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Q8NCM2 (KCNH5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:KCNH5
Synonyms:EAG2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length988 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

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 KCNH1/EAG Probable.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

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

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. Kv10.2/KCNH5 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 BAC11016.1 differs from that shown. Reason: Erroneous termination at position 436. Translated as Gly.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q8NCM2-1)

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: Q8NCM2-2)

Also known as: 2b;

The sequence of this isoform differs from the canonical sequence as follows:
     608-611: GKGD → DHLS
     612-988: Missing.
Isoform 3 (identifier: Q8NCM2-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 988988Potassium voltage-gated channel subfamily H member 5
PRO_0000054010

Regions

Topological domain1 – 217217Cytoplasmic Potential
Transmembrane218 – 23821Helical; Name=Segment S1; Potential
Topological domain239 – 2435Extracellular Potential
Transmembrane244 – 26421Helical; Name=Segment S2; Potential
Topological domain265 – 29127Cytoplasmic Potential
Transmembrane292 – 31221Helical; Name=Segment S3; Potential
Topological domain313 – 3197Extracellular Potential
Transmembrane320 – 34021Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain341 – 3466Cytoplasmic Potential
Transmembrane347 – 36721Helical; Name=Segment S5; Potential
Topological domain368 – 41952Extracellular Potential
Intramembrane420 – 44021Pore-forming; Name=Segment H5; Potential
Topological domain441 – 4466Extracellular Potential
Transmembrane447 – 46721Helical; Name=Segment S6; Potential
Topological domain468 – 988521Cytoplasmic Potential
Domain12 – 9079PAS
Domain91 – 14353PAC
Nucleotide binding550 – 667118cNMP
Region704 – 71512Calmodulin-binding Potential
Region909 – 94840CAD (involved in subunit assembly) By similarity
Motif432 – 4376Selectivity filter By similarity

Amino acid modifications

Glycosylation4031N-linked (GlcNAc...) Potential
Cross-link785Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7

Natural variations

Alternative sequence1 – 5858Missing in isoform 3.
VSP_000972
Alternative sequence608 – 6114GKGD → DHLS in isoform 2.
VSP_000973
Alternative sequence612 – 988377Missing in isoform 2.
VSP_000974
Alternative sequence674 – 6829IIFRKISDV → GWFSMANAL in isoform 3.
VSP_000975
Alternative sequence683 – 988306Missing in isoform 3.
VSP_000976
Natural variant7451A → T. Ref.1 Ref.2 Ref.6
Corresponds to variant rs4902176 [ dbSNP | Ensembl ].
VAR_065162

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 31, 2011. Version 3.
Checksum: A58E4CE0A32C83BC

FASTA988111,877
        10         20         30         40         50         60 
MPGGKRGLVA PQNTFLENIV RRSSESSFLL GNAQIVDWPV VYSNDGFCKL SGYHRADVMQ 

        70         80         90        100        110        120 
KSSTCSFMYG ELTDKKTIEK VRQTFDNYES NCFEVLLYKK NRTPVWFYMQ IAPIRNEHEK 

       130        140        150        160        170        180 
VVLFLCTFKD ITLFKQPIED DSTKGWTKFA RLTRALTNSR SVLQQLTPMN KTEVVHKHSR 

       190        200        210        220        230        240 
LAEVLQLGSD ILPQYKQEAP KTPPHIILHY CAFKTTWDWV ILILTFYTAI MVPYNVSFKT 

       250        260        270        280        290        300 
KQNNIAWLVL DSVVDVIFLV DIVLNFHTTF VGPGGEVISD PKLIRMNYLK TWFVIDLLSC 

       310        320        330        340        350        360 
LPYDIINAFE NVDEGISSLF SSLKVVRLLR LGRVARKLDH YLEYGAAVLV LLVCVFGLVA 

       370        380        390        400        410        420 
HWLACIWYSI GDYEVIDEVT NTIQIDSWLY QLALSIGTPY RYNTSAGIWE GGPSKDSLYV 

       430        440        450        460        470        480 
SSLYFTMTSL TTIGFGNIAP TTDVEKMFSV AMMMVGSLLY ATIFGNVTTI FQQMYANTNR 

       490        500        510        520        530        540 
YHEMLNNVRD FLKLYQVPKG LSERVMDYIV STWSMSKGID TEKVLSICPK DMRADICVHL 

       550        560        570        580        590        600 
NRKVFNEHPA FRLASDGCLR ALAVEFQTIH CAPGDLIYHA GESVDALCFV VSGSLEVIQD 

       610        620        630        640        650        660 
DEVVAILGKG DVFGDIFWKE TTLAHACANV RALTYCDLHI IKREALLKVL DFYTAFANSF 

       670        680        690        700        710        720 
SRNLTLTCNL RKRIIFRKIS DVKKEEEERL RQKNEVTLSI PVDHPVRKLF QKFKQQKELR 

       730        740        750        760        770        780 
NQGSTQGDPE RNQLQVESRS LQNGASITGT SVVTVSQITP IQTSLAYVKT SESLKQNNRD 

       790        800        810        820        830        840 
AMELKPNGGA DQKCLKVNSP IRMKNGNGKG WLRLKNNMGA HEEKKEDWNN VTKAESMGLL 

       850        860        870        880        890        900 
SEDPKSSDSE NSVTKNPLRK TDSCDSGITK SDLRLDKAGE ARSPLEHSPI QADAKHPFYP 

       910        920        930        940        950        960 
IPEQALQTTL QEVKHELKED IQLLSCRMTA LEKQVAEILK ILSEKSVPQA SSPKSQMPLQ 

       970        980 
VPPQIPCQDI FSVSRPESPE SDKDEIHF 

« Hide

Isoform 2 (2b) [UniParc].

Checksum: 7BFDAE4B26410886
Show »

FASTA61169,443
Isoform 3 [UniParc].

Checksum: D6D18C16D9CAA93F
Show »

FASTA62471,123

References

« Hide 'large scale' references
[1]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-745.
Tissue: Brain.
[2]"Molecular identification and characterisation of the human eag2 potassium channel."
Ju M., Wray D.
FEBS Lett. 524:204-210(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT THR-745.
Tissue: Fetal brain.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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), VARIANT THR-745.
Tissue: PNS.
[7]"Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells."
Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.
Proteomics 8:2885-2896(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-785.
Tissue: Cervix carcinoma.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_647479.2. NM_139318.4.
NP_758963.1. NM_172375.2.
UniGeneHs.27043.

3D structure databases

ProteinModelPortalQ8NCM2.
SMRQ8NCM2. Positions 26-135, 419-689.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118024. 1 interaction.
STRING9606.ENSP00000321427.

Chemistry

ChEMBLCHEMBL2362996.

PTM databases

PhosphoSiteQ8NCM2.

Polymorphism databases

DMDM334302891.

Proteomic databases

PaxDbQ8NCM2.
PRIDEQ8NCM2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322893; ENSP00000321427; ENSG00000140015. [Q8NCM2-1]
ENST00000394968; ENSP00000378419; ENSG00000140015. [Q8NCM2-3]
ENST00000420622; ENSP00000395439; ENSG00000140015. [Q8NCM2-2]
GeneID27133.
KEGGhsa:27133.
UCSCuc001xfx.3. human. [Q8NCM2-1]
uc001xfy.3. human. [Q8NCM2-2]
uc001xfz.1. human. [Q8NCM2-3]

Organism-specific databases

CTD27133.
GeneCardsGC14M063173.
HGNCHGNC:6254. KCNH5.
HPAHPA030487.
MIM605716. gene.
neXtProtNX_Q8NCM2.
PharmGKBPA30040.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2202.
HOGENOMHOG000230794.
HOVERGENHBG101348.
InParanoidQ8NCM2.
KOK04908.
OMAPKCLKVN.
OrthoDBEOG7QG43V.
PhylomeDBQ8NCM2.
TreeFamTF313130.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ8NCM2.
BgeeQ8NCM2.
CleanExHS_KCNH5.
GenevestigatorQ8NCM2.

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.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiKCNH5.
GenomeRNAi27133.
NextBio49870.
PROQ8NCM2.
SOURCESearch...

Entry information

Entry nameKCNH5_HUMAN
AccessionPrimary (citable) accession number: Q8NCM2
Secondary accession number(s): C9JP98
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: May 31, 2011
Last modified: April 16, 2014
This is version 121 of the entry and version 3 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM