NCK2

NCK adaptor protein 2
PDB rendering based on 1u5s.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1U5S​, 1WX6​, 1Z3K​, 2B86​, 2CIA​, 2FRW​, 2FRY​, 2JXB​, 4E6R​
Identifiers
Symbols	NCK2 ; GRB4; NCKbeta
External IDs	OMIM: 604930 MGI: 1306821 HomoloGene: 20794 GeneCards: NCK2 Gene
Gene ontology Molecular function • SH3/SH2 adaptor activity • protein binding • cytoskeletal adaptor activity • receptor signaling complex scaffold activity • protein complex binding • scaffold protein binding Cellular component • cytoplasm • endoplasmic reticulum • cytosol • vesicle membrane • neuronal postsynaptic density Biological process • immunological synapse formation • actin filament organization • signal transduction • signal complex assembly • epidermal growth factor receptor signaling pathway • regulation of epidermal growth factor-activated receptor activity • axon guidance • negative regulation of cell proliferation • cell migration • lamellipodium assembly • positive regulation of actin filament polymerization • negative regulation of peptidyl-serine phosphorylation • positive regulation of translation in response to endoplasmic reticulum stress • positive regulation of T cell proliferation • T cell activation • positive regulation of transcription from RNA polymerase II promoter • vascular endothelial growth factor receptor signaling pathway • ephrin receptor signaling pathway • dendritic spine development • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • negative regulation of PERK-mediated unfolded protein response • negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation • negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8440	17974
Ensembl	ENSG00000071051	ENSMUSG00000066877
UniProt	O43639	O55033
RefSeq (mRNA)	NM_001004720	NM_010879
RefSeq (protein)	NP_001004720	NP_035009
Location (UCSC)	Chr 2: 105.74 – 105.89 Mb	Chr 1: 43.44 – 43.57 Mb
PubMed search

Cytoplasmic protein NCK2 (also known as NCK-beta and Grb4) is a protein that in humans is encoded by the NCK2 gene.^[1][2][3]

Function

NCK belongs to family of adaptor proteins,There are two mammalian NCK genes, NCK1 and NCK2. NCK1 is located in chromosome 3 and NCK2 is located in chromosome 2. 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.^[3]

Interactions

NCK2 has been shown to interact with:

• Epidermal growth factor receptor,^[1][4][5]
• LIMS1,^[6][4]
• PDGFRB,^[1][5][7]
• PTK2,^[8]
• T-cell surface glycoprotein CD3 epsilon chain^[9] and
• TrkB.^[10]

References

1. Chen M, She H, Davis EM, Spicer CM, Kim L, Ren R, Le Beau MM, Li W (Sep 1998). "Identification of Nck family genes, chromosomal localization, expression, and signaling specificity". The Journal of Biological Chemistry 273 (39): 25171–8. doi:10.1074/jbc.273.39.25171. PMID 9737977.
2. Liu J, Li M, Ran X, Fan JS, Song J (Jun 2006). "Structural insight into the binding diversity between the human Nck2 SH3 domains and proline-rich proteins". Biochemistry 45 (23): 7171–84. doi:10.1021/bi060091y. PMID 16752908.
3. "Entrez Gene: NCK2 NCK adaptor protein 2".
4. Tu Y, Li F, Wu C (Dec 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". Molecular Biology of the Cell 9 (12): 3367–82. doi:10.1091/mbc.9.12.3367. PMC 25640. PMID 9843575.
5. Braverman LE, Quilliam LA (Feb 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". The Journal of Biological Chemistry 274 (9): 5542–9. doi:10.1074/jbc.274.9.5542. PMID 10026169.
6. Tu Y, Li F, Goicoechea S, Wu C (Mar 1999). "The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells". Molecular and Cellular Biology 19 (3): 2425–34. doi:10.1128/mcb.19.3.2425. PMC 84035. PMID 10022929.
7. Chen M, She H, Kim A, Woodley DT, Li W (Nov 2000). "Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb". Molecular and Cellular Biology 20 (21): 7867–80. doi:10.1128/mcb.20.21.7867-7880.2000. PMC 86398. PMID 11027258.
8. Goicoechea SM, Tu Y, Hua Y, Chen K, Shen TL, Guan JL, Wu C (Jul 2002). "Nck-2 interacts with focal adhesion kinase and modulates cell motility". The International Journal of Biochemistry & Cell Biology 34 (7): 791–805. doi:10.1016/s1357-2725(02)00002-x. PMID 11950595.
9. Gil D, Schamel WW, Montoya M, Sánchez-Madrid F, Alarcón B (Jun 2002). "Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation". Cell 109 (7): 901–12. doi:10.1016/S0092-8674(02)00799-7. PMID 12110186.
10. Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S (Jun 2002). "Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor". Biochemical and Biophysical Research Communications 294 (5): 1087–92. doi:10.1016/S0006-291X(02)00606-X. PMID 12074588.

Further reading

• Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J (Dec 1992). "The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors". Molecular and Cellular Biology 12 (12): 5824–33. doi:10.1128/MCB.12.12.5824. PMC 360522. PMID 1333047.
• Tu Y, Li F, Wu C (Dec 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". Molecular Biology of the Cell 9 (12): 3367–82. doi:10.1091/mbc.9.12.3367. PMC 25640. PMID 9843575.
• Tu Y, Li F, Goicoechea S, Wu C (Mar 1999). "The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells". Molecular and Cellular Biology 19 (3): 2425–34. doi:10.1128/mcb.19.3.2425. PMC 84035. PMID 10022929.
• Braverman LE, Quilliam LA (Feb 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". The Journal of Biological Chemistry 274 (9): 5542–9. doi:10.1074/jbc.274.9.5542. PMID 10026169.
• Coutinho S, Jahn T, Lewitzky M, Feller S, Hutzler P, Peschel C, Duyster J (Jul 2000). "Characterization of Ggrb4, an adapter protein interacting with Bcr-Abl". Blood 96 (2): 618–24. PMID 10887126.
• Chen M, She H, Kim A, Woodley DT, Li W (Nov 2000). "Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb". Molecular and Cellular Biology 20 (21): 7867–80. doi:10.1128/MCB.20.21.7867-7880.2000. PMC 86398. PMID 11027258.
• Tu Y, Kucik DF, Wu C (Mar 2001). "Identification and kinetic analysis of the interaction between Nck-2 and DOCK180". FEBS Letters 491 (3): 193–9. doi:10.1016/S0014-5793(01)02195-0. PMID 11240126.
• Jahn T, Seipel P, Coutinho S, Miething C, Peschel C, Duyster J (Nov 2001). "Grb4/Nckbeta acts as a nuclear repressor of v-Abl-induced transcription from c-jun/c-fos promoter elements". The Journal of Biological Chemistry 276 (46): 43419–27. doi:10.1074/jbc.M107030200. PMID 11514578.
• Cowan CA, Henkemeyer M (Sep 2001). "The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals". Nature 413 (6852): 174–9. doi:10.1038/35093123. PMID 11557983.
• Goicoechea SM, Tu Y, Hua Y, Chen K, Shen TL, Guan JL, Wu C (Jul 2002). "Nck-2 interacts with focal adhesion kinase and modulates cell motility". The International Journal of Biochemistry & Cell Biology 34 (7): 791–805. doi:10.1016/S1357-2725(02)00002-X. PMID 11950595.
• Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S (Jun 2002). "Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor". Biochemical and Biophysical Research Communications 294 (5): 1087–92. doi:10.1016/S0006-291X(02)00606-X. PMID 12074588.
• Gil D, Schamel WW, Montoya M, Sánchez-Madrid F, Alarcón B (Jun 2002). "Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation". Cell 109 (7): 901–12. doi:10.1016/S0092-8674(02)00799-7. PMID 12110186.
• Song J, Vranken W, Xu P, Gingras R, Noyce RS, Yu Z, Shen SH, Ni F (Sep 2002). "Solution structure and backbone dynamics of the functional cytoplasmic subdomain of human ephrin B2, a cell-surface ligand with bidirectional signaling properties". Biochemistry 41 (36): 10942–9. doi:10.1021/bi025815u. PMID 12206665.
• Aspenström P (Sep 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". Experimental Cell Research 279 (1): 21–33. doi:10.1006/excr.2002.5576. PMID 12213210.
• Hafizi S, Alindri F, Karlsson R, Dahlbäck B (Dec 2002). "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin". Biochemical and Biophysical Research Communications 299 (5): 793–800. doi:10.1016/S0006-291X(02)02718-3. PMID 12470648.
• Velyvis A, Vaynberg J, Yang Y, Vinogradova O, Zhang Y, Wu C, Qin J (Jul 2003). "Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling". Nature Structural Biology 10 (7): 558–64. doi:10.1038/nsb938. PMID 12794636.
• Hu Y, Fang X, Dunham SM, Prada C, Stachowiak EK, Stachowiak MK (Jul 2004). "90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling". The Journal of Biological Chemistry 279 (28): 29325–35. doi:10.1074/jbc.M311144200. PMID 15117958.
• Ran X, Song J (May 2005). "Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain". The Journal of Biological Chemistry 280 (19): 19205–12. doi:10.1074/jbc.M500330200. PMID 15764601.
• Song J (Jul 2003). "Tyrosine phosphorylation of the well packed ephrinB cytoplasmic beta-hairpin for reverse signaling. Structural consequences and binding properties". The Journal of Biological Chemistry 278 (27): 24714–20. doi:10.1074/jbc.M210625200. PMID 12606549.
• Liu Z, Guo X, Jiang Y, Zhang H (2013). "NCK2 is significantly associated with opiates addiction in African-origin men". TheScientificWorldJournal 2013: 748979. doi:10.1155/2013/748979. PMID 23533358.

External links

• Nck2 Info with links in the Cell Migration Gateway