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O95259

- KCNH1_HUMAN

UniProt

O95259 - KCNH1_HUMAN

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Protein

Potassium voltage-gated channel subfamily H member 1

Gene

KCNH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi581 – 698118cNMPAdd
BLAST

GO - Molecular functioni

  1. delayed rectifier potassium channel activity Source: ProtInc
  2. phosphorelay sensor kinase activity Source: InterPro

GO - Biological processi

  1. myoblast fusion Source: ProtInc
  2. potassium ion transmembrane transport Source: RefGenome
  3. potassium ion transport Source: ProtInc
  4. regulation of membrane potential Source: RefGenome
  5. synaptic transmission Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Calmodulin-binding, Potassium

Enzyme and pathway databases

ReactomeiREACT_75770. Voltage gated Potassium channels.

Names & Taxonomyi

Protein namesi
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 namesi
Name:KCNH1
Synonyms:EAG, EAG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:6250. KCNH1.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Nucleus inner membrane 1 Publication; Multi-pass membrane protein 1 Publication
Note: Perinuclear KCNH1 is located to NPC-free islands.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 220220CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei221 – 24121Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Topological domaini242 – 2487ExtracellularSequence Analysis
Transmembranei249 – 26921Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Topological domaini270 – 29425CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei295 – 31521Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Topological domaini316 – 34934ExtracellularSequence AnalysisAdd
BLAST
Transmembranei350 – 37021Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
BLAST
Topological domaini371 – 3766CytoplasmicSequence Analysis
Transmembranei377 – 39721Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Topological domaini398 – 45053ExtracellularSequence AnalysisAdd
BLAST
Intramembranei451 – 47121Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST
Topological domaini472 – 4776ExtracellularSequence Analysis
Transmembranei478 – 49821Helical; Name=Segment S6Sequence AnalysisAdd
BLAST
Topological domaini499 – 989491CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. nucleus Source: UniProtKB-KW
  2. plasma membrane Source: Reactome
  3. voltage-gated potassium channel complex Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30037.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 989989Potassium voltage-gated channel subfamily H member 1PRO_0000053994Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi415 – 4151N-linked (GlcNAc...)Sequence Analysis
Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO95259.
PRIDEiO95259.

PTM databases

PhosphoSiteiO95259.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiO95259.
CleanExiHS_KCNH1.
GenevestigatoriO95259.

Organism-specific databases

HPAiHPA019445.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CALM3P621584EBI-2909270,EBI-397435
S100BP026383EBI-2909270,EBI-458452From a different organism.

Protein-protein interaction databases

BioGridi109958. 4 interactions.
IntActiO95259. 7 interactions.
MINTiMINT-138319.
STRINGi9606.ENSP00000271751.

Structurei

3D structure databases

ProteinModelPortaliO95259.
SMRiO95259. Positions 28-137, 449-505, 509-720.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 9481PASPROSITE-ProRule annotationAdd
BLAST
Domaini93 – 14553PACPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni673 – 77098Calmodulin-bindingAdd
BLAST
Regioni924 – 96441CAD (involved in subunit assembly)By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi463 – 4686Selectivity filterBy similarity

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Sequence similaritiesi

Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation
Contains 1 PAC (PAS-associated C-terminal) domain.PROSITE-ProRule annotation
Contains 1 PAS (PER-ARNT-SIM) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2202.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230794.
HOVERGENiHBG101348.
InParanoidiO95259.
KOiK04904.
OMAiHAKLHAP.
OrthoDBiEOG7QG43V.
PhylomeDBiO95259.
TreeFamiTF313130.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. 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]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
PR01464. EAGCHANNEL.
SMARTiSM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
TIGRFAMsiTIGR00229. sensory_box. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
PS50113. PAC. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 2 (identifier: O95259-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC
60 70 80 90 100
KLSGYHRAEV MQKSSTCSFM YGELTDKDTI EKVRQTFENY EMNSFEILMY
110 120 130 140 150
KKNRTPVWFF VKIAPIRNEQ DKVVLFLCTF SDITAFKQPI EDDSCKGWGK
160 170 180 190 200
FARLTRALTS SRGVLQQLAP SVQKGENVHK HSRLAEVLQL GSDILPQYKQ
210 220 230 240 250
EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS FKTRQNNVAW
260 270 280 290 300
LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL
310 320 330 340 350
LSCLPYDVIN AFENVDEVSA FMGDPGKIGF ADQIPPPLEG RESQGISSLF
360 370 380 390 400
SSLKVVRLLR LGRVARKLDH YIEYGAAVLV LLVCVFGLAA HWMACIWYSI
410 420 430 440 450
GDYEIFDEDT KTIRNNSWLY QLAMDIGTPY QFNGSGSGKW EGGPSKNSVY
460 470 480 490 500
ISSLYFTMTS LTSVGFGNIA PSTDIEKIFA VAIMMIGSLL YATIFGNVTT
510 520 530 540 550
IFQQMYANTN RYHEMLNSVR DFLKLYQVPK GLSERVMDYI VSTWSMSRGI
560 570 580 590 600
DTEKVLQICP KDMRADICVH LNRKVFKEHP AFRLASDGCL RALAMEFQTV
610 620 630 640 650
HCAPGDLIYH AGESVDSLCF VVSGSLEVIQ DDEVVAILGK GDVFGDVFWK
660 670 680 690 700
EATLAQSCAN VRALTYCDLH VIKRDALQKV LEFYTAFSHS FSRNLILTYN
710 720 730 740 750
LRKRIVFRKI SDVKREEEER MKRKNEAPLI LPPDHPVRRL FQRFRQQKEA
760 770 780 790 800
RLAAERGGRD LDDLDVEKGN VLTEHASANH SLVKASVVTV RESPATPVSF
810 820 830 840 850
QAASTSGVPD HAKLQAPGSE CLGPKGGGGD CAKRKSWARF KDACGKSEDW
860 870 880 890 900
NKVSKAESME TLPERTKASG EATLKKTDSC DSGITKSDLR LDNVGEARSP
910 920 930 940 950
QDRSPILAEV KHSFYPIPEQ TLQATVLEVR HELKEDIKAL NAKMTNIEKQ
960 970 980
LSEILRILTS RRSSQSPQEL FEISRPQSPE SERDIFGAS
Length:989
Mass (Da):111,423
Last modified:May 1, 1999 - v1
Checksum:iCAA8CB251300C7E5
GO
Isoform 1 (identifier: O95259-2) [UniParc]FASTAAdd to Basket

Also known as: hEAG

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

Show »
Length:962
Mass (Da):108,597
Checksum:i9CC995AFF156582D
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei318 – 34427Missing in isoform 1. 2 PublicationsVSP_000964Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1496.1. [O95259-1]
CCDS31015.1. [O95259-2]
RefSeqiNP_002229.1. NM_002238.3. [O95259-2]
NP_758872.1. NM_172362.2. [O95259-1]
UniGeneiHs.553187.

Genome annotation databases

EnsembliENST00000271751; ENSP00000271751; ENSG00000143473. [O95259-1]
ENST00000367007; ENSP00000355974; ENSG00000143473. [O95259-2]
GeneIDi3756.
KEGGihsa:3756.
UCSCiuc001hib.2. human. [O95259-1]
uc001hic.2. human. [O95259-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS1496.1. [O95259-1 ]
CCDS31015.1. [O95259-2 ]
RefSeqi NP_002229.1. NM_002238.3. [O95259-2 ]
NP_758872.1. NM_172362.2. [O95259-1 ]
UniGenei Hs.553187.

3D structure databases

ProteinModelPortali O95259.
SMRi O95259. Positions 28-137, 449-505, 509-720.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109958. 4 interactions.
IntActi O95259. 7 interactions.
MINTi MINT-138319.
STRINGi 9606.ENSP00000271751.

Chemistry

ChEMBLi CHEMBL2362996.
GuidetoPHARMACOLOGYi 570.

PTM databases

PhosphoSitei O95259.

Proteomic databases

PaxDbi O95259.
PRIDEi O95259.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000271751 ; ENSP00000271751 ; ENSG00000143473 . [O95259-1 ]
ENST00000367007 ; ENSP00000355974 ; ENSG00000143473 . [O95259-2 ]
GeneIDi 3756.
KEGGi hsa:3756.
UCSCi uc001hib.2. human. [O95259-1 ]
uc001hic.2. human. [O95259-2 ]

Organism-specific databases

CTDi 3756.
GeneCardsi GC01M210851.
HGNCi HGNC:6250. KCNH1.
HPAi HPA019445.
MIMi 603305. gene.
neXtProti NX_O95259.
PharmGKBi PA30037.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2202.
GeneTreei ENSGT00760000118772.
HOGENOMi HOG000230794.
HOVERGENi HBG101348.
InParanoidi O95259.
KOi K04904.
OMAi HAKLHAP.
OrthoDBi EOG7QG43V.
PhylomeDBi O95259.
TreeFami TF313130.

Enzyme and pathway databases

Reactomei REACT_75770. Voltage gated Potassium channels.

Miscellaneous databases

GeneWikii KCNH1.
GenomeRNAii 3756.
NextBioi 14711.
PROi O95259.
SOURCEi Search...

Gene expression databases

Bgeei O95259.
CleanExi HS_KCNH1.
Genevestigatori O95259.

Family and domain databases

Gene3Di 2.60.120.10. 1 hit.
InterProi 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 ]
Pfami PF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view ]
PRINTSi PR01463. EAGCHANLFMLY.
PR01464. EAGCHANNEL.
SMARTi SM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view ]
SUPFAMi SSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
TIGRFAMsi TIGR00229. sensory_box. 1 hit.
PROSITEi PS50042. CNMP_BINDING_3. 1 hit.
PS50113. PAC. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiKCNH1_HUMAN
AccessioniPrimary (citable) accession number: O95259
Secondary accession number(s): B1AQ26, O76035, Q14CL3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: May 1, 1999
Last modified: November 26, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3