UniProt functional annotation for Q91132



	UniProt functional annotation for Q91132

UniProt code: Q91132.

Organism: Naja kaouthia (Monocled cobra) (Naja siamensis).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Elapinae; Naja.

Function: Complement-activating protein in cobra venom. It is a structural and functional analog of complement component C3b, the activated form of C3. It binds factor B (CFB), which is subsequently cleaved by factor D (CFD) to form the bimolecular complex CVF/Bb. CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. Structurally, it resembles the C3b degradation product C3c, which is not able to form a C3/C5 convertase. Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions of complement regulatory factors H (CFH) and I (CFI). Therefore, CVF continuously activates complement resulting in the depletion of complement activity.

Subunit: Heterotrimer of alpha, beta and gamma chains; disulfide- linked. Is active with factor B in the presence of factor D. {ECO:0000269|PubMed:19368894, ECO:0000269|PubMed:19574954, ECO:0000269|PubMed:21217642}.

Subcellular location: Secreted.

Tissue specificity: Expressed by the venom gland.

Ptm: First processed by the removal of 4 Arg residues by furin-type protease, forming two chains, alpha and gamma/beta precursor, linked by a disulfide bond. Probably, the cobrin cleaves the C3a-like domain and then the C3d-like domain, generating the mature cobra venom factor (CVF). This mature CVF is composed of three chains: alpha, gamma and beta.

Ptm: Contains 3 N-linked oligosaccharide chains, two in the alpha-chain and one in the beta-chain. Glycosylation is not required for the biological activity. However, it contributes to the immunogenicity of CVF. The carbohydrate content is 7.4. The major oligosaccharide is a symmetric fucosylated biantennary complex-type chain with an unusual alpha-galactosylated Le(x) structure at its non-reducing end. {ECO:0000269|PubMed:11320058, ECO:0000269|PubMed:19574954, ECO:0000269|PubMed:21217642}.

Miscellaneous: CVF has been used to study the complement pathways and to investigate the role of complement in disease pathophysiology. It has also been used to consume complement to prevent the hyperactive rejection of organs in xenotransplantation and for targeted complement- mediated cell killing. CVF can be safely administered to laboratory animals for temporary depletion of complement activity. Interestingly, it is able to deplete complement in serum from all vertebrates tested, except cobras. The only side effect from massive activation of complement in vivo by CVF has been an acute and fleeting inflammatory injury of the lungs (PubMed:20417224). {ECO:0000305|PubMed:20417224}.

Similarity: Belongs to the venom complement C3 homolog family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Naja kaouthia (Monocled cobra) (Naja siamensis).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Elapinae; Naja.



Function:		Complement-activating protein in cobra venom. It is a structural and functional analog of complement component C3b, the activated form of C3. It binds factor B (CFB), which is subsequently cleaved by factor D (CFD) to form the bimolecular complex CVF/Bb. CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. Structurally, it resembles the C3b degradation product C3c, which is not able to form a C3/C5 convertase. Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions of complement regulatory factors H (CFH) and I (CFI). Therefore, CVF continuously activates complement resulting in the depletion of complement activity.


Subunit:		Heterotrimer of alpha, beta and gamma chains; disulfide- linked. Is active with factor B in the presence of factor D. {ECO:0000269\|PubMed:19368894, ECO:0000269\|PubMed:19574954, ECO:0000269\|PubMed:21217642}.
Subcellular location:		Secreted.
Tissue specificity:		Expressed by the venom gland.
Ptm:		First processed by the removal of 4 Arg residues by furin-type protease, forming two chains, alpha and gamma/beta precursor, linked by a disulfide bond. Probably, the cobrin cleaves the C3a-like domain and then the C3d-like domain, generating the mature cobra venom factor (CVF). This mature CVF is composed of three chains: alpha, gamma and beta.
Ptm:		Contains 3 N-linked oligosaccharide chains, two in the alpha-chain and one in the beta-chain. Glycosylation is not required for the biological activity. However, it contributes to the immunogenicity of CVF. The carbohydrate content is 7.4. The major oligosaccharide is a symmetric fucosylated biantennary complex-type chain with an unusual alpha-galactosylated Le(x) structure at its non-reducing end. {ECO:0000269\|PubMed:11320058, ECO:0000269\|PubMed:19574954, ECO:0000269\|PubMed:21217642}.
Miscellaneous:		CVF has been used to study the complement pathways and to investigate the role of complement in disease pathophysiology. It has also been used to consume complement to prevent the hyperactive rejection of organs in xenotransplantation and for targeted complement- mediated cell killing. CVF can be safely administered to laboratory animals for temporary depletion of complement activity. Interestingly, it is able to deplete complement in serum from all vertebrates tested, except cobras. The only side effect from massive activation of complement in vivo by CVF has been an acute and fleeting inflammatory injury of the lungs (PubMed:20417224). {ECO:0000305\|PubMed:20417224}.
Similarity:		Belongs to the venom complement C3 homolog family. {ECO:0000305}.