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 | 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
6
Ensembl
Entrez Gene Symbol
Gene Synonym
hIKCa1hKCa4hSK4IKKCa3.1
Gene Description
Potassium calcium-activated channel subfamily N member 4
Chromosome
19
Position
43766533-43780976
Frequency
17
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
- GO:0005267 potassium channel activity
- GO:0005515 protein binding
- GO:0005516 calmodulin binding
- GO:0015269 calcium-activated potassium channel activity
- GO:0016286 small conductance calcium-activated potassium channel activity
- GO:0019903 protein phosphatase binding
- GO:0022894 intermediate conductance calcium-activated potassium channel activity
- GO:0042803 protein homodimerization activity
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:18796614SIGNOR:17157250ProtMapper:17157250ProtMapper: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) |
|---|---|---|---|---|---|---|---|
| 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 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:18796614SIGNOR:17157250ProtMapper:17157250ProtMapper:18796614 |
| KAPCA | P17612 | KCNN4 | O15554 | Yes | No | Yes | iPTMnetSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:10617655SIGNOR:25274816 |
| PHP14 | Q9NRX4 | KCNN4 | O15554 | Yes | No | Yes | WangSIGNORDEPOD | SIGNOR:18796614DEPOD:18796614 |
Protein Complex Composition
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion Chromatography | Mass spectrometry | 37 | 31685984389386743929045923376485265384822805423931508500340717773987372639443544377027153279541429562735285623353873186825471207268019192688484130071318306087003292775933580265273124282732049635856505376863663849095841201090307605383136640736982312403116163983538640091455381366013311476838612515 |
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
Biomarker
Phase 2; Investigative; Discontinued in Phase 2
Drug Targets
FDA approved drug targets