Q9H252 (KCNH6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily H member 6

Alternative name(s):
Ether-a-go-go-related gene potassium channel 2
Short name=ERG-2
Short name=Eag-related protein 2
Short name=Ether-a-go-go-related protein 2
Short name=hERG-2
Short name=hERG2
Voltage-gated potassium channel subunit Kv11.2

Gene names

Name:	KCNH6
Synonyms:	ERG2

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

General annotation (Comments)

Function	Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current By similarity. Channel properties may be modulated by cAMP and subunit assembly.
Subunit structure	The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimers with KCNH2/ERG1 and KCNH7/ERG3 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in prolactin-secreting adenomas. Ref.4
Domain	The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Sequence similarities	Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.2/KCNH6 sub-subfamily. [View classification] Contains 1 cyclic nucleotide-binding domain. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 1 PAS (PER-ARNT-SIM) domain.

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
Technical term	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	signal transducer activity Inferred from electronic annotation. Source: InterPro voltage-gated potassium channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9H252-1)

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: Q9H252-2)

The sequence of this isoform differs from the canonical sequence as follows:
     419-472: WYAIGNVERPYLEHKIGWLDSLGVQLGKRYNGSDPASGPSVQDKYVTALYFTFS → C
     745-780: Missing.

Isoform 3 (identifier: Q9H252-3)

The sequence of this isoform differs from the canonical sequence as follows:
     501-502: SL → CE
     503-994: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 994	994	Potassium voltage-gated channel subfamily H member 6		PRO_0000054013
Regions
	Topological domain	1 – 261	261	Cytoplasmic Potential
	Transmembrane	262 – 282	21	Helical; Name=Segment S1; Potential
	Topological domain	283 – 298	16	Extracellular Potential
	Transmembrane	299 – 319	21	Helical; Name=Segment S2; Potential
	Topological domain	320 – 340	21	Cytoplasmic Potential
	Transmembrane	341 – 361	21	Helical; Name=Segment S3; Potential
	Topological domain	362 – 370	9	Extracellular Potential
	Transmembrane	371 – 391	21	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	392 – 398	7	Cytoplasmic Potential
	Transmembrane	399 – 419	21	Helical; Name=Segment S5; Potential
	Topological domain	420 – 463	44	Extracellular Potential
	Intramembrane	464 – 484	21	Pore-forming; Name=Segment H5; Potential
	Topological domain	485 – 490	6	Extracellular Potential
	Transmembrane	491 – 511	21	Helical; Name=Segment S6; Potential
	Topological domain	512 – 994	483	Cytoplasmic Potential
	Domain	41 – 70	30	PAS
	Domain	92 – 144	53	PAC
	Nucleotide binding	594 – 711	118	cNMP
	Motif	476 – 481	6	Selectivity filter By similarity
Natural variations
	Alternative sequence	419 – 472	54	WYAIG…YFTFS → C in isoform 2.		VSP_000977
	Alternative sequence	501 – 502	2	SL → CE in isoform 3.		VSP_000979
	Alternative sequence	503 – 994	492	Missing in isoform 3.		VSP_000980
	Alternative sequence	745 – 780	36	Missing in isoform 2.		VSP_000978
	Natural variant	165	1	G → R. Corresponds to variant rs35399062 [ dbSNP | Ensembl ].		VAR_053857
	Natural variant	925	1	T → M. Ref.2 Corresponds to variant rs35819807 [ dbSNP | Ensembl ].		VAR_053858
Experimental info
	Sequence conflict	963	1	F → L in BAC03764. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: BE9ECB349A798576	FASTA	994	109,925
	10 20 30 40 50 60 MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM 70 80 90 100 110 120 QQPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG 130 140 150 160 170 180 AVIMFILNFE DLAQLLAKCS SRSLSQRLLS QSFLGSEGSH GRPGGPGPGT GRGKYRTISQ 190 200 210 220 230 240 IPQFTLNFVE FNLEKHRSSS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ 250 260 270 280 290 300 APRIHRWTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESRR GACSYTCSPL 310 320 330 340 350 360 TVVDLIVDIM FVVDIVINFR TTYVNTNDEV VSHPRRIAVH YFKGWFLIDM VAAIPFDLLI 370 380 390 400 410 420 FRTGSDETTT LIGLLKTARL LRLVRVARKL DRYSEYGAAV LFLLMCTFAL IAHWLACIWY 430 440 450 460 470 480 AIGNVERPYL EHKIGWLDSL GVQLGKRYNG SDPASGPSVQ DKYVTALYFT FSSLTSVGFG 490 500 510 520 530 540 NVSPNTNSEK VFSICVMLIG SLMYASIFGN VSAIIQRLYS GTARYHTQML RVKEFIRFHQ 550 560 570 580 590 600 IPNPLRQRLE EYFQHAWSYT NGIDMNAVLK GFPECLQADI CLHLHRALLQ HCPAFSGAGK 610 620 630 640 650 660 GCLRALAVKF KTTHAPPGDT LVHLGDVLST LYFISRGSIE ILRDDVVVAI LGKNDIFGEP 670 680 690 700 710 720 VSLHAQPGKS SADVRALTYC DLHKIQRADL LEVLDMYPAF AESFWSKLEV TFNLRDAAGG 730 740 750 760 770 780 LHSSPRQAPG SQDHQGFFLS DNQSGSPHEL GPQFPSKGYS LLGPGSQNSM GAGPCAPGHP 790 800 810 820 830 840 DAAPPLSISD ASGLWPELLQ EMPPRHSPQS PQEDPDCWPL KLGSRLEQLQ AQMNRLESRV 850 860 870 880 890 900 SSDLSRILQL LQKPMPQGHA SYILEAPASN DLALVPIASE TTSPGPRLPQ GFLPPAQTPS 910 920 930 940 950 960 YGDLDDCSPK HRNSSPRMPH LAVATDKTLA PSSEQEQPEG LWPPLASPLH PLEVQGLICG 970 980 990 PCFSSLPEHL GSVPKQLDFQ RHGSDPGFAG SWGH
	Isoform 2 [UniParc]. Checksum: 0556E274946D2B7E	FASTA	905	100,450
	10 20 30 40 50 60 MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM 70 80 90 100 110 120 QQPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG 130 140 150 160 170 180 AVIMFILNFE DLAQLLAKCS SRSLSQRLLS QSFLGSEGSH GRPGGPGPGT GRGKYRTISQ 190 200 210 220 230 240 IPQFTLNFVE FNLEKHRSSS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ 250 260 270 280 290 300 APRIHRWTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESRR GACSYTCSPL 310 320 330 340 350 360 TVVDLIVDIM FVVDIVINFR TTYVNTNDEV VSHPRRIAVH YFKGWFLIDM VAAIPFDLLI 370 380 390 400 410 420 FRTGSDETTT LIGLLKTARL LRLVRVARKL DRYSEYGAAV LFLLMCTFAL IAHWLACICS 430 440 450 460 470 480 LTSVGFGNVS PNTNSEKVFS ICVMLIGSLM YASIFGNVSA IIQRLYSGTA RYHTQMLRVK 490 500 510 520 530 540 EFIRFHQIPN PLRQRLEEYF QHAWSYTNGI DMNAVLKGFP ECLQADICLH LHRALLQHCP 550 560 570 580 590 600 AFSGAGKGCL RALAVKFKTT HAPPGDTLVH LGDVLSTLYF ISRGSIEILR DDVVVAILGK 610 620 630 640 650 660 NDIFGEPVSL HAQPGKSSAD VRALTYCDLH KIQRADLLEV LDMYPAFAES FWSKLEVTFN 670 680 690 700 710 720 LRDAAGGLHS SPRQAPGSQD HQGFFLSDNQ SDAAPPLSIS DASGLWPELL QEMPPRHSPQ 730 740 750 760 770 780 SPQEDPDCWP LKLGSRLEQL QAQMNRLESR VSSDLSRILQ LLQKPMPQGH ASYILEAPAS 790 800 810 820 830 840 NDLALVPIAS ETTSPGPRLP QGFLPPAQTP SYGDLDDCSP KHRNSSPRMP HLAVATDKTL 850 860 870 880 890 900 APSSEQEQPE GLWPPLASPL HPLEVQGLIC GPCFSSLPEH LGSVPKQLDF QRHGSDPGFA GSWGH
	Isoform 3 [UniParc]. Checksum: 6CBD9F336841809B	FASTA	502	56,298
	10 20 30 40 50 60 MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM 70 80 90 100 110 120 QQPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG 130 140 150 160 170 180 AVIMFILNFE DLAQLLAKCS SRSLSQRLLS QSFLGSEGSH GRPGGPGPGT GRGKYRTISQ 190 200 210 220 230 240 IPQFTLNFVE FNLEKHRSSS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ 250 260 270 280 290 300 APRIHRWTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESRR GACSYTCSPL 310 320 330 340 350 360 TVVDLIVDIM FVVDIVINFR TTYVNTNDEV VSHPRRIAVH YFKGWFLIDM VAAIPFDLLI 370 380 390 400 410 420 FRTGSDETTT LIGLLKTARL LRLVRVARKL DRYSEYGAAV LFLLMCTFAL IAHWLACIWY 430 440 450 460 470 480 AIGNVERPYL EHKIGWLDSL GVQLGKRYNG SDPASGPSVQ DKYVTALYFT FSSLTSVGFG 490 500 NVSPNTNSEK VFSICVMLIG CE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Eag-related gene member 2 (Herg2) potassium channel." Titus S.A., Ganetzky B.S. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"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] (ISOFORM 2), VARIANT MET-925. Tissue: Amygdala and Kidney.
[3]	"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 3). Tissue: Uterus.
[4]	"HERG K(+) currents in human prolactin-secreting adenoma cells." Bauer C.K., Wulfsen I., Schaefer R., Glassmeier G., Wimmers S., Flitsch J., Luedecke D.K., Schwarz J.R. Pflugers Arch. 445:589-600(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF311913 mRNA. Translation: AAG40871.1. AK090969 mRNA. Translation: BAC03559.1. AK091877 mRNA. Translation: BAC03764.1. BC006334 mRNA. Translation: AAH06334.1.
IPI	IPI00006515. IPI00216624. IPI00216625.
RefSeq	NP_110406.1. NM_030779.2. NP_775115.1. NM_173092.1.
UniGene	Hs.591177.
3D structure databases
ProteinModelPortal	Q9H252.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000318212.
PTM databases
PhosphoSite	Q9H252.
Polymorphism databases
DMDM	26006810.
Proteomic databases
PaxDb	Q9H252.
PRIDE	Q9H252.
Protocols and materials databases
DNASU	81033.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000456941; ENSP00000396900; ENSG00000173826. ENST00000580652; ENSP00000464672; ENSG00000173826. ENST00000581784; ENSP00000463830; ENSG00000173826. ENST00000583023; ENSP00000463533; ENSG00000173826.
GeneID	81033.
KEGG	hsa:81033.
UCSC	uc002jax.1. human. uc002jay.3. human. uc002jaz.1. human.
Organism-specific databases
CTD	81033.
GeneCards	GC17P061600.
HGNC	HGNC:18862. KCNH6.
HPA	CAB006838. CAB022674.
MIM	608168. gene.
neXtProt	NX_Q9H252.
PharmGKB	PA38722.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2202.
HOGENOM	HOG000230793.
HOVERGEN	HBG052232.
InParanoid	Q9H252.
KO	K04909.
OMA	MYPAFAD.
PhylomeDB	Q9H252.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	Q9H252.
CleanEx	HS_KCNH6.
Genevestigator	Q9H252.
GermOnline	ENSG00000173826. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.10. 2 hits.
InterPro	IPR018490. cNMP-bd-like. IPR000595. cNMP-bd_dom. IPR005821. Ion_trans_dom. IPR003938. K_chnl_volt-dep_EAG/ELK/ERG. IPR003967. K_chnl_volt-dep_ERG. IPR001610. PAC. IPR000014. PAS. IPR014710. RmlC-like_jellyroll. [Graphical view]
Pfam	PF00027. cNMP_binding. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01463. EAGCHANLFMLY. PR01470. ERGCHANNEL.
SMART	SM00100. cNMP. 1 hit. SM00086. PAC. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 1 hit. SSF55785. SSF55785. 1 hit.
PROSITE	PS00888. CNMP_BINDING_1. False negative. PS00889. CNMP_BINDING_2. False negative. PS50042. CNMP_BINDING_3. 1 hit. PS50113. PAC. False negative. PS50112. PAS. False negative. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00308. Ibutilide.
GenomeRNAi	81033.
NextBio	71366.
SOURCE	Search...

Entry information

Entry name

KCNH6_HUMAN

Accession

Primary (citable) accession number: Q9H252
Secondary accession number(s): Q9BRD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2002
Last sequence update:	March 1, 2001
Last modified:	May 29, 2013
This is version 116 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.