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Protein

Intermediate conductance calcium-activated potassium channel protein 4

Gene

KCNN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).3 Publications

GO - Molecular functioni

GO - Biological processi

  • calcium ion transport Source: BHF-UCL
  • cell volume homeostasis Source: Ensembl
  • defense response Source: ProtInc
  • immune system process Source: UniProtKB-KW
  • phospholipid translocation Source: Ensembl
  • positive regulation of protein secretion Source: Ensembl
  • positive regulation of T cell receptor signaling pathway Source: BHF-UCL
  • potassium ion transport Source: ProtInc
  • saliva secretion Source: Ensembl
  • stabilization of membrane potential Source: BHF-UCL

Keywordsi

Molecular functionCalmodulin-binding, Ion channel
Biological processImmunity, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1296052 Ca2+ activated K+ channels
SIGNORiO15554

Protein family/group databases

TCDBi1.A.1.16.2 the voltage-gated ion channel (vic) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Intermediate conductance calcium-activated potassium channel protein 4
Short name:
SK4
Short name:
SKCa 4
Short name:
SKCa4
Alternative name(s):
IKCa1
Short name:
IK1
KCa3.1
KCa4
Putative Gardos channel
Gene namesi
Name:KCNN4
Synonyms:IK1, IKCA1, KCA4, SK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000104783.11
HGNCiHGNC:6293 KCNN4
MIMi602754 gene
neXtProtiNX_O15554

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei29 – 49Helical; Name=Segment S1Sequence analysisAdd BLAST21
Transmembranei59 – 79Helical; Name=Segment S2Sequence analysisAdd BLAST21
Transmembranei108 – 128Helical; Name=Segment S3Sequence analysisAdd BLAST21
Transmembranei143 – 163Helical; Name=Segment S4Sequence analysisAdd BLAST21
Transmembranei207 – 227Helical; Name=Segment S5Sequence analysisAdd BLAST21
Intramembranei241 – 261Pore-forming; Name=Segment H5Sequence analysisAdd BLAST21
Transmembranei265 – 285Helical; Name=Segment S6Sequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Dehydrated hereditary stomatocytosis 2 (DHS2)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. Affected individuals typically manifest mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur.
See also OMIM:616689
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074485282V → E in DHS2. 1 PublicationCorresponds to variant dbSNP:rs1057519077Ensembl.1
Natural variantiVAR_074486282V → M in DHS2. 2 PublicationsCorresponds to variant dbSNP:rs1057519076Ensembl.1
Natural variantiVAR_074487352R → H in DHS2; no effect on plasma membrane localization; increases calcium-activated potassium channel activity. 2 PublicationsCorresponds to variant dbSNP:rs774455945EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi250T → S: Loss of sensitivity to triarylmethanes. 1 Publication1
Mutagenesisi275V → A: Loss of sensitivity to triarylmethanes. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

DisGeNETi3783
MalaCardsiKCNN4
MIMi616689 phenotype
OpenTargetsiENSG00000104783
PharmGKBiPA222

Chemistry databases

ChEMBLiCHEMBL4305
DrugBankiDB00257 Clotrimazole
DB00228 Enflurane
DB01159 Halothane
DB01110 Miconazole
DB00721 Procaine
DB00468 Quinine
GuidetoPHARMACOLOGYi384

Polymorphism and mutation databases

BioMutaiKCNN4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001550171 – 427Intermediate conductance calcium-activated potassium channel protein 4Add BLAST427

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei358Phosphohistidine1 Publication1

Post-translational modificationi

Phosphorylation at His-358 by NDKB activates the channel, and conversely it's dephosphorylation by PHPT1 inhibits the channel.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO15554
MaxQBiO15554
PaxDbiO15554
PeptideAtlasiO15554
PRIDEiO15554
ProteomicsDBi48757

PTM databases

iPTMnetiO15554
PhosphoSitePlusiO15554
SwissPalmiO15554

Expressioni

Tissue specificityi

Widely expressed in non-excitable tissues.

Inductioni

Up-regulated by phorbol myristate acetate (PMA) and phytohemagglutinin (PHA) in T-cells.

Gene expression databases

BgeeiENSG00000104783
CleanExiHS_KCNN4
ExpressionAtlasiO15554 baseline and differential
GenevisibleiO15554 HS

Organism-specific databases

HPAiHPA053841
HPA059622

Interactioni

Subunit structurei

Heterotetramer of potassium channel proteins (Probable). Interacts with MTMR6.Curated2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • calmodulin binding Source: GO_Central
  • protein phosphatase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109984, 7 interactors
DIPiDIP-48598N
IntActiO15554, 11 interactors
STRINGi9606.ENSP00000262888

Chemistry databases

BindingDBiO15554

Structurei

Secondary structure

1427
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 50Combined sources39
Turni51 – 56Combined sources6
Helixi57 – 91Combined sources35
Helixi96 – 99Combined sources4
Helixi104 – 114Combined sources11
Helixi149 – 154Combined sources6
Helixi155 – 161Combined sources7
Helixi162 – 170Combined sources9
Turni172 – 174Combined sources3
Helixi177 – 186Combined sources10
Helixi192 – 202Combined sources11
Helixi204 – 226Combined sources23
Turni230 – 233Combined sources4
Helixi237 – 248Combined sources12
Beta strandi254 – 256Combined sources3
Helixi261 – 287Combined sources27
Helixi293 – 330Combined sources38
Turni335 – 337Combined sources3
Helixi338 – 368Combined sources31
Helixi370 – 384Combined sources15

3D structure databases

ProteinModelPortaliO15554
SMRiO15554
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni286 – 347Calmodulin-bindingAdd BLAST62

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3684 Eukaryota
ENOG410XT9D LUCA
GeneTreeiENSGT00500000044784
HOGENOMiHOG000276908
HOVERGENiHBG052241
InParanoidiO15554
KOiK04945
OMAiHAEMLWF
OrthoDBiEOG091G09X0
PhylomeDBiO15554
TreeFamiTF315015

Family and domain databases

InterProiView protein in InterPro
IPR004178 CaM-bd_dom
IPR036122 CaM-bd_dom_sf
IPR015449 K_chnl_Ca-activ_SK
IPR013099 K_chnl_dom
PANTHERiPTHR10153 PTHR10153, 1 hit
PfamiView protein in Pfam
PF02888 CaMBD, 1 hit
PF07885 Ion_trans_2, 1 hit
PF03530 SK_channel, 1 hit
SMARTiView protein in SMART
SM01053 CaMBD, 1 hit
SUPFAMiSSF81327 SSF81327, 1 hit

Sequencei

Sequence statusi: Complete.

O15554-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGGDLVLGLG ALRRRKRLLE QEKSLAGWAL VLAGTGIGLM VLHAEMLWFG
60 70 80 90 100
GCSWALYLFL VKCTISISTF LLLCLIVAFH AKEVQLFMTD NGLRDWRVAL
110 120 130 140 150
TGRQAAQIVL ELVVCGLHPA PVRGPPCVQD LGAPLTSPQP WPGFLGQGEA
160 170 180 190 200
LLSLAMLLRL YLVPRAVLLR SGVLLNASYR SIGALNQVRF RHWFVAKLYM
210 220 230 240 250
NTHPGRLLLG LTLGLWLTTA WVLSVAERQA VNATGHLSDT LWLIPITFLT
260 270 280 290 300
IGYGDVVPGT MWGKIVCLCT GVMGVCCTAL LVAVVARKLE FNKAEKHVHN
310 320 330 340 350
FMMDIQYTKE MKESAARVLQ EAWMFYKHTR RKESHAARRH QRKLLAAINA
360 370 380 390 400
FRQVRLKHRK LREQVNSMVD ISKMHMILYD LQQNLSSSHR ALEKQIDTLA
410 420
GKLDALTELL STALGPRQLP EPSQQSK
Length:427
Mass (Da):47,696
Last modified:January 1, 1998 - v1
Checksum:i23F9AF66609B410F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66S → G in AAK81862 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074485282V → E in DHS2. 1 PublicationCorresponds to variant dbSNP:rs1057519077Ensembl.1
Natural variantiVAR_074486282V → M in DHS2. 2 PublicationsCorresponds to variant dbSNP:rs1057519076Ensembl.1
Natural variantiVAR_074487352R → H in DHS2; no effect on plasma membrane localization; increases calcium-activated potassium channel activity. 2 PublicationsCorresponds to variant dbSNP:rs774455945EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000972 mRNA Translation: AAB82739.1
AF022150 mRNA Translation: AAC23541.1
AF022797 mRNA Translation: AAC51913.1
AF033021 mRNA Translation: AAC36804.1
AF305735
, AF305731, AF305732, AF305733, AF305734 Genomic DNA Translation: AAG26917.1
AF395661 mRNA Translation: AAK81862.1
BT007426 mRNA Translation: AAP36094.1
CH471126 Genomic DNA Translation: EAW57230.1
BC015337 mRNA Translation: AAH15337.1
AF053403 mRNA Translation: AAC35281.1
CCDSiCCDS12630.1
RefSeqiNP_002241.1, NM_002250.2
UniGeneiHs.10082

Genome annotation databases

EnsembliENST00000262888; ENSP00000262888; ENSG00000104783
GeneIDi3783
KEGGihsa:3783
UCSCiuc002oxl.3 human

Similar proteinsi

Entry informationi

Entry nameiKCNN4_HUMAN
AccessioniPrimary (citable) accession number: O15554
Secondary accession number(s): Q53XR4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: January 1, 1998
Last modified: July 18, 2018
This is version 163 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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