B7U540 (IRK18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inward rectifier potassium channel 18

Alternative name(s):
Inward rectifier K(+) channel Kir2.6
Potassium channel, inwardly rectifying subfamily J member 18

Gene names

Name:

KCNJ18

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	433 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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
Subcellular location	Cell membrane; Multi-pass membrane protein Probable.
Tissue specificity	Specifically expressed in skeletal muscle. Ref.1
Induction	Up-regulated by triiodothyronine. Ref.1
Post-translational modification	Probably phosphorylated by PKC; decreases single-channel open probability. Ref.1
Involvement in disease	Thyrotoxic periodic paralysis 2 (TTPP2) [MIM:613239]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.1
Sequence similarities	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ12 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	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)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	inward rectifier potassium channel activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 433	433	Inward rectifier potassium channel 18		PRO_0000395171
Regions
	Topological domain	1 – 84	84	Cytoplasmic Potential
	Transmembrane	85 – 105	21	Helical; Potential
	Topological domain	106 – 156	51	Extracellular Potential
	Transmembrane	157 – 177	21	Helical; Potential
	Topological domain	178 – 433	256	Cytoplasmic Potential
Natural variations
	Natural variant	140	1	T → M in TTPP2. Ref.1		VAR_063286
	Natural variant	205	1	R → H in TTPP2; hypermorphic; longer time required for half-maximal current degradation. Ref.1		VAR_063287
	Natural variant	354	1	T → M in TTPP2; small decrease in current density. Ref.1		VAR_063288
	Natural variant	366	1	K → R in TTPP2; hypermorphic; longer time required for half-maximal current degradation. Ref.1		VAR_063289
Experimental info
	Mutagenesis	354	1	T → E: Decreases the single-channel open probability (Po) without altering its conductance. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	B7U540 [UniParc]. Last modified December 15, 2009. Version 2. Checksum: 04FC98656CD046D1	FASTA	433	48,738
	10 20 30 40 50 60 MTAASQANPY SIVSLEEDGL HLVTMSGAKG FGNGKVHTQH RCRNRFVKKN GQCNIAFANM 70 80 90 100 110 120 DEKSQRYLAD MFTTCVDIRW RYMLLIFSLA FLASWLLFGV IFWVIAVAHG DLEPAEGHGR 130 140 150 160 170 180 TPCVMQVHGF MAAFLFSIET QTTIGYGLRC VTEECLVAVF MVVAQSIVGC IIDSFMIGAI 190 200 210 220 230 240 MAKMARPKKR AHTLLFSHNA VVALRDGKLC LMWRVGNLRK SHIVEAHVRA QLIKPRVTEE 250 260 270 280 290 300 GEYIPLDQVD IDVGFDKGLD RIFLVSPITI LHEIDEASPL LGISRQDLET DDFEIVVILE 310 320 330 340 350 360 GMVEATAMTT QARSSYLANE ILWGHRFEPV LFEEKNQFKI DHSHFHKTYE VPSTPRCSAK 370 380 390 400 410 420 DLVENKFLLP SANSFCYENE LAFLSRDEED EADGDQDGRS RDGLSPQARH DFDRLQAGGG 430 VLEQRPYRRG SEI

References

[1]

"Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis." Ryan D.P., da Silva M.R., Soong T.W., Fontaine B., Donaldson M.R., Kung A.W., Jongjaroenprasert W., Liang M.C., Khoo D.H., Cheah J.S., Ho S.C., Bernstein H.S., Maciel R.M., Brown R.H. Jr., Ptacek L.J. Cell 140:88-98(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION BY TRIIODOTHYRONINE, TISSUE SPECIFICITY, PHOSPHORYLATION, VARIANTS TTPP2 MET-140; HIS-205; MET-354 AND ARG-366, CHARACTERIZATION OF VARIANTS TTPP2 HIS-205; MET-354 AND ARG-366, MUTAGENESIS OF THR-354. Tissue: Brain.

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Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	FJ434338 mRNA. Translation: ACJ64506.2.
IPI	IPI00947376.
UniGene	Hs.200629.
3D structure databases
ProteinModelPortal	B7U540.
SMR	B7U540. Positions 42-372.
ModBase	Search...
Proteomic databases
PRIDE	B7U540.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	uc021tss.1. human.
Organism-specific databases
GeneCards	GC17Pr21596.
HGNC	HGNC:39080. KCNJ18.
HPA	HPA027021.
MIM	613236. gene. 613239. phenotype.
neXtProt	NX_B7U540.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG006178.
Family and domain databases
Gene3D	2.60.40.1400. 1 hit.
InterPro	IPR014756. 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]
PANTHER	PTHR11767. PTHR11767. 1 hit. PTHR11767:SF14. PTHR11767:SF14. 1 hit.
Pfam	PF01007. IRK. 1 hit. PF08466. IRK_N. 1 hit. [Graphical view]
PIRSF	PIRSF005465. GIRK_kir. 1 hit.
PRINTS	PR01325. KIR22CHANNEL. PR01320. KIRCHANNEL.
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
NextBio	33696320.
SOURCE	Search...

Entry information

Entry name

IRK18_HUMAN

Accession

Primary (citable) accession number: B7U540

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 13, 2010
Last sequence update:	December 15, 2009
Last modified:	May 1, 2013
This is version 37 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.