Complement system impairing toxin

The complement system is an intrinsic part of the immune system, with important functions in both innate and adaptive immunity. The complement system consists of approximately twenty plasma proteins as well as numerous receptors and regulatory proteins on the membranes of host cells.

Activation of the complement system occurs through three pathways, the classical pathway , the alternative pathway (Fig.1) and the lectin pathway . All of these pathways share a similar molecular
architecture in that an initial recognition event is amplified by a succession of proteolytic enzymes in a cascade-like fashion, resulting in the generation of numerous biologically active complement activation products.
One activation product of the complement system is the macromolecular membrane attack complex (MAC) , which inserts itself into target membranes, leading to the impairment of membrane function and physical destruction of targets including viruses, bacteria, parasites and tumor cells. Another activation product is C3b which attaches itself covalently to cells, immune complexes and other particles, a process called opsonization. Opsonization tags cells and particles for removal by phagocytes. Further products of proteolytic degradation of C3b (iC3b, C3dg, C3d) are recognized by specific receptors on various immune cells, and have important functions in the regulation of the adaptive immune response. Last but not least, the anaphylatoxins C3a and C5a exhibit important pro-inflammatory activities, such as degranulation of mast cells, increased vascular permeability, and chemotaxis and activation of neutrophils. Both anaphylatoxins are rapidly inactivated by the removal of a C-terminal arginine residue through the action of carboxypeptidase N. However the inactivated form of C5a, C5a-des-Arg, still exhibits its activity for neutrophils, making C5a a particularly powerful pro-inflammatory peptide (reviewed in Vogel et al., 2010, and references therein).

Figure 1: The classical and alternative complement pathways. (Image from Wikimedia / licensed under Creative Commons).

Complement system impairing toxins target or mimic several complement system proteins. Only a few of them have had their activity specifically described. For example, snake venom complement C3 homologs are structural and functional analogs of complement component C3b. The snake venom serine proteinase flavoxobin independently cleaves endogenous C3 and kick-starts the complement cascade, the cobra metalloproteinase oxiagin prevents interaction of component C2 with C4b, while the cobra metalloproteinase atrase-B cleaves complement factors B, C6, C7, and C8. Most complement system impairing toxins have just been investigated for their effects on hemolytic complement activity, without having a more specific function described.

See also UniProt-keyword.

Venom protein entries in UniProtKB/Swiss-Prot

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18 entries grouped by family

5 entries

Ficolin lectin family, Veficolin subfamily

FCNV1_CERRY Ryncolin-1 Cerberus rynchops (Dog-faced water snake)
FCNV1_VARKO Veficolin-1 Varanus komodoensis (Komodo dragon)
FCNV2_CERRY Ryncolin-2 Cerberus rynchops (Dog-faced water snake)
FCNV3_CERRY Ryncolin-3 Cerberus rynchops (Dog-faced water snake)
FCNV4_CERRY Ryncolin-4 Cerberus rynchops (Dog-faced water snake)

3 entries

Peptidase S1 family, Snake venom subfamily

Select_allDeselect_all "Peptidase S1 family" VenomZone page
VSP1_PROFL Thrombin-like enzyme flavoxobin (SVTLE) (EC ... Protobothrops flavoviridis (Habu) (Trimeresurus ...
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)

5 entries

Venom complement C3 homolog family

Select_allDeselect_all "Venom complement C3 homolog family" VenomZone page
VCO31_AUSSU A.superbus venom factor 1 (AVF-1) (CVF-like) ... Austrelaps superbus (Lowland copperhead snake) ...
VCO32_AUSSU A.superbus venom factor 2 (AVF-2) (CVF-like) ... Austrelaps superbus (Lowland copperhead snake) ...
VCO3_CROAD Venom factor (VF) (CVF-like) (Complement C3 ... Crotalus adamanteus (Eastern diamondback ...
VCO3_NAJKA Cobra venom factor (CVF) (CVFk) (Complement C3 ... Naja kaouthia (Monocled cobra) (Naja siamensis)
VCO3_OPHHA Ophiophagus venom factor (OVF) (CVF-like) ... Ophiophagus hannah (King cobra) (Naja hannah)

1 entry

Venom metalloproteinase (M12B) family, P-I subfamily

"Venom metalloproteinase (M12B) family" VenomZone page
VM1B1_BOTAS Snake venom metalloproteinase BaP1 (SVMP) (EC ... Bothrops asper (Terciopelo)

1 entry

Venom metalloproteinase (M12B) family, P-III subfamily

"Venom metalloproteinase (M12B) family" VenomZone page
VM3A2_DEIAC Zinc metalloproteinase recombinant fibrinogenase ... Deinagkistrodon acutus (Hundred-pace snake) ...

2 entries

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

Select_allDeselect_all "Venom metalloproteinase (M12B) family" VenomZone page
VM3B_NAJAT Zinc metalloproteinase-disintegrin-like atrase-B ... Naja atra (Chinese cobra)
VM3_NAJKA Zinc metalloproteinase-disintegrin-like cobrin ... Naja kaouthia (Monocled cobra) (Naja siamensis)

1 entry

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

"Venom metalloproteinase (M12B) family" VenomZone page
VM3_NAJOX Zinc metalloproteinase oxiagin (EC 3.4.24.-) ... Naja oxiana (Central Asian cobra) (Oxus cobra)