NCK1

Domain

Only the first and third SH3 domains seem to be involved in RASA1-binding; the second SH3 domain and the SH2 domains do not seem to be involved.

Function

Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors.

Post-translational modifications

Phosphorylated on Ser and Tyr residues. Phosphorylated in response to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB.

Cellular localization

• Cytoplasm
• Endoplasmic reticulum
• Nucleus
• Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus. Import into the nucleus requires the interaction with SOCS7. Predominantly nuclear following genotoxic stresses, such as UV irradiation, hydroxyurea or mitomycin C treatments.

Alternative names

NCK, NCK1, SH2/SH3 adapter protein NCK1, Cytoplasmic protein NCK1, NCK adapter protein 1, SH2/SH3 adapter protein NCK-alpha, Nck-1

Database links

swissprot:P16333 omim:604930 entrezGene:4690 entrezGene:8440 swissprot:O43639 omim:600508