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

(all links/actions below point to website)

80 entries grouped by species

3 entries

Bitis arietans (African puff adder)

Select_allDeselect_all "Bitis arietans" VenomZone page
SL2_BITAR Snaclec bitiscetin-2 Snaclec family
SLA_BITAR Snaclec bitiscetin subunit alpha Snaclec family
SLB_BITAR Snaclec bitiscetin subunit beta Snaclec family

1 entry

Bothrocophias andianus (Andean lancehead) (Bothrops andianus)

VSP1_BOTAN Thrombin-like enzyme TLBan (SVTLE TLBan) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

1 entry

Bothrops alternatus (Urutu) (Rhinocerophis alternatus)

OXLA_BOTAL L-amino-acid oxidase (Balt-LAAO-I) (LAO) (EC Flavin monoamine oxidase family, ...

2 entries

Bothrops asper (Terciopelo)

Select_allDeselect_all "Bothrops asper" VenomZone page
SLA_BOTAS Snaclec aspercetin subunit alpha Snaclec family
SLB_BOTAS Snaclec aspercetin subunit beta Snaclec family

1 entry

Bothrops atrox (Barba amarilla) (Fer-de-lance)

OXLA_BOTAT L-amino-acid oxidase (BatroxLAAO) (LAO) (EC Flavin monoamine oxidase family, ...

6 entries

Bothrops jararaca (Jararaca) (Bothrops jajaraca)

SLEA_BOTJA Snaclec botrocetin subunit alpha (Platelet coagglutinin) Snaclec family
SLEB_BOTJA Snaclec botrocetin subunit beta (Platelet coagglutinin) Snaclec family
VM3B_BOTJA Zinc metalloproteinase-disintegrin-like botrocetin (EC 3.4.24.-) ... Venom metalloproteinase (M12B) ...
VM3JA_BOTJA Zinc metalloproteinase-disintegrin-like jararhagin (EC ... Venom metalloproteinase (M12B) ...
VSP1_BOTJA Platelet-aggregating proteinase PA-BJ (EC 3.4.21.-) (Snake venom ... Peptidase S1 family, Snake venom ...
VSPA_BOTJA Thrombin-like enzyme bothrombin (SVTLE) (EC (Factor ... Peptidase S1 family, Snake venom ...

1 entry

Bothrops marajoensis (Marajo lancehead)

VSP1_BOTMA Thrombin-like enzyme TLBm (SVTLE TLBm) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

1 entry

Bothrops moojeni (Lance-headed viper) (Caissaca)

OXLA_BOTMO L-amino-acid oxidase BmooLAAO-I (LAO) (EC Flavin monoamine oxidase family, ...

1 entry

Bothrops pauloensis (Neuwied's lancehead) (Bothrops neuwiedi pauloensis)

OXLA_BOTPA L-amino-acid oxidase (Bp-LAAO) (LAO) (EC Flavin monoamine oxidase family, ...

3 entries

Bothrops pirajai (Piraja's lancehead)

Select_allDeselect_all "Bothrops pirajai" VenomZone page
OXLA_BOTPI L-amino-acid oxidase (BpirLAAO-I) (LAO) (EC Flavin monoamine oxidase family, ...
VSP27_BOTPI Thrombin-like enzyme BpirSP27 (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...
VSP41_BOTPI Thrombin-like enzyme BpirSP41 (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

1 entry

Bungarus fasciatus (Banded krait) (Pseudoboa fasciata)

OXLA_BUNFA L-amino-acid oxidase (Bf-LAAO) (LAO) (EC Flavin monoamine oxidase family, ...

2 entries

Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma)

SLYA_CALRH Snaclec rhodocytin subunit alpha (Aggretin alpha chain) ... Snaclec family
SLYB_CALRH Snaclec rhodocytin subunit beta (Aggretin beta chain) ... Snaclec family

5 entries

Cerastes cerastes (Horned desert viper)

OXLAA_CERCE L-amino acid oxidase (CC-LAAO) (LAO) (EC Flavin monoamine oxidase family, ...
VSP4A_CERCE Snake venom serine protease IVa (SVSP) (EC 3.4.21.-) (Basic ... Peptidase S1 family, Snake venom ...
VSPAA_CERCE Snake venom serine protease Afaacytin alpha/beta/beta' chains ... Peptidase S1 family, Snake venom ...
VSPA_CERCE Thrombin-like enzyme cerastotin (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...
VSPP_CERCE Thrombin-like enzyme cerastocytin (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

1 entry

Cerastes vipera (Sahara sand viper)

VSPCE_CERVI Thrombin-like enzyme cerastobin (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

1 entry

Cerberus rynchops (Dog-faced water snake)

VM3_CERRY Zinc metalloproteinase-disintegrin-like (EC 3.4.24.-) (Snake ... Venom metalloproteinase (M12B) ...

1 entry

Crotalus atrox (Western diamondback rattlesnake)

SLBH_CROAT Snaclec convulxin subunit beta homolog Snaclec family

2 entries

Crotalus durissus cascavella (Northeastern Brazilian rattlesnake)

OXLA_CRODC L-amino-acid oxidase (Casca LAO) (LAAO) (EC Flavin monoamine oxidase family, ...
VSP_CRODC Thrombin-like enzyme F202 (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

2 entries

Crotalus durissus terrificus (South American rattlesnake)

SLA_CRODU Snaclec convulxin subunit alpha (CVX-alpha) Snaclec family
SLB_CRODU Snaclec convulxin subunit beta (CVX-beta) Snaclec family

4 entries

Deinagkistrodon acutus (Hundred-pace snake) (Agkistrodon acutus)

SLA1_DEIAC Snaclec agglucetin subunit alpha-1 (Agkisacucetin subunit alpha) Snaclec family
SLA2_DEIAC Snaclec agglucetin subunit alpha-2 (Antithrombin 1 chain A) Snaclec family
SLB1_DEIAC Snaclec agglucetin subunit beta-1 Snaclec family
SLB2_DEIAC Snaclec agglucetin subunit beta-2 (Antithrombin 1 chain B) Snaclec family

2 entries

Echis carinatus (Saw-scaled viper)

SLA_ECHCA Snaclec echicetin subunit alpha Snaclec family
SLB_ECHCA Snaclec echicetin subunit beta Snaclec family

1 entry

Echis carinatus sochureki (Saw-scaled viper)

SLA_ECHCS Snaclec echicetin subunit alpha Snaclec family

1 entry

Eristicophis macmahoni (Leaf-nosed viper)

OXLA_ERIMA L-amino-acid oxidase (LAAO) (LNV-LAO) (EC Flavin monoamine oxidase family, ...

2 entries

Gloydius blomhoffii (Mamushi) (Agkistrodon halys blomhoffi)

SLA_GLOBL Snaclec mamushigin subunit alpha Snaclec family
SLB_GLOBL Snaclec mamushigin subunit beta Snaclec family

2 entries

Gloydius halys (Chinese water mocassin) (Agkistrodon halys)

VAE1_GLOHA Thrombin-like enzyme agkihpin-1 (TLE agkihpin-1) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...
VAE2_GLOHA Thrombin-like enzyme agkihpin-2 (TLE agkihpin-2) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

1 entry

Loxosceles laeta (South American recluse spider) (Scytodes laeta)

B1H_LOXLA Dermonecrotic toxin LlSicTox-betaIA1 (EC 4.6.1.-) (LlH10) (H10) ... Arthropod phospholipase D ...

1 entry

Naja atra (Chinese cobra)

"Naja atra" VenomZone page
OXLA_NAJAT L-amino-acid oxidase (LAO) (NA-LAAO) (EC Flavin monoamine oxidase family, ...

2 entries

Ophiophagus hannah (King cobra) (Naja hannah)

SLA_OPHHA Snaclec ophioluxin subunit alpha Snaclec family
SLB_OPHHA Snaclec ophioluxin subunit beta Snaclec family

1 entry

Proatheris superciliaris (Lowland swamp viper)

VM3PN_PROSR Zinc metalloproteinase-disintegrin-like proatherocytin (SVMP) ... Venom metalloproteinase (M12B) ...

2 entries

Protobothrops jerdonii (Jerdon's pitviper) (Trimeresurus jerdonii)

SLJA_PROJR Snaclec jerdonuxin subunit alpha Snaclec family
SLJB_PROJR Snaclec jerdonuxin subunit beta Snaclec family

7 entries

Protobothrops mucrosquamatus (Taiwan habu) (Trimeresurus mucrosquamatus)

OXLA_PROMU L-amino-acid oxidase (LAAO) (TM-LAO) (EC Flavin monoamine oxidase family, ...
SLEA_PROMU Snaclec mucetin subunit alpha (Trimeresurus mucrosquamatus venom ... Snaclec family
SLEB_PROMU Snaclec mucetin subunit beta (Trimeresurus mucrosquamatus venom ... Snaclec family
SLOA_PROMU Snaclec mucrocetin subunit alpha Snaclec family
SLOB_PROMU Snaclec mucrocetin subunit beta Snaclec family
SLTA_PROMU Snaclec trimecetin subunit alpha Snaclec family
SLTB_PROMU Snaclec trimecetin subunit beta Snaclec family

2 entries

Scolopendra dehaani (Thai centipede) (Scolopendra subspinipes dehaani)

TX14A_SCODE Scoloptoxin SSD14 (SLPTX-SSD14) (Toxin-SSD14) [Cleaved into: ... Not in a family
TX14B_SCODE Scoloptoxin SSD20 Scoloptoxin-11 family

1 entry

Scorpaena plumieri (Spotted scorpionfish)

CTXA_SCOPL Cytolytic toxin-alpha (Sp-CTx-alpha) SNTX/VTX toxin family

1 entry

Synanceia horrida (Estuarine stonefish) (Scorpaena horrida)

STXA_SYNHO Stonustoxin subunit alpha (SNTX subunit alpha) ... SNTX/VTX toxin family

10 entries

Trimeresurus albolabris (White-lipped pit viper) (Cryptelytrops albolabris)

SLA1_TRIAB Snaclec alboaggregin-A subunit alpha (50-kDa alboaggregin) ... Snaclec family
SLA2_TRIAB Snaclec alboaggregin-A subunit alpha' (Alboaggregin-A subunit 2) ... Snaclec family
SLA3_TRIAB Snaclec alboaggregin-A subunit beta (Alboaggregin-A subunit 3) ... Snaclec family
SLA4_TRIAB Snaclec alboaggregin-A subunit beta' (Alboaggregin-A subunit 4) ... Snaclec family
SLBA_TRIAB Snaclec alboaggregin-B subunit alpha (AL-B subunit alpha) ... Snaclec family
SLBB_TRIAB Snaclec alboaggregin-B subunit beta (AL-B subunit beta) (25-kDa ... Snaclec family
SLB_TRIAB Snaclec alboluxin subunit beta Snaclec family
SLDA_TRIAB Snaclec alboaggregin-D subunit alpha Snaclec family
SLDB_TRIAB Snaclec alboaggregin-D subunit beta Snaclec family
VM3AL_TRIAB Zinc metalloproteinase-disintegrin-like alborhagin (EC 3.4.24.-) ... Venom metalloproteinase (M12B) ...

2 entries

Trimeresurus purpureomaculatus (Mangrove pit viper) (Cryptelytrops purpureomaculatus)

SLA_TRIPP Snaclec purpureotin subunit alpha Snaclec family
SLB_TRIPP Snaclec purpureotin subunit beta Snaclec family

2 entries

Tropidolaemus wagleri (Wagler's pit viper) (Trimeresurus wagleri)

SLA_TROWA Snaclec trowaglerix subunit alpha Snaclec family
SLB_TROWA Snaclec trowaglerix subunit beta Snaclec family

1 entry

Vespa magnifica (Hornet)

PA1_VESMG Probable phospholipase A1 magnifin (PLA1) (EC AB hydrolase superfamily, Lipase ...