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O35219

- KCNH2_MOUSE

UniProt

O35219 - KCNH2_MOUSE

Protein

Potassium voltage-gated channel subfamily H member 2

Gene

Kcnh2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 2 (28 Nov 2002)
      Previous versions | rss
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    Functioni

    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.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi744 – 861118cNMPAdd
    BLAST

    GO - Molecular functioni

    1. inward rectifier potassium channel activity Source: MGI
    2. phosphorelay sensor kinase activity Source: InterPro
    3. voltage-gated potassium channel activity Source: MGI

    GO - Biological processi

    1. potassium ion transmembrane transport Source: MGI
    2. regulation of heart rate by cardiac conduction Source: MGI
    3. regulation of membrane potential Source: MGI
    4. regulation of ventricular cardiac muscle cell membrane repolarization Source: MGI

    Keywords - Molecular functioni

    Ion channel, Potassium channel, Voltage-gated channel

    Keywords - Biological processi

    Ion transport, Potassium transport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_199077. Voltage gated Potassium channels.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:Kcnh2
    Synonyms:Erg, Merg1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:1341722. Kcnh2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. integral component of plasma membrane Source: RefGenome
    3. nuclear envelope Source: MGI
    4. plasma membrane Source: MGI

    Keywords - Cellular componenti

    Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11621162Potassium voltage-gated channel subfamily H member 2PRO_0000054000Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei322 – 3221PhosphoserineBy similarity
    Glycosylationi600 – 6001N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Phosphorylated on serine and threonine residues.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiO35219.
    PRIDEiO35219.

    PTM databases

    PhosphoSiteiO35219.

    Expressioni

    Tissue specificityi

    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.

    Gene expression databases

    ArrayExpressiO35219.
    BgeeiO35219.
    GenevestigatoriO35219.

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

    Structurei

    3D structure databases

    ProteinModelPortaliO35219.
    SMRiO35219. Positions 1-135, 572-664, 672-866.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 405405CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini427 – 45226ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini474 – 49724CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini519 – 5224ExtracellularSequence Analysis
    Topological domaini544 – 5496CytoplasmicSequence Analysis
    Topological domaini571 – 61343ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini635 – 6406ExtracellularSequence Analysis
    Topological domaini662 – 1162501CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei614 – 63421Pore-forming; Name=Segment H5Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei406 – 42621Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei453 – 47321Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei498 – 51821Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei523 – 54321Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei550 – 57021Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei641 – 66121Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini17 – 8872PASPROSITE-ProRule annotationAdd
    BLAST
    Domaini92 – 14453PACPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi626 – 6316Selectivity filterBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi299 – 3024Poly-Pro

    Domaini

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

    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.
    GeneTreeiENSGT00680000099663.
    HOGENOMiHOG000230793.
    HOVERGENiHBG052232.
    InParanoidiO35219.
    KOiK04905.
    PhylomeDBiO35219.

    Family and domain databases

    Gene3Di2.60.120.10. 2 hits.
    InterProiIPR018490. 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]
    PfamiPF00027. cNMP_binding. 1 hit.
    PF00520. Ion_trans. 1 hit.
    PF13426. PAS_9. 1 hit.
    [Graphical view]
    PRINTSiPR01463. EAGCHANLFMLY.
    PR01470. ERGCHANNEL.
    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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Experimental confirmation may be lacking for some isoforms.

    Isoform 1 (identifier: O35219-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE     50
    LCGYSRAEVM QRPCTCDFLH GPRTQRRAAA QIAQALLGAE ERKVEIAFYR 100
    KDGSCFLCLV DVVPVKNEDG AVIMFILNFE VVMEKDMVGS PAHDTNHRGP 150
    STSWLASGRA KTFRLKLPAL LALTARESSV RTGSMHSAGA PGAVVVDVDL 200
    TPAAPSSESL ALDEVSAMDN HVAGLGPAEE RRALVGPGSA SPVASIRGPH 250
    PSPRAQSLNP DASGSSCSLA RTRSRESCAS VRRASSADDI EAMRAGALPP 300
    PPRHASTGAM HPLRSGLLNS TSDSDLVRYR TISKIPQITL NFVDLKGDPF 350
    LASPTSDREI IAPKIKERTH NVTEKVTQVL SLGADVLPEY KLQAPRIHRW 400
    TILHYSPFKA VWDWLILLLV IYTAVFTPYS AAFLLKETED GSQAPDCGYA 450
    CQPLAVVDLI VDIMFIVDIL INFRTTYVNA NEEVVSHPGR IAVHYFKGWF 500
    LIDMVAAIPF DLLIFGSGSE ELIGLLKTAR LLRLVRVARK LDRYSEYGAA 550
    VLFLLMCTFA LIAHWLACIW YAIGNMEQPH MDSHIGWLHN LGDQIGKPYN 600
    SSGLGGPSIK DKYVTALYFT FSSLTSVGFG NVSPNTNSEK IFSICVMLIG 650
    SLMYASIFGN VSAIIQRLYS GTARYHTQML RVREFIRFHQ IPNPLRQRLE 700
    EYFQHAWSYT NGIDMNAVLK GFPECLQADI CLHLNRSLLQ HCKPFRGATK 750
    GCLRALAMKF KTTHAPPGDT LVHAGDLLTA LYFISRGSIE ILRGDVVVAI 800
    LGKNDIFGEP LNLYARPGKS NGDVRALTYC DLHKIHRDDL LEVLDMYPEF 850
    SDHFWSSLEI TFNLRDTNMI PGSPGSAELE SGFNRQRKRK LSFRRRTDKD 900
    TEQPGEVSAL GQGPARVGPG PSCRGQPGGP WGESPSSGPS SPESSEDEGP 950
    GRSSSPLRLV PFSSPRPPGD PPGGEPLTED GEKSDTCNPL SGAFSGVSNI 1000
    FSFWGDSRGR QYQELPRCPA PAPSLLNIPL SSPGRRSRGD VESRLDALQR 1050
    QLNRLETRLS ADMATVLQLL QRQMTLVPPA YSAVTTPGPG PTSASPLLPV 1100
    GPVPTLTLDS LSQVSQFVAF EELPAGAPEL PQDGPTRRLS LPGQLGALTS 1150
    QPLHRHGSDP GS 1162
    Length:1,162
    Mass (Da):126,886
    Last modified:November 28, 2002 - v2
    Checksum:iA9455F7F10B61E46
    GO
    Isoform 2 (identifier: O35219-2) [UniParc]FASTAAdd to Basket

    Also known as: 1A'

    The sequence of this isoform differs from the canonical sequence as follows:
         1-59: Missing.

    Show »
    Length:1,103
    Mass (Da):120,195
    Checksum:i28C9E5D432132689
    GO
    Isoform 3 (identifier: O35219-3) [UniParc]FASTAAdd to Basket

    Also known as: 1B, B

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

    Show »
    Length:820
    Mass (Da):90,129
    Checksum:iD86EB7D0F3ADF7C4
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti186 – 1861H → R in strain: BALB/c. 1 Publication
    Natural varianti455 – 4551A → T in strain: BALB/c. 1 Publication
    Natural varianti752 – 7521C → Y in strain: BALB/c. 1 Publication
    Natural varianti1006 – 10061D → N in strain: BALB/c. 1 Publication

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 378378MPVRR…EKVTQ → MAIPTGKESRTGALQPRAQK GRVRRAVRISSLVAQE in isoform 3. 2 PublicationsVSP_000970Add
    BLAST
    Alternative sequencei1 – 5959Missing in isoform 2. 1 PublicationVSP_000969Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS19116.1. [O35219-1]
    RefSeqiXP_006535699.1. XM_006535636.1.
    UniGeneiMm.6539.

    Genome annotation databases

    EnsembliENSMUST00000115098; ENSMUSP00000110750; ENSMUSG00000038319.
    GeneIDi16511.
    KEGGimmu:16511.
    UCSCiuc008wrb.1. mouse. [O35219-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS19116.1. [O35219-1 ]
    RefSeqi XP_006535699.1. XM_006535636.1.
    UniGenei Mm.6539.

    3D structure databases

    ProteinModelPortali O35219.
    SMRi O35219. Positions 1-135, 572-664, 672-866.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei O35219.

    Proteomic databases

    PaxDbi O35219.
    PRIDEi O35219.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000115098 ; ENSMUSP00000110750 ; ENSMUSG00000038319 .
    GeneIDi 16511.
    KEGGi mmu:16511.
    UCSCi uc008wrb.1. mouse. [O35219-3 ]

    Organism-specific databases

    CTDi 3757.
    MGIi MGI:1341722. Kcnh2.

    Phylogenomic databases

    eggNOGi COG2202.
    GeneTreei ENSGT00680000099663.
    HOGENOMi HOG000230793.
    HOVERGENi HBG052232.
    InParanoidi O35219.
    KOi K04905.
    PhylomeDBi O35219.

    Enzyme and pathway databases

    Reactomei REACT_199077. Voltage gated Potassium channels.

    Miscellaneous databases

    PROi O35219.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35219.
    Bgeei O35219.
    Genevestigatori O35219.

    Family and domain databases

    Gene3Di 2.60.120.10. 2 hits.
    InterProi IPR018490. 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 ]
    Pfami PF00027. cNMP_binding. 1 hit.
    PF00520. Ion_trans. 1 hit.
    PF13426. PAS_9. 1 hit.
    [Graphical view ]
    PRINTSi PR01463. EAGCHANLFMLY.
    PR01470. ERGCHANNEL.
    SMARTi SM00100. cNMP. 1 hit.
    SM00086. PAC. 1 hit.
    SM00091. PAS. 1 hit.
    [Graphical view ]
    SUPFAMi SSF51206. SSF51206. 1 hit.
    SSF55785. SSF55785. 1 hit.
    TIGRFAMsi TIGR00229. sensory_box. 1 hit.
    PROSITEi PS50042. CNMP_BINDING_3. 1 hit.
    PS50113. PAC. 1 hit.
    PS50112. PAS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiKCNH2_MOUSE
    AccessioniPrimary (citable) accession number: O35219
    Secondary accession number(s): O35220, O35221, O35989
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2002
    Last sequence update: November 28, 2002
    Last modified: October 1, 2014
    This is version 135 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3