Disease relevance of C1QTNF1

• By using the Folts vascular injury model in nonhuman primates (Macaca fascicularis), we were able to demonstrate that CTRP-1 can prevent platelet thrombosis in vivo [1].

High impact information on C1QTNF1

• These data suggest that CTRP-1 prevents collagen-induced platelet aggregation by specific blockade of VWF binding to collagen [1].
• This effect was achieved in the absence of changes in activated-clotting time (ACT) and template cut bleeding times, suggesting that CTRP-1 has promising antiplatelet thrombotic activity and most likely acts by pacifying the thrombogenic site of vascular injury [1].
• CTRP-1 had no effects on alpha(2)beta(1) integrin I-domain binding to collagen [1].
• CTRP-1 is a novel member of the C1qTNF-related protein family containing family characteristic collagen and TNF-like domains and shows marked expression in vascular wall tissue [1].
• Tumor necrosis factor-alpha and interleukin-1beta increases CTRP1 expression in adipose tissue [2].

Biological context of C1QTNF1

• The protein was named GIP as in G-protein-coupled receptor Interacting Protein; the corresponding gene was located on the 17th chromosome where three exons encode for a 379-amino-acid protein.GIP subcellular localization was studied by immunocytochemistry and also using a biotinylating agent [3].
• Sequence homology inferred that GIP cytosolic domain is folded as a collagen-like helix followed by a globular domain.The interaction of the globular domain with the V2R was confirmed by pull-down experiments indicating that this structural motif can also interact with cytosolic proteins [3].
• We observed that recombinant human CTRP-1 specifically bound to fibrillar collagen and blocked collagen-induced platelet aggregation [1].
• High-level hCTRP1 activity depended on an 11 bp Sp1/Sp3 binding site [4].
• These results suggest that the hCTRP1 is activated by the tissue-ubiquitous transcription factor Sp1 and that an epigenetic process unrelated to CpG methylation represses its activity in hCTR-negative tissues [4].

Anatomical context of C1QTNF1

• The protein was found to be localized, at least in part, on the plasma membrane, probably in the form of a trimer.The results indicated that GIP is a transmembrane protein and the most part of the molecule is intracellular [3].
• These findings indicate that CTRP1 expression may be associated with a low-grade chronic inflammation status in adipose tissues [2].
• Luciferase assays demonstrated that the proximal hCTR promoter (hCTRP1) was transcriptionally active in all cell lines tested [4].
• Addition of increasing concentrations of partially purified GtH induced protein (GIP) to oocyte incubation caused a dose dependent increase in ovarian aromatase activity [5].

Other interactions of C1QTNF1

• Using whole human blood under flow at low and high shear rates, CTRP-1 prevented platelets from accumulating on a collagen-coated surface but had no effects on "platelet-rolling" on a surface coated with VWF [1].

References