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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''CD93''' ('''C'''luster of '''D'''ifferentiation 93) is a [[protein]] that in humans is encoded by the ''CD93'' [[gene]].<ref name="pmid9047234">{{cite journal | vauthors = Nepomuceno RR, Henschen-Edman AH, Burgess WH, Tenner AJ | title = cDNA cloning and primary structure analysis of C1qR(P), the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro | journal = Immunity | volume = 6 | issue = 2 | pages = 119–29 | date = February 1997 | pmid = 9047234 | doi = 10.1016/S1074-7613(00)80419-7 }}</ref><ref name="pmid10648005">{{cite journal | vauthors = Webster SD, Park M, Fonseca MI, Tenner AJ | title = Structural and functional evidence for microglial expression of C1qR(P), the C1q receptor that enhances phagocytosis | journal = Journal of Leukocyte Biology | volume = 67 | issue = 1 | pages = 109–16 | date = January 2000 | pmid = 10648005 | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CD93 CD93 molecule| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22918| access-date = }}</ref> CD93 is a [[C-type lectin]] [[transmembrane protein| transmembrane receptor]] which plays a role not only in cell–cell adhesion processes but also in host defense.<ref name="entrez"/>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Family ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = CD93 molecule
| HGNCid = 15855
| Symbol = CD93
| AltSymbols =; C1QR1; C1qR(P); C1qRP; CDw93; MXRA4; dJ737E23.1
| OMIM = 120577
| ECnumber = 
| Homologene = 7823
| MGIid = 106664
| GeneAtlas_image1 = PBB_GE_CD93_202878_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_CD93_202877_s_at_tn.png
| Function = {{GNF_GO|id=GO:0001849 |text = complement component C1q binding}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005529 |text = sugar binding}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0016023 |text = cytoplasmic membrane-bound vesicle}}
| Process = {{GNF_GO|id=GO:0006909 |text = phagocytosis}} {{GNF_GO|id=GO:0016337 |text = cell-cell adhesion}} {{GNF_GO|id=GO:0042116 |text = macrophage activation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 22918
    | Hs_Ensembl = ENSG00000125810
    | Hs_RefseqProtein = NP_036204
    | Hs_RefseqmRNA = NM_012072
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 20
    | Hs_GenLoc_start = 23007995
    | Hs_GenLoc_end = 23014977
    | Hs_Uniprot = Q9NPY3
    | Mm_EntrezGene = 17064
    | Mm_Ensembl = ENSMUSG00000027435
    | Mm_RefseqmRNA = XM_993058
    | Mm_RefseqProtein = XP_998152
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 148128092
    | Mm_GenLoc_end = 148134985
    | Mm_Uniprot = O89103
  }}
}}
'''CD93''' ('''C'''luster of '''D'''ifferentiation 93) is a human [[protein]] encoded by the {{gene|CD93}} [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CD93 CD93 molecule| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22918| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
CD93 belongs to the Group XIV C-Type [[lectin]] family, a group containing three other members, endosialin ([[CD248]]), CLEC14A<ref>{{cite journal | vauthors = Mura M, Swain RK, Zhuang X, Vorschmitt H, Reynolds G, Durant S, Beesley JF, Herbert JM, Sheldon H, Andre M, Sanderson S, Glen K, Luu NT, McGettrick HM, Antczak P, Falciani F, Nash GB, Nagy ZS, Bicknell R | title = Identification and angiogenic role of the novel tumor endothelial marker CLEC14A | journal = Oncogene | volume = 31 | issue = 3 | pages = 293–305 | date = January 2012 | pmid = 21706054 | doi = 10.1038/onc.2011.233 }}</ref> and [[thrombomodulin]], a well characterized anticoagulant. All of them contain a C-type lectin domain, a series of [[EGF-like_domain|epidermal growth factor like domains]], 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 [[Gene_duplication|duplication]] event.
{{PBB_Summary
| section_title =  
| summary_text = The protein encoded by this gene is a cell-surface glycoprotein and type I membrane protein that was originally identified as a myeloid cell-specific marker. The encoded protein was once 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 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.<ref name="entrez">{{cite web | title = Entrez Gene: CD93 CD93 molecule| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22918| accessdate = }}</ref>
}}


==See also==
== Expression ==
 
CD93 was originally identified in mice as an early [[B cell]] marker through the use of AA4.1 monoclonal antibody.<ref name="pmid6606670">{{cite journal | vauthors = McKearn JP, Baum C, Davie JM | title = Cell surface antigens expressed by subsets of pre-B cells and B cells | journal = Journal of Immunology | volume = 132 | issue = 1 | pages = 332–9 | date = January 1984 | pmid = 6606670 }}</ref><ref name="pmid20387063">{{cite journal | vauthors = Zekavat G, Mozaffari R, Arias VJ, Rostami SY, Badkerhanian A, Tenner AJ, Nichols KE, Naji A, Noorchashm H | title = A novel CD93 polymorphism in non-obese diabetic (NOD) and NZB/W F1 mice is linked to a CD4+ iNKT cell deficient state | journal = Immunogenetics | volume = 62 | issue = 6 | pages = 397–407 | date = June 2010 | pmid = 20387063 | pmc = 2875467 | doi = 10.1007/s00251-010-0442-3 }}</ref> Then this molecule was shown to be expressed on an early population of [[hematopoietic stem cell]]s, 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 [[platelet]]s, [[monocyte]]s, [[microglia]] and [[Endothelium|endothelial]] cells. In the immune system CD93 is also expressed on [[neutrophil]]s, activated [[macrophage]]s, 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_complex|C1q]] receptor.<ref name="pmid11994479">{{cite journal | vauthors = McGreal EP, Ikewaki N, Akatsu H, Morgan BP, Gasque P | title = Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q | journal = Journal of Immunology | volume = 168 | issue = 10 | pages = 5222–32 | date = May 2002 | pmid = 11994479 | doi = 10.4049/jimmunol.168.10.5222 }}</ref> C1q belongs to the [[Complement_system|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 [[Apoptosis|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 has been found to be differentially expressed in grade IV glioma vasculature when compared to low grade glioma or normal brain and its high expression correlated with the poor survival of the patients.<ref>{{cite journal | vauthors = Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomäki H, Teichert M, Huang H, Edqvist PH, Kraus T, Augustin HG, Olofsson T, Larsson E, Söderberg O, Molema G, Pontén F, Georgii-Hemming P, Alafuzoff I, Dimberg A | title = Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization | journal = The Journal of Pathology | volume = 228 | issue = 3 | pages = 378–90 | date = November 2012 | pmid = 22786655 | doi = 10.1002/path.4072 }}</ref><ref name=":0">{{cite journal | vauthors = Langenkamp E, Zhang L, Lugano R, Huang H, Elhassan TE, Georganaki M, Bazzar W, Lööf J, Trendelenburg G, Essand M, Pontén F, Smits A, Dimberg A | title = Elevated expression of the C-type lectin CD93 in the glioblastoma vasculature regulates cytoskeletal rearrangements that enhance vessel function and reduce host survival | journal = Cancer Research | volume = 75 | issue = 21 | pages = 4504–16 | date = November 2015 | pmid = 26363010 | doi = 10.1158/0008-5472.CAN-14-3636 }}</ref>
 
== Function ==
 
CD93 was initially thought to be a receptor for C1q, but now is thought to instead be involved in intercellular [[cell adhesion|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, [[cell migration|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.
 
In the context of the endothelial cells, CD93 is involved in endothelial cell-cell adhesion, cell spreading, cell migration, cell polarization as well as tubular morphogenesis.<ref name=":0" /> Recently it has been found that CD93 is able to control endothelial cell dynamics through its interaction with an extracellular matrix gycoprotein MMRN2.<ref name=":1">{{cite journal | vauthors = Lugano R, Vemuri K, Yu D, Bergqvist M, Smits A, Essand M, Johansson S, Dejana E, Dimberg A | title = CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis | journal = The Journal of Clinical Investigation | volume = 128 | issue = 8 | pages = 3280–3297 | date = August 2018 | pmid = 29763414 | pmc = 6063507 | doi = 10.1172/JCI97459 }}</ref> Absence of CD93 or its interacting partner MMRN2 in the endothelial cells lead to disruption of extracellular matrix protein [[fibronectin]] fibrillogenesis and decreased [[Integrin beta 1|integrin B1]] activation.<ref name=":1" />
 
CD93 plays a significant role in the glioma development. CD93 knockout mice with glioma show smaller tumor size and improved survival.<ref name=":0" /> The tumors also show  disrupted fibronectin fibrillogenesis and decreased [[Integrin beta 1|integrin B1]] activation.<ref name=":1" />
 
== See also ==
* [[Cluster of differentiation]]
* [[Cluster of differentiation]]
* [[C-type lectin]]


==References==
== References ==
{{reflist|2}}
{{reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Chevrier S, Genton C, Kallies A, Karnowski A, Otten LA, Malissen B, Malissen M, Botto M, Corcoran LM, Nutt SL, Acha-Orbea H | title = CD93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 10 | pages = 3895–900 | date = March 2009 | pmid = 19228948 | pmc = 2656176 | doi = 10.1073/pnas.0809736106 }}
| citations =  
* {{cite journal | vauthors = Tenner AJ | title = C1q receptors: regulating specific functions of phagocytic cells | journal = Immunobiology | volume = 199 | issue = 2 | pages = 250–64 | date = August 1998 | pmid = 9777410 | doi = 10.1016/s0171-2985(98)80031-4 }}
*{{cite journal | author=Tenner AJ |title=C1q receptors: regulating specific functions of phagocytic cells. |journal=Immunobiology |volume=199 |issue= 2 |pages= 250-64 |year= 1999 |pmid= 9777410 |doi= }}
* {{cite journal | vauthors = Ghebrehiwet B, Peerschke EI, Hong Y, Munoz P, Gorevic PD | title = 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 | journal = Journal of Leukocyte Biology | volume = 51 | issue = 6 | pages = 546–56 | date = June 1992 | pmid = 1377218 | doi =  }}
*{{cite journal | author=Ghebrehiwet B, Peerschke EI, Hong Y, ''et al.'' |title=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. |journal=J. Leukoc. Biol. |volume=51 |issue= 6 |pages= 546-56 |year= 1992 |pmid= 1377218 |doi=  }}
* {{cite journal | vauthors = Peerschke EI, Ghebrehiwet B | title = Platelet C1q receptor interactions with collagen- and C1q-coated surfaces | journal = Journal of Immunology | volume = 145 | issue = 9 | pages = 2984–8 | date = November 1990 | pmid = 2212670 | doi =  }}
*{{cite journal | author=Peerschke EI, Ghebrehiwet B |title=Platelet C1q receptor interactions with collagen- and C1q-coated surfaces. |journal=J. Immunol. |volume=145 |issue= 9 |pages= 2984-8 |year= 1990 |pmid= 2212670 |doi=  }}
* {{cite journal | vauthors = Eggleton P, Lieu TS, Zappi EG, Sastry K, Coburn J, Zaner KS, Sontheimer RD, Capra JD, Ghebrehiwet B, Tauber AI | title = Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein | journal = Clinical Immunology and Immunopathology | volume = 72 | issue = 3 | pages = 405–9 | date = September 1994 | pmid = 8062452 | doi = 10.1006/clin.1994.1160 }}
*{{cite journal | author=Eggleton P, Lieu TS, Zappi EG, ''et al.'' |title=Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein. |journal=Clin. Immunol. Immunopathol. |volume=72 |issue= 3 |pages= 405-9 |year= 1994 |pmid= 8062452 |doi= }}
* {{cite journal | vauthors = Joseph K, Ghebrehiwet B, Peerschke EI, Reid KB, Kaplan AP | title = 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) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 16 | pages = 8552–7 | date = August 1996 | pmid = 8710908 | pmc = 38710 | doi = 10.1073/pnas.93.16.8552 }}
*{{cite journal | author=Joseph K, Ghebrehiwet B, Peerschke EI, ''et al.'' |title=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). |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 16 |pages= 8552-7 |year= 1996 |pmid= 8710908 |doi= }}
* {{cite journal | vauthors = Cáceres J, Brandan E | title = Interaction between Alzheimer's disease beta A4 precursor protein (APP) and the extracellular matrix: evidence for the participation of heparan sulfate proteoglycans | journal = Journal of Cellular Biochemistry | volume = 65 | issue = 2 | pages = 145–58 | date = May 1997 | pmid = 9136074 | doi = 10.1002/(SICI)1097-4644(199705)65:2<145::AID-JCB2>3.0.CO;2-U }}
*{{cite journal  | author=Nepomuceno RR, Henschen-Edman AH, Burgess WH, Tenner AJ |title=cDNA cloning and primary structure analysis of C1qR(P), the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro. |journal=Immunity |volume=6 |issue= 2 |pages= 119-29 |year= 1997 |pmid= 9047234 |doi=  }}
* {{cite journal | vauthors = Nepomuceno RR, Tenner AJ | title = C1qRP, the C1q receptor that enhances phagocytosis, is detected specifically in human cells of myeloid lineage, endothelial cells, and platelets | journal = Journal of Immunology | volume = 160 | issue = 4 | pages = 1929–35 | date = February 1998 | pmid = 9469455 | doi =  }}
*{{cite journal | author=Cáceres J, Brandan E |title=Interaction between Alzheimer's disease beta A4 precursor protein (APP) and the extracellular matrix: evidence for the participation of heparan sulfate proteoglycans. |journal=J. Cell. Biochem. |volume=65 |issue= 2 |pages= 145-58 |year= 1997 |pmid= 9136074 |doi= }}
* {{cite journal | vauthors = Stuart GR, Lynch NJ, Day AJ, Schwaeble WJ, Sim RB | title = The C1q and collectin binding site within C1q receptor (cell surface calreticulin) | journal = Immunopharmacology | volume = 38 | issue = 1-2 | pages = 73–80 | date = December 1997 | pmid = 9476117 | doi = 10.1016/S0162-3109(97)00076-3 }}
*{{cite journal | author=Nepomuceno RR, Tenner AJ |title=C1qRP, the C1q receptor that enhances phagocytosis, is detected specifically in human cells of myeloid lineage, endothelial cells, and platelets. |journal=J. Immunol. |volume=160 |issue= 4 |pages= 1929-35 |year= 1998 |pmid= 9469455 |doi=  }}
* {{cite journal | vauthors = Nepomuceno RR, Ruiz S, Park M, Tenner AJ | title = C1qRP is a heavily O-glycosylated cell surface protein involved in the regulation of phagocytic activity | journal = Journal of Immunology | volume = 162 | issue = 6 | pages = 3583–9 | date = March 1999 | pmid = 10092817 | doi =  }}
*{{cite journal | author=Stuart GR, Lynch NJ, Day AJ, ''et al.'' |title=The C1q and collectin binding site within C1q receptor (cell surface calreticulin). |journal=Immunopharmacology |volume=38 |issue= 1-2 |pages= 73-80 |year= 1998 |pmid= 9476117 |doi= }}
* {{cite journal | vauthors = Norsworthy PJ, Taylor PR, Walport MJ, Botto M | title = Cloning of the mouse homolog of the 126-kDa human C1q/MBL/SP-A receptor, C1qR(p) | journal = Mammalian Genome | volume = 10 | issue = 8 | pages = 789–93 | date = August 1999 | pmid = 10430665 | doi = 10.1007/s003359901093 }}
*{{cite journal | author=Nepomuceno RR, Ruiz S, Park M, Tenner AJ |title=C1qRP is a heavily O-glycosylated cell surface protein involved in the regulation of phagocytic activity. |journal=J. Immunol. |volume=162 |issue= 6 |pages= 3583-9 |year= 1999 |pmid= 10092817 |doi=  }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
*{{cite journal | author=Norsworthy PJ, Taylor PR, Walport MJ, Botto M |title=Cloning of the mouse homolog of the 126-kDa human C1q/MBL/SP-A receptor, C1qR(p). |journal=Mamm. Genome |volume=10 |issue= 8 |pages= 789-93 |year= 1999 |pmid= 10430665 |doi= }}
* {{cite journal | vauthors = Kittlesen DJ, Chianese-Bullock KA, Yao ZQ, Braciale TJ, Hahn YS | title = Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation | journal = The Journal of Clinical Investigation | volume = 106 | issue = 10 | pages = 1239–49 | date = November 2000 | pmid = 11086025 | pmc = 381434 | doi = 10.1172/JCI10323 }}
*{{cite journal  | author=Webster SD, Park M, Fonseca MI, Tenner AJ |title=Structural and functional evidence for microglial expression of C1qR(P), the C1q receptor that enhances phagocytosis. |journal=J. Leukoc. Biol. |volume=67 |issue= 1 |pages= 109-16 |year= 2000 |pmid= 10648005 |doi=  }}
* {{cite journal | vauthors = Joseph K, Shibayama Y, Ghebrehiwet B, Kaplan AP | title = Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1 | journal = Thrombosis and Haemostasis | volume = 85 | issue = 1 | pages = 119–24 | date = January 2001 | pmid = 11204562 | doi =  }}
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi= }}
* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
*{{cite journal | author=Kittlesen DJ, Chianese-Bullock KA, Yao ZQ, ''et al.'' |title=Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. |journal=J. Clin. Invest. |volume=106 |issue= 10 |pages= 1239-49 |year= 2001 |pmid= 11086025 |doi= }}
* {{cite journal | vauthors = Steinberger P, Szekeres A, Wille S, Stöckl J, Selenko N, Prager E, Staffler G, Madic O, Stockinger H, Knapp W | title = Identification of human CD93 as the phagocytic C1q receptor (C1qRp) by expression cloning | journal = Journal of Leukocyte Biology | volume = 71 | issue = 1 | pages = 133–40 | date = January 2002 | pmid = 11781389 | doi =  }}
*{{cite journal | author=Joseph K, Shibayama Y, Ghebrehiwet B, Kaplan AP |title=Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1. |journal=Thromb. Haemost. |volume=85 |issue= 1 |pages= 119-24 |year= 2001 |pmid= 11204562 |doi=  }}
*{{cite journal | author=Simpson JC, Wellenreuther R, Poustka A, ''et al.'' |title=Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. |journal=EMBO Rep. |volume=1 |issue= 3 |pages= 287-92 |year= 2001 |pmid= 11256614 |doi= 10.1093/embo-reports/kvd058 }}
*{{cite journal | author=Deloukas P, Matthews LH, Ashurst J, ''et al.'' |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865-71 |year= 2002 |pmid= 11780052 |doi= 10.1038/414865a }}
*{{cite journal  | author=Steinberger P, Szekeres A, Wille S, ''et al.'' |title=Identification of human CD93 as the phagocytic C1q receptor (C1qRp) by expression cloning. |journal=J. Leukoc. Biol. |volume=71 |issue= 1 |pages= 133-40 |year= 2002 |pmid= 11781389 |doi=  }}
*{{cite journal  | author=McGreal EP, Ikewaki N, Akatsu H, ''et al.'' |title=Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q. |journal=J. Immunol. |volume=168 |issue= 10 |pages= 5222-32 |year= 2002 |pmid= 11994479 |doi=  }}
}}
{{refend}}
{{refend}}


==External links==
== External links ==
* {{MeshName|CD93+protein,+human}}
* {{MeshName|CD93+protein,+human}}
* {{UCSC gene info|CD93}}


{{membrane-protein-stub}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}
[[Category:Clusters of differentiation]]
[[Category:Clusters of differentiation]]
{{WikiDoc Sources}}

Latest revision as of 07:15, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

CD93 (Cluster of Differentiation 93) is a protein that in humans is encoded by the CD93 gene.[1][2][3] CD93 is a C-type lectin transmembrane receptor which plays a role not only in cell–cell adhesion processes but also in host defense.[3]

Family

CD93 belongs to the Group XIV C-Type lectin family, a group containing three other members, endosialin (CD248), CLEC14A[4] and thrombomodulin, a well characterized anticoagulant. All of them contain a C-type lectin domain, a series of epidermal growth factor like domains, 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.

Expression

CD93 was originally identified in mice as an early B cell marker through the use of AA4.1 monoclonal antibody.[5][6] 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.[7] 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 has been found to be differentially expressed in grade IV glioma vasculature when compared to low grade glioma or normal brain and its high expression correlated with the poor survival of the patients.[8][9]

Function

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.

In the context of the endothelial cells, CD93 is involved in endothelial cell-cell adhesion, cell spreading, cell migration, cell polarization as well as tubular morphogenesis.[9] Recently it has been found that CD93 is able to control endothelial cell dynamics through its interaction with an extracellular matrix gycoprotein MMRN2.[10] Absence of CD93 or its interacting partner MMRN2 in the endothelial cells lead to disruption of extracellular matrix protein fibronectin fibrillogenesis and decreased integrin B1 activation.[10]

CD93 plays a significant role in the glioma development. CD93 knockout mice with glioma show smaller tumor size and improved survival.[9] The tumors also show disrupted fibronectin fibrillogenesis and decreased integrin B1 activation.[10]

See also

References

  1. ↑ 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. doi:10.1016/S1074-7613(00)80419-7. PMID 9047234.
  2. ↑ 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". Journal of Leukocyte Biology. 67 (1): 109–16. PMID 10648005.
  3. ↑ 3.0 3.1 "Entrez Gene: CD93 CD93 molecule".
  4. ↑ Mura M, Swain RK, Zhuang X, Vorschmitt H, Reynolds G, Durant S, Beesley JF, Herbert JM, Sheldon H, Andre M, Sanderson S, Glen K, Luu NT, McGettrick HM, Antczak P, Falciani F, Nash GB, Nagy ZS, Bicknell R (January 2012). "Identification and angiogenic role of the novel tumor endothelial marker CLEC14A". Oncogene. 31 (3): 293–305. doi:10.1038/onc.2011.233. PMID 21706054.
  5. ↑ McKearn JP, Baum C, Davie JM (January 1984). "Cell surface antigens expressed by subsets of pre-B cells and B cells". Journal of Immunology. 132 (1): 332–9. PMID 6606670.
  6. ↑ Zekavat G, Mozaffari R, Arias VJ, Rostami SY, Badkerhanian A, Tenner AJ, Nichols KE, Naji A, Noorchashm H (June 2010). "A novel CD93 polymorphism in non-obese diabetic (NOD) and NZB/W F1 mice is linked to a CD4+ iNKT cell deficient state". Immunogenetics. 62 (6): 397–407. doi:10.1007/s00251-010-0442-3. PMC 2875467. PMID 20387063.
  7. ↑ 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". Journal of Immunology. 168 (10): 5222–32. doi:10.4049/jimmunol.168.10.5222. PMID 11994479.
  8. ↑ Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomäki H, Teichert M, Huang H, Edqvist PH, Kraus T, Augustin HG, Olofsson T, Larsson E, Söderberg O, Molema G, Pontén F, Georgii-Hemming P, Alafuzoff I, Dimberg A (November 2012). "Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization". The Journal of Pathology. 228 (3): 378–90. doi:10.1002/path.4072. PMID 22786655.
  9. ↑ 9.0 9.1 9.2 Langenkamp E, Zhang L, Lugano R, Huang H, Elhassan TE, Georganaki M, Bazzar W, Lööf J, Trendelenburg G, Essand M, Pontén F, Smits A, Dimberg A (November 2015). "Elevated expression of the C-type lectin CD93 in the glioblastoma vasculature regulates cytoskeletal rearrangements that enhance vessel function and reduce host survival". Cancer Research. 75 (21): 4504–16. doi:10.1158/0008-5472.CAN-14-3636. PMID 26363010.
  10. ↑ 10.0 10.1 10.2 Lugano R, Vemuri K, Yu D, Bergqvist M, Smits A, Essand M, Johansson S, Dejana E, Dimberg A (August 2018). "CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis". The Journal of Clinical Investigation. 128 (8): 3280–3297. doi:10.1172/JCI97459. PMC 6063507. PMID 29763414.

Further reading

External links

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