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Protein A004256
Author-entered Data
V1.0, Peer Reviewed
Published 14 Dec 2012
Automated Data
Not Reviewed
As At Publication
Automated Data
Not Reviewed
Latest from 6 Jun 2014

UCSD Molecule Pages
Published online: 14 Dec 2012 | doi:10.6072/H0.MP.A004256.01

Complement factor H

Basis Sequence: Human

Ashok Reddy Dinasarapu1, Anjana Chandrasekhar1, Mihály Józsi2, Shankar Subramaniam3

1Department of Bioengineering, University of California, San Diego, CA 92093, US. 2Department of Immunology, MTA-ELTE “Lendület” Complement Research Group, H-1117, HU. 3Department of Bioengineering, University of California at San Diego, CA 92093, US.

Correspondence should be addressed to Ashok Reddy Dinasarapu:

Complement factor H (fH) is a single chain plasma glycoprotein (approximately 150 kDa in size), with 20 domains termed complement control protein (CCP) domains or short consensus repeats (SCR). The complement factor H gene (CFH) is located on chromosome 1q32 in the regulators of complement activation (RCA) gene cluster, adjacent to the genes that code for the Complement factor H-Related Proteins (CFHRs). The RCA cluster includes additional regulators containing SCR domains, such as C4 Binding Protein (C4BP), Complement receptor type 1 (CR1), Complement decay-accelerating factor (DAF), Membrane cofactor protein (MCP). fH and C4BP are fluid-phase (soluble) complement regulators, while the remaining are membrane-bound and all these regulators share similarities in their structure and function. fH prevents the formation of the alternative pathway C3 (C3bBb) and C5 (C3bBb3b) convertases. This inhibitory effect is either by competition with Complement factor B (fB) for C3b binding, by convertase decay acceleration activity or by acting as a cofactor for the Complement factor I (fI)-mediated degradation of C3b. Important targets for fH binding, in the neighborhood of C3b on host cells, are glycosaminoglycans and sialic acid (polyanionic molecules), which increase the affinity of fH for C3b. In addition to C3b and polyanionic molecules, fH also interacts with various endogenous molecules, such as pentraxins, extracellular matrix (ECM) proteins, prion protein, adrenomedullin, DNA, annexin-II and histones, to inhibit complement activation on certain host surfaces such as glomerular basement membrane, the extracellular matrix, and late apoptotic cells. CFH gene mutations and polymorphisms, and auto-antibodies against fH adversely affect regulatory and target recognition functions of fH. Some of the diseases associated with fH dysfunction are atypical hemolytic uremic syndrome (aHUS), dense deposit disease (DDD; also termed membranoproliferative glomerulonephritis (MPGN) type II) and age-related macular degeneration (AMD). Interestingly, microbes and multicellular pathogens can recruit host fH to their surface in order to protect themselves from complement attack.

Alternative names for this molecule: Adrenomedullin binding protein; Age-related maculopathy susceptibility 1; AHUS1; AMBP1; ARMD4; ARMS1; Beta-1-H-globulin; Beta-1H; CFH; CFHL3; Complement factor H; Factor H; Factor H-like 1; FH; FHL1; H factor 1; H factor 1 (complement); H factor 2 (complement); HF; HF1; HF2; HUS

Transition Network Graph This molecule exists in 60 states, has 60 transitions between these states and has 1 enzyme function.

[map] View high resolution network map

Acknowledgments: The UCSD Signaling Gateway Molecule Pages (SGMP) is funded by NIH/NIGMS Grant 1 R01 GM078005-01 (S.S). The work of M.J is supported by the Hungarian Academy of Sciences (LP2012-43/2012). The authors thank Dr. John D. Lambris, University of Pennsylvania, Philadelphia, UCSD-SGMP editorial board member, for extensive discussions.