NCK2 Gene

HGNC Family	SH2 domain containing
Name	NCK adaptor protein 2
Description	This gene encodes a member of the NCK family of adaptor proteins. The protein contains three SH3 domains and one SH2 domain. The protein has no known catalytic function but has been shown to bind and recruit various proteins involved in the regulation of receptor protein tyrosine kinases. It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies have demonstrated that NCK2 functions as a critical adaptor linking cell surface receptors to intracellular signaling cascades that regulate cytoskeletal dynamics and cell motility. In particular, NCK2 (often referred to as Nck‐β) directly interacts with focal adhesion kinase to modulate adhesion and migration processes (for example, facilitating proper FAK complex formation in motile cells)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, during growth factor–stimulated responses, NCK2 contributes to PDGF‐BB–induced dermal fibroblast migration by channeling Rho signaling required for stress fiber formation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and it has been implicated in regulating synaptic transmission through its preferential association with PAK3 in neuronal contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, the architecture of human NCK2—comprising three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain—accounts for its essential role in signal transduction. High‐resolution structural studies have revealed that the NCK2 SH2 domain possesses a unique short C‐terminal antiparallel β‐sheet that facilitates specific recognition of phosphorylated ligands such as ephrinB peptides."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Moreover, complementary NMR and biophysical analyses have demonstrated that its SH3 domains can adopt dynamic conformations—including pH‐dependent monomer–dimer transitions and altered folding in insoluble mutants—underscoring the adaptability of NCK2 in mediating diverse protein–protein interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and clinical investigations further highlight the multifaceted role of NCK2 in human disease. Variants in the NCK2 gene have been associated with normal tension glaucoma, with studies reporting its expression in the retinal ganglion cell layer and links to altered intraocular phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " In addition, genome‐wide association approaches have identified a strong link between single nucleotide polymorphisms in NCK2 and susceptibility to opiate addiction in specific populations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these data underscore NCK2’s central role as a signaling integrator that connects extracellular cues to cytoskeletal remodeling and gene regulation, thereby impacting cell motility, neural function, and disease pathogenesis.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Silvia M Goicoechea, Yizeng Tu, Yun Hua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nck-2 interacts with focal adhesion kinase and modulates cell motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1357-2725(02)00002-x"}], "href": "https://doi.org/10.1016/s1357-2725(02"}, {"type": "t", "text": "00002-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11950595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11950595"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shengxi Guan, Jianhua Fan, Arum Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Non-compensating roles between Nckalpha and Nckbeta in PDGF-BB signaling to promote human dermal fibroblast migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2008.457"}], "href": "https://doi.org/10.1038/jid.2008.457"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19242519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19242519"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Emmanuel Thévenot, Alexandre William Moreau, Véronique Rousseau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.262246"}], "href": "https://doi.org/10.1074/jbc.M111.262246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21949127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21949127"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaoyuan Ran, Jianxing Song "}, {"type": "b", "children": [{"type": "t", "text": "Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500330200"}], "href": "https://doi.org/10.1074/jbc.M500330200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15764601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15764601"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Susanne Frese, Wolf-Dieter Schubert, Antje C Findeis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M512917200"}], "href": "https://doi.org/10.1074/jbc.M512917200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16636066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16636066"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jingxian Liu, Minfen Li, Xiaoyuan Ran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insight into the binding diversity between the human Nck2 SH3 domains and proline-rich proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi060091y"}], "href": "https://doi.org/10.1021/bi060091y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16752908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16752908"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jingxian Liu, Jianxing Song "}, {"type": "b", "children": [{"type": "t", "text": "Insights into protein aggregation by NMR characterization of insoluble SH3 mutants solubilized in salt-free water."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0007805"}], "href": "https://doi.org/10.1371/journal.pone.0007805"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19956763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19956763"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lydia Rossow, Iris Eke, Ellen Dickreuter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2015.4006"}], "href": "https://doi.org/10.3892/or.2015.4006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26004008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26004008"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "M Akiyama, K Yatsu, M Ota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Ophthalmol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/bjo.2008.139980"}], "href": "https://doi.org/10.1136/bjo.2008.139980"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18723748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18723748"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dong Shi, Tomoyo Funayama, Yukihiko Mashima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0054115"}], "href": "https://doi.org/10.1371/journal.pone.0054115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23349798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23349798"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Seung-Hyun Jung, Young Chun Lee, Mee Yon Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HK2 and NCK2 with normal-tension glaucoma in a population from the Republic of Korea."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Graefes Arch Clin Exp Ophthalmol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00417-019-04467-z"}], "href": "https://doi.org/10.1007/s00417-019-04467-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31512042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31512042"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Zhifa Liu, Xiaobo Guo, Yuan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NCK2 is significantly associated with opiates addiction in African-origin men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ScientificWorldJournal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2013/748979"}], "href": "https://doi.org/10.1155/2013/748979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23533358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23533358"}]}]}]}
Synonyms	GRB4, NCKBETA
Proteins	NCK2_HUMAN
NCBI Gene ID	8440
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NCK2 has 7,196 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for NCK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NCK2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NCK2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NCK2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NCK2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NCK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NCK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NCK2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NCK2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NCK2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NCK2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of NCK2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NCK2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NCK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NCK2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NCK2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NCK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NCK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NCK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NCK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NCK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NCK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NCK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NCK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NCK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NCK2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NCK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NCK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NCK2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NCK2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NCK2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NCK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NCK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NCK2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NCK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NCK2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing NCK2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NCK2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NCK2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NCK2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NCK2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing NCK2 from the GeneSigDB Published Gene Signatures dataset.