Disintegrins: The Challenge of Nomenclature Mary Ann McLane University of Delaware ISTH Subcommittee on Exogenous Hemostatic Factors August 6, 2005 Snake venom proteins active on the hemostatic system (Markland 1998) Factor V activating Factor X activating Factor IX activating Prothrombin activating Fibrinogen clotting Protein C activating Factor IX/factor Xbinding protein Thrombin inhibitor Phospholipase A Fibrin(ogen) degradation Plasminogen activation Hemorrhagic Platelet aggregation inducers Inhibitors of platelet aggregation Inhibitors of serpins Snake venom proteins active on the hemostatic system (Markland 1998) Factor V activating Factor X activating Factor IX activating Prothrombin activating “-arin” Fibrinogen clotting or “activase” added to prefixes derived from Latin Protein C activating species name, plus designation of B, C or DIX/factor based on cofactor A, Factor Xrequirements binding protein Thrombin inhibitor 1991, 2000 Phospholipase A Fibrin(ogen) degradation Plasminogen activation Hemorrhagic Platelet aggregation inducers Inhibitors of platelet aggregation Inhibitors of serpins Snake venom proteins active on the hemostatic system (Markland 1998) Factor V activating Factor X activating Factor IX activating Prothrombin activating Fibrinogen clotting Protein C activating Factor IX/factor Xbinding protein Thrombin inhibitor Phospholipase A Fibrin(ogen) degradation Plasminogen activation Hemorrhagic Platelet aggregation inducers Inhibitors of platelet aggregation Inhibitors of serpins Disintegrins: 80% “-in” Disintegrins: 43% “-in” Halysin Salmosin Applagin Kistrin Gabonin, 1, 2 Bothrasperin Cotiarin Jararacin Rhodostomin Crotatoxin Basilicin Durissin Molossin Crotavirin Cereberin Lutosin Viridin Pyramidin Eristocophin Brevicaudin 1a, 1b, 2b Saxatilin Lachesin Tergeminin Barbourin Alblabrin Falvoridin Triflavin Trigramin Disintegrins: 36% “-tin” Halystatin Accutin Contortrostatin Acostatin Halysetin Piscivostatin Ussuristatin 1, 2 Bitistatin Arietin Batroxostatin Jarastatin Cerastatin Cerastin Schistatin Echistatin leukogastinA, B Multisquamatin Ocellatin Eristostatin Elegantin Flavostatin Trimestatin Jerdonatin Obtustatin Viperostatin Disintegrins: “-statin” Halystatin Accutin Contortrostatin Acostatin Halysetin Piscivostatin Ussuristatin 1, 2 Bitistatin Arietin Batroxostatin Jarastatin Cerastatin Cerastin Schistatin Echistatin leukogastinA, B Multisquamatin Ocellatin Eristostatin Elegantin Flavostatin Trimestatin Jerdonatin Obtustatin Viperostatin Disintegrins: 17% “EF#” CC5 CC8 EMS11 EC3 EC6 EO4 EO5 EMF10 VA6 VB7 VLO4 VLO5 Disintegrins: 3% “acronym#” CTF-I CTF-II Disintegrins: 1% “-or” adinbitor Disintegrins since 2004 Jerdonin (Trimeresurus jerdonii) Bothrostatin (Bothrops jararaca) Total = 75 Note: No information from the name about whether the protein is a monomer or dimer Standardizing nomenclature Realities “statin” = suffix used for naming class of HMG-CoA reductase inhibitors for controlling cholesterol levels Lipitor (atorvastatin) - Pfizer Zocor (simvastatin) - Merck Pravachol (pravastatin) - Bristol-Myers Squibb Lescol (fluvastatin) - Novartis Mevacor (lovastatin) - Merck Crestor (rosuvastatin) - AstraZeneca Standardizing nomenclature Realities Subspecies discoveries Echis…. Echistatin a Echistatin b Echistatin g Standardizing nomenclature Realities Subspecies discoveries http://www.embl-heidelberg.de Echis carinatus Echistatin a1 1969 Echis carinatus sochurecki 1999 Echis sochurecki 2001 Standardizing nomenclature Realities Genus different, species the same carinatin [Tropidechis carinatus] Non-disintegrin carinatin [Echis carinatus] Echistatin a2 http://www.kingsnake.com/oz/snakes/elapids/tcarinata.htm http://itgmv1.fzk.de/www/itg/uetz/herp/photos/Echis_carinatus2.jpg Standardizing nomenclature Realities Genus same, species the same, different proteins discovered Echistatin Schistatin Carinatin EC3 Standardizing nomenclature Recommendation Disintegrins prior to 2004 = retain name This standardization committee will determine how many proteins have been discovered from each genus-speciessubspecies (to get the next number) Include the NCBI protein database http://www.ncbi.nlm.nih.gov/entrez for disintegrins named after cDNA analysis Standardizing nomenclature Recommendation New disintegrins are named by combination of genus-subspecies or species-subspecies Latin name followed by “-min” for monomer or “din” for dimers Numbered sequentially from that point on Standardizing nomenclature Echis carinatus sochurecki Echistatin EC3 EC6 Schistatin Ecarisomin 5 (a monomer) Standardizing nomenclature Echis carinatus sochurecki Echistatin EC3 EC6 Schistatin Ecarisomin 5 (a monomer) Ecarisodin 6 (a dimer) Ecarisotin 7 (unsure of structure; cDNA name) Standardizing nomenclature Gloydius genus Gloydius blomhoffi brevicaudus Gloydius halys brevicaudus Adinbitor Blobrevidin 2 (a dimer) Brevicaudin 1a, 1b, 2b Halybrevimin 4 (a monomer) Gloydius saxatilis Saxitilin Gloysaxatin 2 (unknown structure) Standardizing nomenclature More realities Does not eliminate potential confusion when genus names change Agkistrodon rhodostoma (1930) Calloselasma rhodostoma (1827, 1994) Kistrin (Dennis 1990) Rhodostomin (Au 1991) “-cetin” is also used for naming C-lectin-like proteins targeting GPIba, GPVI and/or a2b1 Discussion!