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1.A.1.20.4
K+ voltage-gated channel, rEAG1; Kv10.1; rat ether a go-go channel 1 (962 aas). Blocked by Cs+, Ba2+ and quinidine (Schwarzer et al., 2008). Cysteines control the N- and C-linker-dependent gating of KCNH1 potassium channels  (Sahoo et al., 2012).  The 3-d structure has been determined at 3.8 Å resolution using single-particle cryo-EM with calmodulin bound. The structure suggests a novel mechanism of voltage-dependent gating. Calmodulin binding closes the potassium pore (Whicher and MacKinnon 2016). Eag1 has three intracellular domains: PAS, C-linker, and CNBHD. Whicher and MacKinnon 2019 demonstrated that the Eag1 intracellular domains are not required for voltage-dependent gating but likely interact with the VS to modulate gating. Specific interactions between the PAS, CNBHD, and VS domains modulate voltage-dependent gating, and VS movement destabilizes these interactions to promote channel opening. Mutations affecting these interactions render Eag1 insensitive to calmodulin inhibition (Whicher and MacKinnon 2019). The structure of the calmodulin insensitive mutant in a pre-open conformation suggests that channel opening may occur through a rotation of the intracellular domains, and calmodulin may prevent this rotation by stabilizing interactions between the VS and the other intracellular domains. Intracellular domains likely play a similar modulatory role in voltage-dependent gating of the related Kv11-12 channels. The human ortholog, EAG or EAG-1, is 989 aas long and is 95% identical to the rat protein.  In ether-a-go-go K+ channels, voltage-dependent activation is modulated by ion binding to a site located in an extracellular-facing crevice between transmembrane segments S2 and S3 in the voltage sensor. Silverman et al. 2004 found that acidic residues, D278 in S2 and D327 in S3, are able to coordinate a variety of divalent cations, including Mg2+, Mn2+, and Ni2+, which have qualitatively similar functional effects, but different half-maximal effective concentrations. EAG (ether-a-go-go) voltage-dependent K+ channels with similarities and Differences in the structural organization and gating (Barros et al. 2020).

Accession Number:Q63472
Protein Name:Potassium voltage-gated channel subfamily H member 1
Length:962
Molecular Weight:108291.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: Q63472
eggNOG: roNOG06149
RefSeq: NP_113930.1   
Entrez Gene ID: 65198   
Pfam: PF00027    PF00520    PF00989   
KEGG: rno:65198   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005516 F:calmodulin binding
GO:0000155 F:two-component sensor activity
GO:0005249 F:voltage-gated potassium channel activity
GO:0006813 P:potassium ion transport
GO:0006355 P:regulation of transcription, DNA-dependent
GO:0007165 P:signal transduction
GO:0055085 P:transmembrane transport
GO:0000160 P:two-component signal transduction system (p...

References (4)

[1] “Functional expression of a rat homologue of the voltage gated ether a go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart.”  Ludwig J.et.al.   7925287
[2] “Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-a-go-go potassium channel.”  Ludwig J.et.al.   9400421
[3] “KCR1, a membrane protein that facilitates functional expression of non-inactivating K+ currents associates with rat EAG voltage-dependent K+ channels.”  Hoshi N.et.al.   9722534
[4] “Expression of mRNA for voltage-dependent and inward-rectifying K channels in GH3/B6 cells and rat pituitary.”  Wulfsen I.et.al.   10718922
Structure:
5k7l   6PBX   6PBY     

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC KLSGYHRAEV 
61:	MQKSSACSFM YGELTDKDTV EKVRQTFENY EMNSFEILMY KKNRTPVWFF VKIAPIRNEQ 
121:	DKVVLFLCTF SDITAFKQPI EDDSCKGWGK FARLTRALTS SRGVLQQLAP SVQKGENVHK 
181:	HSRLAEVLQL GSDILPQYKQ EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS 
241:	FKTRQNNVAW LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL 
301:	LSCLPYDVIN AFENVDEGIS SLFSSLKVVR LLRLGRVARK LDHYIEYGAA VLVLLVCVFG 
361:	LAAHWMACIW YSIGDYEIFD EDTKTIRNNS WLYQLALDIG TPYQFNGSGS GKWEGGPSKN 
421:	SVYISSLYFT MTSLTSVGFG NIAPSTDIEK IFAVAIMMIG SLLYATIFGN VTTIFQQMYA 
481:	NTNRYHEMLN SVRDFLKLYQ VPKGLSERVM DYIVSTWSMS RGIDTEKVLQ ICPKDMRADI 
541:	CVHLNRKVFK EHPAFRLASD GCLRALAMEF QTVHCAPGDL IYHAGESVDS LCFVVSGSLE 
601:	VIQDDEVVAI LGKGDVFGDV FWKEATLAQS CANVRALTYC DLHVIKRDAL QKVLEFYTAF 
661:	SHSFSRNLIL TYNLRKRIVF RKISDVKREE EERMKRKNEA PLILPPDHPV RRLFQRFRQQ 
721:	KEARLAAERG GRDLDDLDVE KGNALTDHTS ANHSLVKASV VTVRESPATP VSFQAASTST 
781:	VSDHAKLHAP GSECLGPKAG GGDPAKRKGW ARFKDACGKG EDWNKVSKAE SMETLPERTK 
841:	ASGEATLKKT DSCDSGITKS DLRLDNVGEA RSPQDRSPIL AEVKHSFYPI PEQTLQATVL 
901:	EVKHELKEDI KALNAKMTSI EKQLSEILRI LMSRGSSQSP QDTCEVSRPQ SPESDRDIFG 
961:	AS