Property Summary

NCBI Gene PubMed Count 64
PubMed Score 34.79
PubTator Score 32.74

Knowledge Summary


No data available


  Disease (3)


  Differential Expression (4)

Disease log2 FC p
osteosarcoma -1.020 5.4e-03
glioblastoma 1.100 1.1e-03
Breast cancer 2.800 2.4e-02
ovarian cancer 1.200 2.9e-03

 GWAS Trait (1)

Gene RIF (26)

27033705 Nck1 and Nck2 Interact with WTIP. Nck1/2 integrates nephrin with the Hippo kinase cascade through association with the adaptor protein WTIP.
26004008 Data suggest that PINCH1 and Nck2 critically participate in the regulation of cellular radiosensitivity and EGFR function and downstream signaling in a cellular model of human squamous cell carcinoma.
25482634 Tir-Intimin interaction recruits the Nck adaptor to a Tir tyrosine phosphorylated residue where it activates neural Wiskott-Aldrich syndrome protein (N-WASP).
24287595 Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics.
24162774 HIV-1 gp120 downregulates the expression of NCK adaptor protein 2 (NCK2) in human B cells
23533358 NCK2 is involved in the susceptibility to opiates addiction.
23524290 The hNck2 SH3 domain also exhibited pH dependent monomer-dimer transition.
23349798 Data show that both HK2 and NCK2 are expressed in the retinal ganglion cell layer.
21992144 Nck2 effectively influences human melanoma phenotype progression.
21949127 p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor.
21880263 Nck2 is an adaptor protein composed of 3N-SH3 domains followed by a unique Cterminal SH2 domain. It interacts with PINCH in integrin signal transduction, cell migratio and survival. Review.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
19956763 biophysical analysis of Nck2 SH3 domain
19242519 independent roles and mechanisms of action of Nckalpha and Nckbeta in dermal fibroblast migration, which is critical for wound healing.
18723748 Results point to NCK2 as a disease candidate gene and further supports the GLC1B locus as an important genomic region that is associated with the genetic predisposition to glaucoma.
18555270 Data show that Nck forms a complex with an atypical PxxDY motif of the CD3epsilon tail, which encompasses Tyr166 within the activation motif and a T-cell receptor endocytosis signal.
17906149 the adaptors Nck and ShcA influenced adherence of S. Typhimurium to non-phagocytic cells.
17803907 Demonstrate connection between septins/SOCS7/NCK signaling and the DNA damage response.
16835242 Data show that Nck (isoforms 1 and 2) as a component of the CReP/PP1c holophosphatase complex contributes to maintain eIF2alpha in a hypophosphorylated state, and modulates translation and eIF2alpha signaling in response to ER stress.
16752908 determined the NMR structures and dynamic properties of the hNck2 SH3 domains and to define their ligand binding preferences with nine proline-rich peptides derived from Wire, CAP-1, CAP-2, Prk, Wrch1, Wrch2, and Nogo
16636066 Nck1 (Nckalpha) and Nck2 (Nckbeta and Grb4): binding specificities of both SH2 domains are essentially indistinguishable
16604428 Molecular model of the first SRC homology 3 domain of Nck2.
15764601 analysis of binding between the Tyr-phosphorylated human ephrinB2 and Nck2 SH2 domain
12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation.
11950595 Nck-2 interacts with focal adhesion kinase and modulates cell motility. Using a mutational strategy, the formation of the Nck-2-FAK complex is mediated by interactions involving multiple SH2 and SH3 domains of Nck-2.

AA Sequence

TMDELVEHYKKAPIFTSEHGEKLYLVRALQ                                            351 - 380

Text Mined References (71)

PMID Year Title
27033705 2016 Nephrin Suppresses Hippo Signaling through the Adaptor Proteins Nck and WTIP.
26871637 2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
26004008 2015 Targeting of the EGFR/?1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures.
25814554 2015 Phospho-tyrosine dependent protein-protein interaction network.
25482634 2014 Nck adaptors, besides promoting N-WASP mediated actin-nucleation activity at pedestals, influence the cellular levels of enteropathogenic Escherichia coli Tir effector.
25468996 2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
25416956 2014 A proteome-scale map of the human interactome network.
24728074 2014 Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome.
24287595 2013 Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics.
24058526 2013 Genome-wide meta-analysis of systolic blood pressure in children with sickle cell disease.
23533358 2013 NCK2 is significantly associated with opiates addiction in African-origin men.
23524290 Structural study of hNck2 SH3 domain protein in solution by circular dichroism and X-ray solution scattering.
23455922 2013 Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS.
23349798 2013 Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22223895 2012 Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-?-acetylation features.
22074159 2012 Improved two-dimensional reversed phase-reversed phase LC-MS/MS approach for identification of peptide-protein interactions.
21992144 2011 Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo.
21949127 2011 p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor.
21880263 [A uNick protein].
21516116 2011 Next-generation sequencing to generate interactome datasets.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
19956763 2009 Insights into protein aggregation by NMR characterization of insoluble SH3 mutants solubilized in salt-free water.
19807924 2009 Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19242519 2009 Non-compensating roles between Nckalpha and Nckbeta in PDGF-BB signaling to promote human dermal fibroblast migration.
18723748 2008 Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma.
18555270 2008 Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity.
18539162 2008 Distinct interactions between ubiquitin and the SH3 domains involved in immune signaling.
18088087 2008 Phosphoproteome of resting human platelets.
18086875 2008 The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine kinases Pyk2 and Src in regulating cytoskeletal dynamics.
17906149 2007 Src homology domain 2 adaptors affect adherence of Salmonella enterica serovar Typhimurium to non-phagocytic cells.
17803907 2007 Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7.
16835242 2006 Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress.
16752908 2006 Structural insight into the binding diversity between the human Nck2 SH3 domains and proline-rich proteins.
16636066 2006 The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains.
16604428 2006 Solution structure of the first SRC homology 3 domain of human Nck2.
16525419 2006 Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes.
16337946 2006 Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1.
16273093 2006 A quantitative protein interaction network for the ErbB receptors using protein microarrays.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15900300 2005 Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays.
15764601 2005 Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain.
15721255 2005 Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15350535 2004 Wrch1 is a GTPase-deficient Cdc42-like protein with unusual binding characteristics and cellular effects.
15096211 2004 Single phosphorylation of Tyr304 in the cytoplasmic tail of ephrin B2 confers high-affinity and bifunctional binding to both the SH2 domain of Grb4 and the PDZ domain of the PDZ-RGS3 protein.
12794636 2003 Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling.
12606549 2003 Tyrosine phosphorylation of the well packed ephrinB cytoplasmic beta-hairpin for reverse signaling. Structural consequences and binding properties.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12470648 2002 Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin.
12213210 2002 The WASP-binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor.
12206665 2002 Solution structure and backbone dynamics of the functional cytoplasmic subdomain of human ephrin B2, a cell-surface ligand with bidirectional signaling properties.
12110186 2002 Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation.
12074588 2002 Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor.
11950595 2002 Nck-2 interacts with focal adhesion kinase and modulates cell motility.
11557983 2001 The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals.
11514578 2001 Grb4/Nckbeta acts as a nuclear repressor of v-Abl-induced transcription from c-jun/c-fos promoter elements.
11240126 2001 Identification and kinetic analysis of the interaction between Nck-2 and DOCK180.
11027258 2000 Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb.
10887126 2000 Characterization of Ggrb4, an adapter protein interacting with Bcr-Abl.
10574708 1999 Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats.
10330411 1999 Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling.
10026169 1999 Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck.
10022929 1999 The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells.
9843575 1998 Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways.
9737977 1998 Identification of Nck family genes, chromosomal localization, expression, and signaling specificity.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
1333047 1992 The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors.