KCNAE_DROME
ID KCNAE_DROME Reviewed; 1174 AA.
AC Q02280; Q9VXZ6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Potassium voltage-gated channel protein eag;
DE AltName: Full=Ether-a-go-go protein;
GN Name=eag; ORFNames=CG10952;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC TISSUE=Head;
RX PubMed=1840699; DOI=10.1126/science.1840699;
RA Warmke J., Drysdale R.A., Ganetzky B.;
RT "A distinct potassium channel polypeptide encoded by the Drosophila eag
RT locus.";
RL Science 252:1560-1562(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP FUNCTION.
RX PubMed=11517334; DOI=10.1073/pnas.191107698;
RA Yager J., Richards S., Hekmat-Scafe D.S., Hurd D.D., Sundaresan V.,
RA Caprette D.R., Saxton W.M., Carlson J.R., Stern M.;
RT "Control of Drosophila perineurial glial growth by interacting
RT neurotransmitter-mediated signaling pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10445-10450(2001).
RN [5]
RP FUNCTION, PHOSPHORYLATION AT THR-787, MUTAGENESIS OF THR-787, AND TISSUE
RP SPECIFICITY.
RX PubMed=11980904; DOI=10.1074/jbc.m201949200;
RA Wang Z., Wilson G.F., Griffith L.C.;
RT "Calcium/calmodulin-dependent protein kinase II phosphorylates and
RT regulates the Drosophila eag potassium channel.";
RL J. Biol. Chem. 277:24022-24029(2002).
RN [6]
RP FUNCTION, INTERACTION WITH CASK, AND SUBCELLULAR LOCATION.
RX PubMed=15901771; DOI=10.1523/jneurosci.4566-04.2005;
RA Marble D.D., Hegle A.P., Snyder E.D. II, Dimitratos S., Bryant P.J.,
RA Wilson G.F.;
RT "Camguk/CASK enhances Ether-a-go-go potassium current by a phosphorylation-
RT dependent mechanism.";
RL J. Neurosci. 25:4898-4907(2005).
CC -!- FUNCTION: Structural component of a potassium channel. Mediates the
CC potassium permeability of membranes; potassium current is regulated by
CC CaMKII and CASK. Has a role in growth of the perineurial glial layer of
CC the larval peripheral nerve. {ECO:0000269|PubMed:11517334,
CC ECO:0000269|PubMed:11980904, ECO:0000269|PubMed:15901771,
CC ECO:0000269|PubMed:1840699}.
CC -!- SUBUNIT: The voltage-dependent potassium channel is a heterotetramer of
CC potassium channel proteins (By similarity). Interaction with CASK.
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q02280; Q24210: CASK; NbExp=10; IntAct=EBI-85304, EBI-214423;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15901771}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:15901771}. Note=Eag recruits
CC CASK to the plasma membrane.
CC -!- TISSUE SPECIFICITY: Expressed in the axon and the terminal boutons of
CC motor neurons. {ECO:0000269|PubMed:11980904}.
CC -!- PTM: When in complex with CASK, the efficiency of Thr-787
CC phosphorylation is increased. {ECO:0000269|PubMed:11980904}.
CC -!- DISRUPTION PHENOTYPE: Increased growth of the perineurial glial layer
CC of the larval peripheral nerve. Hyperexcitability at the larval
CC neuromuscular junction (NMJ) and memory formation defects in the adult.
CC {ECO:0000269|PubMed:1840699}.
CC -!- MISCELLANEOUS: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position.
CC -!- MISCELLANEOUS: The segment H5 is thought to line the channel pore.
CC -!- SIMILARITY: Belongs to the potassium channel family. H (Eag) (TC
CC 1.A.1.20) subfamily. Eag sub-subfamily. {ECO:0000305}.
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DR EMBL; M61157; AAA28495.1; -; mRNA.
DR EMBL; AE014298; AAF48410.1; -; Genomic_DNA.
DR PIR; A40853; A40853.
DR RefSeq; NP_511158.2; NM_078603.4.
DR PDB; 5FG8; X-ray; 1.96 A; B=768-820.
DR PDB; 5H9B; X-ray; 2.25 A; B=770-820.
DR PDB; 5HU3; X-ray; 1.89 A; B=768-820.
DR PDBsum; 5FG8; -.
DR PDBsum; 5H9B; -.
DR PDBsum; 5HU3; -.
DR AlphaFoldDB; Q02280; -.
DR SMR; Q02280; -.
DR BioGRID; 58786; 8.
DR IntAct; Q02280; 3.
DR STRING; 7227.FBpp0110308; -.
DR TCDB; 1.A.1.20.6; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q02280; 3 sites.
DR iPTMnet; Q02280; -.
DR PaxDb; Q02280; -.
DR EnsemblMetazoa; FBtr0073955; FBpp0073772; FBgn0000535.
DR GeneID; 32428; -.
DR KEGG; dme:Dmel_CG10952; -.
DR CTD; 32428; -.
DR FlyBase; FBgn0000535; eag.
DR VEuPathDB; VectorBase:FBgn0000535; -.
DR eggNOG; KOG0501; Eukaryota.
DR GeneTree; ENSGT00940000155793; -.
DR HOGENOM; CLU_005746_3_1_1; -.
DR InParanoid; Q02280; -.
DR OMA; HEMISNV; -.
DR PhylomeDB; Q02280; -.
DR Reactome; R-DME-1296072; Voltage gated Potassium channels.
DR BioGRID-ORCS; 32428; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 32428; -.
DR PRO; PR:Q02280; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0000535; Expressed in brain and 7 other tissues.
DR ExpressionAtlas; Q02280; baseline and differential.
DR Genevisible; Q02280; DM.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IPI:FlyBase.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:FlyBase.
DR GO; GO:0022843; F:voltage-gated cation channel activity; IDA:FlyBase.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:FlyBase.
DR GO; GO:0048150; P:behavioral response to ether; NAS:FlyBase.
DR GO; GO:0007619; P:courtship behavior; TAS:FlyBase.
DR GO; GO:0007612; P:learning; IMP:FlyBase.
DR GO; GO:0007611; P:learning or memory; NAS:FlyBase.
DR GO; GO:0042066; P:perineurial glial growth; IGI:FlyBase.
DR GO; GO:1903818; P:positive regulation of voltage-gated potassium channel activity; IDA:FlyBase.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:FlyBase.
DR GO; GO:0008016; P:regulation of heart contraction; NAS:FlyBase.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0007608; P:sensory perception of smell; NAS:FlyBase.
DR CDD; cd00038; CAP_ED; 1.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003949; K_chnl_volt-dep_EAG.
DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR000700; PAS-assoc_C.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF13426; PAS_9; 1.
DR PRINTS; PR01463; EAGCHANLFMLY.
DR PRINTS; PR01464; EAGCHANNEL.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS50113; PAC; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Differentiation; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Neurogenesis; Phosphoprotein;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..1174
FT /note="Potassium voltage-gated channel protein eag"
FT /id="PRO_0000053964"
FT TOPO_DOM 1..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..246
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 247..268
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..291
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 314..335
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 336..342
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..369
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..371
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 372..393
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394..441
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 442..467
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 468..470
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 471..493
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 494..1174
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 43..97
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 113..165
FT /note="PAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141"
FT REGION 742..763
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 778..842
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 865..884
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..977
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1022..1097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1115..1174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 453..458
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 818..832
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 867..883
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1071..1095
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1115..1166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 571..688
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT MOD_RES 787
FT /note="Phosphothreonine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:11980904"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 424
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 787
FT /note="T->A: Reduced eag channel amplitude and accelerated
FT inactivation. Does not affect binding with CASK."
FT /evidence="ECO:0000269|PubMed:11980904"
FT CONFLICT 548
FT /note="Y -> C (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 567
FT /note="N -> D (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 571
FT /note="A -> T (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 699
FT /note="K -> R (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 769
FT /note="F -> L (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 894
FT /note="I -> V (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 934
FT /note="G -> S (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1015
FT /note="N -> D (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1042
FT /note="R -> G (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1049
FT /note="K -> E (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1088
FT /note="T -> A (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1142
FT /note="T -> I (in Ref. 1; AAA28495)"
FT /evidence="ECO:0000305"
FT STRAND 788..791
FT /evidence="ECO:0007829|PDB:5FG8"
SQ SEQUENCE 1174 AA; 126371 MW; B8F86ACBB5627FD3 CRC64;
MPGGRRGLVA PQNTFLENII RRSNSQPDSS FLLANAQIVD FPIVYCNESF CKISGYNRAE
VMQKSCRYVC GFMYGELTDK ETVGRLEYTL ENQQQDQFEI LLYKKNNLQC GCALSQFGKA
QTQETPLWLL LQVAPIRNER DLVVLFLLTF RDITALKQPI DSEDTKGVLG LSKFAKLARS
VTRSRQFSAH LPTLKDPTKQ SNLAHMMSLS ADIMPQYRQE APKTPPHILL HYCAFKAIWD
WVILCLTFYT AIMVPYNVAF KNKTSEDVSL LVVDSIVDVI FFIDIVLNFH TTFVGPGGEV
VSDPKVIRMN YLKSWFIIDL LSCLPYDVFN AFDRDEDGIG SLFSALKVVR LLRLGRVVRK
LDRYLEYGAA MLILLLCFYM LVAHWLACIW YSIGRSDADN GIQYSWLWKL ANVTQSPYSY
IWSNDTGPEL VNGPSRKSMY VTALYFTMTC MTSVGFGNVA AETDNEKVFT ICMMIIAALL
YATIFGHVTT IIQQMTSATA KYHDMLNNVR EFMKLHEVPK ALSERVMDYV VSTWAMTKGL
DTEKVLNYCP KDMKADICVH LNRKVFNEHP AFRLASDGCL RALAMHFMMS HSAPGDLLYH
TGESIDSLCF IVTGSLEVIQ DDEVVAILGK GDVFGDQFWK DSAVGQSAAN VRALTYCDLH
AIKRDKLLEV LDFYSAFANS FARNLVLTYN LRHRLIFRKV ADVKREKELA ERRKNEPQLP
QNQDHLVRKI FSKFRRTPQV QAGSKELVGG SGQSDVEKGD GEVERTKVFP KAPKLQASQA
TLARQDTIDE GGEVDSSPPS RDSRVVIEGA AVSSATVGPS PPVATTSSAA AGAGVSGGPG
SGGTVVAIVT KADRNLALER ERQIEMASSR ATTSDTYDTG LRETPPTLAQ RDLIATVLDM
KVDVRLELQR MQQRIGRIED LLGELVKRLA PGAGSGGNAP DNSSGQTTPG DEICAGCGAG
GGGTPTTQAP PTSAVTSPVD TVITISSPGA SGSGSGTGAG AGSAVAGAGG AGLLNPGATV
VSSAGGNGLG PLMLKKRRSK SRKAPAPPKQ TLASTAGTAT AAPAGVAGSG MTSSAPASAD
QQQQHQSTAD QSPTTPGAEL LHLRLLEEDF TAAQLPSTSS GGAGGGGGSG SGATPTTPPP
TTAGGSGSGT PTSTTATTTP TGSGTATRGK LDFL
