SH2D1A

SH₂ domain-containing protein 1A (SH2D1A / SAP) is a 128 amino acid protein, containing a single Src homology 2 (SH₂) domain, flanked by 5 amino acids at the N-terminus and 25 amino acids at the C-terminus. The absence of a catalytic domain and the presence of an SH₂ domain suggest that SH2D1A regulates one or more signal transduction pathways. SH2D1A interacts with signaling lymphocytic activation molecule (SLAM), which is a transmembrane protein expressed on the surface of activated T and B cells. SH2D1A (SAP) interacts via its SH₂ domain with a motif (TIYXXV) present in the cytoplasmic tail of the cell-surface receptors, including CD150 / SLAM, CD84, CD229 / Ly-9, and CD244 / 2B4. SH2D1A was expressed in EBV-carrying, tumor phenotype representative (type I), but not in EBV-carrying lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt lymphoma (BL) lines. It has been supposed to be related to the X-linked lymphoproliferative disease which is also known as Duncan's disease or Purtilo syndrome.

SH2D1A Alternative Names

RP5-1052M9.3, DSHP, EBVS, FLJ18687, FLJ92177, IMD5, LYP, MTCP1 [Homo sapiens]

RP23-280E8.1, Gm686, SAP [Mus musculus]

Summaries for SH2D1A

Entrez Gene summary for SH2D1A:

SH2D1A 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 SH2D1A 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 SH2D1A gene. [provided by RefSeq, Jul 2008]

Wikipedia summary for SH2D1A:

SH2 domain-containing protein 1A is a protein that in humans is encoded by the SH2D1A gene.
It is associated with X-linked lymphoproliferative disease.

Human SH2D1A Protein General Information

 

• Protein names: SH2 domain-containing protein 1A
  Short name=SH2D1A
• Sequence length: 128 AA.
• Domain: SH2 domain
• Sequence similarities: Contains 1 SH2 domain.
• Subunit structure: Interacts with NTRK1, NTRK2 and NTRK3 . Interacts with CD84, CD244, LY9, SLAMF1 and FYN.
• Subcellular location: Cytoplasm
• Tissue specificity: Expressed at a high level in thymus and lung, with a lower level of expression in spleen and liver.
• Involvement in disease: Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) ; also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease. XLP is 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.

General information above from UniProt

Function for SH2D1A Protein

UniProtKB:

SH2D1A is inhibitor of the SLAM self-association. SH2D1A acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. SH2D1A mediates interaction between FYN and SLAMF1. SH2D1A may also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.

Genatlas:

• SH2D1A is putative regulator of the signal transduction pathways initiated by interactions between the SLAM molecules at the interface between T and B cells
• SH2D1A sustains the immune response by blocking inhibitory signal A mediated by INPP5D
• SH2D1A compels for binding of phosphotyrosine to FCgammaRIIB (FCGR2B)
• SH2D1A may be involved in regulation of B-cell differentiation via switching of SLAMF1-mediated signaling pathways
• SH2D1A is required for the recruitment of ARHGEF6, ARHGEF7 to the SLAM-family receptors
• SH2D1A may serving as a negative regulator of TRK receptor activation and downstream signaling
• SH2D1A acts as an intracellular adaptor protein by recruiting the protein tyrosine kinase FYN to the cytoplasmic domains of some of these receptors, which results in the initiation of specific downstream signal transduction pathways
• SH2D1A may play an important role in balancing positive versus negative immune responses (Li 2008)
• SH2D1A plays a role in the development of innate-like T cell lineages including natural killer T cells and in the regulation of interactions between B cells and T cells that are required for germinal center formation and long-term humoral immunity (Schwartzberg 2009)
• SH2D1A plays a novel role in B cells and extends its function to inhibitory immunoreceptor signaling and calcium mobilization (Ostrakhovitch 2009)
• SH2D1A regulates T cell proliferation through the MAP-kinase Erk (Li 2009)
• SH2D1A is intracellular adaptor molecule expressed in T cells, natural killer (NK) cells, and some B cells (Li 2008)

Homology for human SH2D1A

• homolog to murine Sh2d1a
• homolog to C.elegans Y51H7BR.5
• homolog to INPP5D

Phenotype Information for SH2D1A

• Gene/Locus: SH2D1A, LYP, IMD5, XLP, XLPD
• Phenotype: Lymphoproliferative syndrome, X-linked

Phenotype Information for SH2D1A from OMIM (Online Mendelian Inheritance in Man)