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O43526

- KCNQ2_HUMAN

UniProt

O43526 - KCNQ2_HUMAN

Protein

Potassium voltage-gated channel subfamily KQT member 2

Gene

KCNQ2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 157 (01 Oct 2014)
      Sequence version 2 (01 Jun 2001)
      Previous versions | rss
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    Functioni

    Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors.

    GO - Molecular functioni

    1. ankyrin binding Source: BHF-UCL
    2. delayed rectifier potassium channel activity Source: RefGenome
    3. potassium channel activity Source: ProtInc
    4. voltage-gated potassium channel activity Source: ProtInc

    GO - Biological processi

    1. axon guidance Source: Reactome
    2. nervous system development Source: ProtInc
    3. potassium ion transport Source: ProtInc
    4. synaptic transmission Source: Reactome
    5. transmission of nerve impulse Source: Ensembl

    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_22266. Interaction between L1 and Ankyrins.
    REACT_75770. Voltage gated Potassium channels.

    Protein family/group databases

    TCDBi1.A.1.15.2. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Potassium voltage-gated channel subfamily KQT member 2
    Alternative name(s):
    KQT-like 2
    Neuroblastoma-specific potassium channel subunit alpha KvLQT2
    Voltage-gated potassium channel subunit Kv7.2
    Gene namesi
    Name:KCNQ2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:6296. KCNQ2.

    Subcellular locationi

    GO - Cellular componenti

    1. axon initial segment Source: BHF-UCL
    2. node of Ranvier Source: BHF-UCL
    3. plasma membrane Source: BHF-UCL
    4. voltage-gated potassium channel complex Source: ProtInc

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200]: A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti207 – 2071R → W in BFNS1; phenotype manifestations include myokymia in some patients; leads to a shift of voltage-dependent activation of the channel and a dramatic slowing of activation upon depolarization. 1 Publication
    VAR_026987
    Natural varianti208 – 2081M → V in BFNS1; minor effect on maximal current but clearly exhibits a faster rate of deactivation. 1 Publication
    VAR_026988
    Natural varianti214 – 2141R → W in BFNS1. 1 Publication
    Corresponds to variant rs28939684 [ dbSNP | Ensembl ].
    VAR_010929
    Natural varianti228 – 2281H → Q in BFNS1. 1 Publication
    VAR_026989
    Natural varianti243 – 2431L → F in BFNS1. 1 Publication
    VAR_026990
    Natural varianti284 – 2841Y → C in BFNS1; 30%-60% reduction of wt heteromeric current. Ratio 1:1 or 20%-30%; ratio of 1:1:2. 2 Publications
    Corresponds to variant rs28939683 [ dbSNP | Ensembl ].
    VAR_010930
    Natural varianti306 – 3061A → T in BFNS1; 20%-40% reduction of wt heteromeric current. Ratio of 1:1:2. 2 Publications
    VAR_010931
    Natural varianti333 – 3331R → Q in BFNS1; moderate effect; less than 50% reduction in current compared with wt heteromeric channels. 1 Publication
    VAR_026992
    Natural varianti554 – 5541K → N in BFNS1 and EIEE7; decreases the voltage-dependence of the channel. 1 Publication
    VAR_026993
    Epileptic encephalopathy, early infantile, 7 (EIEE7) [MIM:613720]: An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti247 – 2471S → W in EIEE7; reduces channel currents by more than 50% in homomeric channels. 1 Publication
    VAR_026991
    Natural varianti554 – 5541K → N in BFNS1 and EIEE7; decreases the voltage-dependence of the channel. 1 Publication
    VAR_026993

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi52 – 521S → E: 40% increase in potassium current amplitude. Ratio of 1:1. 1 Publication
    Mutagenesisi52 – 521S → Q: Decrease of PKA stimulation. Ratio of 1:1. 1 Publication
    Mutagenesisi217 – 2171T → A: No effect on current or expression. 1 Publication
    Mutagenesisi217 – 2171T → D: Abolishes currents without reducing channel protein expression. 1 Publication
    Mutagenesisi279 – 2791G → S: More than 50% reduction of wt heteromeric current. Ratio of 1:1 and 1:1:2. 1 Publication

    Keywords - Diseasei

    Disease mutation, Epilepsy, Mental retardation

    Organism-specific databases

    MIMi121200. phenotype.
    613720. phenotype.
    Orphaneti306. Benign familial infantile seizures.
    1949. Benign familial neonatal seizures.
    140927. Benign familial neonatal-infantile seizures.
    1934. Early infantile epileptic encephalopathy.
    PharmGKBiPA30074.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 872872Potassium voltage-gated channel subfamily KQT member 2PRO_0000054030Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei52 – 521Phosphoserine; by PKA1 Publication
    Modified residuei217 – 2171Phosphothreonine1 Publication

    Post-translational modificationi

    In Xenopus oocytes KCNQ2/KCNQ3 heteromeric current can be increased by intracellular cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the N-terminal region.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiO43526.
    PRIDEiO43526.

    PTM databases

    PhosphoSiteiO43526.

    Expressioni

    Tissue specificityi

    In adult and fetal brain. Highly expressed in areas containing neuronal cell bodies, low in spinal chord and corpus callosum. Isoform 2 is preferentially expressed in differentiated neurons. Isoform 6 is prominent in fetal brain, undifferentiated neuroblastoma cells and brain tumors.1 Publication

    Gene expression databases

    ArrayExpressiO43526.
    BgeeiO43526.
    CleanExiHS_KCNQ2.
    GenevestigatoriO43526.

    Organism-specific databases

    HPAiHPA016642.

    Interactioni

    Subunit structurei

    Heteromultimer with KCNQ3. May associate with KCNE2.

    Protein-protein interaction databases

    BioGridi109986. 5 interactions.
    IntActiO43526. 1 interaction.
    MINTiMINT-8402812.
    STRINGi9606.ENSP00000352035.

    Structurei

    3D structure databases

    ProteinModelPortaliO43526.
    SMRiO43526. Positions 65-316.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini113 – 12210ExtracellularSequence Analysis
    Topological domaini144 – 16623CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini188 – 1958ExtracellularSequence Analysis
    Topological domaini219 – 23113CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini253 – 26412ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini286 – 2916ExtracellularSequence Analysis
    Topological domaini313 – 872560CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei265 – 28521Pore-forming; Name=Segment H5Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei92 – 11221Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei123 – 14321Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei167 – 18721Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei196 – 21823Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei232 – 25221Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei292 – 31221Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi277 – 2826Selectivity filterBy similarity

    Domaini

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

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1226.
    HOVERGENiHBG059014.
    KOiK04927.
    OrthoDBiEOG73804Z.
    PhylomeDBiO43526.
    TreeFamiTF315186.

    Family and domain databases

    InterProiIPR020969. Ankyrin-G_BS.
    IPR005821. Ion_trans_dom.
    IPR003091. K_chnl.
    IPR003937. K_chnl_volt-dep_KCNQ.
    IPR003947. K_chnl_volt-dep_KCNQ2.
    IPR013821. K_chnl_volt-dep_KCNQ_C.
    IPR028325. VG_K_chnl.
    [Graphical view]
    PANTHERiPTHR11537. PTHR11537. 1 hit.
    PfamiPF00520. Ion_trans. 1 hit.
    PF03520. KCNQ_channel. 1 hit.
    PF11956. KCNQC3-Ank-G_bd. 1 hit.
    [Graphical view]
    PRINTSiPR00169. KCHANNEL.
    PR01461. KCNQ2CHANNEL.
    PR01459. KCNQCHANNEL.

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: O43526-1) [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

    MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR    50
    GSILSKPRAG GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF 100
    LLVFSCLVLS VFSTIKEYEK SSEGALYILE IVTIVVFGVE YFVRIWAAGC 150
    CCRYRGWRGR LKFARKPFCV IDIMVLIASI AVLAAGSQGN VFATSALRSL 200
    RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF LCLILASFLV 250
    YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 300
    GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN 350
    LSRTDLHSTW QYYERTVTVP MYSSQTQTYG ASRLIPPLNQ LELLRNLKSK 400
    SGLAFRKDPP PEPSPSKGSP CRGPLCGCCP GRSSQKVSLK DRVFSSPRGV 450
    AAKGKGSPQA QTVRRSPSAD QSLEDSPSKV PKSWSFGDRS RARQAFRIKG 500
    AASRQNSEEA SLPGEDIVDD KSCPCEFVTE DLTPGLKVSI RAVCVMRFLV 550
    SKRKFKESLR PYDVMDVIEQ YSAGHLDMLS RIKSLQSRVD QIVGRGPAIT 600
    DKDRTKGPAE AELPEDPSMM GRLGKVEKQV LSMEKKLDFL VNIYMQRMGI 650
    PPTETEAYFG AKEPEPAPPY HSPEDSREHV DRHGCIVKIV RSSSSTGQKN 700
    FSAPPAAPPV QCPPSTSWQP QSHPRQGHGT SPVGDHGSLV RIPPPPAHER 750
    SLSAYGGGNR ASMEFLRQED TPGCRPPEGN LRDSDTSISI PSVDHEELER 800
    SFSGFSISQS KENLDALNSC YAAVAPCAKV RPYIAEGESD TDSDLCTPCG 850
    PPPRSATGEG PFGDVGWAGP RK 872
    Length:872
    Mass (Da):95,848
    Last modified:June 1, 2001 - v2
    Checksum:i22E8A0880A27B58C
    GO
    Isoform 2 (identifier: O43526-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         417-434: Missing.

    Show »
    Length:854
    Mass (Da):94,100
    Checksum:iCF3F5EC2E23E21FC
    GO
    Isoform 3 (identifier: O43526-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         373-382: Missing.
         417-434: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Show »
    Length:844
    Mass (Da):93,089
    Checksum:i5228E1B8C3D8C17F
    GO
    Isoform 4 (identifier: O43526-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         417-446: Missing.
         509-509: Missing.

    Show »
    Length:841
    Mass (Da):92,596
    Checksum:i065E37AF63726B10
    GO
    Isoform 5 (identifier: O43526-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         310-320: Missing.
         417-434: Missing.

    Show »
    Length:843
    Mass (Da):93,057
    Checksum:iAF6F5146789F4167
    GO
    Isoform 6 (identifier: O43526-6) [UniParc]FASTAAdd to Basket

    Also known as: HNSPC

    The sequence of this isoform differs from the canonical sequence as follows:
         373-393: SSQTQTYGASRLIPPLNQLEL → RYRRRAPATKQLFHFLFSICS
         394-872: Missing.

    Show »
    Length:393
    Mass (Da):44,261
    Checksum:i9415BC4FC2F84675
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti699 – 6991K → E in AAD16988. (PubMed:9836639)Curated
    Sequence conflicti854 – 8541R → C in AAD16988. (PubMed:9836639)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti207 – 2071R → Q in a patient with isolated myokymia and no history of neonatal seizures; leads to a shift of voltage-dependent activation. 1 Publication
    VAR_043819
    Natural varianti207 – 2071R → W in BFNS1; phenotype manifestations include myokymia in some patients; leads to a shift of voltage-dependent activation of the channel and a dramatic slowing of activation upon depolarization. 1 Publication
    VAR_026987
    Natural varianti208 – 2081M → V in BFNS1; minor effect on maximal current but clearly exhibits a faster rate of deactivation. 1 Publication
    VAR_026988
    Natural varianti214 – 2141R → W in BFNS1. 1 Publication
    Corresponds to variant rs28939684 [ dbSNP | Ensembl ].
    VAR_010929
    Natural varianti228 – 2281H → Q in BFNS1. 1 Publication
    VAR_026989
    Natural varianti243 – 2431L → F in BFNS1. 1 Publication
    VAR_026990
    Natural varianti247 – 2471S → W in EIEE7; reduces channel currents by more than 50% in homomeric channels. 1 Publication
    VAR_026991
    Natural varianti284 – 2841Y → C in BFNS1; 30%-60% reduction of wt heteromeric current. Ratio 1:1 or 20%-30%; ratio of 1:1:2. 2 Publications
    Corresponds to variant rs28939683 [ dbSNP | Ensembl ].
    VAR_010930
    Natural varianti306 – 3061A → T in BFNS1; 20%-40% reduction of wt heteromeric current. Ratio of 1:1:2. 2 Publications
    VAR_010931
    Natural varianti333 – 3331R → Q in BFNS1; moderate effect; less than 50% reduction in current compared with wt heteromeric channels. 1 Publication
    VAR_026992
    Natural varianti554 – 5541K → N in BFNS1 and EIEE7; decreases the voltage-dependence of the channel. 1 Publication
    VAR_026993
    Natural varianti780 – 7801N → T.1 Publication
    Corresponds to variant rs1801475 [ dbSNP | Ensembl ].
    VAR_010932

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei310 – 32011Missing in isoform 5. 1 PublicationVSP_000984Add
    BLAST
    Alternative sequencei373 – 39321SSQTQ…NQLEL → RYRRRAPATKQLFHFLFSIC S in isoform 6. 2 PublicationsVSP_000986Add
    BLAST
    Alternative sequencei373 – 38210Missing in isoform 3. 1 PublicationVSP_000985
    Alternative sequencei394 – 872479Missing in isoform 6. 2 PublicationsVSP_000987Add
    BLAST
    Alternative sequencei417 – 44630Missing in isoform 4. 1 PublicationVSP_000989Add
    BLAST
    Alternative sequencei417 – 43418Missing in isoform 2, isoform 3 and isoform 5. 3 PublicationsVSP_000988Add
    BLAST
    Alternative sequencei509 – 5091Missing in isoform 4. 1 PublicationVSP_000990

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D82346 mRNA. Translation: BAA11557.1.
    AF033348 mRNA. Translation: AAB97315.1.
    Y15065 mRNA. Translation: CAA75348.1.
    AF110020 mRNA. Translation: AAD16988.1.
    AF074247 mRNA. Translation: AAC25921.1.
    AL353658, AL121827, AL121829 Genomic DNA. Translation: CAH72958.1.
    AL353658, AL121827, AL121829 Genomic DNA. Translation: CAH72959.1.
    AL121827, AL121829, AL353658 Genomic DNA. Translation: CAI95054.1.
    AL121829, AL121827, AL353658 Genomic DNA. Translation: CAI95740.1.
    AL121829, AL121827, AL353658 Genomic DNA. Translation: CAI95744.1.
    BC000699 mRNA. Translation: AAH00699.1.
    CCDSiCCDS13518.1. [O43526-3]
    CCDS13519.1. [O43526-2]
    CCDS13520.1. [O43526-1]
    CCDS13521.1. [O43526-6]
    CCDS46629.1. [O43526-4]
    PIRiJC5275.
    RefSeqiNP_004509.2. NM_004518.4. [O43526-3]
    NP_742104.1. NM_172106.1. [O43526-2]
    NP_742105.1. NM_172107.2. [O43526-1]
    NP_742106.1. NM_172108.3. [O43526-4]
    NP_742107.1. NM_172109.1. [O43526-6]
    UniGeneiHs.161851.
    Hs.652468.

    Genome annotation databases

    EnsembliENST00000344425; ENSP00000345523; ENSG00000075043. [O43526-6]
    ENST00000344462; ENSP00000339611; ENSG00000075043. [O43526-4]
    ENST00000357249; ENSP00000349789; ENSG00000075043. [O43526-2]
    ENST00000359125; ENSP00000352035; ENSG00000075043. [O43526-1]
    ENST00000360480; ENSP00000353668; ENSG00000075043. [O43526-3]
    GeneIDi3785.
    KEGGihsa:3785.
    UCSCiuc002yey.1. human. [O43526-1]
    uc002yez.1. human. [O43526-4]
    uc002yfa.1. human. [O43526-2]
    uc002yfb.1. human. [O43526-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D82346 mRNA. Translation: BAA11557.1 .
    AF033348 mRNA. Translation: AAB97315.1 .
    Y15065 mRNA. Translation: CAA75348.1 .
    AF110020 mRNA. Translation: AAD16988.1 .
    AF074247 mRNA. Translation: AAC25921.1 .
    AL353658 , AL121827 , AL121829 Genomic DNA. Translation: CAH72958.1 .
    AL353658 , AL121827 , AL121829 Genomic DNA. Translation: CAH72959.1 .
    AL121827 , AL121829 , AL353658 Genomic DNA. Translation: CAI95054.1 .
    AL121829 , AL121827 , AL353658 Genomic DNA. Translation: CAI95740.1 .
    AL121829 , AL121827 , AL353658 Genomic DNA. Translation: CAI95744.1 .
    BC000699 mRNA. Translation: AAH00699.1 .
    CCDSi CCDS13518.1. [O43526-3 ]
    CCDS13519.1. [O43526-2 ]
    CCDS13520.1. [O43526-1 ]
    CCDS13521.1. [O43526-6 ]
    CCDS46629.1. [O43526-4 ]
    PIRi JC5275.
    RefSeqi NP_004509.2. NM_004518.4. [O43526-3 ]
    NP_742104.1. NM_172106.1. [O43526-2 ]
    NP_742105.1. NM_172107.2. [O43526-1 ]
    NP_742106.1. NM_172108.3. [O43526-4 ]
    NP_742107.1. NM_172109.1. [O43526-6 ]
    UniGenei Hs.161851.
    Hs.652468.

    3D structure databases

    ProteinModelPortali O43526.
    SMRi O43526. Positions 65-316.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109986. 5 interactions.
    IntActi O43526. 1 interaction.
    MINTi MINT-8402812.
    STRINGi 9606.ENSP00000352035.

    Chemistry

    BindingDBi O43526.
    ChEMBLi CHEMBL2362996.
    DrugBanki DB00321. Amitriptyline.
    GuidetoPHARMACOLOGYi 561.

    Protein family/group databases

    TCDBi 1.A.1.15.2. the voltage-gated ion channel (vic) superfamily.

    PTM databases

    PhosphoSitei O43526.

    Proteomic databases

    PaxDbi O43526.
    PRIDEi O43526.

    Protocols and materials databases

    DNASUi 3785.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000344425 ; ENSP00000345523 ; ENSG00000075043 . [O43526-6 ]
    ENST00000344462 ; ENSP00000339611 ; ENSG00000075043 . [O43526-4 ]
    ENST00000357249 ; ENSP00000349789 ; ENSG00000075043 . [O43526-2 ]
    ENST00000359125 ; ENSP00000352035 ; ENSG00000075043 . [O43526-1 ]
    ENST00000360480 ; ENSP00000353668 ; ENSG00000075043 . [O43526-3 ]
    GeneIDi 3785.
    KEGGi hsa:3785.
    UCSCi uc002yey.1. human. [O43526-1 ]
    uc002yez.1. human. [O43526-4 ]
    uc002yfa.1. human. [O43526-2 ]
    uc002yfb.1. human. [O43526-3 ]

    Organism-specific databases

    CTDi 3785.
    GeneCardsi GC20M062038.
    GeneReviewsi KCNQ2.
    HGNCi HGNC:6296. KCNQ2.
    HPAi HPA016642.
    MIMi 121200. phenotype.
    602235. gene.
    613720. phenotype.
    neXtProti NX_O43526.
    Orphaneti 306. Benign familial infantile seizures.
    1949. Benign familial neonatal seizures.
    140927. Benign familial neonatal-infantile seizures.
    1934. Early infantile epileptic encephalopathy.
    PharmGKBi PA30074.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1226.
    HOVERGENi HBG059014.
    KOi K04927.
    OrthoDBi EOG73804Z.
    PhylomeDBi O43526.
    TreeFami TF315186.

    Enzyme and pathway databases

    Reactomei REACT_22266. Interaction between L1 and Ankyrins.
    REACT_75770. Voltage gated Potassium channels.

    Miscellaneous databases

    ChiTaRSi KCNQ2. human.
    GeneWikii KvLQT2.
    GenomeRNAii 3785.
    NextBioi 14859.
    PROi O43526.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43526.
    Bgeei O43526.
    CleanExi HS_KCNQ2.
    Genevestigatori O43526.

    Family and domain databases

    InterProi IPR020969. Ankyrin-G_BS.
    IPR005821. Ion_trans_dom.
    IPR003091. K_chnl.
    IPR003937. K_chnl_volt-dep_KCNQ.
    IPR003947. K_chnl_volt-dep_KCNQ2.
    IPR013821. K_chnl_volt-dep_KCNQ_C.
    IPR028325. VG_K_chnl.
    [Graphical view ]
    PANTHERi PTHR11537. PTHR11537. 1 hit.
    Pfami PF00520. Ion_trans. 1 hit.
    PF03520. KCNQ_channel. 1 hit.
    PF11956. KCNQC3-Ank-G_bd. 1 hit.
    [Graphical view ]
    PRINTSi PR00169. KCHANNEL.
    PR01461. KCNQ2CHANNEL.
    PR01459. KCNQCHANNEL.
    ProtoNeti Search...

    Publicationsi

    1. "Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles."
      Yokoyama M., Nishi Y., Yoshii J., Okubo K., Matsubara K.
      DNA Res. 3:311-320(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
      Tissue: Neuroblastoma.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS BFNS1 CYS-284 AND THR-306.
      Tissue: Brain, Fetal brain and Temporal cortex.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
      Tissue: Fetal brain.
    4. "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel."
      Wang H.-S., Pan Z., Shi W., Brown B.S., Wymore R.S., Cohen I.S., Dixon J.E., McKinnon D.
      Science 282:1890-1893(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
    5. "The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3."
      Tinel N., Lauritzen I., Chouabe C., Lazdunski M., Borsotto M.
      FEBS Lett. 438:171-176(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 5).
    6. "Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy."
      Yang W.-P., Levesque P.C., Little W.A., Conder M.L., Ramakrishnan P., Neubauer M.G., Blanar M.A.
      J. Biol. Chem. 273:19419-19423(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
      Tissue: Brain and Fetal brain.
    7. "Differential expression of KCNQ2 splice variants: implications to M current function during neuronal development."
      Smith J.S., Iannotti C.A., Dargis P.G., Christian E.P., Aiyar J.
      J. Neurosci. 21:1096-1103(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Brain.
    8. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
      Tissue: Eye.
    10. "Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy."
      Schroeder B.C., Kubisch C., Stein V., Jentsch T.J.
      Nature 396:687-690(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF SER-52 AND GLY-279, PHOSPHORYLATION AT SER-52, CHARACTERIZATION OF VARIANTS CYS-284 AND THR-306.
    11. "Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell."
      Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Delmas P., Buckley N.J., London B., Brown D.A.
      J. Neurosci. 19:7742-7756(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN M-LIKE CURRENT.
    12. "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit."
      Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M.
      FEBS Lett. 480:137-141(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH KCNE2.
    13. "Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy."
      Schwake M., Pusch M., Kharkovets T., Jentsch T.J.
      J. Biol. Chem. 275:13343-13348(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SURFACE EXPRESSION OF HETEROMERS.
    14. "Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current."
      Shapiro M.S., Roche J.P., Kaftan E.J., Cruzblanca H., Mackie K., Hille B.
      J. Neurosci. 20:1710-1721(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
    15. "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors."
      Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Jentsch T.J., Brown D.A.
      J. Physiol. (Lond.) 522:349-355(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
    16. "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine."
      Main M.J., Cryan J.E., Dupere J.R., Cox B., Clare J.J., Burbidge S.A.
      Mol. Pharmacol. 58:253-262(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVATION BY RETICABINE.
    17. "Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels."
      Wickenden A.D., Yu W., Zou A., Jegla T., Wagoner P.K.
      Mol. Pharmacol. 58:591-600(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVATION BY RETICABINE.
    18. "The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transfected with human KCNQ2/3 subunits."
      Rundfeldt C., Netzer R.
      Neurosci. Lett. 282:73-76(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVATION BY RETICABINE.
    19. "Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy."
      Cooper E.C., Aldape K.D., Abosch A., Barbaro N.M., Berger M.S., Peacock W.S., Jan Y.N., Jan L.Y.
      Proc. Natl. Acad. Sci. U.S.A. 97:4914-4919(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, BIOCHEMICAL CHARACTERIZATION.
    20. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
    21. "Identification by mass spectrometry and functional characterization of two phosphorylation sites of KCNQ2/KCNQ3 channels."
      Surti T.S., Huang L., Jan Y.N., Jan L.Y., Cooper E.C.
      Proc. Natl. Acad. Sci. U.S.A. 102:17828-17833(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-217, MUTAGENESIS OF THR-217.
    22. "Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions."
      Biervert C., Steinlein O.K.
      Hum. Genet. 104:234-240(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT THR-780.
    23. "Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor."
      Miraglia del Giudice E., Coppola G., Scuccimarra G., Cirillo G., Bellini G., Pascotto A.
      Eur. J. Hum. Genet. 8:994-997(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT BFNS1 TRP-214.
    24. "Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel."
      Dedek K., Kunath B., Kananura C., Reuner U., Jentsch T.J., Steinlein O.K.
      Proc. Natl. Acad. Sci. U.S.A. 98:12272-12277(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT BFNS1 TRP-207, CHARACTERIZATION OF VARIANT BFNS1 TRP-207.
    25. "KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum."
      The BFNC physician consortium
      Singh N.A., Westenskow P., Charlier C., Pappas C., Leslie J., Dillon J., Anderson V.E., Sanguinetti M.C., Leppert M.F.
      Brain 126:2726-2737(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS BFNS1 VAL-208; GLN-228; PHE-243; CYS-284; THR-306 AND GLN-333, CHARACTERIZATION OF VARIANTS BFNS1 VAL-208 AND GLN-333.
    26. "Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2."
      Dedek K., Fusco L., Teloy N., Steinlein O.K.
      Epilepsy Res. 54:21-27(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT EIEE7 TRP-247, CHARACTERIZATION OF VARIANT EIEE7 TRP-247.
    27. Cited for: VARIANT BFNS1 ASN-554, VARIANT EIEE7 ASN-554, CHARACTERIZATION OF VARIANT BFNS1 ASN-554.
    28. "Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations."
      Wuttke T.V., Jurkat-Rott K., Paulus W., Garncarek M., Lehmann-Horn F., Lerche H.
      Neurology 69:2045-2053(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT GLN-207, CHARACTERIZATION OF VARIANT GLN-207.

    Entry informationi

    Entry nameiKCNQ2_HUMAN
    AccessioniPrimary (citable) accession number: O43526
    Secondary accession number(s): O43796
    , O75580, O95845, Q4VXP4, Q4VXR6, Q5VYT8, Q96J59, Q99454
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 2001
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 157 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Inclusion of isoform 6 in heteromultimers results in attenuation of potassium current. Prominent expression of isoform 6 in the developing brain may alter firing repertoires of immature neurons excitability to provide cues for proliferation rather than differentiation.
    Mutagenesis experiments were carried out in Xenopus oocytes by coexpression of either KCNQ2(mut) and KCNQ3 at the ratio of 1:1, or of KCNQ2(mut), KCNQ2(wt) and KCNQ3 at the ratio of 1:1:2, to mimic the situation in a heterozygous patient with BFNC1 disease.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3