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Q14654

- KCJ11_HUMAN

UniProt

Q14654 - KCJ11_HUMAN

Protein

ATP-sensitive inward rectifier potassium channel 11

Gene

KCNJ11

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 (27 Sep 2005)
      Previous versions | rss
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    Functioni

    This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium By similarity. Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.By similarity2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei160 – 1601Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity

    GO - Molecular functioni

    1. ankyrin binding Source: BHF-UCL
    2. ATP-activated inward rectifier potassium channel activity Source: BHF-UCL
    3. ATP binding Source: BHF-UCL
    4. ion channel binding Source: BHF-UCL
    5. potassium ion binding Source: BHF-UCL
    6. voltage-gated potassium channel activity Source: BHF-UCL

    GO - Biological processi

    1. cellular response to glucose stimulus Source: Ensembl
    2. cellular response to nicotine Source: Ensembl
    3. cellular response to tumor necrosis factor Source: Ensembl
    4. energy reserve metabolic process Source: Reactome
    5. glucose metabolic process Source: BHF-UCL
    6. negative regulation of insulin secretion Source: BHF-UCL
    7. neurological system process Source: BHF-UCL
    8. positive regulation of cation channel activity Source: Ensembl
    9. potassium ion import Source: BHF-UCL
    10. potassium ion transmembrane transport Source: BHF-UCL
    11. regulation of insulin secretion Source: BHF-UCL
    12. regulation of membrane potential Source: BHF-UCL
    13. response to ATP Source: BHF-UCL
    14. response to drug Source: BHF-UCL
    15. response to estradiol Source: Ensembl
    16. response to ischemia Source: Ensembl
    17. response to testosterone Source: Ensembl
    18. small molecule metabolic process Source: Reactome
    19. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel, Voltage-gated channel

    Keywords - Biological processi

    Ion transport, Potassium transport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_18325. Regulation of insulin secretion.
    REACT_75775. ATP sensitive Potassium channels.
    SignaLinkiQ14654.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    ATP-sensitive inward rectifier potassium channel 11
    Alternative name(s):
    IKATP
    Inward rectifier K(+) channel Kir6.2
    Potassium channel, inwardly rectifying subfamily J member 11
    Gene namesi
    Name:KCNJ11
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:6257. KCNJ11.

    Subcellular locationi

    GO - Cellular componenti

    1. ATP-sensitive potassium channel complex Source: BHF-UCL
    2. axolemma Source: Ensembl
    3. cell body fiber Source: Ensembl
    4. cytosol Source: Ensembl
    5. endoplasmic reticulum Source: Ensembl
    6. endosome Source: Ensembl
    7. integral component of plasma membrane Source: ProtInc
    8. intercalated disc Source: Ensembl
    9. mitochondrion Source: Ensembl
    10. myelin sheath Source: Ensembl
    11. neuronal cell body Source: Ensembl
    12. nuclear envelope Source: Ensembl
    13. plasma membrane Source: BHF-UCL
    14. T-tubule Source: BHF-UCL
    15. voltage-gated potassium channel complex Source: BHF-UCL

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Familial hyperinsulinemic hypoglycemia 2 (HHF2) [MIM:601820]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.10 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341R → H in HHF2. 1 Publication
    VAR_031329
    Natural varianti40 – 401G → D in HHF2. 1 Publication
    VAR_031330
    Natural varianti55 – 551F → L in HHF2; does neither affect channel expression nor channel response to MgADP. 1 Publication
    VAR_031335
    Natural varianti67 – 671K → N in HHF2. 1 Publication
    VAR_026506
    Natural varianti91 – 911W → R in HHF2. 1 Publication
    VAR_026507
    Natural varianti101 – 1011A → D in HHF2. 2 Publications
    VAR_031336
    Natural varianti116 – 1161S → P in HHF2. 1 Publication
    VAR_031337
    Natural varianti134 – 1341G → A in HHF2. 1 Publication
    VAR_031338
    Natural varianti136 – 1361R → L in HHF2. 2 Publications
    VAR_031339
    Natural varianti147 – 1471L → P in HHF2. 2 Publications
    Corresponds to variant rs28936678 [ dbSNP | Ensembl ].
    VAR_001557
    Natural varianti254 – 2541P → L in HHF2; impairs trafficking of the mutant channel. 1 Publication
    VAR_026513
    Natural varianti259 – 2591H → R in HHF2; impairs trafficking and abolishes channel function. 1 Publication
    VAR_031345
    Natural varianti266 – 2661P → L in HHF2. 1 Publication
    VAR_031346
    Natural varianti301 – 3011R → H in HHF2. 2 Publications
    VAR_031347
    Diabetes mellitus, permanent neonatal (PNDM) [MIM:606176]: A rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.8 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti35 – 351F → L in PNDM. 1 Publication
    VAR_026498
    Natural varianti35 – 351F → V in PNDM. 1 Publication
    VAR_026499
    Natural varianti46 – 461H → Y in PNDM; one patient with mild dysmorphic features. 2 Publications
    VAR_031332
    Natural varianti50 – 501R → P in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current; one patient with developmental delay. 2 Publications
    VAR_026500
    Natural varianti50 – 501R → Q in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 Publications
    VAR_031333
    Natural varianti52 – 521Q → R in PNDM; with developmental delay and epilepsy; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201. 2 Publications
    VAR_026501
    Natural varianti53 – 531G → D in PNDM; with developmental delay and epilepsy. 1 Publication
    VAR_031334
    Natural varianti53 – 531G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026502
    Natural varianti53 – 531G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026503
    Natural varianti59 – 591V → G in PNDM; with developmental delay and epilepsy; with neurologic features; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201; decreases ATP sensitivity indirectly by favoring the open conformation of the channel. 2 Publications
    VAR_026504
    Natural varianti59 – 591V → M in PNDM; four patients with developmental delay and muscle weakness. 5 Publications
    VAR_026505
    Natural varianti164 – 1641L → P in PNDM. 2 Publications
    VAR_031341
    Natural varianti166 – 1661C → Y in PNDM; individual also diagnosed with West syndrome. 1 Publication
    VAR_031342
    Natural varianti170 – 1701K → N in PNDM. 1 Publication
    VAR_026508
    Natural varianti170 – 1701K → R in PNDM. 1 Publication
    VAR_026509
    Natural varianti170 – 1701K → T in PNDM. 1 Publication
    VAR_031343
    Natural varianti201 – 2011R → C in PNDM; two individuals with developmental delay; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59. 5 Publications
    VAR_026511
    Natural varianti201 – 2011R → H in PNDM; ability of ATP to block mutant channels greatly reduced. 5 Publications
    VAR_026512
    Natural varianti201 – 2011R → L in PNDM. 1 Publication
    VAR_031344
    Natural varianti296 – 2961I → L in PNDM; with developmental delay and epilepsy. 2 Publications
    VAR_026514
    Natural varianti322 – 3221E → K in PNDM. 1 Publication
    VAR_026515
    Natural varianti330 – 3301Y → C in PNDM. 2 Publications
    VAR_026516
    Natural varianti330 – 3301Y → S in PNDM. 1 Publication
    VAR_031348
    Natural varianti333 – 3331F → I in PNDM; alters gating characteristics, decreases sensitivity to inhibition by ATP and increases intrinsic open probability. 1 Publication
    VAR_026517
    Transient neonatal diabetes mellitus 3 (TNDM3) [MIM:610582]: Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. In a significant number of patients with transient neonatal diabetes mellitus, diabetes type 2 appears later in life. The onset and severity of TNDM3 is variable with childhood-onset diabetes, gestational diabetes or adult-onset diabetes described.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti42 – 421C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. 1 Publication
    VAR_031331
    Natural varianti53 – 531G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026502
    Natural varianti53 – 531G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026503
    Natural varianti182 – 1821I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026510
    Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2.

    Keywords - Diseasei

    Diabetes mellitus, Disease mutation

    Organism-specific databases

    MIMi601820. phenotype.
    606176. phenotype.
    610582. phenotype.
    Orphaneti276580. Autosomal dominant hyperinsulinism due to Kir6.2 deficiency.
    79644. Autosomal recessive hyperinsulinism due to Kir6.2 deficiency.
    79134. DEND syndrome.
    276603. Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency.
    552. MODY syndrome.
    99885. Permanent neonatal diabetes mellitus.
    99886. Transient neonatal diabetes mellitus.
    PharmGKBiPA217.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 390390ATP-sensitive inward rectifier potassium channel 11PRO_0000154957Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei341 – 3411Phosphothreonine; by MAPK11 Publication
    Modified residuei385 – 3851Phosphoserine; by MAPK11 Publication

    Post-translational modificationi

    Phosphorylation by MAPK1 results in changes in channel gating that destabilize the closed states and reduce the ATP sensitivity.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ14654.
    PRIDEiQ14654.

    PTM databases

    PhosphoSiteiQ14654.

    Expressioni

    Gene expression databases

    ArrayExpressiQ14654.
    BgeeiQ14654.
    CleanExiHS_KCNJ11.
    GenevestigatoriQ14654.

    Organism-specific databases

    HPAiHPA048891.

    Interactioni

    Subunit structurei

    Interacts with ABCC8/SUR. Interacts with ABCC9/SUR2.2 Publications

    Protein-protein interaction databases

    DIPiDIP-58643N.
    IntActiQ14654. 1 interaction.
    STRINGi9606.ENSP00000345708.

    Structurei

    3D structure databases

    ProteinModelPortaliQ14654.
    SMRiQ14654. Positions 32-356.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 6868CytoplasmicBy similarityAdd
    BLAST
    Topological domaini94 – 11623ExtracellularBy similarityAdd
    BLAST
    Topological domaini136 – 1449ExtracellularBy similarity
    Topological domaini167 – 390224CytoplasmicBy similarityAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei117 – 12812Helical; Pore-forming; Name=H5By similarityAdd
    BLAST
    Intramembranei129 – 1357Pore-formingBy similarity

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei69 – 9325Helical; Name=M1By similarityAdd
    BLAST
    Transmembranei145 – 16622Helical; Name=M2By similarityAdd
    BLAST

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi130 – 1356Selectivity filterBy similarity

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG72812.
    HOGENOMiHOG000237325.
    HOVERGENiHBG006178.
    InParanoidiQ14654.
    KOiK05004.
    OrthoDBiEOG7XPZ5K.
    PhylomeDBiQ14654.
    TreeFamiTF313676.

    Family and domain databases

    Gene3Di2.60.40.1400. 1 hit.
    InterProiIPR014756. Ig_E-set.
    IPR016449. K_chnl_inward-rec_Kir.
    IPR003279. K_chnl_inward-rec_Kir6.2.
    IPR013518. K_chnl_inward-rec_Kir_cyto.
    [Graphical view]
    PANTHERiPTHR11767. PTHR11767. 1 hit.
    PfamiPF01007. IRK. 1 hit.
    [Graphical view]
    PIRSFiPIRSF005465. GIRK_kir. 1 hit.
    PRINTSiPR01332. KIR62CHANNEL.
    PR01320. KIRCHANNEL.
    SUPFAMiSSF81296. SSF81296. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q14654-1) [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

    MLSRKGIIPE EYVLTRLAED PAEPRYRARQ RRARFVSKKG NCNVAHKNIR    50
    EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMAW WLIAFAHGDL 100
    APSEGTAEPC VTSIHSFSSA FLFSIEVQVT IGFGGRMVTE ECPLAILILI 150
    VQNIVGLMIN AIMLGCIFMK TAQAHRRAET LIFSKHAVIA LRHGRLCFML 200
    RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM ENGVGGNSIF 250
    LVAPLIIYHV IDANSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA 300
    RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTIKVP TPLCTARQLD 350
    EDHSLLEALT LASARGPLRK RSVPMAKAKP KFSISPDSLS 390
    Length:390
    Mass (Da):43,541
    Last modified:September 27, 2005 - v2
    Checksum:i8345E7DBCE897344
    GO
    Isoform 2 (identifier: Q14654-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-87: Missing.

    Show »
    Length:303
    Mass (Da):33,263
    Checksum:iCBB99A32291CD64B
    GO

    Sequence cautioni

    The sequence AAH40617.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti370 – 3701K → E in BAG63046. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti10 – 101E → K Rare polymorphism. 1 Publication
    VAR_008659
    Natural varianti18 – 181A → G.
    Corresponds to variant rs41309072 [ dbSNP | Ensembl ].
    VAR_055978
    Natural varianti23 – 231E → K Linked to V-337. 6 Publications
    Corresponds to variant rs5219 [ dbSNP | Ensembl ].
    VAR_008660
    Natural varianti34 – 341R → H in HHF2. 1 Publication
    VAR_031329
    Natural varianti35 – 351F → L in PNDM. 1 Publication
    VAR_026498
    Natural varianti35 – 351F → V in PNDM. 1 Publication
    VAR_026499
    Natural varianti40 – 401G → D in HHF2. 1 Publication
    VAR_031330
    Natural varianti42 – 421C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. 1 Publication
    VAR_031331
    Natural varianti46 – 461H → Y in PNDM; one patient with mild dysmorphic features. 2 Publications
    VAR_031332
    Natural varianti50 – 501R → P in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current; one patient with developmental delay. 2 Publications
    VAR_026500
    Natural varianti50 – 501R → Q in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 Publications
    VAR_031333
    Natural varianti52 – 521Q → R in PNDM; with developmental delay and epilepsy; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201. 2 Publications
    VAR_026501
    Natural varianti53 – 531G → D in PNDM; with developmental delay and epilepsy. 1 Publication
    VAR_031334
    Natural varianti53 – 531G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026502
    Natural varianti53 – 531G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026503
    Natural varianti55 – 551F → L in HHF2; does neither affect channel expression nor channel response to MgADP. 1 Publication
    VAR_031335
    Natural varianti59 – 591V → G in PNDM; with developmental delay and epilepsy; with neurologic features; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201; decreases ATP sensitivity indirectly by favoring the open conformation of the channel. 2 Publications
    VAR_026504
    Natural varianti59 – 591V → M in PNDM; four patients with developmental delay and muscle weakness. 5 Publications
    VAR_026505
    Natural varianti67 – 671K → N in HHF2. 1 Publication
    VAR_026506
    Natural varianti91 – 911W → R in HHF2. 1 Publication
    VAR_026507
    Natural varianti101 – 1011A → D in HHF2. 2 Publications
    VAR_031336
    Natural varianti116 – 1161S → P in HHF2. 1 Publication
    VAR_031337
    Natural varianti134 – 1341G → A in HHF2. 1 Publication
    VAR_031338
    Natural varianti136 – 1361R → L in HHF2. 2 Publications
    VAR_031339
    Natural varianti147 – 1471L → P in HHF2. 2 Publications
    Corresponds to variant rs28936678 [ dbSNP | Ensembl ].
    VAR_001557
    Natural varianti148 – 1481I → S.2 Publications
    VAR_031340
    Natural varianti164 – 1641L → P in PNDM. 2 Publications
    VAR_031341
    Natural varianti166 – 1661C → Y in PNDM; individual also diagnosed with West syndrome. 1 Publication
    VAR_031342
    Natural varianti170 – 1701K → N in PNDM. 1 Publication
    VAR_026508
    Natural varianti170 – 1701K → R in PNDM. 1 Publication
    VAR_026509
    Natural varianti170 – 1701K → T in PNDM. 1 Publication
    VAR_031343
    Natural varianti182 – 1821I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication
    VAR_026510
    Natural varianti195 – 1951R → H.
    Corresponds to variant rs5217 [ dbSNP | Ensembl ].
    VAR_014929
    Natural varianti201 – 2011R → C in PNDM; two individuals with developmental delay; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59. 5 Publications
    VAR_026511
    Natural varianti201 – 2011R → H in PNDM; ability of ATP to block mutant channels greatly reduced. 5 Publications
    VAR_026512
    Natural varianti201 – 2011R → L in PNDM. 1 Publication
    VAR_031344
    Natural varianti254 – 2541P → L in HHF2; impairs trafficking of the mutant channel. 1 Publication
    VAR_026513
    Natural varianti259 – 2591H → R in HHF2; impairs trafficking and abolishes channel function. 1 Publication
    VAR_031345
    Natural varianti266 – 2661P → L in HHF2. 1 Publication
    VAR_031346
    Natural varianti270 – 2701L → V.2 Publications
    Corresponds to variant rs1800467 [ dbSNP | Ensembl ].
    VAR_008661
    Natural varianti296 – 2961I → L in PNDM; with developmental delay and epilepsy. 2 Publications
    VAR_026514
    Natural varianti301 – 3011R → H in HHF2. 2 Publications
    VAR_031347
    Natural varianti322 – 3221E → K in PNDM. 1 Publication
    VAR_026515
    Natural varianti330 – 3301Y → C in PNDM. 2 Publications
    VAR_026516
    Natural varianti330 – 3301Y → S in PNDM. 1 Publication
    VAR_031348
    Natural varianti333 – 3331F → I in PNDM; alters gating characteristics, decreases sensitivity to inhibition by ATP and increases intrinsic open probability. 1 Publication
    VAR_026517
    Natural varianti337 – 3371I → V Linked to K-23. 6 Publications
    Corresponds to variant rs5215 [ dbSNP | Ensembl ].
    VAR_008662
    Natural varianti355 – 3551L → P in NIDDM; Afro-Caribbean. 1 Publication
    VAR_008663
    Natural varianti380 – 3801P → PKP in NIDDM.
    VAR_008664
    Natural varianti385 – 3851S → C.1 Publication
    Corresponds to variant rs41282930 [ dbSNP | Ensembl ].
    VAR_008665

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 8787Missing in isoform 2. 2 PublicationsVSP_045270Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D50582 Genomic DNA. Translation: BAA09131.1.
    AK301550 mRNA. Translation: BAG63046.1.
    AC124798 Genomic DNA. No translation available.
    BC064497 mRNA. Translation: AAH64497.1.
    BC040617 mRNA. Translation: AAH40617.1. Different initiation.
    BC112358 mRNA. Translation: AAI12359.1.
    CCDSiCCDS31436.1. [Q14654-1]
    CCDS53606.1. [Q14654-2]
    PIRiA57616.
    RefSeqiNP_001159762.1. NM_001166290.1.
    UniGeneiHs.248141.

    Genome annotation databases

    EnsembliENST00000339994; ENSP00000345708; ENSG00000187486.
    ENST00000528731; ENSP00000434755; ENSG00000187486.
    GeneIDi3767.
    KEGGihsa:3767.

    Polymorphism databases

    DMDMi76803775.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D50582 Genomic DNA. Translation: BAA09131.1 .
    AK301550 mRNA. Translation: BAG63046.1 .
    AC124798 Genomic DNA. No translation available.
    BC064497 mRNA. Translation: AAH64497.1 .
    BC040617 mRNA. Translation: AAH40617.1 . Different initiation.
    BC112358 mRNA. Translation: AAI12359.1 .
    CCDSi CCDS31436.1. [Q14654-1 ]
    CCDS53606.1. [Q14654-2 ]
    PIRi A57616.
    RefSeqi NP_001159762.1. NM_001166290.1.
    UniGenei Hs.248141.

    3D structure databases

    ProteinModelPortali Q14654.
    SMRi Q14654. Positions 32-356.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-58643N.
    IntActi Q14654. 1 interaction.
    STRINGi 9606.ENSP00000345708.

    Chemistry

    BindingDBi Q14654.
    ChEMBLi CHEMBL2096972.
    DrugBanki DB01119. Diazoxide.
    DB01016. Glibenclamide.
    DB00222. Glimepiride.
    DB00308. Ibutilide.
    DB00922. Levosimendan.
    DB01252. Mitiglinide.
    DB00731. Nateglinide.
    DB00912. Repaglinide.
    DB00661. Verapamil.
    GuidetoPHARMACOLOGYi 442.

    PTM databases

    PhosphoSitei Q14654.

    Polymorphism databases

    DMDMi 76803775.

    Proteomic databases

    PaxDbi Q14654.
    PRIDEi Q14654.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000339994 ; ENSP00000345708 ; ENSG00000187486 .
    ENST00000528731 ; ENSP00000434755 ; ENSG00000187486 .
    GeneIDi 3767.
    KEGGi hsa:3767.

    Organism-specific databases

    CTDi 3767.
    GeneCardsi GC11M017406.
    GeneReviewsi KCNJ11.
    H-InvDB HIX0035982.
    HGNCi HGNC:6257. KCNJ11.
    HPAi HPA048891.
    MIMi 600937. gene.
    601820. phenotype.
    606176. phenotype.
    610582. phenotype.
    neXtProti NX_Q14654.
    Orphaneti 276580. Autosomal dominant hyperinsulinism due to Kir6.2 deficiency.
    79644. Autosomal recessive hyperinsulinism due to Kir6.2 deficiency.
    79134. DEND syndrome.
    276603. Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency.
    552. MODY syndrome.
    99885. Permanent neonatal diabetes mellitus.
    99886. Transient neonatal diabetes mellitus.
    PharmGKBi PA217.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG72812.
    HOGENOMi HOG000237325.
    HOVERGENi HBG006178.
    InParanoidi Q14654.
    KOi K05004.
    OrthoDBi EOG7XPZ5K.
    PhylomeDBi Q14654.
    TreeFami TF313676.

    Enzyme and pathway databases

    Reactomei REACT_18325. Regulation of insulin secretion.
    REACT_75775. ATP sensitive Potassium channels.
    SignaLinki Q14654.

    Miscellaneous databases

    ChiTaRSi KCNJ11. human.
    GeneWikii Kir6.2.
    GenomeRNAii 3767.
    NextBioi 14771.
    PROi Q14654.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14654.
    Bgeei Q14654.
    CleanExi HS_KCNJ11.
    Genevestigatori Q14654.

    Family and domain databases

    Gene3Di 2.60.40.1400. 1 hit.
    InterProi IPR014756. Ig_E-set.
    IPR016449. K_chnl_inward-rec_Kir.
    IPR003279. K_chnl_inward-rec_Kir6.2.
    IPR013518. K_chnl_inward-rec_Kir_cyto.
    [Graphical view ]
    PANTHERi PTHR11767. PTHR11767. 1 hit.
    Pfami PF01007. IRK. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF005465. GIRK_kir. 1 hit.
    PRINTSi PR01332. KIR62CHANNEL.
    PR01320. KIRCHANNEL.
    SUPFAMi SSF81296. SSF81296. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor."
      Inagaki N., Gonoi T., Clement J.P. IV, Namba N., Inazawa J., Gonzalez G., Aguilar-Bryan L., Seino S., Bryan J.
      Science 270:1166-1170(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-148.
      Tissue: Placenta.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Mammary gland.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS LYS-23 AND VAL-337.
    4. "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] (ISOFORMS 1 AND 2).
      Tissue: Ovary and Spleen.
    5. "Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells."
      Babenko A.P., Gonzalez G., Aguilar-Bryan L., Bryan J.
      Circ. Res. 83:1132-1143(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ABCC9.
    6. "Molecular basis for Kir6.2 channel inhibition by adenine nucleotides."
      Ribalet B., John S.A., Weiss J.N.
      Biophys. J. 84:266-276(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: MOLECULAR BASIS OF ATP SENSITIVITY.
    7. "Congenital hyperinsulinism: molecular basis of a heterogeneous disease."
      Meissner T., Beinbrech B., Mayatepek E.
      Hum. Mutat. 13:351-361(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON VARIANTS.
    8. "A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit."
      Tammaro P., Ashcroft F.M.
      J. Physiol. (Lond.) 584:743-753(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CHARACTERIZATION OF VARIANT PNDM ILE-333, INTERACTION WITH ABCC9.
    9. "Functional modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation."
      Lin Y.F., Chai Y.
      Neuroscience 152:371-380(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-341 AND SER-385.
    10. "Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy."
      Thomas P.M., Cote G.J., Hallman D.M., Mathew P.M.
      Am. J. Hum. Genet. 56:416-421(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHF2 PRO-147.
    11. "Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy."
      Thomas P., Ye Y., Lightner E.
      Hum. Mol. Genet. 5:1809-1812(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHF2 PRO-147.
    12. "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro."
      Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M.
      Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385.
    13. "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM."
      Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A.
      Diabetes 46:502-507(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337.
    14. "Molecular biology of adenosine triphosphate-sensitive potassium channels."
      Aguilar-Bryan L., Bryan J.
      Endocr. Rev. 20:101-135(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHF2 ARG-91.
    15. "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."
      Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.
      Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LYS-23 AND VAL-337.
    16. Cited for: VARIANT HHF2 ASN-67.
    17. "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy."
      Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R.
      Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.
    18. "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients."
      Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M.
      Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.
    19. "Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel."
      Gloyn A.L., Cummings E.A., Edghill E.L., Harries L.W., Scott R., Costa T., Temple I.K., Hattersley A.T., Ellard S.
      J. Clin. Endocrinol. Metab. 89:3932-3935(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PNDM CYS-201.
    20. Cited for: VARIANT HHF2 LEU-254, CHARACTERIZATION OF VARIANT HHF2 LEU-254.
    21. Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201.
    22. "Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features."
      Proks P., Antcliff J.F., Lippiat J., Gloyn A.L., Hattersley A.T., Ashcroft F.M.
      Proc. Natl. Acad. Sci. U.S.A. 101:17539-17544(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS PNDM ARG-52; GLY-59 AND CYS-201.
    23. "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy."
      Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J.
      Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337.
    24. Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.
    25. Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.
    26. "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes."
      Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A.
      J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.
    27. "The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus."
      Yorifuji T., Nagashima K., Kurokawa K., Kawai M., Oishi M., Akazawa Y., Hosokawa M., Yamada Y., Inagaki N., Nakahata T.
      J. Clin. Endocrinol. Metab. 90:3174-3178(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TNDM3 ARG-42, CHARACTERIZATION OF VARIANT TNDM3 ARG-42.
    28. "Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function."
      Marthinet E., Bloc A., Oka Y., Tanizawa Y., Wehrle-Haller B., Bancila V., Dubuis J.-M., Philippe J., Schwitzgebel V.M.
      J. Clin. Endocrinol. Metab. 90:5401-5406(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHF2 ARG-259, CHARACTERIZATION OF VARIANT HHF2 ARG-259.
    29. "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects."
      Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M.
      Diabetes 55:1705-1712(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PNDM GLN-50 AND PRO-50, CHARACTERIZATION OF VARIANTS PNDM GLN-50 AND PRO-50.
    30. "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype."
      Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T.
      Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.
    31. "Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI)."
      Fernandez-Marmiesse A., Salas A., Vega A., Fernandez-Lorenzo J.R., Barreiro J., Carracedo A.
      Hum. Mutat. 27:214-214(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LYS-23 AND VAL-337.
    32. "A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels."
      Lin Y.-W., MacMullen C., Ganguly A., Stanley C.A., Shyng S.-L.
      J. Biol. Chem. 281:3006-3012(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHF2 LEU-55, CHARACTERIZATION OF VARIANT HHF2 LEU-55.
    33. "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism."
      Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A.
      Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.
    34. "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers."
      Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I.
      J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.

    Entry informationi

    Entry nameiKCJ11_HUMAN
    AccessioniPrimary (citable) accession number: Q14654
    Secondary accession number(s): B4DWI4
    , E9PNK0, Q2M1H7, Q58EX3, Q8IW96
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: September 27, 2005
    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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: 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

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