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Protein

Potassium voltage-gated channel subfamily H member 1

Gene

Kcnh1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:19671703, PubMed:23975098). 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 similarity2 Publications

Enzyme regulationi

Channel activity is inhibited by interaction with Ca2+-bound calmodulin. Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure (By similarity). Channel activity is not regulated by cyclic nucleotides (PubMed:19671703). 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

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Ion channel, Potassium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandLipid-binding, Potassium

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1341721 Kcnh1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 220CytoplasmicBy similarityAdd BLAST220
Transmembranei221 – 241Helical; Name=Segment S1By similarityAdd BLAST21
Topological domaini242 – 248ExtracellularBy similarity7
Transmembranei249 – 269Helical; Name=Segment S2By similarityAdd BLAST21
Topological domaini270 – 290CytoplasmicBy similarityAdd BLAST21
Transmembranei291 – 309Helical; Name=Segment S3By similarityAdd BLAST19
Topological domaini310 – 345ExtracellularBy similarityAdd BLAST36
Transmembranei346 – 368Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST23
Topological domaini369 – 377CytoplasmicBy similarity9
Transmembranei378 – 399Helical; Name=Segment S5By similarityAdd BLAST22
Topological domaini400 – 448ExtracellularBy similarityAdd BLAST49
Intramembranei449 – 470Pore-forming; Name=Segment H5By similarityAdd BLAST22
Topological domaini471 – 477ExtracellularBy similarity7
Transmembranei478 – 498Helical; Name=Segment S6By similarityAdd BLAST21
Topological domaini499 – 989CytoplasmicBy similarityAdd BLAST491

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are viable and fertile, and have normal brain morphology. Likewise, there is no change in the electrophysiological properties of cerebellar Purkinje cells and in the shape and frequency of action potentials.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7 – 8RR → AA or EE: Strongly shifts the voltage-dependent channel activation to more depolarized membrane potentials. 1 Publication2
Mutagenesisi57R → D: Decreases the rate of channel opening. No effect; when associated with R-642. 1 Publication1
Mutagenesisi627E → A or R: Strongly shifts the voltage-dependent channel activation to much more depolarized membrane potentials. 1 Publication1
Mutagenesisi628V → A or L: Mildly increases the affinity for CALM. 1 Publication1
Mutagenesisi642D → R: Decreases the rate of channel opening. No effect; when associated with D-57. 1 Publication1
Mutagenesisi697 – 699LTY → ATA: Increases the affinity for CALM. 1 Publication3
Mutagenesisi699 – 701YNL → ANA: Increases the affinity for CALM. 1 Publication3
Mutagenesisi699Y → W: Mildly increases the affinity for CALM. 1 Publication1
Mutagenesisi705 – 707IVF → AAA: Decreases the affinity for CALM. 1 Publication3
Mutagenesisi737V → A: No effect on affinity for CALM; when associated with A-740. 1 Publication1
Mutagenesisi737V → S: Decreases affinity for CALM 230-fold; when associated with S-740. 1 Publication1
Mutagenesisi740L → A: No effect on affinity for CALM; when associated with A-737. 1 Publication1
Mutagenesisi740L → S: Decreases affinity for CALM 230-fold; when associated with S-737. 1 Publication1
Mutagenesisi741F → S: Decreases affinity for CALM about 30-fold. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539951 – 989Potassium voltage-gated channel subfamily H member 1Add BLAST989

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi415N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi433N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei974PhosphoserineCombined sources1
Modified residuei978PhosphoserineCombined sources1
Modified residuei981PhosphoserineCombined sources1

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

iPTMnetiQ60603
PhosphoSitePlusiQ60603

Expressioni

Tissue specificityi

Detected in brain (at protein level) (PubMed:23424202, PubMed:25556795). Highly expressed in olfactory bulb. Detected in brain cortex, hippocampus, brain stem, striatum, thalamus, hypothalamus and spinal cord (PubMed:23424202).2 Publications

Gene expression databases

BgeeiENSMUSG00000058248
GenevisibleiQ60603 MM

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. Heteromultimer with KCNH5/EAG2 (By similarity). Interacts with ALG10B (By similarity). Interacts with RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN. Interacts (via C-terminal cytoplasmic region) with Ca2+-bound calmodulin (PubMed:27618660).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ60603, 1 interactor
MINTiQ60603
STRINGi10090.ENSMUSP00000077563

Structurei

Secondary structure

1989
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi17 – 22Combined sources6
Beta strandi29 – 34Combined sources6
Beta strandi41 – 45Combined sources5
Helixi47 – 53Combined sources7
Helixi57 – 60Combined sources4
Helixi68 – 70Combined sources3
Helixi77 – 88Combined sources12
Beta strandi93 – 100Combined sources8
Beta strandi106 – 117Combined sources12
Beta strandi123 – 132Combined sources10
Turni134 – 136Combined sources3
Beta strandi555 – 559Combined sources5
Helixi565 – 571Combined sources7
Helixi573 – 576Combined sources4
Helixi580 – 582Combined sources3
Helixi587 – 596Combined sources10
Beta strandi598 – 602Combined sources5
Beta strandi607 – 609Combined sources3
Beta strandi613 – 615Combined sources3
Beta strandi617 – 624Combined sources8
Beta strandi626 – 630Combined sources5
Beta strandi633 – 638Combined sources6
Beta strandi643 – 645Combined sources3
Turni647 – 651Combined sources5
Beta strandi658 – 673Combined sources16
Helixi674 – 683Combined sources10
Helixi685 – 694Combined sources10
Beta strandi698 – 700Combined sources3
Helixi710 – 718Combined sources9
Helixi736 – 741Combined sources6

3D structure databases

ProteinModelPortaliQ60603
SMRiQ60603
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
Regioni673 – 770Calmodulin-binding2 PublicationsAdd BLAST98
Regioni699 – 701Interaction with cyclic nucleotide-binding pocket1 Publication3
Regioni924 – 964CAD (involved in subunit assembly)By similarityAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi463 – 468Selectivity filterBy similarity6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.By similarity
The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating.1 Publication1 Publication
The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating (PubMed:23975098). 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.By similarity1 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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
HOGENOMiHOG000230794
HOVERGENiHBG101348
InParanoidiQ60603
KOiK04904
OrthoDBiEOG091G0OXR
PhylomeDBiQ60603
TreeFamiTF313130

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
cd00130 PAS, 1 hit
Gene3Di2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 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
IPR035965 PAS-like_dom_sf
IPR014710 RmlC-like_jellyroll
PANTHERiPTHR10217:SF530 PTHR10217:SF530, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF13426 PAS_9, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
PR01464 EAGCHANNEL
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SM00086 PAC, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
SSF55785 SSF55785, 1 hit
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50042 CNMP_BINDING_3, 1 hit
PS50113 PAC, 1 hit
PS50112 PAS, 1 hit

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
QAATTSTVSD 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):111,282
Last modified:November 30, 2016 - v2
Checksum:iAEC4C730E253DDC1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti808V → M in AAA62474 (PubMed:8159766).1
Sequence conflicti808V → M in BAE24272 (PubMed:16141072).1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U04294 mRNA Translation: AAA62474.1
AK140193 mRNA Translation: BAE24272.1
CH466555 Genomic DNA Translation: EDL12967.1
BC109013 mRNA Translation: AAI09014.1
CCDSiCCDS15627.1
PIRiI48912
RefSeqiNP_034730.1, NM_010600.3
UniGeneiMm.4489

Genome annotation databases

GeneIDi16510
KEGGimmu:16510
UCSCiuc007edo.2 mouse

Similar proteinsi

Entry informationi

Entry nameiKCNH1_MOUSE
AccessioniPrimary (citable) accession number: Q60603
Secondary accession number(s): Q32MR6, Q3USQ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: November 30, 2016
Last modified: June 20, 2018
This is version 173 of the entry and version 2 of the sequence. See 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

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