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Q12809

- KCNH2_HUMAN

UniProt

Q12809 - KCNH2_HUMAN

Protein

Potassium voltage-gated channel subfamily H member 2

Gene

KCNH2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 169 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      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). 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 – 842101cNMPAdd
    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

    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 2 Publications; Multi-pass membrane protein 2 Publications

    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

    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 2.23 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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. 1 Publication
    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. 2 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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 2PRO_0000053999Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei320 – 3201Phosphoserine2 Publications
    Glycosylationi598 – 5981N-linked (GlcNAc...)1 Publication

    Post-translational modificationi

    Phosphorylated on serine and threonine residues. Phosphorylation by PKA inhibits ion conduction.2 Publications

    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.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself6EBI-720643,EBI-720643

    Protein-protein interaction databases

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

    Structurei

    Secondary structure

    1
    1159
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ12809.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 403403CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini425 – 45026ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini472 – 49524CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini517 – 5204ExtracellularSequence Analysis
    Topological domaini542 – 5476CytoplasmicSequence Analysis
    Topological domaini569 – 61143ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini633 – 6386ExtracellularSequence Analysis
    Topological domaini660 – 1159500CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei612 – 63221Pore-forming; Name=Segment H5Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei404 – 42421Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei451 – 47121Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei496 – 51621Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei521 – 54121Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei548 – 56821Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei639 – 65921Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini41 – 7030PASPROSITE-ProRule annotationAdd
    BLAST
    Domaini92 – 14453PACPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi624 – 6296Selectivity filterBy 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

    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.
    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.

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    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. 1 Publication
    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. 2 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 ].