P57789 (KCNKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium channel subfamily K member 10

Alternative name(s):
Outward rectifying potassium channel protein TREK-2
TREK-2 K(+) channel subunit

Gene names

Name:	KCNK10
Synonyms:	TREK2

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

Protein attributes

Sequence length	538 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Outward rectifying potassium channel. Produces rapidly activating and non-inactivating outward rectifier K+ currents. Activated by arachidonic acid and other naturally occurring unsaturated free fatty acids.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Abundantly expressed in pancreas and kidney and to a lower level in brain, testis, colon, and small intestine. Isoform bis strongly expressed in kidney (primarily in the proximal tubule) and pancreas, whereas isoform cis abundantly expressed in brain.
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	signal transduction Non-traceable author statement Ref.1. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome transport Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral component of membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	potassium channel activity Traceable author statement Ref.1. Source: ProtInc voltage-gated ion channel activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P57789-1)

Also known as: TREK-2a;

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 B (identifier: P57789-4)

Also known as: TREK-2b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MFFLYTDFFLSL → MEDGFKGDRTEGCRSDS

Isoform C (identifier: P57789-3)

Also known as: TREK-2c;

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MFFLYTDFFLSL → MKFPIETPRKQVNWDPK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 538

538

Potassium channel subfamily K member 10

PRO_0000101758

Regions

Topological domain

1 – 71

71

Cytoplasmic Potential

Transmembrane

72 – 92

21

Helical; Potential

Intramembrane

154 – 180

27

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

Transmembrane

182 – 202

21

Helical; Potential

Topological domain

203 – 233

31

Cytoplasmic Potential

Transmembrane

234 – 254

21

Helical; Potential

Intramembrane

263 – 294

32

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

Transmembrane

299 – 319

21

Helical; Potential

Topological domain

320 – 538

219

Cytoplasmic Potential

Amino acid modifications

Glycosylation

144

1

N-linked (GlcNAc...) Potential

Glycosylation

147

1

N-linked (GlcNAc...) Potential

Glycosylation

148

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 12

12

MFFLY…FFLSL → MEDGFKGDRTEGCRSDS in isoform B.

VSP_006697

Alternative sequence

1 – 12

12

MFFLY…FFLSL → MKFPIETPRKQVNWDPK in isoform C.

VSP_006698

Natural variant

70

1

K → Q.
Corresponds to variant rs398263 [ dbSNP | Ensembl ].

VAR_060216

Natural variant

512

1

A → T. Ref.4
Corresponds to variant rs17762463 [ dbSNP | Ensembl ].

VAR_052428

Experimental info

Sequence conflict

529

1

E → G in AAL95705. Ref.2

Sequence conflict

529

1

E → G in AAL95706. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

538

Helix Strand Turn

Details...

Helix

69 – 115

47

Helix

121 – 136

16

Beta strand

151 – 153

3

Helix

154 – 165

12

Helix

178 – 222

45

Helix

232 – 247

16

Helix

249 – 258

10

Helix

263 – 274

12

Beta strand

280 – 282

3

Helix

296 – 325

30

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (TREK-2a) [UniParc]. Last modified April 27, 2001. Version 1. Checksum: 8EA615B08D147FBC	FASTA	538	59,765
	10 20 30 40 50 60 MFFLYTDFFL SLVAVPAAAP VCQPKSATNG QPPAPAPTPT PRLSISSRAT VVARMEGTSQ 70 80 90 100 110 120 GGLQTVMKWK TVVAIFVVVV VYLVTGGLVF RALEQPFESS QKNTIALEKA EFLRDHVCVS 130 140 150 160 170 180 PQELETLIQH ALDADNAGVS PIGNSSNNSS HWDLGSAFFF AGTVITTIGY GNIAPSTEGG 190 200 210 220 230 240 KIFCILYAIF GIPLFGFLLA GIGDQLGTIF GKSIARVEKV FRKKQVSQTK IRVISTILFI 250 260 270 280 290 300 LAGCIVFVTI PAVIFKYIEG WTALESIYFV VVTLTTVGFG DFVAGGNAGI NYREWYKPLV 310 320 330 340 350 360 WFWILVGLAY FAAVLSMIGD WLRVLSKKTK EEVGEIKAHA AEWKANVTAE FRETRRRLSV 370 380 390 400 410 420 EIHDKLQRAA TIRSMERRRL GLDQRAHSLD MLSPEKRSVF AALDTGRFKA SSQESINNRP 430 440 450 460 470 480 NNLRLKGPEQ LNKHGQGASE DNIINKFGST SRLTKRKNKD LKKTLPEDVQ KIYKTFRNYS 490 500 510 520 530 LDEEKKEEET EKMCNSDNSS TAMLTDCIQQ HAELENGMIP TDTKDREPEN NSLLEDRN
	Isoform B (TREK-2b) [UniParc]. Checksum: 17DB1AFAFAB07C46	FASTA	543	60,111
	10 20 30 40 50 60 MEDGFKGDRT EGCRSDSVAV PAAAPVCQPK SATNGQPPAP APTPTPRLSI SSRATVVARM 70 80 90 100 110 120 EGTSQGGLQT VMKWKTVVAI FVVVVVYLVT GGLVFRALEQ PFESSQKNTI ALEKAEFLRD 130 140 150 160 170 180 HVCVSPQELE TLIQHALDAD NAGVSPIGNS SNNSSHWDLG SAFFFAGTVI TTIGYGNIAP 190 200 210 220 230 240 STEGGKIFCI LYAIFGIPLF GFLLAGIGDQ LGTIFGKSIA RVEKVFRKKQ VSQTKIRVIS 250 260 270 280 290 300 TILFILAGCI VFVTIPAVIF KYIEGWTALE SIYFVVVTLT TVGFGDFVAG GNAGINYREW 310 320 330 340 350 360 YKPLVWFWIL VGLAYFAAVL SMIGDWLRVL SKKTKEEVGE IKAHAAEWKA NVTAEFRETR 370 380 390 400 410 420 RRLSVEIHDK LQRAATIRSM ERRRLGLDQR AHSLDMLSPE KRSVFAALDT GRFKASSQES 430 440 450 460 470 480 INNRPNNLRL KGPEQLNKHG QGASEDNIIN KFGSTSRLTK RKNKDLKKTL PEDVQKIYKT 490 500 510 520 530 540 FRNYSLDEEK KEEETEKMCN SDNSSTAMLT DCIQQHAELE NGMIPTDTKD REPENNSLLE DRN
	Isoform C (TREK-2c) [UniParc]. Checksum: B158DF9AF076444D	FASTA	543	60,335
	10 20 30 40 50 60 MKFPIETPRK QVNWDPKVAV PAAAPVCQPK SATNGQPPAP APTPTPRLSI SSRATVVARM 70 80 90 100 110 120 EGTSQGGLQT VMKWKTVVAI FVVVVVYLVT GGLVFRALEQ PFESSQKNTI ALEKAEFLRD 130 140 150 160 170 180 HVCVSPQELE TLIQHALDAD NAGVSPIGNS SNNSSHWDLG SAFFFAGTVI TTIGYGNIAP 190 200 210 220 230 240 STEGGKIFCI LYAIFGIPLF GFLLAGIGDQ LGTIFGKSIA RVEKVFRKKQ VSQTKIRVIS 250 260 270 280 290 300 TILFILAGCI VFVTIPAVIF KYIEGWTALE SIYFVVVTLT TVGFGDFVAG GNAGINYREW 310 320 330 340 350 360 YKPLVWFWIL VGLAYFAAVL SMIGDWLRVL SKKTKEEVGE IKAHAAEWKA NVTAEFRETR 370 380 390 400 410 420 RRLSVEIHDK LQRAATIRSM ERRRLGLDQR AHSLDMLSPE KRSVFAALDT GRFKASSQES 430 440 450 460 470 480 INNRPNNLRL KGPEQLNKHG QGASEDNIIN KFGSTSRLTK RKNKDLKKTL PEDVQKIYKT 490 500 510 520 530 540 FRNYSLDEEK KEEETEKMCN SDNSSTAMLT DCIQQHAELE NGMIPTDTKD REPENNSLLE DRN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids and Gs, Gi, and Gq protein-coupled receptors." Lesage F., Terrenoire C., Romey G., Lazdunski M. J. Biol. Chem. 275:28398-28405(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]	"Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2." Gu W., Schlichthorl G., Hirsch J.R., Engels H., Karschin C., Karschin A., Derst C., Steinlein O.K., Daut J. J. Physiol. (Lond.) 539:657-668(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C).
[3]	"Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein." Gierten J., Ficker E., Bloehs R., Schlomer K., Kathofer S., Scholz E., Zitron E., Kiesecker C., Bauer A., Becker R., Katus H.A., Karle C.A., Thomas D. Br. J. Pharmacol. 154:1680-1690(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C). Tissue: Brain, Kidney and Pancreas.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C), VARIANT THR-512. Tissue: Brain and Cerebellum.
[5]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton 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]	"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 B).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF279890 mRNA. Translation: AAG15191.1.
AF385399 mRNA. Translation: AAL95705.1.
AF385400 mRNA. Translation: AAL95706.1.
EU978938 mRNA. Translation: ACH86097.1.
EU978939 mRNA. Translation: ACH86098.1.
EU978940 mRNA. Translation: ACH86099.1.
EU978941 mRNA. Translation: ACH86100.1.
AK313499 mRNA. Translation: BAG36281.1.
AK315263 mRNA. Translation: BAG37680.1.
AL049834 Genomic DNA. No translation available.
AL133279 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81373.1.
CH471061 Genomic DNA. Translation: EAW81374.1.
CH471061 Genomic DNA. Translation: EAW81375.1.
BC075021 mRNA. Translation: AAH75021.1.
BC075022 mRNA. Translation: AAH75022.1.

CCDS

CCDS9880.1. [P57789-1]
CCDS9881.1. [P57789-3]
CCDS9882.1. [P57789-4]

RefSeq

NP_066984.1. NM_021161.4. [P57789-1]
NP_612190.1. NM_138317.2. [P57789-3]
NP_612191.1. NM_138318.2. [P57789-4]

UniGene

Hs.560255.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4BW5	X-ray	3.20	A/B/C/D	62-335	[»]

ProteinModelPortal

P57789.

SMR

P57789. Positions 68-327.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

119924. 2 interactions.

IntAct

P57789. 2 interactions.

MINT

MINT-4050532.

STRING

9606.ENSP00000310568.

Chemistry

ChEMBL

CHEMBL2331041.

GuidetoPHARMACOLOGY

521.

PTM databases

PhosphoSite

P57789.

Polymorphism databases

DMDM

13431412.

Proteomic databases

PaxDb

P57789.

PRIDE

P57789.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000312350; ENSP00000310568; ENSG00000100433. [P57789-4]
ENST00000319231; ENSP00000312811; ENSG00000100433. [P57789-3]
ENST00000340700; ENSP00000343104; ENSG00000100433. [P57789-1]

GeneID

54207.

KEGG

hsa:54207.

UCSC

uc001xwm.3. human. [P57789-4]
uc001xwn.3. human. [P57789-3]
uc001xwo.3. human. [P57789-1]

Organism-specific databases

CTD

54207.

GeneCards

GC14M089829.

HGNC

HGNC:6273. KCNK10.

HPA

HPA030462.

MIM

605873. gene.

neXtProt

NX_P57789.

PharmGKB

PA30053.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG308296.

HOGENOM

HOG000013106.

HOVERGEN

HBG052234.

KO

K04920.

OMA

QLNKHGQ.

OrthoDB

EOG77M8NK.

PhylomeDB

P57789.

TreeFam

TF313947.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

P57789.

Bgee

P57789.

CleanEx

HS_KCNK10.

Genevestigator

P57789.

Family and domain databases

InterPro

IPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR003976. 2pore_dom_K_chnl_TREK.
[Graphical view]

Pfam

PF07885. Ion_trans_2. 2 hits.
[Graphical view]

PRINTS

PR01333. 2POREKCHANEL.
PR01499. TREKCHANNEL.

ProtoNet

Search...

Other

GeneWiki

KCNK10.

GenomeRNAi

54207.

NextBio

56534.

PRO

P57789.

SOURCE

Search...

Entry information

Entry name

KCNKA_HUMAN

Accession

Primary (citable) accession number: P57789
Secondary accession number(s): B2R8T4 , B2RCT3, B5TJL4, Q6B014, Q8TDK7, Q8TDK8, Q9HB59

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 27, 2001
Last modified:	July 9, 2014
This is version 120 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.