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Q14654 (IRK11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:KCNJ11
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length390 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.8

Subunit structure

Interacts with ABCC8/SUR. Interacts with ABCC9/SUR2. Ref.5 Ref.8

Subcellular location

Membrane; Multi-pass membrane protein.

Post-translational modification

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

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.14 Ref.16 Ref.20 Ref.24 Ref.27 Ref.29 Ref.33 Ref.34

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.26 Ref.30 Ref.31 Ref.35

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25 Ref.28

Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2. Ref.12

Sequence similarities

Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily. [View classification]

Sequence caution

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

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDiabetes mellitus
Disease mutation
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Voltage-gated channel
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to nicotine

Inferred from electronic annotation. Source: Ensembl

cellular response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

energy reserve metabolic process

Traceable author statement. Source: Reactome

glucose metabolic process

Inferred from mutant phenotype Ref.21Ref.11. Source: BHF-UCL

negative regulation of insulin secretion

Inferred from mutant phenotype Ref.11. Source: BHF-UCL

neurological system process

Inferred from mutant phenotype Ref.21PubMed 18073297. Source: BHF-UCL

positive regulation of cation channel activity

Inferred from electronic annotation. Source: Ensembl

potassium ion import

Inferred from sequence or structural similarity. Source: BHF-UCL

potassium ion transmembrane transport

Inferred from direct assay PubMed 19805355. Source: BHF-UCL

regulation of insulin secretion

Inferred from mutant phenotype Ref.21. Source: BHF-UCL

regulation of membrane potential

Inferred from direct assay PubMed 18073297. Source: BHF-UCL

response to ATP

Inferred from direct assay Ref.23PubMed 18073297. Source: BHF-UCL

response to drug

Inferred from mutant phenotype PubMed 18073297. Source: BHF-UCL

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to ischemia

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentATP-sensitive potassium channel complex

Inferred from direct assay PubMed 19805355. Source: BHF-UCL

T-tubule

Inferred from sequence or structural similarity. Source: BHF-UCL

axolemma

Inferred from electronic annotation. Source: Ensembl

cell body fiber

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

endosome

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.11. Source: ProtInc

intercalated disc

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

myelin sheath

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nuclear envelope

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay PubMed 19805355. Source: BHF-UCL

voltage-gated potassium channel complex

Inferred from direct assay PubMed 20610380. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from sequence or structural similarity PubMed 12860923. Source: BHF-UCL

ATP-activated inward rectifier potassium channel activity

Inferred from sequence or structural similarity. Source: BHF-UCL

ankyrin binding

Inferred from physical interaction PubMed 20610380. Source: BHF-UCL

ion channel binding

Inferred from physical interaction PubMed 20610380. Source: BHF-UCL

potassium ion binding

Traceable author statement Ref.11. Source: BHF-UCL

voltage-gated potassium channel activity

Inferred from direct assay PubMed 19805355. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14654-1)

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.
Isoform 2 (identifier: Q14654-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 390390ATP-sensitive inward rectifier potassium channel 11
PRO_0000154957

Regions

Topological domain1 – 6868Cytoplasmic By similarity
Transmembrane69 – 9325Helical; Name=M1; By similarity
Topological domain94 – 11623Extracellular By similarity
Intramembrane117 – 12812Helical; Pore-forming; Name=H5; By similarity
Intramembrane129 – 1357Pore-forming; By similarity
Topological domain136 – 1449Extracellular By similarity
Transmembrane145 – 16622Helical; Name=M2; By similarity
Topological domain167 – 390224Cytoplasmic By similarity
Motif130 – 1356Selectivity filter By similarity

Sites

Site1601Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity

Amino acid modifications

Modified residue3411Phosphothreonine; by MAPK1 Ref.9
Modified residue3851Phosphoserine; by MAPK1 Ref.9

Natural variations

Alternative sequence1 – 8787Missing in isoform 2.
VSP_045270
Natural variant101E → K Rare polymorphism. Ref.13
VAR_008659
Natural variant181A → G.
Corresponds to variant rs41309072 [ dbSNP | Ensembl ].
VAR_055978
Natural variant231E → K Linked to V-337. Ref.3 Ref.12 Ref.13 Ref.15 Ref.24 Ref.32
Corresponds to variant rs5219 [ dbSNP | Ensembl ].
VAR_008660
Natural variant341R → H in HHF2. Ref.24
VAR_031329
Natural variant351F → L in PNDM. Ref.18
VAR_026498
Natural variant351F → V in PNDM. Ref.17
VAR_026499
Natural variant401G → D in HHF2. Ref.34
VAR_031330
Natural variant421C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. Ref.28
VAR_031331
Natural variant461H → Y in PNDM; one patient with mild dysmorphic features. Ref.31 Ref.35
VAR_031332
Natural variant501R → P in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current; one patient with developmental delay. Ref.26 Ref.30
VAR_026500
Natural variant501R → Q in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. Ref.30 Ref.31
VAR_031333
Natural variant521Q → 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. Ref.21 Ref.23 Ref.31
VAR_026501
Natural variant531G → D in PNDM; with developmental delay and epilepsy. Ref.31
VAR_031334
Natural variant531G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. Ref.25
VAR_026502
Natural variant531G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. Ref.25
VAR_026503
Natural variant551F → L in HHF2; does neither affect channel expression nor channel response to MgADP. Ref.33
VAR_031335
Natural variant591V → 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. Ref.21 Ref.23 Ref.31
VAR_026504
Natural variant591V → M in PNDM; four patients with developmental delay and muscle weakness. Ref.17 Ref.18 Ref.21 Ref.26 Ref.31
VAR_026505
Natural variant671K → N in HHF2. Ref.16
VAR_026506
Natural variant911W → R in HHF2. Ref.14
VAR_026507
Natural variant1011A → D in HHF2. Ref.27 Ref.34
VAR_031336
Natural variant1161S → P in HHF2. Ref.34
VAR_031337
Natural variant1341G → A in HHF2. Ref.27
VAR_031338
Natural variant1361R → L in HHF2. Ref.27 Ref.34
VAR_031339
Natural variant1471L → P in HHF2. Ref.10 Ref.11
Corresponds to variant rs28936678 [ dbSNP | Ensembl ].
VAR_001557
Natural variant1481I → S. Ref.1 Ref.24
VAR_031340
Natural variant1641L → P in PNDM. Ref.31 Ref.35
VAR_031341
Natural variant1661C → Y in PNDM; individual also diagnosed with West syndrome. Ref.31
VAR_031342
Natural variant1701K → N in PNDM. Ref.26
VAR_026508
Natural variant1701K → R in PNDM. Ref.26
VAR_026509
Natural variant1701K → T in PNDM. Ref.31
VAR_031343
Natural variant1821I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. Ref.25
VAR_026510
Natural variant1951R → H.
Corresponds to variant rs5217 [ dbSNP | Ensembl ].
VAR_014929
Natural variant2011R → 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. Ref.18 Ref.19 Ref.21 Ref.23 Ref.26 Ref.31
VAR_026511
Natural variant2011R → H in PNDM; ability of ATP to block mutant channels greatly reduced. Ref.17 Ref.18 Ref.21 Ref.31 Ref.35
VAR_026512
Natural variant2011R → L in PNDM. Ref.31
VAR_031344
Natural variant2541P → L in HHF2; impairs trafficking of the mutant channel. Ref.20
VAR_026513
Natural variant2591H → R in HHF2; impairs trafficking and abolishes channel function. Ref.29
VAR_031345
Natural variant2661P → L in HHF2. Ref.27
VAR_031346
Natural variant2701L → V. Ref.12 Ref.13
Corresponds to variant rs1800467 [ dbSNP | Ensembl ].
VAR_008661
Natural variant2961I → L in PNDM; with developmental delay and epilepsy. Ref.21 Ref.31
VAR_026514
Natural variant3011R → H in HHF2. Ref.27 Ref.34
VAR_031347
Natural variant3221E → K in PNDM. Ref.18
VAR_026515
Natural variant3301Y → C in PNDM. Ref.17 Ref.18
VAR_026516
Natural variant3301Y → S in PNDM. Ref.31
VAR_031348
Natural variant3331F → I in PNDM; alters gating characteristics, decreases sensitivity to inhibition by ATP and increases intrinsic open probability. Ref.8 Ref.17
VAR_026517
Natural variant3371I → V Linked to K-23. Ref.3 Ref.12 Ref.13 Ref.15 Ref.24 Ref.32
Corresponds to variant rs5215 [ dbSNP | Ensembl ].
VAR_008662
Natural variant3551L → P in NIDDM; Afro-Caribbean. Ref.12
VAR_008663
Natural variant3801P → PKP in NIDDM.
VAR_008664
Natural variant3851S → C. Ref.12
Corresponds to variant rs41282930 [ dbSNP | Ensembl ].
VAR_008665

Experimental info

Sequence conflict3701K → E in BAG63046. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 27, 2005. Version 2.
Checksum: 8345E7DBCE897344

FASTA39043,541
        10         20         30         40         50         60 
MLSRKGIIPE EYVLTRLAED PAEPRYRARQ RRARFVSKKG NCNVAHKNIR EQGRFLQDVF 

        70         80         90        100        110        120 
TTLVDLKWPH TLLIFTMSFL CSWLLFAMAW WLIAFAHGDL APSEGTAEPC VTSIHSFSSA 

       130        140        150        160        170        180 
FLFSIEVQVT IGFGGRMVTE ECPLAILILI VQNIVGLMIN AIMLGCIFMK TAQAHRRAET 

       190        200        210        220        230        240 
LIFSKHAVIA LRHGRLCFML RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM 

       250        260        270        280        290        300 
ENGVGGNSIF LVAPLIIYHV IDANSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA 

       310        320        330        340        350        360 
RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTIKVP TPLCTARQLD EDHSLLEALT 

       370        380        390 
LASARGPLRK RSVPMAKAKP KFSISPDSLS 

« Hide

Isoform 2 [UniParc].

Checksum: CBB99A32291CD64B
Show »

FASTA30333,263

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
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]"Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism."
Huopio H., Jaeaeskelaeinen J., Komulainen J., Miettinen R., Kaerkkaeinen P., Laakso M., Tapanainen P., Voutilainen R., Otonkoski T.
J. Clin. Endocrinol. Metab. 87:4502-4507(2002) [PubMed] [Europe PMC] [Abstract]
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]"Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity."
Tornovsky S., Crane A., Cosgrove K.E., Hussain K., Lavie J., Heyman M., Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O., Nahari E., Potikha T., Zangen D., Tenenbaum-Rakover Y., de Vries L., Argente J., Gracia R., Landau H. expand/collapse author list , Eliakim A., Lindley K., Dunne M.J., Aguilar-Bryan L., Glaser B.
J. Clin. Endocrinol. Metab. 89:6224-6234(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 LEU-254, CHARACTERIZATION OF VARIANT HHF2 LEU-254.
[21]"Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes."
Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. expand/collapse author list , Clark P., Gorman S., Aisenberg J., Ellard S., Njoelstad P.R., Ashcroft F.M., Hattersley A.T.
N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201.
[22]Erratum
Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. expand/collapse author list , Clark P., Gorman S., Aisenberg J., Ellard S., Njoelstad P.R., Ashcroft F.M., Hattersley A.T.
N. Engl. J. Med. 351:1470-1470(2004)
[23]"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.
[24]"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.
[25]"Relapsing diabetes can result from moderately activating mutations in KCNJ11."
Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T.
Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.
[26]"KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes."
The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes
Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F.
Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.
[27]"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.
[28]"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.
[29]"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.
[30]"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.
[31]"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.
[32]"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.
[33]"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.
[34]"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.
[35]"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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA57616.
RefSeqNP_001159762.1. NM_001166290.1.
UniGeneHs.248141.

3D structure databases

ProteinModelPortalQ14654.
SMRQ14654. Positions 32-356.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-58643N.
IntActQ14654. 1 interaction.
STRING9606.ENSP00000345708.

Chemistry

BindingDBQ14654.
ChEMBLCHEMBL2095198.
DrugBankDB01119. Diazoxide.
DB01016. Glibenclamide.
DB00222. Glimepiride.
DB00308. Ibutilide.
DB00922. Levosimendan.
DB01252. Mitiglinide.
DB00731. Nateglinide.
DB00912. Repaglinide.
DB00661. Verapamil.
GuidetoPHARMACOLOGY442.

PTM databases

PhosphoSiteQ14654.

Polymorphism databases

DMDM76803775.

Proteomic databases

PaxDbQ14654.
PRIDEQ14654.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339994; ENSP00000345708; ENSG00000187486.
ENST00000528731; ENSP00000434755; ENSG00000187486.
GeneID3767.
KEGGhsa:3767.

Organism-specific databases

CTD3767.
GeneCardsGC11M017406.
H-InvDBHIX0035982.
HGNCHGNC:6257. KCNJ11.
HPAHPA048891.
MIM600937. gene.
601820. phenotype.
606176. phenotype.
610582. phenotype.
neXtProtNX_Q14654.
Orphanet276580. 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.
PharmGKBPA217.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG72812.
HOGENOMHOG000237325.
HOVERGENHBG006178.
InParanoidQ14654.
KOK05004.
OrthoDBEOG7XPZ5K.
PhylomeDBQ14654.
TreeFamTF313676.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_13685. Neuronal System.
SignaLinkQ14654.

Gene expression databases

ArrayExpressQ14654.
BgeeQ14654.
CleanExHS_KCNJ11.
GenevestigatorQ14654.

Family and domain databases

Gene3D2.60.40.1400. 1 hit.
InterProIPR014756. 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]
PANTHERPTHR11767. PTHR11767. 1 hit.
PfamPF01007. IRK. 1 hit.
[Graphical view]
PIRSFPIRSF005465. GIRK_kir. 1 hit.
PRINTSPR01332. KIR62CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

ChiTaRSKCNJ11. human.
GeneWikiKir6.2.
GenomeRNAi3767.
NextBio14771.
PROQ14654.
SOURCESearch...

Entry information

Entry nameIRK11_HUMAN
AccessionPrimary (citable) accession number: Q14654
Secondary accession number(s): B4DWI4 expand/collapse secondary AC list , E9PNK0, Q2M1H7, Q58EX3, Q8IW96
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 27, 2005
Last modified: April 16, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM