Protein detail

KCNN4

Intermediate conductance calcium-activated potassium channel protein 4 (SKCa 4) (SKCa4) (hSK4) (Gardos channel) (IKCa1) (hIK1) (KCa3.1) (Putative Gardos channel) (hKCa4)

Protein symbol KCNN4	UniProt ID O15554	EVMP score 0.72
Frequency 17	Transmembrane count 6	Protein classification Disease related genesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsTransportersVoltage-gated ion channels

Basic Information

Protein Names

Intermediate conductance calcium-activated potassium channel protein 4 (SKCa 4) (SKCa4) (hSK4) (Gardos channel) (IKCa1) (hIK1) (KCa3.1) (Putative Gardos channel) (hKCa4)

Protein Class

Disease related genesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsTransportersVoltage-gated ion channels

Protein Function

Human disease related genes:Cardiovascular diseases:Hematologic diseases
Predicted intracellular proteins
Voltage-gated ion channels:Calcium-Activated Potassium Channels
Transporters:Transporter channels and pores
Disease related genes
FDA approved drug targets:Small molecule drugs

Transmembrane

29..49; Helical; Name=Segment S1; 59..79; Helical; Name=Segment S2; 108..128; Helical; Name=Segment S3; 143..163; Helical; Name=Segment S4; 207..227; Helical; Name=Segment S5; 265..285; Helical; Name=Segment S6

Transmembrane Count

Ensembl

ENSG00000104783

Entrez Gene Symbol

KCNN4

Gene Synonym

hIKCa1hKCa4hSK4IKKCa3.1

Gene Description

Potassium calcium-activated channel subfamily N member 4

Chromosome

Position

43766533-43780976

Frequency

EVMP Score

0.72

Fluorescence & Localization

Tissue SpecificbrainCell SpecificAdrenal medulla cellsSingle-Nuclei Brain Specificoligodendrocyte

Function & Pathway

Protein Function

Human disease related genes:Cardiovascular diseases:Hematologic diseases
Predicted intracellular proteins
Voltage-gated ion channels:Calcium-Activated Potassium Channels
Transporters:Transporter channels and pores
Disease related genes
FDA approved drug targets:Small molecule drugs

Cellular Component

Molecular Function

Biological Process

KEGG

Reactome

Canonical Pathways

M187 Pid trkr pathway

Mediation Categories

Clinical-translation mediationFusion and delivery mediationImmune mediation

Relations & Evidence

Enzyme-Mediated Modification

3 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
KCNN4	NME2	P22392	H	358	phosphorylation	PhosphoSite_MIMPMIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSite	SIGNOR:18796614 SIGNOR:17157250 ProtMapper:17157250 ProtMapper:18796614
KCNN4	PHPT1	Q9NRX4	H	358	dephosphorylation	DEPOD	DEPOD:18796614
KCNN4	PRKACA	P17612	S	334	phosphorylation	PhosphoSitePhosphoSite_ProtMapperProtMapper

Ligand-Receptor Signaling

24 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
transporter	transporter	OmniPath	No	Yes	No	No	No
ion_channel	ion_channel	OmniPath	No	Yes	No	No	No
transmembrane	transmembrane	UniProt_location	No	No	No	No	No
transmembrane	transmembrane	UniProt_topology	No	No	No	No	No
transmembrane	transmembrane	UniProt_keyword	No	No	No	No	No
transmembrane	transmembrane	TopDB	No	No	No	No	No
transmembrane	transmembrane	LOCATE	No	No	No	No	No
transmembrane	transmembrane	Ramilowski_location	No	No	No	No	No
transmembrane	transmembrane	OmniPath	No	No	No	No	No
peripheral	peripheral	UniProt_topology	No	No	No	No	No

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Regulatory Interaction Network

3 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
NDKB	P22392	KCNN4	O15554	Yes	Yes	No	PhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperSIGNOR_ProtMapper	SIGNOR:18796614 SIGNOR:17157250 ProtMapper:17157250 ProtMapper:18796614
KAPCA	P17612	KCNN4	O15554	Yes	No	Yes	iPTMnetSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:10617655 SIGNOR:25274816
PHP14	Q9NRX4	KCNN4	O15554	Yes	No	Yes	WangSIGNORDEPOD	SIGNOR:18796614 DEPOD:18796614

Protein Complex Composition

2 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	KCNN4	O15554	2	PDB	PDB:6d42
	CALM1 KCNN4	O15554 P0DP23	4:4	PDB	PDB:9o48PDB:6cnmPDB:6cnoPDB:6cnnPDB:9o53PDB:9o51PDB:9o5o

Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion Chromatography	Mass spectrometry	37	31685984 38938674 39290459 23376485 26538482 28054239 31508500 34071777 39873726 39443544 37702715 32795414 29562735 28562335 38731868 25471207 26801919 26884841 30071318 30608700 32927759 33580265 27312428 27320496 35856505 37686366 38490958 41201090 30760538 31366407 36982312 40311616 39835386 40091455 38136601 33114768 38612515

Sequence, Structure & Domains

Sequences

Length

427

Mass

47,696

Sequence

MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFLVKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPAPVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYRSIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDTLWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRKLREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLPEPSQQSK

3D Structural Models

Turn

51..56; 172..174; 230..233; 335..337

Helix

12..50; 57..91; 96..99; 104..114; 149..154; 155..161; 162..170; 177..186; 192..202; 204..226; 237..248; 261..287; 293..330; 338..368; 378..413

Beta Strand

254..256

3D Structure

Electron microscopy (4); X-ray crystallography (1)

Domain & Motif Annotations

Domain (CC)

Transmembrane helices S5 and S6 form the ion channel pore, which is surrounded bymembrane embedded helices S1 to S4 (PubMed:29724949). The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon calmodulin binding to open the channel pore (PubMed:29724949).

Region

286..347; Calmodulin-binding

Protein Families

Potassium channel KCNN family
KCa3.1/KCNN4 subfamily

Sequence Similarities

Belongs to the potassium channel KCNN family. KCa3.1/KCNN4 subfamily.

Clinical Relevance

Disease Involvement

Disease variantFDA approved drug targetsHereditary hemolytic anemia

Related Diseases

Alzheimer disease Chronic pain Conjunctiva disorder Neutropenia

Biomarker

Phase 2; Investigative; Discontinued in Phase 2

Drug Targets

FDA approved drug targets

Drugs

SENICAPOC ASP-0819 CHLORZOXAZONE

Antibody

HPA013367 HPA053841 HPA059622