Q9NYG8 (KCNK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium channel subfamily K member 4

Alternative name(s):
TWIK-related arachidonic acid-stimulated potassium channel protein
Short name=TRAAK
Two pore potassium channel KT4.1
Short name=Two pore K(+) channel KT4.1

Gene names

Name:	KCNK4
Synonyms:	TRAAK

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

General annotation (Comments)

Function	Voltage insensitive, instantaneous, outwardly rectifying potassium channel. Outward rectification is reversed at high external K+ concentrations By similarity.
Subunit structure	Homodimer; disulfide-linked. Ref.8
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Sequence similarities	Belongs to the two pore domain potassium channel (TC 1.A.1.8) family. [View classification]
Sequence caution	The sequence AAF64062.1 differs from that shown. Reason: Erroneous initiation.

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	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	potassium channel activity Traceable author statement Ref.3. Source: ProtInc voltage-gated ion channel activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9NYG8-1)

Also known as: KT4.1a;

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: Q9NYG8-2)

Also known as: KT4.1b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MTTAPQEPPARPLQAGSGAGPAPGRAM

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 393

393

Potassium channel subfamily K member 4

PRO_0000101747

Regions

Topological domain

1 – 3

3

Cytoplasmic Potential

Transmembrane

4 – 24

21

Helical; Potential

Intramembrane

89 – 113

25

Pore-forming; Name=Pore-forming 1; Potential

Transmembrane

118 – 138

21

Helical; Potential

Topological domain

139 – 171

33

Cytoplasmic Potential

Transmembrane

172 – 192

21

Helical; Potential

Intramembrane

197 – 221

25

Pore-forming; Name=Pore-forming 2; Potential

Transmembrane

234 – 254

21

Helical; Potential

Topological domain

255 – 393

139

Cytoplasmic Potential

Amino acid modifications

Glycosylation

78

1

N-linked (GlcNAc...) Potential

Glycosylation

82

1

N-linked (GlcNAc...) Potential

Disulfide bond

52

Interchain Ref.8

Natural variations

Alternative sequence

1

1

M → MTTAPQEPPARPLQAGSGAG PAPGRAM in isoform 2.

VSP_006689

Natural variant

328

1

P → L. Ref.2
Corresponds to variant rs953778 [ dbSNP | Ensembl ].

VAR_020206

Secondary structure

1

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393

Helix Strand Turn

Details...

Helix

3 – 28

26

Helix

29 – 31

3

Helix

34 – 49

16

Helix

55 – 70

16

Helix

90 – 101

12

Helix

114 – 159

46

Helix

164 – 183

20

Helix

185 – 195

11

Helix

199 – 210

12

Beta strand

216 – 218

3

Helix

231 – 259

29

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (KT4.1a) [UniParc]. Last modified February 21, 2001. Version 2. Checksum: 7F18E53A0A9AD57D	FASTA	393	42,704
	10 20 30 40 50 60 MRSTTLLALL ALVLLYLVSG ALVFRALEQP HEQQAQRELG EVREKFLRAH PCVSDQELGL 70 80 90 100 110 120 LIKEVADALG GGADPETNST SNSSHSAWDL GSAFFFSGTI ITTIGYGNVA LRTDAGRLFC 130 140 150 160 170 180 IFYALVGIPL FGILLAGVGD RLGSSLRHGI GHIEAIFLKW HVPPELVRVL SAMLFLLIGC 190 200 210 220 230 240 LLFVLTPTFV FCYMEDWSKL EAIYFVIVTL TTVGFGDYVA GADPRQDSPA YQPLVWFWIL 250 260 270 280 290 300 LGLAYFASVL TTIGNWLRVV SRRTRAEMGG LTAQAASWTG TVTARVTQRA GPAAPPPEKE 310 320 330 340 350 360 QPLLPPPPCP AQPLGRPRSP SPPEKAQPPS PPTASALDYP SENLAFIDES SDTQSERGCP 370 380 390 LPRAPRGRRR PNPPRKPVRP RGPGRPRDKG VPV
	Isoform 2 (KT4.1b) [UniParc]. Checksum: E7DEDE17B30C0FBF	FASTA	419	45,173
	10 20 30 40 50 60 MTTAPQEPPA RPLQAGSGAG PAPGRAMRST TLLALLALVL LYLVSGALVF RALEQPHEQQ 70 80 90 100 110 120 AQRELGEVRE KFLRAHPCVS DQELGLLIKE VADALGGGAD PETNSTSNSS HSAWDLGSAF 130 140 150 160 170 180 FFSGTIITTI GYGNVALRTD AGRLFCIFYA LVGIPLFGIL LAGVGDRLGS SLRHGIGHIE 190 200 210 220 230 240 AIFLKWHVPP ELVRVLSAML FLLIGCLLFV LTPTFVFCYM EDWSKLEAIY FVIVTLTTVG 250 260 270 280 290 300 FGDYVAGADP RQDSPAYQPL VWFWILLGLA YFASVLTTIG NWLRVVSRRT RAEMGGLTAQ 310 320 330 340 350 360 AASWTGTVTA RVTQRAGPAA PPPEKEQPLL PPPPCPAQPL GRPRSPSPPE KAQPPSPPTA 370 380 390 400 410 SALDYPSENL AFIDESSDTQ SERGCPLPRA PRGRRRPNPP RKPVRPRGPG RPRDKGVPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel." Chapman C.G., Meadows H.J., Godden R.J., Campbell D.A., Duckworth M., Kelsell R.E., Murdock P.R., Randall A.D., Rennie G.I., Gloger I.S. Brain Res. Mol. Brain Res. 82:74-83(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Assignment of KCNK4 encoding the human potassium channel TRAAK to chromosome 11." Gray A.T. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-328. Tissue: Frontal cortex.
[3]	"Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel." Lesage F., Maingret F., Lazdunski M. FEBS Lett. 471:137-140(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression." Ozaita A., Vega-Saenz de Miera E. Brain Res. Mol. Brain Res. 102:18-27(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]	"Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel." Brohawn S.G., del Marmol J., MacKinnon R. Science 335:436-441(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.31 ANGSTROMS) OF 1-274, DISULFIDE BOND.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF248242 mRNA. Translation: AAG31731.1.
AF247042 mRNA. Translation: AAF64062.1. Different initiation.
AF259500 mRNA. Translation: AAK49389.1.
AF259501 mRNA. Translation: AAK49390.1.
EU978935 mRNA. Translation: ACH86094.1.
CH471076 Genomic DNA. Translation: EAW74242.1.

IPI

IPI00020981.
IPI00414796.

RefSeq

NP_201567.1. NM_033310.2.

UniGene

Hs.647233.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3UM7	X-ray	3.31	A/B	1-274	[»]
4I9W	X-ray	2.75	A/B	1-274	[»]

ProteinModelPortal

Q9NYG8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NYG8. 2 interactions.

STRING

9606.ENSP00000378033.

PTM databases

PhosphoSite

Q9NYG8.

Polymorphism databases

DMDM

13124080.

Proteomic databases

PaxDb

Q9NYG8.

PRIDE

Q9NYG8.

Protocols and materials databases

DNASU

50801.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000394525; ENSP00000378033; ENSG00000182450.
ENST00000422670; ENSP00000402797; ENSG00000182450.
ENST00000539216; ENSP00000444948; ENSG00000182450.

GeneID

50801.

KEGG

hsa:50801.

UCSC

uc001nzj.1. human.

Organism-specific databases

CTD

50801.

GeneCards

GC11P064058.

HGNC

HGNC:6279. KCNK4.

MIM

605720. gene.

neXtProt

NX_Q9NYG8.

PharmGKB

PA30061.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG280717.

HOGENOM

HOG000013106.

HOVERGEN

HBG052234.

InParanoid

Q9NYG8.

KO

K04915.

OrthoDB

EOG42JNS5.

PhylomeDB

Q9NYG8.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

Q9NYG8.

Bgee

Q9NYG8.

CleanEx

HS_KCNK4.

Genevestigator

Q9NYG8.

GermOnline

ENSG00000182450. Homo sapiens.

Family and domain databases

InterPro

IPR003280. 2pore_dom_K_chnl.
IPR008074. 2pore_dom_K_chnl_TRAAK.
IPR013099. Ion_trans_2.
[Graphical view]

Pfam

PF07885. Ion_trans_2. 2 hits.
[Graphical view]

PRINTS

PR01333. 2POREKCHANEL.
PR01691. TRAAKCHANNEL.

ProtoNet

Search...

Other

GenomeRNAi

50801.

NextBio

53228.

SOURCE

Search...

Entry information

Entry name

KCNK4_HUMAN

Accession

Primary (citable) accession number: Q9NYG8
Secondary accession number(s): B5TJL1, Q96T94

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	February 21, 2001
Last modified:	May 1, 2013
This is version 109 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.