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Q12809

- KCNH2_HUMAN

UniProt

Q12809 - KCNH2_HUMAN

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Protein
Potassium voltage-gated channel subfamily H member 2
Gene
KCNH2, ERG, ERG1, HERG
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein 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). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi742 – 842101cNMP
Add
BLAST

GO - Molecular functioni

  1. delayed rectifier potassium channel activity Source: BHF-UCL
  2. identical protein binding Source: IntAct
  3. inward rectifier potassium channel activity Source: BHF-UCL
  4. phosphorelay sensor kinase activity Source: InterPro
  5. protein binding Source: UniProtKB
  6. protein homodimerization activity Source: BHF-UCL
  7. ubiquitin protein ligase binding Source: BHF-UCL
  8. voltage-gated potassium channel activity Source: BHF-UCL
  9. voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization Source: BHF-UCL

GO - Biological processi

  1. cardiac muscle contraction Source: BHF-UCL
  2. cellular response to drug Source: BHF-UCL
  3. membrane depolarization during action potential Source: BHF-UCL
  4. membrane repolarization during action potential Source: BHF-UCL
  5. membrane repolarization during cardiac muscle cell action potential Source: BHF-UCL
  6. negative regulation of potassium ion export Source: BHF-UCL
  7. negative regulation of potassium ion transmembrane transport Source: BHF-UCL
  8. positive regulation of potassium ion transmembrane transport Source: BHF-UCL
  9. potassium ion export Source: BHF-UCL
  10. potassium ion homeostasis Source: BHF-UCL
  11. potassium ion transmembrane transport Source: BHF-UCL
  12. regulation of heart rate by cardiac conduction Source: BHF-UCL
  13. regulation of heart rate by hormone Source: BHF-UCL
  14. regulation of membrane potential Source: BHF-UCL
  15. regulation of membrane repolarization Source: BHF-UCL
  16. regulation of potassium ion transmembrane transport Source: BHF-UCL
  17. regulation of ventricular cardiac muscle cell membrane repolarization Source: BHF-UCL
  18. synaptic transmission Source: Reactome
  19. ventricular cardiac muscle cell action potential Source: BHF-UCL
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_75770. Voltage gated Potassium channels.
SignaLinkiQ12809.

Protein family/group databases

TCDBi1.A.1.20.1. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily H member 2
Alternative name(s):
Eag homolog
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:
H-ERG
Short name:
hERG-1
Short name:
hERG1
Voltage-gated potassium channel subunit Kv11.1
Gene namesi
Name:KCNH2
Synonyms:ERG, ERG1, HERG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:6251. KCNH2.

Subcellular locationi

Cell membrane; Multi-pass membrane protein 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 403403Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei404 – 42421Helical; Name=Segment S1; Reviewed prediction
Add
BLAST
Topological domaini425 – 45026Extracellular Reviewed prediction
Add
BLAST
Transmembranei451 – 47121Helical; Name=Segment S2; Reviewed prediction
Add
BLAST
Topological domaini472 – 49524Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei496 – 51621Helical; Name=Segment S3; Reviewed prediction
Add
BLAST
Topological domaini517 – 5204Extracellular Reviewed prediction
Transmembranei521 – 54121Helical; Voltage-sensor; Name=Segment S4; Reviewed prediction
Add
BLAST
Topological domaini542 – 5476Cytoplasmic Reviewed prediction
Transmembranei548 – 56821Helical; Name=Segment S5; Reviewed prediction
Add
BLAST
Topological domaini569 – 61143Extracellular Reviewed prediction
Add
BLAST
Intramembranei612 – 63221Pore-forming; Name=Segment H5; Reviewed prediction
Add
BLAST
Topological domaini633 – 6386Extracellular Reviewed prediction
Transmembranei639 – 65921Helical; Name=Segment S6; Reviewed prediction
Add
BLAST
Topological domaini660 – 1159500Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. cytoplasm Source: Ensembl
  3. nuclear envelope Source: Ensembl
  4. plasma membrane Source: BHF-UCL
  5. voltage-gated potassium channel complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Long QT syndrome 2 (LQT2) [MIM:613688]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Deafness is often associated with long QT syndrome type 2.
Note: The disease is caused by mutations affecting the gene represented in this entry.24 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti26 – 261S → I in LQT2. 1 Publication
VAR_068249
Natural varianti29 – 291F → L in LQT2. 2 Publications
VAR_008907
Natural varianti31 – 311I → S in LQT2. 1 Publication
VAR_068250
Natural varianti33 – 331N → T in LQT2. 1 Publication
VAR_008908
Natural varianti47 – 471G → V in LQT2.
VAR_009909
Natural varianti53 – 531G → R in LQT2. 2 Publications
VAR_008909
Natural varianti55 – 551S → L in LQT2. 1 Publication
VAR_068251
Natural varianti56 – 561R → Q in LQT2. 1 Publication
VAR_008910
Natural varianti65 – 651T → P in LQT2. 2 Publications
Corresponds to variant rs28933095 [ dbSNP | Ensembl ].
VAR_014371
Natural varianti66 – 661C → G in LQT2. 1 Publication
VAR_008911
Natural varianti70 – 701H → R in LQT2. 2 Publications
VAR_008912
Natural varianti72 – 721P → Q in LQT2.
VAR_009910
Natural varianti78 – 781A → P in LQT2. 2 Publications
VAR_008913
Natural varianti85 – 851A → V in LQT2. 1 Publication
VAR_068252
Natural varianti86 – 861L → R in LQT2. 1 Publication
VAR_008914
Natural varianti100 – 1001R → G in LQT2; digenic; associated with the Asn-1819 mutation on the SCN5A gene. 1 Publication
VAR_036669
Natural varianti100 – 1001R → Q in LQT2. 1 Publication
VAR_068253
Natural varianti176 – 1761R → W in LQT2. 1 Publication
Corresponds to variant rs36210422 [ dbSNP | Ensembl ].
VAR_008915
Natural varianti238 – 2381G → S in LQT2. 1 Publication
VAR_068254
Natural varianti306 – 3061G → W in LQT2. 1 Publication
VAR_068255
Natural varianti312 – 3121R → C in LQT2.
VAR_009911
Natural varianti320 – 3201S → L in LQT2. 1 Publication
VAR_068256
Natural varianti328 – 3281R → C in LQT2. 1 Publication
VAR_068257
Natural varianti347 – 3471P → S in LQT2.
VAR_009912
Natural varianti420 – 4201Y → C in LQT2. 1 Publication
VAR_068258
Natural varianti421 – 4211T → M in LQT2. 1 Publication
VAR_068259
Natural varianti422 – 4221A → T in LQT2. 1 Publication
VAR_068260
Natural varianti427 – 4271Y → S in LQT2. 1 Publication
VAR_068261
Natural varianti436 – 4361T → M in LQT2.
VAR_008916
Natural varianti451 – 4511P → L in LQT2. 1 Publication
VAR_014373
Natural varianti456 – 4561D → Y in LQT2. 1 Publication
VAR_068262
Natural varianti470 – 4701N → D in LQT2; aberrant protein folding increases the association of mutant KCNH2 with CANX and results in defective protein trafficking. 2 Publications
VAR_008578
Natural varianti474 – 4741T → I in LQT2. 1 Publication
VAR_008917
Natural varianti475 – 4751Missing in LQT2. 1 Publication
VAR_068263
Natural varianti500 – 5089Missing in LQT2.
VAR_009178
Natural varianti531 – 5311R → Q in LQT2.
VAR_009913
Natural varianti534 – 5341R → C in LQT2. 2 Publications
VAR_008579
Natural varianti552 – 5521L → S in LQT2. 1 Publication
VAR_008918
Natural varianti558 – 5581A → P in LQT2. 1 Publication
VAR_008919
Natural varianti561 – 5611A → T in LQT2. 2 Publications
VAR_014374
Natural varianti561 – 5611A → V in LQT2; the mutation reduces wild-type channel expression. 3 Publications
VAR_008580
Natural varianti562 – 5621H → P in LQT2. 1 Publication
VAR_068264
Natural varianti564 – 5641L → P in LQT2.
VAR_008920
Natural varianti569 – 5691Y → H in LQT2. 1 Publication
VAR_008921
Natural varianti571 – 5711I → L in LQT2. 1 Publication
VAR_068265
Natural varianti572 – 5721G → C in LQT2. 1 Publication
VAR_008923
Natural varianti572 – 5721G → R in LQT2; severe form. 1 Publication
VAR_008922
Natural varianti572 – 5721G → S in LQT2. 1 Publication
VAR_068266
Natural varianti582 – 5821R → C in LQT2. 2 Publications
VAR_008581
Natural varianti584 – 5841G → S in LQT2. 2 Publications
VAR_008924
Natural varianti585 – 5851W → C in LQT2.
VAR_009914
Natural varianti588 – 5881N → D in LQT2. 2 Publications
VAR_008925
Natural varianti593 – 5931I → R in LQT2. 1 Publication
Corresponds to variant rs28928904 [ dbSNP | Ensembl ].
VAR_008582
Natural varianti593 – 5931I → T in LQT2.
VAR_009915
Natural varianti596 – 5961P → R in LQT2. 1 Publication
VAR_068267
Natural varianti601 – 6011G → S in LQT2. 2 Publications
VAR_008926
Natural varianti604 – 6041G → S in LQT2. 2 Publications
VAR_008927
Natural varianti609 – 6091D → N in LQT2.
VAR_009916
Natural varianti611 – 6111Y → H in LQT2. 1 Publication
VAR_008928
Natural varianti612 – 6121V → L in LQT2. 1 Publication
VAR_008929
Natural varianti613 – 6131T → M in LQT2. 3 Publications
VAR_008930
Natural varianti614 – 6141A → V in LQT2. 4 Publications
VAR_008931
Natural varianti615 – 6151L → V in LQT2.
VAR_014375
Natural varianti622 – 6221L → F in LQT2. 1 Publication
VAR_068268
Natural varianti623 – 6231T → I in LQT2. 1 Publication
VAR_068269
Natural varianti626 – 6261G → S in LQT2.
VAR_014376
Natural varianti627 – 6271F → L in LQT2.
VAR_014377
Natural varianti628 – 6281G → S in LQT2. 2 Publications
VAR_008583
Natural varianti628 – 6281G → V in LQT2. 1 Publication
VAR_068270
Natural varianti629 – 6291N → D in LQT2. 1 Publication
VAR_008932
Natural varianti629 – 6291N → K in LQT2. 1 Publication
VAR_008933
Natural varianti629 – 6291N → S in LQT2. 1 Publication
VAR_009179
Natural varianti630 – 6301V → A in LQT2. 2 Publications
VAR_008935
Natural varianti630 – 6301V → L in LQT2. 1 Publication
VAR_008934
Natural varianti632 – 6321P → S in LQT2.
VAR_014378
Natural varianti633 – 6331N → S in LQT2. 2 Publications
VAR_008936
Natural varianti635 – 6351N → I in LQT2. 1 Publication
VAR_068271
Natural varianti637 – 6371E → K in LQT2. 1 Publication
VAR_014379
Natural varianti638 – 6381K → E in LQT2.
VAR_014380
Natural varianti638 – 6381Missing in LQT2.
VAR_014381
Natural varianti640 – 6401F → L in LQT2. 1 Publication
VAR_008937
Natural varianti640 – 6401F → V in LQT2. 1 Publication
VAR_068272
Natural varianti641 – 6411S → F in LQT2. 1 Publication
VAR_068273
Natural varianti645 – 6451M → L in LQT2.
VAR_014382
Natural varianti671 – 6755Missing in LQT2.
VAR_068274
Natural varianti721 – 7211P → L in LQT2. 1 Publication
VAR_068275
Natural varianti744 – 7441R → P in LQT2; impairs channel function; exhibits reduced activating currents compared to wild-type; cell surface trafficking is not impaired; does not exert dominant-negative effects on wild-type channel; the half-maximal activation voltage is not significantly affected by the mutation. 1 Publication
VAR_068276
Natural varianti752 – 7521R → Q in LQT2. 1 Publication
VAR_036675
Natural varianti752 – 7521R → W in LQT2.
VAR_014383
Natural varianti774 – 7741D → Y in LQT2. 1 Publication
VAR_068277
Natural varianti784 – 7841R → W Predisposes to LQT2 and torsades de pointes while taking the drug amiodarone; in vitro studies confirmed a significant reduction in potassium currents; the ECG abnormalities reversed on drug withdrawal. 2 Publications
VAR_036676
Natural varianti788 – 7881E → D in LQT2. 1 Publication
VAR_068278
Natural varianti805 – 8051F → C in LQT2. 1 Publication
VAR_014384
Natural varianti805 – 8051F → S in LQT2.
VAR_014385
Natural varianti818 – 8181S → L in LQT2. 1 Publication
VAR_008938
Natural varianti820 – 8201G → R in LQT2. 1 Publication
VAR_068279
Natural varianti822 – 8221V → M in LQT2. 2 Publications
VAR_008584
Natural varianti823 – 8231R → W in LQT2.
VAR_014386
Natural varianti837 – 8371D → G in LQT2. 1 Publication
VAR_068280
Natural varianti861 – 8611N → I in LQT2. 1 Publication
VAR_014387
Natural varianti887 – 8871R → H in LQT2. 1 Publication
VAR_068281
Natural varianti913 – 9131A → V in LQT2. 1 Publication
VAR_068282
Natural varianti917 – 9171P → L in LQT2.
VAR_014389
Natural varianti922 – 9221R → W in LQT2.
VAR_014390
Natural varianti925 – 9251G → R in LQT2. 1 Publication
VAR_068283
Natural varianti983 – 9831T → I in LQT2. 1 Publication
VAR_068284
Natural varianti996 – 9961N → I in LQT2. 1 Publication
VAR_068285
Natural varianti1036 – 10361G → D in LQT2. 1 Publication
VAR_068286
Short QT syndrome 1 (SQT1) [MIM:609620]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti588 – 5881N → K in SQT1. 2 Publications
VAR_023840

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi29 – 291F → A: Slows down deactivation. 1 Publication
Mutagenesisi43 – 431Y → A: Slows down deactivation. 1 Publication
Mutagenesisi283 – 2831S → A: Abolishes phosphorylation; when associated with A-890; A-895 and A-1137. 1 Publication
Mutagenesisi598 – 5981N → Q: No effect on cell surface expression, but changes inactivation kinetics; when associated with A-631. 1 Publication
Mutagenesisi629 – 6291N → Q: Abolishes cell surface expression; has no effect on N-glycosylation. 1 Publication
Mutagenesisi631 – 6311S → A: No effect on cell surface expression, but changes inactivation kinetics; when associated with Q-598. 1 Publication
Mutagenesisi890 – 8901S → A: Abolishes phosphorylation; when associated with A-283; A-895 and A-1137. 1 Publication
Mutagenesisi895 – 8951T → A: Abolishes phosphorylation; when associated with A-283; A-890 and A-1137. 1 Publication
Mutagenesisi1137 – 11371S → A: Abolishes phosphorylation; when associated with A-283; A-890 and A-895. 1 Publication

Keywords - Diseasei

Deafness, Disease mutation, Long QT syndrome, Short QT syndrome

Organism-specific databases

MIMi609620. phenotype.
613688. phenotype.
Orphaneti51083. Familial short QT syndrome.
101016. Romano-Ward syndrome.
PharmGKBiPA212.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11591159Potassium voltage-gated channel subfamily H member 2
PRO_0000053999Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei320 – 3201Phosphoserine1 Publication
Glycosylationi598 – 5981N-linked (GlcNAc...)1 Publication

Post-translational modificationi

Phosphorylated on serine and threonine residues. Phosphorylation by PKA inhibits ion conduction.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ12809.
PRIDEiQ12809.

PTM databases

PhosphoSiteiQ12809.

Expressioni

Tissue specificityi

Highly expressed in heart and brain. Isoforms USO are frequently overexpressed in cancer cells.1 Publication

Gene expression databases

ArrayExpressiQ12809.
BgeeiQ12809.
CleanExiHS_ERG.
HS_KCNH2.
GenevestigatoriQ12809.

Organism-specific databases

HPAiCAB006838.

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 and KCNH7/ERG3. Interacts with ALG10B By similarity. Heteromultimer with KCNE1 and KCNE2. Interacts with CANX.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-720643,EBI-720643

Protein-protein interaction databases

BioGridi109959. 20 interactions.
DIPiDIP-48929N.
IntActiQ12809. 6 interactions.
MINTiMINT-1427435.
STRINGi9606.ENSP00000262186.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi15 – 195
Turni23 – 264
Beta strandi29 – 335
Beta strandi36 – 383
Beta strandi40 – 445
Helixi46 – 527
Helixi56 – 594
Helixi67 – 693
Helixi76 – 8712
Beta strandi88 – 903
Beta strandi92 – 998
Beta strandi105 – 11612
Beta strandi118 – 1203
Beta strandi122 – 13413
Turni538 – 5403
Helixi542 – 5498
Beta strandi577 – 5804
Helixi586 – 5938
Helixi605 – 6106

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BYWX-ray2.60A26-135[»]
1UJLNMR-A570-611[»]
2L0WNMR-A1-135[»]
2L1MNMR-A1-135[»]
2L4RNMR-A1-135[»]
2LE7NMR-A532-551[»]
4HP9X-ray2.12A10-135[»]
4HQAX-ray1.96A1-135[»]
ProteinModelPortaliQ12809.
SMRiQ12809. Positions 1-135, 570-662, 670-864.

Miscellaneous databases

EvolutionaryTraceiQ12809.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 7030PAS
Add
BLAST
Domaini92 – 14453PAC
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi624 – 6296Selectivity filter By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi297 – 3004Poly-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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2202.
HOVERGENiHBG052232.
InParanoidiQ12809.
KOiK04905.
OMAiPARDTNH.
OrthoDBiEOG75B879.
PhylomeDBiQ12809.
TreeFamiTF313130.

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 (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. Align

Note: Experimental confirmation may be lacking for some isoforms.

Isoform A (identifier: Q12809-1) [UniParc]FASTAAdd to Basket

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
PTSWLAPGRA KTFRLKLPAL LALTARESSV RSGGAGGAGA PGAVVVDVDL 200
TPAAPSSESL ALDEVTAMDN HVAGLGPAEE RRALVGPGSP PRSAPGQLPS 250
PRAHSLNPDA SGSSCSLART RSRESCASVR RASSADDIEA MRAGVLPPPP 300
RHASTGAMHP LRSGLLNSTS DSDLVRYRTI SKIPQITLNF VDLKGDPFLA 350
SPTSDREIIA PKIKERTHNV TEKVTQVLSL GADVLPEYKL QAPRIHRWTI 400
LHYSPFKAVW DWLILLLVIY TAVFTPYSAA FLLKETEEGP PATECGYACQ 450
PLAVVDLIVD IMFIVDILIN FRTTYVNANE EVVSHPGRIA VHYFKGWFLI 500
DMVAAIPFDL LIFGSGSEEL IGLLKTARLL RLVRVARKLD RYSEYGAAVL 550
FLLMCTFALI AHWLACIWYA IGNMEQPHMD SRIGWLHNLG DQIGKPYNSS 600
GLGGPSIKDK YVTALYFTFS SLTSVGFGNV SPNTNSEKIF SICVMLIGSL 650
MYASIFGNVS AIIQRLYSGT ARYHTQMLRV REFIRFHQIP NPLRQRLEEY 700
FQHAWSYTNG IDMNAVLKGF PECLQADICL HLNRSLLQHC KPFRGATKGC 750
LRALAMKFKT THAPPGDTLV HAGDLLTALY FISRGSIEIL RGDVVVAILG 800
KNDIFGEPLN LYARPGKSNG DVRALTYCDL HKIHRDDLLE VLDMYPEFSD 850
HFWSSLEITF NLRDTNMIPG SPGSTELEGG FSRQRKRKLS FRRRTDKDTE 900
QPGEVSALGP GRAGAGPSSR GRPGGPWGES PSSGPSSPES SEDEGPGRSS 950
SPLRLVPFSS PRPPGEPPGG EPLMEDCEKS SDTCNPLSGA FSGVSNIFSF 1000
WGDSRGRQYQ ELPRCPAPTP SLLNIPLSSP GRRPRGDVES RLDALQRQLN 1050
RLETRLSADM ATVLQLLQRQ MTLVPPAYSA VTTPGPGPTS TSPLLPVSPL 1100
PTLTLDSLSQ VSQFMACEEL PPGAPELPQE GPTRRLSLPG QLGALTSQPL 1150
HRHGSDPGS 1159
Length:1,159
Mass (Da):126,655
Last modified:November 1, 1996 - v1
Checksum:iD03BD4F657641FBA
GO
Isoform B (identifier: Q12809-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-376: MPVRRGHVAP...THNVTEKVTQ → MAAPAGKASR...VRISSLVAQE

Show »
Length:819
Mass (Da):90,108
Checksum:i6C3F360C310C178A
GO
Isoform 4 (identifier: Q12809-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     139-195: Missing.

Note: No experimental confirmation available.

Show »
Length:1,102
Mass (Da):121,029
Checksum:i9501F6136737A384
GO
Isoform A-USO (identifier: Q12809-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     801-888: KNDIFGEPLN...GGFSRQRKRK → MGWGAGTGLE...HKQTLFASLK
     889-1159: Missing.

Note: Twice more abundant than isoform 1 in heart.

Show »
Length:888
Mass (Da):97,542
Checksum:i2C9582876D520E39
GO
Isoform B-USO (identifier: Q12809-6) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARV → MAAPAGKASRTGALRPRAQKGRVRRAVRISSLVAQE
     37-376: Missing.
     801-888: KNDIFGEPLN...GGFSRQRKRK → MGWGAGTGLE...HKQTLFASLK
     889-1159: Missing.

Show »
Length:548
Mass (Da):60,995
Checksum:iB479DEA5B3163A13
GO
Isoform 3.1 (identifier: Q12809-7) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MPVRRGHVAP...KVEIAFYRKD → MSSHSA

Note: Primate-specific. Lacks a domain that is crucial for slow channel deactivation.

Show »
Length:1,063
Mass (Da):115,636
Checksum:i6C9DFEF9A38A3034
GO

Sequence cautioni

The sequence CAA09232.1 differs from that shown. Reason: Erroneous gene model prediction.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti26 – 261S → I in LQT2. 1 Publication
VAR_068249
Natural varianti29 – 291F → L in LQT2. 2 Publications
VAR_008907
Natural varianti31 – 311I → S in LQT2. 1 Publication
VAR_068250
Natural varianti33 – 331N → T in LQT2. 1 Publication
VAR_008908
Natural varianti47 – 471G → V in LQT2.
VAR_009909
Natural varianti53 – 531G → R in LQT2. 2 Publications
VAR_008909
Natural varianti55 – 551S → L in LQT2. 1 Publication
VAR_068251
Natural varianti56 – 561R → Q in LQT2. 1 Publication
VAR_008910
Natural varianti65 – 651T → P in LQT2. 2 Publications
Corresponds to variant rs28933095 [ dbSNP | Ensembl ].
VAR_014371
Natural varianti66 – 661C → G in LQT2. 1 Publication
VAR_008911
Natural varianti70 – 701H → R in LQT2. 2 Publications
VAR_008912
Natural varianti72 – 721P → Q in LQT2.
VAR_009910
Natural varianti78 – 781A → P in LQT2. 2 Publications
VAR_008913
Natural varianti85 – 851A → V in LQT2. 1 Publication
VAR_068252
Natural varianti86 – 861L → R in LQT2. 1 Publication
VAR_008914
Natural varianti100 – 1001R → G in LQT2; digenic; associated with the Asn-1819 mutation on the SCN5A gene. 1 Publication
VAR_036669
Natural varianti100 – 1001R → Q in LQT2. 1 Publication
VAR_068253
Natural varianti176 – 1761R → W in LQT2. 1 Publication
Corresponds to variant rs36210422 [ dbSNP | Ensembl ].
VAR_008915
Natural varianti181 – 1811R → Q.
Corresponds to variant rs41308954 [ dbSNP | Ensembl ].
VAR_036670
Natural varianti189 – 1891G → GGAG.1 Publication
VAR_014372
Natural varianti238 – 2381G → S in LQT2. 1 Publication
VAR_068254
Natural varianti306 – 3061G → W in LQT2. 1 Publication
VAR_068255
Natural varianti312 – 3121R → C in LQT2.
VAR_009911
Natural varianti320 – 3201S → L in LQT2. 1 Publication
VAR_068256
Natural varianti328 – 3281R → C in LQT2. 1 Publication
VAR_068257
Natural varianti347 – 3471P → S in LQT2.
VAR_009912
Natural varianti420 – 4201Y → C in LQT2. 1 Publication
VAR_068258
Natural varianti421 – 4211T → M in LQT2. 1 Publication
VAR_068259
Natural varianti422 – 4221A → T in LQT2. 1 Publication
VAR_068260
Natural varianti427 – 4271Y → S in LQT2. 1 Publication
VAR_068261
Natural varianti436 – 4361T → M in LQT2.
VAR_008916
Natural varianti451 – 4511P → L in LQT2. 1 Publication
VAR_014373
Natural varianti456 – 4561D → Y in LQT2. 1 Publication
VAR_068262
Natural varianti470 – 4701N → D in LQT2; aberrant protein folding increases the association of mutant KCNH2 with CANX and results in defective protein trafficking. 2 Publications
VAR_008578
Natural varianti474 – 4741T → I in LQT2. 1 Publication
VAR_008917
Natural varianti475 – 4751Missing in LQT2. 1 Publication
VAR_068263
Natural varianti490 – 4901A → T in long QT syndrome; bradycardia-induced. 1 Publication
Corresponds to variant rs28928905 [ dbSNP | Ensembl ].
VAR_036671
Natural varianti500 – 5089Missing in LQT2.
VAR_009178
Natural varianti525 – 5251K → N in long QT syndrome 2/3; located on the same allele as Pro-528. 1 Publication
VAR_036672
Natural varianti528 – 5281R → P in long QT syndrome 2/3; located on the same allele as Asn-525. 1 Publication
VAR_036673
Natural varianti531 – 5311R → Q in LQT2.
VAR_009913
Natural varianti534 – 5341R → C in LQT2. 2 Publications
VAR_008579
Natural varianti552 – 5521L → S in LQT2. 1 Publication
VAR_008918
Natural varianti558 – 5581A → P in LQT2. 1 Publication
VAR_008919
Natural varianti561 – 5611A → T in LQT2. 2 Publications
VAR_014374
Natural varianti561 – 5611A → V in LQT2; the mutation reduces wild-type channel expression. 3 Publications
VAR_008580
Natural varianti562 – 5621H → P in LQT2. 1 Publication
VAR_068264
Natural varianti564 – 5641L → P in LQT2.
VAR_008920
Natural varianti569 – 5691Y → H in LQT2. 1 Publication
VAR_008921
Natural varianti571 – 5711I → L in LQT2. 1 Publication
VAR_068265
Natural varianti572 – 5721G → C in LQT2. 1 Publication
VAR_008923
Natural varianti572 – 5721G → R in LQT2; severe form. 1 Publication
VAR_008922
Natural varianti572 – 5721G → S in LQT2. 1 Publication
VAR_068266
Natural varianti582 – 5821R → C in LQT2. 2 Publications
VAR_008581
Natural varianti584 – 5841G → S in LQT2. 2 Publications
VAR_008924
Natural varianti585 – 5851W → C in LQT2.
VAR_009914
Natural varianti588 – 5881N → D in LQT2. 2 Publications
VAR_008925
Natural varianti588 – 5881N → K in SQT1. 2 Publications
VAR_023840
Natural varianti593 – 5931I → R in LQT2. 1 Publication
Corresponds to variant rs28928904 [ dbSNP | Ensembl ].
VAR_008582
Natural varianti593 – 5931I → T in LQT2.
VAR_009915
Natural varianti596 – 5961P → R in LQT2. 1 Publication
VAR_068267
Natural varianti601 – 6011G → S in LQT2. 2 Publications
VAR_008926
Natural varianti604 – 6041G → S in LQT2. 2 Publications
VAR_008927
Natural varianti609 – 6091D → N in LQT2.
VAR_009916
Natural varianti611 – 6111Y → H in LQT2. 1 Publication
VAR_008928
Natural varianti612 – 6121V → L in LQT2. 1 Publication
VAR_008929
Natural varianti613 – 6131T → M in LQT2. 3 Publications
VAR_008930
Natural varianti614 – 6141A → V in LQT2. 4 Publications
VAR_008931
Natural varianti615 – 6151L → V in LQT2.
VAR_014375
Natural varianti622 – 6221L → F in LQT2. 1 Publication
VAR_068268
Natural varianti623 – 6231T → I in LQT2. 1 Publication
VAR_068269
Natural varianti626 – 6261G → S in LQT2.
VAR_014376
Natural varianti627 – 6271F → L in LQT2.
VAR_014377
Natural varianti628 – 6281G → S in LQT2. 2 Publications
VAR_008583
Natural varianti628 – 6281G → V in LQT2. 1 Publication
VAR_068270
Natural varianti629 – 6291N → D in LQT2. 1 Publication
VAR_008932
Natural varianti629 – 6291N → K in LQT2. 1 Publication
VAR_008933
Natural varianti629 – 6291N → S in LQT2. 1 Publication
VAR_009179
Natural varianti630 – 6301V → A in LQT2. 2 Publications
VAR_008935
Natural varianti630 – 6301V → L in LQT2. 1 Publication
VAR_008934
Natural varianti632 – 6321P → S in LQT2.
VAR_014378
Natural varianti633 – 6331N → S in LQT2. 2 Publications
VAR_008936
Natural varianti635 – 6351N → I in LQT2. 1 Publication
VAR_068271
Natural varianti637 – 6371E → K in LQT2. 1 Publication
VAR_014379
Natural varianti638 – 6381K → E in LQT2.
VAR_014380
Natural varianti638 – 6381Missing in LQT2.
VAR_014381
Natural varianti640 – 6401F → L in LQT2. 1 Publication
VAR_008937
Natural varianti640 – 6401F → V in LQT2. 1 Publication
VAR_068272
Natural varianti641 – 6411S → F in LQT2. 1 Publication
VAR_068273
Natural varianti645 – 6451M → L in LQT2.
VAR_014382
Natural varianti671 – 6755Missing in LQT2.
VAR_068274
Natural varianti696 – 6961R → C in long QT syndrome 2/3. 1 Publication
VAR_036674
Natural varianti721 – 7211P → L in LQT2. 1 Publication
VAR_068275
Natural varianti744 – 7441R → P in LQT2; impairs channel function; exhibits reduced activating currents compared to wild-type; cell surface trafficking is not impaired; does not exert dominant-negative effects on wild-type channel; the half-maximal activation voltage is not significantly affected by the mutation. 1 Publication
VAR_068276
Natural varianti752 – 7521R → Q in LQT2. 1 Publication
VAR_036675
Natural varianti752 – 7521R → W in LQT2.
VAR_014383
Natural varianti774 – 7741D → Y in LQT2. 1 Publication
VAR_068277
Natural varianti784 – 7841R → W Predisposes to LQT2 and torsades de pointes while taking the drug amiodarone; in vitro studies confirmed a significant reduction in potassium currents; the ECG abnormalities reversed on drug withdrawal. 2 Publications
VAR_036676
Natural varianti788 – 7881E → D in LQT2. 1 Publication
VAR_068278
Natural varianti805 – 8051F → C in LQT2. 1 Publication
VAR_014384
Natural varianti805 – 8051F → S in LQT2.
VAR_014385
Natural varianti818 – 8181S → L in LQT2. 1 Publication
VAR_008938
Natural varianti820 – 8201G → R in LQT2. 1 Publication
VAR_068279
Natural varianti822 – 8221V → M in LQT2. 2 Publications
VAR_008584
Natural varianti823 – 8231R → W in LQT2.
VAR_014386
Natural varianti837 – 8371D → G in LQT2. 1 Publication
VAR_068280
Natural varianti861 – 8611N → I in LQT2. 1 Publication
VAR_014387
Natural varianti887 – 8871R → H in LQT2. 1 Publication
VAR_068281
Natural varianti897 – 8971K → T.2 Publications
Corresponds to variant rs1805123 [ dbSNP | Ensembl ].
VAR_014388
Natural varianti913 – 9131A → V in LQT2. 1 Publication
VAR_068282
Natural varianti917 – 9171P → L in LQT2.
VAR_014389
Natural varianti922 – 9221R → W in LQT2.
VAR_014390
Natural varianti925 – 9251G → R in LQT2. 1 Publication
VAR_068283
Natural varianti948 – 9481R → C in long QT syndrome 2/3. 1 Publication
VAR_036677
Natural varianti983 – 9831T → I in LQT2. 1 Publication
VAR_068284
Natural varianti996 – 9961N → I in LQT2. 1 Publication
VAR_068285
Natural varianti1016 – 10161P → L.
Corresponds to variant rs41313074 [ dbSNP | Ensembl ].
VAR_036679
Natural varianti1016 – 10161P → S.
Corresponds to variant rs41307280 [ dbSNP | Ensembl ].
VAR_036678
Natural varianti1020 – 10201P → S.
Corresponds to variant rs41307274 [ dbSNP | Ensembl ].
VAR_036680
Natural varianti1026 – 10261P → L.
Corresponds to variant rs41307271 [ dbSNP | Ensembl ].
VAR_036681
Natural varianti1036 – 10361G → D in LQT2. 1 Publication
VAR_068286
Natural varianti1055 – 10551R → Q.
Corresponds to variant rs41307270 [ dbSNP | Ensembl ].
VAR_036682

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 376376MPVRR…EKVTQ → MAAPAGKASRTGALRPRAQK GRVRRAVRISSLVAQE in isoform B.
VSP_000965Add
BLAST
Alternative sequencei1 – 102102MPVRR…FYRKD → MSSHSA in isoform 3.1.
VSP_047877Add
BLAST
Alternative sequencei1 – 3636MPVRR…ANARV → MAAPAGKASRTGALRPRAQK GRVRRAVRISSLVAQE in isoform B-USO.
VSP_047878Add
BLAST
Alternative sequencei37 – 376340Missing in isoform B-USO.
VSP_047879Add
BLAST
Alternative sequencei139 – 19557Missing in isoform 4.
VSP_000966Add
BLAST
Alternative sequencei801 – 88888KNDIF…QRKRK → MGWGAGTGLEMPSAASRGAS LLNMQSLGLWTWDCLQGHWA PLIHLNSGPPSGAMERSPTW GEAAELWGSHILLPFRIRHK QTLFASLK in isoform A-USO and isoform B-USO.
VSP_047880Add
BLAST
Alternative sequencei889 – 1159271Missing in isoform A-USO and isoform B-USO.
VSP_047881Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U04270 mRNA. Translation: AAA62473.1.
AB009071 Genomic DNA. Translation: BAA37096.1.
AB044806 mRNA. Translation: BAB19682.1.
AF363636 mRNA. Translation: AAL37559.1.
AJ512214 mRNA. Translation: CAD54447.1.
AJ609614 mRNA. Translation: CAE82156.1.
FJ938021 mRNA. Translation: ACR24650.1.
DQ784808 Genomic DNA. Translation: ABQ01243.1.
AC006343 Genomic DNA. No translation available.
AC011234 Genomic DNA. No translation available.
CH471173 Genomic DNA. Translation: EAW54072.1.
AJ010538
, AJ010539, AJ010540, AJ010541, AJ010542, AJ010543, AJ010544, AJ010545, AJ010546, AJ010547, AJ010548, AJ010549, AJ010550, AJ010551 Genomic DNA. Translation: CAA09232.1. Sequence problems.
CH471173 Genomic DNA. Translation: EAW54075.1.
BC001914 mRNA. Translation: AAH01914.2.
BC004311 mRNA. Translation: AAH04311.2.
AF052728 mRNA. Translation: AAC69709.1.
CCDSiCCDS47747.1. [Q12809-5]
CCDS5910.1. [Q12809-1]
CCDS5911.1. [Q12809-2]
PIRiI38465.
RefSeqiNP_000229.1. NM_000238.3. [Q12809-1]
NP_001191727.1. NM_001204798.1. [Q12809-6]
NP_742053.1. NM_172056.2. [Q12809-5]
NP_742054.1. NM_172057.2. [Q12809-2]
UniGeneiHs.647099.

Genome annotation databases

EnsembliENST00000262186; ENSP00000262186; ENSG00000055118. [Q12809-1]
ENST00000330883; ENSP00000328531; ENSG00000055118. [Q12809-2]
ENST00000392968; ENSP00000376695; ENSG00000055118. [Q12809-7]
ENST00000430723; ENSP00000387657; ENSG00000055118. [Q12809-5]
GeneIDi3757.
KEGGihsa:3757.
UCSCiuc003wib.3. human. [Q12809-2]
uc003wic.3. human. [Q12809-1]

Polymorphism databases

DMDMi7531135.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Ether-a-go-go potassium channels entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U04270 mRNA. Translation: AAA62473.1 .
AB009071 Genomic DNA. Translation: BAA37096.1 .
AB044806 mRNA. Translation: BAB19682.1 .
AF363636 mRNA. Translation: AAL37559.1 .
AJ512214 mRNA. Translation: CAD54447.1 .
AJ609614 mRNA. Translation: CAE82156.1 .
FJ938021 mRNA. Translation: ACR24650.1 .
DQ784808 Genomic DNA. Translation: ABQ01243.1 .
AC006343 Genomic DNA. No translation available.
AC011234 Genomic DNA. No translation available.
CH471173 Genomic DNA. Translation: EAW54072.1 .
AJ010538
, AJ010539 , AJ010540 , AJ010541 , AJ010542 , AJ010543 , AJ010544 , AJ010545 , AJ010546 , AJ010547 , AJ010548 , AJ010549 , AJ010550 , AJ010551 Genomic DNA. Translation: CAA09232.1 . Sequence problems.
CH471173 Genomic DNA. Translation: EAW54075.1 .
BC001914 mRNA. Translation: AAH01914.2 .
BC004311 mRNA. Translation: AAH04311.2 .
AF052728 mRNA. Translation: AAC69709.1 .
CCDSi CCDS47747.1. [Q12809-5 ]
CCDS5910.1. [Q12809-1 ]
CCDS5911.1. [Q12809-2 ]
PIRi I38465.
RefSeqi NP_000229.1. NM_000238.3. [Q12809-1 ]
NP_001191727.1. NM_001204798.1. [Q12809-6 ]
NP_742053.1. NM_172056.2. [Q12809-5 ]
NP_742054.1. NM_172057.2. [Q12809-2 ]
UniGenei Hs.647099.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1BYW X-ray 2.60 A 26-135 [» ]
1UJL NMR - A 570-611 [» ]
2L0W NMR - A 1-135 [» ]
2L1M NMR - A 1-135 [» ]
2L4R NMR - A 1-135 [» ]
2LE7 NMR - A 532-551 [» ]
4HP9 X-ray 2.12 A 10-135 [» ]
4HQA X-ray 1.96 A 1-135 [» ]
ProteinModelPortali Q12809.
SMRi Q12809. Positions 1-135, 570-662, 670-864.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109959. 20 interactions.
DIPi DIP-48929N.
IntActi Q12809. 6 interactions.
MINTi MINT-1427435.
STRINGi 9606.ENSP00000262186.

Chemistry

BindingDBi Q12809.
ChEMBLi CHEMBL2362996.
DrugBanki DB01118. Amiodarone.
DB00276. Amsacrine.
DB00637. Astemizole.
DB01136. Carvedilol.
DB00604. Cisapride.
DB00204. Dofetilide.
DB01218. Halofantrine.
DB00308. Ibutilide.
DB01100. Pimozide.
DB01182. Propafenone.
DB00908. Quinidine.
DB06144. Sertindole.
DB00489. Sotalol.
DB00342. Terfenadine.
DB00661. Verapamil.
GuidetoPHARMACOLOGYi 572.

Protein family/group databases

TCDBi