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Protein A004228
Author-entered Data
V1.0, Peer Reviewed
Published 9 Oct 2012
Automated Data
Not Reviewed
As At Publication
Automated Data
Not Reviewed
Latest from 6 Jun 2014

UCSD Molecule Pages
Published online: 9 Oct 2012 | doi:10.6072/H0.MP.A004228.01

Complement C1q subcomponent subunit A

Basis Sequence: Human

Anjana Chandrasekhar1, Ashok Reddy Dinasarapu1, Andrea J Tenner2, Shankar Subramaniam3

1Department of Bioengineering, University of California, San Diego, CA 92093, US. 2University of California, Irvine, CA 92697, US. 3Department of Bioengineering, University of California at San Diego, CA 92093, US.

Correspondence should be addressed to Anjana Chandrasekhar: a4chandra@ucsd.edu


Complement C1q subcomponent subunit A (C1qA) is one of the three components of C1q molecule. Functional C1q is composed of eighteen polypeptide chains: six C1qA chains, six C1qB chains, and six C1qC chains, which are arranged as six heterotrimers of ABC: (ABC)6. Each of the individual C1q polypeptide chain consists of a N-terminal region and a C-terminal globular region (gC1q), of ~135 residues. Each N-terminal consists of 2-11 amino acid segments containing a half-cysteine residue that is involved in formation of inter-chain disulphide bonds, followed by a collagen-like region (CLR) consisting of ~81 residues. The collagen-like regions in A, B and C chains of each heterotrimer come together to form a triple helical collagen like structure. Further, A and B chains in each heterotrimer are bound by a disulphide bond, while C chain forms a disulphide bond with a C chain from the adjoining heterotrimer. Therefore the eighteen subunits come together to form six globular heads (gC1q), which are clusters of 3 independently folded C-terminal domains of the A, B and C chain. These globular domains recognize an array of self, non-self and altered-self ligands. C1q associates with the proenzymes C1r and C1s (2 molecules of each, in the molar ratio of 1:2:2 in a calcium dependent manner) to yield an active C1 complex, the first component of the serum complement system. C1r, upon binding of gC1q to an inciting stimulus, autoactivates itself and catalyzes breakage of a C1s ester bond, resulting in C1s activation and subsequent cleavage of C2 and C4 into their respective “a” and “b” fragments. Recognition of ligands by C1q molecule also defines C1q as a pattern recognition molecule (PRM). C1q recognizes distinct structures either directly on microbial structures and apoptotic cells, or indirectly after their recognition by antibodies or C-reactive protein (CRP). C1q in turn binds to multiple receptors (such as cC1qR (calreticulin), integrin α2β1 or other molecules on the surface of specific cell types of either myeloid or endothelial cell orgin) and shows regulated broad physiological functions beyond complement activation.

Alternative names for this molecule: C1QA; Complement C1q subcomponent subunit A; Complement component 1, q subcomponent, A chain; Complement component 1, q subcomponent, alpha polypeptide; Complement component C1q, A chain

Transition Network Graph This molecule exists in 46 states, has 47 transitions between these states and has 2 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, Philadelphia, UCSD-SGMP editorial board member, for extensive discussions.