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PR00286

Identifier
CHARYBDTOXIN  [View Relations]  [View Alignment]  
Accession
PR00286
No. of Motifs
2
Creation Date
01-JUL-1994  (UPDATE 27-JUN-1999)
Title
Charybdotoxin signature
Database References
PRINTS; PR00284 TOXIN
PROSITE; PS01138 SCORP_SHORT_TOXIN
INTERPRO; IPR001947
PDB; 2CRD
SCOP; 2CRD
Literature References
1. GIMENEZ-GALLEGO, G., NAVIA, M.A., REUBEN, J.P., KATZ, G.M., 
KACZOROWSKI, G.J. AND GARCIA, M.L.
Purification, sequence and model structure of charybdotoxin, a potent
selective inhibitor of calcium-activated potassium channels.
PROC.NATL.ACAD.SCI.U.S.A. 85 3329-3333 (1988). 
 
2. CREST, M., JACQUET, G., GOLA, M., ZERROUK, H., BENSLIMANE, A.,
ROCHAT, H., MANSUELLE, P. AND MARTIN-EAUCLAIRE, M.F.
Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-
activated K+ channels characterised from Androctonus mauretanicus 
mauretanicus venom.
J.BIOL.CHEM. 267 1640-1647 (1992).
 
3. MARTIN, B.M., POSSANI, L.D., DENT, M.A.R. AND MAELICKE, A.
N-terminal sequence of toxin-II.9.2.2 from the venom of the scorpion
centruroides-noxius.
TOXICON. 20(1) 74 (1982). 
 
4. GALVEZ, A., GIMENEZ-GALLEGO, G., REUBEN, J.P., ROY-CONTANCIN, L.,
FEIGENBAUM, P., KACZOROWSKI, G.J. AND GARCIA, M.L.
Purification and characterisation of a unique, potent peptidyl probe
for the high conductance calcium-activated potassium channel from venom
of the scorpion Buthus tamulus.
J.BIOL.CHEM. 265 11083-11090 (1990).
 
5. JOHNSON, B.A. AND SUGG, E.E.
Determination of the 3-dimensional structure of iberiotoxin in solution
by 1H nuclear magnetic resonance spectroscopy.
BIOCHEMISTRY 31 8151-8159 (1992).

Documentation
Charybdotoxin is a protein present in scorpion venom [1]. The protein
consists of a single polypeptide chain and is a potent, selective
inhibitor of calcium-activated potassium channels in pituitary and
aortic smooth muscle cells - the toxin reversibly blocks channel
activity by interacting at the external pore of the channel protein.
 
The primary structure of the toxin is similar to a number of neurotoxins
of diverse origin, including kaliotoxin [2], noxiustoxin [3] and 
iberiotoxin [4,5]: this suggests that the toxin belongs to a superfamily
of proteins that modify ion-channel activities. The tertiary structure
of the toxins comprises a 3-stranded beta-sheet and a short helix, and
is stabilised by a number of disulphide bridges [5].
 
CHARYBDTOXIN is a 2-element fingerprint that provides a signature for the
charybdotoxins and related peptides. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs each encode 3 conserved Cys
residues from the N- and C-terminal portions of the alignment, which are
involved in disulphide bond formation in the folded structure. Two
iterations on OWL23.1 were required to reach convergence, at which point
a true set comprising 8 sequences was identified (no match was made with
the fragment SCK2_TITSE, which lacks most of motif 2).  
 
An update on SPTR37_9f identified a true set of 18 sequences.
Summary Information
18 codes involving  2 elements
Composite Feature Index
21818
12
True Positives
SCA1_LEIQH    SCA2_LEIQH    SCA3_LEIQH    SCK1_ANDMA    
SCK1_CENLL SCK1_ORTSC SCK2_ANDMA SCK2_LEIQH
SCK3_LEIQH SCK5_ANDMA SCKA_TITSE SCKB_PANIM
SCKC_LEIQH SCKI_MESTA SCKL_LEIQH SCKM_CENMA
SCKN_CENNO SCXM_SCOMA
Sequence Titles
SCA1_LEIQH  AGITOXIN 1 (AGTX-1) (LEIUROTOXIN II) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION). 
SCA2_LEIQH AGITOXIN 2 (AGTX-2) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION).
SCA3_LEIQH AGITOXIN 3 (AGTX-3) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION).
SCK1_ANDMA KALIOTOXIN 1 (KTX 1) - ANDROCTONUS MAURETANICUS MAURETANICUS (SCORPION).
SCK1_CENLL TOXIN I (TOXIN II.10.9.1) - CENTRUROIDES LIMPIDUS LIMPIDUS (MEXICAN SCORPION).
SCK1_ORTSC TOXIN OSK1 (OSK-1) - ORTHOCHIRUS SCROBICULOSUS (CENTRAL ASIAN SCORPION).
SCK2_ANDMA KALIOTOXIN 2 PRECURSOR (KTX 2) - ANDROCTONUS MAURETANICUS MAURETANICUS (SCORPION).
SCK2_LEIQH CHARYBDOTOXIN 2 (CHTX-LQ2) (TOXIN 18-2) (LQH 18-2) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION).
SCK3_LEIQH POTASSIUM CHANNEL BLOCKING TOXIN 15-1 (LQH 15-1) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION).
SCK5_ANDMA LEIUROTOXIN I-LIKE TOXIN P05 - ANDROCTONUS MAURETANICUS MAURETANICUS (SCORPION).
SCKA_TITSE TITYUSTOXIN K ALPHA (TSTX-K ALPHA) (TSK4) - TITYUS SERRULATUS (BRAZILIAN SCORPION).
SCKB_PANIM POTASSIUM CHANNEL BLOCKING TOXIN PITX-K-BETA - PANDINUS IMPERATOR (SCORPION).
SCKC_LEIQH CHARYBDOTOXIN (CHTX) (CHTX-LQ1) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION).
SCKI_MESTA IBERIOTOXIN (IBTX) - MESOBUTHUS TAMULUS (EASTERN INDIAN SCORPION) (BUTHUS TAMULUS).
SCKL_LEIQH LEIUROTOXIN I (LETX I) (SCYLLATOXIN) - LEIURUS QUINQUESTRIATUS HEBRAEUS (SCORPION).
SCKM_CENMA MARGATOXIN (MGTX) - CENTRUROIDES MARGARITATUS (SCORPION).
SCKN_CENNO NOXIUSTOXIN (NTX) (TOXIN II.11) - CENTRUROIDES NOXIUS (MEXICAN SCORPION).
SCXM_SCOMA MAUROTOXIN (MTX) - SCORPIO MAURUS PALMATUS (CHACTOID SCORPION).
Scan History
OWL23_1    2  100  NSINGLE    
OWL26_0 1 100 NSINGLE
SPTR37_9f 3 100 NSINGLE
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
CSVSKECWSVCKDL SCKI_BUTTA 7 7 -
CSGSPQCLKPCKDA SCKK_ANDMA 8 8 -
CTSPKQCSKPCKEL SCKN_CENNO 7 7 -
CTTSKECWSVCQRL SCKC_LEIQH 7 7 -
VCNLRRCQLSCRSL SCK5_ANDMA 2 2 -
FCNLRMCQLSCRSL SCKL_LEIQH 2 2 -

Motif 2 width=14
Element Seqn Id St Int Rpt
GLLGKCIGVKCECV SCK5_ANDMA 16 0 -
GLLGKCIGDKCECV SCKL_LEIQH 16 0 -
VDRGKCMGKKCRCY SCKI_BUTTA 23 2 -
MRFGKCMNRKCHCT SCKK_ANDMA 23 1 -
SAGAKCMNGKCKCY SCKN_CENNO 24 3 -
TSRGKCMNKKCRCY SCKC_LEIQH 23 2 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
CTGSPQCLKPCKDA SCA1_LEIQH 8 8 -
CTGSPQCIKPCKDA SCA2_LEIQH 8 8 -
CTGSPQCIKPCKDA SCA3_LEIQH 8 8 -
CSGSPQCLKPCKDA SCK1_ANDMA 8 8 -
CKHSGQCLKPCKDA SCK2_ANDMA 29 29 -
CKISRQCLEPCKKA SCK1_ORTSC 8 8 -
CTSPKQCSKPCKEL SCKN_CENNO 7 7 -
CTSPKQCLPPCKAQ SCKM_CENMA 7 7 -
CTSPQQCLRPCKDR SCK1_CENLL 7 7 -
CTASNQCWSICKRL SCK2_LEIQH 7 7 -
CRGSPECLPKCKEA SCKA_TITSE 7 7 -
CTTSKECWSVCQRL SCKC_LEIQH 7 7 -
CSVSKECWSVCKDL SCKI_MESTA 7 7 -
CTNEKQCYPHCKKE SCKB_PANIM 4 4 -
CYDSRQCWIACKKV SCK3_LEIQH 7 7 -
CTGSKDCYAPCRKQ SCXM_SCOMA 3 3 -
VCNLRRCQLSCRSL SCK5_ANDMA 2 2 -
FCNLRMCQLSCRSL SCKL_LEIQH 2 2 -

Motif 2 width=14
Element Seqn Id St Int Rpt
MRFGKCINGKCHCT SCA1_LEIQH 23 1 -
MRFGKCMNRKCHCT SCA2_LEIQH 23 1 -
MRFGKCMNRKCHCT SCA3_LEIQH 23 1 -
MRFGKCMNRKCHCT SCK1_ANDMA 23 1 -
MRFGKCMNGKCDCT SCK2_ANDMA 44 1 -
MRFGKCMNGKCHCT SCK1_ORTSC 23 1 -
SAGAKCMNGKCKCY SCKN_CENNO 24 3 -
SAGAKCMNGKCKCY SCKM_CENMA 24 3 -
HAGGKCINGKCKCY SCK1_CENLL 24 3 -
TNRGKCMNKKCRCY SCK2_LEIQH 23 2 -
KAAGKCMNGKCKCY SCKA_TITSE 23 2 -
TSRGKCMNKKCRCY SCKC_LEIQH 23 2 -
VDRGKCMGKKCRCY SCKI_MESTA 23 2 -
YPNAKCMNRKCKCF SCKB_PANIM 20 2 -
STQGKCQNKQCRCY SCK3_LEIQH 23 2 -
CPNAKCINKSCKCY SCXM_SCOMA 19 2 -
GLLGKCIGVKCECV SCK5_ANDMA 16 0 -
GLLGKCIGDKCECV SCKL_LEIQH 16 0 -