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Protein

Potassium voltage-gated channel subfamily H member 1

Gene

Kcnh1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:7925287, PubMed:9400421, PubMed:24495567, PubMed:27516594). Channel properties are modulated by subunit assembly. Mediates IK(NI) current in myoblasts. Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (By similarity).By similarity4 Publications

Enzyme regulationi

Channel activity is inhibited by interaction with Ca2+-bound calmodulin (PubMed:27516594). Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure. Channel activity is not regulated by cyclic nucleotides. Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (By similarity).By similarity1 Publication

GO - Molecular functioni

  • 14-3-3 protein binding Source: RGD
  • calmodulin binding Source: UniProtKB
  • delayed rectifier potassium channel activity Source: UniProtKB
  • identical protein binding Source: RGD
  • ion channel binding Source: RGD
  • phosphatidylinositol bisphosphate binding Source: UniProtKB
  • phosphorelay sensor kinase activity Source: InterPro
  • protein heterodimerization activity Source: RGD
  • protein kinase binding Source: RGD
  • voltage-gated potassium channel activity Source: GO_Central

GO - Biological processi

  • cellular response to calcium ion Source: UniProtKB
  • ion transmembrane transport Source: RGD
  • phosphatidylinositol-mediated signaling Source: UniProtKB
  • potassium ion transmembrane transport Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • regulation of membrane potential Source: GO_Central
  • startle response Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Calmodulin-binding, Lipid-binding, Potassium

Enzyme and pathway databases

ReactomeiR-RNO-1296072. Voltage gated Potassium channels.

Protein family/group databases

TCDBi1.A.1.20.4. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily H member 1
Alternative name(s):
Ether-a-go-go potassium channel 1
Short name:
EAG channel 1
Short name:
EAG1
Short name:
r-eag1 Publication
Voltage-gated potassium channel subunit Kv10.1
Gene namesi
Name:Kcnh1
Synonyms:Eag1 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi68398. Kcnh1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 220Cytoplasmic1 PublicationAdd BLAST220
Transmembranei221 – 241Helical; Name=Segment S11 PublicationAdd BLAST21
Topological domaini242 – 248Extracellular1 Publication7
Transmembranei249 – 269Helical; Name=Segment S21 PublicationAdd BLAST21
Topological domaini270 – 290Cytoplasmic1 PublicationAdd BLAST21
Transmembranei291 – 309Helical; Name=Segment S31 PublicationAdd BLAST19
Topological domaini310 – 318Extracellular1 Publication9
Transmembranei319 – 341Helical; Voltage-sensor; Name=Segment S41 PublicationAdd BLAST23
Topological domaini342 – 350Cytoplasmic1 Publication9
Transmembranei351 – 372Helical; Name=Segment S51 PublicationAdd BLAST22
Topological domaini373 – 421Extracellular1 PublicationAdd BLAST49
Intramembranei422 – 443Pore-forming; Name=Segment H51 PublicationAdd BLAST22
Topological domaini444 – 450Extracellular1 Publication7
Transmembranei451 – 471Helical; Name=Segment S61 PublicationAdd BLAST21
Topological domaini472 – 962Cytoplasmic1 PublicationAdd BLAST491

GO - Cellular componenti

  • axolemma Source: RGD
  • axon Source: RGD
  • cell surface Source: RGD
  • dendrite Source: RGD
  • early endosome membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • neuronal cell body Source: RGD
  • nuclear inner membrane Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • plasma membrane Source: RGD
  • potassium channel complex Source: UniProtKB
  • presynaptic membrane Source: RGD
  • synapse Source: RGD
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Endosome, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Chemistry databases

GuidetoPHARMACOLOGYi570.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539961 – 962Potassium voltage-gated channel subfamily H member 1Add BLAST962

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi388N-linked (GlcNAc...)Sequence analysis1 Publication1
Glycosylationi406N-linked (GlcNAc...)Sequence analysis1
Modified residuei947PhosphoserineBy similarity1
Modified residuei951PhosphoserineBy similarity1
Modified residuei954PhosphoserineBy similarity1

Post-translational modificationi

Channel activity is regulated via tyrosine phosphorylation/dephosphorylation by SRC and PTPN6.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ63472.
PRIDEiQ63472.

PTM databases

iPTMnetiQ63472.
PhosphoSitePlusiQ63472.

Expressioni

Tissue specificityi

Detected in cerebellum, at parallel fiber synapses on Purkinje cell spines (PubMed:25556795). Detected in hippocampus neurons (at protein level) (PubMed:24495567). Detected in brain, but not in the other tissues tested; expression is highest in granular cells of the dentate gyrus, in hippocampus CA3 pyramidal cells, and in cerebellar granule cells (PubMed:7925287). Detected in pituitary (PubMed:10718922).4 Publications

Gene expression databases

BgeeiENSRNOG00000003841.
ExpressionAtlasiQ63472. baseline and differential.
GenevisibleiQ63472. RN.

Interactioni

Subunit structurei

The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits (PubMed:9400421, PubMed:27516594). Heteromultimer with KCNH5/EAG2 (By similarity). Interacts with ALG10B (PubMed:9722534). Interacts with RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN (PubMed:23144454). Interacts (via cytoplasmic region) with Ca2+-bound calmodulin (PubMed:27516594).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rabep1O355502EBI-7991592,EBI-7991542

GO - Molecular functioni

  • 14-3-3 protein binding Source: RGD
  • calmodulin binding Source: UniProtKB
  • identical protein binding Source: RGD
  • ion channel binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein kinase binding Source: RGD

Protein-protein interaction databases

IntActiQ63472. 2 interactors.
MINTiMINT-8386100.
STRINGi10116.ENSRNOP00000005209.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5K7Lelectron microscopy3.78A1-962[»]
ProteinModelPortaliQ63472.
SMRiQ63472.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 94PASPROSITE-ProRule annotationAdd BLAST81
Domaini93 – 145PACPROSITE-ProRule annotationAdd BLAST53

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni151 – 162Required for phosphatidylinositol bisphosphate bindingBy similarityAdd BLAST12
Regioni646 – 743Calmodulin-bindingBy similarityAdd BLAST98
Regioni672 – 674Interaction with cyclic nucleotide-binding pocketBy similarity3
Regioni897 – 937CAD (involved in subunit assembly)1 PublicationAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi436 – 441Selectivity filter1 Publication6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.1 Publication
The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating.By similarity
The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating. Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure.1 Publication
The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides. Instead, residues from the C-terminal domain (the so-called intrinsic ligand) bind in the cavity that would be expected to bind cyclic nucleotides. Interaction with the C-terminal region hinders interaction with CALM and reduces the affinity for CALM.By similarity

Sequence similaritiesi

Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation
Contains 1 PAC (PAS-associated C-terminal) domain.PROSITE-ProRule annotation
Contains 1 PAS (PER-ARNT-SIM) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOVERGENiHBG101348.
InParanoidiQ63472.
KOiK04904.
PhylomeDBiQ63472.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR003949. K_chnl_volt-dep_EAG.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR001610. PAC.
IPR000014. PAS.
IPR000700. PAS-assoc_C.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
PR01464. EAGCHANNEL.
SMARTiSM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
TIGRFAMsiTIGR00229. sensory_box. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
PS50113. PAC. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63472-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC
60 70 80 90 100
KLSGYHRAEV MQKSSACSFM YGELTDKDTV EKVRQTFENY EMNSFEILMY
110 120 130 140 150
KKNRTPVWFF VKIAPIRNEQ DKVVLFLCTF SDITAFKQPI EDDSCKGWGK
160 170 180 190 200
FARLTRALTS SRGVLQQLAP SVQKGENVHK HSRLAEVLQL GSDILPQYKQ
210 220 230 240 250
EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS FKTRQNNVAW
260 270 280 290 300
LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL
310 320 330 340 350
LSCLPYDVIN AFENVDEGIS SLFSSLKVVR LLRLGRVARK LDHYIEYGAA
360 370 380 390 400
VLVLLVCVFG LAAHWMACIW YSIGDYEIFD EDTKTIRNNS WLYQLALDIG
410 420 430 440 450
TPYQFNGSGS GKWEGGPSKN SVYISSLYFT MTSLTSVGFG NIAPSTDIEK
460 470 480 490 500
IFAVAIMMIG SLLYATIFGN VTTIFQQMYA NTNRYHEMLN SVRDFLKLYQ
510 520 530 540 550
VPKGLSERVM DYIVSTWSMS RGIDTEKVLQ ICPKDMRADI CVHLNRKVFK
560 570 580 590 600
EHPAFRLASD GCLRALAMEF QTVHCAPGDL IYHAGESVDS LCFVVSGSLE
610 620 630 640 650
VIQDDEVVAI LGKGDVFGDV FWKEATLAQS CANVRALTYC DLHVIKRDAL
660 670 680 690 700
QKVLEFYTAF SHSFSRNLIL TYNLRKRIVF RKISDVKREE EERMKRKNEA
710 720 730 740 750
PLILPPDHPV RRLFQRFRQQ KEARLAAERG GRDLDDLDVE KGNALTDHTS
760 770 780 790 800
ANHSLVKASV VTVRESPATP VSFQAASTST VSDHAKLHAP GSECLGPKAG
810 820 830 840 850
GGDPAKRKGW ARFKDACGKG EDWNKVSKAE SMETLPERTK ASGEATLKKT
860 870 880 890 900
DSCDSGITKS DLRLDNVGEA RSPQDRSPIL AEVKHSFYPI PEQTLQATVL
910 920 930 940 950
EVKHELKEDI KALNAKMTSI EKQLSEILRI LMSRGSSQSP QDTCEVSRPQ
960
SPESDRDIFG AS
Length:962
Mass (Da):108,291
Last modified:November 1, 1996 - v1
Checksum:i69DF4CE2DC435608
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z34264 mRNA. Translation: CAA84018.1.
PIRiI53197.
RefSeqiNP_113930.1. NM_031742.1.
XP_006250553.1. XM_006250491.3.
UniGeneiRn.11071.

Genome annotation databases

EnsembliENSRNOT00000005209; ENSRNOP00000005209; ENSRNOG00000003841.
ENSRNOT00000077014; ENSRNOP00000068394; ENSRNOG00000003841.
GeneIDi65198.
KEGGirno:65198.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z34264 mRNA. Translation: CAA84018.1.
PIRiI53197.
RefSeqiNP_113930.1. NM_031742.1.
XP_006250553.1. XM_006250491.3.
UniGeneiRn.11071.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5K7Lelectron microscopy3.78A1-962[»]
ProteinModelPortaliQ63472.
SMRiQ63472.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63472. 2 interactors.
MINTiMINT-8386100.
STRINGi10116.ENSRNOP00000005209.

Chemistry databases

GuidetoPHARMACOLOGYi570.

Protein family/group databases

TCDBi1.A.1.20.4. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetiQ63472.
PhosphoSitePlusiQ63472.

Proteomic databases

PaxDbiQ63472.
PRIDEiQ63472.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000005209; ENSRNOP00000005209; ENSRNOG00000003841.
ENSRNOT00000077014; ENSRNOP00000068394; ENSRNOG00000003841.
GeneIDi65198.
KEGGirno:65198.

Organism-specific databases

CTDi3756.
RGDi68398. Kcnh1.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOVERGENiHBG101348.
InParanoidiQ63472.
KOiK04904.
PhylomeDBiQ63472.

Enzyme and pathway databases

ReactomeiR-RNO-1296072. Voltage gated Potassium channels.

Miscellaneous databases

PROiQ63472.

Gene expression databases

BgeeiENSRNOG00000003841.
ExpressionAtlasiQ63472. baseline and differential.
GenevisibleiQ63472. RN.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR003949. K_chnl_volt-dep_EAG.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR001610. PAC.
IPR000014. PAS.
IPR000700. PAS-assoc_C.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
PR01464. EAGCHANNEL.
SMARTiSM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
TIGRFAMsiTIGR00229. sensory_box. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
PS50113. PAC. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKCNH1_RAT
AccessioniPrimary (citable) accession number: Q63472
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.