O95259 (KCNH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily H member 1

Alternative name(s):
Ether-a-go-go potassium channel 1
Short name=EAG channel 1
Short name=h-eag
Short name=hEAG1
Voltage-gated potassium channel subunit Kv10.1

Gene names

Name:	KCNH1
Synonyms:	EAG, EAG1

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

General annotation (Comments)

Function	Pore-forming (alpha) subunit of voltage-gated non-inactivating delayed rectifier potassium channel. Channel properties may be modulated by cAMP and subunit assembly. Mediates IK(NI) current in myoblasts.
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 KCNH5/EAG2. Interacts with ALG10B By similarity. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein. Nucleus inner membrane; Multi-pass membrane protein. Note: Perinuclear KCNH1 is located to NPC-free islands. Ref.8
Tissue specificity	Highly expressed in brain and in myoblasts at the onset of fusion, but not in other tissues. Detected in HeLa (cervical carcinoma), SH-SY5Y (neuroblastoma) and MCF-7 (epithelial tumor) cells, but not in normal epithelial cells.
Domain	The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Ref.6
Sequence similarities	Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 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	Cell membrane Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Calmodulin-binding Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	myoblast fusion Traceable author statement Ref.1. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	nuclear inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell voltage-gated potassium channel complex Traceable author statement Ref.1. Source: ProtInc
Molecular_function	delayed rectifier potassium channel activity Traceable author statement Ref.1. Source: ProtInc phosphorelay sensor kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALM3	P62158	2	EBI-2909270,EBI-397435

Alternative products

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

Isoform 2 (identifier: O95259-1)

Also known as: hEAGB;

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 1 (identifier: O95259-2)

Also known as: hEAG;

The sequence of this isoform differs from the canonical sequence as follows:
     318-344: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 989	989	Potassium voltage-gated channel subfamily H member 1		PRO_0000053994
Regions
	Topological domain	1 – 220	220	Cytoplasmic Potential
	Transmembrane	221 – 241	21	Helical; Name=Segment S1; Potential
	Topological domain	242 – 248	7	Extracellular Potential
	Transmembrane	249 – 269	21	Helical; Name=Segment S2; Potential
	Topological domain	270 – 294	25	Cytoplasmic Potential
	Transmembrane	295 – 315	21	Helical; Name=Segment S3; Potential
	Topological domain	316 – 349	34	Extracellular Potential
	Transmembrane	350 – 370	21	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	371 – 376	6	Cytoplasmic Potential
	Transmembrane	377 – 397	21	Helical; Name=Segment S5; Potential
	Topological domain	398 – 450	53	Extracellular Potential
	Intramembrane	451 – 471	21	Pore-forming; Name=Segment H5; Potential
	Topological domain	472 – 477	6	Extracellular Potential
	Transmembrane	478 – 498	21	Helical; Name=Segment S6; Potential
	Topological domain	499 – 989	491	Cytoplasmic Potential
	Domain	14 – 94	81	PAS
	Domain	93 – 145	53	PAC
	Nucleotide binding	581 – 698	118	cNMP
	Region	673 – 770	98	Calmodulin-binding
	Region	924 – 964	41	CAD (involved in subunit assembly) By similarity
	Motif	463 – 468	6	Selectivity filter By similarity
Amino acid modifications
	Glycosylation	415	1	N-linked (GlcNAc...) Potential
	Glycosylation	433	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	318 – 344	27	Missing in isoform 1.		VSP_000964

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (hEAGB) [UniParc]. Last modified May 1, 1999. Version 1. Checksum: CAA8CB251300C7E5	FASTA	989	111,423
	10 20 30 40 50 60 MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC KLSGYHRAEV 70 80 90 100 110 120 MQKSSTCSFM YGELTDKDTI EKVRQTFENY EMNSFEILMY KKNRTPVWFF VKIAPIRNEQ 130 140 150 160 170 180 DKVVLFLCTF SDITAFKQPI EDDSCKGWGK FARLTRALTS SRGVLQQLAP SVQKGENVHK 190 200 210 220 230 240 HSRLAEVLQL GSDILPQYKQ EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS 250 260 270 280 290 300 FKTRQNNVAW LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL 310 320 330 340 350 360 LSCLPYDVIN AFENVDEVSA FMGDPGKIGF ADQIPPPLEG RESQGISSLF SSLKVVRLLR 370 380 390 400 410 420 LGRVARKLDH YIEYGAAVLV LLVCVFGLAA HWMACIWYSI GDYEIFDEDT KTIRNNSWLY 430 440 450 460 470 480 QLAMDIGTPY QFNGSGSGKW EGGPSKNSVY ISSLYFTMTS LTSVGFGNIA PSTDIEKIFA 490 500 510 520 530 540 VAIMMIGSLL YATIFGNVTT IFQQMYANTN RYHEMLNSVR DFLKLYQVPK GLSERVMDYI 550 560 570 580 590 600 VSTWSMSRGI DTEKVLQICP KDMRADICVH LNRKVFKEHP AFRLASDGCL RALAMEFQTV 610 620 630 640 650 660 HCAPGDLIYH AGESVDSLCF VVSGSLEVIQ DDEVVAILGK GDVFGDVFWK EATLAQSCAN 670 680 690 700 710 720 VRALTYCDLH VIKRDALQKV LEFYTAFSHS FSRNLILTYN LRKRIVFRKI SDVKREEEER 730 740 750 760 770 780 MKRKNEAPLI LPPDHPVRRL FQRFRQQKEA RLAAERGGRD LDDLDVEKGN VLTEHASANH 790 800 810 820 830 840 SLVKASVVTV RESPATPVSF QAASTSGVPD HAKLQAPGSE CLGPKGGGGD CAKRKSWARF 850 860 870 880 890 900 KDACGKSEDW NKVSKAESME TLPERTKASG EATLKKTDSC DSGITKSDLR LDNVGEARSP 910 920 930 940 950 960 QDRSPILAEV KHSFYPIPEQ TLQATVLEVR HELKEDIKAL NAKMTNIEKQ LSEILRILTS 970 980 RRSSQSPQEL FEISRPQSPE SERDIFGAS
	Isoform 1 (hEAG) [UniParc]. Checksum: 9CC995AFF156582D	FASTA	962	108,597
	10 20 30 40 50 60 MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC KLSGYHRAEV 70 80 90 100 110 120 MQKSSTCSFM YGELTDKDTI EKVRQTFENY EMNSFEILMY KKNRTPVWFF VKIAPIRNEQ 130 140 150 160 170 180 DKVVLFLCTF SDITAFKQPI EDDSCKGWGK FARLTRALTS SRGVLQQLAP SVQKGENVHK 190 200 210 220 230 240 HSRLAEVLQL GSDILPQYKQ EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS 250 260 270 280 290 300 FKTRQNNVAW LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL 310 320 330 340 350 360 LSCLPYDVIN AFENVDEGIS SLFSSLKVVR LLRLGRVARK LDHYIEYGAA VLVLLVCVFG 370 380 390 400 410 420 LAAHWMACIW YSIGDYEIFD EDTKTIRNNS WLYQLAMDIG TPYQFNGSGS GKWEGGPSKN 430 440 450 460 470 480 SVYISSLYFT MTSLTSVGFG NIAPSTDIEK IFAVAIMMIG SLLYATIFGN VTTIFQQMYA 490 500 510 520 530 540 NTNRYHEMLN SVRDFLKLYQ VPKGLSERVM DYIVSTWSMS RGIDTEKVLQ ICPKDMRADI 550 560 570 580 590 600 CVHLNRKVFK EHPAFRLASD GCLRALAMEF QTVHCAPGDL IYHAGESVDS LCFVVSGSLE 610 620 630 640 650 660 VIQDDEVVAI LGKGDVFGDV FWKEATLAQS CANVRALTYC DLHVIKRDAL QKVLEFYTAF 670 680 690 700 710 720 SHSFSRNLIL TYNLRKRIVF RKISDVKREE EERMKRKNEA PLILPPDHPV RRLFQRFRQQ 730 740 750 760 770 780 KEARLAAERG GRDLDDLDVE KGNVLTEHAS ANHSLVKASV VTVRESPATP VSFQAASTSG 790 800 810 820 830 840 VPDHAKLQAP GSECLGPKGG GGDCAKRKSW ARFKDACGKS EDWNKVSKAE SMETLPERTK 850 860 870 880 890 900 ASGEATLKKT DSCDSGITKS DLRLDNVGEA RSPQDRSPIL AEVKHSFYPI PEQTLQATVL 910 920 930 940 950 960 EVRHELKEDI KALNAKMTNI EKQLSEILRI LTSRRSSQSP QELFEISRPQ SPESERDIFG AS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion." Occhiodoro T., Bernheim L., Liu J.-H., Bijlenga P., Sinnreich M., Bader C.R., Fischer-Lougheed J. FEBS Lett. 434:177-182(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Myoblast.
[2]	"Oncogenic potential of EAG K(+) channels." Pardo L.A., del Camino D., Sanchez A., Alves F., Brueggemann A., Beckh S., Stuehmer W. EMBO J. 18:5540-5547(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Brain.
[6]	"Inhibition of human ether a go-go potassium channels by Ca(2+)/calmodulin." Schoenherr R., Lober K., Heinemann S.H. EMBO J. 19:3263-3271(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CALMODULIN-BINDING DOMAIN.
[7]	"Functional distinction of human EAG1 and EAG2 potassium channels." Schoenherr R., Gessner G., Loeber K., Heinemann S.H. FEBS Lett. 514:204-208(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNH5.
[8]	"Functional K(v)10.1 channels localize to the inner nuclear membrane." Chen Y., Sanchez A., Rubio M.E., Kohl T., Pardo L.A., Stuhmer W. PLoS ONE 6:E19257-E19257(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ001366 mRNA. Translation: CAA04700.1. AF078741 mRNA. Translation: AAC68668.1. AF078742 mRNA. Translation: AAC68669.1. AL590132 , AC092017, AC096636, AC099755 Genomic DNA. Translation: CAH71752.1. AL590132 , AC092017, AC096636, AC099755 Genomic DNA. Translation: CAH71753.1. CH471100 Genomic DNA. Translation: EAW93424.1. CH471100 Genomic DNA. Translation: EAW93425.1. BC113709 mRNA. Translation: AAI13710.1. BC143599 mRNA. Translation: AAI43600.1.
IPI	IPI00098591. IPI00221201.
RefSeq	NP_002229.1. NM_002238.3. NP_758872.1. NM_172362.2.
UniGene	Hs.553187.
3D structure databases
ProteinModelPortal	O95259.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95259. 1 interaction.
STRING	9606.ENSP00000271751.
PTM databases
PhosphoSite	O95259.
Proteomic databases
PaxDb	O95259.
PRIDE	O95259.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000271751; ENSP00000271751; ENSG00000143473. ENST00000367007; ENSP00000355974; ENSG00000143473.
GeneID	3756.
KEGG	hsa:3756.
UCSC	uc001hib.2. human.
Organism-specific databases
CTD	3756.
GeneCards	GC01M210851.
HGNC	HGNC:6250. KCNH1.
HPA	HPA019445.
MIM	603305. gene.
neXtProt	NX_O95259.
PharmGKB	PA30037.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2202.
HOGENOM	HOG000230794.
HOVERGEN	HBG101348.
InParanoid	O95259.
KO	K04904.
OMA	RYHEMIS.
OrthoDB	EOG47PX5C.
PhylomeDB	O95259.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	O95259.
CleanEx	HS_KCNH1.
Genevestigator	O95259.
GermOnline	ENSG00000143473. 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. IPR003949. K_chnl_volt-dep_EAG. IPR003938. K_chnl_volt-dep_EAG/ELK/ERG. IPR001610. PAC. IPR000014. PAS. IPR000700. PAS-assoc_C. IPR014710. RmlC-like_jellyroll. [Graphical view]
Pfam	PF00027. cNMP_binding. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01463. EAGCHANLFMLY. PR01464. EAGCHANNEL.
SMART	SM00100. cNMP. 1 hit. SM00086. PAC. 1 hit. SM00091. PAS. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 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. 1 hit. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O95259.
ChEMBL	CHEMBL3841.
GenomeRNAi	3756.
NextBio	14711.
SOURCE	Search...

Entry information

Entry name

KCNH1_HUMAN

Accession

Primary (citable) accession number: O95259
Secondary accession number(s): B1AQ26, O76035, Q14CL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2002
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 124 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.