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Protein A004235
Author-entered Data
V1.0, Peer Reviewed
Published 5 Oct 2012
Automated Data
Not Reviewed
As At Publication
Automated Data
Not Reviewed
Latest from 6 Jun 2014

UCSD Molecule Pages
Published online: 5 Oct 2012 | doi:10.6072/H0.MP.A004235.01

Complement C3

Basis Sequence: Human

Ashok Reddy Dinasarapu1, Anjana Chandrasekhar1, Arvind Sahu2, Shankar Subramaniam3

1Department of Bioengineering, University of California, San Diego, CA 92093, US. 2National Centre for Cell Science, Pune, 411007, IN. 3Department of Bioengineering, University of California at San Diego, CA 92093, US.

Correspondence should be addressed to Ashok Reddy Dinasarapu:

Complement C3 is the central component of the human complement system. It is ~186 kDa in size, consisting of an α-chain (~110 kDa) and a β-chain (~75 kDa) that are connected by cysteine bridges. C3 in its native form is inactive. Cleavage of C3 into C3b (~177 kDa) and C3a (~9 kDa) is a crucial step in the complement activation cascade, which can be initiated by one or more of the three distinct pathways, called alternative, classical and lectin complement pathways. In the alternative pathway, hydrated C3 (C3(H20)) recruits complement factor B (fB), which is then cleaved by complement factor D (fD) to result in formation of the minor form of C3-convertase (C3(H20)Bb) that cleaves C3 into C3a and C3b. A small percent of the resulting C3b is rapidly deposited (opsonization through covalent bond) in the immediate vicinity of the site of activation (e.g. pathogen surface) and now forms the major form of C3-convertase (C3bBb), thereby creating an efficient cycle of C3 cleavage. Properdin, a positive regulator of the alternative pathway convertases, provides a hub for the assembly of C3bBb in addition to stabilization of the convertase. Classical and lectin pathways, when activated with recognition of pathogens or immune complexes use another C3-convertase (C4b2a) to cleave C3 into C3a and C3b. Although the three pathways are activated independently, they converge at C3 and use C3 as a substrate for their pathway specific C3-convertase: C3(H20)Bb, C3bBb or C4b2a. Further, C3b undergoes successive proteolytic cleavages by the regulatory complement factor I (fI) in presence of cofactors and lead to generation of iC3b (~174 kDa), C3d/C3dg (~33 kDa), C3c (~142 kDa) and C3f (~2 kDa). C3a is an anaphylatoxin while C3b is involved in opsonization of pathogens or apoptotic cells. Covalently bound C3b on pathogen/apoptotic cell surface is recognized by host immune cells through phagocytic (or complement component) receptors and induce subsequent immune response or directly target pathogen for clearance. The C3a fragment functions as a chemokine, and thereby recruits phagocytic and granulocytic cells to the sites of inflammation and cause strong pro-inflammatory signaling through their G-protein coupled receptors (GPCRs). As pathogen or apoptotic cell surface bound C3-convertases (C3bBb or C4b2a) can induce the amplification of the alternative pathway, this pathway might contribute to the major part of the complement activation process, even when initially triggered by the classical pathway and/or lectin pathway. Continuous activation of complement pathways shifts the substrate preference from C3 to C5 by formation of C5-convertase (formed by addition of C3b fragment to C3-convertases, C3(H20)Bb3b, C3bBb3b and C4b2a3b). C5-convertase activates C5, which by series of additional steps, promotes killing of target cell (pathogen) by pore formation.

Alternative names for this molecule: Acylation-stimulating protein cleavage product; AHUS5; ARMD9; ASP; C3; C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1; Complement C3; Complement component 3; Complement component C3; CPAMD1

Transition Network Graph This molecule exists in 101 states, has 131 transitions between these states and has 4 enzyme functions.

[map] View high resolution network map

Acknowledgments: The UCSD Signaling Gateway Molecule Pages (SGMP) is funded by NIH/NIGMS Grant 1 R01 GM078005-01. The authors thank Dr. John D. Lambris, University of Pennsylvania School of Medicine, Philadelphia, UCSD-SGMP editorial board member, for extensive discussions.