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FLASH GENE

Symbol

KCNN4

contributors: mct - updated : 25-08-2015

HGNC name	potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4
HGNC id	6293

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002250 9 - 2240 NP_002241 47.6 427 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       moderately   intestine       highly Homo sapiens Endocrine pancreas       highly Lymphoid/Immune spleen         Reproductive female system uterus cervix   moderately   female system placenta     predominantly   male system prostate     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective bone     moderately

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Homo sapiens Lymphoid/Immune lymphocyte

cell lineage
cell lines	ovarian tumors
fluid/secretion	moderately in lymph

at STAGE

physiological period

fetal, pregnancy

Text	liver, placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six putative transmembrane domains
	a conserved porc region
	a leucine zipper-like motif near the C terminus

mono polymer

heteromer , tetramer

HOMOLOGY

interspecies	homolog to rattus Kcnn4 (85.8 pc)
	homolog to murine Kcnn4 (87.5 pc)

Homologene

FAMILY	SK channel family
	potassium channel KCNN family

CATEGORY

immunity/defense , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
text	multi-pass membrane protein
	KCNN4 channels in the apical membrane of intestinal epithelial cells

basic FUNCTION	acting as a voltage-independent potassium channel
	plays an important role in T lymphocyte Ca(2+) signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca(2+) influx
	involved in lung dendritic cells migration to lymphatic chemokines
	KCNN4 channel in the apical and basolateral membranes of epithelial cells play important roles in agonist-induced fluid secretion in intestine and colon
	plays a key role in human fibrocyte migration

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development , immunity/defense

text	K+ transport

PATHWAY

metabolism

signaling

a component

heterotetramer of potassium channel proteins

INTERACTION

DNA

RNA

small molecule

protein	binding to calmodulin
	functional link between KCNN4 and PRKAG1 (regulation of KCNN4 by AMPK in a functional epithelium through protein/protein interactions)
	time-dependent association between KCNN4 and USP8 following endocytosis
	both PI3KC2B and TRIM27 play critical but opposite roles in FCER1A-stimulated activation of KCNN4, Ca2+ influx, degranulation, and cytokine production in bone marrow mast cells
	by dephosphorylating NME2, PGAM5 negatively regulates CD4(+) T cells by inhibiting NME2-mediated histidine phosphorylation and activation of the KCNN4

cell & other

REGULATION

activated by

intracellular calcium

induced by

phorbol myristate acetate (PMA) and phytohemagglutinin (PHA) in T-cells

Other

blocked by clotrimazole and charybdotoxin

ASSOCIATED DISORDERS

corresponding disease(s)

DHS2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in pancreas and ovarian tumors

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed allergy asthm   currently available KCNN4 blockers might therefore attenuate tissue fibrosis and remodeling in patients with diseases such as idiopathic pulmonary fibrosis and asthma through the inhibition of fibrocyte recruitment immunology autoimmune digestive it may be possible to rapidly test whether KCa3.1 inhibitors are efficacious in patients with inflammatory bowel diseases such as Crohn disease and ulcerative colitis cardiovascular atheroma   CKCNN4 blockers represent a promising therapeutic strategy for atherosclerosis. miscelleaneous urinary chronic kidney disease pharmacological inhibitors of KCNN4 channels may provide a novel and effective therapy to delay progression to kidney failure in patients with ADPKD

ANIMAL & CELL MODELS