|Symbols||; C1QR1; C1qR(P); C1qRP; CDw93; ECSM3; MXRA4; dJ737E23.1|
|RNA expression pattern|
|File:PBB GE CD93 202878 s at tn.png|
|File:PBB GE CD93 202877 s at tn.png|
CD93 (Cluster of Differentiation 93) is a protein that in humans is encoded by the CD93 gene. CD93 is a C-type lectin transmembrane receptor which play a role not only in cell–cell adhesion processes but also in host defence.
CD93 belongs to the Group XIV C-Type lectin family, a group containing two other members, endosialin (CD248) and thrombomodulin, a well characterized anticoagulant. All of them contain a C-type lectin domain, a series of epidermal growth factor like domains (EGF), a highly glycosylated mucin-like domain, a unique transmembrane domain and a short cytoplasmic tail. Due to their strong homology and their close proximity on chromosome 20, CD93 has been suggested to have arisen from the thrombomodulin gene through a duplication event
CD93 was originally identified in mice as an early B cell marker through the use of AA4.1 monoclonal antibody. Then this molecule was shown to be expressed on an early population of hematopoietic stem cells, which give rise to the entire spectrum of mature cells in the blood. Now CD93 is known to be expressed by a wide variety of cells such as platelets, monocytes, microglia and endothelial cells. In the immune system CD93 is also expressed on neutrophils, activated macrophages, B cell precursors until the T2 stage in the spleen, a subset of dendritic cells and of natural killer cells. Molecular characterization of CD93 revealed that this protein is identical with C1qRp, a human protein identified as a putative C1q receptor. C1q belongs to the complement activation proteins and plays a major role in the activation of the classical pathway of the complement, which leads to the formation of the membrane attack complex. C1q is also involved in other immunological processes such as enhancement of bacterial phagocytosis, clearance of apoptotic cells or neutralisation of virus. Strikingly, it has been shown that anti-C1qRp significantly reduced C1q enhanced phagocytosis. A more recent study confirmed that C1qRp is identical to CD93 protein, but failed to demonstrate a direct interaction between CD93 and C1q under physiological conditions. Recently it has been shown that CD93 is re-expressed during the late B cell differentiation and CD93 can be used in this context as a plasma cell maturation marker.
CD93 was initially thought to be a receptor for C1q, but now is thought to instead be involved in intercellular adhesion and in the clearance of apoptotic cells. The intracellular cytoplasmic tail of this protein contains two highly conserved domains which may be involved in CD93 function. Indeed, the highly charged juxtamembrane domain has been found to interact with moesin, a protein known to play a role in linking transmembrane proteins to the cytoskeleton and in the remodelling of the cytoskeleton. This process appears crucial for both adhesion, migration and phagocytosis, three functions in which CD93 may be involved.
In the context of late B cell differentiation, CD93 has been shown to be important for the maintenance of high antibody titres after immunization and in the survival of long-lived plasma cells in the bone marrow. Indeed, CD93 deficient mice failed to maintain high antibody level upon immunization and present a lower amount of antigen specific plasma cells in the bone marrow.
- Nepomuceno RR, Henschen-Edman AH, Burgess WH, Tenner AJ (February 1997). "cDNA cloning and primary structure analysis of C1qR(P), the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro". Immunity 6 (2): 119–29. PMID 9047234. doi:10.1016/S1074-7613(00)80419-7.
- Webster SD, Park M, Fonseca MI, Tenner AJ (January 2000). "Structural and functional evidence for microglial expression of C1qR(P), the C1q receptor that enhances phagocytosis". J. Leukoc. Biol. 67 (1): 109–16. PMID 10648005.
- "Entrez Gene: CD93 CD93 molecule".
- McGreal EP, Ikewaki N, Akatsu H, Morgan BP, Gasque P (May 2002). "Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q". J. Immunol. 168 (10): 5222–32. PMID 11994479. doi:10.4049/jimmunol.168.10.5222.
- Chevrier S; Genton, C; Kallies, A; Karnowski, A; Otten, LA; Malissen, B; Malissen, M; Botto, M et al. (2009). "CD93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche". PNAS 106 (10): 3895–3900. PMC 2656176. PMID 19228948. doi:10.1073/pnas.0809736106.
- Tenner AJ (1999). "C1q receptors: regulating specific functions of phagocytic cells". Immunobiology 199 (2): 250–64. PMID 9777410. doi:10.1016/s0171-2985(98)80031-4.
- Ghebrehiwet B; Peerschke EI; Hong Y et al. (1992). "Short amino acid sequences derived from C1q receptor (C1q-R) show homology with the alpha chains of fibronectin and vitronectin receptors and collagen type IV". J. Leukoc. Biol. 51 (6): 546–56. PMID 1377218.
- Peerschke EI, Ghebrehiwet B (1990). "Platelet C1q receptor interactions with collagen- and C1q-coated surfaces". J. Immunol. 145 (9): 2984–8. PMID 2212670.
- Eggleton P; Lieu TS; Zappi EG et al. (1994). "Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein". Clin. Immunol. Immunopathol. 72 (3): 405–9. PMID 8062452. doi:10.1006/clin.1994.1160.
- Joseph K; Ghebrehiwet B; Peerschke EI et al. (1996). "Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular "heads" of C1q (gC1q-R)". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8552–7. PMC 38710. PMID 8710908. doi:10.1073/pnas.93.16.8552.
- Cáceres J, Brandan E (1997). "Interaction between Alzheimer's disease beta A4 precursor protein (APP) and the extracellular matrix: evidence for the participation of heparan sulfate proteoglycans". J. Cell. Biochem. 65 (2): 145–58. PMID 9136074. doi:10.1002/(SICI)1097-4644(199705)65:2<145::AID-JCB2>3.0.CO;2-U.
- Nepomuceno RR, Tenner AJ (1998). "C1qRP, the C1q receptor that enhances phagocytosis, is detected specifically in human cells of myeloid lineage, endothelial cells, and platelets". J. Immunol. 160 (4): 1929–35. PMID 9469455.
- Stuart GR; Lynch NJ; Day AJ et al. (1998). "The C1q and collectin binding site within C1q receptor (cell surface calreticulin)". Immunopharmacology 38 (1–2): 73–80. PMID 9476117. doi:10.1016/S0162-3109(97)00076-3.
- Nepomuceno RR, Ruiz S, Park M, Tenner AJ (1999). "C1qRP is a heavily O-glycosylated cell surface protein involved in the regulation of phagocytic activity". J. Immunol. 162 (6): 3583–9. PMID 10092817.
- Norsworthy PJ, Taylor PR, Walport MJ, Botto M (1999). "Cloning of the mouse homolog of the 126-kDa human C1q/MBL/SP-A receptor, C1qR(p)". Mamm. Genome 10 (8): 789–93. PMID 10430665. doi:10.1007/s003359901093.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. PMC 310948. PMID 11076863. doi:10.1101/gr.143000.
- Kittlesen DJ; Chianese-Bullock KA; Yao ZQ et al. (2001). "Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation". J. Clin. Invest. 106 (10): 1239–49. PMC 381434. PMID 11086025. doi:10.1172/JCI10323.
- Joseph K, Shibayama Y, Ghebrehiwet B, Kaplan AP (2001). "Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1". Thromb. Haemost. 85 (1): 119–24. PMID 11204562.
- Simpson JC; Wellenreuther R; Poustka A et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. PMC 1083732. PMID 11256614. doi:10.1093/embo-reports/kvd058.
- Deloukas P; Matthews LH; Ashurst J et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature 414 (6866): 865–71. PMID 11780052. doi:10.1038/414865a.
- Steinberger P; Szekeres A; Wille S et al. (2002). "Identification of human CD93 as the phagocytic C1q receptor (C1qRp) by expression cloning". J. Leukoc. Biol. 71 (1): 133–40. PMID 11781389.