocytosis. Blood · 2015
Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. Proc. Natl. Acad. Sci. U.S.A. · 2014
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc. Natl. Acad. Sci. U.S.A. · 2008
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
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
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
… and 7 more in the literature graph

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