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O15554

- KCNN4_HUMAN

UniProt

O15554 - KCNN4_HUMAN

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Protein

Intermediate conductance calcium-activated potassium channel protein 4

Gene

KCNN4

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. calcium-activated potassium channel activity Source: BHF-UCL
  2. calmodulin binding Source: RefGenome
  3. Intermediate conductance calcium-activated potassium channel activity Source: RefGenome
  4. protein phosphatase binding Source: BHF-UCL

GO - Biological processi

  1. calcium ion transport Source: BHF-UCL
  2. cell volume homeostasis Source: Ensembl
  3. defense response Source: ProtInc
  4. immune system process Source: UniProtKB-KW
  5. phospholipid translocation Source: Ensembl
  6. positive regulation of protein secretion Source: Ensembl
  7. positive regulation of T cell receptor signaling pathway Source: BHF-UCL
  8. potassium ion export Source: Ensembl
  9. potassium ion transmembrane transport Source: RefGenome
  10. potassium ion transport Source: ProtInc
  11. saliva secretion Source: Ensembl
  12. stabilization of membrane potential Source: BHF-UCL
  13. 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: Chromosome 19

Organism-specific databases

HGNCiHGNC:6293. KCNN4.

Subcellular locationi

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. basolateral plasma membrane Source: Ensembl
  3. membrane raft Source: Ensembl
  4. neuronal cell body Source: RefGenome
  5. plasma membrane Source: RefGenome
  6. voltage-gated potassium channel complex Source: BHF-UCL
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.

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 MTMR6.2 PublicationsCurated

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliO15554.
SMRiO15554. Positions 207-373.
ModBaseiSearch...
MobiDBiSearch...

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei241 – 26121Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST

Transmembrane

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
Transmembranei265 – 28521Helical; Name=Segment S6Sequence AnalysisAdd
BLAST

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.
OMAiKCMISIS.
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. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS12630.1.
RefSeqi NP_002241.1. NM_002250.2.
UniGenei Hs.10082.

3D structure databases

ProteinModelPortali O15554.
SMRi O15554. Positions 207-373.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109984. 6 interactions.
DIPi DIP-48598N.
IntActi O15554. 1 interaction.
STRINGi 9606.ENSP00000262888.

Chemistry

BindingDBi O15554.
ChEMBLi CHEMBL4305.
DrugBanki DB00257. Clotrimazole.
DB00228. Enflurane.
DB01159. Halothane.
DB01110. Miconazole.
DB00721. Procaine.
DB00468. Quinine.
GuidetoPHARMACOLOGYi 384.

Protein family/group databases

TCDBi 1.A.1.16.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSitei O15554.

Proteomic databases

MaxQBi O15554.
PaxDbi O15554.
PRIDEi O15554.

Protocols and materials databases

DNASUi 3783.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262888 ; ENSP00000262888 ; ENSG00000104783 .
GeneIDi 3783.
KEGGi hsa:3783.
UCSCi uc002oxl.3. human.

Organism-specific databases

CTDi 3783.
GeneCardsi GC19M044270.
HGNCi HGNC:6293. KCNN4.
HPAi HPA053841.
HPA059622.
MIMi 602754. gene.
neXtProti NX_O15554.
PharmGKBi PA222.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG323309.
GeneTreei ENSGT00500000044784.
HOGENOMi HOG000276908.
HOVERGENi HBG052241.
InParanoidi O15554.
KOi K04945.
OMAi KCMISIS.
PhylomeDBi O15554.
TreeFami TF315015.

Enzyme and pathway databases

Reactomei REACT_75896. Ca2+ activated K+ channels.

Miscellaneous databases

GeneWikii KCNN4.
GenomeRNAii 3783.
NextBioi 14849.
PROi O15554.
SOURCEi Search...

Gene expression databases

Bgeei O15554.
CleanExi HS_KCNN4.
ExpressionAtlasi O15554. baseline and differential.
Genevestigatori O15554.

Family and domain databases

InterProi IPR013099. 2pore_dom_K_chnl_dom.
IPR004178. CaM-bd_dom.
IPR015449. K_chnl_Ca-activ_SK.
[Graphical view ]
PANTHERi PTHR10153. PTHR10153. 1 hit.
Pfami PF02888. CaMBD. 1 hit.
PF07885. Ion_trans_2. 1 hit.
PF03530. SK_channel. 1 hit.
[Graphical view ]
SMARTi SM01053. CaMBD. 1 hit.
[Graphical view ]
SUPFAMi SSF81327. SSF81327. 1 hit.
ProtoNeti Search...

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: October 29, 2014
This is version 133 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