SH2/SH3 adapter protein NCK1

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.

Classification

Family (Pfam)

PF00017 SH2, PF00018 SH3_1

InterPro

NCK, Nck1_SH2, Nck1_SH3_1, Nck1_SH3_2, Nck1_SH3_3, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyrosine-phos_adapter

Functional cluster

Protein Serine/Threonine Kinases

Experimental structures · PDB · 15

• 2CI8 X-ray 1.80A
• 2CI9 X-ray 1.50A
• 2CUB NMR
• 2JS0 NMR
• 2JS2 NMR
• 2JW4 NMR
• 5QU1 X-ray 1.08A
• 5QU2 X-ray 1.04A
• 5QU3 X-ray 1.02A
• 5QU4 X-ray 1.05A
• 5QU5 X-ray 1.11A
• 5QU6 X-ray 1.82A
• … and 3 more

A predicted model is available from AlphaFold.

Gene Ontology · 40

• GO:0005911 cell-cell junction
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005783 endoplasmic reticulum
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0000164 protein phosphatase type 1 complex
• GO:0005840 ribosome
• GO:0012506 vesicle membrane
• GO:0045296 cadherin binding
• GO:0008093 cytoskeletal anchor activity
• GO:0046875 ephrin receptor binding
• GO:0071074 eukaryotic initiation factor eIF2 binding
• GO:0140693 molecular condensate scaffold activity
• GO:0019904 protein domain specific binding
• GO:0004860 protein kinase inhibitor activity
• GO:0140311 protein sequestering activity
• GO:0030674 protein-macromolecule adaptor activity
• GO:0030971 receptor tyrosine kinase binding
• GO:0035591 signaling adaptor activity
• GO:0005102 signaling receptor binding
• GO:0030159 signaling receptor complex adaptor activity
• GO:0140374 antiviral innate immune response
• GO:0016477 cell migration
• GO:0048013 ephrin receptor signaling pathway
• GO:0046627 negative regulation of insulin receptor signaling pathway
• GO:1903898 negative regulation of PERK-mediated unfolded protein response
• GO:0050860 negative regulation of T cell receptor signaling pathway
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0030838 positive regulation of actin filament polymerization
• GO:1903676 positive regulation of cap-dependent translational initiation
• GO:1903679 positive regulation of cap-independent translational initiation
• GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
• GO:0042102 positive regulation of T cell proliferation
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0036493 positive regulation of translation in response to endoplasmic reticulum stress
• GO:0036491 regulation of translation initiation in response to endoplasmic reticulum stress
• GO:0034976 response to endoplasmic reticulum stress
• GO:0007172 signal complex assembly
• GO:0042110 T cell activation

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• SH2/SH3 adapter protein Nck1 1.00
• Cytoplasmic protein NCK2 0.96
• Cytoplasmic protein NCK2 0.94
• Growth factor receptor-bound protein 2-A 0.82
• Growth factor receptor-bound protein 2-B 0.82
• Growth factor receptor-bound protein 2 0.81
• Crk-like protein 0.81
• Protein E(sev)2B 0.81
• Growth factor receptor-bound protein 2 0.81
• Crk-like protein 0.81
• Adapter molecule crk 0.81
• Crk-like protein 0.81

Co-cited proteins · studied together in the literature

• Ras GTPase-activating protein 1 3 shared papers
• Nck-associated protein 5 1 shared papers
• Misshapen-like kinase 1 1 shared papers
• Caveolin-2 2 shared papers
• Suppressor of cytokine signaling 7 2 shared papers
• Caveolin-2 1 shared papers
• Tyrosine-protein kinase SYK 1 shared papers
• Insulin receptor substrate 1 1 shared papers
• Receptor-type tyrosine-protein phosphatase F 1 shared papers
• Ephrin type-B receptor 1 1 shared papers
• Ephrin type-B receptor 1 1 shared papers
• Ras-specific guanine nucleotide-releasing factor RalGPS1 1 shared papers

Literature · 37 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Receptor protein tyrosine phosphatase-receptor tyrosine kinase substrate screen identifies EphA2 as a target for LAR in cell migration. Mol. Cell. Biol. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
• Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling. Biochem. J. · 2011
• Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and regulates its activity. Cell. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. · 2009
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Nck-1 interacts with PKR and modulates its activation by dsRNA. Biochem. Biophys. Res. Commun. · 2008
• … and 25 more in the literature graph