SHC-transforming protein 4 (SH2 domain protein C4, Src homology 2 domain-containing-transforming protein C4, Rai-like protein, RaLP, hShcD, SHC4)

Function

• contributes to the early phases of agrin-induced Tyr phosphorylation of CHRNB1
• interacts (via PID domain) with phosphorylated MUSK (via NPXY motif); undergoes Tyr phosphorylation downstream of activated MUSK
• interacts with GRB2, interaction
  • dependent on Tyr-424
  • increased by EGF
• phosphorylation is enhanced by EGF
• phosphorylation at Tyr-424 is required for the interaction with GRB2

Structure

• contains 1 PID domain
• contains 1 SH2 domain

Compartment

• cell junction, synapse, postsynaptic cell membrane
• colocalized with MUSK at the neuromuscular junction

Alternative splicing

named isoforms=2

Expression

• weakly expressed in normal melanocytes & benign nevi

Pathology

• expressed in melanomas
• highly expressed at the transition from radial growth phase to vertical growth phase & metastatic melanomas, when tumor cells acquire migratory competence & invasive potential
• activates both Ras-dependent & Ras-independent migratory pathways in melanomas

More general terms

• phosphoprotein

Database

• UniProt: http://www.uniprot.org/uniprot/Q6S5L8.html