Q14654 (KCJ11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

KCNJ11

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	390 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular 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_component	ATP-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_function	ATP 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 390	390	ATP-sensitive inward rectifier potassium channel 11		PRO_0000154957
Regions
	Topological domain	1 – 68	68	Cytoplasmic By similarity
	Transmembrane	69 – 93	25	Helical; Name=M1; By similarity
	Topological domain	94 – 116	23	Extracellular By similarity
	Intramembrane	117 – 128	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	129 – 135	7	Pore-forming; By similarity
	Topological domain	136 – 144	9	Extracellular By similarity
	Transmembrane	145 – 166	22	Helical; Name=M2; By similarity
	Topological domain	167 – 390	224	Cytoplasmic By similarity
	Motif	130 – 135	6	Selectivity filter By similarity
Sites
	Site	160	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Amino acid modifications
	Modified residue	341	1	Phosphothreonine; by MAPK1 Ref.9
	Modified residue	385	1	Phosphoserine; by MAPK1 Ref.9
Natural variations
	Alternative sequence	1 – 87	87	Missing in isoform 2.		VSP_045270
	Natural variant	10	1	E → K Rare polymorphism. Ref.13		VAR_008659
	Natural variant	18	1	A → G. Corresponds to variant rs41309072 [ dbSNP | Ensembl ].		VAR_055978
	Natural variant	23	1	E → 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 variant	34	1	R → H in HHF2. Ref.24		VAR_031329
	Natural variant	35	1	F → L in PNDM. Ref.18		VAR_026498
	Natural variant	35	1	F → V in PNDM. Ref.17		VAR_026499
	Natural variant	40	1	G → D in HHF2. Ref.34		VAR_031330
	Natural variant	42	1	C → 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 variant	46	1	H → Y in PNDM; one patient with mild dysmorphic features. Ref.31 Ref.35		VAR_031332
	Natural variant	50	1	R → 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 variant	50	1	R → Q in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. Ref.30 Ref.31		VAR_031333
	Natural variant	52	1	Q → 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 variant	53	1	G → D in PNDM; with developmental delay and epilepsy. Ref.31		VAR_031334
	Natural variant	53	1	G → 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 variant	53	1	G → 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 variant	55	1	F → L in HHF2; does neither affect channel expression nor channel response to MgADP. Ref.33		VAR_031335
	Natural variant	59	1	V → 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 variant	59	1	V → M in PNDM; four patients with developmental delay and muscle weakness. Ref.17 Ref.18 Ref.21 Ref.26 Ref.31		VAR_026505
	Natural variant	67	1	K → N in HHF2. Ref.16		VAR_026506
	Natural variant	91	1	W → R in HHF2. Ref.14		VAR_026507
	Natural variant	101	1	A → D in HHF2. Ref.27 Ref.34		VAR_031336
	Natural variant	116	1	S → P in HHF2. Ref.34		VAR_031337
	Natural variant	134	1	G → A in HHF2. Ref.27		VAR_031338
	Natural variant	136	1	R → L in HHF2. Ref.27 Ref.34		VAR_031339
	Natural variant	147	1	L → P in HHF2. Ref.10 Ref.11 Corresponds to variant rs28936678 [ dbSNP | Ensembl ].		VAR_001557
	Natural variant	148	1	I → S. Ref.1 Ref.24		VAR_031340
	Natural variant	164	1	L → P in PNDM. Ref.31 Ref.35		VAR_031341
	Natural variant	166	1	C → Y in PNDM; individual also diagnosed with West syndrome. Ref.31		VAR_031342
	Natural variant	170	1	K → N in PNDM. Ref.26		VAR_026508
	Natural variant	170	1	K → R in PNDM. Ref.26		VAR_026509
	Natural variant	170	1	K → T in PNDM. Ref.31		VAR_031343
	Natural variant	182	1	I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. Ref.25		VAR_026510
	Natural variant	195	1	R → H. Corresponds to variant rs5217 [ dbSNP | Ensembl ].		VAR_014929
	Natural variant	201	1	R → 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 variant	201	1	R → 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 variant	201	1	R → L in PNDM. Ref.31		VAR_031344
	Natural variant	254	1	P → L in HHF2; impairs trafficking of the mutant channel. Ref.20		VAR_026513
	Natural variant	259	1	H → R in HHF2; impairs trafficking and abolishes channel function. Ref.29		VAR_031345
	Natural variant	266	1	P → L in HHF2. Ref.27		VAR_031346
	Natural variant	270	1	L → V. Ref.12 Ref.13 Corresponds to variant rs1800467 [ dbSNP | Ensembl ].		VAR_008661
	Natural variant	296	1	I → L in PNDM; with developmental delay and epilepsy. Ref.21 Ref.31		VAR_026514
	Natural variant	301	1	R → H in HHF2. Ref.27 Ref.34		VAR_031347
	Natural variant	322	1	E → K in PNDM. Ref.18		VAR_026515
	Natural variant	330	1	Y → C in PNDM. Ref.17 Ref.18		VAR_026516
	Natural variant	330	1	Y → S in PNDM. Ref.31		VAR_031348
	Natural variant	333	1	F → I in PNDM; alters gating characteristics, decreases sensitivity to inhibition by ATP and increases intrinsic open probability. Ref.8 Ref.17		VAR_026517
	Natural variant	337	1	I → 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 variant	355	1	L → P in NIDDM; Afro-Caribbean. Ref.12		VAR_008663
	Natural variant	380	1	P → PKP in NIDDM.		VAR_008664
	Natural variant	385	1	S → C. Ref.12 Corresponds to variant rs41282930 [ dbSNP | Ensembl ].		VAR_008665
Experimental info
	Sequence conflict	370	1	K → E in BAG63046. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: 8345E7DBCE897344	FASTA	390	43,541
	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
	Isoform 2 [UniParc]. Checksum: CBB99A32291CD64B	FASTA	303	33,263
	10 20 30 40 50 60 MAWWLIAFAH GDLAPSEGTA EPCVTSIHSF SSAFLFSIEV QVTIGFGGRM VTEECPLAIL 70 80 90 100 110 120 ILIVQNIVGL MINAIMLGCI FMKTAQAHRR AETLIFSKHA VIALRHGRLC FMLRVGDLRK 130 140 150 160 170 180 SMIISATIHM QVVRKTTSPE GEVVPLHQVD IPMENGVGGN SIFLVAPLII YHVIDANSPL 190 200 210 220 230 240 YDLAPSDLHH HQDLEIIVIL EGVVETTGIT TQARTSYLAD EILWGQRFVP IVAEEDGRYS 250 260 270 280 290 300 VDYSKFGNTI KVPTPLCTAR QLDEDHSLLE ALTLASARGP LRKRSVPMAK AKPKFSISPD SLS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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. , 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.

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.
CCDS	CCDS31436.1. [Q14654-1] CCDS53606.1. [Q14654-2]
PIR	A57616.
RefSeq	NP_001159762.1. NM_001166290.1.
UniGene	Hs.248141.
3D structure databases
ProteinModelPortal	Q14654.
SMR	Q14654. Positions 32-356.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
DIP	DIP-58643N.
IntAct	Q14654. 1 interaction.
STRING	9606.ENSP00000345708.
Chemistry
BindingDB	Q14654.
ChEMBL	CHEMBL2096972.
DrugBank	DB01119. Diazoxide. DB01016. Glibenclamide. DB00222. Glimepiride. DB00308. Ibutilide. DB00922. Levosimendan. DB01252. Mitiglinide. DB00731. Nateglinide. DB00912. Repaglinide. DB00661. Verapamil.
GuidetoPHARMACOLOGY	442.
PTM databases
PhosphoSite	Q14654.
Polymorphism databases
DMDM	76803775.
Proteomic databases
PaxDb	Q14654.
PRIDE	Q14654.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000339994; ENSP00000345708; ENSG00000187486. ENST00000528731; ENSP00000434755; ENSG00000187486.
GeneID	3767.
KEGG	hsa:3767.
Organism-specific databases
CTD	3767.
GeneCards	GC11M017406.
GeneReviews	KCNJ11.
H-InvDB	HIX0035982.
HGNC	HGNC:6257. KCNJ11.
HPA	HPA048891.
MIM	600937. gene. 601820. phenotype. 606176. phenotype. 610582. phenotype.
neXtProt	NX_Q14654.
Orphanet	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.
PharmGKB	PA217.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG72812.
HOGENOM	HOG000237325.
HOVERGEN	HBG006178.
InParanoid	Q14654.
KO	K05004.
OrthoDB	EOG7XPZ5K.
PhylomeDB	Q14654.
TreeFam	TF313676.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_13685. Neuronal System.
SignaLink	Q14654.
Gene expression databases
ArrayExpress	Q14654.
Bgee	Q14654.
CleanEx	HS_KCNJ11.
Genevestigator	Q14654.
Family and domain databases
Gene3D	2.60.40.1400. 1 hit.
InterPro	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]
PANTHER	PTHR11767. PTHR11767. 1 hit.
Pfam	PF01007. IRK. 1 hit. [Graphical view]
PIRSF	PIRSF005465. GIRK_kir. 1 hit.
PRINTS	PR01332. KIR62CHANNEL. PR01320. KIRCHANNEL.
SUPFAM	SSF81296. SSF81296. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	KCNJ11. human.
GeneWiki	Kir6.2.
GenomeRNAi	3767.
NextBio	14771.
PRO	Q14654.
SOURCE	Search...

Entry information

Entry name

KCJ11_HUMAN

Accession

Primary (citable) accession number: Q14654
Secondary accession number(s): B4DWI4 , E9PNK0, Q2M1H7, Q58EX3, Q8IW96

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	September 27, 2005
Last modified:	July 9, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.