Structure and function of gC1q-R: a multiligand binding cellular protein.
gC1q-R is a 33 kDa, single chain, highly acidic protein, which was first isolated from membrane preparation of Raji cells and now appears to be ubiquitously distributed. Although, gC1q-R was originally identified as a protein which binds to the globular "heads" of C1q, recent evidence suggests that the molecule is in fact a multiligand binding, multifunctional protein with affinity for diverse ligands which at best are functionally related. These molecules include: thrombin, vitronectin, and high molecular weight kininogen. The gC1q-R molecule, which is identical to the transcription factors SF2 and the Tat-associated protein, or TAP, is the product of a single gene localized on chromosome 17p13.3 in human, and chromosome 11 in mouse, and is encoded by an approximately 1.5-1.6 kb mRNA. The full length cDNA encodes a primary translation protein of 282 residues and the 'mature' or membrane form of the protein isolated from Raji cells corresponds to residues 74-282 and is presumed to be generated by a site-specific cleavage and removal of the highly basic, 73-residues long, N-terminal segment during post-translational processing. The translated amino acid sequence does not predict for the presence of a conventional sequence motif compatible with a transmembrane segment and does not have a consensus site for a GPI anchor. However, there is strong evidence which indicates that gC1q-R is expressed both inside the cell and on the membrane. First, certain mAbs raised against gC1q-R react moderately with intact Raji cells in suspension and this binding increases when the cells are first bound to poly-L-lysine coated surfaces and then fixed with glutaraldehyde. Second, surface labeling of cells using the membrane impermeable sulfo-NHS-LC-biotin shows that gC1q-R on the surface incorporates biotin whereas intracellular gC1q-R does not. In addition, the membrane expression of gC1q-R can be upregulated with inflammatory cytokines such as INF-gamma, TNF-alpha, or LPS. These results suggest, that gC1q-R, is localized both as an intracellular and as a cell surface protein and may have important biological functions in both compartments of the cell.
Ghebrehiwet
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Department of Medicine, State University of New York, Stony Brook, USA. berhane@mail.som.sunysb.edu
Peerschke
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D000818:Animals; D002352:Carrier Proteins; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D015922:Complement C1q / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D019679:Kininogen, High-Molecular-Weight / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins; D051379:Mice; D024101:Mitochondrial Proteins; D011951:Receptors, Complement / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D019679:Kininogen, High-Molecular-Weight; D008024:Ligands; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D019096:Vitronectin; C032402:complement 1q receptor; D015922:Complement C1q; D005174:Factor XII; D013917:Thrombin