Summary: Conotoxin

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

Wikipedia: Conotoxin
Wikipedia: Contryphan
Pfam
InterPro

This is the Wikipedia entry entitled "Conotoxin". More...

The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.

Does Pfam agree with the content of the Wikipedia entry ?

Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.

Editing Wikipedia articles

Before you edit for the first time

Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.

You should take a few minutes to view the following pages:

How your contribution will be recorded

Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.

If you have problems editing a particular page, contact us at pfam-help@sanger.ac.uk and we will try to help.

Contact us

The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.

Conotoxin Edit Wikipedia article

Alpha conotoxin precursor

α-Conotoxin PnIB from C. pennaceus, disulfide bonds shown in yellow. From the University of Michigan's Orientations of Proteins in Membranes database, PDB: 1AKG.

Identifiers

Symbol

Toxin_8

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Omega conotoxin

Schematic diagram of the three-dimensional structure of ω-conotoxin MVIIA (ziconotide). Disulfide bonds are shown in gold. From PDB: 1DW5.

Identifiers

Symbol

Conotoxin

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.

Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of these peptides modulate the activity of ion channels.^[1] Over the last few decades conotoxins have been the subject of pharmacological interest.^[2]

Hypervariability

Conotoxins are hypervariable even within the same species; the genes that encode them do not act endogenously,^[3] and thus are less conserved and more likely to experience gene duplication events and nonsynonymous mutations which lead to the development of novel functions.^[4] These genes will experience less selection against mutations, and therefore mutations will remain in the genome longer, allowing more time for potentially beneficial novel functions to arise.^[5] Variability in conotoxin components reduces the likelihood that prey organisms will develop resistance; thus cone snails are under constant selective pressure to maintain polymorphism in these genes because failing to evolve and adapt will lead to extinction (Red Queen hypothesis).^[6]

Disulfide connectivities

Types of conotoxins also differ in the number and pattern of disulfide bonds.^[7] The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.^[8]

Types and biological activities

The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. Each of the five types of conotoxins attacks a different target:

α-conotoxin inhibits nicotinic acetylcholine receptors at nerves and muscles.^[9]
δ-conotoxin inhibits the inactivation of voltage-dependent sodium channels.^[10]
κ-conotoxin inhibits potassium channels.^[11]
μ-conotoxin inhibits voltage-dependent sodium channels in muscles.^[12]
ω-conotoxin inhibits N-type voltage-dependent calcium channels.^[13] Because N-type voltage-dependent calcium channels are related to algesia (sensitivity to pain) in the nervous system, ω-conotoxin has an analgesic effect: the effect of ω-conotoxin M VII A is 100 to 1000 times that of morphine.^[14] Therefore, a synthetic version of ω-conotoxin M VII A has found application as an analgesic drug ziconotide (Prialt).^[15]

Alpha

Alpha conotoxins have two types of cysteine arrangements,^[16] and are competitive nicotinic acetylcholine receptor antagonists.

Delta and kappa, and omega

Omega, delta and kappa families of conotoxins have a knottin or inhibitor cystine knot scaffold. The knottin scaffold is a very special disulfide-through-disulfide knot, in which the III-VI disulfide bond crosses the macrocycle formed by two other disulfide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N-terminus. The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers.^[7]

Mu

Mu-conotoxin

nmr solution structure of piiia toxin, nmr, 20 structures

Identifiers

Symbol

Mu-conotoxin

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed.^[17] Mu-conotoxins target the muscle-specific voltage-gated sodium channels,^[7] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.^[17]^[18] Mu-conotoxins target the voltage-gated sodium channels, preferentially those of skeletal muscle,^[19] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.^[20]

Different subtypes of voltage-gated sodium channels are found in different tissues in mammals, e.g., in muscle and brain, and studies have been carried out to determine the sensitivity and specificity of the mu-conotoxins for the different isoforms.^[21]

References

^ Terlau H, Olivera BM (2004). "Conus venoms: a rich source of novel ion channel-targeted peptides". Physiol. Rev. 84 (1): 41–68. doi:10.1152/physrev.00020.2003. PMID 14715910.
^ Olivera BM, Teichert RW (2007). "Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery.". Mol Interv 7 (5): 251–60. doi:10.1124/mi.7.5.7. PMID 17932414.
^ Biggs JS, Watkins M, Puillandre N, Ownby JP, Lopez-Vera E, Christensen S, Moreno KJ, Bernaldez J, Licea-Navarro A, Corneli PS, Olivera BM (July 2010). "Evolution of Conus peptide toxins: analysis of Conus californicus Reeve, 1844". Mol. Phylogenet. Evol. 56 (1): 1–12. doi:10.1016/j.ympev.2010.03.029. PMC 3488448. PMID 20363338.
^ Olivera BM, Watkins M, Bandyopadhyay P, Imperial JS, de la Cotera EP, Aguilar MB, Vera EL, Concepcion GP, Lluisma A (September 2012). "Adaptive radiation of venomous marine snail lineages and the accelerated evolution of venom peptide genes". Ann. N. Y. Acad. Sci. 1267 (1): 61–70. doi:10.1111/j.1749-6632.2012.06603.x. PMC 3488454. PMID 22954218.
^ Wong ES, Belov K (March 2012). "Venom evolution through gene duplications". Gene 496 (1): 1–7. doi:10.1016/j.gene.2012.01.009. PMID 22285376.
^ Liow LH, Van Valen L, Stenseth NC (July 2011). "Red Queen: from populations to taxa and communities". Trends Ecol. Evol. (Amst.) 26 (7): 349–58. doi:10.1016/j.tree.2011.03.016. PMID 21511358.
^ ^a ^b ^c Jones RM, McIntosh JM (2001). "Cone venom--from accidental stings to deliberate injection". Toxicon 39 (10): 1447–1451. doi:10.1016/S0041-0101(01)00145-3. PMID 11478951.
^ Sato K, Kini RM, Gopalakrishnakone P, Balaji RA, Ohtake A, Seow KT, Bay BH (2000). "lambda-conotoxins, a new family of conotoxins with unique disulfide pattern and protein folding. Isolation and characterization from the venom of Conus marmoreus". J. Biol. Chem. 275 (50): 39516–39522. doi:10.1074/jbc.M006354200. PMID 10988292.
^ Nicke A, Wonnacott S, Lewis RJ (2004). "Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes". Eur. J. Biochem. 271 (12): 2305–2319. doi:10.1111/j.1432-1033.2004.04145.x. PMID 15182346.
^ Leipold E, Hansel A, Olivera BM, Terlau H, Heinemann SH (2005). "Molecular interaction of delta-conotoxins with voltage-gated sodium channels". FEBS Lett. 579 (18): 3881–3884. doi:10.1016/j.febslet.2005.05.077. PMID 15990094.
^ Shon KJ, Stocker M, Terlau H, Stühmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM (1998). "kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel". J. Biol. Chem. 273 (1): 33–38. doi:10.1074/jbc.273.1.33. PMID 9417043.
^ Li RA, Tomaselli GF (2004). "Using the deadly mu-conotoxins as probes of voltage-gated sodium channels". Toxicon 44 (2): 117–122. doi:10.1016/j.toxicon.2004.03.028. PMC 2698010. PMID 15246758.
^ Nielsen KJ, Schroeder T, Lewis R (2000). "Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels" (abstract). J. Mol. Recognit. 13 (2): 55–70. doi:10.1002/(SICI)1099-1352(200003/04)13:2<55::AID-JMR488>3.0.CO;2-O. PMID 10822250.
^ Bowersox SS, Luther R (1998). "Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus". Toxicon 36 (11): 1651–1658. doi:10.1016/S0041-0101(98)00158-5. PMID 9792182.
^ Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today 42 (6): 369–78. doi:10.1358/dot.2006.42.6.973534. PMID 16845440.
^ Gray WR, Olivera BM, Zafaralla GC, Ramilo CA, Yoshikami D, Nadasdi L, Hammerland LG, Kristipati R, Ramachandran J, Miljanich G (1992). "Novel alpha- and omega-conotoxins from Conus striatus venom". Biochemistry 31 (41): 11864–11873. doi:10.1021/bi00162a027. PMID 1390774.
^ ^a ^b Nielsen KJ, Watson M, Adams DJ, Hammarström AK, Gage PW, Hill JM, Craik DJ, Thomas L, Adams D, Alewood PF, Lewis RJ (July 2002). "Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels". J. Biol. Chem. 277 (30): 27247–55. doi:10.1074/jbc.M201611200. PMID 12006587.
^ Zeikus RD, Gray WR, Cruz LJ, Olivera BM, Kerr L, Moczydlowski E, Yoshikami D (1985). "Conus geographus toxins that discriminate between neuronal and muscle sodium channels". J. Biol. Chem. 260 (16): 9280–8. PMID 2410412.
^ McIntosh JM, Jones RM (October 2001). "Cone venom--from accidental stings to deliberate injection". Toxicon 39 (10): 1447–51. doi:10.1016/S0041-0101(01)00145-3. PMID 11478951.
^ Cruz LJ, Gray WR, Olivera BM, Zeikus RD, Kerr L, Yoshikami D, Moczydlowski E (August 1985). "Conus geographus toxins that discriminate between neuronal and muscle sodium channels". J. Biol. Chem. 260 (16): 9280–8. PMID 2410412.
^ Floresca CZ (2003). "A comparison of the mu-conotoxins by [3H]saxitoxin binding assays in neuronal and skeletal muscle sodium channel.". Toxicol Appl Pharmacol 190 (2): 95–101. doi:10.1016/s0041-008x(03)00153-4. PMID 12878039.

External links

Conotoxins at the US National Library of Medicine Medical Subject Headings (MeSH)
Baldomero "Toto" Olivera's short talk. "Conus Peptides".
Kaas Q, Westermann JC, Halai R, Wang CK, Craik DJ. "ConoServer". Institute of Molecular Bioscience, The University of Queensland, Australia. Retrieved 2009-06-02. A database for conopeptide sequences and structures

v t e Protein tertiary structure

General	Structural domain Protein folding Structure determination methods

All-α folds:	Helix bundle Globin fold Homeodomain fold Alpha solenoid

All-β folds:	Immunoglobulin domain Beta barrel Beta-propeller

α/β folds:	TIM barrel Leucine-rich repeat Flavodoxin fold Rossmann fold Thioredoxin fold Trefoil knot fold

α+β folds:	DNA clamp Ferredoxin fold Ribonuclease A SH2-like fold

Irregular folds:	Conotoxin

Cholinergics

Receptor ligands

mACh	Agonists: 77-LH-28-1 AC-42 AC-260,584 Aceclidine Acetylcholine AF30 AF150(S) AF267B AFDX-384 Alvameline AQRA-741 Arecoline Bethanechol Butyrylcholine Carbachol CDD-0034 CDD-0078 CDD-0097 CDD-0098 CDD-0102 Cevimeline Choline cis-Dioxolane Ethoxysebacylcholine Itameline LY-593,039 L-689,660 LY-2,033,298 McNA343 Methacholine Milameline Muscarine NGX-267 Ocvimeline Oxotremorine PD-151,832 Pilocarpine RS86 Sabcomeline SDZ 210-086 Sebacylcholine Suberyldicholine Talsaclidine Tazomeline Thiopilocarpine Vedaclidine VU-0029767 VU-0090157 VU-0152099 VU-0152100 VU-0238429 WAY-132,983 Xanomeline YM-796 Antagonists: 3-Quinuclidinyl benzilate 4-DAMP Aclidinium bromide Anisodamine Anisodine Antihistamines (first-generation) (e.g., brompheniramine, chlorphenamine, cyproheptadine, dimenhydrinate, diphenhydramine, doxylamine, mepyramine (pyrilamine), phenindamine, pheniramine, promethazine, tripelennamine, triprolidine) Atropine Atropine methonitrate Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, zotepine) Benactyzine Benzatropine (benztropine) Benzilylcholine mustard Benzydamine BIBN 99 Biperiden Bornaprine CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 Caramiphen Cloperastine CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Dimethindene Dexetimide DIBD Dicyclomine (dicycloverine) Ditran EA-3167 EA-3443 EA-3580 EA-3834 Etanautine Etybenzatropine (ethybenztropine) Flavoxate Himbacine HL-031,120 Ipratropium bromide J-104,129 Hyoscyamine Mamba toxin 3 Mamba toxin 7 Mazaticol Mebeverine Methoctramine Metixene N-Ethyl-3-piperidyl benzilate N-Methyl-3-piperidyl benzilate Orphenadrine Otenzepad Oxybutynin PBID PD-102,807 PD-0298029 Phenglutarimide Phenyltoloxamine Pipenzolate bromide Pirenzepine Piroheptine Procyclidine Profenamine Revefenacin RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine (hyoscine) Sofpironium bromide Solifenacin Telenzepine Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tiotropium bromide Tolterodine Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, lofepramine, nortriptyline, protriptyline, trimipramine) Trihexyphenidyl Tripitamine Tropatepine Tropicamide Typical antipsychotics (e.g., chlorpromazine, loxapine, thioridazine) WIN-2299 Xanomeline Zamifenacin

nACh	Agonists: 5-HIAA A-84,543 A-366,833 A-582,941 A-867,744 ABT-202 ABT-418 ABT-560 ABT-894 Acetylcholine Altinicline Anabasine Anatoxin-a AR-R17779 Butinoline Butyrylcholine Carbachol Choline Cotinine Cytisine Decamethonium Desformylflustrabromine Dianicline Dimethylphenylpiperazinium Epibatidine Epiboxidine Ethanol Ethoxysebacylcholine EVP-4473 EVP-6124 Galantamine GTS-21 Ispronicline Ivermectin Levamisole Lobeline MEM-63,908 (RG-3487) Morantel Nicotine (tobacco) NS-1738 PHA-543,613 PHA-709,829 PNU-120,596 PNU-282,987 Pozanicline Rivanicline RJR-2429 Sazetidine A SB-206553 Sebacylcholine SIB-1508Y SIB-1553A SSR-180,711 Suberyldicholine Suxamethonium (succinylcholine) TC-1698 TC-1734 TC-1827 TC-2216 TC-5214 TC-5619 TC-6683 Tebanicline Tropisetron UB-165 Varenicline WAY-317,538 XY-4083 Antagonists: 18-MAC 18-MC α-Neurotoxins (e.g., α-bungarotoxin, α-cobratoxin, α-conotoxin, many others) ABT-126 Alcuronium Allopregnanolone Amantadine Anatruxonium AQW051 Atracurium Barbiturates (e.g., pentobarbital, sodium thiopental) Bungarotoxins (e.g., α-bungarotoxin, κ-bungarotoxin) Bupropion Chandonium Chlorisondamine Cisatracurium Coclaurine Coronaridine Cyclopropane Dacuronium Decamethonium Dehydronorketamine Desflurane Dextromethorphan Dextropropoxyphene Dextrorphan Diadonium DHβE Dihydrochandonium Dimethyltubocurarine (metocurine) Dipyrandium Dizocilpine (MK-801) Doxacurium Encenicline Enflurane Esketamine Fazadinium Gallamine Halothane Hexafluronium Hexamethonium (benzohexonium) Hydroxybupropion Hydroxynorketamine Ibogaine Isoflurane Ketamine Kynurenic acid Laudexium (laudolissin) Levacetylmethadol Levomethadone Malouetine ME-18-MC Mecamylamine Memantine Methadone Methorphan (racemethorphan) Methyllycaconitine Metocurine Mivacurium Morphanol (racemorphan) Neramexane Nitrous oxide Norketamine Pancuronium bromide Pempidine Pentamine Pentolinium Phencyclidine Pipecuronium Progesterone Promegestone Radafaxine Rapacuronium Reboxetine Rocuronium Sevoflurane Surugatoxin Thiocolchicoside Toxiferine Tramadol Trimetaphan camsilate (trimethaphan camsylate) Tropeinium Tubocurarine Vanoxerine Vecuronium Xenon

Transporter ligands

CHT	Inhibitors: Hemicholinium-3 (hemicholine) Triethylcholine Enhancers: Coluracetam

VAChT	Inhibitors: Vesamicol

Enzyme modulators

ChAT	Inhibitors: 1-(-Benzoylethyl)pyridinium 2-(α-Naphthoyl)ethyltrimethylammonium 3-Chloro-4-stillbazole 4-(1-Naphthylvinyl)pyridine Acetylseco hemicholinium-3 Acryloylcholine AF64A B115 BETA CM-54,903 N,N-Dimethylaminoethylacrylate N,N-Dimethylaminoethylchloroacetate

AChE	Inhibitors: Reversible: Carbamates: Aldicarb Bendiocarb Bufencarb Caffeine Carbaryl Carbendazim Carbetamide Carbofuran Chlorbufam Chloropropham Ethienocarb Ethiofencarb Fenobucarb Fenoxycarb Formetanate Furadan Ladostigil Methiocarb Methomyl Miotine Oxamyl Phenmedipham Pinmicarb Pirimicarb Propamocarb Propham Propoxur; Stigmines: Distigmine bromide Eptastigmine Ganstigmine Neostigmine Phenserine Physostigmine Pyridostigmine bromide Quilostigmine Rivastigmine Terestigmine; Others: Acotiamide Ambenonium Donepezil Caffeine Edrophonium Galantamine Huperzine A Ipidacrine Minaprine Tacrine Zanapezil Irreversible: Organophosphates: Acephate Azinphos-methyl Bensulide Cadusafos Chlorethoxyfos Chlorfenvinphos Chlorpyrifos Chlorpyrifos-methyl Coumaphos Cyclosarin Demeton Demeton-S-methyl Diazinon Dichlorvos Dicrotophos Diisopropyl fluorophosphate Diisopropylphosphate Dimethoate Dioxathion Disulfoton EA-3148 Echothiophate Ethion Ethoprop Fenamiphos Fenitrothion Fenthion Fosthiazate GV Isofluorophate Isoxathion Malaoxon Malathion Methamidophos Methidathion Metrifonate Mevinphos Monocrotophos Naled Novichok agent Omethoate Oxydemeton-methyl Paraoxon Parathion Parathion-methyl Phorate Phosalone Phosmet Phoxim Pirimiphos-methyl Sarin Soman Tabun Tebupirimfos Temefos Terbufos Tetrachlorvinphos Tribufos Trichlorfon VE VG VM VR VX; Others: Demecarium Fasciculins (green mamba toxins) (1, 2, 3, 4) Onchidal (Onchidella binneyi) Reactivators: Asoxime Obidoxime Pralidoxime

BChE	Inhibitors: Cymserine Many of the AChE inhibitors listed above

Release modulators

Inhibitors	SNAP-25 inactivators: Botulinum toxin (A, C, E) VAMP inactivators: Botulinum toxin (B, D, F, G) Others: Bungarotoxins (β-bungarotoxin, γ-bungarotoxin)

Enhancers	LPHN agonists: α-Latrotoxin Others: Atracotoxin (e.g., robustoxin, versutoxin) Crotoxin

Others

Precursors / prodrugs	Adafenoxate Choline (lecithin) Citicoline Cyprodenate Dimethylethanolamine Glycerophosphocholine Meclofenoxate (centrophenoxine) Phosphatidylcholine Phosphatidylethanolamine Phosphorylcholine Pirisudanol

Cofactors	Acetic acid Acetylcarnitine Acetyl-coA Vitamin B₅

Ion channel modulators

Calcium (Ca²⁺)

Blockers	L-type-selective: Dihydropyridines: Amlodipine Aranidipine Azelnidipine Barnidipine Clevidipine Cronidipine Darodipine Dexniguldipine Elgodipine Elnadipine Felodipine Flordipine Furnidipine Iganidipine Isradipine Lacidipine Lemildipine Lercanidipine Levamlodipine Levniguldipine Manidipine Mepirodipine Mesudipine Nicardipine Nifedipine Niguldipine Niludipine Nilvadipine Nimodipine Nisoldipine Nitrendipine Olradipine Oxodipine Palonidipine Pranidipine Ryodipine (riodipine) Sagandipine Sornidipine Teludipine Tiamdipine Trombodipine Vatanidipine; Diltiazem derivatives: Clentiazem Diltiazem Iprotiazem Nictiazem Siratiazem; Phenylalkylamines: Anipamil Dagapamil Devapamil Dexverapamil Emopamil Etripamil Falipamil Gallopamil Levemopamil Nexopamil Norverapamil Ronipamil Tiapamil Verapamil; Others: AH-1058 Brinazarone Budiodarone Celivarone Cyproheptadine Dronedarone Fantofarone SR-33805 N-type-selective: ω-Conotoxins ω-Conotoxin GVIA Caroverine Huwentoxin XVI Leconotide (ω-conotoxin CVID) PD-173212 Ralfinamide Safinamide Z160 Ziconotide (ω-conotoxin MVIIA) P-type-selective: ω-Agatoxin IVA ω-Agatoxin IVB R-type-selective: SNX-482 T-type-selective: ABT-639 ML-218 Niflumic acid NNC 55-0396 ProTx I Z944 Zonisamide Non-selective: ω-Agatoxin TK ω-Conotoxin MVIIC Benidipine Bepridil Cilnidipine Cinnarizine Dotarizine Efonidipine Flunarizine Lamotrigine Levetiracetam Lomerizine Loperamide Mibefradil NP078585 Ruthenium red TROX-1 α₂δ subunit-selective (gabapentinoids): 4-Methylpregabalin Arbaclofen Arbaclofen placarbil Atagabalin Baclofen Gabapentin Gabapentin enacarbil Imagabalin Mirogabalin PD-200,347 PD-217,014 PD-299,685 Phenibut Pregabalin Others/unsorted: Bencyclane Berbamine Bevantolol Canadine Carboxyamidotriazole Cycleanine Dauricine Dimeditiapramine Diproteverine Enpiperate Eperisone Elpetrigine Ethadione Ethosuximide Fasudil Fendiline Fostedil JTV-519 Lidoflazine Magnesium Manoalide Mesuximide Monatepil Naftopidil Ochratoxin A Osthol Otilonium bromide Paramethadione Phensuximide Pinaverium Prenylamine Rhynchophylline Sesamodil Silperisone Sipatrigine Terodiline Tetrahydropalmatine Tetrandrine Tolperisone Trimethadione Valperinol

Openers	L-type-selective: Bay K8644

Potassium (K⁺)

Blockers	3,4-Diaminopyridine (amifampridine) 4-Aminopyridine (fampridine/dalfampridine) Adekalant Almokalant Amiodarone Azimilide Bretylium Bunaftine Charybdotoxin Clamikalant Conotoxins Dalazatide Dendrotoxin Dofetilide Dronedarone E-4031 Hanatoxin Ibutilide Inakalant Kaliotoxin Linopirdine Maurotoxin Nifekalant Notoxin Paxilline Pinokalant ShK-186 Sotalol Tedisamil Terikalant Tetraethylammonium Vernakalant GIRK blockers: Barium Caramiphen Cloperastine Clozapine Dextromethorphan Ethosuximide Ifenprodil Tertiapin Tipepidine hERG blockers: Ajmaline Amiodarone AmmTX3 Astemizole Azaspiracid AZD1305 Azimilide Bedaquiline BeKm-1 BmTx3 BRL-32872 Chlorpromazine Cisapride Clarithromycin Darifenacin Dextropropoxyphene Diallyl trisulfide Domperidone E-4031 Ergtoxins Erythromycin Gigactonine Haloperidol Ketoconazole Norpropoxyphene Orphenadrine Pimozide PNU-282,987 Promethazine Roxithromycin Sertindole Solifenacin Tamulotoxin Terodiline Terfenadine Thioridazine Tolterodine Vanoxerine Vernakalant

Openers	K_ATP openers: Aprikalim Bimakalim Cromakalim Emakalim Levcromakalim Mazokalim Rilmakalim Sarakalim Others: Diazoxide Flupirtine Minoxidil ML-297 Naminidil Nicorandil Pinacidil Retigabine Rottlerin

Sodium (Na⁺)

Blockers	VGSC blockers: Antiarrhythmics (class I): Ajmaline Aprindine Disopyramide Dronedarone Encainide Flecainide Lidocaine Lorajmine Lorcainide Mexiletine Moricizine Pilsicainide Prajmaline Procainamide Propafenone Quinidine Sparteine Tocainide; Anticonvulsants: Acetylpheneturide Carbamazepine Cenobamate Chlorphenacemide Elpetrigine Eslicarbazepine acetate Ethotoin Fosphenytoin Lacosamide Licarbazepine Mephenytoin Oxcarbazepine Oxitriptyline Phenacemide Pheneturide Phenytoin Rufinamide Sipatrigine Topiramate Sodium valproate Valnoctamide Valproate pivoxil Valproate semisodium Valproic acid Valpromide Zonisamide; Diuretics: Amiloride Benzamil Triamterene; Local anesthetics: pFBT Amylocaine Articaine Benzocaine Bupivacaine (Levobupivacaine, Ropivacaine) Butacaine Butamben Chloroprocaine Cinchocaine Cocaine Cyclomethycaine Dimethocaine Diphenhydramine Etidocaine Hexylcaine Iontocaine Lidocaine Mepivacaine Meprylcaine Metabutoxycaine Orthocaine Piperocaine Prilocaine Procaine Propoxycaine Proxymetacaine Risocaine Tetracaine Trimecaine; Analgesics: AZD-3161 DSP-2230 Funapide GDC-0276 NKTR-171 PF-04531083 PF-05089771 Ralfinamide Raxatrigine RG7893 (GDC-0287); Toxins: Conotoxins Neosaxitoxin Saxitoxin Tetrodotoxin; Others: Buprenorphine Evenamide Menthol Safinamide Tricyclic antidepressants

Openers	VGSC openers: Atracotoxins (Robustoxin, Versutoxin) Ciguatoxins ENaC openers: Solnatide

Chloride (Cl⁻)

Blockers	Bumetanide DIDS Flufenamic acid Furosemide Glibenclamide Lonidamine Meclofenamic acid Mefenamic acid Mepacrine Niflumic acid Piretanide Talniflumate Tolfenamic acid Trifluoperazine

Openers	CFTR openers: 1,7-Phenanthroline 1,10-Phenanthroline 4,7-Phenanthroline 7,8-Benzoquinoline Phenanthridine

This article incorporates text from the public domain Pfam and InterPro IPR004214 This article incorporates text from the public domain Pfam and InterPro IPR008036

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Contryphan". More...

The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.

Does Pfam agree with the content of the Wikipedia entry ?

Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.

Editing Wikipedia articles

Before you edit for the first time

Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.

You should take a few minutes to view the following pages:

How your contribution will be recorded

Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.

If you have problems editing a particular page, contact us at pfam-help@sanger.ac.uk and we will try to help.

Contact us

The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.

Contryphan Edit Wikipedia article

Contryphan

NMR structure of Contryphan-Vn. The peptide backbone is depicted by a curved tube while the amino acid side-chains are represented by capped sticks. Carbon atoms are colored grey, nitrogen atoms blue, oxygen atoms red, and sulfur atoms yellow.^[1]
.

Identifiers

Symbol

Contryphan_CS

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

The contryphans (conus + tryptophan) are a family of peptides that are active constituents of the potent venom produced by cone snail (genus conus). The two amino acid cysteine residues in contryphans are linked by a disulfide bond. In addition, contryphans undergo an unusual degree of post-translational modification including epimerization of leucine and tryptophan, tryptophan bromination, amidation of the C-terminus, and proline hydroxylation.^[2]

Family members

Conus textile, which produces contryphans

Contryphan family members include:

Peptide	Sequence	Species	Reference
Des(Gly1)contryphan-R	COwEPWC-NH2	C. radiatus	^[3]
Contryphan-R	GCOwEPWC-NH2	Conus radiatus	^[3]
Bromocontyphan-R	GCOwEPXC-NH2	C. radiatus	^[4]
Contryphan-Sm	GCOwQPWC-NH2	Conus stercusmuscarum	^[5]
Contryphan-P	GCOwDPWC-NH₂	C. purpurascens	^[5]
Contryphan-R/Tx	GCOwEPWC-NH2	Conus textile	^[5]
Contryphan-Tx	GCOWQPYC-NH2	Conus textile	^[5]
Contryphan-Vn	GDCPwKPWC-NH₂	Conus ventricosus	^[6]
Leu-contryphan-P	GCVlLPWC-OH	Conus purpurascens	^[7]
Leu-contryphan-Tx	CVlYPWC-NH₂	Conus textile	^[5]
Glaconryphan-M	NγSγCPWHPWC-NH₂	Conus marmoreus	^[2]

where the sequence abbreviations stand for:

O = 4-trans-hydroxyproline,
l = D-leucine, L = L-leucine,
w = D-tryptophan, W = L-tryptophan,
γ = gamma-carboxyglutamic acid,
NH₂ = C-terminal amidation

and the remainder of the letters refer to the standard one letter abbreviations for amino acids.

Mechanism of toxicity

The venom of cone snails cause paralysis of their fish prey. The molecular target has not been determined for all contryphan peptides, however it is known that contryphan-Vn is a Ca²⁺-dependent K⁺ channel modulator,^[6] while glacontryphan-M is a L-type calcium channel blocker.^[2]

References

^ PDB: 1NXN; Eliseo T, Cicero DO, Romeo C, Schininà ME, Massilia GR, Polticelli F, Ascenzi P, Paci M (June 2004). "Solution structure of the cyclic peptide contryphan-Vn, a Ca²⁺-dependent K⁺ channel modulator". Biopolymers 74 (3): 189–98. doi:10.1002/bip.20025. PMID 15150794.
^ ^a ^b ^c Hansson K, Ma X, Eliasson L, Czerwiec E, Furie B, Furie BC, Rorsman P, Stenflo J (2004). "The first gamma-carboxyglutamic acid-containing contryphan. A selective L-type calcium ion channel blocker isolated from the venom of Conus marmoreus". J. Biol. Chem. 279 (31): 32453–63. doi:10.1074/jbc.M313825200. PMID 15155730.
^ ^a ^b Jimenéz EC, Olivera BM, Gray WR, Cruz LJ (1996). "Contryphan is a D-tryptophan-containing Conus peptide". J. Biol. Chem. 271 (45): 28002–5. doi:10.1074/jbc.271.45.28002. PMID 8910408.
^ Jimenez EC, Craig AG, Watkins M, Hillyard DR, Gray WR, Gulyas J, Rivier JE, Cruz LJ, Olivera BM (1997). "Bromocontryphan: post-translational bromination of tryptophan". Biochemistry 36 (5): 989–94. doi:10.1021/bi962840p. PMID 9033387.
^ ^a ^b ^c ^d ^e Jacobsen R, Jimenez EC, Grilley M, Watkins M, Hillyard D, Cruz LJ, Olivera BM (1998). "The contryphans, a D-tryptophan-containing family of Conus peptides: interconversion between conformers". J. Pept. Res. 51 (3): 173–9. doi:10.1111/j.1399-3011.1998.tb01213.x. PMID 9531419.
^ ^a ^b Massilia GR, Schininà ME, Ascenzi P, Polticelli F (2001). "Contryphan-Vn: a novel peptide from the venom of the Mediterranean snail Conus ventricosus". Biochem. Biophys. Res. Commun. 288 (4): 908–13. doi:10.1006/bbrc.2001.5833. PMID 11688995.
^ Jacobsen RB, Jimenez EC, De la Cruz RG, Gray WR, Cruz LJ, Olivera BM (1999). "A novel D-leucine-containing Conus peptide: diverse conformational dynamics in the contryphan family". J. Pept. Res. 54 (2): 93–9. doi:10.1034/j.1399-3011.1999.00093.x. PMID 10461743.

External links

Contryphan at the US National Library of Medicine Medical Subject Headings (MeSH)

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Conotoxin Provide feedback

Conotoxins are small snail toxins that block ion channels.

Literature references

Gray WR, Olivera BM, Cruz LJ; , Annu Rev Biochem 1988;57:665-700.: Peptide toxins from venomous Conus snails. PUBMED:3052286 EPMC:3052286
Pallaghy PK, Duggan BM, Pennington MW, Norton RS; , J Mol Biol 1993;234:405-420.: Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin PUBMED:8230223 EPMC:8230223

Internal database links

SCOOP:	GRP DUF2615 UPF0506 O-antigen_lig DUF4834
Similarity to PfamA using HHSearch:	Chi-conotoxin

External database links

SCOP:

2cco

This tab holds annotation information from the InterPro database.

InterPro entry IPR004214

Cone snail toxins, conotoxins, are small neurotoxic peptides with disulphide connectivity that target ion-channels or G-protein coupled receptors. Based on the number and pattern of disulphide bonds and biological activities, conotoxins can be classified into several families [PUBMED:11478951]. Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine knot scaffold. The knottin scaffold is a very special disulphide-through-disulphide knot, in which the III-VI disulphide bond crosses the macrocycle formed by two other disulphide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N terminus.

The disulphide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins [PUBMED:10988292]. The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers [PUBMED:11478951]. Mu conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu conotoxins target the voltage-gated sodium channels [PUBMED:11478951], and are useful probes for investigating voltage-dependent sodium channels of excitable tissues [PUBMED:2410412]. Alpha conotoxins have two types of cysteine arrangements [PUBMED:1390774], and are competitive nicotinic acetylcholine receptor antagonists.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Cellular component	extracellular region (GO:0005576)
Molecular function	ion channel inhibitor activity (GO:0008200)
Biological process	pathogenesis (GO:0009405)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Omega_toxin (CL0083), which has the following description:

This clan contains a set of related small protein toxins and what appears to be the functionally distinct Albumin I domain. All members of this clan have a knottin-like fold. Additional information about this clan may be found from [1].

The clan contains the following 25 members:

Agouti Albumin_I Albumin_I_a Atracotoxin Chi-conotoxin Conotoxin Mu-conotoxin Omega-toxin Tachystatin_A Tachystatin_B Toxin_11 Toxin_12 Toxin_16 Toxin_18 Toxin_20 Toxin_21 Toxin_22 Toxin_23 Toxin_24 Toxin_27 Toxin_30 Toxin_7 Toxin_9 UPF0506 Viral_cys_rich

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (98)	Full (10)	Representative proteomes				UniProt (1890)	NCBI (1776)	Meta (0)
	Seed (98)	Full (10)	RP15 (4)	RP35 (6)	RP55 (10)	RP75 (12)	UniProt (1890)	NCBI (1776)	Meta (0)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (98)	Full (10)	Representative proteomes				UniProt (1890)	NCBI (1776)	Meta (0)
	Seed (98)	Full (10)	RP15 (4)	RP35 (6)	RP55 (10)	RP75 (12)	UniProt (1890)	NCBI (1776)	Meta (0)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (98)	Full (10)	Representative proteomes				UniProt (1890)	NCBI (1776)	Meta (0)
	Seed (98)	Full (10)	RP15 (4)	RP35 (6)	RP55 (10)	RP75 (12)	UniProt (1890)	NCBI (1776)	Meta (0)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_529 (release 6.4)

Previous IDs:

none

Type:

Domain

Author:

Bateman A

Number in seed:

98

Number in full:

10

Average length of the domain:

78.60 aa

Average identity of full alignment:

36 %

Average coverage of the sequence by the domain:

90.55 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	25.1	25.1
Trusted cut-off	26.2	25.8
Noise cut-off	24.6	24.3

Model length:

75

Family (HMM) version:

15

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Hide

Weight segments by...

number of sequences
number of species

Change the size of the sunburst

Small

Large

Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Conotoxin domain has been found. There are 30 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...

Family: Conotoxin (PF02950)

Jump to...

Summary: Conotoxin

Does Pfam agree with the content of the Wikipedia entry ?

Editing Wikipedia articles

Before you edit for the first time

How your contribution will be recorded

Contact us

Conotoxin Edit Wikipedia article

Contents

Hypervariability

Disulfide connectivities

Types and biological activities

Alpha

Delta and kappa, and omega

Mu

See also

References

External links

Does Pfam agree with the content of the Wikipedia entry ?

Editing Wikipedia articles

Before you edit for the first time

How your contribution will be recorded

Contact us

Contryphan Edit Wikipedia article

Contents

Family members

Mechanism of toxicity

See also

References

External links

Conotoxin Provide feedback

Literature references

Internal database links

External database links

InterPro entry IPR004214

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Structures