SLP76

Domain

The SH2 domain mediates interaction with phosphorylated CD6 (PubMed:16914752). The SH2 domain mediates interaction with SHB (PubMed:12084069).

Possesses an N-terminal acidic domain containing three tyrosine phosphorylation motifs, a central proline-rich region, and a C-terminal SH2 domain.

Function

Adapter protein primarily involved in signaling pathways within T-cells, as well as other immune cells such as platelets, mast cells, and natural killer (NK) cells (PubMed:11313406, PubMed:33159816). Plays a crucial role for transducing signal from the T-cell receptor (TCR) after antigen recognition leading to T-cell activation. Mechanistically, once phosphorylated by the kinase ZAP70, mediates interactions with the guanine-nucleotide exchange factor VAV1, the adapter protein NCK and the kinase ITK (PubMed:8673706, PubMed:8702662). In turn, stimulates the activation of PKC-theta/PRKCQ and NF-kappa-B transcriptional activity in response to CD3 and CD28 costimulation (PubMed:11313406). Plays also an essential role in AGER-induced signaling pathways including p38 MAPK and ERK1/2 activation leading to cytokine release and pro-inflammatory responses (PubMed:33436632).

Involvement in disease

Immunodeficiency 81

IMD81

An autosomal recessive disorder characterized by recurrent infections, including fungal infections, associated with T cell, neutrophil, and NK cell dysfunction. B cells may also show maturation abnormalities. Other features include autoimmune hemolytic anemia and abnormal platelet aggregation.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated after T-cell receptor activation by ZAP70, ITK and TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2. SYK-dependent phosphorylation is required for recruitment of PI3K signaling components.

Tissue specificity

Highly expressed in spleen, thymus and peripheral blood leukocytes. Highly expressed also in T-cell and monocytic cell lines, expressed at lower level in B-cell lines. Not detected in fibroblast or neuroblastoma cell lines.

Cellular localization

• Cytoplasm

Alternative names

• Lymphocyte cytosolic protein 2
• SH2 domain-containing leukocyte protein of 76 kDa
• SLP-76 tyrosine phosphoprotein
• SLP76
• LCP2

Database links

• entrezGene:3937
• omim:601603
• swissprot:Q13094

Target type

Proteins

Primary research area

Immuno-oncology

Molecular weight

60188Da