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O35219

- KCNH2_MOUSE

UniProt

O35219 - KCNH2_MOUSE

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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

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
Complete GO annotation...

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
Complete GO annotation...

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

MaxQBiO35219.
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

BgeeiO35219.
ExpressionAtlasiO35219. baseline and differential.
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.
GeneTreeiENSGT00760000118772.
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

        10         20         30         40         50
MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE
60 70 80 90 100
LCGYSRAEVM QRPCTCDFLH GPRTQRRAAA QIAQALLGAE ERKVEIAFYR
110 120 130 140 150
KDGSCFLCLV DVVPVKNEDG AVIMFILNFE VVMEKDMVGS PAHDTNHRGP
160 170 180 190 200
STSWLASGRA KTFRLKLPAL LALTARESSV RTGSMHSAGA PGAVVVDVDL
210 220 230 240 250
TPAAPSSESL ALDEVSAMDN HVAGLGPAEE RRALVGPGSA SPVASIRGPH
260 270 280 290 300
PSPRAQSLNP DASGSSCSLA RTRSRESCAS VRRASSADDI EAMRAGALPP
310 320 330 340 350
PPRHASTGAM HPLRSGLLNS TSDSDLVRYR TISKIPQITL NFVDLKGDPF
360 370 380 390 400
LASPTSDREI IAPKIKERTH NVTEKVTQVL SLGADVLPEY KLQAPRIHRW
410 420 430 440 450
TILHYSPFKA VWDWLILLLV IYTAVFTPYS AAFLLKETED GSQAPDCGYA
460 470 480 490 500
CQPLAVVDLI VDIMFIVDIL INFRTTYVNA NEEVVSHPGR IAVHYFKGWF
510 520 530 540 550
LIDMVAAIPF DLLIFGSGSE ELIGLLKTAR LLRLVRVARK LDRYSEYGAA
560 570 580 590 600
VLFLLMCTFA LIAHWLACIW YAIGNMEQPH MDSHIGWLHN LGDQIGKPYN
610 620 630 640 650
SSGLGGPSIK DKYVTALYFT FSSLTSVGFG NVSPNTNSEK IFSICVMLIG
660 670 680 690 700
SLMYASIFGN VSAIIQRLYS GTARYHTQML RVREFIRFHQ IPNPLRQRLE
710 720 730 740 750
EYFQHAWSYT NGIDMNAVLK GFPECLQADI CLHLNRSLLQ HCKPFRGATK
760 770 780 790 800
GCLRALAMKF KTTHAPPGDT LVHAGDLLTA LYFISRGSIE ILRGDVVVAI
810 820 830 840 850
LGKNDIFGEP LNLYARPGKS NGDVRALTYC DLHKIHRDDL LEVLDMYPEF
860 870 880 890 900
SDHFWSSLEI TFNLRDTNMI PGSPGSAELE SGFNRQRKRK LSFRRRTDKD
910 920 930 940 950
TEQPGEVSAL GQGPARVGPG PSCRGQPGGP WGESPSSGPS SPESSEDEGP
960 970 980 990 1000
GRSSSPLRLV PFSSPRPPGD PPGGEPLTED GEKSDTCNPL SGAFSGVSNI
1010 1020 1030 1040 1050
FSFWGDSRGR QYQELPRCPA PAPSLLNIPL SSPGRRSRGD VESRLDALQR
1060 1070 1080 1090 1100
QLNRLETRLS ADMATVLQLL QRQMTLVPPA YSAVTTPGPG PTSASPLLPV
1110 1120 1130 1140 1150
GPVPTLTLDS LSQVSQFVAF EELPAGAPEL PQDGPTRRLS LPGQLGALTS
1160
QPLHRHGSDP GS
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]
RefSeqiNP_001281091.1. NM_001294162.1.
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 NP_001281091.1. NM_001294162.1.
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

MaxQBi O35219.
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 ENSGT00760000118772.
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

Bgeei O35219.
ExpressionAtlasi O35219. baseline and differential.
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 29, 2014
This is version 136 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