CLEC4M explained

C-type lectin domain family 4 member M is a protein that in humans is encoded by the CLEC4M gene.^[1] CLEC4M has also been designated as CD299 (cluster of differentiation 299).

This gene encodes L-SIGN (liver/lymph node-specific intracellular adhesion molecules-3 grabbing non-integrin), a type II integral membrane protein that is 77% identical to CD209 antigen, an HIV gp120-binding protein. This protein, like CD209, efficiently binds both intercellular adhesion molecule 3 (ICAM3) and HIV-1 gp120, and enhances HIV-1 infection of T cells. This gene is mapped to 19p13.3, in a cluster with the CD209 and CD23/FCER2 genes. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.^[2]

Further reading

• Baribaud F, Doms RW, Pöhlmann S . The role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential therapeutics block virus transmission and dissemination? . Expert Opin. Ther. Targets . 6 . 4 . 423–31 . 2006 . 12223058 . 10.1517/14728222.6.4.423 . 21541850 .
• Becker Y . HIV-1 gp120 binding to dendritic cell receptors mobilize the virus to the lymph nodes, but the induced IL-4 synthesis by FcepsilonRI+ hematopoietic cells damages the adaptive immunity--a review, hypothesis, and implications. . Virus Genes . 29 . 1 . 147–65 . 2004 . 15215692 . 10.1023/B:VIRU.0000032797.43537.d3 . 5666009 . free .
• Lalor PF, Lai WK, Curbishley SM . Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo. . World J. Gastroenterol. . 12 . 34 . 5429–39 . 2006 . 17006978 . 4088223 . 10.3748/wjg.v12.i34.5429. etal . free .
• Curtis BM, Scharnowske S, Watson AJ . Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120. . Proc. Natl. Acad. Sci. U.S.A. . 89 . 17 . 8356–60 . 1992 . 1518869 . 10.1073/pnas.89.17.8356 . 49917 . 1992PNAS...89.8356C . free .
• Gattegno L, Ramdani A, Jouault T . Lectin-carbohydrate interactions and infectivity of human immunodeficiency virus type 1 (HIV-1). . AIDS Res. Hum. Retroviruses . 8 . 1 . 27–37 . 1992 . 1736938 . 10.1089/aid.1992.8.27 . etal.
• Soilleux EJ, Barten R, Trowsdale J . DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. . J. Immunol. . 165 . 6 . 2937–42 . 2000 . 10975799 . 10.4049/jimmunol.165.6.2937. free .
• Pöhlmann S, Soilleux EJ, Baribaud F . DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans. . Proc. Natl. Acad. Sci. U.S.A. . 98 . 5 . 2670–5 . 2001 . 11226297 . 10.1073/pnas.051631398 . 30196 . 2001PNAS...98.2670P . etal. free .
• Bashirova AA, Geijtenbeek TB, van Duijnhoven GC . A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. . J. Exp. Med. . 193 . 6 . 671–8 . 2001 . 11257134 . 10.1084/jem.193.6.671 . 2193415 . etal.
• Mummidi S, Catano G, Lam L . Extensive repertoire of membrane-bound and soluble dendritic cell-specific ICAM-3-grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-individual variation in expression of DC-SIGN transcripts. . J. Biol. Chem. . 276 . 35 . 33196–212 . 2001 . 11337487 . 10.1074/jbc.M009807200 . etal. free.
• Mitchell DA, Fadden AJ, Drickamer K . A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. . J. Biol. Chem. . 276 . 31 . 28939–45 . 2001 . 11384997 . 10.1074/jbc.M104565200 . free .
• Feinberg H, Mitchell DA, Drickamer K, Weis WI . Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. . Science . 294 . 5549 . 2163–6 . 2002 . 11739956 . 10.1126/science.1066371 . 25046581 .
• Alvarez CP, Lasala F, Carrillo J . C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. . J. Virol. . 76 . 13 . 6841–4 . 2002 . 12050398 . 10.1128/JVI.76.13.6841-6844.2002 . 136246 . etal.
• Soilleux EJ, Morris LS, Rushbrook S . Expression of human immunodeficiency virus (HIV)-binding lectin DC-SIGNR: Consequences for HIV infection and immunity. . Hum. Pathol. . 33 . 6 . 652–9 . 2002 . 12152166 . 10.1053/hupa.2002.124036 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Lin G, Simmons G, Pöhlmann S . Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. . J. Virol. . 77 . 2 . 1337–46 . 2003 . 12502850 . 10.1128/JVI.77.2.1337-1346.2003 . 140807 . etal.
• Pöhlmann S, Zhang J, Baribaud F . Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. . J. Virol. . 77 . 7 . 4070–80 . 2003 . 12634366 . 10.1128/JVI.77.7.4070-4080.2003 . 150620 . etal.
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Engering A, van Vliet SJ, Hebeda K . Dynamic populations of dendritic cell-specific ICAM-3 grabbing nonintegrin-positive immature dendritic cells and liver/lymph node-specific ICAM-3 grabbing nonintegrin-positive endothelial cells in the outer zones of the paracortex of human lymph nodes. . Am. J. Pathol. . 164 . 5 . 1587–95 . 2004 . 15111305 . 10.1016/S0002-9440(10)63717-0. 1615649 . etal.

Notes and References

1. Yokoyama-Kobayashi M, Yamaguchi T, Sekine S, Kato S . Selection of cDNAs encoding putative type II membrane proteins on the cell surface from a human full-length cDNA bank . Gene . 228 . 1–2 . 161–7 . Apr 1999 . 10072769 . 10.1016/S0378-1119(99)00004-9 .
2. Web site: Entrez Gene: CLEC4M C-type lectin domain family 4, member M.