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Protein

Potassium channel subfamily K member 3

Gene

KCNK3

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

Functioni

pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward.2 Publications

Miscellaneous

Inhibited by external acidification. Activated by halothane and isoflurane.

GO - Molecular functioni

  • growth factor activity Source: InterPro
  • ion channel activity Source: UniProtKB
  • open rectifier potassium channel activity Source: Ensembl
  • potassium channel activity Source: Reactome
  • potassium ion leak channel activity Source: UniProtKB
  • protein C-terminus binding Source: Ensembl
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: Ensembl
  • S100 protein binding Source: UniProtKB

GO - Biological processi

  • brain development Source: Ensembl
  • cardiac conduction Source: Reactome
  • cellular response to hypoxia Source: Ensembl
  • cellular response to zinc ion Source: Ensembl
  • chemical synaptic transmission Source: ProtInc
  • cochlea development Source: Ensembl
  • ion transmembrane transport Source: UniProtKB
  • negative regulation of cytosolic calcium ion concentration Source: Ensembl
  • potassium ion transport Source: ProtInc
  • response to drug Source: Ensembl
  • stabilization of membrane potential Source: GO_Central

Keywordsi

Molecular functionIon channel, Potassium channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1299316. TWIK-releated acid-sensitive K+ channel (TASK).
R-HSA-5576886. Phase 4 - resting membrane potential.
SIGNORiO14649.

Protein family/group databases

TCDBi1.A.1.9.2. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium channel subfamily K member 3
Alternative name(s):
Acid-sensitive potassium channel protein TASK-1
TWIK-related acid-sensitive K(+) channel 1
Two pore potassium channel KT3.1
Short name:
Two pore K(+) channel KT3.1
Gene namesi
Name:KCNK3
Synonyms:TASK, TASK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000171303.6.
HGNCiHGNC:6278. KCNK3.

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
Topological domaini1 – 8CytoplasmicSequence analysis8
Transmembranei9 – 29HelicalSequence analysisAdd BLAST21
Intramembranei78 – 101Pore-forming; Name=Pore-forming 1Sequence analysisAdd BLAST24
Transmembranei108 – 128HelicalSequence analysisAdd BLAST21
Topological domaini129 – 158CytoplasmicSequence analysisAdd BLAST30
Transmembranei159 – 179HelicalSequence analysisAdd BLAST21
Intramembranei184 – 207Pore-forming; Name=Pore-forming 2Sequence analysisAdd BLAST24
Transmembranei223 – 243HelicalSequence analysisAdd BLAST21
Topological domaini244 – 394CytoplasmicSequence analysisAdd BLAST151

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Pulmonary hypertension, primary, 4 (PPH4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
See also OMIM:615344
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0701268T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication1
Natural variantiVAR_07012797G → R in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123040Ensembl.1
Natural variantiVAR_070128182E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 PublicationCorresponds to variant dbSNP:rs398123042Ensembl.1
Natural variantiVAR_070129192Y → C in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123043Ensembl.1
Natural variantiVAR_070130203G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 PublicationCorresponds to variant dbSNP:rs398123039Ensembl.1
Natural variantiVAR_070131221V → L in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123041Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi98H → N: Greatly reduces pH sensitivity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3777.
MalaCardsiKCNK3.
MIMi615344. phenotype.
OpenTargetsiENSG00000171303.
Orphaneti275777. Heritable pulmonary arterial hypertension.
275766. Idiopathic pulmonary arterial hypertension.
PharmGKBiPA30060.

Chemistry databases

ChEMBLiCHEMBL2321613.
DrugBankiDB00561. Doxapram.
DB01159. Halothane.
GuidetoPHARMACOLOGYi515.

Polymorphism and mutation databases

BioMutaiKCNK3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001017441 – 394Potassium channel subfamily K member 3Add BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi53N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO14649.
PeptideAtlasiO14649.
PRIDEiO14649.

PTM databases

iPTMnetiO14649.
PhosphoSitePlusiO14649.

Expressioni

Tissue specificityi

Widespread expression in adult. Strongest expression in pancreas and placenta. Lower expression in brain, lung, prostate, heart, kidney, uterus, small intestine and colon.

Gene expression databases

BgeeiENSG00000171303.
CleanExiHS_KCNK3.
ExpressionAtlasiO14649. baseline and differential.
GenevisibleiO14649. HS.

Interactioni

Subunit structurei

Homodimer (Probable). Heterodimer with KCNK1.Curated1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109978. 3 interactors.
IntActiO14649. 1 interactor.
MINTiMINT-1645466.
STRINGi9606.ENSP00000306275.

Chemistry databases

BindingDBiO14649.

Structurei

3D structure databases

ProteinModelPortaliO14649.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4404. Eukaryota.
ENOG410XRZJ. LUCA.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000231463.
HOVERGENiHBG052239.
InParanoidiO14649.
KOiK04914.
OMAiCSGTQRS.
OrthoDBiEOG091G08DH.
PhylomeDBiO14649.
TreeFamiTF313947.

Family and domain databases

InterProiView protein in InterPro
IPR003280. 2pore_dom_K_chnl.
IPR003092. 2pore_dom_K_chnl_TASK.
IPR022341. IGF-I.
IPR013099. K_chnl_dom.
IPR005406. KCNK3.
PANTHERiPTHR11003:SF138. PTHR11003:SF138. 1 hit.
PfamiView protein in Pfam
PF07885. Ion_trans_2. 2 hits.
PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
PRINTSiPR01333. 2POREKCHANEL.
PR01584. TASK1CHANNEL.
PR01095. TASKCHANNEL.

Sequencei

Sequence statusi: Complete.

O14649-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA
60 70 80 90 100
RYNLSQGGYE ELERVVLRLK PHKAGVQWRF AGSFYFAITV ITTIGYGHAA
110 120 130 140 150
PSTDGGKVFC MFYALLGIPL TLVMFQSLGE RINTLVRYLL HRAKKGLGMR
160 170 180 190 200
RADVSMANMV LIGFFSCIST LCIGAAAFSH YEHWTFFQAY YYCFITLTTI
210 220 230 240 250
GFGDYVALQK DQALQTQPQY VAFSFVYILT GLTVIGAFLN LVVLRFMTMN
260 270 280 290 300
AEDEKRDAEH RALLTRNGQA GGGGGGGSAH TTDTASSTAA AGGGGFRNVY
310 320 330 340 350
AEVLHFQSMC SCLWYKSREK LQYSIPMIIP RDLSTSDTCV EQSHSSPGGG
360 370 380 390
GRYSDTPSRR CLCSGAPRSA ISSVSTGLHS LSTFRGLMKR RSSV
Length:394
Mass (Da):43,518
Last modified:January 1, 1998 - v1
Checksum:i9FF4C8266F615FB7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0701268T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication1
Natural variantiVAR_07012797G → R in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123040Ensembl.1
Natural variantiVAR_070128182E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 PublicationCorresponds to variant dbSNP:rs398123042Ensembl.1
Natural variantiVAR_070129192Y → C in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123043Ensembl.1
Natural variantiVAR_070130203G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 PublicationCorresponds to variant dbSNP:rs398123039Ensembl.1
Natural variantiVAR_070131221V → L in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123041Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF006823 mRNA. Translation: AAC51777.1.
AF065163 mRNA. Translation: AAG29340.1.
AC015977 Genomic DNA. Translation: AAY24312.1.
CH471053 Genomic DNA. Translation: EAX00678.1.
CH471053 Genomic DNA. Translation: EAX00679.1.
CCDSiCCDS1727.1.
RefSeqiNP_002237.1. NM_002246.2.
UniGeneiHs.24040.
Hs.645288.

Genome annotation databases

EnsembliENST00000302909; ENSP00000306275; ENSG00000171303.
GeneIDi3777.
KEGGihsa:3777.
UCSCiuc002rhn.3. human.

Similar proteinsi

Entry informationi

Entry nameiKCNK3_HUMAN
AccessioniPrimary (citable) accession number: O14649
Secondary accession number(s): Q53SU2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 1, 1998
Last modified: October 25, 2017
This is version 156 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. SIMILARITY comments
    Index of protein domains and families