SH2D1A

This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SH2D1A

Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2. Initially it has been proposed that association with SLAMF1 prevents SLAMF1 binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2 (PubMed:11806999).
However, by simultaneous interactions, recruits FYN which subsequently phosphorylates and activates SLAMF1 (PubMed:12458214).
Positively regulates CD244/2B4- and CD84-mediated natural killer (NK) cell functions. Can also promote CD48-, SLAMF6 -, LY9-, and SLAMF7-mediated NK cell activation. In the context of NK cell-mediated cytotoxicity enhances conjugate formation with target cells (By similarity).
May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.

Biological Process adaptive immune responseIEA:UniProtKB-KW
Biological Process cell-cell signalingIEA:InterPro
Biological Process cellular defense responseIEA:InterPro
Biological Process humoral immune responseIEA:Ensembl
Biological Process natural killer cell mediated cytotoxicityIEA:Ensembl
Biological Process negative regulation of T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of natural killer cell mediated cytotoxicityManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of signal transductionManual Assertion Based On ExperimentIBA:GO_Central

Cytoplasm

Lymphoproliferative syndrome, X-linked, 1 (XLP1):
A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.