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Protein

Potassium voltage-gated channel subfamily H member 1

Gene

KCNH1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:9524140). 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 similarity1 Publication

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). Extracellular magnesium ion concentrations up to 4 mM modulate channel activity by slowing down current activation in a reversible fashion. Channel activity is not regulated by cyclic nucleotides (PubMed:9524140). 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

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

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:
bEAG
Voltage-gated potassium channel subunit Kv10.1
Gene namesi
Name:KCNH1
Synonyms:EAG
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein By similarity
  • Nucleus inner membrane By similarity; Multi-pass membrane protein By similarity
  • Cell projectiondendrite By similarity
  • Cell projectionaxon By similarity
  • Cell junctionsynapsepresynaptic cell membrane By similarity
  • Perikaryon By similarity
  • Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity
  • Early endosome membrane By similarity

  • Note: Perinuclear KCNH1 is located to NPC-free islands.By similarity

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 – 987CytoplasmicBy similarityAdd BLAST489

GO - Cellular componenti

  • early endosome membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • nuclear inner membrane Source: UniProtKB-SubCell
  • 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539931 – 987Potassium voltage-gated channel subfamily H member 1Add BLAST987

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi415N-linked (GlcNAc...)Sequence analysis1
Glycosylationi433N-linked (GlcNAc...)Sequence analysis1
Modified residuei972PhosphoserineBy similarity1
Modified residuei976PhosphoserineBy similarity1
Modified residuei979PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiO18965.

Expressioni

Tissue specificityi

Detected in cerebellum, cortex and retina.1 Publication

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 (By similarity). Interacts (via C-terminus) with CTTN. Interacts (via C-terminal cytoplasmic region) with Ca2+-bound calmodulin (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliO18965.
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-bindingBy similarityAdd BLAST98
Regioni699 – 701Interaction with cyclic nucleotide-binding pocketBy similarity3
Regioni922 – 962CAD (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.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.By similarity
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

HOVERGENiHBG101348.
InParanoidiO18965.
KOiK04904.

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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: O18965-1) [UniParc]FASTAAdd to basket
Also known as: EAG2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTMAGGRKGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC
60 70 80 90 100
KLSGYHRAEV MQKSSTCSFM YGELTDKDTI 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 QLAMDIGTPY 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 LDDLDVEKGS VLTEHSHHGL AKASVVTVRE SPATPVAFPA
810 820 830 840 850
AAAPAGLDHA RLQAPGAEGL GPKAGGADCA KRKGWARFKD ACGQAEDWSK
860 870 880 890 900
VSKAESMETL PERTKAAGEA TLKKTDSCDS GITKSDLRLD NVGEARSPQD
910 920 930 940 950
RSPILAEVKH SFYPIPEQTL QAAVLEVKHE LKEDIKALST KMTSIEKQLS
960 970 980
EILRILTSRR SSQSPQELFE ISRPQSPESE RDIFGAS
Length:987
Mass (Da):110,918
Last modified:November 28, 2002 - v2
Checksum:i0EF9FB866297DC4F
GO
Isoform 1 (identifier: O18965-2) [UniParc]FASTAAdd to basket
Also known as: EAG1

The sequence of this isoform differs from the canonical sequence as follows:
     318-344: Missing.

Show »
Length:960
Mass (Da):108,092
Checksum:i86FCD3303A3E3B08
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000963318 – 344Missing in isoform 1. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13430 mRNA. Translation: CAA73842.1.
Y13431 mRNA. Translation: CAA73843.1.
RefSeqiNP_776797.1. NM_174372.2. [O18965-1]
UniGeneiBt.91775.

Genome annotation databases

GeneIDi281881.
KEGGibta:281881.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13430 mRNA. Translation: CAA73842.1.
Y13431 mRNA. Translation: CAA73843.1.
RefSeqiNP_776797.1. NM_174372.2. [O18965-1]
UniGeneiBt.91775.

3D structure databases

ProteinModelPortaliO18965.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiO18965.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281881.
KEGGibta:281881.

Organism-specific databases

CTDi3756.

Phylogenomic databases

HOVERGENiHBG101348.
InParanoidiO18965.
KOiK04904.

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_BOVIN
AccessioniPrimary (citable) accession number: O18965
Secondary accession number(s): O18966
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: November 28, 2002
Last modified: November 30, 2016
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.