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Q14500 (KCJ12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ATP-sensitive inward rectifier potassium channel 12
Alternative name(s):
Inward rectifier K(+) channel Kir2.2
Short name=IRK-2
Inward rectifier K(+) channel Kir2.2v
Potassium channel, inwardly rectifying subfamily J member 12
Gene names
Name:KCNJ12
Synonyms:IRK2, KCNJN1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length433 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. 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. Ref.1 Ref.2 Ref.3 Ref.7

Subunit structure

Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking By similarity. Homotetramer. Forms heteromer with KCNJ4. Ref.7

Subcellular location

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein Ref.1 Ref.2 Ref.3 Ref.7.

Domain

Phosphatidylinositol 4,5-bisphosphate binding to the cytoplasmic side of the channel triggers a conformation change leading to channel opening By similarity.

Sequence similarities

Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ12 subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 433433ATP-sensitive inward rectifier potassium channel 12
PRO_0000154962

Regions

Topological domain1 – 8282Cytoplasmic By similarity
Transmembrane83 – 10725Helical; Name=M1; By similarity
Topological domain108 – 12316Extracellular By similarity
Intramembrane124 – 1285 By similarity
Intramembrane129 – 14113Helical; Pore-forming; Name=H5; By similarity
Intramembrane142 – 15110Pore-forming; By similarity
Topological domain152 – 1565Extracellular By similarity
Transmembrane157 – 18125Helical; Name=M2; By similarity
Topological domain182 – 433252Cytoplasmic By similarity
Motif79 – 813Interaction with phosphatidylinositides By similarity
Motif143 – 1486Selectivity filter By similarity
Motif183 – 1908Interaction with phosphatidylinositides By similarity
Motif431 – 4333PDZ-binding Potential

Sites

Site1731Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity

Amino acid modifications

Disulfide bond155Interchain By similarity

Natural variations

Natural variant61R → Q.
Corresponds to variant rs3752032 [ dbSNP | Ensembl ].
VAR_024509
Natural variant151S → L.
Corresponds to variant rs1657738 [ dbSNP | Ensembl ].
VAR_049671
Natural variant1001I → V. Ref.2
Corresponds to variant rs8076599 [ dbSNP | Ensembl ].
VAR_059365
Natural variant1181R → Q.
Corresponds to variant rs1657740 [ dbSNP | Ensembl ].
VAR_059366
Natural variant1561P → L.
Corresponds to variant rs1714864 [ dbSNP | Ensembl ].
VAR_049672
Natural variant1921Q → H.
Corresponds to variant rs1657742 [ dbSNP | Ensembl ].
VAR_059367
Natural variant2491I → V.
Corresponds to variant rs4985866 [ dbSNP | Ensembl ].
VAR_049673
Natural variant4301E → G.
Corresponds to variant rs5021699 [ dbSNP | Ensembl ].
VAR_059368

Experimental info

Sequence conflict431R → H in AAC50615. Ref.2
Sequence conflict711M → I in AAC50615. Ref.2
Sequence conflict1391E → K in AAC50615. Ref.2
Sequence conflict1421T → N in AAC50615. Ref.2
Sequence conflict1451G → S in AAC50615. Ref.2
Sequence conflict1731D → N in AAC50615. Ref.2
Sequence conflict1841M → V in AAC01951. Ref.5
Sequence conflict1851A → V in AAC50615. Ref.2
Sequence conflict2111L → F in AAC50615. Ref.2
Sequence conflict2391E → K in AAC50615. Ref.2
Sequence conflict261 – 2622RI → HS in AAC50615. Ref.2
Sequence conflict2851Missing in AAA65122. Ref.1
Sequence conflict289 – 2902ET → QM in AAC50615. Ref.2
Sequence conflict2971V → I in AAC50615. Ref.2
Sequence conflict3021M → I in AAC50615. Ref.2
Sequence conflict3341Missing in AAC50615. Ref.2
Sequence conflict3351Missing in AAC01951. Ref.5
Sequence conflict3431S → L in AAC50615. Ref.2
Sequence conflict3711S → R in AAC50615. Ref.2
Sequence conflict3781E → K in AAC50615. Ref.2
Sequence conflict4021D → E in AAC50615. Ref.2
Sequence conflict4051S → I in AAC50615. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q14500 [UniParc].

Last modified October 11, 2005. Version 2.
Checksum: 082027A1765B6F4E

FASTA43349,001
        10         20         30         40         50         60 
MTAASRANPY SIVSSEEDGL HLVTMSGANG FGNGKVHTRR RCRNRFVKKN GQCNIEFANM 

        70         80         90        100        110        120 
DEKSQRYLAD MFTTCVDIRW RYMLLIFSLA FLASWLLFGI IFWVIAVAHG DLEPAEGRGR 

       130        140        150        160        170        180 
TPCVMQVHGF MAAFLFSIET QTTIGYGLRC VTEECPVAVF MVVAQSIVGC IIDSFMIGAI 

       190        200        210        220        230        240 
MAKMARPKKR AQTLLFSHNA VVALRDGKLC LMWRVGNLRK SHIVEAHVRA QLIKPRVTEE 

       250        260        270        280        290        300 
GEYIPLDQID IDVGFDKGLD RIFLVSPITI LHEIDEASPL FGISRQDLET DDFEIVVILE 

       310        320        330        340        350        360 
GMVEATAMTT QARSSYLANE ILWGHRFEPV LFEEKNQYKI DYSHFHKTYE VPSTPRCSAK 

       370        380        390        400        410        420 
DLVENKFLLP SANSFCYENE LAFLSRDEED EADGDQDGRS RDGLSPQARH DFDRLQAGGG 

       430 
VLEQRPYRRE SEI 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and functional expression of an inwardly rectifying K+ channel from human atrium."
Wible B.A., de Biasi M., Majumder K., Taglialatela M., Brown A.M.
Circ. Res. 76:343-350(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
Tissue: Heart atrium.
[2]"Kir2.2v: a possible negative regulator of the inwardly rectifying K+ channel Kir2.2."
Namba N., Inagaki N., Gonoi T., Seino Y., Seino S.
FEBS Lett. 386:211-214(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, VARIANT VAL-100.
[3]"Identification of human Kir2.2 (KCNJ12) gene encoding functional inward rectifier potassium channel in both mammalian cells and Xenopus oocytes."
Kaibara M., Ishihara K., Doi Y., Hayashi H., Ehara T., Taniyama K.
FEBS Lett. 531:250-254(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, SUBCELLULAR LOCATION.
[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].
Tissue: Eye.
[5]"An alternate promoter directs expression of a truncated, muscle-specific isoform of the human ankyrin 1 gene."
Gallagher P.G., Forget B.G.
J. Biol. Chem. 273:1339-1348(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 161-433.
Tissue: Skeletal muscle.
[6]"Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome."
Preisig-Muller R., Schlichthorl G., Goerge T., Heinen S., Bruggemann A., Rajan S., Derst C., Veh R.W., Daut J.
Proc. Natl. Acad. Sci. U.S.A. 99:7774-7779(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCNJ4.
[7]"Direct and specific activation of human inward rectifier K+ channels by membrane phosphatidylinositol 4,5-bisphosphate."
D'Avanzo N., Cheng W.W., Doyle D.A., Nichols C.G.
J. Biol. Chem. 285:37129-37132(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L36069 mRNA. Translation: AAA65122.1.
U53143 Genomic DNA. Translation: AAC50615.1.
AB074970 Genomic DNA. Translation: BAC02718.1.
AB182123 mRNA. Translation: BAD23901.1.
BC027982 mRNA. Translation: AAH27982.1.
AF005214 mRNA. Translation: AAC01951.1.
CCDSCCDS11219.1.
PIRI52864.
S71341.
RefSeqNP_066292.2. NM_021012.4.
XP_005256682.1. XM_005256625.2.
UniGeneHs.200629.

3D structure databases

ProteinModelPortalQ14500.
SMRQ14500. Positions 42-372.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109970. 17 interactions.
STRING9606.ENSP00000328150.

Chemistry

DrugBankDB00204. Dofetilide.
GuidetoPHARMACOLOGY431.

Protein family/group databases

TCDB1.A.2.1.9. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteQ14500.

Polymorphism databases

DMDM77416868.

Proteomic databases

PaxDbQ14500.
PRIDEQ14500.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331718; ENSP00000328150; ENSG00000184185.
ENST00000563509; ENSP00000456250; ENSG00000261309.
ENST00000583088; ENSP00000463778; ENSG00000184185.
ENST00000609903; ENSP00000476405; ENSG00000261309.
GeneID3768.
KEGGhsa:3768.
UCSCuc002gyv.1. human.

Organism-specific databases

CTD3768.
GeneCardsGC17P021532.
HGNCHGNC:6258. KCNJ12.
HPAHPA027021.
MIM602323. gene.
neXtProtNX_Q14500.
PharmGKBPA218.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG72812.
HOGENOMHOG000237325.
HOVERGENHBG006178.
InParanoidQ14500.
KOK05005.
OMACFMIGAI.
OrthoDBEOG7XPZ5K.
PhylomeDBQ14500.
TreeFamTF313676.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeQ14500.
GenevestigatorQ14500.

Family and domain databases

Gene3D2.60.40.1400. 1 hit.
InterProIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003272. K_chnl_inward-rec_Kir2.2.
IPR013518. K_chnl_inward-rec_Kir_cyto.
IPR013673. K_chnl_inward-rec_Kir_N.
[Graphical view]
PANTHERPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF14. PTHR11767:SF14. 1 hit.
PfamPF01007. IRK. 1 hit.
PF08466. IRK_N. 1 hit.
[Graphical view]
PIRSFPIRSF005465. GIRK_kir. 1 hit.
PRINTSPR01325. KIR22CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

GeneWikiKCNJ12.
GenomeRNAi3768.
NextBio14775.
PROQ14500.
SOURCESearch...

Entry information

Entry nameKCJ12_HUMAN
AccessionPrimary (citable) accession number: Q14500
Secondary accession number(s): O43401, Q15756, Q8NG63
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 11, 2005
Last modified: July 9, 2014
This is version 140 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 17

Human chromosome 17: entries, gene names and cross-references to MIM