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Protein

G protein-activated inward rectifier potassium channel 2

Gene

KCNJ6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This potassium channel may be involved in the regulation of insulin secretion by glucose and/or neurotransmitters acting through G-protein-coupled receptors. 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei182 – 1821Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity

GO - Molecular functioni

  • G-protein activated inward rectifier potassium channel activity Source: ProtInc
  • inward rectifier potassium channel activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiREACT_25004. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
REACT_75831. Activation of G protein gated Potassium channels.

Protein family/group databases

TCDBi1.A.2.1.10. inward rectifier k(+) channel (irk-c) family.

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-activated inward rectifier potassium channel 2
Short name:
GIRK-2
Alternative name(s):
BIR1
Inward rectifier K(+) channel Kir3.2
KATP-2
Potassium channel, inwardly rectifying subfamily J member 6
Gene namesi
Name:KCNJ6
Synonyms:GIRK2, KATP2, KCNJ7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:6267. KCNJ6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8989CytoplasmicBy similarityAdd
BLAST
Transmembranei90 – 11425Helical; Name=M1By similarityAdd
BLAST
Topological domaini115 – 13824ExtracellularBy similarityAdd
BLAST
Intramembranei139 – 15012Helical; Pore-forming; Name=H5By similarityAdd
BLAST
Intramembranei151 – 1577Pore-formingBy similarity
Topological domaini158 – 1669ExtracellularBy similarity
Transmembranei167 – 18822Helical; Name=M2By similarityAdd
BLAST
Topological domaini189 – 423235CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: UniProtKB
  • voltage-gated potassium channel complex Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Keppen-Lubinsky syndrome (KPLBS)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA rare disease characterized by severe developmental delay, intellectual disability, severe generalized lipodystrophy, dysmorphic features including microcephaly, large prominent eyes, narrow nasal bridge, tented upper lip, high palate, open mouth, tightly adherent skin, and aged appearance.

See also OMIM:614098
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti152 – 1521Missing in KPLBS. 1 Publication
VAR_073430
Natural varianti154 – 1541G → S in KPLBS. 1 Publication
VAR_073431

Keywords - Diseasei

Congenital generalized lipodystrophy, Disease mutation

Organism-specific databases

MIMi614098. phenotype.
PharmGKBiPA30049.

Chemistry

DrugBankiDB01159. Halothane.

Polymorphism and mutation databases

BioMutaiKCNJ6.
DMDMi1352487.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 423423G protein-activated inward rectifier potassium channel 2PRO_0000154942Add
BLAST

Proteomic databases

PaxDbiP48051.
PRIDEiP48051.

PTM databases

PhosphoSiteiP48051.

Expressioni

Tissue specificityi

Most abundant in cerebellum, and to a lesser degree in islets and exocrine pancreas.

Gene expression databases

BgeeiP48051.
CleanExiHS_KCNJ6.
GenevisibleiP48051. HS.

Organism-specific databases

HPAiCAB012452.

Interactioni

Subunit structurei

Associates with GIRK1 or GIRK4 to form a G-protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane (By similarity).By similarity

Protein-protein interaction databases

BioGridi109965. 5 interactions.
STRINGi9606.ENSP00000288309.

Structurei

3D structure databases

ProteinModelPortaliP48051.
SMRiP48051. Positions 53-378.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi152 – 1576Selectivity filterBy similarity
Motifi420 – 4234PDZ-binding

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP48051.
KOiK05000.
OMAiTIHQPKL.
OrthoDBiEOG7XPZ5K.
PhylomeDBiP48051.
TreeFamiTF313676.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003275. K_chnl_inward-rec_Kir3.2.
IPR013518. K_chnl_inward-rec_Kir_cyto.
[Graphical view]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF19. PTHR11767:SF19. 1 hit.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01328. KIR32CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

P48051-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKLTESMTN VLEGDSMDQD VESPVAIHQP KLPKQARDDL PRHISRDRTK
60 70 80 90 100
RKIQRYVRKD GKCNVHHGNV RETYRYLTDI FTTLVDLKWR FNLLIFVMVY
110 120 130 140 150
TVTWLFFGMI WWLIAYIRGD MDHIEDPSWT PCVTNLNGFV SAFLFSIETE
160 170 180 190 200
TTIGYGYRVI TDKCPEGIIL LLIQSVLGSI VNAFMVGCMF VKISQPKKRA
210 220 230 240 250
ETLVFSTHAV ISMRDGKLCL MFRVGDLRNS HIVEASIRAK LIKSKQTSEG
260 270 280 290 300
EFIPLNQTDI NVGYYTGDDR LFLVSPLIIS HEINQQSPFW EISKAQLPKE
310 320 330 340 350
ELEIVVILEG MVEATGMTCQ ARSSYITSEI LWGYRFTPVL TLEDGFYEVD
360 370 380 390 400
YNSFHETYET STPSLSAKEL AELASRAELP LSWSVSSKLN QHAELETEEE
410 420
EKNLEEQTER NGDVANLENE SKV
Length:423
Mass (Da):48,451
Last modified:February 1, 1996 - v1
Checksum:i7A02F6B0FBF8B7D4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti152 – 1521Missing in KPLBS. 1 Publication
VAR_073430
Natural varianti154 – 1541G → S in KPLBS. 1 Publication
VAR_073431

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24660 mRNA. Translation: AAC50258.1.
L78480 mRNA. Translation: AAB02277.1.
D87327 mRNA. Translation: BAA13331.1.
U52153 mRNA. Translation: AAB07044.1.
BC101547 mRNA. Translation: AAI01548.1.
S78685, S78684 Genomic DNA. Translation: AAB34738.2.
G02354 Genomic DNA. No translation available.
CCDSiCCDS42927.1.
PIRiI38979.
RefSeqiNP_002231.1. NM_002240.4.
XP_011527860.1. XM_011529558.1.
XP_011527861.1. XM_011529559.1.
UniGeneiHs.626242.
Hs.658533.
Hs.741904.

Genome annotation databases

EnsembliENST00000609713; ENSP00000477437; ENSG00000157542.
GeneIDi3763.
KEGGihsa:3763.
UCSCiuc002ywo.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24660 mRNA. Translation: AAC50258.1.
L78480 mRNA. Translation: AAB02277.1.
D87327 mRNA. Translation: BAA13331.1.
U52153 mRNA. Translation: AAB07044.1.
BC101547 mRNA. Translation: AAI01548.1.
S78685, S78684 Genomic DNA. Translation: AAB34738.2.
G02354 Genomic DNA. No translation available.
CCDSiCCDS42927.1.
PIRiI38979.
RefSeqiNP_002231.1. NM_002240.4.
XP_011527860.1. XM_011529558.1.
XP_011527861.1. XM_011529559.1.
UniGeneiHs.626242.
Hs.658533.
Hs.741904.

3D structure databases

ProteinModelPortaliP48051.
SMRiP48051. Positions 53-378.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109965. 5 interactions.
STRINGi9606.ENSP00000288309.

Chemistry

BindingDBiP48051.
ChEMBLiCHEMBL3038490.
DrugBankiDB01159. Halothane.
GuidetoPHARMACOLOGYi435.

Protein family/group databases

TCDBi1.A.2.1.10. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteiP48051.

Polymorphism and mutation databases

BioMutaiKCNJ6.
DMDMi1352487.

Proteomic databases

PaxDbiP48051.
PRIDEiP48051.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000609713; ENSP00000477437; ENSG00000157542.
GeneIDi3763.
KEGGihsa:3763.
UCSCiuc002ywo.3. human.

Organism-specific databases

CTDi3763.
GeneCardsiGC21M038996.
HGNCiHGNC:6267. KCNJ6.
HPAiCAB012452.
MIMi600877. gene.
614098. phenotype.
neXtProtiNX_P48051.
PharmGKBiPA30049.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP48051.
KOiK05000.
OMAiTIHQPKL.
OrthoDBiEOG7XPZ5K.
PhylomeDBiP48051.
TreeFamiTF313676.

Enzyme and pathway databases

ReactomeiREACT_25004. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
REACT_75831. Activation of G protein gated Potassium channels.

Miscellaneous databases

ChiTaRSiKCNJ6. human.
GeneWikiiKCNJ6.
GenomeRNAii3763.
NextBioi14755.
PROiP48051.
SOURCEiSearch...

Gene expression databases

BgeeiP48051.
CleanExiHS_KCNJ6.
GenevisibleiP48051. HS.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003275. K_chnl_inward-rec_Kir3.2.
IPR013518. K_chnl_inward-rec_Kir_cyto.
[Graphical view]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF19. PTHR11767:SF19. 1 hit.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01328. KIR32CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels."
    Ferrer J., Nichols C.G., Makhina E.N., Salkoff L., Bernstein J., Gerhard D., Wasson J., Ramanadham S., Permutt A.
    J. Biol. Chem. 270:26086-26091(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Insulinoma.
  2. "Subunit interactions in the assembly of neuronal G protein-activated inwardly rectifying K+ channels."
    Dissmann E., Karschin A.
    Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Hippocampus.
  3. "Gene identification in the 1.6 Mb of the Down syndrome region on chromosome 21."
    Ohira M., Seki N., Nagase T., Suzuki E., Nomura N., Ohara O., Saito T., Ichikawa H., Ohki M.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  4. "Co-expression of human Kir3 subunits can yield channels with different functional properties."
    Schoots O., Wilson J.M., Ethier N., Bigras E., Hebert T.E., Van Tol H.H.M.
    Cell. Signal. 11:871-883(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Cerebellum.
  5. "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].
    Tissue: Placenta.
  6. "Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit."
    Sakura H., Bond C., Warren-Perry M., Horsley S., Kearney L., Tucker S., Adelman J., Turner R., Ashcroft F.M.
    FEBS Lett. 367:193-197(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 17-423.
  7. "Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM."
    Tsaur M.-L., Menzel S., Lai F.-P., Espinosa R. III, Concannon P., Spielman R.S., Hanis C.L., Cox N.J., le Beau M.M., German M.S., Jan L.Y., Bell G.I., Stoffel M.
    Diabetes 44:592-596(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 116-211.
  8. "Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying K+ channel encoded by KCNJ6."
    Masotti A., Uva P., Davis-Keppen L., Basel-Vanagaite L., Cohen L., Pisaneschi E., Celluzzi A., Bencivenga P., Fang M., Tian M., Xu X., Cappa M., Dallapiccola B.
    Am. J. Hum. Genet. 96:295-300(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN KPLBS, VARIANTS KPLBS THR-152 DEL AND SER-154.

Entry informationi

Entry nameiKCNJ6_HUMAN
AccessioniPrimary (citable) accession number: P48051
Secondary accession number(s): Q3MJ74, Q53WW6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 22, 2015
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.