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)

Entry name KCNN4	UniProt ID O15554	EVMP confidence score 0.72
Supporting publications (n) 17	Transmembrane count 6	Protein classification Disease related genesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsTransportersVoltage-gated ion channels

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

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 (7)

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

Protein Function (6)

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 (5)

hIKCa1hKCa4hSK4IKKCa3.1

Gene Description

Potassium calcium-activated channel subfamily N member 4

Chromosome

Position

43766533-43780976

Supporting publications (n)

EVMP confidence score

0.72

Fluorescence & Localization4

Tissue SpecificbrainCell SpecificAdrenal medulla cellsSingle-Nuclei Brain Specificoligodendrocyte

Function & Pathway8

Protein Function (6)

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 (7)

Molecular Function (8)

Biological Process (3)

KEGG (4)

Reactome (3)

Canonical Pathways

M187 Pid trkr pathway

Mediation Categories (3)

Clinical-translation mediationFusion and delivery mediationImmune mediation

Relations & Evidence33

Enzyme-Mediated Modification (3)

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)

24 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
intracellular	intracellular	LOCATE	No	No	No	No	No
intracellular	intracellular	ComPPI	No	No	No	No	No
intracellular	intracellular	GO_Intercell	No	No	No	No	No
intracellular	intracellular	OmniPath	No	No	No	No	No
ion_channel	ion_channel	DGIdb	No	Yes	No	No	No
calcium_activated_potassium	ion_channel	HGNC	No	Yes	No	No	No
ion_channel	ion_channel	HGNC	No	Yes	No	No	No
ion_channel	ion_channel	Almen2009	No	Yes	No	No	No
calcium_activated_potassium	ion_channel	Almen2009	No	Yes	No	No	No
voltage_gated	ion_channel	Almen2009	No	Yes	No	No	No

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Regulatory Interaction Network (3)

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)

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)

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 & Domains11

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 (2)

Potassium channel KCNN family
KCa3.1/KCNN4 subfamily

Sequence Similarities

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

Clinical Relevance6

Disease Involvement (3)

Disease variantFDA approved drug targetsHereditary hemolytic anemia

Related Diseases (4)

Alzheimer disease Chronic pain Conjunctiva disorder Neutropenia

Biomarker

Phase 2; Investigative; Discontinued in Phase 2

Drug Targets

FDA approved drug targets

Drugs (3)

SENICAPOC ASP-0819 CHLORZOXAZONE

Antibody (3)

HPA013367 HPA053841 HPA059622

Supporting Publications17

PMID	Title	Abstract
38731868	The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer.	No abstract available
39001700	Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles.	No abstract available
39873726	Size-Dependent Separation of Extracellular Vesicle Subtypes with Exodisc Enabling Proteomic Analysis in Prostate Cancer.	No abstract available
40091455	Potential Role of Menstrual Fluid-Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesiss.	No abstract available
40098346	Toward Identification of Markers for Brain-Derived Extracellular Vesicles in Cerebrospinal Fluid: A Large-Scale, Unbiased Analysis Using Proximity Extension Assays.	No abstract available
40545963	Extracellular Vesicle Proteome Analysis Improves Diagnosis of Recurrence in Triple-Negative Breast Cancer.	No abstract available
41315767	Multi-omics identify hallmark protein and lipid features of small extracellular vesicles circulating in human plasma.	No abstract available

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