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O95259 (KCNH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length989 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CALM3P621584EBI-2909270,EBI-397435
S100BP026383EBI-2909270,EBI-458452From a different organism.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 989989Potassium voltage-gated channel subfamily H member 1
PRO_0000053994

Regions

Topological domain1 – 220220Cytoplasmic Potential
Transmembrane221 – 24121Helical; Name=Segment S1; Potential
Topological domain242 – 2487Extracellular Potential
Transmembrane249 – 26921Helical; Name=Segment S2; Potential
Topological domain270 – 29425Cytoplasmic Potential
Transmembrane295 – 31521Helical; Name=Segment S3; Potential
Topological domain316 – 34934Extracellular Potential
Transmembrane350 – 37021Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain371 – 3766Cytoplasmic Potential
Transmembrane377 – 39721Helical; Name=Segment S5; Potential
Topological domain398 – 45053Extracellular Potential
Intramembrane451 – 47121Pore-forming; Name=Segment H5; Potential
Topological domain472 – 4776Extracellular Potential
Transmembrane478 – 49821Helical; Name=Segment S6; Potential
Topological domain499 – 989491Cytoplasmic Potential
Domain14 – 9481PAS
Domain93 – 14553PAC
Nucleotide binding581 – 698118cNMP
Region673 – 77098Calmodulin-binding
Region924 – 96441CAD (involved in subunit assembly) By similarity
Motif463 – 4686Selectivity filter By similarity

Amino acid modifications

Glycosylation4151N-linked (GlcNAc...) Potential
Glycosylation4331N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence318 – 34427Missing in isoform 1.
VSP_000964

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (hEAGB) [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: CAA8CB251300C7E5

FASTA989111,423
        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 

« Hide

Isoform 1 (hEAG) [UniParc].

Checksum: 9CC995AFF156582D
Show »

FASTA962108,597

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ001366 mRNA. Translation: CAA04700.1.
AF078741 mRNA. Translation: AAC68668.1.
AF078742 mRNA. Translation: AAC68669.1.
AL590132 expand/collapse EMBL AC list , AC092017, AC096636, AC099755 Genomic DNA. Translation: CAH71752.1.
AL590132 expand/collapse EMBL AC list , 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.
CCDSCCDS1496.1. [O95259-1]
CCDS31015.1. [O95259-2]
RefSeqNP_002229.1. NM_002238.3. [O95259-2]
NP_758872.1. NM_172362.2. [O95259-1]
UniGeneHs.553187.

3D structure databases

ProteinModelPortalO95259.
SMRO95259. Positions 28-137, 449-503, 509-720.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109958. 4 interactions.
IntActO95259. 7 interactions.
MINTMINT-138319.
STRING9606.ENSP00000271751.

Chemistry

BindingDBO95259.
ChEMBLCHEMBL2362996.
GuidetoPHARMACOLOGY570.

PTM databases

PhosphoSiteO95259.

Proteomic databases

PaxDbO95259.
PRIDEO95259.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000271751; ENSP00000271751; ENSG00000143473. [O95259-1]
ENST00000367007; ENSP00000355974; ENSG00000143473. [O95259-2]
GeneID3756.
KEGGhsa:3756.
UCSCuc001hib.2. human. [O95259-1]
uc001hic.2. human. [O95259-2]

Organism-specific databases

CTD3756.
GeneCardsGC01M210851.
HGNCHGNC:6250. KCNH1.
HPAHPA019445.
MIM603305. gene.
neXtProtNX_O95259.
PharmGKBPA30037.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2202.
HOGENOMHOG000230794.
HOVERGENHBG101348.
InParanoidO95259.
KOK04904.
OMAHAKLHAP.
OrthoDBEOG7QG43V.
PhylomeDBO95259.
TreeFamTF313130.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeO95259.
CleanExHS_KCNH1.
GenevestigatorO95259.

Family and domain databases

Gene3D2.60.120.10. 1 hit.
InterProIPR018490. 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]
PfamPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSPR01463. EAGCHANLFMLY.
PR01464. EAGCHANNEL.
SMARTSM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 1 hit.
PS50113. PAC. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiKCNH1.
GenomeRNAi3756.
NextBio14711.
PROO95259.
SOURCESearch...

Entry information

Entry nameKCNH1_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM