KCNH1_BOVIN
ID KCNH1_BOVIN Reviewed; 987 AA.
AC O18965; O18966;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Potassium voltage-gated channel subfamily H member 1;
DE AltName: Full=Ether-a-go-go potassium channel 1;
DE Short=EAG channel 1;
DE Short=bEAG;
DE AltName: Full=Voltage-gated potassium channel subunit Kv10.1;
GN Name=KCNH1; Synonyms=EAG;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ACTIVITY
RP REGULATION, LACK OF REGULATION BY CYCLIC NUCLEOTIDES, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=9524140; DOI=10.1085/jgp.111.4.583;
RA Frings S., Bruell N., Dzeja C., Angele A., Hagen V., Kaupp U.B.,
RA Baumann A.;
RT "Characterization of ether-a-go-go channels present in photoreceptors
RT reveals similarity to IKx, a K current in rod inner segments.";
RL J. Gen. Physiol. 111:583-599(1998).
CC -!- FUNCTION: Pore-forming (alpha) subunit of a voltage-gated delayed
CC rectifier potassium channel (PubMed:9524140). Channel properties are
CC modulated by subunit assembly. Mediates IK(NI) current in myoblasts.
CC Involved in the regulation of cell proliferation and differentiation,
CC in particular adipogenic and osteogenic differentiation in bone marrow-
CC derived mesenchymal stem cells (MSCs) (By similarity).
CC {ECO:0000250|UniProtKB:O95259, ECO:0000269|PubMed:9524140}.
CC -!- ACTIVITY REGULATION: Channel activity is inhibited by interaction with
CC Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha
CC subunit with a calmodulin chain is sufficient to promote channel
CC closure (By similarity). Extracellular magnesium ion concentrations up
CC to 4 mM modulate channel activity by slowing down current activation in
CC a reversible fashion. Channel activity is not regulated by cyclic
CC nucleotides (PubMed:9524140). Channel activity is inhibited by binding
CC intracellular phosphatidylinositol-3,5-bisphosphate and
CC phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by
CC phosphatidylinositol 4-phosphate (By similarity).
CC {ECO:0000250|UniProtKB:O95259, ECO:0000250|UniProtKB:Q60603,
CC ECO:0000269|PubMed:9524140}.
CC -!- SUBUNIT: The potassium channel is composed of a homo- or
CC heterotetrameric complex of pore-forming alpha subunits that can
CC associate with modulating beta subunits. Heteromultimer with KCNH5/EAG2
CC (By similarity). Interacts with ALG10B (By similarity). Interacts with
CC RABEP1 (By similarity). Interacts (via C-terminus) with CTTN. Interacts
CC (via C-terminal cytoplasmic region) with Ca(2+)-bound calmodulin (By
CC similarity). {ECO:0000250|UniProtKB:O95259}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9524140};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:O95259}. Nucleus
CC inner membrane {ECO:0000250|UniProtKB:O95259}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:O95259}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q63472}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q63472}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q63472}. Perikaryon
CC {ECO:0000250|UniProtKB:Q63472}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q63472}. Early endosome membrane
CC {ECO:0000250|UniProtKB:O95259}. Note=Perinuclear KCNH1 is located to
CC NPC-free islands. {ECO:0000250|UniProtKB:O95259}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=EAG2;
CC IsoId=O18965-1; Sequence=Displayed;
CC Name=1; Synonyms=EAG1;
CC IsoId=O18965-2; Sequence=VSP_000963;
CC -!- TISSUE SPECIFICITY: Detected in cerebellum, cortex and retina.
CC {ECO:0000269|PubMed:9524140}.
CC -!- DOMAIN: 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. {ECO:0000250|UniProtKB:Q63472}.
CC -!- DOMAIN: The C-terminal region interacts with the cyclic nucleotide-
CC binding domain and contributes to regulate channel gating.
CC {ECO:0000250|UniProtKB:Q60603}.
CC -!- DOMAIN: The PAS and PAC domain interact with the cyclic nucleotide-
CC binding domain and contribute to the regulation of channel gating.
CC Calmodulin binding clamps together the PAS and PAC domain with the
CC cyclic nucleotide-binding domain from a neighboring subunit and causes
CC a conformation change that leads to channel closure.
CC {ECO:0000250|UniProtKB:Q63472}.
CC -!- DOMAIN: The cyclic nucleotide-binding domain lacks residues that are
CC essential for nucleotide-binding and cannot bind cyclic nucleotides.
CC Instead, residues from the C-terminal domain (the so-called intrinsic
CC ligand) bind in the cavity that would be expected to bind cyclic
CC nucleotides. Interaction with the C-terminal region hinders interaction
CC with CALM and reduces the affinity for CALM.
CC {ECO:0000250|UniProtKB:Q60603}.
CC -!- PTM: Channel activity is regulated via tyrosine
CC phosphorylation/dephosphorylation by SRC and PTPN6.
CC {ECO:0000250|UniProtKB:O95259}.
CC -!- SIMILARITY: Belongs to the potassium channel family. H (Eag) (TC
CC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily. {ECO:0000305}.
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DR EMBL; Y13430; CAA73842.1; -; mRNA.
DR EMBL; Y13431; CAA73843.1; -; mRNA.
DR RefSeq; NP_776797.1; NM_174372.2. [O18965-1]
DR AlphaFoldDB; O18965; -.
DR SMR; O18965; -.
DR STRING; 9913.ENSBTAP00000011477; -.
DR PRIDE; O18965; -.
DR Ensembl; ENSBTAT00000011477; ENSBTAP00000011477; ENSBTAG00000008710. [O18965-1]
DR GeneID; 281881; -.
DR KEGG; bta:281881; -.
DR CTD; 3756; -.
DR VEuPathDB; HostDB:ENSBTAG00000008710; -.
DR eggNOG; KOG0501; Eukaryota.
DR GeneTree; ENSGT00940000155793; -.
DR InParanoid; O18965; -.
DR OMA; HEMISNV; -.
DR OrthoDB; 464006at2759; -.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000008710; Expressed in oocyte and 32 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:1902936; F:phosphatidylinositol bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
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; IPR030170; EAG1.
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; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR000700; PAS-assoc_C.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR PANTHER; PTHR10217:SF530; PTHR10217:SF530; 1.
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 SMART; SM00086; PAC; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS50113; PAC; 1.
DR PROSITE; PS50112; PAS; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calmodulin-binding; Cell membrane; Cell projection;
KW Endosome; Glycoprotein; Ion channel; Ion transport; Lipid-binding;
KW Membrane; Nucleus; Phosphoprotein; Postsynaptic cell membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Synapse;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..987
FT /note="Potassium voltage-gated channel subfamily H member
FT 1"
FT /id="PRO_0000053993"
FT TOPO_DOM 1..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TRANSMEM 221..241
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 242..248
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TRANSMEM 249..269
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 270..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TRANSMEM 291..309
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 310..345
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TRANSMEM 346..368
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 369..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TRANSMEM 378..399
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 400..448
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT INTRAMEM 449..470
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 471..477
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TRANSMEM 478..498
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT TOPO_DOM 499..987
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT DOMAIN 14..94
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 93..145
FT /note="PAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141"
FT REGION 151..162
FT /note="Required for phosphatidylinositol bisphosphate
FT binding"
FT /evidence="ECO:0000250|UniProtKB:O95259"
FT REGION 673..770
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q60603"
FT REGION 699..701
FT /note="Interaction with cyclic nucleotide-binding pocket"
FT /evidence="ECO:0000250|UniProtKB:Q60603"
FT REGION 922..962
FT /note="CAD (involved in subunit assembly)"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT REGION 960..987
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 463..468
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:Q63472"
FT MOD_RES 972
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60603"
FT MOD_RES 976
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60603"
FT MOD_RES 979
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60603"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 318..344
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:9524140"
FT /id="VSP_000963"
SQ SEQUENCE 987 AA; 110918 MW; 0EF9FB866297DC4F CRC64;
MTMAGGRKGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC KLSGYHRAEV
MQKSSTCSFM YGELTDKDTI EKVRQTFENY EMNSFEILMY KKNRTPVWFF VKIAPIRNEQ
DKVVLFLCTF SDITAFKQPI EDDSCKGWGK FARLTRALTS SRGVLQQLAP SVQKGENVHK
HSRLAEVLQL GSDILPQYKQ EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS
FKTRQNNVAW LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL
LSCLPYDVIN AFENVDEVSA FMGDPGKIGF ADQIPPPLEG RESQGISSLF SSLKVVRLLR
LGRVARKLDH YIEYGAAVLV LLVCVFGLAA HWMACIWYSI GDYEIFDEDT KTIRNNSWLY
QLAMDIGTPY QFNGSGSGKW EGGPSKNSVY ISSLYFTMTS LTSVGFGNIA PSTDIEKIFA
VAIMMIGSLL YATIFGNVTT IFQQMYANTN RYHEMLNSVR DFLKLYQVPK GLSERVMDYI
VSTWSMSRGI DTEKVLQICP KDMRADICVH LNRKVFKEHP AFRLASDGCL RALAMEFQTV
HCAPGDLIYH AGESVDSLCF VVSGSLEVIQ DDEVVAILGK GDVFGDVFWK EATLAQSCAN
VRALTYCDLH VIKRDALQKV LEFYTAFSHS FSRNLILTYN LRKRIVFRKI SDVKREEEER
MKRKNEAPLI LPPDHPVRRL FQRFRQQKEA RLAAERGGRD LDDLDVEKGS VLTEHSHHGL
AKASVVTVRE SPATPVAFPA AAAPAGLDHA RLQAPGAEGL GPKAGGADCA KRKGWARFKD
ACGQAEDWSK VSKAESMETL PERTKAAGEA TLKKTDSCDS GITKSDLRLD NVGEARSPQD
RSPILAEVKH SFYPIPEQTL QAAVLEVKHE LKEDIKALST KMTSIEKQLS EILRILTSRR
SSQSPQELFE ISRPQSPESE RDIFGAS
