O54853 (KCNH6_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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
Voltage-gated potassium channel subunit Kv11.2

Gene names

Name:	Kcnh6
Synonyms:	Erg2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	950 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, 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 KCNH2/ERG1 and KCNH7/ERG3.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Highly expressed in celiac and superior mesenteric ganglia, but not detected in brain or in heart. Detected at low levels in retina. Also found in pituitary. Also found in the olfactory bulb (granular and mitral cell layers) (Ref.4). Ref.2 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.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein heterooligomerization Inferred from direct assay Ref.3. Source: RGD regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to plasma membrane Inferred from direct assay PubMed 11804849. Source: RGD
Molecular_function	inward rectifier potassium channel activity Inferred from direct assay PubMed 15677682. Source: RGD signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 950	950	Potassium voltage-gated channel subfamily H member 6		PRO_0000054014
Regions
	Topological domain	1 – 261	261	Cytoplasmic Potential
	Transmembrane	262 – 282	21	Helical; Name=Segment S1; Potential
	Topological domain	283 – 298	16	Extracellular Potential
	Transmembrane	299 – 319	21	Helical; Name=Segment S2; Potential
	Topological domain	320 – 340	21	Cytoplasmic Potential
	Transmembrane	341 – 361	21	Helical; Name=Segment S3; Potential
	Topological domain	362 – 370	9	Extracellular Potential
	Transmembrane	371 – 391	21	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	392 – 398	7	Cytoplasmic Potential
	Transmembrane	399 – 419	21	Helical; Name=Segment S5; Potential
	Topological domain	420 – 463	44	Extracellular Potential
	Intramembrane	464 – 484	21	Pore-forming; Name=Segment H5; Potential
	Topological domain	485 – 490	6	Extracellular Potential
	Transmembrane	491 – 511	21	Helical; Name=Segment S6; Potential
	Topological domain	512 – 950	439	Cytoplasmic Potential
	Domain	41 – 70	30	PAS
	Domain	92 – 144	53	PAC
	Nucleotide binding	594 – 711	118	cNMP
	Motif	476 – 481	6	Selectivity filter By similarity
Experimental info
	Mutagenesis	480	1	G → S: Dominant negative mutant; abolishes ERG current. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O54853 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: AB5AE674B08776F0	FASTA	950	105,706
	10 20 30 40 50 60 MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM 70 80 90 100 110 120 QRPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG 130 140 150 160 170 180 AVIMFILNFE DLAQLLAKSS SRSLTQRLLS HSFLGSEGSH SRPSGQGPGP GRGKYRTVSQ 190 200 210 220 230 240 IPQFTLNFVE FNLEKHRSGS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ 250 260 270 280 290 300 APRIHRGTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESQR GTCGYTCSPL 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 EPKIGWLDSL GAQLGKQYNG 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 HCPAFRGASK 610 620 630 640 650 660 GCLRALAVKF KTTHAPPGDT LVHLGDVLST LYFISRGSIE ILRDDVVVAI LGKNDIFGEP 670 680 690 700 710 720 ASLHARPGKS SADVRALTYC DLHKIHRADL LEVLDMYPAF ADTFWNKLEV TFNLRDADGG 730 740 750 760 770 780 LQSTPRQAPG HQDPQGFFLN DSQSGAAPSL SISDTSALWP ELLQQMPPSP PNPRQDLDCW 790 800 810 820 830 840 HRELGFKLEQ LQAQMNRLES RVSSDLSRIL QLLQHPQGRP SYILGASASS DLASFPETSV 850 860 870 880 890 900 TRSSESTLLV GHVPSAQTLS YGDLDDHIQT PRNFSPRTPH VAMAMDKTLV PSSEQEQPGG 910 920 930 940 950 LLSPLASPLR PLEVPGLGGS RFPSLPEHLS SVPKQLEFQR HGSDPGFTRS

References

[1]	"Identification of two nervous system-specific members of the erg potassium channel gene family." Shi W., Wymore R.S., Wang H.-S., Pan Z., Cohen I.S., McKinnon D., Dixon J.E. J. Neurosci. 17:9423-9432(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cervical ganglion.
[2]	"Expression of mRNA for voltage-dependent and inward-rectifying K channels in GH3/B6 cells and rat pituitary." Wulfsen I., Hauber H.-P., Schiemann D., Bauer C.K., Schwarz J.R. J. Neuroendocrinol. 12:263-272(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[3]	"Erg1, erg2 and erg3 K channel subunits are able to form heteromultimers." Wimmers S., Wulfsen I., Bauer C.K., Schwarz J.R. Pflugers Arch. 441:450-455(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNH2 AND KCNH7, MUTAGENESIS OF GLY-480.
[4]	"Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain." Saganich M.J., Machado E., Rudy B. J. Neurosci. 21:4609-4624(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF016192 mRNA. Translation: AAB94742.1.
IPI	IPI00199027.
RefSeq	NP_446389.1. NM_053937.1.
UniGene	Rn.10875.
3D structure databases
ProteinModelPortal	O54853.
SMR	O54853. Positions 26-130, 421-463.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000010816.
Protein family/group databases
TCDB	1.A.1.20.2. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	O54853.
Proteomic databases
PRIDE	O54853.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	116745.
KEGG	rno:116745.
UCSC	RGD:620304. rat.
Organism-specific databases
CTD	81033.
RGD	620304. Kcnh6.
Phylogenomic databases
eggNOG	COG2202.
HOGENOM	HOG000230793.
HOVERGEN	HBG052232.
InParanoid	O54853.
KO	K04909.
OrthoDB	EOG4RJG0T.
Gene expression databases
ArrayExpress	O54853.
Genevestigator	O54853.
GermOnline	ENSRNOG00000008078. Rattus norvegicus.
Family and domain databases
Gene3D	2.60.120.10. 2 hits.
InterPro	IPR018490. 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]
Pfam	PF00027. cNMP_binding. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01463. EAGCHANLFMLY. PR01470. ERGCHANNEL.
SMART	SM00100. cNMP. 1 hit. SM00086. PAC. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 1 hit.
TIGRFAMs	TIGR00229. sensory_box. 1 hit.
PROSITE	PS00888. CNMP_BINDING_1. False negative. PS00889. CNMP_BINDING_2. False negative. PS50042. CNMP_BINDING_3. 1 hit. PS50113. PAC. False negative. PS50112. PAS. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	619690.

Entry information

Entry name

KCNH6_RAT

Accession

Primary (citable) accession number: O54853

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2002
Last sequence update:	June 1, 1998
Last modified:	April 3, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program