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PR01470

Identifier
ERGCHANNEL  [View Relations]  [View Alignment]  
Accession
PR01470
No. of Motifs
5
Creation Date
12-MAR-2001
Title
ERG potassium channel family signature
Database References
PRINTS; PR00169 KCHANNEL; PR01463 EAGCHANLFMLY
Literature References
1. MILLER, C.
An overview of the potassium channel family.
GENOME BIOL. 1(4) 1-5 (2000).
 
2. ASHCROFT, F.M.
Voltage-gated K+ channels.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.97-123.
 
3. WANG, X.J.,REYNOLDS, E.R., DEAK, P., AND HALL, L.M.
The seizure locus encodes the Drosophila homolog of the HERG potassium
channel.
J.NEUROSCIENCE 17 882-890 (1997).
 
4. TRUDEAU, M.C. WARMKE, J.W., GANETZKY, B. AND ROBERTSON, G.A.
HERG, a human inward rectifier in the voltage-gated potassium channel
family.
SCIENCE 269 92-95 (1995).
 
5. SPLAWSKI, I., SHEN, J.X., TIMOTHY, K.W., LEHMANN, M.H., PRIORI, S.,
ROBINSON, J.L., MOSS, A.J., SCHWARTZ, P.J., TOWBIN, J.A., VINCENT, G.M.
AND KEATING, M.T.
Spectrum of mutations in long QT syndrome genes KVLQT1, HERG, SCN5A, KCNE1
and KCNE2.
CIRCULATION 102(10) 1178-1185 (2000).
 
6. CHEN J., ZOU A., SPLAWSKI I., KEATING M.T. AND SANGUINETTI M.C.
Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain
of HERG potassium channels accelerate channel deactivation
J.BIOL.CHEM. 274 10113-10118 (1999). 

Documentation
Potassium ion (K+) channels are a structurally diverse group of proteins
that facilitate the flow of K+ ions across cell membranes. They are
ubiquitous, being present in virtually all cell types. Activation of K+
channels tends to hyperpolarise cells, reducing the membrane's electrical
resistance, dampening nervous activity. In eukaryotic cells, K+ channels
are involved in neural signalling and generation of the cardiac rhythm, and
act as effectors in signal transduction pathways involving G protein-
coupled receptors (GPCRs). In prokaryotic cells, they play a role in the
maintenance of ionic homeostasis [1].
 
Structurally, EAG channels belong to the subfamily of K+ channels whose
subunits contain 6 transmembrane (TM) domains: these are the voltage-gated
K+ channels, the KCNQ channels, the EAG-like K+ channels and 3 kinds of
Ca2+-activated K+ channel (BK, IK and SK) [2]. All K+ channels share a
characteristic sequence feature: a TMxTVGYG motif that resides between the
2 C-terminal membrane-spanning helices, and forms the K+-selective pore 
domain [1]. However, unlike other families within this structural class,
EAG channels possess a cyclic nucleotide binding domain within their 
putative intracellular C-termini.
 
The first EAG K+ channel was identified in Drosophila, following a screen 
for mutations giving rise to behavioural abnormalities. Disruption of the
Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies
have revealed a conserved multi-gene family of EAG-like K+ channels, which
are present in Homo sapiens and many other species. Based on the varying
functional properties of the channels, the family has been divided into
3 subfamilies: EAG, ELK and ERG. Interestingly, C.elegans appears to lack
the ELK type [3].
 
The human ether-a-go-go-related gene (HERG), cloned from hippocampus, shares
49% amino acid identity with EAG. It is also found in the heart, where it 
helps to control K+ efflux [4]. Mutations in HERG result in the disruption
of the repolarising current and the disease LQT2 syndrome, an inherited
disorder of cardiac repolarisation that predisposes affected individuals to
life-threatening arrhythmias [5,6].
 
ERGKCHANNEL is a 5-element fingerprint that provides a signature for the ERG
potassium channel family. The fingerprint was derived from an initial
alignment of 9 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those regions that
characterise the ERG channels but distinguish them from other members of the
K+ channel superfamily - motif 1 spans the loop between TM domains 1 and 2;
motifs 2, 3 and 4 are situated in the C-terminus; and motif 5 spans the 
cyclic nucleotide binding domain. Two iterations on SPTR39_15f were 
required to reach convergence, at which point a true set comprising 14 
sequences was identified.
Summary Information
14 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51414141414
400000
300000
200000
12345
True Positives
HERG_HUMAN    O02497        O08962        O19119        
O35219 O35220 O35221 O35989
O54852 O54853 Q18325 Q9NG78
Q9NS40 Q9TSZ3
Sequence Titles
HERG_HUMAN  VOLTAGE-GATED POTASSIUM CHANNEL HERG (POTASSIUM CHANNEL, VOLTAGE-GATED SUBFAMILY H MEMBER 2) (ETHER-A-GO-GO-RELATED PROTEIN) - Homo sapiens (Human). 
O02497 SEI PROTEIN - Drosophila melanogaster (Fruit fly).
O08962 R-ERG - Rattus norvegicus (Rat).
O19119 VENTRICULAR ERG K+ CHANNEL SUBUNIT - Oryctolagus cuniculus (Rabbit).
O35219 LONG (ELECTOCARDIOGRAPHIC) QT SYNDROME 2 (ETHER-A-GO-GO-RELATED PROTEIN ISOFORM MERG1A) - Mus musculus (Mouse).
O35220 LONG (ELECTOCARDIOGRAPHIC) QT SYNDROME 2 (MERG1B) - Mus musculus (Mouse).
O35221 MERG1A (MERG1A') - Mus musculus (Mouse).
O35989 ERG B K+ CHANNEL ISOFORM - Mus musculus (Mouse).
O54852 POTASSIUM CHANNEL - Rattus norvegicus (Rat).
O54853 POTASSIUM CHANNEL - Rattus norvegicus (Rat).
Q18325 UNC-103 PROTEIN - Caenorhabditis elegans.
Q9NG78 HERG-LIKE POTASSIUM CHANNEL - Caenorhabditis elegans.
Q9NS40 POTASSIUM CHANNEL SUBUNIT - Homo sapiens (Human).
Q9TSZ3 POTASSIUM CHANNEL - Canis familiaris (Dog).
Scan History
SPTR39_15f 2  14   NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
IYTAVFTPYSAAF O35989 79 79 -
IYTAVFTPYSAAF O35221 421 421 -
IYTAVFTPYSAAF O35219 421 421 -
IYTAVFTPYSAAF O19119 404 404 -
IYTAVFTPYSAAF O08962 421 421 -
IYTAVFTPYSAAF O54853 268 268 -
IYTAIFTPYSAAF O54852 419 419 -
MYTAIFTPYVAAF O02497 332 332 -

Motif 2 width=16
Element Seqn Id St Int Rpt
IRFHQIPNPLRQRLEE O35989 344 252 -
IRFHQIPNPLRQRLEE O35221 686 252 -
IRFHQIPNPLRQRLEE O35219 686 252 -
IRFHQIPNPLRQRLEE O19119 669 252 -
IRFHQIPNPLRQRLEE O08962 686 252 -
IRFHQIPNPLRQRLEE O54853 536 255 -
IRFHQIPNPLRQRLEE O54852 687 255 -
IRFHQIPNPLRQRLEE O02497 599 254 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FQHAWSYTNGID O35989 361 1 -
FQHAWSYTNGID O35221 703 1 -
FQHAWSYTNGID O35219 703 1 -
FQHAWSYTNGID O19119 686 1 -
FQHAWSYTNGID O08962 703 1 -
FQHAWSYTNGID O54853 553 1 -
FQHAWTYTNGID O54852 704 1 -
FQHAWTYTNGID O02497 616 1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
KFKTTHAPPGDTLVH O35989 417 44 -
KFKTTHAPPGDTLVH O35221 759 44 -
KFKTTHAPPGDTLVH O35219 759 44 -
KFKTTHAPPGDTLVH O19119 742 44 -
KFKTTHAPPGDTLVH O08962 759 44 -
KFKTTHAPPGDTLVH O54853 609 44 -
KFKTTHAPPGDTLVH O54852 760 44 -
KFKTTHAPPGDILVH O02497 672 44 -

Motif 5 width=13
Element Seqn Id St Int Rpt
ILGKNDIFGEPLN O35989 458 26 -
ILGKNDIFGEPLN O35221 800 26 -
ILGKNDIFGEPLN O35219 800 26 -
ILGKNDIFGEPLN O19119 783 26 -
ILGKNDIFGEPLN O08962 800 26 -
ILGKNDIFGEPAS O54853 650 26 -
ILGKNDIFGEMVH O54852 801 26 -
VLGKNDIFGENPC O02497 712 25 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
IYTAVFTPYSAAF HERG_HUMAN 419 419 -
IYTAVFTPYSAAF Q9TSZ3 418 418 -
IYTAVFTPYSAAF O35989 79 79 -
IYTAVFTPYSAAF O35221 421 421 -
IYTAVFTPYSAAF O35220 79 79 -
IYTAVFTPYSAAF O35219 421 421 -
IYTAVFTPYSAAF O19119 404 404 -
IYTAVFTPYSAAF O08962 421 421 -
IYTAVFTPYSAAF O54853 268 268 -
IYTAIFTPYSAAF O54852 419 419 -
IYTAIFTPYSAAF Q9NS40 419 419 -
IYTAVFTPYVAAF Q18325 92 92 -
IYTAVFTPYVAAF Q9NG78 92 92 -
MYTAIFTPYVAAF O02497 332 332 -

Motif 2 width=16
Element Seqn Id St Int Rpt
IRFHQIPNPLRQRLEE HERG_HUMAN 684 252 -
IRFHQIPNPLRQRLEE Q9TSZ3 683 252 -
IRFHQIPNPLRQRLEE O35989 344 252 -
IRFHQIPNPLRQRLEE O35221 686 252 -
IRFHQIPNPLRQRLEE O35220 344 252 -
IRFHQIPNPLRQRLEE O35219 686 252 -
IRFHQIPNPLRQRLEE O19119 669 252 -
IRFHQIPNPLRQRLEE O08962 686 252 -
IRFHQIPNPLRQRLEE O54853 536 255 -
IRFHQIPNPLRQRLEE O54852 687 255 -
IRFHQIPNPLRQRLEE Q9NS40 687 255 -
IRFHQIPNPLRQRLEE Q18325 362 257 -
IRFHQIPNPLRQRLEE Q9NG78 362 257 -
IRFHQIPNPLRQRLEE O02497 599 254 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FQHAWSYTNGID HERG_HUMAN 701 1 -
FQHAWSYTNGID Q9TSZ3 700 1 -
FQHAWSYTNGID O35989 361 1 -
FQHAWSYTNGID O35221 703 1 -
FQHAWSYTNGID O35220 361 1 -
FQHAWSYTNGID O35219 703 1 -
FQHAWSYTNGID O19119 686 1 -
FQHAWSYTNGID O08962 703 1 -
FQHAWSYTNGID O54853 553 1 -
FQHAWTYTNGID O54852 704 1 -
FQHAWTYTNGID Q9NS40 704 1 -
FQHAWSYTNGID Q18325 379 1 -
FQHAWSYTNGID Q9NG78 379 1 -
FQHAWTYTNGID O02497 616 1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
KFKTTHAPPGDTLVH HERG_HUMAN 757 44 -
KFKTTHAPPGDTLVH Q9TSZ3 756 44 -
KFKTTHAPPGDTLVH O35989 417 44 -
KFKTTHAPPGDTLVH O35221 759 44 -
KFKTTHAPPGDTLVH O35220 417 44 -
KFKTTHAPPGDTLVH O35219 759 44 -
KFKTTHAPPGDTLVH O19119 742 44 -
KFKTTHAPPGDTLVH O08962 759 44 -
KFKTTHAPPGDTLVH O54853 609 44 -
KFKTTHAPPGDTLVH O54852 760 44 -
KFKTTHALQGDTLVH Q9NS40 760 44 -
RFRTTHSPPGDTLVH Q18325 435 44 -
RFRTTHSPPGDTLVH Q9NG78 435 44 -
KFKTTHAPPGDILVH O02497 672 44 -

Motif 5 width=13
Element Seqn Id St Int Rpt
ILGKNDIFGEPLN HERG_HUMAN 798 26 -
ILGKNDIFGEPLN Q9TSZ3 797 26 -
ILGKNDIFGEPLN O35989 458 26 -
ILGKNDIFGEPLN O35221 800 26 -
ILGKNDIFGEPLN O35220 458 26 -
ILGKNDIFGEPLN O35219 800 26 -
ILGKNDIFGEPLN O19119 783 26 -
ILGKNDIFGEPLN O08962 800 26 -
ILGKNDIFGEPAS O54853 650 26 -
ILGKNDIFGEMVH O54852 801 26 -
ILGKNDIFGEMVH Q9NS40 801 26 -
ILGKDDIFGENPL Q18325 477 27 -
ILGKDDIFGENPL Q9NG78 477 27 -
VLGKNDIFGENPC O02497 712 25 -