CD6 explained

CD6 (Cluster of Differentiation 6) is a human protein encoded by the gene.^{[1] [2]}

Function

This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation.^[1]

Clinical significance

Certain alleles of this gene may be associated with susceptibility to multiple sclerosis.^{[3] [4]}

See also

• Cluster of differentiation

Further reading

• Aruffo A, Melnick MB, Linsley PS, Seed B . The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins . J. Exp. Med. . 174 . 4 . 949–52 . 1991 . 1919444 . 2118957 . 10.1084/jem.174.4.949 .
• Swack JA, Mier JW, Romain PL, Hull SR, Rudd CE . Biosynthesis and post-translational modification of CD6, a T cell signal-transducing molecule . J. Biol. Chem. . 266 . 11 . 7137–43 . 1991 . 10.1016/S0021-9258(20)89621-5 . 2016320 . free .
• Tsuge I, Utsumi KR, Ueda R, Takamoto S, Takahashi T . Assignment of gene coding human T-cell differentiation antigen, Tp120, to chromosome 11 . Somat. Cell Mol. Genet. . 11 . 3 . 217–22 . 1985 . 3923629 . 10.1007/BF01534678 . 39343360 .
• Whitney GS, Starling GC, Bowen MA, Modrell B, Siadak AW, Aruffo A . The membrane-proximal scavenger receptor cysteine-rich domain of CD6 contains the activated leukocyte cell adhesion molecule binding site . J. Biol. Chem. . 270 . 31 . 18187–90 . 1995 . 7543097 . 10.1074/jbc.270.31.18187 . free .
• Robinson WH, Neuman de Vegvar HE, Prohaska SS, Rhee JW, Parnes JR . Human CD6 possesses a large, alternatively spliced cytoplasmic domain . Eur. J. Immunol. . 25 . 10 . 2765–9 . 1995 . 7589069 . 10.1002/eji.1830251008 . 8996113 .
• Wee S, Schieven GL, Kirihara JM, Tsu TT, Ledbetter JA, Aruffo A . Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors . J. Exp. Med. . 177 . 1 . 219–23 . 1993 . 7678115 . 2190871 . 10.1084/jem.177.1.219 .
• Bowen MA, Whitney GS, Neubauer M, Starling GC, Palmer D, Zhang J, Nowak NJ, Shows TB, Aruffo A . Structure and chromosomal location of the human CD6 gene: detection of five human CD6 isoforms . J. Immunol. . 158 . 3 . 1149–56 . 1997 . 10.4049/jimmunol.158.3.1149 . 9013954 . 24196035 . free .
• Kobarg J, Whitney GS, Palmer D, Aruffo A, Bowen MA . Analysis of the tyrosine phosphorylation and calcium fluxing of human CD6 isoforms with different cytoplasmatic domains . Eur. J. Immunol. . 27 . 11 . 2971–80 . 1998 . 9394826 . 10.1002/eji.1830271133 . 20897222 .
• Singer NG, Mitra R, Lialios F, Richardson BC, Marks RM, Pesando JM, Fox DA, Nickoloff BJ . CD6 dependent interactions of T cells and keratinocytes: functional evidence for a second CD6 ligand on gamma-interferon activated keratinocytes . Immunol. Lett. . 58 . 1 . 9–14 . 1998 . 9436462 . 10.1016/S0165-2478(97)02707-7 .
• Gimferrer I, Farnós M, Calvo M, Mittelbrunn M, Enrich C, Sánchez-Madrid F, Vives J, Lozano F . The accessory molecules CD5 and CD6 associate on the membrane of lymphoid T cells . J. Biol. Chem. . 278 . 10 . 8564–71 . 2003 . 12473675 . 10.1074/jbc.M209591200 . free .
• Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM . Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function . J. Biol. Chem. . 278 . 9 . 7607–16 . 2003 . 12493773 . 10.1074/jbc.M210455200 . free .
• Gimferrer I, Ibáñez A, Farnós M, Sarrias MR, Fenutría R, Roselló S, Zimmermann P, David G, Vives J, Serra-Pagès C, Lozano F . The lymphocyte receptor CD6 interacts with syntenin-1, a scaffolding protein containing PDZ domains . J. Immunol. . 175 . 3 . 1406–14 . 2005 . 16034076 . 10.4049/jimmunol.175.3.1406 . free .
• Kato Y, Tanaka Y, Hayashi M, Okawa K, Minato N . Involvement of CD166 in the activation of human gamma delta T cells by tumor cells sensitized with nonpeptide antigens . J. Immunol. . 177 . 2 . 877–84 . 2006 . 16818742 . 10.4049/jimmunol.177.2.877 . free .
• Ibáñez A, Sarrias MR, Farnós M, Gimferrer I, Serra-Pagès C, Vives J, Lozano F . Mitogen-activated protein kinase pathway activation by the CD6 lymphocyte surface receptor . J. Immunol. . 177 . 2 . 1152–9 . 2006 . 16818773 . 10.4049/jimmunol.177.2.1152 . free .
• Hassan NJ, Simmonds SJ, Clarkson NG, Hanrahan S, Puklavec MJ, Bomb M, Barclay AN, Brown MH . CD6 Regulates T-Cell Responses through Activation-Dependent Recruitment of the Positive Regulator SLP-76 . Mol. Cell. Biol. . 26 . 17 . 6727–38 . 2006 . 16914752 . 1592849 . 10.1128/MCB.00688-06 .
• Castro MA, Oliveira MI, Nunes RJ, Fabre S, Barbosa R, Peixoto A, Brown MH, Parnes JR, Bismuth G, Moreira A, Rocha B, Carmo AM . Extracellular isoforms of CD6 generated by alternative splicing regulate targeting of CD6 to the immunological synapse . J. Immunol. . 178 . 7 . 4351–61 . 2007 . 17371992 . 10.4049/jimmunol.178.7.4351 . free .
• Sarrias MR, Farnós M, Mota R, Sánchez-Barbero F, Ibáñez A, Gimferrer I, Vera J, Fenutría R, Casals C, Yélamos J, Lozano F . CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock . Proc. Natl. Acad. Sci. U.S.A. . 104 . 28 . 11724–9 . 2007 . 17601777 . 1913855 . 10.1073/pnas.0702815104 . 2007PNAS..10411724S . free .

Notes and References

1. Web site: Entrez Gene: CD6 CD6 molecule.
2. Bowen MA, Patel DD, Li X, Modrell B, Malacko AR, Wang WC, Marquardt H, Neubauer M, Pesando JM, Francke U . Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand . J. Exp. Med. . 181 . 6 . 2213–20 . 1995 . 7760007 . 2192054 . 10.1084/jem.181.6.2213.
3. De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, Baranzini SE, McCauley JL, Pericak-Vance MA, Haines JL, Gibson RA, Naeglin Y, Uitdehaag B, Matthews PM, Kappos L, Polman C, McArdle WL, Strachan DP, Evans D, Cross AH, Daly MJ, Compston A, Sawcer SJ, Weiner HL, Hauser SL, Hafler DA, Oksenberg JR . Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci . Nat. Genet. . 41 . 7 . 776–82 . 2009 . 19525953 . 2757648 . 10.1038/ng.401 .
4. Kofler DM, Severson CA, Mousissian N, De Jager PL, Hafler DA . The CD6 multiple sclerosis susceptibility allele is associated with alterations in CD4+ T cell proliferation . J. Immunol. . 187 . 6 . 3286–91 . 2011 . 21849685 . 10.4049/jimmunol.1100626 . free .