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Protein

Potassium voltage-gated channel subfamily H member 1

Gene

Kcnh1

Organism
Mus musculus (Mouse)
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:19671703, PubMed:23975098). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (PubMed:19671703). Mediates IK(NI) current in myoblasts (By similarity). Involved in the regulation of cell proliferation and differentiation, as adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (By similarity).By similarity2 Publications

GO - Molecular functioni

  1. phosphorelay sensor kinase activity Source: InterPro
  2. voltage-gated potassium channel activity Source: GO_Central

GO - Biological processi

  1. potassium ion transmembrane transport Source: GO_Central
  2. regulation of membrane potential Source: GO_Central
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, Potassium

Enzyme and pathway databases

ReactomeiREACT_199077. Voltage gated Potassium channels.

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:
m-eag
Voltage-gated potassium channel subunit Kv10.1
Gene namesi
Name:Kcnh1
Synonyms:Eag
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:1341721. Kcnh1.

Subcellular locationi

Cell membrane 2 Publications; Multi-pass membrane protein By similarity. Nucleus inner membrane By similarity; Multi-pass membrane protein By similarity. Early endosome membrane By similarity
Note: Perinuclear KCNH1 is located to NPC-free islands.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 220220CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei221 – 24121Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Topological domaini242 – 2487ExtracellularSequence Analysis
Transmembranei249 – 26921Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Topological domaini270 – 29425CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei295 – 31521Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Topological domaini316 – 34934ExtracellularSequence AnalysisAdd
BLAST
Transmembranei350 – 37021Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
BLAST
Topological domaini371 – 3766CytoplasmicSequence Analysis
Transmembranei377 – 39721Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Topological domaini398 – 45053ExtracellularSequence AnalysisAdd
BLAST
Intramembranei451 – 47121Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST
Topological domaini472 – 4776ExtracellularSequence Analysis
Transmembranei478 – 49821Helical; Name=Segment S6Sequence AnalysisAdd
BLAST
Topological domaini499 – 989491CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. integral component of plasma membrane Source: GO_Central
  3. nuclear inner membrane Source: UniProtKB-SubCell
  4. nucleoplasm Source: MGI
  5. plasma membrane Source: MGI
  6. voltage-gated potassium channel complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi7 – 82RR → AA or EE: Strongly shifts the voltage-dependent channel activation to more depolarized membrane potentials. 1 Publication
Mutagenesisi57 – 571R → D: Decreases the rate of channel opening. No effect; when associated with R-642. 1 Publication
Mutagenesisi627 – 6271E → A or R: Strongly shifts the voltage-dependent channel activation to much more depolarized membrane potentials. 1 Publication
Mutagenesisi628 – 6281V → A or L: Mildly increases the affinity for CALM. 1 Publication
Mutagenesisi642 – 6421D → R: Decreases the rate of channel opening. No effect; when associated with D-57. 1 Publication
Mutagenesisi697 – 6993LTY → ATA: Increases the affinity for CALM. 1 Publication
Mutagenesisi699 – 7013YNL → ANA: Increases the affinity for CALM. 1 Publication
Mutagenesisi699 – 6991Y → W: Mildly increases the affinity for CALM. 1 Publication
Mutagenesisi705 – 7073IVF → AAA: Decreases the affinity for CALM. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 989989Potassium voltage-gated channel subfamily H member 1PRO_0000053995Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi415 – 4151N-linked (GlcNAc...)Sequence Analysis
Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ60603.
PRIDEiQ60603.

PTM databases

PhosphoSiteiQ60603.

Expressioni

Gene expression databases

BgeeiQ60603.
ExpressionAtlasiQ60603. baseline and differential.
GenevestigatoriQ60603.

Interactioni

Subunit structurei

The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH5/EAG2. Interacts with ALG10B (By similarity). Interacts with RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN (By similarity).By similarity1 Publication

Protein-protein interaction databases

IntActiQ60603. 1 interaction.

Structurei

Secondary structure

1
989
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi17 – 226Combined sources
Beta strandi29 – 346Combined sources
Beta strandi41 – 455Combined sources
Helixi47 – 537Combined sources
Helixi57 – 604Combined sources
Helixi68 – 703Combined sources
Helixi77 – 8812Combined sources
Beta strandi93 – 1008Combined sources
Beta strandi106 – 11712Combined sources
Beta strandi123 – 13210Combined sources
Turni134 – 1363Combined sources
Beta strandi555 – 5595Combined sources
Helixi565 – 5717Combined sources
Helixi573 – 5764Combined sources
Helixi580 – 5823Combined sources
Helixi587 – 59610Combined sources
Beta strandi598 – 6025Combined sources
Beta strandi607 – 6093Combined sources
Beta strandi613 – 6153Combined sources
Beta strandi617 – 6248Combined sources
Beta strandi626 – 6305Combined sources
Beta strandi633 – 6386Combined sources
Beta strandi643 – 6453Combined sources
Turni647 – 6515Combined sources
Beta strandi658 – 67316Combined sources
Helixi674 – 68310Combined sources
Helixi685 – 69410Combined sources
Beta strandi698 – 7003Combined sources
Helixi710 – 7189Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4F8AX-ray2.20A552-707[»]
4HOIX-ray1.85A/B/C/D28-137[»]
4LLOX-ray2.00A/C/E/G552-724[»]
B/D/F/H6-136[»]
ProteinModelPortaliQ60603.
SMRiQ60603. Positions 28-137, 449-503, 509-720.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 9481PASPROSITE-ProRule annotationAdd
BLAST
Domaini93 – 14553PACPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni673 – 77098Calmodulin-binding1 PublicationAdd
BLAST
Regioni699 – 7013Interaction with cyclic nucleotide-binding pocket1 Publication
Regioni924 – 96441CAD (involved in subunit assembly)By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi463 – 4686Selectivity filterBy similarity

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating.1 Publication1 Publication
The PAS domain interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating.1 Publication
The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides (PubMed:19671703). 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.3 Publications

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

eggNOGiCOG2202.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230794.
HOVERGENiHBG101348.
InParanoidiQ60603.
KOiK04904.
OMAiHAKLHAP.
OrthoDBiEOG7QG43V.
PhylomeDBiQ60603.
TreeFamiTF313130.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR030170. EAG1.
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]
PANTHERiPTHR10217:SF377. PTHR10217:SF377. 1 hit.
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.
SM00091. PAS. 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.

Q60603-1 [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 AFENVDEVSA FMGDPGKIGF ADQIPPPLEG RESQGISSLF
360 370 380 390 400
SSLKVVRLLR LGRVARKLDH YIEYGAAVLV LLVCVFGLAA HWMACIWYSI
410 420 430 440 450
GDYEIFDEDT KTIRNNSWLY QLALDIGTPY QFNGSGSGKW EGGPSKNSVY
460 470 480 490 500
ISSLYFTMTS LTSVGFGNIA PSTDIEKIFA VAIMMIGSLL YATIFGNVTT
510 520 530 540 550
IFQQMYANTN RYHEMLNSVR DFLKLYQVPK GLSERVMDYI VSTWSMSRGI
560 570 580 590 600
DTEKVLQICP KDMRADICVH LNRKVFKEHP AFRLASDGCL RALAMEFQTV
610 620 630 640 650
HCAPGDLIYH AGESVDSLCF VVSGSLEVIQ DDEVVAILGK GDVFGDVFWK
660 670 680 690 700
EATLAQSCAN VRALTYCDLH VIKRDALQKV LEFYTAFSHS FSRNLILTYN
710 720 730 740 750
LRKRIVFRKI SDVKREEEER MKRKNEAPLI LPPDHPVRRL FQRFRQQKEA
760 770 780 790 800
RLAAERGGRD LDDLDVEKGN ALTDHTSANH SLVKASVVTV RESPATPVSF
810 820 830 840 850
QAATTSTMSD HAKLHAPGSE CLGPKAVSCD PAKRKGWARF KDACGKGEDW
860 870 880 890 900
NKVSKAESME TLPERTKAPG EATLKKTDSC DSGITKSDLR LDNVGETRSP
910 920 930 940 950
QDRSPILAEV KHSFYPIPEQ TLQATVLEVK YELKEDIKAL NAKMTSIEKQ
960 970 980
LSEILRILMS RGSAQSPQET GEISRPQSPE SDRDIFGAS
Length:989
Mass (Da):111,314
Last modified:November 1, 1996 - v1
Checksum:iBA9B8C30F958CDCA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U04294 mRNA. Translation: AAA62474.1.
CCDSiCCDS15627.1.
PIRiI48912.
RefSeqiNP_034730.1. NM_010600.3.
UniGeneiMm.4489.

Genome annotation databases

EnsembliENSMUST00000078470; ENSMUSP00000077563; ENSMUSG00000058248.
GeneIDi16510.
KEGGimmu:16510.
UCSCiuc007edo.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U04294 mRNA. Translation: AAA62474.1.
CCDSiCCDS15627.1.
PIRiI48912.
RefSeqiNP_034730.1. NM_010600.3.
UniGeneiMm.4489.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4F8AX-ray2.20A552-707[»]
4HOIX-ray1.85A/B/C/D28-137[»]
4LLOX-ray2.00A/C/E/G552-724[»]
B/D/F/H6-136[»]
ProteinModelPortaliQ60603.
SMRiQ60603. Positions 28-137, 449-503, 509-720.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ60603. 1 interaction.

PTM databases

PhosphoSiteiQ60603.

Proteomic databases

PaxDbiQ60603.
PRIDEiQ60603.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000078470; ENSMUSP00000077563; ENSMUSG00000058248.
GeneIDi16510.
KEGGimmu:16510.
UCSCiuc007edo.1. mouse.

Organism-specific databases

CTDi3756.
MGIiMGI:1341721. Kcnh1.

Phylogenomic databases

eggNOGiCOG2202.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230794.
HOVERGENiHBG101348.
InParanoidiQ60603.
KOiK04904.
OMAiHAKLHAP.
OrthoDBiEOG7QG43V.
PhylomeDBiQ60603.
TreeFamiTF313130.

Enzyme and pathway databases

ReactomeiREACT_199077. Voltage gated Potassium channels.

Miscellaneous databases

NextBioi289847.
PROiQ60603.
SOURCEiSearch...

Gene expression databases

BgeeiQ60603.
ExpressionAtlasiQ60603. baseline and differential.
GenevestigatoriQ60603.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR030170. EAG1.
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]
PANTHERiPTHR10217:SF377. PTHR10217:SF377. 1 hit.
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.
SM00091. PAS. 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...

Publicationsi

  1. "A family of potassium channel genes related to eag in Drosophila and mammals."
    Warmke J.W., Ganetzky B.
    Proc. Natl. Acad. Sci. U.S.A. 91:3438-3442(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "Absence of direct cyclic nucleotide modulation of mEAG1 and hERG1 channels revealed with fluorescence and electrophysiological methods."
    Brelidze T.I., Carlson A.E., Zagotta W.N.
    J. Biol. Chem. 284:27989-27997(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF CYCLIC NUCLEOTIDE BINDING, FUNCTION, SUBCELLULAR LOCATION, DOMAIN.
  3. "Physical and functional interaction of KV10.1 with Rabaptin-5 impacts ion channel trafficking."
    Ninkovic M., Mitkovski M., Kohl T., Stuhmer W., Pardo L.A.
    FEBS Lett. 586:3077-3084(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RABEP1.
  4. "Structural, biochemical, and functional characterization of the cyclic nucleotide binding homology domain from the mouse EAG1 potassium channel."
    Marques-Carvalho M.J., Sahoo N., Muskett F.W., Vieira-Pires R.S., Gabant G., Cadene M., Schonherr R., Morais-Cabral J.H.
    J. Mol. Biol. 423:34-46(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 552-707, DOMAIN, CALMODULIN-BINDING REGION, MUTAGENESIS OF VAL-628; 697-LEU--TYR-699; TYR-699; 699-TYR--LEU-701 AND 705-ILE--PHE-707.
  5. "The structural mechanism of KCNH-channel regulation by the eag domain."
    Haitin Y., Carlson A.E., Zagotta W.N.
    Nature 501:444-448(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-136 AND 552-724, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF 7-ARG-ARG-8; ARG-57; GLU-627 AND ASP-642.
  6. "Structural properties of PAS domains from the KCNH potassium channels."
    Adaixo R., Harley C.A., Castro-Rodrigues A.F., Morais-Cabral J.H.
    PLoS ONE 8:E59265-E59265(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 28-137.

Entry informationi

Entry nameiKCNH1_MOUSE
AccessioniPrimary (citable) accession number: Q60603
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: November 1, 1996
Last modified: March 4, 2015
This is version 142 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.