Disintegrins:The Challenge of Nomenclature

Mary Ann McLaneUniversity of Delaware

ISTH Subcommittee on Exogenous Hemostatic FactorsAugust 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 X-

binding 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 activatingFactor V activating Factor X activatingFactor X activating Factor IX activatingFactor IX activating Prothrombin

activating Fibrinogen clotting Protein C activating Factor IX/factor X-

binding protein Thrombin inhibitor

Phospholipase APhospholipase A Fibrin(ogen) Fibrin(ogen)

degradationdegradation Plasminogen activationPlasminogen activation HemorrhagicHemorrhagic Platelet aggregation Platelet aggregation

inducersinducers Inhibitors of platelet Inhibitors of platelet

aggregationaggregation Inhibitors of serpinsInhibitors of serpins

1991,2000 “-arin” or “activase” added to

prefixes derived from Latin species name, plus designation of A, B, C or D based on cofactor requirements

Snake venom proteins active on the hemostatic system (Markland 1998)

Factor V activatingFactor V activating Factor X activatingFactor X activating Factor IX activatingFactor IX activating Prothrombin Prothrombin

activatingactivating Fibrinogen clottingFibrinogen clotting Protein C activatingProtein C activating Factor IX/factor X-Factor IX/factor X-

binding proteinbinding protein Thrombin inhibitorThrombin inhibitor

Phospholipase APhospholipase A Fibrin(ogen) Fibrin(ogen)

degradationdegradation Plasminogen activationPlasminogen activation HemorrhagicHemorrhagic Platelet aggregation Platelet aggregation

inducersinducers Inhibitors of platelet

aggregation Inhibitors of serpinsInhibitors 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 AccutinAccutin Contortrostatin Acostatin HalysetinHalysetin Piscivostatin Ussuristatin 1, 2 Bitistatin ArietinArietin Batroxostatin Jarastatin Cerastatin

CerastinCerastin Schistatin Echistatin leukogastinA, BleukogastinA, B MultisquamatinMultisquamatin OcellatinOcellatin Eristostatin ElegantinElegantin Flavostatin Trimestatin JerdonatinJerdonatin 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 Echistatin Echistatin

Standardizing nomenclature

Realities Subspecies discoveries http://www.embl-heidelberg.de

Echis carinatus Echistatin

Echis carinatus sochurecki

Echis sochurecki

1969

1999 2001

Standardizing nomenclature Realities

Genus different, species the same carinatin [Tropidechis carinatus]

Non-disintegrin carinatin [Echis carinatus]

Echistatin 2

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-species-subspecies (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

Adinbitor Blobrevidin 2 (a dimer)

Gloydius halys brevicaudus 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)

Kistrin (Dennis 1990) Calloselasma rhodostoma (1827, 1994)

Rhodostomin (Au 1991)

“-cetin” is also used for naming C-lectin-like proteins targeting GPIb, GPVI and/or 21

Discussion!