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1.A.1.8.2
TASK-2 (KCNK5) two-pore domain, pH-sensitive, voltage-insensitive, outward rectifying K+ channel (K+ > Rb+ >> Cs+ > NH4+ > Na+ ≈ Li+), present in renal epithelia.  Regulated [inhibited] via group 1 metabolotropic glutamate receptors and by inositol phosphates (Chemin et al., 2003).  TASK-2 gating is controlled by changes in both extra- and intracellular pH through separate sensors: arginine 224 and lysine 245, located at the extra- and intracellular ends of transmembrane domain 4, respectively. TASK-2 is inhibited by a direct effect of CO2 and is regulated by and interacts with G protein subunits. TASK-2 takes part in regulatory adjustments and is a mediator in the chemoreception process in neurons of the retrotrapezoid nucleus where its pHi sensitivity could be important in regulating excitability and therefore signalling of the O2/CO2 status. Extracellular pH increases, brought about by HCO3- efflux from proximal tubule epithelial cells may couple to TASK-2 activation to maintain electrochemical gradients favourable to HCO3- reabsorption. TASK-2 is expressed at the basolateral membrane of proximal tubule cells (López-Cayuqueo et al. 2014). Mutations are associated with the Balkan Endemic Nephropathy (BEN) chronic tubulointerstitial renal disease (Reed et al. 2016).  

Accession Number:O95279
Protein Name:TASK2 aka KCNK5
Length:499
Molecular Weight:55130.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+, Rb+, Cs+, NH4+, Na+, Li+

Cross database links:

Genevestigator: O95279
eggNOG: prNOG07388
HEGENOM: HBG716001
RefSeq: NP_003731.1   
Entrez Gene ID: 8645   
Pfam: PF07885   
OMIM: 603493  gene
KEGG: hsa:8645   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005267 F:potassium channel activity
GO:0005244 F:voltage-gated ion channel activity
GO:0007588 P:excretion
GO:0006813 P:potassium ion transport

References (6)

[1] “Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney.”  Reyes R.et.al.   9812978
[2] “Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein.”  Gierten J.et.al.   18516069
[3] “The DNA sequence and analysis of human chromosome 6.”  Mungall A.J.et.al.   14574404
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Extracellular conserved cysteine forms an intersubunit disulphide bridge in the KCNK5 (TASK-2) K+ channel without having an essential effect upon activity.”  Niemeyer M.I.et.al.   12851074
[6] “Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.”  Daub H.et.al.   18691976

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MVDRGPLLTS AIIFYLAIGA AIFEVLEEPH WKEAKKNYYT QKLHLLKEFP CLGQEGLDKI 
61:	LEVVSDAAGQ GVAITGNQTF NNWNWPNAMI FAATVITTIG YGNVAPKTPA GRLFCVFYGL 
121:	FGVPLCLTWI SALGKFFGGR AKRLGQFLTK RGVSLRKAQI TCTVIFIVWG VLVHLVIPPF 
181:	VFMVTEGWNY IEGLYYSFIT ISTIGFGDFV AGVNPSANYH ALYRYFVELW IYLGLAWLSL 
241:	FVNWKVSMFV EVHKAIKKRR RRRKESFESS PHSRKALQVK GSTASKDVNI FSFLSKKEET 
301:	YNDLIKQIGK KAMKTSGGGE TGPGPGLGPQ GGGLPALPPS LVPLVVYSKN RVPTLEEVSQ 
361:	TLRSKGHVSR SPDEEAVARA PEDSSPAPEV FMNQLDRISE ECEPWDAQDY HPLIFQDASI 
421:	TFVNTEAGLS DEETSKSSLE DNLAGEESPQ QGAEAKAPLN MGEFPSSSES TFTSTESELS 
481:	VPYEQLMNEY NKANSPKGT