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O35219 (KCNH2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium voltage-gated channel subfamily H member 2
Alternative name(s):
Ether-a-go-go-related gene potassium channel 1
Short name=ERG-1
Short name=Eag-related protein 1
Short name=Ether-a-go-go-related protein 1
Short name=MERG
Voltage-gated potassium channel subunit Kv11.1
Gene names
Name:Kcnh2
Synonyms:Erg, Merg1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1162 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) By similarity.

Subunit structure

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 KCNH6/ERG2, KCNH7/ERG3, KCNE1 and KCNE2. Interacts with ALG10B By similarity. Interacts with CANX By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Isoform 1 is expressed in heart, brain and testis and at low levels in lung. Isoform 3 is expressed predominantly in heart. The expression of isoform 2 is low in all tissues tested.

Domain

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Post-translational modification

Phosphorylated on serine and threonine residues By similarity.

Sequence similarities

Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily. [View classification]

Contains 1 cyclic nucleotide-binding domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 1 PAS (PER-ARNT-SIM) domain.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Potassium channel
Voltage-gated channel
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpotassium ion transmembrane transport

Inferred from direct assay Ref.2Ref.1. Source: MGI

regulation of heart rate by cardiac conduction

Inferred from direct assay PubMed 10843886. Source: MGI

regulation of membrane potential

Inferred from direct assay Ref.2Ref.1. Source: MGI

regulation of ventricular cardiac muscle cell membrane repolarization

Inferred from direct assay PubMed 10843886. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14668215. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

nuclear envelope

Inferred from direct assay PubMed 14668215. Source: MGI

plasma membrane

Inferred from direct assay PubMed 14668215. Source: MGI

   Molecular_functioninward rectifier potassium channel activity

Inferred from direct assay Ref.1. Source: MGI

phosphorelay sensor kinase activity

Inferred from electronic annotation. Source: InterPro

voltage-gated potassium channel activity

Inferred from direct assay Ref.2. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: O35219-1)

Also known as: 1A; A;

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.
Isoform 2 (identifier: O35219-2)

Also known as: 1A';

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.
Isoform 3 (identifier: O35219-3)

Also known as: 1B; B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-378: MPVRRGHVAP...THNVTEKVTQ → MAIPTGKESR...VRISSLVAQE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11621162Potassium voltage-gated channel subfamily H member 2
PRO_0000054000

Regions

Topological domain1 – 405405Cytoplasmic Potential
Transmembrane406 – 42621Helical; Name=Segment S1; Potential
Topological domain427 – 45226Extracellular Potential
Transmembrane453 – 47321Helical; Name=Segment S2; Potential
Topological domain474 – 49724Cytoplasmic Potential
Transmembrane498 – 51821Helical; Name=Segment S3; Potential
Topological domain519 – 5224Extracellular Potential
Transmembrane523 – 54321Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain544 – 5496Cytoplasmic Potential
Transmembrane550 – 57021Helical; Name=Segment S5; Potential
Topological domain571 – 61343Extracellular Potential
Intramembrane614 – 63421Pore-forming; Name=Segment H5; Potential
Topological domain635 – 6406Extracellular Potential
Transmembrane641 – 66121Helical; Name=Segment S6; Potential
Topological domain662 – 1162501Cytoplasmic Potential
Domain17 – 8872PAS
Domain92 – 14453PAC
Nucleotide binding744 – 861118cNMP
Motif626 – 6316Selectivity filter By similarity
Compositional bias299 – 3024Poly-Pro

Amino acid modifications

Modified residue3221Phosphoserine By similarity
Glycosylation6001N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 378378MPVRR…EKVTQ → MAIPTGKESRTGALQPRAQK GRVRRAVRISSLVAQE in isoform 3.
VSP_000970
Alternative sequence1 – 5959Missing in isoform 2.
VSP_000969
Natural variant1861H → R in strain: BALB/c. Ref.1
Natural variant4551A → T in strain: BALB/c. Ref.1
Natural variant7521C → Y in strain: BALB/c. Ref.1
Natural variant10061D → N in strain: BALB/c. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (1A) (A) [UniParc].

Last modified November 28, 2002. Version 2.
Checksum: A9455F7F10B61E46

FASTA1,162126,886
        10         20         30         40         50         60 
MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM 

        70         80         90        100        110        120 
QRPCTCDFLH GPRTQRRAAA QIAQALLGAE ERKVEIAFYR KDGSCFLCLV DVVPVKNEDG 

       130        140        150        160        170        180 
AVIMFILNFE VVMEKDMVGS PAHDTNHRGP STSWLASGRA KTFRLKLPAL LALTARESSV 

       190        200        210        220        230        240 
RTGSMHSAGA PGAVVVDVDL TPAAPSSESL ALDEVSAMDN HVAGLGPAEE RRALVGPGSA 

       250        260        270        280        290        300 
SPVASIRGPH PSPRAQSLNP DASGSSCSLA RTRSRESCAS VRRASSADDI EAMRAGALPP 

       310        320        330        340        350        360 
PPRHASTGAM HPLRSGLLNS TSDSDLVRYR TISKIPQITL NFVDLKGDPF LASPTSDREI 

       370        380        390        400        410        420 
IAPKIKERTH NVTEKVTQVL SLGADVLPEY KLQAPRIHRW TILHYSPFKA VWDWLILLLV 

       430        440        450        460        470        480 
IYTAVFTPYS AAFLLKETED GSQAPDCGYA CQPLAVVDLI VDIMFIVDIL INFRTTYVNA 

       490        500        510        520        530        540 
NEEVVSHPGR IAVHYFKGWF LIDMVAAIPF DLLIFGSGSE ELIGLLKTAR LLRLVRVARK 

       550        560        570        580        590        600 
LDRYSEYGAA VLFLLMCTFA LIAHWLACIW YAIGNMEQPH MDSHIGWLHN LGDQIGKPYN 

       610        620        630        640        650        660 
SSGLGGPSIK DKYVTALYFT FSSLTSVGFG NVSPNTNSEK IFSICVMLIG SLMYASIFGN 

       670        680        690        700        710        720 
VSAIIQRLYS GTARYHTQML RVREFIRFHQ IPNPLRQRLE EYFQHAWSYT NGIDMNAVLK 

       730        740        750        760        770        780 
GFPECLQADI CLHLNRSLLQ HCKPFRGATK GCLRALAMKF KTTHAPPGDT LVHAGDLLTA 

       790        800        810        820        830        840 
LYFISRGSIE ILRGDVVVAI LGKNDIFGEP LNLYARPGKS NGDVRALTYC DLHKIHRDDL 

       850        860        870        880        890        900 
LEVLDMYPEF SDHFWSSLEI TFNLRDTNMI PGSPGSAELE SGFNRQRKRK LSFRRRTDKD 

       910        920        930        940        950        960 
TEQPGEVSAL GQGPARVGPG PSCRGQPGGP WGESPSSGPS SPESSEDEGP GRSSSPLRLV 

       970        980        990       1000       1010       1020 
PFSSPRPPGD PPGGEPLTED GEKSDTCNPL SGAFSGVSNI FSFWGDSRGR QYQELPRCPA 

      1030       1040       1050       1060       1070       1080 
PAPSLLNIPL SSPGRRSRGD VESRLDALQR QLNRLETRLS ADMATVLQLL QRQMTLVPPA 

      1090       1100       1110       1120       1130       1140 
YSAVTTPGPG PTSASPLLPV GPVPTLTLDS LSQVSQFVAF EELPAGAPEL PQDGPTRRLS 

      1150       1160 
LPGQLGALTS QPLHRHGSDP GS 

« Hide

Isoform 2 (1A') [UniParc].

Checksum: 28C9E5D432132689
Show »

FASTA1,103120,195
Isoform 3 (1B) (B) [UniParc].

Checksum: D86EB7D0F3ADF7C4
Show »

FASTA82090,129

References

[1]"Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current."
London B., Trudeau M.C., Newton K.P., Beyer A.K., Copeland N.G., Gilbert D.J., Jenkins N.A., Satler C.A., Robertson G.A.
Circ. Res. 81:870-878(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), VARIANTS ARG-186; THR-455; TYR-752 AND ASN-1006.
Strain: 129/Sv and BALB/c.
Tissue: Heart.
[2]"Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts."
Lees-Miller J.P., Kondo C., Wang L., Duff H.J.
Circ. Res. 81:719-726(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
Tissue: Atrial tumor.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF012868 mRNA. Translation: AAC53418.1.
AF012869 mRNA. Translation: AAC53419.1.
AF012871, AF012870 Genomic DNA. Translation: AAC53420.1.
AF012871 Genomic DNA. Translation: AAC53421.1.
AF012871, AF012870 Genomic DNA. Translation: AAC53422.1.
AF034762 mRNA. Translation: AAB87571.1.
CCDSCCDS19116.1. [O35219-1]
RefSeqXP_006535699.1. XM_006535636.1.
UniGeneMm.6539.

3D structure databases

ProteinModelPortalO35219.
SMRO35219. Positions 1-135, 572-664, 672-866.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteO35219.

Proteomic databases

PaxDbO35219.
PRIDEO35219.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000115098; ENSMUSP00000110750; ENSMUSG00000038319.
GeneID16511.
KEGGmmu:16511.
UCSCuc008wrb.1. mouse. [O35219-3]

Organism-specific databases

CTD3757.
MGIMGI:1341722. Kcnh2.

Phylogenomic databases

eggNOGCOG2202.
GeneTreeENSGT00680000099663.
HOGENOMHOG000230793.
HOVERGENHBG052232.
InParanoidO35219.
KOK04905.
PhylomeDBO35219.

Gene expression databases

ArrayExpressO35219.
BgeeO35219.
GenevestigatorO35219.

Family and domain databases

Gene3D2.60.120.10. 2 hits.
InterProIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR003967. K_chnl_volt-dep_ERG.
IPR001610. PAC.
IPR000014. PAS.
IPR000700. PAS-assoc_C.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSPR01463. EAGCHANLFMLY.
PR01470. ERGCHANNEL.
SMARTSM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 1 hit.
PS50113. PAC. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROO35219.
SOURCESearch...

Entry information

Entry nameKCNH2_MOUSE
AccessionPrimary (citable) accession number: O35219
Secondary accession number(s): O35220, O35221, O35989
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: November 28, 2002
Last modified: July 9, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot