UniProtKB - O14649 (KCNK3_HUMAN)
Protein
Potassium channel subfamily K member 3
Gene
KCNK3
Organism
Homo sapiens (Human)
Status
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
- ion channel activity Source: UniProtKB
- open rectifier potassium channel activity Source: Ensembl
- potassium channel activity Source: ProtInc
- potassium ion leak channel activity Source: UniProtKB
- protein C-terminus binding 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 transmembrane transport Source: GO_Central
- potassium ion transport Source: ProtInc
- response to drug Source: Ensembl
- stabilization of membrane potential Source: GO_Central
Keywordsi
Molecular function | Ion channel, Potassium channel |
Biological process | Ion transport, Potassium transport, Transport |
Ligand | Potassium |
Enzyme and pathway databases
PathwayCommonsi | O14649 |
Reactomei | R-HSA-1299316, TWIK-releated acid-sensitive K+ channel (TASK) R-HSA-5576886, Phase 4 - resting membrane potential |
SIGNORi | O14649 |
Protein family/group databases
TCDBi | 1.A.1.9.2, the voltage-gated ion channel (vic) superfamily |
Names & Taxonomyi
Protein namesi | Recommended name: Potassium channel subfamily K member 3Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000171303.6 |
HGNCi | HGNC:6278, KCNK3 |
MIMi | 603220, gene |
neXtProti | NX_O14649 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein Curated
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- synapse Source: GOC
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 8 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 9 – 29 | HelicalSequence analysisAdd BLAST | 21 | |
Intramembranei | 78 – 101 | Pore-forming; Name=Pore-forming 1Sequence analysisAdd BLAST | 24 | |
Transmembranei | 108 – 128 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 129 – 158 | CytoplasmicSequence analysisAdd BLAST | 30 | |
Transmembranei | 159 – 179 | HelicalSequence analysisAdd BLAST | 21 | |
Intramembranei | 184 – 207 | Pore-forming; Name=Pore-forming 2Sequence analysisAdd BLAST | 24 | |
Transmembranei | 223 – 243 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 244 – 394 | CytoplasmicSequence analysisAdd BLAST | 151 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070126 | 8 | T → 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:rs1085307438EnsemblClinVar. | 1 | |
Natural variantiVAR_070127 | 97 | G → R in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123040EnsemblClinVar. | 1 | |
Natural variantiVAR_070128 | 182 | E → 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:rs398123042EnsemblClinVar. | 1 | |
Natural variantiVAR_070129 | 192 | Y → C in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123043EnsemblClinVar. | 1 | |
Natural variantiVAR_070130 | 203 | G → 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:rs398123039EnsemblClinVar. | 1 | |
Natural variantiVAR_070131 | 221 | V → L in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123041EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 98 | H → N: Greatly reduces pH sensitivity. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 3777 |
GeneReviewsi | KCNK3 |
MalaCardsi | KCNK3 |
MIMi | 615344, phenotype |
OpenTargetsi | ENSG00000171303 |
Orphaneti | 275777, Heritable pulmonary arterial hypertension |
PharmGKBi | PA30060 |
Miscellaneous databases
Pharosi | O14649, Tclin |
Chemistry databases
ChEMBLi | CHEMBL2321613 |
DrugBanki | DB00561, Doxapram DB01159, Halothane |
DrugCentrali | O14649 |
GuidetoPHARMACOLOGYi | 515 |
Polymorphism and mutation databases
BioMutai | KCNK3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000101744 | 1 – 394 | Potassium channel subfamily K member 3Add BLAST | 394 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 53 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
MassIVEi | O14649 |
PaxDbi | O14649 |
PeptideAtlasi | O14649 |
PRIDEi | O14649 |
ProteomicsDBi | 48147 |
PTM databases
GlyGeni | O14649, 1 site |
iPTMneti | O14649 |
PhosphoSitePlusi | O14649 |
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
Bgeei | ENSG00000171303, Expressed in adrenal gland and 174 other tissues |
ExpressionAtlasi | O14649, baseline and differential |
Genevisiblei | O14649, HS |
Organism-specific databases
HPAi | ENSG00000171303, Tissue enhanced (adrenal) |
Interactioni
Subunit structurei
Homodimer (Probable). Heterodimer with KCNK1.
Curated1 PublicationGO - Molecular functioni
- protein C-terminus binding Source: Ensembl
- S100 protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 109978, 4 interactors |
IntActi | O14649, 2 interactors |
MINTi | O14649 |
STRINGi | 9606.ENSP00000306275 |
Chemistry databases
BindingDBi | O14649 |
Miscellaneous databases
RNActi | O14649, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O14649 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4404, Eukaryota |
GeneTreei | ENSGT00940000158248 |
HOGENOMi | CLU_022504_4_0_1 |
InParanoidi | O14649 |
OMAi | SDTCVEH |
OrthoDBi | 1109218at2759 |
PhylomeDBi | O14649 |
TreeFami | TF313947 |
Family and domain databases
InterProi | View protein in InterPro IPR003280, 2pore_dom_K_chnl IPR003092, 2pore_dom_K_chnl_TASK IPR013099, K_chnl_dom IPR005406, KCNK3 |
PANTHERi | PTHR11003:SF138, PTHR11003:SF138, 1 hit |
Pfami | View protein in Pfam PF07885, Ion_trans_2, 2 hits |
PIRSFi | PIRSF038061, K_channel_subfamily_K_type, 1 hit |
PRINTSi | PR01333, 2POREKCHANEL PR01584, TASK1CHANNEL PR01095, TASKCHANNEL |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O14649-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB9EIJ4 | B9EIJ4_HUMAN | KCNK3 protein | KCNK3 | 271 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070126 | 8 | T → 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:rs1085307438EnsemblClinVar. | 1 | |
Natural variantiVAR_070127 | 97 | G → R in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123040EnsemblClinVar. | 1 | |
Natural variantiVAR_070128 | 182 | E → 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:rs398123042EnsemblClinVar. | 1 | |
Natural variantiVAR_070129 | 192 | Y → C in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123043EnsemblClinVar. | 1 | |
Natural variantiVAR_070130 | 203 | G → 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:rs398123039EnsemblClinVar. | 1 | |
Natural variantiVAR_070131 | 221 | V → L in PPH4; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398123041EnsemblClinVar. | 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 |
CCDSi | CCDS1727.1 |
RefSeqi | NP_002237.1, NM_002246.2 |
Genome annotation databases
Ensembli | ENST00000302909; ENSP00000306275; ENSG00000171303 |
GeneIDi | 3777 |
KEGGi | hsa:3777 |
UCSCi | uc002rhn.3, human |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS1727.1 |
RefSeqi | NP_002237.1, NM_002246.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6RV2 | X-ray | 3.00 | A/B/C/D | 1-259 | [»] | |
6RV3 | X-ray | 2.90 | A/B/C/D | 1-259 | [»] | |
6RV4 | X-ray | 3.10 | A/B/C/D | 1-259 | [»] | |
SMRi | O14649 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109978, 4 interactors |
IntActi | O14649, 2 interactors |
MINTi | O14649 |
STRINGi | 9606.ENSP00000306275 |
Chemistry databases
BindingDBi | O14649 |
ChEMBLi | CHEMBL2321613 |
DrugBanki | DB00561, Doxapram DB01159, Halothane |
DrugCentrali | O14649 |
GuidetoPHARMACOLOGYi | 515 |
Protein family/group databases
TCDBi | 1.A.1.9.2, the voltage-gated ion channel (vic) superfamily |
PTM databases
GlyGeni | O14649, 1 site |
iPTMneti | O14649 |
PhosphoSitePlusi | O14649 |
Polymorphism and mutation databases
BioMutai | KCNK3 |
Proteomic databases
MassIVEi | O14649 |
PaxDbi | O14649 |
PeptideAtlasi | O14649 |
PRIDEi | O14649 |
ProteomicsDBi | 48147 |
Protocols and materials databases
Antibodypediai | 13387, 219 antibodies |
Genome annotation databases
Ensembli | ENST00000302909; ENSP00000306275; ENSG00000171303 |
GeneIDi | 3777 |
KEGGi | hsa:3777 |
UCSCi | uc002rhn.3, human |
Organism-specific databases
CTDi | 3777 |
DisGeNETi | 3777 |
EuPathDBi | HostDB:ENSG00000171303.6 |
GeneCardsi | KCNK3 |
GeneReviewsi | KCNK3 |
HGNCi | HGNC:6278, KCNK3 |
HPAi | ENSG00000171303, Tissue enhanced (adrenal) |
MalaCardsi | KCNK3 |
MIMi | 603220, gene 615344, phenotype |
neXtProti | NX_O14649 |
OpenTargetsi | ENSG00000171303 |
Orphaneti | 275777, Heritable pulmonary arterial hypertension |
PharmGKBi | PA30060 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4404, Eukaryota |
GeneTreei | ENSGT00940000158248 |
HOGENOMi | CLU_022504_4_0_1 |
InParanoidi | O14649 |
OMAi | SDTCVEH |
OrthoDBi | 1109218at2759 |
PhylomeDBi | O14649 |
TreeFami | TF313947 |
Enzyme and pathway databases
PathwayCommonsi | O14649 |
Reactomei | R-HSA-1299316, TWIK-releated acid-sensitive K+ channel (TASK) R-HSA-5576886, Phase 4 - resting membrane potential |
SIGNORi | O14649 |
Miscellaneous databases
BioGRID-ORCSi | 3777, 1 hit in 840 CRISPR screens |
ChiTaRSi | KCNK3, human |
GeneWikii | KCNK3 |
GenomeRNAii | 3777 |
Pharosi | O14649, Tclin |
PROi | PR:O14649 |
RNActi | O14649, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000171303, Expressed in adrenal gland and 174 other tissues |
ExpressionAtlasi | O14649, baseline and differential |
Genevisiblei | O14649, HS |
Family and domain databases
InterProi | View protein in InterPro IPR003280, 2pore_dom_K_chnl IPR003092, 2pore_dom_K_chnl_TASK IPR013099, K_chnl_dom IPR005406, KCNK3 |
PANTHERi | PTHR11003:SF138, PTHR11003:SF138, 1 hit |
Pfami | View protein in Pfam PF07885, Ion_trans_2, 2 hits |
PIRSFi | PIRSF038061, K_channel_subfamily_K_type, 1 hit |
PRINTSi | PR01333, 2POREKCHANEL PR01584, TASK1CHANNEL PR01095, TASKCHANNEL |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KCNK3_HUMAN | |
Accessioni | O14649Primary (citable) accession number: O14649 Secondary accession number(s): Q53SU2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 21, 2001 |
Last sequence update: | January 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 178 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations