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Protein

Potassium voltage-gated channel subfamily H member 5

Gene

KCNH5

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

Functioni

Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a non-inactivating outward rectifying current. Channel properties may be modulated by cAMP and subunit assembly.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi550 – 667cNMPAdd BLAST118

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Ion channel, Potassium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily H member 5
Alternative name(s):
Ether-a-go-go potassium channel 2
Short name:
hEAG2
Voltage-gated potassium channel subunit Kv10.2
Gene namesi
Name:KCNH5
Synonyms:EAG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000140015.19
HGNCiHGNC:6254 KCNH5
MIMi605716 gene
neXtProtiNX_Q8NCM2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 217CytoplasmicSequence analysisAdd BLAST217
Transmembranei218 – 238Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini239 – 243ExtracellularSequence analysis5
Transmembranei244 – 264Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini265 – 291CytoplasmicSequence analysisAdd BLAST27
Transmembranei292 – 312Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini313 – 319ExtracellularSequence analysis7
Transmembranei320 – 340Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini341 – 346CytoplasmicSequence analysis6
Transmembranei347 – 367Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini368 – 419ExtracellularSequence analysisAdd BLAST52
Intramembranei420 – 440Pore-forming; Name=Segment H5Sequence analysisAdd BLAST21
Topological domaini441 – 446ExtracellularSequence analysis6
Transmembranei447 – 467Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini468 – 988CytoplasmicSequence analysisAdd BLAST521

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi27133
OpenTargetsiENSG00000140015
PharmGKBiPA30040

Chemistry databases

ChEMBLiCHEMBL2362996
GuidetoPHARMACOLOGYi571

Polymorphism and mutation databases

BioMutaiKCNH5
DMDMi334302891

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540101 – 988Potassium voltage-gated channel subfamily H member 5Add BLAST988

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi403N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki785Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei883PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8NCM2
PeptideAtlasiQ8NCM2
PRIDEiQ8NCM2

PTM databases

iPTMnetiQ8NCM2
PhosphoSitePlusiQ8NCM2

Expressioni

Tissue specificityi

Detected in brain, skeletal muscle, heart, placenta, lung and liver, and at low levels in kidney.

Gene expression databases

BgeeiENSG00000140015
CleanExiHS_KCNH5
GenevisibleiQ8NCM2 HS

Organism-specific databases

HPAiHPA030487

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 KCNH1/EAG (Probable).Curated

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9606.ENSP00000321427

Structurei

3D structure databases

ProteinModelPortaliQ8NCM2
SMRiQ8NCM2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 90PASAdd BLAST79
Domaini91 – 143PACPROSITE-ProRule annotationAdd BLAST53

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni704 – 715Calmodulin-bindingSequence analysisAdd BLAST12
Regioni909 – 948CAD (involved in subunit assembly)By similarityAdd BLAST40

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi432 – 437Selectivity filterBy similarity6

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140833
HOGENOMiHOG000230794
HOVERGENiHBG101348
InParanoidiQ8NCM2
KOiK04908
OMAiDKAGETR
OrthoDBiEOG091G0OXR
PhylomeDBiQ8NCM2
TreeFamiTF313130

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
cd00130 PAS, 1 hit
Gene3Di1.20.120.350, 1 hit
2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 cNMP-bd-like
IPR000595 cNMP-bd_dom
IPR030171 EAG2
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
IPR035965 PAS-like_dom_sf
IPR014710 RmlC-like_jellyroll
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR10217:SF533 PTHR10217:SF533, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF13426 PAS_9, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
PR01464 EAGCHANNEL
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SM00086 PAC, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
SSF55785 SSF55785, 1 hit
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50042 CNMP_BINDING_3, 1 hit
PS50113 PAC, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q8NCM2-1) [UniParc]FASTAAdd to basket

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
MPGGKRGLVA PQNTFLENIV RRSSESSFLL GNAQIVDWPV VYSNDGFCKL
60 70 80 90 100
SGYHRADVMQ KSSTCSFMYG ELTDKKTIEK VRQTFDNYES NCFEVLLYKK
110 120 130 140 150
NRTPVWFYMQ IAPIRNEHEK VVLFLCTFKD ITLFKQPIED DSTKGWTKFA
160 170 180 190 200
RLTRALTNSR SVLQQLTPMN KTEVVHKHSR LAEVLQLGSD ILPQYKQEAP
210 220 230 240 250
KTPPHIILHY CAFKTTWDWV ILILTFYTAI MVPYNVSFKT KQNNIAWLVL
260 270 280 290 300
DSVVDVIFLV DIVLNFHTTF VGPGGEVISD PKLIRMNYLK TWFVIDLLSC
310 320 330 340 350
LPYDIINAFE NVDEGISSLF SSLKVVRLLR LGRVARKLDH YLEYGAAVLV
360 370 380 390 400
LLVCVFGLVA HWLACIWYSI GDYEVIDEVT NTIQIDSWLY QLALSIGTPY
410 420 430 440 450
RYNTSAGIWE GGPSKDSLYV SSLYFTMTSL TTIGFGNIAP TTDVEKMFSV
460 470 480 490 500
AMMMVGSLLY ATIFGNVTTI FQQMYANTNR YHEMLNNVRD FLKLYQVPKG
510 520 530 540 550
LSERVMDYIV STWSMSKGID TEKVLSICPK DMRADICVHL NRKVFNEHPA
560 570 580 590 600
FRLASDGCLR ALAVEFQTIH CAPGDLIYHA GESVDALCFV VSGSLEVIQD
610 620 630 640 650
DEVVAILGKG DVFGDIFWKE TTLAHACANV RALTYCDLHI IKREALLKVL
660 670 680 690 700
DFYTAFANSF SRNLTLTCNL RKRIIFRKIS DVKKEEEERL RQKNEVTLSI
710 720 730 740 750
PVDHPVRKLF QKFKQQKELR NQGSTQGDPE RNQLQVESRS LQNGASITGT
760 770 780 790 800
SVVTVSQITP IQTSLAYVKT SESLKQNNRD AMELKPNGGA DQKCLKVNSP
810 820 830 840 850
IRMKNGNGKG WLRLKNNMGA HEEKKEDWNN VTKAESMGLL SEDPKSSDSE
860 870 880 890 900
NSVTKNPLRK TDSCDSGITK SDLRLDKAGE ARSPLEHSPI QADAKHPFYP
910 920 930 940 950
IPEQALQTTL QEVKHELKED IQLLSCRMTA LEKQVAEILK ILSEKSVPQA
960 970 980
SSPKSQMPLQ VPPQIPCQDI FSVSRPESPE SDKDEIHF
Length:988
Mass (Da):111,877
Last modified:May 31, 2011 - v3
Checksum:iA58E4CE0A32C83BC
GO
Isoform 2 (identifier: Q8NCM2-2) [UniParc]FASTAAdd to basket
Also known as: 2b

The sequence of this isoform differs from the canonical sequence as follows:
     608-611: GKGD → DHLS
     612-988: Missing.

Show »
Length:611
Mass (Da):69,443
Checksum:i7BFDAE4B26410886
GO
Isoform 3 (identifier: Q8NCM2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.
     674-682: IIFRKISDV → GWFSMANAL
     683-988: Missing.

Show »
Length:624
Mass (Da):71,123
Checksum:iD6D18C16D9CAA93F
GO

Sequence cautioni

The sequence BAC11016 differs from that shown. Reason: Erroneous termination at position 436. Translated as Gly.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077834327R → H Found in a child with sporadic epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777164EnsemblClinVar.1
Natural variantiVAR_065162745A → T3 PublicationsCorresponds to variant dbSNP:rs4902176Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0009721 – 58Missing in isoform 3. 1 PublicationAdd BLAST58
Alternative sequenceiVSP_000973608 – 611GKGD → DHLS in isoform 2. 1 Publication4
Alternative sequenceiVSP_000974612 – 988Missing in isoform 2. 1 PublicationAdd BLAST377
Alternative sequenceiVSP_000975674 – 682IIFRKISDV → GWFSMANAL in isoform 3. 1 Publication9
Alternative sequenceiVSP_000976683 – 988Missing in isoform 3. 1 PublicationAdd BLAST306

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF418206 mRNA Translation: AAM28435.1
AF472412 mRNA Translation: AAM49565.1
AF493798 mRNA Translation: AAM49574.1
AK074484 mRNA Translation: BAC11016.1 Sequence problems.
AL109985 Genomic DNA No translation available.
AL132666 Genomic DNA No translation available.
AL137191 Genomic DNA No translation available.
AL355101 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW80819.1
BC073979 mRNA Translation: AAH73979.1
CCDSiCCDS45122.1 [Q8NCM2-2]
CCDS9756.1 [Q8NCM2-1]
RefSeqiNP_647479.2, NM_139318.4 [Q8NCM2-1]
NP_758963.1, NM_172375.2 [Q8NCM2-2]
UniGeneiHs.27043

Genome annotation databases

EnsembliENST00000322893; ENSP00000321427; ENSG00000140015 [Q8NCM2-1]
ENST00000394968; ENSP00000378419; ENSG00000140015 [Q8NCM2-3]
ENST00000420622; ENSP00000395439; ENSG00000140015 [Q8NCM2-2]
GeneIDi27133
KEGGihsa:27133
UCSCiuc001xfx.5 human [Q8NCM2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKCNH5_HUMAN
AccessioniPrimary (citable) accession number: Q8NCM2
Secondary accession number(s): C9JP98
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: May 31, 2011
Last modified: May 23, 2018
This is version 157 of the entry and version 3 of the sequence. See 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 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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