Q9NS40 (KCNH7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily H member 7

Alternative name(s):
Ether-a-go-go-related gene potassium channel 3
Short name=ERG-3
Short name=Eag-related protein 3
Short name=Ether-a-go-go-related protein 3
Short name=hERG-3
Voltage-gated potassium channel subunit Kv11.3

Gene names

Name:	KCNH7
Synonyms:	ERG3

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	1196 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Pore-forming (alpha) subunit of voltage-gated potassium channel. 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. Heteromultimer with KCNH2/ERG1 and KCNH6/ERG2 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. Kv11.3/KCNH7 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.
Sequence caution	The sequence AAD01946.1 differs from that shown. Reason: Frameshift at positions 792 and 795.

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	circadian rhythm Inferred from electronic annotation. Source: Compara protein heterooligomerization Inferred from electronic annotation. Source: Compara 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	inward rectifier potassium channel activity Inferred from electronic annotation. Source: Compara signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9NS40-1)

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: Q9NS40-2)

The sequence of this isoform differs from the canonical sequence as follows:
     298-304: Missing.
     720-739: LKGFPECLQADICLHLNQTL → CMSVFQNESAAGIIVIAKME
     740-1196: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1196	1196	Potassium voltage-gated channel subfamily H member 7		PRO_0000054015
Regions
	Topological domain	1 – 412	412	Cytoplasmic Potential
	Transmembrane	413 – 433	21	Helical; Name=Segment S1; Potential
	Topological domain	434 – 449	16	Extracellular Potential
	Transmembrane	450 – 470	21	Helical; Name=Segment S2; Potential
	Topological domain	471 – 494	24	Cytoplasmic Potential
	Transmembrane	495 – 515	21	Helical; Name=Segment S3; Potential
	Topological domain	516 – 521	6	Extracellular Potential
	Transmembrane	522 – 542	21	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	543 – 549	7	Cytoplasmic Potential
	Transmembrane	550 – 570	21	Helical; Name=Segment S5; Potential
	Topological domain	571 – 614	44	Extracellular Potential
	Intramembrane	615 – 635	21	Pore-forming; Name=Segment H5; Potential
	Topological domain	636 – 641	6	Extracellular Potential
	Transmembrane	642 – 662	21	Helical; Name=Segment S6; Potential
	Topological domain	663 – 1196	534	Cytoplasmic Potential
	Domain	41 – 70	30	PAS
	Domain	92 – 144	53	PAC
	Nucleotide binding	745 – 862	118	cNMP
	Motif	627 – 632	6	Selectivity filter By similarity
Amino acid modifications
	Glycosylation	600	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	298 – 304	7	Missing in isoform 2.		VSP_037116
	Alternative sequence	720 – 739	20	LKGFP…LNQTL → CMSVFQNESAAGIIVIAKME in isoform 2.		VSP_037117
	Alternative sequence	740 – 1196	457	Missing in isoform 2.		VSP_037118
	Natural variant	958	1	G → A. Corresponds to variant rs6757850 [ dbSNP | Ensembl ].		VAR_057767
Experimental info
	Sequence conflict	555	1	L → S in AAD01946. Ref.1
	Sequence conflict	562	1	I → N in AAD01946. Ref.1
	Sequence conflict	767 – 768	2	PP → LQ in AAD01946. Ref.1
	Sequence conflict	797	1	I → M in AAD01946. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: A22D046D02C2A759	FASTA	1,196	135,000
	10 20 30 40 50 60 MPVRRGHVAP QNTFLGTIIR KFEGQNKKFI IANARVQNCA IIYCNDGFCE MTGFSRPDVM 70 80 90 100 110 120 QKPCTCDFLH GPETKRHDIA QIAQALLGSE ERKVEVTYYH KNGSTFICNT HIIPVKNQEG 130 140 150 160 170 180 VAMMFIINFE YVTDNENAAT PERVNPILPI KTVNRKFFGF KFPGLRVLTY RKQSLPQEDP 190 200 210 220 230 240 DVVVIDSSKH SDDSVAMKHF KSPTKESCSP SEADDTKALI QPSKCSPLVN ISGPLDHSSP 250 260 270 280 290 300 KRQWDRLYPD MLQSSSQLSH SRSRESLCSI RRASSVHDIE GFGVHPKNIF RDRHASEDNG 310 320 330 340 350 360 RNVKGPFNHI KSSLLGSTSD SNLNKYSTIN KIPQLTLNFS EVKTEKKNSS PPSSDKTIIA 370 380 390 400 410 420 PKVKDRTHNV TEKVTQVLSL GADVLPEYKL QTPRINKFTI LHYSPFKAVW DWLILLLVIY 430 440 450 460 470 480 TAIFTPYSAA FLLNDREEQK RRECGYSCSP LNVVDLIVDI MFIIDILINF RTTYVNQNEE 490 500 510 520 530 540 VVSDPAKIAI HYFKGWFLID MVAAIPFDLL IFGSGSDETT TLIGLLKTAR LLRLVRVARK 550 560 570 580 590 600 LDRYSEYGAA VLMLLMCIFA LIAHWLACIW YAIGNVERPY LTDKIGWLDS LGQQIGKRYN 610 620 630 640 650 660 DSDSSSGPSI KDKYVTALYF TFSSLTSVGF GNVSPNTNSE KIFSICVMLI GSLMYASIFG 670 680 690 700 710 720 NVSAIIQRLY SGTARYHMQM LRVKEFIRFH QIPNPLRQRL EEYFQHAWTY TNGIDMNMVL 730 740 750 760 770 780 KGFPECLQAD ICLHLNQTLL QNCKAFRGAS KGCLRALAMK FKTTHAPPGD TLVHCGDVLT 790 800 810 820 830 840 ALYFLSRGSI EILKDDIVVA ILGKNDIFGE MVHLYAKPGK SNADVRALTY CDLHKIQRED 850 860 870 880 890 900 LLEVLDMYPE FSDHFLTNLE LTFNLRHESA KADLLRSQSM NDSEGDNCKL RRRKLSFESE 910 920 930 940 950 960 GEKENSTNDP EDSADTIRHY QSSKRHFEEK KSRSSSFISS IDDEQKPLFS GIVDSSPGIG 970 980 990 1000 1010 1020 KASGLDFEET VPTSGRMHID KRSHSCKDIT DMRSWERENA HPQPEDSSPS ALQRAAWGIS 1030 1040 1050 1060 1070 1080 ETESDLTYGE VEQRLDLLQE QLNRLESQMT TDIQTILQLL QKQTTVVPPA YSMVTAGSEY 1090 1100 1110 1120 1130 1140 QRPIIQLMRT SQPEASIKTD RSFSPSSQCP EFLDLEKSKL KSKESLSSGV HLNTASEDNL 1150 1160 1170 1180 1190 TSLLKQDSDL SLELHLRQRK TYVHPIRHPS LPDSSLSTVG IVGLHRHVSD PGLPGK
	Isoform 2 [UniParc]. Checksum: 42E86D3AA12E495D	FASTA	732	82,904
	10 20 30 40 50 60 MPVRRGHVAP QNTFLGTIIR KFEGQNKKFI IANARVQNCA IIYCNDGFCE MTGFSRPDVM 70 80 90 100 110 120 QKPCTCDFLH GPETKRHDIA QIAQALLGSE ERKVEVTYYH KNGSTFICNT HIIPVKNQEG 130 140 150 160 170 180 VAMMFIINFE YVTDNENAAT PERVNPILPI KTVNRKFFGF KFPGLRVLTY RKQSLPQEDP 190 200 210 220 230 240 DVVVIDSSKH SDDSVAMKHF KSPTKESCSP SEADDTKALI QPSKCSPLVN ISGPLDHSSP 250 260 270 280 290 300 KRQWDRLYPD MLQSSSQLSH SRSRESLCSI RRASSVHDIE GFGVHPKNIF RDRHASEGPF 310 320 330 340 350 360 NHIKSSLLGS TSDSNLNKYS TINKIPQLTL NFSEVKTEKK NSSPPSSDKT IIAPKVKDRT 370 380 390 400 410 420 HNVTEKVTQV LSLGADVLPE YKLQTPRINK FTILHYSPFK AVWDWLILLL VIYTAIFTPY 430 440 450 460 470 480 SAAFLLNDRE EQKRRECGYS CSPLNVVDLI VDIMFIIDIL INFRTTYVNQ NEEVVSDPAK 490 500 510 520 530 540 IAIHYFKGWF LIDMVAAIPF DLLIFGSGSD ETTTLIGLLK TARLLRLVRV ARKLDRYSEY 550 560 570 580 590 600 GAAVLMLLMC IFALIAHWLA CIWYAIGNVE RPYLTDKIGW LDSLGQQIGK RYNDSDSSSG 610 620 630 640 650 660 PSIKDKYVTA LYFTFSSLTS VGFGNVSPNT NSEKIFSICV MLIGSLMYAS IFGNVSAIIQ 670 680 690 700 710 720 RLYSGTARYH MQMLRVKEFI RFHQIPNPLR QRLEEYFQHA WTYTNGIDMN MVCMSVFQNE 730 SAAGIIVIAK ME

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Polynucleotides encoding herg-3 potassium channel." Ganetzky B., Titus S.A. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 2). Tissue: Brain.
[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	AF032897 mRNA. Translation: AAD01946.1. Frameshift. AC010876 Genomic DNA. Translation: AAX93139.1. AC007740 Genomic DNA. Translation: AAX93153.1. AC104822 Genomic DNA. Translation: AAY24106.1. BC035815 mRNA. Translation: AAH35815.1.
IPI	IPI00175643. IPI00299946.
RefSeq	NP_150375.2. NM_033272.3. NP_775185.1. NM_173162.2.
UniGene	Hs.657413.
3D structure databases
ProteinModelPortal	Q9NS40.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NS40. 1 interaction.
STRING	9606.ENSP00000331727.
PTM databases
PhosphoSite	Q9NS40.
Polymorphism databases
DMDM	229462892.
Proteomic databases
PaxDb	Q9NS40.
PRIDE	Q9NS40.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328032; ENSP00000333781; ENSG00000184611. ENST00000332142; ENSP00000331727; ENSG00000184611.
GeneID	90134.
KEGG	hsa:90134.
UCSC	uc002uch.2. human. uc002uci.3. human.
Organism-specific databases
CTD	90134.
GeneCards	GC02M163191.
HGNC	HGNC:18863. KCNH7.
HPA	HPA018039.
MIM	608169. gene.
neXtProt	NX_Q9NS40.
PharmGKB	PA38723.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2202.
HOGENOM	HOG000230793.
HOVERGEN	HBG052232.
InParanoid	Q9NS40.
KO	K04910.
OMA	PERVNPI.
OrthoDB	EOG4STS3W.
PhylomeDB	Q9NS40.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	Q9NS40.
CleanEx	HS_KCNH7.
Genevestigator	Q9NS40.
GermOnline	ENSG00000184611. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.10. 1 hit.
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. SM00091. PAS. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 1 hit. SSF55785. SSF55785. 1 hit.
TIGRFAMs	TIGR00229. sensory_box. 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	90134.
NextBio	76541.
SOURCE	Search...

Entry information

Entry name

KCNH7_HUMAN

Accession

Primary (citable) accession number: Q9NS40
Secondary accession number(s): Q53QU4 , Q53TB7, Q53TP9, Q8IV15

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2002
Last sequence update:	May 5, 2009
Last modified:	May 29, 2013
This is version 115 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.