Complement Protein Fragment Nomenclature

Complement Protein Fragment Nomenclature

In 2009 the International Complement Society (ICS) and the European Complement Network (ECN) began a joint reevaluation of the nomenclature for the complement system. Effective communication of scientific results requires terminology that is as simple, as clear and as unambiguous as possible. The last review was published in 1981 and much has changed since then. Complement is now known to be initiated by three independent pathways - the classical, alternative and lectin pathways - and many new proteins and receptors have been discovered.

In 1963, it was agreed that the components of complement were to be designated by the letter "C", the prime symbol, and numbers with activated products designated by the letter "a" added to the symbols (as in C1a for activated C1 and C2a for activated C2). At the time known components consisted of only nine proteins C'1, C'2, C'3, C'4, C'5, C'6 and C'7 with C'1 known to be a complex between C'1q, C'1r and C'1s.

By 1981 an entirely new pathway had been characterized and new proteins and complexes had been described. A subcommittee of the Nomenclature Committee of the International Union of Immunological Societies formalized the nomenclature for this "alternative" pathway of complement activation. Rather than continue numbering the components beyond C9 it was agreed that the components of this new pathway would be designated by letter symbols except for the C3 protein which was shared with the original activation pathway. The originally described pathway has since been referred to as the "classical" pathway of complement activation. Thus, constituents of the alternative pathway were designated factors B, D, H, I and P plus C3 and enzymatically active complexes were given designations such as C3b,Bb and C3b,Bb,C3b,P.

With the discovery of the lectin pathway and the characterization of many cellular receptors for complement activation fragments an entirely new set of components are now known to be involved in the activation of and the biological responses to complement. As is characteristic of any discovery process the nomenclature used for these new components is not uniform and is often redundant. Thus, the committee was charged with conducting the first formal evaluation of complement nomenclature since 1981.

Complement Components Nomenclature List

Recommended Name Comments
C1-INH C1 Inhibitor (C1 esterase inhibitor)
C3(H2O) Thioester-hydrolyzed form of C3
C3a Anaphylatoxin from C3
C3a-desArg C3a without C-terminal Arginine
iC3b Inactivated C3b
C4a-desArg C4a without C-terminal Arginine
C4BP C4b binding protein
C5a Anaphylatoxin from C5
C5a-desArg C5a without C-terminal Arginine
Vn Vitronectin (S protein, S40)
FB Factor B
FD Factor D
FH Factor H
FI Factor I
MBL Mannose binding lectin
Ficolin-1 M-Ficolin
Ficolin-2 L- Ficolin
Ficolin-3 H-Ficolin
MASP-1 MBL-associated serine protease 1
MASP-2 MBL-associated serine protease 2
MASP-3 MBL-associated serine protease 3
FHL-1 Factor H-like protein 1
FHR-1 Factor H-related protein 1
FHR-2 Factor H-related protein 2
FHR-3 Factor H-related protein 3
FHR-4 Factor H-related protein 4
FHR-5 Factor H-related protein 5
CD59 Protectin, Homologous restriction factor
Cn Clusterin (Apolipoprotein J, SP-40,40)
C5b6 Terminal pathway complex of C5b + C6
C5b-7 Terminal pathway complex of C5b6 + C7
C5b-8 Terminal pathway complex of C5b-7 + C8
C5b-9 Terminal pathway complete complex
sC5b-9 Soluble C5b-9 with Vn or Cn bound
C3bBb Alternative pathway C3 convertase
C3bBbP Alternative pathway C3 convertase with Properdin
C3bBbC3b AP C3/C5 convertase
C4BP-Protein S C4BP bound to Protein S
CR1 CD35 (C3b/C4b Receptor)
CR2 CD21 (C3d Receptor)
CR3 CD11b/CD18 complex
CR4 CD11c/CD18 complex
C3aR Requesting CD number
C5aR1 CD88 (C5aR)
C5aR2 (C5L2) Requesting CD number
CRIg Complement receptor of the Ig family
C1qR C1q receptor
gC1qR Recognizes globular C1q domains
cC1qR Calreticulin, Recognizes collagen domain
LHR Long homologous repeat [in CR1]

Complement Protein Fragment Nomenclature References

1. Kemper C, et al. (2014). Complement nomenclature 2014. Molecular immunology, 61(2), 56-58.
2. Alper C A, et al. (1981). Nomenclature of the alternative activating pathway of complement. J. Immunol. 127, 1261-1262.
3. Austen K F, et al. (1968). Nomenclature of complement. Bull. World Health Organ. 39, 935-938.
4. Karlson P, et al. (1981). Enzyme nomenclature. Recommendations 1978, Suppl.2, corrections and addition. Eur. J. Biochem. 116, 423-435.
5. Rapp H J, et al. (1963). Complement and hemolysis. Science 141, 738–740.