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1.A.1.3.1
Large conductance, voltage- and Ca2+-activated K+ (BK or Slo) channel. Four pairs of RCK1 and RICK2 domains form the Ca2+-sensing apparatus known as the "gating ring" in Big Potassium (BK) channel proteins (Savalli et al., 2012). Gating of BK channels does not seem to require a physical gate. Instead, changes in the pore shape and surface hydrophobicity in the Ca2+-free state allow the channel to readily undergo hydrophobic dewetting transitions, giving rise to a large free energy barrier for K+ permeation (Jia et al. 2018).  Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor (Miranda et al. 2018). Slo channels are targets for insecticides and antiparasitic drugs. Raisch et al. 2021 reported structures of Drosophila Slo in the Ca2+-bound and Ca2+-free forms and in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside. The architecture and gating mechanism of Slo channels are conserved, but potential insect-specific binding pockets are present. Verruculogen inhibits K+ transport by blocking the Ca2+-induced activation signal and precludes K+ from entering the selectivity filter while emodepside decreases the conductance by suboptimal K+ coordination and uncouples ion gating from Ca2+ and voltage sensing (Raisch et al. 2021). In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Carrasquel-Ursulaez et al. 2022 demonstrated that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. The energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). 

Accession Number:Q03720
Protein Name:Calcium-activated potassium channel slowpoke
Length:1200
Molecular Weight:133102.00
Species: [7227]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

RefSeq: NP_001014651.1    NP_001014652.1    NP_001014653.1    NP_001014654.1    NP_001014655.1    NP_001014656.1    NP_001014657.1    NP_001014658.1    NP_001014659.1    NP_001014660.1    NP_001014661.2    NP_001014662.1    NP_001014663.1    NP_001014664.1    NP_524486.2    NP_733029.1    NP_996289.1   
Entrez Gene ID: 42940   
Pfam: PF03493    PF00520   
KEGG: dme:Dmel_CG1069   

Gene Ontology

GO:0043005 C:neuron projection
GO:0043025 C:neuronal cell body
GO:0008076 C:voltage-gated potassium channel complex
GO:0015269 F:calcium-activated potassium channel activity
GO:0003824 F:catalytic activity
GO:0005515 F:protein binding
GO:0005249 F:voltage-gated potassium channel activity
GO:0048512 P:circadian behavior
GO:0045433 P:male courtship behavior, veined wing genera...
GO:0008152 P:metabolic process
GO:0006813 P:potassium ion transport
GO:0042493 P:response to drug
GO:0055085 P:transmembrane transport

References (13)

[1] “A component of calcium-activated potassium channels encoded by the Drosophila slo locus.”  Atkinson N.S.et.al.   1857984
[2] “Calcium-activated potassium channels expressed from cloned complementary DNAs.”  Adelman J.P.et.al.   1497890
[3] “The genome sequence of Drosophila melanogaster.”  Adams M.D.et.al.   10731132
[4] “Annotation of the Drosophila melanogaster euchromatic genome: a systematic review.”  Misra S.et.al.   12537572
[5] “A Drosophila full-length cDNA resource.”  Stapleton M.et.al.   12537569
[6] “Tissue-specific expression of a Ca(2+)-activated K+ channel is controlled by multiple upstream regulatory elements.”  Brenner R.et.al.   8774450
[7] “Tissue-specific expression of a Drosophila calcium-activated potassium channel.”  Becker M.N.et.al.   7666207
[8] “dSLo interacting protein 1, a novel protein that interacts with large-conductance calcium-activated potassium channels.”  Xia X.-M.et.al.   9502797
[9] “Slob, a novel protein that interacts with the Slowpoke calcium-dependent potassium channel.”  Schopperle W.M.et.al.   9539129
[10] “Simultaneous binding of two protein kinases to a calcium-dependent potassium channel.”  Wang J.et.al.   10234050
[11] “A dynamically regulated 14-3-3, Slob, and Slowpoke potassium channel complex in Drosophila presynaptic nerve terminals.”  Zhou Y.et.al.   10230800
[12] “Ca2+-binding activity of a COOH-terminal fragment of the Drosophila BK channel involved in Ca2+-dependent activation.”  Bian S.et.al.   11274367
[13] “Modulation of Drosophila slowpoke calcium-dependent potassium channel activity by bound protein kinase a catalytic subunit.”  Zhou Y.et.al.   12019304

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MASGLIDTNF SSTLANGMSG CDQSTVESLA DDPTDSPFDA DDCLKVRKYW CFLLSSIFTF 
61:	LAGLLVVLLW RAFAFVCCRK EPDLGPNDPK QKEQKASRNK QEFEGTFMTE AKDWAGELIS 
121:	GQTTTGRILV VLVFILSIAS LIIYFVDASS EEVERCQKWS NNITQQIDLA FNIFFMVYFF 
181:	IRFIAASDKL WFMLEMYSFV DYFTIPPSFV SIYLDRTWIG LRFLRALRLM TVPDILQYLN 
241:	VLKTSSSIRL AQLVSIFISV WLTAAGIIHL LENSGDPLDF NNAHRLSYWT CVYFLIVTMS 
301:	TVGYGDVYCE TVLGRTFLVF FLLVGLAMFA SSIPEIIELV GSGNKYGGEL KREHGKRHIV 
361:	VCGHITYESV SHFLKDFLHE DREDVDVEVV FLHRKPPDLE LEGLFKRHFT TVEFFQGTIM 
421:	NPIDLQRVKV HEADACLVLA NKYCQDPDAE DAANIMRVIS IKNYSDDIRV IIQLMQYHNK 
481:	AYLLNIPSWD WKQGDDVICL AELKLGFIAQ SCLAPGFSTM MANLFAMRSF KTSPDMQSWT 
541:	NDYLRGTGME MYTETLSPTF IGIPFAQATE LCFSKLKLLL LAIEIKGAEE GADSKISINP 
601:	RGAKIQANTQ GFFIAQSADE VKRAWFYCKA CHEDIKDETL IKKCKCKNLT VQPRSKFDDL 
661:	DEHHPAPTFT PPELPKRVHV RGSVSGDITR DREDTNLLNR NVRRPNGTGN GTGGMHHMNN 
721:	TAAAAAAAAA AGKQVNKVKP TVNVSRQVEG QVISPSQYNR PTSRSSGTGT QNQNGGVSLP 
781:	AGIADDQSKD FDFEKTEMKY DSTGMFHWSP AKSLEDCILD RNQAAMTVLN GHVVVCLFAD 
841:	PDSPLIGLRN LVMPLRASNF HYHELKHVVI VGSVDYIRRE WKMLQNLPKI SVLNGSPLSR 
901:	ADLRAVNVNL CDMCCILSAK VPSNDDPTLA DKEAILASLN IKAMTFDDTI GVLSQRGPEF 
961:	DNLSATAGSP IVLQRRGSVY GANVPMITEL VNDSNVQFLD QDDDDDPDTE LYLTQPFACG 
1021:	TAFAVSVLDS LMSTTYFNQN ALTLIRSLIT GGATPELELI LAEGAGLRGG YSTVESLSNR 
1081:	DRCRVGQISL YDGPLAQFGE CGKYGDLFVA ALKSYGMLCI GLYRFRDTSS SCDASSKRYV 
1141:	ITNPPDDFSL LPTDQVFVLM QFDPGLEYKP PAVRAPAGGR GTNTQGSGVG GGGSNKDDNS