Gene Symbol: C5ar2
Description: complement component 5a receptor 2
Alias: C5L2, E030029A11Rik, Gpr77, C5a anaphylatoxin chemotactic receptor 2, C5a anaphylatoxin chemotactic receptor C5L2, G protein-coupled receptor 77
Species: mouse
Products:     C5ar2

Top Publications

  1. Gao H, Neff T, Guo R, Speyer C, Sarma J, Tomlins S, et al. Evidence for a functional role of the second C5a receptor C5L2. FASEB J. 2005;19:1003-5 pubmed
    ..In the current study, we have analyzed the expression of the second C5a receptor C5L2, the putative "default" or nonsignaling receptor for C5a...
  2. Gerard N, Lu B, Liu P, Craig S, Fujiwara Y, Okinaga S, et al. An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. J Biol Chem. 2005;280:39677-80 pubmed
    b>C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils...
  3. Chen N, Mirtsos C, Suh D, Lu Y, Lin W, McKerlie C, et al. C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a. Nature. 2007;446:203-7 pubmed
    ..C5L2 (also known as GPR77) is a relatively new GPCR thought to be a non-signalling receptor binding to C5a, on the basis of sequence ..
  4. Paglialunga S, Schrauwen P, Roy C, Moonen Kornips E, Lu H, Hesselink M, et al. Reduced adipose tissue triglyceride synthesis and increased muscle fatty acid oxidation in C5L2 knockout mice. J Endocrinol. 2007;194:293-304 pubmed
    Activation of C5L2, a G-protein-coupled receptor, by acylation-stimulating protein/complement C3adesArg (ASP/C3adesArg) has been shown to stimulate triglyceride (TG) synthesis in both mature adipocytes and preadipocytes...
  5. Rittirsch D, Flierl M, Nadeau B, Day D, Huber Lang M, Mackay C, et al. Functional roles for C5a receptors in sepsis. Nat Med. 2008;14:551-7 pubmed publisher
    The function of the C5a receptors, C5ar (encoded by C5ar) and C5l2 (encoded by Gpr77), especially of C5l2, which was originally termed a 'default receptor', remains a controversial topic...
  6. Zhang X, Schmudde I, Laumonnier Y, Pandey M, Clark J, Konig P, et al. A critical role for C5L2 in the pathogenesis of experimental allergic asthma. J Immunol. 2010;185:6741-52 pubmed publisher
    ..C5a can bind to two distinct receptors (i.e., C5a receptor and C5a receptor-like 2 [C5L2]). The functional role of C5L2 in vivo remains enigmatic...
  7. Okinaga S, Slattery D, Humbles A, Zsengeller Z, Morteau O, Kinrade M, et al. C5L2, a nonsignaling C5A binding protein. Biochemistry. 2003;42:9406-15 pubmed
    ..Here, we show that an orphan receptor, identified as C5L2, is a high affinity C5a binding protein...
  8. Valenzuela D, Murphy A, Frendewey D, Gale N, Economides A, Auerbach W, et al. High-throughput engineering of the mouse genome coupled with high-resolution expression analysis. Nat Biotechnol. 2003;21:652-9 pubmed
    ..5-1.0% of the entire genome. We also provide dozens of informative expression patterns involving cells in the nervous system, immune system, vasculature, skeleton, fat and other tissues. ..
  9. MacLaren R, Kalant D, Cianflone K. The ASP receptor C5L2 is regulated by metabolic hormones associated with insulin resistance. Biochem Cell Biol. 2007;85:11-21 pubmed
    Acylation-stimulating protein (ASP) and interaction with its receptor C5L2 influences adipocyte metabolism...

More Information


  1. Wen Y, Wang H, MacLaren R, Lu H, Hu X, Cianflone K. Sex steroid hormones induce acylation stimulating protein resistance in 3T3-L1 adipocytes. J Cell Biochem. 2008;105:404-13 pubmed publisher
    Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose transport via its receptor C5L2. In human studies, ASP is increased in insulin resistant states such as obesity, diabetes, polycystic ovary syndrome and ..
  2. Cui W, Lapointe M, Gauvreau D, Kalant D, Cianflone K. Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation. Mol Immunol. 2009;46:3207-17 pubmed publisher
    b>C5L2 is a recently identified receptor for C5a/C5adesArg, C3a and C3adesArg (ASP). C5a/C5adesArg bind with high affinity, with no identified activation...
  3. Poursharifi P, Lapointe M, Pétrin D, Devost D, Gauvreau D, Hebert T, et al. C5L2 and C5aR interaction in adipocytes and macrophages: insights into adipoimmunology. Cell Signal. 2013;25:910-8 pubmed publisher
    ..C5aR-like receptor 2 (C5L2) has been identified as a receptor for acylation-stimulating protein (ASP) and the inflammatory factor C5a, which ..
  4. Bosmann M, Haggadone M, Hemmila M, Zetoune F, Sarma J, Ward P. Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages. J Immunol. 2012;188:5086-93 pubmed publisher
    ..C5a suppressed IL-27(p28) in LPS-stimulated macrophages via interactions with the C5aR receptor rather than the C5L2 receptor...
  5. Scola A, Higginbottom A, Partridge L, Reid R, Woodruff T, Taylor S, et al. The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding. J Biol Chem. 2007;282:3664-71 pubmed
    b>C5L2 is a new cellular receptor found to interact with the human anaphylatoxins complement factor C5a and its C-terminal cleavage product C5a des Arg...
  6. Chehoud C, Rafail S, Tyldsley A, Seykora J, Lambris J, Grice E. Complement modulates the cutaneous microbiome and inflammatory milieu. Proc Natl Acad Sci U S A. 2013;110:15061-6 pubmed publisher
    ..Additionally, we reveal a role for complement in homeostatic host-microbiome interactions of the skin. ..
  7. Biggins P, Brennan F, Taylor S, Woodruff T, Ruitenberg M. The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury. J Neurotrauma. 2017;34:2075-2085 pubmed publisher
    This study investigated the role of the alternative receptor for complement activation fragment C5a, C5aR2, in secondary inflammatory pathology after contusive spinal cord injury (SCI) in mice...
  8. Poursharifi P, Lapointe M, Fisette A, Lu H, Roy C, Munkonda M, et al. C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue. Mol Cell Endocrinol. 2014;382:325-333 pubmed publisher
    Recent studies suggested that the immunometabolic receptors; C5aR and C5L2, constitutively self-associate into homo-/heterodimers and that acylation stimulating protein (ASP/C3adesArg) or C5a treatment of adipocytes increased their ..
  9. Wang R, Lu B, Gerard C, Gerard N. Disruption of the complement anaphylatoxin receptor C5L2 exacerbates inflammation in allergic contact dermatitis. J Immunol. 2013;191:4001-9 pubmed publisher
    ..This anaphylatoxin functions by interacting with two 7-transmembrane segment receptors, the C5aR and C5L2. The C5aR is a classical G protein coupled receptor, whereas C5L2 is deficient in coupling to G proteins because of ..
  10. Gauvreau D, Gupta A, Fisette A, Tom F, Cianflone K. Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice. PLoS ONE. 2013;8:e60795 pubmed publisher
    ..b>C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (..
  11. Karsten C, Wiese A, Mey F, Figge J, Woodruff T, Reuter T, et al. Monitoring C5aR2 Expression Using a Floxed tdTomato-C5aR2 Knock-In Mouse. J Immunol. 2017;199:3234-3248 pubmed publisher
    ..Specific ligation of C5aR2 inhibits C5a-induced ERK1/2 activation, strengthening the view that C5aR2 regulates C5aR1-mediated effector ..
  12. Kovtun A, Bergdolt S, Hägele Y, Matthes R, Lambris J, Huber Lang M, et al. Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair. Sci Rep. 2017;7:14061 pubmed publisher
    ..of the posttraumatic immune response is the complement anaphylatoxin C5a, which acts via two receptors, C5aR1 and C5aR2, expressed on immune and bone cells...
  13. Li R, Coulthard L, Wu M, Taylor S, Woodruff T. C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB J. 2013;27:855-64 pubmed publisher
    ..In 2000, a second C5a receptor, C5L2 (previously known as GPR77), was discovered; yet, despite 12 yr of intensive research, its biological, or pathophysiological, function is ..
  14. Roy C, Paglialunga S, Schaart G, Moonen Kornips E, Meex R, Phielix E, et al. Relationship of C5L2 receptor to skeletal muscle substrate utilization. PLoS ONE. 2013;8:e57494 pubmed publisher
    To investigate the role of Acylation Stimulating Protein (ASP) receptor C5L2 in skeletal muscle fatty acid accumulation and metabolism as well as insulin sensitivity in both mice and human models of diet-induced insulin resistance...
  15. Bosmann M, Haggadone M, Zetoune F, Sarma J, Ward P. The interaction between C5a and both C5aR and C5L2 receptors is required for production of G-CSF during acute inflammation. Eur J Immunol. 2013;43:1907-13 pubmed publisher
    ..C5a and C5adesArg bind to their receptors, C5aR and C5L2, but the functional roles of C5L2 remain controversial...
  16. Poppelaars F, van Werkhoven M, Kotimaa J, Veldhuis Z, Ausema A, Broeren S, et al. Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury. FASEB J. 2017;31:3193-3204 pubmed publisher
    ..The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium...
  17. Wen Y, Wang H, MacLaren R, Wu J, Lu H, Cianflone K. Palmitate and oleate induction of acylation stimulating protein resistance in 3T3-L1 adipocytes and preadipocytes. J Cell Biochem. 2008;104:391-401 pubmed
    Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose transport via its receptor C5L2. The aims were (i) to evaluate ASP response under insulin-resistant conditions and (ii) to identify mechanisms of ASP ..
  18. He S, Atkinson C, Qiao F, Cianflone K, Chen X, Tomlinson S. A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice. J Clin Invest. 2009;119:2304-16 pubmed publisher
    ..Furthermore, liver regeneration was dependent on the putative ASP receptor, C5L2. Several potential mechanisms of hepatoprotection and recovery were identified in mice treated with low-dose CR2-..
  19. Xu G, Chen J, Yang F, Li G, Zheng L, Wu Y. C5a/C5aR pathway is essential for the pathogenesis of murine viral fulminant hepatitis by way of potentiating Fgl2/fibroleukin expression. Hepatology. 2014;60:114-24 pubmed publisher
    ..Inhibition of C5a/C5aR interactions is expected to be beneficial in the clinical treatment of FH patients. ..
  20. Hsu W, Yang F, Lin C, Hsieh S, Chen N. C5L2 is required for C5a-triggered receptor internalization and ERK signaling. Cell Signal. 2014;26:1409-19 pubmed publisher
    b>C5L2 is a receptor that binds to C5a and belongs to the family of G protein-coupled receptors, but its role in physiological C5a-mediated responses remains under debate...
  21. Nomaru H, Sakumi K, Katogi A, Ohnishi Y, Kajitani K, Tsuchimoto D, et al. Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia. Glia. 2014;62:1284-98 pubmed publisher
    ..Of these genes, we focused on C5ar1 and C5ar2, which encode receptors for complement C5a...
  22. Vijayan S, Asare Y, Grommes J, Soehnlein O, Lutgens E, Shagdarsuren G, et al. High expression of C5L2 correlates with high proinflammatory cytokine expression in advanced human atherosclerotic plaques. Am J Pathol. 2014;184:2123-33 pubmed publisher
    The complement anaphylatoxin C5a functions through its two receptors, C5aR (CD88) and C5a receptor-like 2 (C5L2). Their role in atherosclerosis is incompletely understood...
  23. Pandey M, Burrow T, Rani R, Martin L, Witte D, SETCHELL K, et al. Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease. Nature. 2017;543:108-112 pubmed publisher
  24. Wang R, Lu B, Gerard C, Gerard N. C5L2, the Second C5a Anaphylatoxin Receptor, Suppresses LPS-Induced Acute Lung Injury. Am J Respir Cell Mol Biol. 2016;55:657-666 pubmed
    ..In the mouse model, however, the precise role of C5a and its receptors is unclear. C5L2, an enigmatic second receptor for C5a, has been characterized, and results have generated substantial debate ..
  25. Kim H, Erdman L, Lu Z, Serghides L, Zhong K, Dhabangi A, et al. Functional roles for C5a and C5aR but not C5L2 in the pathogenesis of human and experimental cerebral malaria. Infect Immun. 2014;82:371-9 pubmed publisher
    ..C5a signaling contributes to the pathogenesis of CM, we investigated a causal role for the C5a receptors C5aR and C5L2 in a mouse model of experimental CM (ECM) induced by Plasmodium berghei ANKA infection, and using a case-control ..
  26. Selle J, Asare Y, Köhncke J, Alampour Rajabi S, Shagdarsuren G, Klos A, et al. Atheroprotective role of C5ar2 deficiency in apolipoprotein E-deficient mice. Thromb Haemost. 2015;114:848-58 pubmed publisher
    ..between high expressions of the second receptor for complement anaphylatoxin C5a, the C5a receptor-like 2 (C5L2, C5aR2), with high pro-inflammatory cytokine expression in advanced human atherosclerotic plaques...
  27. Fisette A, Munkonda M, Oikonomopoulou K, Paglialunga S, Lambris J, Cianflone K. C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice. Immunobiology. 2013;218:127-33 pubmed publisher
    ..These effects are mediated by C5L2 receptor, which has also been associated with inflammatory effects...
  28. Fusakio M, Mohammed J, Laumonnier Y, Hoebe K, Köhl J, Mattner J. C5a regulates NKT and NK cell functions in sepsis. J Immunol. 2011;187:5805-12 pubmed publisher
    ..Functional roles for both C5a receptors, that is, complement receptor C5a (C5aR) and C5a receptor-like 2 (C5L2), in sepsis have been demonstrated...
  29. Raby A, Holst B, Davies J, Colmont C, Laumonnier Y, Coles B, et al. TLR activation enhances C5a-induced pro-inflammatory responses by negatively modulating the second C5a receptor, C5L2. Eur J Immunol. 2011;41:2741-52 pubmed publisher
    ..Rather, TLRs targeted another C5a receptor, C5L2 (acting as a negative modulator of C5aR), by reducing C5L2 activity...