| Structural highlights
Function
[SLAF5_HUMAN] Plays a role as adhesion receptor functioning by homophilic interactions and by clustering. Recruits SH2 domain-containing proteins SH2D1A/SAP. Increases proliferative responses of activated T-cells and SH2D1A/SAP does not seen be required for this process. Homophilic interactions enhance interferon gamma/IFNG secretion in lymphocytes and induce platelet stimulation via a SH2D1A/SAP-dependent pathway. May serve as a marker for hematopoietic progenitor cells.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The signaling lymphocyte activation molecule (SLAM) family includes homophilic and heterophilic receptors that modulate both adaptive and innate immune responses. These receptors share a common ectodomain organization: a membrane-proximal immunoglobulin constant domain and a membrane-distal immunoglobulin variable domain that is responsible for ligand recognition. CD84 is a homophilic family member that enhances IFN-gamma secretion in activated T cells. Our solution studies revealed that CD84 strongly self-associates with a K(d) in the submicromolar range. These data, in combination with previous reports, demonstrate that the SLAM family homophilic affinities span at least three orders of magnitude and suggest that differences in the affinities may contribute to the distinct signaling behavior exhibited by the individual family members. The 2.0 A crystal structure of the human CD84 immunoglobulin variable domain revealed an orthogonal homophilic dimer with high similarity to the recently reported homophilic dimer of the SLAM family member NTB-A. Structural and chemical differences in the homophilic interfaces provide a mechanism to prevent the formation of undesired heterodimers among the SLAM family homophilic receptors. These structural data also suggest that, like NTB-A, all SLAM family homophilic dimers adopt a highly kinked organization spanning an end-to-end distance of approximately 140 A. This common molecular dimension provides an opportunity for all two-domain SLAM family receptors to colocalize within the immunological synapse and bridge the T cell and antigen-presenting cell.
Structure of CD84 provides insight into SLAM family function.,Yan Q, Malashkevich VN, Fedorov A, Fedorov E, Cao E, Lary JW, Cole JL, Nathenson SG, Almo SC Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10583-8. Epub 2007 Jun 11. PMID:17563375[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Martin M, Romero X, de la Fuente MA, Tovar V, Zapater N, Esplugues E, Pizcueta P, Bosch J, Engel P. CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1. J Immunol. 2001 Oct 1;167(7):3668-76. PMID:11564780
- ↑ Tangye SG, van de Weerdt BC, Avery DT, Hodgkin PD. CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2. Eur J Immunol. 2002 Jun;32(6):1640-9. PMID:12115647 doi:<1640::AID-IMMU1640>3.0.CO;2-S http://dx.doi.org/10.1002/1521-4141(200206)32:6<1640::AID-IMMU1640>3.0.CO;2-S
- ↑ Tangye SG, Nichols KE, Hare NJ, van de Weerdt BC. Functional requirements for interactions between CD84 and Src homology 2 domain-containing proteins and their contribution to human T cell activation. J Immunol. 2003 Sep 1;171(5):2485-95. PMID:12928397
- ↑ Zaiss M, Hirtreiter C, Rehli M, Rehm A, Kunz-Schughart LA, Andreesen R, Hennemann B. CD84 expression on human hematopoietic progenitor cells. Exp Hematol. 2003 Sep;31(9):798-805. PMID:12962726
- ↑ Nanda N, Andre P, Bao M, Clauser K, Deguzman F, Howie D, Conley PB, Terhorst C, Phillips DR. Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling. Blood. 2005 Nov 1;106(9):3028-34. Epub 2005 Jul 21. PMID:16037392 doi:http://dx.doi.org/10.1182/blood-2005-01-0333
- ↑ Yan Q, Malashkevich VN, Fedorov A, Fedorov E, Cao E, Lary JW, Cole JL, Nathenson SG, Almo SC. Structure of CD84 provides insight into SLAM family function. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10583-8. Epub 2007 Jun 11. PMID:17563375
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