| Structural highlights
Function
CD5L_HUMAN Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection or atherosclerosis. Able to inhibit lipid droplet size in adipocytes. Following incorporation into mature adipocytes via CD36-mediated endocytosis, associates with cytosolic FASN, inhibiting fatty acid synthase activity and leading to lipolysis, the degradation of triacylglycerols into glycerol and free fatty acids (FFA). CD5L-induced lipolysis occurs with progression of obesity: participates in obesity-associated inflammation following recruitment of inflammatory macrophages into adipose tissues, a cause of insulin resistance and obesity-related metabolic disease. Regulation of intracellular lipids mediated by CD5L has a direct effect on transcription regulation mediated by nuclear receptors ROR-gamma (RORC). Acts as a key regulator of metabolic switch in T-helper Th17 cells. Regulates the expression of pro-inflammatory genes in Th17 cells by altering the lipid content and limiting synthesis of cholesterol ligand of RORC, the master transcription factor of Th17-cell differentiation. CD5L is mainly present in non-pathogenic Th17 cells, where it decreases the content of polyunsaturated fatty acyls (PUFA), affecting two metabolic proteins MSMO1 and CYP51A1, which synthesize ligands of RORC, limiting RORC activity and expression of pro-inflammatory genes. Participates in obesity-associated autoimmunity via its association with IgM, interfering with the binding of IgM to Fcalpha/mu receptor and enhancing the development of long-lived plasma cells that produce high-affinity IgG autoantibodies (By similarity). Also acts as an inhibitor of apoptosis in macrophages: promotes macrophage survival from the apoptotic effects of oxidized lipids in case of atherosclerosis (PubMed:24295828). Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (PubMed:16030018, PubMed:24223991, PubMed:24583716, PubMed:25713983).[UniProtKB:Q9QWK4][1] [2] [3] [4] [5]
References
- ↑ Sarrias MR, Roselló S, Sánchez-Barbero F, Sierra JM, Vila J, Yélamos J, Vives J, Casals C, Lozano F. A role for human Sp alpha as a pattern recognition receptor. J Biol Chem. 2005 Oct 21;280(42):35391-8. PMID:16030018 doi:10.1074/jbc.M505042200
- ↑ Sanjurjo L, Amézaga N, Vilaplana C, Cáceres N, Marzo E, Valeri M, Cardona PJ, Sarrias MR. The scavenger protein apoptosis inhibitor of macrophages (AIM) potentiates the antimicrobial response against Mycobacterium tuberculosis by enhancing autophagy. PLoS One. 2013 Nov 4;8(11):e79670. PMID:24223991 doi:10.1371/journal.pone.0079670
- ↑ Amézaga N, Sanjurjo L, Julve J, Aran G, Pérez-Cabezas B, Bastos-Amador P, Armengol C, Vilella R, Escolà-Gil JC, Blanco-Vaca F, Borràs FE, Valledor AF, Sarrias MR. Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL uptake. J Leukoc Biol. 2014 Mar;95(3):509-20. PMID:24295828 doi:10.1189/jlb.1212660
- ↑ Martinez VG, Escoda-Ferran C, Tadeu Simões I, Arai S, Orta Mascaró M, Carreras E, Martínez-Florensa M, Yelamos J, Miyazaki T, Lozano F. The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression. Cell Mol Immunol. 2014 Jul;11(4):343-54. PMID:24583716 doi:10.1038/cmi.2014.12
- ↑ Sanjurjo L, Amézaga N, Aran G, Naranjo-Gómez M, Arias L, Armengol C, Borràs FE, Sarrias MR. The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses. Autophagy. 2015;11(3):487-502. PMID:25713983 doi:10.1080/15548627.2015.1017183
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