The X-ray Crystallographic Structure of Human EAT2 (SH2D1B)

Abstract

Ewing's Sarcoma transcript-2 (EAT2) also known as SH2D1B is involved in regulation of signalling lymphocytic activation molecule (SLAM) family receptor functions. Cytoplasmic tails of SLAM family receptors contain tyrosine residues which mediate the downstream signal transduction through their phosphorylation. EAT2, composed of a single SH2 domain and a short C-terminal tail, binds to the phosphotyrosine residues and regulates SLAM family receptor signalling. We have determined the crystal structure of the human EAT2 protein in an unliganded form. Compared with the mouse EAT2-peptide complex structure, we observe conformational differences in the loops involved in ligand binding. When compared with SAP, the other single SH2 domain protein in human, EAT2 shows similar binding energies to unphosphorylated ligands. This is inconsistent to the previous data showing low affinity of EAT2 toward unphosphorylated peptides compared to SAP which shows high affinity. Additional factors other than the SH2 domains may contribute to the reported differences.

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“…Furthermore, a previous study ranked CST1 as the number 1 differentially expressed mRNA in AR during an investigation aiming to construct an AR‐specific transcriptional regulatory network . The involvement of SH2D1B, also known as Ewing's sarcoma transcript‐2, has been implicated in the modulation of signaling the lymphocytic activation molecule family receptor function . SH2D1B, is predominantly expressed in the innate immune cells, such as the macrophages and dendritic cells, whose upregulation has been speculated to help modulate the kinetics of a series of vital proinflammatory cytokine and chemokine responses .…”

“…9 The involvement of SH2D1B, also known as Ewing's sarcoma transcript-2, has been implicated in the modulation of signaling the lymphocytic activation molecule family receptor function. 24 SH2D1B, is predominantly expressed in the innate immune cells, such as the macrophages and dendritic cells, whose upregulation has been speculated to help modulate the kinetics of a series of vital proinflammatory cytokine and chemokine responses. 25 DPP4, also referred to CD26, is a type II transmembrane protein that exhibits enhanced levels in an extensive range of metabolic diseases involving diabetes, cardiovascular diseases, and obesity, as well as nonalcoholic fatty liver diseases.…”