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Showing Protein Growth factor receptor-bound protein 2 (HMDBP11487)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 4 metabolites
Identification
HMDB Protein ID HMDBP11487
Secondary Accession Numbers
  • 17838
Name Growth factor receptor-bound protein 2
Synonyms
  1. Adapter protein GRB2
  2. Protein Ash
  3. SH2/SH3 adapter GRB2
Gene Name GRB2
Protein Type Unknown
Biological Properties
General Function Involved in protein binding
Specific Function Isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death
Pathways
  • Bafetinib Inhibition of BCR-ABL
  • BCR-ABL Action in CML Pathogenesis
  • Bosutinib Inhibition of BCR-ABL
  • Dasatinib Inhibition of BCR-ABL
  • Fc Epsilon Receptor I Signaling in Mast Cells
  • Imatinib Inhibition of BCR-ABL
  • Insulin Signalling
  • Nilotinib Inhibition of BCR-ABL
  • Ponatinib Inhibition of BCR-ABL
Reactions Not Available
GO Classification
Function
binding
protein binding
Cellular Location
  1. Golgi apparatus
Gene Properties
Chromosome Location Chromosome:1
Locus 17q24-q25
SNPs GRB2
Gene Sequence 
>654 bp
ATGGAAGCCATCGCCAAATATGACTTCAAAGCTACTGCAGACGACGAGCTGAGCTTCAAA
AGGGGGGACATCCTCAAGGTTTTGAACGAAGAATGTGATCAGAACTGGTACAAGGCAGAG
CTTAATGGAAAAGACGGCTTCATTCCCAAGAACTACATAGAAATGAAACCACATCCGTGG
TTTTTTGGCAAAATCCCCAGAGCCAAGGCAGAAGAAATGCTTAGCAAACAGCGGCACGAT
GGGGCCTTTCTTATCCGAGAGAGTGAGAGCGCTCCTGGGGACTTCTCCCTCTCTGTCAAG
TTTGGAAACGATGTGCAGCACTTCAAGGTGCTCCGAGATGGAGCCGGGAAGTACTTCCTC
TGGGTGGTGAAGTTCAATTCTTTGAATGAGCTGGTGGATTATCACAGATCTACATCTGTC
TCCAGAAACCAGCAGATATTCCTGCGGGACATAGAACAGGTGCCACAGCAGCCGACATAC
GTCCAGGCCCTCTTTGACTTTGATCCCCAGGAGGATGGAGAGCTGGGCTTCCGCCGGGGA
GATTTTATCCATGTCATGGATAACTCAGACCCCAACTGGTGGAAAGGAGCTTGCCACGGG
CAGACCGGCATGTTTCCCCGCAATTATGTCACCCCCGTGAACCGGAACGTCTAA
Protein Properties
Number of Residues 217
Molecular Weight 25206.2
Theoretical pI 6.25
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Growth factor receptor-bound protein 2
MEAIAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIEMKPHPW
FFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFL
WVVKFNSLNELVDYHRSTSVSRNQQIFLRDIEQVPQQPTYVQALFDFDPQEDGELGFRRG
DFIHVMDNSDPNWWKGACHGQTGMFPRNYVTPVNRNV
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P62993
UniProtKB/Swiss-Prot Entry Name GRB2_HUMAN
PDB IDs
GenBank Gene ID M96995
GeneCard ID GRB2
GenAtlas ID GRB2
HGNC ID HGNC:4566
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  5. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 1998 Jan 9;92(1):83-92. [PubMed:9489702 ]
  6. Korkaya H, Jameel S, Gupta D, Tyagi S, Kumar R, Zafrullah M, Mazumdar M, Lal SK, Xiaofang L, Sehgal D, Das SR, Sahal D: The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK. J Biol Chem. 2001 Nov 9;276(45):42389-400. Epub 2001 Aug 22. [PubMed:11518702 ]
  7. Rebhun JF, Chen H, Quilliam LA: Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral. J Biol Chem. 2000 May 5;275(18):13406-10. [PubMed:10747847 ]
  8. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE: Insulin receptor substrate 4 associates with the protein IRAS. J Biol Chem. 2002 May 31;277(22):19439-47. Epub 2002 Mar 23. [PubMed:11912194 ]
  9. Zhong JL, Poghosyan Z, Pennington CJ, Scott X, Handsley MM, Warn A, Gavrilovic J, Honert K, Kruger A, Span PN, Sweep FC, Edwards DR: Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma. Mol Cancer Res. 2008 Mar;6(3):383-94. doi: 10.1158/1541-7786.MCR-07-2028. Epub 2008 Feb 22. [PubMed:18296648 ]
  10. Wheeler M, Domin J: Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2. Mol Cell Biol. 2001 Oct;21(19):6660-7. [PubMed:11533253 ]
  11. Pfrepper KI, Marie-Cardine A, Simeoni L, Kuramitsu Y, Leo A, Spicka J, Hilgert I, Scherer J, Schraven B: Structural and functional dissection of the cytoplasmic domain of the transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor protein). Eur J Immunol. 2001 Jun;31(6):1825-36. [PubMed:11433379 ]
  12. Schiering N, Casale E, Caccia P, Giordano P, Battistini C: Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex. Biochemistry. 2000 Nov 7;39(44):13376-82. [PubMed:11063574 ]
  13. Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE: Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells. J Biol Chem. 1998 Apr 24;273(17):10726-32. [PubMed:9553137 ]
  14. Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S: cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999 Mar 11;18(10):1855-66. [PubMed:10086340 ]
  15. Zhu M, Janssen E, Leung K, Zhang W: Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. J Biol Chem. 2002 Nov 29;277(48):46151-8. Epub 2002 Sep 30. [PubMed:12359715 ]
  16. Pandey P, Kharbanda S, Kufe D: Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein. Cancer Res. 1995 Sep 15;55(18):4000-3. [PubMed:7664271 ]
  17. Ikeda M, Ishida O, Hinoi T, Kishida S, Kikuchi A: Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral. J Biol Chem. 1998 Jan 9;273(2):814-21. [PubMed:9422736 ]
  18. Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens LS, Majerus PW, Williams LT: Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2. Curr Biol. 1996 Apr 1;6(4):438-45. [PubMed:8723348 ]
  19. Odai H, Sasaki K, Iwamatsu A, Nakamoto T, Ueno H, Yamagata T, Mitani K, Yazaki Y, Hirai H: Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl. Blood. 1997 Apr 15;89(8):2745-56. [PubMed:9108392 ]
  20. Upshaw JL, Arneson LN, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ: NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nat Immunol. 2006 May;7(5):524-32. Epub 2006 Apr 2. [PubMed:16582911 ]
  21. Brdicka T, Imrich M, Angelisova P, Brdickova N, Horvath O, Spicka J, Hilgert I, Luskova P, Draber P, Novak P, Engels N, Wienands J, Simeoni L, Osterreicher J, Aguado E, Malissen M, Schraven B, Horejsi V: Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling. J Exp Med. 2002 Dec 16;196(12):1617-26. [PubMed:12486104 ]
  22. Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu YC: Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. Oncogene. 1999 Feb 4;18(5):1147-56. [PubMed:10022120 ]
  23. Asazuma N, Wilde JI, Berlanga O, Leduc M, Leo A, Schweighoffer E, Tybulewicz V, Bon C, Liu SK, McGlade CJ, Schraven B, Watson SP: Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin. J Biol Chem. 2000 Oct 27;275(43):33427-34. [PubMed:10942756 ]
  24. Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A: A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature. 1997 Mar 13;386(6621):181-6. [PubMed:9062191 ]
  25. Gil-Henn H, Volohonsky G, Toledano-Katchalski H, Gandre S, Elson A: Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control. Oncogene. 2000 Sep 7;19(38):4375-84. [PubMed:10980613 ]
  26. Tan SL, Nakao H, He Y, Vijaysri S, Neddermann P, Jacobs BL, Mayer BJ, Katze MG: NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5533-8. [PubMed:10318918 ]
  27. Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J: The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. [PubMed:1322798 ]
  28. Matuoka K, Shibata M, Yamakawa A, Takenawa T: Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9015-9. [PubMed:1384039 ]
  29. Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B: Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. [PubMed:8178156 ]
  30. Bochmann H, Gehrisch S, Jaross W: The gene structure of the human growth factor bound protein GRB2. Genomics. 1999 Mar 1;56(2):203-7. [PubMed:10051406 ]
  31. Tobe K, Matuoka K, Tamemoto H, Ueki K, Kaburagi Y, Asai S, Noguchi T, Matsuda M, Tanaka S, Hattori S, et al.: Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. J Biol Chem. 1993 May 25;268(15):11167-71. [PubMed:8388384 ]
  32. Skolnik EY, Lee CH, Batzer A, Vicentini LM, Zhou M, Daly R, Myers MJ Jr, Backer JM, Ullrich A, White MF, et al.: The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J. 1993 May;12(5):1929-36. [PubMed:8491186 ]
  33. Yokouchi M, Suzuki R, Masuhara M, Komiya S, Inoue A, Yoshimura A: Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation. Oncogene. 1997 Jul 3;15(1):7-15. [PubMed:9233773 ]
  34. Welsh M, Songyang Z, Frantz JD, Trub T, Reedquist KA, Karlsson T, Miyazaki M, Cantley LC, Band H, Shoelson SE: Stimulation through the T cell receptor leads to interactions between SHB and several signaling proteins. Oncogene. 1998 Feb 19;16(7):891-901. [PubMed:9484780 ]
  35. Wu L, Yu Z, Shen SH: SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation. J Biol Chem. 2002 Oct 25;277(43):40420-7. Epub 2002 Aug 8. [PubMed:12171928 ]
  36. Janssen E, Zhu M, Zhang W, Koonpaew S, Zhang W: LAB: a new membrane-associated adaptor molecule in B cell activation. Nat Immunol. 2003 Feb;4(2):117-23. Epub 2003 Jan 6. [PubMed:12514734 ]
  37. Liu Y, Zhang W: Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells. J Leukoc Biol. 2008 Sep;84(3):842-51. doi: 10.1189/jlb.0208087. Epub 2008 Jun 17. [PubMed:18559951 ]
  38. Zhou R, Niwa S, Homma N, Takei Y, Hirokawa N: KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development. Cell. 2009 Nov 13;139(4):802-13. doi: 10.1016/j.cell.2009.10.023. [PubMed:19914172 ]
  39. Thornton KH, Mueller WT, McConnell P, Zhu G, Saltiel AR, Thanabal V: Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain. Biochemistry. 1996 Sep 10;35(36):11852-64. [PubMed:8794768 ]
  40. Kohda D, Terasawa H, Ichikawa S, Ogura K, Hatanaka H, Mandiyan V, Ullrich A, Schlessinger J, Inagaki F: Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. Structure. 1994 Nov 15;2(11):1029-40. [PubMed:7881903 ]
  41. Maignan S, Guilloteau JP, Fromage N, Arnoux B, Becquart J, Ducruix A: Crystal structure of the mammalian Grb2 adaptor. Science. 1995 Apr 14;268(5208):291-3. [PubMed:7716522 ]
  42. Rahuel J, Garcia-Echeverria C, Furet P, Strauss A, Caravatti G, Fretz H, Schoepfer J, Gay B: Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide ligands. J Mol Biol. 1998 Jun 19;279(4):1013-22. [PubMed:9642078 ]
  43. Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW: Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1). J Med Chem. 1999 Mar 25;42(6):971-80. [PubMed:10090780 ]
  44. Furet P, Garcia-Echeverria C, Gay B, Schoepfer J, Zeller M, Rahuel J: Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic. J Med Chem. 1999 Jul 1;42(13):2358-63. [PubMed:10395476 ]
  45. Nioche P, Liu WQ, Broutin I, Charbonnier F, Latreille MT, Vidal M, Roques B, Garbay C, Ducruix A: Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor. J Mol Biol. 2002 Feb 1;315(5):1167-77. [PubMed:11827484 ]
  46. Harkiolaki M, Tsirka T, Lewitzky M, Simister PC, Joshi D, Bird LE, Jones EY, O'Reilly N, Feller SM: Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. Structure. 2009 Jun 10;17(6):809-22. doi: 10.1016/j.str.2009.03.017. [PubMed:19523899 ]