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Protein

ATP-sensitive inward rectifier potassium channel 12

Gene

KCNJ12

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

Functioni

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.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei173 – 1731Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity

GO - Molecular functioni

  1. inward rectifier potassium channel activity Source: UniProtKB

GO - Biological processi

  1. muscle contraction Source: ProtInc
  2. potassium ion import Source: GO_Central
  3. potassium ion transport Source: UniProtKB
  4. protein homotetramerization Source: UniProtKB
  5. regulation of heart contraction Source: ProtInc
  6. regulation of ion transmembrane transport Source: GO_Central
  7. synaptic transmission Source: Reactome
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.
REACT_75870. Classical Kir channels.

Protein family/group databases

TCDBi1.A.2.1.9. inward rectifier k(+) channel (irk-c) family.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:KCNJ12
Synonyms:IRK2, KCNJN1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6258. KCNJ12.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8282CytoplasmicBy similarityAdd
BLAST
Transmembranei83 – 10725Helical; Name=M1By similarityAdd
BLAST
Topological domaini108 – 12316ExtracellularBy similarityAdd
BLAST
Intramembranei124 – 1285By similarity
Intramembranei129 – 14113Helical; Pore-forming; Name=H5By similarityAdd
BLAST
Intramembranei142 – 15110Pore-formingBy similarity
Topological domaini152 – 1565ExtracellularBy similarity
Transmembranei157 – 18125Helical; Name=M2By similarityAdd
BLAST
Topological domaini182 – 433252CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: GO_Central
  2. intrinsic component of membrane Source: UniProtKB
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA218.

Chemistry

DrugBankiDB00204. Dofetilide.
DB01392. Yohimbine.

Polymorphism and mutation databases

BioMutaiKCNJ12.
DMDMi77416868.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 433433ATP-sensitive inward rectifier potassium channel 12PRO_0000154962Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei75 – 751S-nitrosocysteineBy similarity
Disulfide bondi155 – 155InterchainBy similarity

Keywords - PTMi

Disulfide bond, S-nitrosylation

Proteomic databases

PaxDbiQ14500.
PRIDEiQ14500.

PTM databases

PhosphoSiteiQ14500.

Expressioni

Gene expression databases

BgeeiQ14500.
GenevestigatoriQ14500.

Organism-specific databases

HPAiHPA027021.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

BioGridi109970. 17 interactions.
STRINGi9606.ENSP00000328150.

Structurei

3D structure databases

ProteinModelPortaliQ14500.
SMRiQ14500. Positions 42-372.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi79 – 813Interaction with phosphatidylinositidesBy similarity
Motifi143 – 1486Selectivity filterBy similarity
Motifi183 – 1908Interaction with phosphatidylinositidesBy similarity
Motifi431 – 4333PDZ-bindingSequence Analysis

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiQ14500.
KOiK05005.
OMAiTPCVLQV.
OrthoDBiEOG7XPZ5K.
PhylomeDBiQ14500.
TreeFamiTF313676.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. 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]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF14. PTHR11767:SF14. 1 hit.
PfamiPF01007. IRK. 1 hit.
PF08466. IRK_N. 1 hit.
[Graphical view]
PRINTSiPR01325. KIR22CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

Q14500-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAASRANPY SIVSSEEDGL HLVTMSGANG FGNGKVHTRR RCRNRFVKKN
60 70 80 90 100
GQCNIEFANM DEKSQRYLAD MFTTCVDIRW RYMLLIFSLA FLASWLLFGI
110 120 130 140 150
IFWVIAVAHG DLEPAEGRGR TPCVMQVHGF MAAFLFSIET QTTIGYGLRC
160 170 180 190 200
VTEECPVAVF MVVAQSIVGC IIDSFMIGAI MAKMARPKKR AQTLLFSHNA
210 220 230 240 250
VVALRDGKLC LMWRVGNLRK SHIVEAHVRA QLIKPRVTEE GEYIPLDQID
260 270 280 290 300
IDVGFDKGLD RIFLVSPITI LHEIDEASPL FGISRQDLET DDFEIVVILE
310 320 330 340 350
GMVEATAMTT QARSSYLANE ILWGHRFEPV LFEEKNQYKI DYSHFHKTYE
360 370 380 390 400
VPSTPRCSAK DLVENKFLLP SANSFCYENE LAFLSRDEED EADGDQDGRS
410 420 430
RDGLSPQARH DFDRLQAGGG VLEQRPYRRE SEI
Length:433
Mass (Da):49,001
Last modified:October 11, 2005 - v2
Checksum:i082027A1765B6F4E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti43 – 431R → H in AAC50615 (PubMed:8647284).Curated
Sequence conflicti71 – 711M → I in AAC50615 (PubMed:8647284).Curated
Sequence conflicti139 – 1391E → K in AAC50615 (PubMed:8647284).Curated
Sequence conflicti142 – 1421T → N in AAC50615 (PubMed:8647284).Curated
Sequence conflicti145 – 1451G → S in AAC50615 (PubMed:8647284).Curated
Sequence conflicti173 – 1731D → N in AAC50615 (PubMed:8647284).Curated
Sequence conflicti184 – 1841M → V in AAC01951 (PubMed:9430667).Curated
Sequence conflicti185 – 1851A → V in AAC50615 (PubMed:8647284).Curated
Sequence conflicti211 – 2111L → F in AAC50615 (PubMed:8647284).Curated
Sequence conflicti239 – 2391E → K in AAC50615 (PubMed:8647284).Curated
Sequence conflicti261 – 2622RI → HS in AAC50615 (PubMed:8647284).Curated
Sequence conflicti285 – 2851Missing in AAA65122 (PubMed:7859381).Curated
Sequence conflicti289 – 2902ET → QM in AAC50615 (PubMed:8647284).Curated
Sequence conflicti297 – 2971V → I in AAC50615 (PubMed:8647284).Curated
Sequence conflicti302 – 3021M → I in AAC50615 (PubMed:8647284).Curated
Sequence conflicti334 – 3341Missing in AAC50615 (PubMed:8647284).Curated
Sequence conflicti335 – 3351Missing in AAC01951 (PubMed:9430667).Curated
Sequence conflicti343 – 3431S → L in AAC50615 (PubMed:8647284).Curated
Sequence conflicti371 – 3711S → R in AAC50615 (PubMed:8647284).Curated
Sequence conflicti378 – 3781E → K in AAC50615 (PubMed:8647284).Curated
Sequence conflicti402 – 4021D → E in AAC50615 (PubMed:8647284).Curated
Sequence conflicti405 – 4051S → I in AAC50615 (PubMed:8647284).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61R → Q.
Corresponds to variant rs3752032 [ dbSNP | Ensembl ].
VAR_024509
Natural varianti15 – 151S → L.
Corresponds to variant rs1657738 [ dbSNP | Ensembl ].
VAR_049671
Natural varianti100 – 1001I → V.1 Publication
Corresponds to variant rs8076599 [ dbSNP | Ensembl ].
VAR_059365
Natural varianti118 – 1181R → Q.
Corresponds to variant rs1657740 [ dbSNP | Ensembl ].
VAR_059366
Natural varianti156 – 1561P → L.
Corresponds to variant rs1714864 [ dbSNP | Ensembl ].
VAR_049672
Natural varianti192 – 1921Q → H.
Corresponds to variant rs1657742 [ dbSNP | Ensembl ].
VAR_059367
Natural varianti249 – 2491I → V.
Corresponds to variant rs4985866 [ dbSNP | Ensembl ].
VAR_049673
Natural varianti430 – 4301E → G.
Corresponds to variant rs5021699 [ dbSNP | Ensembl ].
VAR_059368

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11219.1.
PIRiI52864.
S71341.
RefSeqiNP_066292.2. NM_021012.4.
XP_005256682.1. XM_005256625.3.
UniGeneiHs.200629.

Genome annotation databases

EnsembliENST00000331718; ENSP00000328150; ENSG00000184185.
ENST00000583088; ENSP00000463778; ENSG00000184185.
GeneIDi3768.
KEGGihsa:3768.
UCSCiuc002gyv.1. human.

Polymorphism and mutation databases

BioMutaiKCNJ12.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11219.1.
PIRiI52864.
S71341.
RefSeqiNP_066292.2. NM_021012.4.
XP_005256682.1. XM_005256625.3.
UniGeneiHs.200629.

3D structure databases

ProteinModelPortaliQ14500.
SMRiQ14500. Positions 42-372.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109970. 17 interactions.
STRINGi9606.ENSP00000328150.

Chemistry

DrugBankiDB00204. Dofetilide.
DB01392. Yohimbine.
GuidetoPHARMACOLOGYi431.

Protein family/group databases

TCDBi1.A.2.1.9. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteiQ14500.

Polymorphism and mutation databases

BioMutaiKCNJ12.
DMDMi77416868.

Proteomic databases

PaxDbiQ14500.
PRIDEiQ14500.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331718; ENSP00000328150; ENSG00000184185.
ENST00000583088; ENSP00000463778; ENSG00000184185.
GeneIDi3768.
KEGGihsa:3768.
UCSCiuc002gyv.1. human.

Organism-specific databases

CTDi3768.
GeneCardsiGC17P022222.
HGNCiHGNC:6258. KCNJ12.
HPAiHPA027021.
MIMi602323. gene.
neXtProtiNX_Q14500.
PharmGKBiPA218.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiQ14500.
KOiK05005.
OMAiTPCVLQV.
OrthoDBiEOG7XPZ5K.
PhylomeDBiQ14500.
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.
REACT_75870. Classical Kir channels.

Miscellaneous databases

ChiTaRSiKCNJ12. human.
GeneWikiiKCNJ12.
GenomeRNAii3768.
NextBioi14775.
PROiQ14500.
SOURCEiSearch...

Gene expression databases

BgeeiQ14500.
GenevestigatoriQ14500.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. 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]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF14. PTHR11767:SF14. 1 hit.
PfamiPF01007. IRK. 1 hit.
PF08466. IRK_N. 1 hit.
[Graphical view]
PRINTSiPR01325. KIR22CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiKCJ12_HUMAN
AccessioniPrimary (citable) accession number: Q14500
Secondary accession number(s): O43401, Q15756, Q8NG63
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 11, 2005
Last modified: April 29, 2015
This is version 149 of the entry and version 2 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 17
    Human chromosome 17: 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.