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Protein

Intermediate conductance calcium-activated potassium channel protein 4

Gene

KCNN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Forms a voltage-independent potassium channel that is activated by intracellular calcium. 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.2 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 export Source: Ensembl
  • potassium ion transmembrane transport Source: GO_Central
  • potassium ion transport Source: ProtInc
  • saliva secretion Source: Ensembl
  • stabilization of membrane potential Source: BHF-UCL
  • synaptic transmission Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Immunity, Ion transport, Transport

Keywords - Ligandi

Calmodulin-binding

Enzyme and pathway databases

ReactomeiREACT_75896. Ca2+ activated K+ channels.

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
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6293. KCNN4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei29 – 4921Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Transmembranei59 – 7921Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Transmembranei108 – 12821Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Transmembranei143 – 16321Helical; Name=Segment S4Sequence AnalysisAdd
BLAST
Transmembranei207 – 22721Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Intramembranei241 – 26121Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST
Transmembranei265 – 28521Helical; Name=Segment S6Sequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi250 – 2501T → S: Loss of sensitivity to triarylmethanes. 1 Publication
Mutagenesisi275 – 2751V → A: Loss of sensitivity to triarylmethanes. 1 Publication

Organism-specific databases

PharmGKBiPA222.

Chemistry

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

Polymorphism and mutation databases

BioMutaiKCNN4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 427427Intermediate conductance calcium-activated potassium channel protein 4PRO_0000155017Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei358 – 3581Phosphohistidine1 Publication

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

MaxQBiO15554.
PaxDbiO15554.
PRIDEiO15554.

PTM databases

PhosphoSiteiO15554.

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

BgeeiO15554.
CleanExiHS_KCNN4.
ExpressionAtlasiO15554. baseline and differential.
GenevestigatoriO15554.

Organism-specific databases

HPAiHPA053841.
HPA059622.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi109984. 6 interactions.
DIPiDIP-48598N.
IntActiO15554. 1 interaction.
STRINGi9606.ENSP00000262888.

Structurei

3D structure databases

ProteinModelPortaliO15554.
SMRiO15554. Positions 287-373.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni286 – 34762Calmodulin-bindingAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG323309.
GeneTreeiENSGT00500000044784.
HOGENOMiHOG000276908.
HOVERGENiHBG052241.
InParanoidiO15554.
KOiK04945.
OMAiDIHYAKE.
PhylomeDBiO15554.
TreeFamiTF315015.

Family and domain databases

InterProiIPR013099. 2pore_dom_K_chnl_dom.
IPR004178. CaM-bd_dom.
IPR015449. K_chnl_Ca-activ_SK.
[Graphical view]
PANTHERiPTHR10153. PTHR10153. 1 hit.
PfamiPF02888. CaMBD. 1 hit.
PF07885. Ion_trans_2. 1 hit.
PF03530. SK_channel. 1 hit.
[Graphical view]
SMARTiSM01053. CaMBD. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661S → G in AAK81862 (Ref. 6) Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliO15554.
SMRiO15554. Positions 287-373.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109984. 6 interactions.
DIPiDIP-48598N.
IntActiO15554. 1 interaction.
STRINGi9606.ENSP00000262888.

Chemistry

BindingDBiO15554.
ChEMBLiCHEMBL4305.
DrugBankiDB00257. Clotrimazole.
DB00228. Enflurane.
DB01159. Halothane.
DB01110. Miconazole.
DB00721. Procaine.
DB00468. Quinine.
GuidetoPHARMACOLOGYi384.

Protein family/group databases

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

PTM databases

PhosphoSiteiO15554.

Polymorphism and mutation databases

BioMutaiKCNN4.

Proteomic databases

MaxQBiO15554.
PaxDbiO15554.
PRIDEiO15554.

Protocols and materials databases

DNASUi3783.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3783.
GeneCardsiGC19M044270.
HGNCiHGNC:6293. KCNN4.
HPAiHPA053841.
HPA059622.
MIMi602754. gene.
neXtProtiNX_O15554.
PharmGKBiPA222.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG323309.
GeneTreeiENSGT00500000044784.
HOGENOMiHOG000276908.
HOVERGENiHBG052241.
InParanoidiO15554.
KOiK04945.
OMAiDIHYAKE.
PhylomeDBiO15554.
TreeFamiTF315015.

Enzyme and pathway databases

ReactomeiREACT_75896. Ca2+ activated K+ channels.

Miscellaneous databases

ChiTaRSiKCNN4. human.
GeneWikiiKCNN4.
GenomeRNAii3783.
NextBioi14849.
PROiO15554.
SOURCEiSearch...

Gene expression databases

BgeeiO15554.
CleanExiHS_KCNN4.
ExpressionAtlasiO15554. baseline and differential.
GenevestigatoriO15554.

Family and domain databases

InterProiIPR013099. 2pore_dom_K_chnl_dom.
IPR004178. CaM-bd_dom.
IPR015449. K_chnl_Ca-activ_SK.
[Graphical view]
PANTHERiPTHR10153. PTHR10153. 1 hit.
PfamiPF02888. CaMBD. 1 hit.
PF07885. Ion_trans_2. 1 hit.
PF03530. SK_channel. 1 hit.
[Graphical view]
SMARTiSM01053. CaMBD. 1 hit.
[Graphical view]
SUPFAMiSSF81327. SSF81327. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "hSK4, a member of a novel subfamily of calcium-activated potassium channels."
    Joiner W.J., Wang L.-Y., Tang M.D., Kaczmarek L.K.
    Proc. Natl. Acad. Sci. U.S.A. 94:11013-11018(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Placenta.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pancreas.
  3. "A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes."
    Logsdon N.J., Kang J., Togo J.A., Christian E.P., Aiyar J.
    J. Biol. Chem. 272:32723-32726(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lymph node.
  4. "Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia."
    Ghanshani S., Coleman M., Gustavsson P., Wu A.C., Gargus J.J., Gutman G.A., Dahl N., Mohrenweiser H., Chandy K.G.
    Genomics 51:160-161(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences."
    Ghanshani S., Wulff H., Miller M.J., Rohm H., Neben A., Gutman G.A., Cahalan M.D., Chandy K.G.
    J. Biol. Chem. 275:37137-37149(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "Characterization of calcium-activated potassium channels in human myometrium."
    Mazzone J.N., Kaiser R.A., Buxton I.L.O.
    Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Myometrium.
  7. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  10. "hIK1 (putative Gardos channel) PCR product amplified from the K562 human erythroleukemic cell line."
    Golding S., Culliford S.J., Ellory J.C.
    Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 227-367.
  11. "Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1."
    Fanger C.M., Ghanshani S., Logsdon N.J., Rauer H., Kalman K., Zhou J., Beckingham K., Chandy K.G., Cahalan M.D., Aiyar J.
    J. Biol. Chem. 274:5746-5754(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CALMODULIN.
  12. "Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1."
    Wulff H., Gutman G.A., Cahalan M.D., Chandy K.G.
    J. Biol. Chem. 276:32040-32045(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF THR-250 AND VAL-275.
  13. "The phosphatidylinositol 3-phosphate phosphatase myotubularin-related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1."
    Srivastava S., Li Z., Lin L., Liu G., Ko K., Coetzee W.A., Skolnik E.Y.
    Mol. Cell. Biol. 25:3630-3638(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MTMR6.
  14. "Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells."
    Srivastava S., Li Z., Ko K., Choudhury P., Albaqumi M., Johnson A.K., Yan Y., Backer J.M., Unutmaz D., Coetzee W.A., Skolnik E.Y.
    Mol. Cell 24:665-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT HIS-358.
  15. "Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1."
    Srivastava S., Zhdanova O., Di L., Li Z., Albaqumi M., Wulff H., Skolnik E.Y.
    Proc. Natl. Acad. Sci. U.S.A. 105:14442-14446(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INHIBITIVE DEPHOSPHORYLATION BY PTHP1.
  16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiKCNN4_HUMAN
AccessioniPrimary (citable) accession number: O15554
Secondary accession number(s): Q53XR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: January 1, 1998
Last modified: April 29, 2015
This is version 137 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.