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O15554 (KCNN4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:KCNN4
Synonyms:IK1, IKCA1, KCA4, SK4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.14 Ref.15

Subunit structure

Heterotetramer of potassium channel proteins Probable. Interacts with MTMR6. Ref.11 Ref.13

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Widely expressed in non-excitable tissues.

Induction

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

Post-translational modification

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

Sequence similarities

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

Ontologies

Keywords
   Biological processImmunity
Ion transport
Transport
   Cellular componentMembrane
   DomainTransmembrane
Transmembrane helix
   LigandCalmodulin-binding
   Molecular functionIon channel
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transport

Inferred from direct assay Ref.15. Source: BHF-UCL

cell volume homeostasis

Inferred from electronic annotation. Source: Ensembl

defense response

Traceable author statement Ref.3. Source: ProtInc

immune system process

Inferred from electronic annotation. Source: UniProtKB-KW

phospholipid translocation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell receptor signaling pathway

Inferred from direct assay Ref.15. Source: BHF-UCL

positive regulation of protein secretion

Inferred from electronic annotation. Source: Ensembl

potassium ion export

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Traceable author statement Ref.1. Source: ProtInc

saliva secretion

Inferred from electronic annotation. Source: Ensembl

stabilization of membrane potential

Inferred from direct assay Ref.15. Source: BHF-UCL

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

voltage-gated potassium channel complex

Inferred by curator Ref.15. Source: BHF-UCL

   Molecular_functionIntermediate conductance calcium-activated potassium channel activity

Inferred from electronic annotation. Source: Ensembl

calcium-activated potassium channel activity

Inferred from direct assay Ref.15. Source: BHF-UCL

protein phosphatase binding

Inferred from physical interaction Ref.15. Source: BHF-UCL

small conductance calcium-activated potassium channel activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 427427Intermediate conductance calcium-activated potassium channel protein 4
PRO_0000155017

Regions

Transmembrane29 – 4921Helical; Name=Segment S1; Potential
Transmembrane59 – 7921Helical; Name=Segment S2; Potential
Transmembrane108 – 12821Helical; Name=Segment S3; Potential
Transmembrane143 – 16321Helical; Name=Segment S4; Potential
Transmembrane207 – 22721Helical; Name=Segment S5; Potential
Intramembrane241 – 26121Pore-forming; Name=Segment H5; Potential
Transmembrane265 – 28521Helical; Name=Segment S6; Potential
Region286 – 34762Calmodulin-binding

Amino acid modifications

Modified residue3581Phosphohistidine Ref.14

Experimental info

Mutagenesis2501T → S: Loss of sensitivity to triarylmethanes. Ref.12
Mutagenesis2751V → A: Loss of sensitivity to triarylmethanes. Ref.12
Sequence conflict661S → G in AAK81862. Ref.6

Sequences

Sequence LengthMass (Da)Tools
O15554 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 23F9AF66609B410F

FASTA42747,696
        10         20         30         40         50         60 
MGGDLVLGLG ALRRRKRLLE QEKSLAGWAL VLAGTGIGLM VLHAEMLWFG GCSWALYLFL 

        70         80         90        100        110        120 
VKCTISISTF LLLCLIVAFH AKEVQLFMTD NGLRDWRVAL TGRQAAQIVL ELVVCGLHPA 

       130        140        150        160        170        180 
PVRGPPCVQD LGAPLTSPQP WPGFLGQGEA LLSLAMLLRL YLVPRAVLLR SGVLLNASYR 

       190        200        210        220        230        240 
SIGALNQVRF RHWFVAKLYM NTHPGRLLLG LTLGLWLTTA WVLSVAERQA VNATGHLSDT 

       250        260        270        280        290        300 
LWLIPITFLT IGYGDVVPGT MWGKIVCLCT GVMGVCCTAL LVAVVARKLE FNKAEKHVHN 

       310        320        330        340        350        360 
FMMDIQYTKE MKESAARVLQ EAWMFYKHTR RKESHAARRH QRKLLAAINA FRQVRLKHRK 

       370        380        390        400        410        420 
LREQVNSMVD ISKMHMILYD LQQNLSSSHR ALEKQIDTLA GKLDALTELL STALGPRQLP 


EPSQQSK 

« Hide

References

« Hide 'large scale' references
[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]"A human intermediate conductance calcium-activated potassium channel."
Ishii T.M., Silvia C., Hirschberg B., Bond C.T., Adelman J.P., Maylie J.
Proc. Natl. Acad. Sci. U.S.A. 94:11651-11656(1997) [PubMed] [Europe PMC] [Abstract]
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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF000972 mRNA. Translation: AAB82739.1.
AF022150 mRNA. Translation: AAC23541.1.
AF022797 mRNA. Translation: AAC51913.1.
AF033021 mRNA. Translation: AAC36804.1.
AF305735 expand/collapse EMBL AC list , 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.
RefSeqNP_002241.1. NM_002250.2.
UniGeneHs.10082.

3D structure databases

ProteinModelPortalO15554.
SMRO15554. Positions 207-373, 376-414.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109984. 6 interactions.
DIPDIP-48598N.
IntActO15554. 1 interaction.
STRING9606.ENSP00000262888.

Chemistry

BindingDBO15554.
ChEMBLCHEMBL4305.
DrugBankDB00257. Clotrimazole.
DB01159. Halothane.
DB00468. Quinine.
GuidetoPHARMACOLOGY384.

Protein family/group databases

TCDB1.A.1.16.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteO15554.

Proteomic databases

PaxDbO15554.
PRIDEO15554.

Protocols and materials databases

DNASU3783.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262888; ENSP00000262888; ENSG00000104783.
GeneID3783.
KEGGhsa:3783.
UCSCuc002oxl.3. human.

Organism-specific databases

CTD3783.
GeneCardsGC19M044270.
HGNCHGNC:6293. KCNN4.
HPAHPA053841.
HPA059622.
MIM602754. gene.
neXtProtNX_O15554.
PharmGKBPA222.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG323309.
HOGENOMHOG000276908.
HOVERGENHBG052241.
InParanoidO15554.
KOK04945.
OMACMISIST.
PhylomeDBO15554.
TreeFamTF315015.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressO15554.
BgeeO15554.
CleanExHS_KCNN4.
GenevestigatorO15554.

Family and domain databases

InterProIPR013099. 2pore_dom_K_chnl_dom.
IPR004178. CaM-bd_dom.
IPR015449. K_chnl_Ca-activ_SK.
[Graphical view]
PANTHERPTHR10153. PTHR10153. 1 hit.
PfamPF02888. CaMBD. 1 hit.
PF07885. Ion_trans_2. 1 hit.
PF03530. SK_channel. 1 hit.
[Graphical view]
SMARTSM01053. CaMBD. 1 hit.
[Graphical view]
SUPFAMSSF81327. SSF81327. 1 hit.
ProtoNetSearch...

Other

GeneWikiKCNN4.
GenomeRNAi3783.
NextBio14849.
PROO15554.
SOURCESearch...

Entry information

Entry nameKCNN4_HUMAN
AccessionPrimary (citable) accession number: O15554
Secondary accession number(s): Q53XR4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM