SH2 domain-containing protein 4A (SH2D4A)

SH2D4A is a ubiquitously expressed adapter protein defined by a single C-terminal SH2 (Src homology 2) domain highly homologous to signaling proteins TSAd and ALX. It is primarily cytoplasmic and involved in mediating protein-protein interactions important for signal transduction, especially in immune cells (T cells, B cells, macrophages, dendritic cells). SH2D4A modulates estrogen receptor (ESR1) signaling by inhibiting estrogen-induced cell proliferation, and acts as a tumor suppressor by interacting with the transcription factor STAT3 and mitochondrial prohibitins; loss of SH2D4A contributes to increased mitochondrial respiration and cancer progression. Despite structural similarity to key adapter proteins regulating TCR signaling, SH2D4A is dispensable for T cell development and function under normal conditions in both mice and humans. Chromosomal loss or deletion (chromosome 8p) is associated with several cancers, implicating SH2D4A as a potential tumor suppressor and therapeutic target.

Other names

SH2 domain-containing protein 4ASH2D4APPP1R38SH2AFLJ20967Protein SH(2)AProtein phosphatase 1 regulatory subunit 38

FL3: disrupts the interaction of SH2D4A with prohibitin and STAT3, modulates mitochondrial STAT3 signaling, counteracts increased mitochondrial respiration caused by SH2D4A loss SH2D4A blocks PLCG binding to ESR1 (estrogen receptor), repressing estrogen-induced transcriptional response