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Q9H252 (KCNH6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. 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 6
Alternative name(s):
Ether-a-go-go-related gene potassium channel 2
Short name=ERG-2
Short name=Eag-related protein 2
Short name=Ether-a-go-go-related protein 2
Short name=hERG-2
Short name=hERG2
Voltage-gated potassium channel subunit Kv11.2
Gene names
Name:KCNH6
Synonyms:ERG2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length994 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current By similarity. 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. Heteromultimers with KCNH2/ERG1 and KCNH7/ERG3 By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in prolactin-secreting adenomas. Ref.4

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. Kv11.2/KCNH6 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.

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: Q9H252-1)

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: Q9H252-2)

The sequence of this isoform differs from the canonical sequence as follows:
     419-472: WYAIGNVERPYLEHKIGWLDSLGVQLGKRYNGSDPASGPSVQDKYVTALYFTFS → C
     745-780: Missing.
Isoform 3 (identifier: Q9H252-3)

The sequence of this isoform differs from the canonical sequence as follows:
     501-502: SL → CE
     503-994: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 994994Potassium voltage-gated channel subfamily H member 6
PRO_0000054013

Regions

Topological domain1 – 261261Cytoplasmic Potential
Transmembrane262 – 28221Helical; Name=Segment S1; Potential
Topological domain283 – 29816Extracellular Potential
Transmembrane299 – 31921Helical; Name=Segment S2; Potential
Topological domain320 – 34021Cytoplasmic Potential
Transmembrane341 – 36121Helical; Name=Segment S3; Potential
Topological domain362 – 3709Extracellular Potential
Transmembrane371 – 39121Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain392 – 3987Cytoplasmic Potential
Transmembrane399 – 41921Helical; Name=Segment S5; Potential
Topological domain420 – 46344Extracellular Potential
Intramembrane464 – 48421Pore-forming; Name=Segment H5; Potential
Topological domain485 – 4906Extracellular Potential
Transmembrane491 – 51121Helical; Name=Segment S6; Potential
Topological domain512 – 994483Cytoplasmic Potential
Domain41 – 7030PAS
Domain92 – 14453PAC
Nucleotide binding594 – 711118cNMP
Motif476 – 4816Selectivity filter By similarity

Amino acid modifications

Glycosylation4491N-linked (GlcNAc...) (complex) Ref.5

Natural variations

Alternative sequence419 – 47254WYAIG…YFTFS → C in isoform 2.
VSP_000977
Alternative sequence501 – 5022SL → CE in isoform 3.
VSP_000979
Alternative sequence503 – 994492Missing in isoform 3.
VSP_000980
Alternative sequence745 – 78036Missing in isoform 2.
VSP_000978
Natural variant1651G → R.
Corresponds to variant rs35399062 [ dbSNP | Ensembl ].
VAR_053857
Natural variant9251T → M. Ref.2
Corresponds to variant rs35819807 [ dbSNP | Ensembl ].
VAR_053858

Experimental info

Sequence conflict9631F → L in BAC03764. Ref.2

Sequences

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

Last modified March 1, 2001. Version 1.
Checksum: BE9ECB349A798576

FASTA994109,925
        10         20         30         40         50         60 
MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM 

        70         80         90        100        110        120 
QQPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG 

       130        140        150        160        170        180 
AVIMFILNFE DLAQLLAKCS SRSLSQRLLS QSFLGSEGSH GRPGGPGPGT GRGKYRTISQ 

       190        200        210        220        230        240 
IPQFTLNFVE FNLEKHRSSS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ 

       250        260        270        280        290        300 
APRIHRWTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESRR GACSYTCSPL 

       310        320        330        340        350        360 
TVVDLIVDIM FVVDIVINFR TTYVNTNDEV VSHPRRIAVH YFKGWFLIDM VAAIPFDLLI 

       370        380        390        400        410        420 
FRTGSDETTT LIGLLKTARL LRLVRVARKL DRYSEYGAAV LFLLMCTFAL IAHWLACIWY 

       430        440        450        460        470        480 
AIGNVERPYL EHKIGWLDSL GVQLGKRYNG SDPASGPSVQ DKYVTALYFT FSSLTSVGFG 

       490        500        510        520        530        540 
NVSPNTNSEK VFSICVMLIG SLMYASIFGN VSAIIQRLYS GTARYHTQML RVKEFIRFHQ 

       550        560        570        580        590        600 
IPNPLRQRLE EYFQHAWSYT NGIDMNAVLK GFPECLQADI CLHLHRALLQ HCPAFSGAGK 

       610        620        630        640        650        660 
GCLRALAVKF KTTHAPPGDT LVHLGDVLST LYFISRGSIE ILRDDVVVAI LGKNDIFGEP 

       670        680        690        700        710        720 
VSLHAQPGKS SADVRALTYC DLHKIQRADL LEVLDMYPAF AESFWSKLEV TFNLRDAAGG 

       730        740        750        760        770        780 
LHSSPRQAPG SQDHQGFFLS DNQSGSPHEL GPQFPSKGYS LLGPGSQNSM GAGPCAPGHP 

       790        800        810        820        830        840 
DAAPPLSISD ASGLWPELLQ EMPPRHSPQS PQEDPDCWPL KLGSRLEQLQ AQMNRLESRV 

       850        860        870        880        890        900 
SSDLSRILQL LQKPMPQGHA SYILEAPASN DLALVPIASE TTSPGPRLPQ GFLPPAQTPS 

       910        920        930        940        950        960 
YGDLDDCSPK HRNSSPRMPH LAVATDKTLA PSSEQEQPEG LWPPLASPLH PLEVQGLICG 

       970        980        990 
PCFSSLPEHL GSVPKQLDFQ RHGSDPGFAG SWGH 

« Hide

Isoform 2 [UniParc].

Checksum: 0556E274946D2B7E
Show »

FASTA905100,450
Isoform 3 [UniParc].

Checksum: 6CBD9F336841809B
Show »

FASTA50256,298

References

« Hide 'large scale' references
[1]"Human Eag-related gene member 2 (Herg2) potassium channel."
Titus S.A., Ganetzky B.S.
Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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 2), VARIANT MET-925.
Tissue: Amygdala and Kidney.
[3]"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 3).
Tissue: Uterus.
[4]"HERG K(+) currents in human prolactin-secreting adenoma cells."
Bauer C.K., Wulfsen I., Schaefer R., Glassmeier G., Wimmers S., Flitsch J., Luedecke D.K., Schwarz J.R.
Pflugers Arch. 445:589-600(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-449.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF311913 mRNA. Translation: AAG40871.1.
AK090969 mRNA. Translation: BAC03559.1.
AK091877 mRNA. Translation: BAC03764.1.
BC006334 mRNA. Translation: AAH06334.1.
RefSeqNP_001265848.1. NM_001278919.1.
NP_001265849.1. NM_001278920.1.
NP_110406.1. NM_030779.3.
NP_775115.1. NM_173092.2.
UniGeneHs.591177.

3D structure databases

ProteinModelPortalQ9H252.
SMRQ9H252. Positions 1-164, 421-513, 522-716.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000318212.

Chemistry

ChEMBLCHEMBL2362996.
DrugBankDB00308. Ibutilide.
GuidetoPHARMACOLOGY573.

PTM databases

PhosphoSiteQ9H252.

Polymorphism databases

DMDM26006810.

Proteomic databases

PaxDbQ9H252.
PRIDEQ9H252.

Protocols and materials databases

DNASU81033.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000456941; ENSP00000396900; ENSG00000173826. [Q9H252-2]
ENST00000580652; ENSP00000464672; ENSG00000173826. [Q9H252-3]
ENST00000581784; ENSP00000463830; ENSG00000173826. [Q9H252-2]
ENST00000583023; ENSP00000463533; ENSG00000173826. [Q9H252-1]
GeneID81033.
KEGGhsa:81033.
UCSCuc002jax.1. human. [Q9H252-3]
uc002jay.3. human. [Q9H252-1]
uc002jaz.1. human. [Q9H252-2]

Organism-specific databases

CTD81033.
GeneCardsGC17P061600.
HGNCHGNC:18862. KCNH6.
HPACAB006838.
CAB022674.
MIM608168. gene.
neXtProtNX_Q9H252.
PharmGKBPA38722.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2202.
HOGENOMHOG000230793.
HOVERGENHBG052232.
InParanoidQ9H252.
KOK04909.
OMAMYPAFAD.
OrthoDBEOG75B879.
PhylomeDBQ9H252.
TreeFamTF313130.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ9H252.
BgeeQ9H252.
CleanExHS_KCNH6.
GenevestigatorQ9H252.

Family and domain databases

Gene3D2.60.120.10. 2 hits.
InterProIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR003967. K_chnl_volt-dep_ERG.
IPR001610. PAC.
IPR000014. PAS.
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.
PR01470. ERGCHANNEL.
SMARTSM00100. cNMP. 1 hit.
SM00086. PAC. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
SSF55785. SSF55785. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiKCNH6.
GenomeRNAi81033.
NextBio71366.
PROQ9H252.
SOURCESearch...

Entry information

Entry nameKCNH6_HUMAN
AccessionPrimary (citable) accession number: Q9H252
Secondary accession number(s): Q9BRD7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 125 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 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 17

Human chromosome 17: entries, gene names and cross-references to MIM