UniProtKB - Q14654 (KCJ11_HUMAN)
Protein
ATP-sensitive inward rectifier potassium channel 11
Gene
KCNJ11
Organism
Homo sapiens (Human)
Status
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 similarity3 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 160 | Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity | 1 |
GO - Molecular functioni
- ankyrin binding Source: BHF-UCL
- ATP-activated inward rectifier potassium channel activity Source: BHF-UCL
- ATPase-coupled cation transmembrane transporter activity Source: ARUK-UCL
- ATP binding Source: BHF-UCL
- heat shock protein binding Source: Ensembl
- inward rectifier potassium channel activity Source: GO_Central
- ion channel binding Source: BHF-UCL
- potassium ion binding Source: BHF-UCL
- protein C-terminus binding Source: Ensembl
- voltage-gated potassium channel activity Source: BHF-UCL
GO - Biological processi
- cellular response to glucose stimulus Source: Ensembl
- cellular response to nicotine Source: Ensembl
- cellular response to tumor necrosis factor Source: Ensembl
- glucose metabolic process Source: BHF-UCL
- inorganic cation transmembrane transport Source: ARUK-UCL
- negative regulation of insulin secretion Source: BHF-UCL
- nervous system process Source: BHF-UCL
- positive regulation of cation channel activity Source: Ensembl
- positive regulation of protein localization to plasma membrane Source: Ensembl
- potassium ion import across plasma membrane Source: BHF-UCL
- potassium ion transmembrane transport Source: BHF-UCL
- regulation of cardiac conduction Source: Reactome
- regulation of insulin secretion Source: BHF-UCL
- regulation of ion transmembrane transport Source: GO_Central
- regulation of membrane potential Source: BHF-UCL
- response to ATP Source: BHF-UCL
- response to drug Source: BHF-UCL
- response to estradiol Source: Ensembl
- response to ischemia Source: Ensembl
- response to testosterone Source: Ensembl
- transmembrane transport Source: Reactome
Keywordsi
Molecular function | Ion channel, Voltage-gated channel |
Biological process | Ion transport, Potassium transport, Transport |
Ligand | Potassium |
Enzyme and pathway databases
PathwayCommonsi | Q14654 |
Reactomei | R-HSA-1296025, ATP sensitive Potassium channels R-HSA-382556, ABC-family proteins mediated transport R-HSA-422356, Regulation of insulin secretion R-HSA-5578775, Ion homeostasis R-HSA-5678420, Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome R-HSA-5683177, Defective ABCC8 can cause hypo- and hyper-glycemias |
SignaLinki | Q14654 |
SIGNORi | Q14654 |
Protein family/group databases
TCDBi | 1.A.2.1.17, the inward rectifier k(+) channel (irk-c) family |
Names & Taxonomyi
Protein namesi | Recommended name: ATP-sensitive inward rectifier potassium channel 11Alternative name(s): IKATP Inward rectifier K(+) channel Kir6.2 Potassium channel, inwardly rectifying subfamily J member 11 |
Gene namesi | Name:KCNJ11 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6257, KCNJ11 |
MIMi | 600937, gene |
neXtProti | NX_Q14654 |
VEuPathDBi | HostDB:ENSG00000187486.5 |
Subcellular locationi
Other locations
Cytosol
- cytosol Source: Ensembl
Endoplasmic reticulum
- endoplasmic reticulum Source: Ensembl
Endosome
- endosome Source: Ensembl
Mitochondrion
- mitochondrion Source: Ensembl
Nucleus
- nuclear envelope Source: Ensembl
Plasma Membrane
- axolemma Source: Ensembl
- integral component of plasma membrane Source: ProtInc
- inward rectifying potassium channel Source: BHF-UCL
- plasma membrane Source: BHF-UCL
- T-tubule Source: BHF-UCL
Other locations
- acrosomal vesicle Source: Ensembl
- cell body fiber Source: Ensembl
- intercalated disc Source: Ensembl
- myelin sheath Source: Ensembl
- neuronal cell body Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 68 | CytoplasmicBy similarityAdd BLAST | 68 | |
Transmembranei | 69 – 93 | Helical; Name=M1By similarityAdd BLAST | 25 | |
Topological domaini | 94 – 116 | ExtracellularBy similarityAdd BLAST | 23 | |
Intramembranei | 117 – 128 | Helical; Pore-forming; Name=H5By similarityAdd BLAST | 12 | |
Intramembranei | 129 – 135 | Pore-formingBy similarity | 7 | |
Topological domaini | 136 – 144 | ExtracellularBy similarity | 9 | |
Transmembranei | 145 – 166 | Helical; Name=M2By similarityAdd BLAST | 22 | |
Topological domaini | 167 – 390 | CytoplasmicBy similarityAdd BLAST | 224 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Involvement in diseasei
Familial hyperinsulinemic hypoglycemia 2 (HHF2)12 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionMost common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_031329 | 34 | R → H in HHF2. 1 PublicationCorresponds to variant dbSNP:rs141145502Ensembl. | 1 | |
Natural variantiVAR_031330 | 40 | G → D in HHF2. 1 PublicationCorresponds to variant dbSNP:rs1001873841EnsemblClinVar. | 1 | |
Natural variantiVAR_031335 | 55 | F → L in HHF2; does neither affect channel expression nor channel response to MgADP. 2 PublicationsCorresponds to variant dbSNP:rs1343400778Ensembl. | 1 | |
Natural variantiVAR_026506 | 67 | K → N in HHF2. 1 PublicationCorresponds to variant dbSNP:rs747719667Ensembl. | 1 | |
Natural variantiVAR_026507 | 91 | W → R in HHF2. 1 Publication | 1 | |
Natural variantiVAR_031336 | 101 | A → D in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs1014454531EnsemblClinVar. | 1 | |
Natural variantiVAR_031337 | 116 | S → P in HHF2. 1 Publication | 1 | |
Natural variantiVAR_031338 | 134 | G → A in HHF2. 1 Publication | 1 | |
Natural variantiVAR_031339 | 136 | R → L in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs1479483693Ensembl. | 1 | |
Natural variantiVAR_001557 | 147 | L → P in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs28936678EnsemblClinVar. | 1 | |
Natural variantiVAR_073683 | 156 | G → R in HHF2. 1 PublicationCorresponds to variant dbSNP:rs1404429785EnsemblClinVar. | 1 | |
Natural variantiVAR_073685 | 204 | D → E in HHF2. 1 PublicationCorresponds to variant dbSNP:rs577757932Ensembl. | 1 | |
Natural variantiVAR_026513 | 254 | P → L in HHF2; impairs trafficking of the mutant channel. 1 PublicationCorresponds to variant dbSNP:rs104894237EnsemblClinVar. | 1 | |
Natural variantiVAR_031345 | 259 | H → R in HHF2; impairs trafficking and abolishes channel function. 1 PublicationCorresponds to variant dbSNP:rs104894248EnsemblClinVar. | 1 | |
Natural variantiVAR_031346 | 266 | P → L in HHF2. 1 PublicationCorresponds to variant dbSNP:rs1554901679EnsemblClinVar. | 1 | |
Natural variantiVAR_073687 | 282 | E → K in HHF2; prevents the ER export and surface expression of the channel. 1 PublicationCorresponds to variant dbSNP:rs267607196EnsemblClinVar. | 1 | |
Natural variantiVAR_031347 | 301 | R → H in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs74339576EnsemblClinVar. | 1 |
Diabetes mellitus, permanent neonatal 2 (PNDM2)13 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM2 patients may also have developmental delay, muscle weakness, epilepsy and dysmorphic features. PNDM2 transmission pattern is consistent with autosomal dominant inheritance.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026498 | 35 | F → L in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs193929333EnsemblClinVar. | 1 | |
Natural variantiVAR_026499 | 35 | F → V in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs193929333EnsemblClinVar. | 1 | |
Natural variantiVAR_031332 | 46 | H → Y in PNDM2. 2 Publications | 1 | |
Natural variantiVAR_026500 | 50 | R → P in PNDM2; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 PublicationsCorresponds to variant dbSNP:rs80356611EnsemblClinVar. | 1 | |
Natural variantiVAR_031333 | 50 | R → Q in PNDM2; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 PublicationsCorresponds to variant dbSNP:rs80356611EnsemblClinVar. | 1 | |
Natural variantiVAR_026501 | 52 | Q → R in PNDM2; with neurologic features; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201. 3 PublicationsCorresponds to variant dbSNP:rs193929337EnsemblClinVar. | 1 | |
Natural variantiVAR_031334 | 53 | G → D in PNDM2; with neurologic features. 1 PublicationCorresponds to variant dbSNP:rs80356615EnsemblClinVar. | 1 | |
Natural variantiVAR_026504 | 59 | V → G in PNDM2; 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. 3 PublicationsCorresponds to variant dbSNP:rs80356617EnsemblClinVar. | 1 | |
Natural variantiVAR_026505 | 59 | V → M in PNDM2; with neurologic features. 5 PublicationsCorresponds to variant dbSNP:rs80356616EnsemblClinVar. | 1 | |
Natural variantiVAR_073681 | 60 | F → Y in PNDM2; found in a patient who also carries L-64 in cis; thought to be the pathogenic mutation in this double allele; displays gain of function; increases the intrinsic channel open probability and decreases sensitivity toward ATP inhibition; variant L-64 associated in cis is thought to ameliorate the effect of the Y-60 mutation on the channel ATP sensitivity. 1 PublicationCorresponds to variant dbSNP:rs387906783Ensembl. | 1 | |
Natural variantiVAR_073682 | 64 | V → L in PNDM2; found in a patient who also carries Y-60 in cis; unknown pathological significance; only subtle effects, if any, on channel ATP sensitivity; thought to attenuate the deleterious effect of the Y-60 mutation associated in cis on the channel ATP sensitivity. 2 PublicationsCorresponds to variant dbSNP:rs115716690Ensembl. | 1 | |
Natural variantiVAR_031341 | 164 | L → P in PNDM2. 2 Publications | 1 | |
Natural variantiVAR_031342 | 166 | C → Y in PNDM2; individual also diagnosed with West syndrome. 1 PublicationCorresponds to variant dbSNP:rs80356618EnsemblClinVar. | 1 | |
Natural variantiVAR_073684 | 167 | I → L in PNDM2; has severely impaired sensitivity to ATP and markedly increases open channel probability. 1 PublicationCorresponds to variant dbSNP:rs80356620EnsemblClinVar. | 1 | |
Natural variantiVAR_026508 | 170 | K → N in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs80356622EnsemblClinVar. | 1 | |
Natural variantiVAR_026509 | 170 | K → R in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs80356621EnsemblClinVar. | 1 | |
Natural variantiVAR_031343 | 170 | K → T in PNDM2. 1 Publication | 1 | |
Natural variantiVAR_026511 | 201 | R → C in PNDM2; with neurologic features; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59. 6 PublicationsCorresponds to variant dbSNP:rs80356625EnsemblClinVar. | 1 | |
Natural variantiVAR_026512 | 201 | R → H in PNDM2; ability of ATP to block mutant channels greatly reduced. 5 PublicationsCorresponds to variant dbSNP:rs80356624EnsemblClinVar. | 1 | |
Natural variantiVAR_031344 | 201 | R → L in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs80356624EnsemblClinVar. | 1 | |
Natural variantiVAR_026514 | 296 | I → L in PNDM2; with neurologic features. 2 PublicationsCorresponds to variant dbSNP:rs193929353EnsemblClinVar. | 1 | |
Natural variantiVAR_026515 | 322 | E → K in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs193929355EnsemblClinVar. | 1 | |
Natural variantiVAR_026516 | 330 | Y → C in PNDM2. 2 PublicationsCorresponds to variant dbSNP:rs193929356EnsemblClinVar. | 1 | |
Natural variantiVAR_031348 | 330 | Y → S in PNDM2. 1 Publication | 1 | |
Natural variantiVAR_026517 | 333 | F → I in PNDM2; alters gating characteristics; decreases sensitivity to inhibition by ATP and increases intrinsic open probability. 2 PublicationsCorresponds to variant dbSNP:rs193929357EnsemblClinVar. | 1 |
Transient neonatal diabetes mellitus 3 (TNDM3)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionNeonatal 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_031331 | 42 | C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. 1 PublicationCorresponds to variant dbSNP:rs80356610EnsemblClinVar. | 1 | |
Natural variantiVAR_026502 | 53 | G → R in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs80356613EnsemblClinVar. | 1 | |
Natural variantiVAR_026503 | 53 | G → S in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs80356613EnsemblClinVar. | 1 | |
Natural variantiVAR_026510 | 182 | I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs193929348EnsemblClinVar. | 1 |
Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2.
Maturity-onset diabetes of the young 13 (MODY13)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_073686 | 227 | E → K in MODY13. 1 PublicationCorresponds to variant dbSNP:rs587783672EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 64 | V → M: Displays gain of function; increased open state stability, reduced ATP sensitivity and increased channel activity; almost completely abolishes high affinity sensitivity to glibenclamide, an inhibitor of ATP-sensitive potassium channels. 1 Publication | 1 |
Keywords - Diseasei
Diabetes mellitus, Disease variantOrganism-specific databases
DisGeNETi | 3767 |
GeneReviewsi | KCNJ11 |
MalaCardsi | KCNJ11 |
MIMi | 601820, phenotype 610582, phenotype 616329, phenotype 618856, phenotype |
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 99989, Intermediate DEND syndrome 552, MODY 99885, Permanent neonatal diabetes mellitus 99886, Transient neonatal diabetes mellitus |
PharmGKBi | PA217 |
Miscellaneous databases
Pharosi | Q14654, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1886 |
DrugBanki | DB11148, Butamben DB01119, Diazoxide DB00222, Glimepiride DB01016, Glyburide DB00308, Ibutilide DB11633, Isavuconazole DB00922, Levosimendan DB01154, Thiamylal DB00839, Tolazamide DB00661, Verapamil DB01392, Yohimbine |
DrugCentrali | Q14654 |
Genetic variation databases
BioMutai | KCNJ11 |
DMDMi | 76803775 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154957 | 1 – 390 | ATP-sensitive inward rectifier potassium channel 11Add BLAST | 390 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 341 | Phosphothreonine; by MAPK11 Publication | 1 | |
Modified residuei | 385 | Phosphoserine; by MAPK11 Publication | 1 |
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
PhosphoproteinProteomic databases
MassIVEi | Q14654 |
PaxDbi | Q14654 |
PeptideAtlasi | Q14654 |
PRIDEi | Q14654 |
ProteomicsDBi | 22438 60093 [Q14654-1] |
PTM databases
iPTMneti | Q14654 |
PhosphoSitePlusi | Q14654 |
SwissPalmi | Q14654 |
Expressioni
Gene expression databases
Bgeei | ENSG00000187486, Expressed in gastrocnemius and 117 other tissues |
ExpressionAtlasi | Q14654, baseline and differential |
Genevisiblei | Q14654, HS |
Organism-specific databases
HPAi | ENSG00000187486, Tissue enriched (skeletal) |
Interactioni
Subunit structurei
Interacts with ABCC8/SUR.
Interacts with ABCC9/SUR2.
2 PublicationsBinary interactionsi
Hide detailsQ14654
With | #Exp. | IntAct |
---|---|---|
ABCC8 - isoform 1 [Q09428-1] | 2 | EBI-2866553,EBI-15807650 |
ANK2 [Q01484] | 6 | EBI-2866553,EBI-941975 |
EXOSC8 [Q96B26] | 3 | EBI-2866553,EBI-371922 |
GO - Molecular functioni
- ankyrin binding Source: BHF-UCL
- heat shock protein binding Source: Ensembl
- ion channel binding Source: BHF-UCL
- protein C-terminus binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 109969, 17 interactors |
ComplexPortali | CPX-195, Inward rectifying potassium channel complex, Kir6.2-SUR1 CPX-197, Inward rectifying potassium channel complex, Kir6.2-SUR2A CPX-199, Inward rectifying potassium channel complex, Kir6.2-SUR2B |
CORUMi | Q14654 |
DIPi | DIP-58643N |
ELMi | Q14654 |
IntActi | Q14654, 14 interactors |
STRINGi | 9606.ENSP00000345708 |
Chemistry databases
BindingDBi | Q14654 |
Miscellaneous databases
RNActi | Q14654, protein |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 130 – 135 | Selectivity filterBy similarity | 6 |
Sequence similaritiesi
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily. [View classification]Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3827, Eukaryota |
HOGENOMi | CLU_022738_4_0_1 |
InParanoidi | Q14654 |
PhylomeDBi | Q14654 |
TreeFami | TF313676 |
Family and domain databases
Gene3Di | 2.60.40.1400, 1 hit |
InterProi | View protein in InterPro IPR014756, Ig_E-set IPR041647, IRK_C IPR016449, K_chnl_inward-rec_Kir IPR003279, K_chnl_inward-rec_Kir6.2 IPR013518, K_chnl_inward-rec_Kir_cyto IPR040445, Kir_TM |
PANTHERi | PTHR11767, PTHR11767, 1 hit PTHR11767:SF44, PTHR11767:SF44, 1 hit |
Pfami | View protein in Pfam PF01007, IRK, 1 hit PF17655, IRK_C, 1 hit |
PIRSFi | PIRSF005465, GIRK_kir, 1 hit |
PRINTSi | PR01332, KIR62CHANNEL PR01320, KIRCHANNEL |
SUPFAMi | SSF81296, SSF81296, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q14654-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLSRKGIIPE EYVLTRLAED PAEPRYRARQ RRARFVSKKG NCNVAHKNIR
60 70 80 90 100
EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMAW WLIAFAHGDL
110 120 130 140 150
APSEGTAEPC VTSIHSFSSA FLFSIEVQVT IGFGGRMVTE ECPLAILILI
160 170 180 190 200
VQNIVGLMIN AIMLGCIFMK TAQAHRRAET LIFSKHAVIA LRHGRLCFML
210 220 230 240 250
RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM ENGVGGNSIF
260 270 280 290 300
LVAPLIIYHV IDANSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA
310 320 330 340 350
RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTIKVP TPLCTARQLD
360 370 380 390
EDHSLLEALT LASARGPLRK RSVPMAKAKP KFSISPDSLS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PPF1 | E9PPF1_HUMAN | ATP-sensitive inward rectifier pota... | KCNJ11 | 153 | Annotation score: | ||
H0YES9 | H0YES9_HUMAN | ATP-sensitive inward rectifier pota... | KCNJ11 | 155 | Annotation score: |
Sequence cautioni
The sequence AAH40617 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 370 | K → E in BAG63046 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008659 | 10 | E → K1 PublicationCorresponds to variant dbSNP:rs587783667EnsemblClinVar. | 1 | |
Natural variantiVAR_055978 | 18 | A → G. Corresponds to variant dbSNP:rs41309072Ensembl. | 1 | |
Natural variantiVAR_008660 | 23 | E → K Linked to V-337. 6 PublicationsCorresponds to variant dbSNP:rs5219Ensembl. | 1 | |
Natural variantiVAR_031329 | 34 | R → H in HHF2. 1 PublicationCorresponds to variant dbSNP:rs141145502Ensembl. | 1 | |
Natural variantiVAR_026498 | 35 | F → L in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs193929333EnsemblClinVar. | 1 | |
Natural variantiVAR_026499 | 35 | F → V in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs193929333EnsemblClinVar. | 1 | |
Natural variantiVAR_031330 | 40 | G → D in HHF2. 1 PublicationCorresponds to variant dbSNP:rs1001873841EnsemblClinVar. | 1 | |
Natural variantiVAR_031331 | 42 | C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. 1 PublicationCorresponds to variant dbSNP:rs80356610EnsemblClinVar. | 1 | |
Natural variantiVAR_031332 | 46 | H → Y in PNDM2. 2 Publications | 1 | |
Natural variantiVAR_026500 | 50 | R → P in PNDM2; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 PublicationsCorresponds to variant dbSNP:rs80356611EnsemblClinVar. | 1 | |
Natural variantiVAR_031333 | 50 | R → Q in PNDM2; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 PublicationsCorresponds to variant dbSNP:rs80356611EnsemblClinVar. | 1 | |
Natural variantiVAR_026501 | 52 | Q → R in PNDM2; with neurologic features; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201. 3 PublicationsCorresponds to variant dbSNP:rs193929337EnsemblClinVar. | 1 | |
Natural variantiVAR_031334 | 53 | G → D in PNDM2; with neurologic features. 1 PublicationCorresponds to variant dbSNP:rs80356615EnsemblClinVar. | 1 | |
Natural variantiVAR_026502 | 53 | G → R in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs80356613EnsemblClinVar. | 1 | |
Natural variantiVAR_026503 | 53 | G → S in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs80356613EnsemblClinVar. | 1 | |
Natural variantiVAR_031335 | 55 | F → L in HHF2; does neither affect channel expression nor channel response to MgADP. 2 PublicationsCorresponds to variant dbSNP:rs1343400778Ensembl. | 1 | |
Natural variantiVAR_026504 | 59 | V → G in PNDM2; 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. 3 PublicationsCorresponds to variant dbSNP:rs80356617EnsemblClinVar. | 1 | |
Natural variantiVAR_026505 | 59 | V → M in PNDM2; with neurologic features. 5 PublicationsCorresponds to variant dbSNP:rs80356616EnsemblClinVar. | 1 | |
Natural variantiVAR_073681 | 60 | F → Y in PNDM2; found in a patient who also carries L-64 in cis; thought to be the pathogenic mutation in this double allele; displays gain of function; increases the intrinsic channel open probability and decreases sensitivity toward ATP inhibition; variant L-64 associated in cis is thought to ameliorate the effect of the Y-60 mutation on the channel ATP sensitivity. 1 PublicationCorresponds to variant dbSNP:rs387906783Ensembl. | 1 | |
Natural variantiVAR_073682 | 64 | V → L in PNDM2; found in a patient who also carries Y-60 in cis; unknown pathological significance; only subtle effects, if any, on channel ATP sensitivity; thought to attenuate the deleterious effect of the Y-60 mutation associated in cis on the channel ATP sensitivity. 2 PublicationsCorresponds to variant dbSNP:rs115716690Ensembl. | 1 | |
Natural variantiVAR_026506 | 67 | K → N in HHF2. 1 PublicationCorresponds to variant dbSNP:rs747719667Ensembl. | 1 | |
Natural variantiVAR_026507 | 91 | W → R in HHF2. 1 Publication | 1 | |
Natural variantiVAR_031336 | 101 | A → D in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs1014454531EnsemblClinVar. | 1 | |
Natural variantiVAR_031337 | 116 | S → P in HHF2. 1 Publication | 1 | |
Natural variantiVAR_031338 | 134 | G → A in HHF2. 1 Publication | 1 | |
Natural variantiVAR_031339 | 136 | R → L in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs1479483693Ensembl. | 1 | |
Natural variantiVAR_001557 | 147 | L → P in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs28936678EnsemblClinVar. | 1 | |
Natural variantiVAR_031340 | 148 | I → S2 Publications | 1 | |
Natural variantiVAR_073683 | 156 | G → R in HHF2. 1 PublicationCorresponds to variant dbSNP:rs1404429785EnsemblClinVar. | 1 | |
Natural variantiVAR_031341 | 164 | L → P in PNDM2. 2 Publications | 1 | |
Natural variantiVAR_031342 | 166 | C → Y in PNDM2; individual also diagnosed with West syndrome. 1 PublicationCorresponds to variant dbSNP:rs80356618EnsemblClinVar. | 1 | |
Natural variantiVAR_073684 | 167 | I → L in PNDM2; has severely impaired sensitivity to ATP and markedly increases open channel probability. 1 PublicationCorresponds to variant dbSNP:rs80356620EnsemblClinVar. | 1 | |
Natural variantiVAR_026508 | 170 | K → N in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs80356622EnsemblClinVar. | 1 | |
Natural variantiVAR_026509 | 170 | K → R in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs80356621EnsemblClinVar. | 1 | |
Natural variantiVAR_031343 | 170 | K → T in PNDM2. 1 Publication | 1 | |
Natural variantiVAR_026510 | 182 | I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs193929348EnsemblClinVar. | 1 | |
Natural variantiVAR_014929 | 195 | R → H. Corresponds to variant dbSNP:rs5217EnsemblClinVar. | 1 | |
Natural variantiVAR_026511 | 201 | R → C in PNDM2; with neurologic features; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59. 6 PublicationsCorresponds to variant dbSNP:rs80356625EnsemblClinVar. | 1 | |
Natural variantiVAR_026512 | 201 | R → H in PNDM2; ability of ATP to block mutant channels greatly reduced. 5 PublicationsCorresponds to variant dbSNP:rs80356624EnsemblClinVar. | 1 | |
Natural variantiVAR_031344 | 201 | R → L in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs80356624EnsemblClinVar. | 1 | |
Natural variantiVAR_073685 | 204 | D → E in HHF2. 1 PublicationCorresponds to variant dbSNP:rs577757932Ensembl. | 1 | |
Natural variantiVAR_073686 | 227 | E → K in MODY13. 1 PublicationCorresponds to variant dbSNP:rs587783672EnsemblClinVar. | 1 | |
Natural variantiVAR_026513 | 254 | P → L in HHF2; impairs trafficking of the mutant channel. 1 PublicationCorresponds to variant dbSNP:rs104894237EnsemblClinVar. | 1 | |
Natural variantiVAR_031345 | 259 | H → R in HHF2; impairs trafficking and abolishes channel function. 1 PublicationCorresponds to variant dbSNP:rs104894248EnsemblClinVar. | 1 | |
Natural variantiVAR_031346 | 266 | P → L in HHF2. 1 PublicationCorresponds to variant dbSNP:rs1554901679EnsemblClinVar. | 1 | |
Natural variantiVAR_008661 | 270 | L → V2 PublicationsCorresponds to variant dbSNP:rs1800467EnsemblClinVar. | 1 | |
Natural variantiVAR_073687 | 282 | E → K in HHF2; prevents the ER export and surface expression of the channel. 1 PublicationCorresponds to variant dbSNP:rs267607196EnsemblClinVar. | 1 | |
Natural variantiVAR_026514 | 296 | I → L in PNDM2; with neurologic features. 2 PublicationsCorresponds to variant dbSNP:rs193929353EnsemblClinVar. | 1 | |
Natural variantiVAR_031347 | 301 | R → H in HHF2. 2 PublicationsCorresponds to variant dbSNP:rs74339576EnsemblClinVar. | 1 | |
Natural variantiVAR_026515 | 322 | E → K in PNDM2. 1 PublicationCorresponds to variant dbSNP:rs193929355EnsemblClinVar. | 1 | |
Natural variantiVAR_026516 | 330 | Y → C in PNDM2. 2 PublicationsCorresponds to variant dbSNP:rs193929356EnsemblClinVar. | 1 | |
Natural variantiVAR_031348 | 330 | Y → S in PNDM2. 1 Publication | 1 | |
Natural variantiVAR_026517 | 333 | F → I in PNDM2; alters gating characteristics; decreases sensitivity to inhibition by ATP and increases intrinsic open probability. 2 PublicationsCorresponds to variant dbSNP:rs193929357EnsemblClinVar. | 1 | |
Natural variantiVAR_008662 | 337 | I → V Linked to K-23. 6 PublicationsCorresponds to variant dbSNP:rs5215Ensembl. | 1 | |
Natural variantiVAR_008663 | 355 | L → P in NIDDM; Afro-Caribbean. 1 PublicationCorresponds to variant dbSNP:rs797045635EnsemblClinVar. | 1 | |
Natural variantiVAR_008664 | 380 | P → PKP in NIDDM. | 1 | |
Natural variantiVAR_008665 | 385 | S → C1 PublicationCorresponds to variant dbSNP:rs41282930EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045270 | 1 – 87 | Missing in isoform 2. 2 PublicationsAdd BLAST | 87 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi 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 |
Genome annotation databases
Ensembli | ENST00000339994; ENSP00000345708; ENSG00000187486 ENST00000528731; ENSP00000434755; ENSG00000187486 |
GeneIDi | 3767 |
KEGGi | hsa:3767 |
UCSCi | uc001mna.4, human [Q14654-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi 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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6C3O | electron microscopy | 3.90 | A/B/C/D | 1-390 | [»] | |
6C3P | electron microscopy | 5.60 | A/B/C/D | 1-390 | [»] | |
SMRi | Q14654 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109969, 17 interactors |
ComplexPortali | CPX-195, Inward rectifying potassium channel complex, Kir6.2-SUR1 CPX-197, Inward rectifying potassium channel complex, Kir6.2-SUR2A CPX-199, Inward rectifying potassium channel complex, Kir6.2-SUR2B |
CORUMi | Q14654 |
DIPi | DIP-58643N |
ELMi | Q14654 |
IntActi | Q14654, 14 interactors |
STRINGi | 9606.ENSP00000345708 |
Chemistry databases
BindingDBi | Q14654 |
ChEMBLi | CHEMBL1886 |
DrugBanki | DB11148, Butamben DB01119, Diazoxide DB00222, Glimepiride DB01016, Glyburide DB00308, Ibutilide DB11633, Isavuconazole DB00922, Levosimendan DB01154, Thiamylal DB00839, Tolazamide DB00661, Verapamil DB01392, Yohimbine |
DrugCentrali | Q14654 |
Protein family/group databases
TCDBi | 1.A.2.1.17, the inward rectifier k(+) channel (irk-c) family |
PTM databases
iPTMneti | Q14654 |
PhosphoSitePlusi | Q14654 |
SwissPalmi | Q14654 |
Genetic variation databases
BioMutai | KCNJ11 |
DMDMi | 76803775 |
Proteomic databases
MassIVEi | Q14654 |
PaxDbi | Q14654 |
PeptideAtlasi | Q14654 |
PRIDEi | Q14654 |
ProteomicsDBi | 22438 60093 [Q14654-1] |
Protocols and materials databases
Antibodypediai | 24845, 438 antibodies |
Genome annotation databases
Ensembli | ENST00000339994; ENSP00000345708; ENSG00000187486 ENST00000528731; ENSP00000434755; ENSG00000187486 |
GeneIDi | 3767 |
KEGGi | hsa:3767 |
UCSCi | uc001mna.4, human [Q14654-1] |
Organism-specific databases
CTDi | 3767 |
DisGeNETi | 3767 |
GeneCardsi | KCNJ11 |
GeneReviewsi | KCNJ11 |
HGNCi | HGNC:6257, KCNJ11 |
HPAi | ENSG00000187486, Tissue enriched (skeletal) |
MalaCardsi | KCNJ11 |
MIMi | 600937, gene 601820, phenotype 610582, phenotype 616329, phenotype 618856, 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 99989, Intermediate DEND syndrome 552, MODY 99885, Permanent neonatal diabetes mellitus 99886, Transient neonatal diabetes mellitus |
PharmGKBi | PA217 |
VEuPathDBi | HostDB:ENSG00000187486.5 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3827, Eukaryota |
HOGENOMi | CLU_022738_4_0_1 |
InParanoidi | Q14654 |
PhylomeDBi | Q14654 |
TreeFami | TF313676 |
Enzyme and pathway databases
PathwayCommonsi | Q14654 |
Reactomei | R-HSA-1296025, ATP sensitive Potassium channels R-HSA-382556, ABC-family proteins mediated transport R-HSA-422356, Regulation of insulin secretion R-HSA-5578775, Ion homeostasis R-HSA-5678420, Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome R-HSA-5683177, Defective ABCC8 can cause hypo- and hyper-glycemias |
SignaLinki | Q14654 |
SIGNORi | Q14654 |
Miscellaneous databases
BioGRID-ORCSi | 3767, 7 hits in 877 CRISPR screens |
ChiTaRSi | KCNJ11, human |
GeneWikii | Kir6.2 |
GenomeRNAii | 3767 |
Pharosi | Q14654, Tclin |
PROi | PR:Q14654 |
RNActi | Q14654, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000187486, Expressed in gastrocnemius and 117 other tissues |
ExpressionAtlasi | Q14654, baseline and differential |
Genevisiblei | Q14654, HS |
Family and domain databases
Gene3Di | 2.60.40.1400, 1 hit |
InterProi | View protein in InterPro IPR014756, Ig_E-set IPR041647, IRK_C IPR016449, K_chnl_inward-rec_Kir IPR003279, K_chnl_inward-rec_Kir6.2 IPR013518, K_chnl_inward-rec_Kir_cyto IPR040445, Kir_TM |
PANTHERi | PTHR11767, PTHR11767, 1 hit PTHR11767:SF44, PTHR11767:SF44, 1 hit |
Pfami | View protein in Pfam PF01007, IRK, 1 hit PF17655, IRK_C, 1 hit |
PIRSFi | PIRSF005465, GIRK_kir, 1 hit |
PRINTSi | PR01332, KIR62CHANNEL PR01320, KIRCHANNEL |
SUPFAMi | SSF81296, SSF81296, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KCJ11_HUMAN | |
Accessioni | Q14654Primary (citable) accession number: Q14654 Secondary accession number(s): B4DWI4 Q8IW96 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | September 27, 2005 | |
Last modified: | February 10, 2021 | |
This is version 213 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families