SRC Gene: Function, Mutations, and Role in Cancer | Biomedical Database

The SRC gene encodes a membrane-associated non-receptor tyrosine kinase that is a member of the Src family kinases (SFKs). It is a critical node in multiple signaling pathways, including those initiated by growth factor receptors, integrins, and G-protein-coupled receptors. SRC regulates diverse cellular processes such as proliferation, differentiation, survival, adhesion, and motility. Aberrant activation of SRC, through mutation or overexpression, is frequently observed in various human cancers and is associated with tumor progression, invasion, and metastasis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• ErbB signaling pathway

• Focal adhesion

• VEGF signaling pathway

• T cell receptor signaling pathway

• B cell receptor signaling pathway

• Regulation of actin cytoskeleton

• Pathways in cancer

The SRC protein (c-Src) is a 60 kDa non-receptor tyrosine kinase that is anchored to the inner leaflet of the plasma membrane via myristoylation. It contains an N-terminal SH4 domain, a unique domain, an SH3 domain, an SH2 domain, a catalytic kinase domain (SH1), and a C-terminal regulatory tail. In its inactive state, the protein is held in a closed conformation by intramolecular interactions: the SH2 domain binds to a phosphorylated tyrosine (Tyr530) in the C-terminal tail, and the SH3 domain binds to a proline-rich region in the SH2-kinase linker. Activation occurs when these interactions are disrupted, either by dephosphorylation of Tyr530 or by binding of high-affinity ligands to the SH2 or SH3 domains. This leads to an open, active conformation, allowing autophosphorylation at Tyr419 and subsequent phosphorylation of downstream substrates. SRC is a master regulator of signaling cascades that control cell growth, differentiation, survival, and motility.