Platelet aggregation activating toxin

Toxin which activates platelet aggregation, the self-adhesion of platelets via adhesion molecules.

See also UniProtKB-keyword


Numerous snake venom families are able to activate platelet aggregation by enzymatic and non-enzymatic mechanisms. Enzymatic protein families include L-amino-acid oxidases, serine proteases and metalloproteinases, while non-enzymatic protein families regroup Snaclecs and disintegrins (or disintegrin domain of metalloproteinases). One protein of the AB hydrolase family has also been described to activate platelet aggregation.

image Figure 1: Different platelet receptors and one of their ligand. Receptors are the targets of venom proteins that activate platelet aggregation (see text for more details).

Platelet aggregation activating toxins act by binding to platelet receptors as well as to their ligands. Until now, one ligand and five platelet receptors have been described to be activated by venom proteins:

- von Willebrand Factor (vWF) is a large glycoprotein that is released from endothelial cells in blood plasma as well as from platelets. Under high shear stress conditions, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-V-IX. It also acts as a chaperone for coagulation factor VIII (F8), delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma (Swieringa et al., 2014).
- GPIb (GP1BA) is a component of the GPIb-V-IX complex. This complex binds vWF (A1 domain), allowing platelet adhesion and platelet plug formation at sites of vascular injury. GPIb is composed of two disulfide-linked GPIbβ subunits that are non covalently linked to one GPIbα subunit.
- Integrin α2/β1 (ITGA2/ITGB1) is a receptor for collagen, and its function depends on conformational changes. Its activation depends on cytoskeleton-mediated kindlin-3 and talin-1 interactions. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression (Nieswandt et al., 2009, Swieringa et al., 2014).
- Platelet glycoprotein VI (GPVI or GP6) is the principal signaling receptor for collagen on platelets. It is a member of the immunoglobulin superfamily, which associates with the ITAM-bearing FcRγ-chain. GPVI is only expressed on platelets and megakaryocytes. Stimulation via GPVI leads to full platelet activation, including integrin activation, secretion and procoagulant activity (Swieringa et al., 2014).
- Protease-activated receptors PAR1/F2R and PAR4/F2RL3 are G-protein coupled receptors that are activated by a subset of serine proteases, most notably thrombin. PAR1 is activated by thrombin with ~30 fold greater sensitivity than PAR4 (Sidhu et al., 2014).
- CLEC-2 (CLEC1B) is a C-type lectin-like receptor for which the physiological ligand is still unclear. However, two ligands have been described, the snake venom toxin rhodocytin and the mammalian glycoprotein podoplanin (Swieringa et al., 2014).



The table below shows the different platelet receptors and the ligand of one of them, as well as the families of venom proteins that target them.

Platelet receptor activator Families of venom proteins
von Willebrand Factor (vWF) image (its interaction with GPIb is induced by the toxin) Snaclec image
disintegrin domain of metalloproteinases image
Platelet receptors Families of venom proteins
GPIb (GP1BA) image

Snaclec image
α2/β1 (ITGA2/ITGB1) image

Snaclec image
GPVI (GP6) image Snaclec image
metalloproteinase image
Protease-activated receptors
PAR1/F2R image and PAR4/F2RL3 image
serine protease image
CLEC-2 (CLEC1B) image

Snaclec image

Venom protein entries in UniProtKB/Swiss-Prot

78 entries grouped by family (browse by taxonomy, browse by keywords)

1 entry

AB hydrolase superfamily, Lipase family

PA1_VESMG Probable phospholipase A1 magnifin (EC 3.1.1.32) Vespa magnifica (Hornet)

1 entry

Arthropod phospholipase D family, Class II subfamily, Class IIb sub-subfamily

B1H_LOXLA Dermonecrotic toxin LlSicTox-betaIA1 (EC ... Loxosceles laeta (South American recluse spider) ...

11 entries

Flavin monoamine oxidase family, FIG1 subfamily

Select_allDeselect_all "Flavin monoamine oxidase family" VenomZone page
OXLAA_CERCE L-amino acid oxidase (CC-LAAO) (LAO) (EC ... Cerastes cerastes (Horned desert viper)
OXLA_BOTAL L-amino-acid oxidase (Balt-LAAO-I) (LAO) (EC ... Bothrops alternatus (Urutu) (Rhinocerophis ...
OXLA_BOTAT L-amino-acid oxidase (BatroxLAAO) (LAO) (EC ... Bothrops atrox (Barba amarilla) (Fer-de-lance)
OXLA_BOTMO L-amino-acid oxidase (BmooLAAO-I) (LAO) (EC ... Bothrops moojeni (Lance-headed viper) (Caissaca)
OXLA_BOTPA L-amino-acid oxidase (Bp-LAAO) (LAO) (EC ... Bothrops pauloensis (Neuwied's lancehead) ...
OXLA_BOTPI L-amino-acid oxidase (BpirLAAO-I) (LAO) (EC ... Bothrops pirajai (Piraja's lancehead)
OXLA_BUNFA L-amino-acid oxidase (Bf-LAAO) (LAO) (EC ... Bungarus fasciatus (Banded krait) (Pseudoboa ...
OXLA_CRODC L-amino-acid oxidase (Casca LAO) (LAAO) (EC ... Crotalus durissus cascavella (Northeastern ...
OXLA_ERIMA L-amino-acid oxidase (LAAO) (LNV-LAO) (EC ... Eristicophis macmahoni (Leaf-nosed viper)
OXLA_NAJAT L-amino-acid oxidase (LAO) (NA-LAAO) (EC ... Naja atra (Chinese cobra)
OXLA_PROMU L-amino-acid oxidase (LAAO) (TM-LAO) (EC ... Protobothrops mucrosquamatus (Taiwan habu) ...

1 entry

Not in a family

TX14A_SCODE Scoloptoxin SSD14 (SLPTX-SSD14) (Toxin-SSD14) ... Scolopendra dehaani (Thai centipede) ...

12 entries

Peptidase S1 family, Snake venom subfamily

Select_allDeselect_all "Peptidase S1 family" VenomZone page
VSP1_BOTAN Thrombin-like enzyme TLBan (SVTLE TLBan) (EC ... Bothrocophias andianus (Andean lancehead) ...
VSP1_BOTJA Platelet-aggregating proteinase PA-BJ (EC ... Bothrops jararaca (Jararaca) (Bothrops jajaraca)
VSP1_BOTMA Thrombin-like enzyme TLBm (SVTLE TLBm) (EC ... Bothrops marajoensis (Marajo lancehead)
VSP27_BOTPI Thrombin-like enzyme BpirSP27 (SVTLE) (EC ... Bothrops pirajai (Piraja's lancehead)
VSP41_BOTPI Thrombin-like enzyme BpirSP41 (SVTLE) (EC ... Bothrops pirajai (Piraja's lancehead)
VSP4A_CERCE Snake venom serine protease IVa (SVSP) (EC ... Cerastes cerastes (Horned desert viper)
VSPAA_CERCE Snake venom serine protease Afaacytin ... Cerastes cerastes (Horned desert viper)
VSPA_BOTJA Thrombin-like enzyme bothrombin (SVTLE) (EC ... Bothrops jararaca (Jararaca) (Bothrops jajaraca)
VSPA_CERCE Thrombin-like enzyme cerastotin (SVTLE) (EC ... Cerastes cerastes (Horned desert viper)
VSPCE_CERVI Thrombin-like enzyme cerastobin (SVTLE) (EC ... Cerastes vipera (Sahara sand viper)
VSPP_CERCE Thrombin-like enzyme cerastocytin (SVTLE) (EC ... Cerastes cerastes (Horned desert viper)
VSP_CRODC Thrombin-like enzyme F202 (SVTLE) (EC 3.4.21.-) ... Crotalus durissus cascavella (Northeastern ...

1 entry

Scoloptoxin-11 family

TX14B_SCODE Scoloptoxin SSD20 (Fragment) Scolopendra dehaani (Thai centipede) ...

44 entries

Snaclec family

Select_allDeselect_all "Snaclec family" VenomZone page
SL2_BITAR Snaclec bitiscetin-2 (Fragment) Bitis arietans (African puff adder)
SLA1_DEIAC Snaclec agglucetin subunit alpha-1 ... Deinagkistrodon acutus (Hundred-pace snake) ...
SLA1_TRIAB Snaclec alboaggregin-A subunit alpha (50-kDa ... Trimeresurus albolabris (White-lipped pit viper) ...
SLA2_DEIAC Snaclec agglucetin subunit alpha-2 (Antithrombin ... Deinagkistrodon acutus (Hundred-pace snake) ...
SLA2_TRIAB Snaclec alboaggregin-A subunit alpha' ... Trimeresurus albolabris (White-lipped pit viper) ...
SLA3_TRIAB Snaclec alboaggregin-A subunit beta ... Trimeresurus albolabris (White-lipped pit viper) ...
SLA4_TRIAB Snaclec alboaggregin-A subunit beta' ... Trimeresurus albolabris (White-lipped pit viper) ...
SLA_BITAR Snaclec bitiscetin subunit alpha Bitis arietans (African puff adder)
SLA_BOTAS Snaclec aspercetin subunit alpha (Fragment) Bothrops asper (Terciopelo)
SLA_CRODU Snaclec convulxin subunit alpha (CVX-alpha) Crotalus durissus terrificus (South American ...
SLA_ECHCA Snaclec echicetin subunit alpha (Fragment) Echis carinatus (Saw-scaled viper)
SLA_ECHCS Snaclec echicetin subunit alpha Echis carinatus sochureki (Saw-scaled viper)
SLA_GLOBL Snaclec mamushigin subunit alpha Gloydius blomhoffii (Mamushi) (Agkistrodon halys ...
SLA_OPHHA Snaclec ophioluxin subunit alpha (Fragment) Ophiophagus hannah (King cobra) (Naja hannah)
SLA_TRIPP Snaclec purpureotin subunit alpha Trimeresurus purpureomaculatus (Mangrove pit ...
SLA_TROWA Snaclec trowaglerix subunit alpha (Fragment) Tropidolaemus wagleri (Wagler's pit viper) ...
SLB1_DEIAC Snaclec agglucetin subunit beta-1 Deinagkistrodon acutus (Hundred-pace snake) ...
SLB2_DEIAC Snaclec agglucetin subunit beta-2 (Antithrombin ... Deinagkistrodon acutus (Hundred-pace snake) ...
SLBA_TRIAB Snaclec alboaggregin-B subunit alpha (AL-B ... Trimeresurus albolabris (White-lipped pit viper) ...
SLBB_TRIAB Snaclec alboaggregin-B subunit beta (AL-B ... Trimeresurus albolabris (White-lipped pit viper) ...
SLBH_CROAT Snaclec convulxin subunit beta homolog ... Crotalus atrox (Western diamondback rattlesnake)
SLB_BITAR Snaclec bitiscetin subunit beta Bitis arietans (African puff adder)
SLB_BOTAS Snaclec aspercetin subunit beta (Fragment) Bothrops asper (Terciopelo)
SLB_CRODU Snaclec convulxin subunit beta (CVX-beta) Crotalus durissus terrificus (South American ...
SLB_ECHCA Snaclec echicetin subunit beta Echis carinatus (Saw-scaled viper)
SLB_GLOBL Snaclec mamushigin subunit beta Gloydius blomhoffii (Mamushi) (Agkistrodon halys ...
SLB_OPHHA Snaclec ophioluxin subunit beta (Fragment) Ophiophagus hannah (King cobra) (Naja hannah)
SLB_TRIAB Snaclec alboluxin subunit beta (Fragment) Trimeresurus albolabris (White-lipped pit viper) ...
SLB_TRIPP Snaclec purpureotin subunit beta Trimeresurus purpureomaculatus (Mangrove pit ...
SLB_TROWA Snaclec trowaglerix subunit beta (Fragment) Tropidolaemus wagleri (Wagler's pit viper) ...
SLDA_TRIAB Snaclec alboaggregin-D subunit alpha Trimeresurus albolabris (White-lipped pit viper) ...
SLDB_TRIAB Snaclec alboaggregin-D subunit beta Trimeresurus albolabris (White-lipped pit viper) ...
SLEA_BOTJA Snaclec botrocetin subunit alpha (Platelet ... Bothrops jararaca (Jararaca) (Bothrops jajaraca)
SLEA_PROMU Snaclec mucetin subunit alpha (Trimeresurus ... Protobothrops mucrosquamatus (Taiwan habu) ...
SLEB_BOTJA Snaclec botrocetin subunit beta (Platelet ... Bothrops jararaca (Jararaca) (Bothrops jajaraca)
SLEB_PROMU Snaclec mucetin subunit beta (Trimeresurus ... Protobothrops mucrosquamatus (Taiwan habu) ...
SLJA_PROJR Snaclec jerdonuxin subunit alpha Protobothrops jerdonii (Jerdon's pitviper) ...
SLJB_PROJR Snaclec jerdonuxin subunit beta Protobothrops jerdonii (Jerdon's pitviper) ...
SLOA_PROMU Snaclec mucrocetin subunit alpha Protobothrops mucrosquamatus (Taiwan habu) ...
SLOB_PROMU Snaclec mucrocetin subunit beta Protobothrops mucrosquamatus (Taiwan habu) ...
SLTA_PROMU Snaclec trimecetin subunit alpha Protobothrops mucrosquamatus (Taiwan habu) ...
SLTB_PROMU Snaclec trimecetin subunit beta Protobothrops mucrosquamatus (Taiwan habu) ...
SLYA_CALRH Snaclec rhodocytin subunit alpha (Aggretin alpha ... Calloselasma rhodostoma (Malayan pit viper) ...
SLYB_CALRH Snaclec rhodocytin subunit beta (Aggretin beta ... Calloselasma rhodostoma (Malayan pit viper) ...

2 entries

SNTX/VTX toxin family

Select_allDeselect_all
CTXA_SCOPL Cytolytic toxin-alpha (Sp-CTx-alpha) Scorpaena plumieri (Spotted scorpionfish)
STXA_SYNHO Stonustoxin subunit alpha (SNTX subunit alpha) ... Synanceia horrida (Estuarine stonefish) ...

1 entry

Venom metalloproteinase (M12B) family

"Venom metalloproteinase (M12B) family" VenomZone page
VM3PN_PROSR Zinc metalloproteinase-disintegrin-like ... Proatheris superciliaris (Lowland swamp viper)

1 entry

Venom metalloproteinase (M12B) family, P-III subfamily, P-IIIa sub-subfamily

"Venom metalloproteinase (M12B) family" VenomZone page
VM3_CERRY Zinc metalloproteinase-disintegrin-like (EC ... Cerberus rynchops (Dog-faced water snake)

3 entries

Venom metalloproteinase (M12B) family, P-III subfamily, P-IIIb sub-subfamily

Select_allDeselect_all "Venom metalloproteinase (M12B) family" VenomZone page
VM3AL_TRIAB Zinc metalloproteinase-disintegrin-like ... Trimeresurus albolabris (White-lipped pit viper) ...
VM3B_BOTJA Zinc metalloproteinase-disintegrin-like ... Bothrops jararaca (Jararaca) (Bothrops jajaraca)
VM3JA_BOTJA Zinc metalloproteinase-disintegrin-like ... Bothrops jararaca (Jararaca) (Bothrops jajaraca)