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1.A.1.9.4
Outward rectifying mechanosensitive 2-P (4 TMS) domain K+ channel, TREK-2 (KCNKA; KCNK10; K2P10). Activated by membrane stretch, acidic pH, arachidonic acid and unsaturated fatty acids.  Dong et al. 2015 described crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. This provides an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac (Dong et al. 2015).  The unique gating properties of TREK-2 and the mechanisms by which extracellular and intracellular stimuli harness pore gating allosterically have been studied (Zhuo et al. 2016). TREK-2 moves from the "down" to "up" conformation in direct response to membrane stretch. Aryal et al. 2017 showed how state-dependent interactions with lipids affect the movement of TREK-2, and how stretch influences both the inner pore and selectivity filter. They also demonstrated why direct pore block by lipid tails does not represent theprincipal mechanism of mechanogating (Aryal et al. 2017). The M2-hinges of TREK-1 and TREK-2 channels control their macroscopic current, subcellular localization and gating (Zhuo et al. 2017).

Accession Number:Q9JIS4
Protein Name:Potassium channel subfamily K member 10 aka Kcnk10 aka Trek2
Length:538
Molecular Weight:59801.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: Q9JIS4
eggNOG: roNOG11640
RefSeq: NP_075584.1   
Entrez Gene ID: 65272   
Pfam: PF07885   
KEGG: rno:65272   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005267 F:potassium channel activity
GO:0005244 F:voltage-gated ion channel activity
GO:0006813 P:potassium ion transport

References (2)

[1] “TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family.”  Bang H.et.al.   10747911
[2] “Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2.”  Gu W.et.al.   11897838
Structure:
4bw5     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKFPIETPRK QVNWDPKVAV PAAAPPVCQP KSATNGHHPV PRLSISSRAT VVARMEGASQ 
61:	GGLQTVMKWK TVVAIFVVVV VYLVTGGLVF RALEQPFESS QKNTIALEKA EFLRDHICVS 
121:	PQELETLIQH ALDADNAGVS PVGNSSNSSS HWDLGSAFFF AGTVITTIGY GNIAPSTEGG 
181:	KIFCILYAIF GIPLFGFLLA GIGDQLGTIF GKSIARVEKV FRKKQVSQTK IRVISTILFI 
241:	LAGCIVFVTI PAVIFKYIEG WTALESIYFV VVTLTTVGFG DFVAGGNAGI NYREWYKPLV 
301:	WFWILVGLAY FAAVLSMIGD WLRVLSKKTK EEVGEIKAHA AEWKANVTAE FRETRRRLSV 
361:	EIHDKLQRAA TIRSMERRRL GLDQRAHSLD MLSPEKRSVF AALDTGRFKA SSQESINNRP 
421:	NNLRLKGPEQ LNKHGQGASE DNIINKFGST SKLTKRKNKD LKKTLPEDVQ KIYKTFRNYS 
481:	LDEEKKEDET EKMCNSDNSS TAMLTECIQQ QAEMENGMVP MDTKDQGLEN NSLLEDRN