O15554 (KCNN4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	KCNN4
Synonyms:	IK1, IKCA1, KCA4, SK4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Immunity Ion transport Transport
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Calmodulin-binding
Molecular function	Ion channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion transport Inferred from direct assay Ref.15. Source: BHF-UCL cell volume homeostasis Inferred from electronic annotation. Source: Compara defense response Traceable author statement Ref.3. Source: ProtInc phospholipid translocation Inferred from electronic annotation. Source: Compara 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: Compara saliva secretion Inferred from electronic annotation. Source: Compara stabilization of membrane potential Inferred from direct assay Ref.15. Source: BHF-UCL synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	voltage-gated potassium channel complex Inferred by curator Ref.15. Source: BHF-UCL
Molecular_function	calcium-activated potassium channel activity Inferred from direct assay 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 427	427	Intermediate conductance calcium-activated potassium channel protein 4		PRO_0000155017
Regions
	Transmembrane	29 – 49	21	Helical; Name=Segment S1; Potential
	Transmembrane	59 – 79	21	Helical; Name=Segment S2; Potential
	Transmembrane	108 – 128	21	Helical; Name=Segment S3; Potential
	Transmembrane	143 – 163	21	Helical; Name=Segment S4; Potential
	Transmembrane	207 – 227	21	Helical; Name=Segment S5; Potential
	Intramembrane	241 – 261	21	Pore-forming; Name=Segment H5; Potential
	Transmembrane	265 – 285	21	Helical; Name=Segment S6; Potential
	Region	286 – 347	62	Calmodulin-binding
Amino acid modifications
	Modified residue	358	1	Phosphohistidine Ref.14
Experimental info
	Mutagenesis	250	1	T → S: Loss of sensitivity to triarylmethanes. Ref.12
	Mutagenesis	275	1	V → A: Loss of sensitivity to triarylmethanes. Ref.12
	Sequence conflict	66	1	S → G in AAK81862. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	O15554 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 23F9AF66609B410F	FASTA	427	47,696
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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 , 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.
IPI	IPI00032466.
RefSeq	NP_002241.1. NM_002250.2.
UniGene	Hs.10082.
3D structure databases
ProteinModelPortal	O15554.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48598N.
IntAct	O15554. 1 interaction.
STRING	9606.ENSP00000262888.
Protein family/group databases
TCDB	1.A.1.16.2. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	O15554.
Proteomic databases
PaxDb	O15554.
PRIDE	O15554.
Protocols and materials databases
DNASU	3783.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262888; ENSP00000262888; ENSG00000104783.
GeneID	3783.
KEGG	hsa:3783.
UCSC	uc002oxl.3. human.
Organism-specific databases
CTD	3783.
GeneCards	GC19M044270.
HGNC	HGNC:6293. KCNN4.
MIM	602754. gene.
neXtProt	NX_O15554.
PharmGKB	PA222.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG323309.
HOGENOM	HOG000276908.
HOVERGEN	HBG052241.
InParanoid	O15554.
KO	K04945.
OMA	CMISIST.
OrthoDB	EOG42FSHQ.
PhylomeDB	O15554.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	O15554.
CleanEx	HS_KCNN4.
Genevestigator	O15554.
GermOnline	ENSG00000104783. Homo sapiens.
Family and domain databases
InterPro	IPR004178. CaM-bd_dom. IPR013099. Ion_trans_2. IPR015449. K_chnl_Ca-activ_SK. [Graphical view]
PANTHER	PTHR10153. PTHR10153. 1 hit.
Pfam	PF02888. CaMBD. 1 hit. PF07885. Ion_trans_2. 1 hit. PF03530. SK_channel. 1 hit. [Graphical view]
SMART	SM01053. CaMBD. 1 hit. [Graphical view]
SUPFAM	SSF81327. CaM_bd. 1 hit.
ProtoNet	Search...
Other
BindingDB	O15554.
ChEMBL	CHEMBL4305.
DrugBank	DB00257. Clotrimazole. DB01159. Halothane. DB00468. Quinine.
GenomeRNAi	3783.
NextBio	14849.
SOURCE	Search...

Entry information

Entry name

KCNN4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.