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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). pH sensing in TASK2 channels is conferred by the combined action of several charged residues in the large extracellular M1-P1 loop (Morton et al. 2005).  

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:

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  • 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