Q9Y257 (KCNK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium channel subfamily K member 6

Alternative name(s):
Inward rectifying potassium channel protein TWIK-2
TWIK-originated similarity sequence

Gene names

Name:	KCNK6
Synonyms:	TOSS, TWIK2

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	313 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Exhibits outward rectification in a physiological K+ gradient and mild inward rectification in symmetrical K+ conditions.
Subunit structure	Homodimer Potential.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Widespread expression, detected in all tissues tested except for skeletal muscle. Strongest expression in placenta, pancreas, heart, colon and spleen, lower levels detected in peripheral blood leukocytes, lung, liver, kidney and thymus. Lowest expression detected in brain.
Miscellaneous	Inhibited by internal acidification and, to a small degree, by zinc. Not inhibited by quinine, quinidine or barium.
Sequence similarities	Belongs to the two pore domain potassium channel (TC 1.A.1.8) family. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	voltage-gated potassium channel complex Traceable author statement Ref.2. Source: ProtInc
Molecular_function	inward rectifier potassium channel activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y257-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y257-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-134: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 313	313	Potassium channel subfamily K member 6		PRO_0000101750
Regions
	Topological domain	1 – 4	4	Cytoplasmic Potential
	Transmembrane	5 – 25	21	Helical; Potential
	Intramembrane	90 – 115	26	Pore-forming; Name=Pore-forming 1; Potential
	Transmembrane	121 – 141	21	Helical; Potential
	Topological domain	142 – 172	31	Cytoplasmic Potential
	Transmembrane	173 – 193	21	Helical; Potential
	Intramembrane	199 – 223	25	Pore-forming; Name=Pore-forming 2; Potential
	Transmembrane	236 – 256	21	Helical; Potential
	Topological domain	257 – 313	57	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	85	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 134	134	Missing in isoform 2.		VSP_006692
	Natural variant	150	1	T → I. Corresponds to variant rs35762773 [ dbSNP | Ensembl ].		VAR_052426
	Natural variant	240	1	V → I. Corresponds to variant rs35496032 [ dbSNP | Ensembl ].		VAR_059842
	Natural variant	259	1	V → M. Corresponds to variant rs34989303 [ dbSNP | Ensembl ].		VAR_052427
Experimental info
	Mutagenesis	53	1	C → A: No channel activity. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 1379382DFB0575DE	FASTA	313	33,747
	10 20 30 40 50 60 MRRGALLAGA LAAYAAYLVL GALLVARLEG PHEARLRAEL ETLRAQLLQR SPCVAAPALD 70 80 90 100 110 120 AFVERVLAAG RLGRVVLANA SGSANASDPA WDFASALFFA STLITTVGYG YTTPLTDAGK 130 140 150 160 170 180 AFSIAFALLG VPTTMLLLTA SAQRLSLLLT HVPLSWLSMR WGWDPRRAAC WHLVALLGVV 190 200 210 220 230 240 VTVCFLVPAV IFAHLEEAWS FLDAFYFCFI SLSTIGLGDY VPGEAPGQPY RALYKVLVTV 250 260 270 280 290 300 YLFLGLVAMV LVLQTFRHVS DLHGLTELIL LPPPCPASFN ADEDDRVDIL GPQPESHQQL 310 SASSHTDYAS IPR
	Isoform 2 [UniParc]. Checksum: 21805E679C6A83F6	FASTA	179	19,903
	10 20 30 40 50 60 MLLLTASAQR LSLLLTHVPL SWLSMRWGWD PRRAACWHLV ALLGVVVTVC FLVPAVIFAH 70 80 90 100 110 120 LEEAWSFLDA FYFCFISLST IGLGDYVPGE APGQPYRALY KVLVTVYLFL GLVAMVLVLQ 130 140 150 160 170 TFRHVSDLHG LTELILLPPP CPASFNADED DRVDILGPQP ESHQQLSASS HTDYASIPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and cloning of TWIK-originated similarity sequence (TOSS): a novel human 2-pore K+ channel principal subunit." Pountney D.J., Gulkarov I., Vega-Saenz de Miera E., Holmes D., Saganich M., Rudy B., Artman M., Coetzee W.A. FEBS Lett. 450:191-196(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Testis.
[2]	"TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family." Chavez R.A., Gray A.T., Zhao B.B., Kindler C.H., Mazurek M.J., Mehta Y., Forsayeth J.R., Yost C.S. J. Biol. Chem. 274:7887-7892(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF CYS-53. Tissue: Brain.
[3]	Erratum Chavez R.A., Gray A.T., Zhao B.B., Kindler C.H., Mazurek M.J., Mehta Y., Forsayeth J.R., Yost C.S. J. Biol. Chem. 274:24440-24440(1999)
[4]	"TWIK-2, an inactivating 2P domain K+ channel." Patel A.J., Maingret F., Magnone V., Fosset M., Lazdunski M., Honore E. J. Biol. Chem. 275:28722-28730(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CHARACTERIZATION.
[5]	"Genomic structure and mutation screening of the TWIK-2 gene." Chen A.F., Gray A.T., Chen A.H., Kindler C.H., Mhatre A.N., Yost C.S., Lalwani A.K., Smith R.J.H. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[6]	"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] (ISOFORM 1). Tissue: Pancreas.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF134149 mRNA. Translation: AAD22980.1. AF117708 mRNA. Translation: AAD24000.1. AF281302 mRNA. Translation: AAG10506.1. AF281303 mRNA. Translation: AAG10507.1. AJ297404, AJ297405 Genomic DNA. Translation: CAC15489.1. BC004367 mRNA. Translation: AAH04367.1.
IPI	IPI00031756. IPI00216922.
RefSeq	NP_004814.1. NM_004823.1.
UniGene	Hs.240395.
3D structure databases
ProteinModelPortal	Q9Y257.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000263372.
Protein family/group databases
TCDB	1.A.1.8.3. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	Q9Y257.
Polymorphism databases
DMDM	13124108.
Proteomic databases
PaxDb	Q9Y257.
PRIDE	Q9Y257.
Protocols and materials databases
DNASU	9424.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263372; ENSP00000263372; ENSG00000099337.
GeneID	9424.
KEGG	hsa:9424.
UCSC	uc002oic.3. human.
Organism-specific databases
CTD	9424.
GeneCards	GC19P038810.
H-InvDB	HIX0202814.
HGNC	HGNC:6281. KCNK6.
HPA	CAB022637.
MIM	603939. gene.
neXtProt	NX_Q9Y257.
PharmGKB	PA30063.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG290832.
HOGENOM	HOG000286014.
HOVERGEN	HBG052237.
InParanoid	Q9Y257.
KO	K04917.
OMA	LLQRSPC.
OrthoDB	EOG4PC9T5.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q9Y257.
Bgee	Q9Y257.
CleanEx	HS_KCNK6.
Genevestigator	Q9Y257.
GermOnline	ENSG00000099337. Homo sapiens.
Family and domain databases
InterPro	IPR003280. 2pore_dom_K_chnl. IPR022306. 2pore_dom_K_chnl_TASK/TWIK. IPR005408. 2pore_dom_K_chnl_TWIK. IPR005409. 2pore_dom_K_chnl_TWIK2. IPR013099. Ion_trans_2. [Graphical view]
Pfam	PF07885. Ion_trans_2. 2 hits. [Graphical view]
PIRSF	PIRSF038061. K_channel_subfamily_K_type. 1 hit.
PRINTS	PR01333. 2POREKCHANEL. PR01587. TWIK2CHANNEL. PR01586. TWIKCHANNEL.
ProtoNet	Search...
Other
DrugBank	DB00308. Ibutilide. DB00908. Quinidine.
GenomeRNAi	9424.
NextBio	35302.
SOURCE	Search...

Entry information

Entry name

KCNK6_HUMAN

Accession

Primary (citable) accession number: Q9Y257
Secondary accession number(s): Q9HB47

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 118 of the entry and version 1 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.