Classification and Nomenclature of Disintegrins Isolated from Snake Venoms On behalf of the Registry of Exogenous Hemostatic Factors of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis

Viper venoms from the Elapidae, Hydrophiidae, Atractaspididae, Viperidae and Colubridae families contain at least 25 separate classes of biologically active compounds [1]. Nomenclature standardization of these molecules by structure and function have been reported for prothrombin activators [2; 3]. No such agreement has been made for the nomenclature and classification of disintegrins which, for this report, are defined as those small molecular weight (4 – 16 kDa), non-enzymatic soluble monomeric or dimeric molecules from viper venom possessing an RGDlike motif and a cysteine arrangement significantly homologous to others in this protein family [4]. At the 51 Annual SSC Meeting in Sydney Australia (August 2005), we reported the variety of names given to the 78 disintegrins then known: 36% called “-tin” (and half of those being “statin”), and 43% placing “-in” after some combination of genus, species or both. Seventeen percent were named according to the eluted fraction they had during HPLC purification, and 3% used an acronym based on the genus and species plus a number to indicate isomers of the same protein. Only 1% of all disintegrins used the suffix “-or” in the name (Table 5 in [4]). For all of these disintegrins, the naming was done concurrently with the biochemical characterization of the protein in its initial purification from crude venom. Since that time, 15 additional disintegrins have been described (Table 1). The technology of proteomics [5; 6], deduced sequences from cloned cDNA [5; 7], as well as actual recombinant expression of disintegrins even before the protein has been isolated from the crude venom [8; 9], underscore the need for a standardized method of nomenclature for these molecules. The most confusing naming pattern happens when cDNA clones, used to deduce a disintegrin amino acid sequence and named with a letter abbreviation followed by a molecular clone number, are linked with an actual venom-derived protein isolated by HPLC, but the protein is not called the same name as the “gene”. An example is the cDNA clone ML2/8/15 shown to be the same sequence as HPLC fractions ML11 and ML12 [5]. It becomes very challenging for future investigators to know which “name” to associate with their own experiments with that particular viper’s venom. In addition, naming a disintegrin by its HPLC elution fraction number also becomes confusing if the venom is purified under a different gradient or purification method than originally used. Multiple disintegrins, both monomers and dimers, are being isolated each year from the snakes in the Family Viperidae, and we can anticipate this to continue as the venoms of heretofore untested species are being characterized, especially by molecular cloning. Use of a standard nomenclature system will lessen confusion as well as assist in valid comparisons of purified disintegrin activities.