1i3z

Structural highlights

Function

SH21B_MOUSE Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244. In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4. However, conflicting results are reported which may reflect the use of different strain backgrounds. Proposed to act as an inhibitor of CD244-mediated NK cell function including cytotoxicity and IFN-gamma production, the latter found also by triggering KLRA4 and KLRK1 next to CD244 (PubMed:16127454). Seems to positively regulate CD244- and CD84-dependent NK cell functions implicating CD244-mediated phosphorylation of VAV1. Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (PubMed:19151721, PubMed:20962259, PubMed:24687958). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (PubMed:26432891).[UniProtKB:O14796]^{[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.

References

1. ↑ Roncagalli R, Taylor JE, Zhang S, Shi X, Chen R, Cruz-Munoz ME, Yin L, Latour S, Veillette A. Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor. Nat Immunol. 2005 Oct;6(10):1002-10. PMID:16127454 doi:10.1038/ni1242
2. ↑ Cruz-Munoz ME, Dong Z, Shi X, Zhang S, Veillette A. Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function. Nat Immunol. 2009 Mar;10(3):297-305. PMID:19151721 doi:10.1038/ni.1693
3. ↑ Wang N, Calpe S, Westcott J, Castro W, Ma C, Engel P, Schatzle JD, Terhorst C. Cutting edge: The adapters EAT-2A and -2B are positive regulators of CD244 CD84-dependent NK cell functions in the C57BL/6 mouse. J Immunol. 2010 Nov 15;185(10):5683-7. PMID:20962259 doi:10.4049/jimmunol.1001974
4. ↑ Perez-Quintero LA, Roncagalli R, Guo H, Latour S, Davidson D, Veillette A. EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase Cgamma, Ca++, and Erk, leading to granule polarization. J Exp Med. 2014 Apr 7;211(4):727-42. doi: 10.1084/jem.20132038. Epub 2014 Mar 31. PMID:24687958 doi:http://dx.doi.org/10.1084/jem.20132038
5. ↑ Talaei N, Yu T, Manion K, Bremner R, Wither JE. Identification of the SLAM Adapter Molecule EAT-2 as a Lupus-Susceptibility Gene That Acts through Impaired Negative Regulation of Dendritic Cell Signaling. J Immunol. 2015 Nov 15;195(10):4623-31. PMID:26432891 doi:10.4049/jimmunol.1500552