GRB2 (growth factor receptor bound protein 2)

Gene

• Entrez ID: 2885
• Gene name: Growth factor receptor bound protein 2
• Gene symbol: GRB2
• Synonyms: ASH, EGFRBP-GRB2, Grb3-3, MST084, MSTP084, NCKAP2
• Chromosome: 17
• Chromosome location: 17q25.1
• Summary: The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001201	hsa-miR-433-3p	Luciferase reporter assay, Western blot	19531230
MIRT007278	hsa-miR-378a-3p	Luciferase reporter assay	23447532
MIRT007278	hsa-miR-378a-3p	Luciferase reporter assay	23625957
MIRT022221	hsa-miR-124-3p	Microarray	18668037
MIRT025255	hsa-miR-34a-5p	Sequencing	20371350
MIRT025709	hsa-miR-7-5p	Sequencing	20371350
MIRT027965	hsa-miR-93-5p	Sequencing	20371350
MIRT031431	hsa-miR-16-5p	Proteomics	18668040
MIRT031431	hsa-miR-16-5p	PAR-CLIP	21572407
MIRT031431	hsa-miR-16-5p	PAR-CLIP	20371350
MIRT040690	hsa-miR-92b-3p	CLASH	23622248
MIRT048495	hsa-miR-100-5p	CLASH	23622248
MIRT053350	hsa-miR-376c-3p	Luciferase reporter assay, qRT-PCR, Western blot	23922722
MIRT437946	hsa-miR-27a-3p	ChIP-seq, qRT-PCR, Luciferase reporter assay, Western blot	24725595
MIRT438100	hsa-miR-200a-3p	Luciferase reporter assay	23874841
MIRT440533	hsa-miR-541-5p	HITS-CLIP	24374217
MIRT476076	hsa-miR-6834-5p	PAR-CLIP	23592263
MIRT476076	hsa-miR-6834-5p	PAR-CLIP	26701625
MIRT476077	hsa-miR-3915	PAR-CLIP	23592263
MIRT476077	hsa-miR-3915	PAR-CLIP	26701625
MIRT476078	hsa-miR-5196-5p	PAR-CLIP	23592263
MIRT476078	hsa-miR-5196-5p	PAR-CLIP	26701625
MIRT476079	hsa-miR-6787-5p	PAR-CLIP	23592263
MIRT476079	hsa-miR-6787-5p	PAR-CLIP	26701625
MIRT476080	hsa-miR-4747-5p	PAR-CLIP	23592263
MIRT476080	hsa-miR-4747-5p	PAR-CLIP	26701625
MIRT476081	hsa-miR-663a	PAR-CLIP	23592263
MIRT476081	hsa-miR-663a	PAR-CLIP	26701625
MIRT476082	hsa-miR-1908-5p	PAR-CLIP	23592263
MIRT476082	hsa-miR-1908-5p	PAR-CLIP	26701625
MIRT476083	hsa-miR-1255b-5p	PAR-CLIP	23592263
MIRT476084	hsa-miR-1255a	PAR-CLIP	23592263
MIRT476085	hsa-miR-6077	PAR-CLIP	23592263
MIRT476085	hsa-miR-6077	PAR-CLIP	26701625
MIRT476086	hsa-miR-4749-5p	PAR-CLIP	23592263
MIRT476086	hsa-miR-4749-5p	PAR-CLIP	26701625
MIRT476087	hsa-miR-4706	PAR-CLIP	23592263
MIRT476087	hsa-miR-4706	PAR-CLIP	26701625
MIRT476088	hsa-miR-6133	PAR-CLIP	23592263
MIRT476088	hsa-miR-6133	PAR-CLIP	26701625
MIRT476089	hsa-miR-6130	PAR-CLIP	23592263
MIRT476089	hsa-miR-6130	PAR-CLIP	26701625
MIRT476090	hsa-miR-6129	PAR-CLIP	23592263
MIRT476090	hsa-miR-6129	PAR-CLIP	26701625
MIRT476091	hsa-miR-6127	PAR-CLIP	23592263
MIRT476091	hsa-miR-6127	PAR-CLIP	26701625
MIRT476092	hsa-miR-4510	PAR-CLIP	23592263
MIRT476092	hsa-miR-4510	PAR-CLIP	26701625
MIRT476093	hsa-miR-6875-5p	PAR-CLIP	23592263
MIRT476093	hsa-miR-6875-5p	PAR-CLIP	26701625
MIRT476094	hsa-miR-4419a	PAR-CLIP	23592263
MIRT476094	hsa-miR-4419a	PAR-CLIP	26701625
MIRT476095	hsa-miR-3126-5p	PAR-CLIP	23592263
MIRT476095	hsa-miR-3126-5p	PAR-CLIP	26701625
MIRT476096	hsa-miR-3928-3p	PAR-CLIP	23592263
MIRT476096	hsa-miR-3928-3p	PAR-CLIP	26701625
MIRT476097	hsa-miR-9500	PAR-CLIP	23592263
MIRT476097	hsa-miR-9500	PAR-CLIP	26701625
MIRT476098	hsa-miR-6165	PAR-CLIP	23592263
MIRT476100	hsa-miR-5586-3p	PAR-CLIP	23592263
MIRT476100	hsa-miR-5586-3p	PAR-CLIP	26701625
MIRT502280	hsa-miR-3934-5p	PAR-CLIP	24398324
MIRT502280	hsa-miR-3934-5p	PAR-CLIP	21572407
MIRT502281	hsa-miR-7853-5p	PAR-CLIP	24398324
MIRT502281	hsa-miR-7853-5p	PAR-CLIP	21572407
MIRT502282	hsa-miR-105-5p	PAR-CLIP	24398324
MIRT502282	hsa-miR-105-5p	PAR-CLIP	21572407
MIRT502283	hsa-miR-522-3p	PAR-CLIP	24398324
MIRT502283	hsa-miR-522-3p	PAR-CLIP	21572407
MIRT502284	hsa-miR-224-3p	PAR-CLIP	24398324
MIRT502284	hsa-miR-224-3p	PAR-CLIP	21572407
MIRT548005	hsa-miR-2054	PAR-CLIP	21572407
MIRT548005	hsa-miR-2054	PAR-CLIP	20371350
MIRT548006	hsa-miR-6739-5p	PAR-CLIP	21572407
MIRT548006	hsa-miR-6739-5p	PAR-CLIP	20371350
MIRT548007	hsa-miR-6733-5p	PAR-CLIP	21572407
MIRT548007	hsa-miR-6733-5p	PAR-CLIP	20371350
MIRT548008	hsa-miR-3153	PAR-CLIP	21572407
MIRT548008	hsa-miR-3153	PAR-CLIP	20371350
MIRT548009	hsa-miR-6081	PAR-CLIP	21572407
MIRT548009	hsa-miR-6081	PAR-CLIP	20371350
MIRT548010	hsa-miR-6783-5p	PAR-CLIP	21572407
MIRT548011	hsa-miR-4779	PAR-CLIP	21572407
MIRT548012	hsa-miR-4519	PAR-CLIP	21572407
MIRT548012	hsa-miR-4519	PAR-CLIP	20371350
MIRT548013	hsa-miR-6838-5p	PAR-CLIP	21572407
MIRT548013	hsa-miR-6838-5p	PAR-CLIP	20371350
MIRT548014	hsa-miR-497-5p	PAR-CLIP	21572407
MIRT548014	hsa-miR-497-5p	PAR-CLIP	20371350
MIRT548015	hsa-miR-424-5p	PAR-CLIP	21572407
MIRT548015	hsa-miR-424-5p	PAR-CLIP	20371350
MIRT548016	hsa-miR-195-5p	PAR-CLIP	21572407
MIRT548016	hsa-miR-195-5p	PAR-CLIP	20371350
MIRT548017	hsa-miR-15b-5p	PAR-CLIP	21572407
MIRT548017	hsa-miR-15b-5p	PAR-CLIP	20371350
MIRT548018	hsa-miR-15a-5p	PAR-CLIP	21572407
MIRT548018	hsa-miR-15a-5p	PAR-CLIP	20371350
MIRT548019	hsa-miR-6891-5p	PAR-CLIP	21572407
MIRT548020	hsa-miR-3173-3p	PAR-CLIP	21572407
MIRT548021	hsa-miR-583	PAR-CLIP	21572407
MIRT548021	hsa-miR-583	PAR-CLIP	20371350
MIRT548022	hsa-miR-4282	PAR-CLIP	21572407
MIRT548022	hsa-miR-4282	PAR-CLIP	20371350
MIRT562257	hsa-miR-548x-3p	PAR-CLIP	20371350
MIRT562258	hsa-miR-548j-3p	PAR-CLIP	20371350
MIRT562259	hsa-miR-548aq-3p	PAR-CLIP	20371350
MIRT562260	hsa-miR-548am-3p	PAR-CLIP	20371350
MIRT562261	hsa-miR-548aj-3p	PAR-CLIP	20371350
MIRT562262	hsa-miR-548ah-3p	PAR-CLIP	20371350
MIRT562263	hsa-miR-548ae-3p	PAR-CLIP	20371350
MIRT562264	hsa-miR-548z	PAR-CLIP	20371350
MIRT562265	hsa-miR-548h-3p	PAR-CLIP	20371350
MIRT562266	hsa-miR-548d-3p	PAR-CLIP	20371350
MIRT562267	hsa-miR-548bb-3p	PAR-CLIP	20371350
MIRT562268	hsa-miR-548ac	PAR-CLIP	20371350
MIRT731549	hsa-miR-329-3p	Luciferase reporter assay	26885689
MIRT732351	hsa-miR-411-5p	Luciferase reporter assay, qRT-PCR, Western blot	27264952
MIRT733604	hsa-miR-96-3p	Luciferase reporter assay	26782545
MIRT736985	hsa-miR-1281	PAR-CLIP	26701625
MIRT738295	hsa-miR-18a-3p	PAR-CLIP	26701625
MIRT738488	hsa-miR-1913	PAR-CLIP	26701625
MIRT739074	hsa-miR-221-5p	PAR-CLIP	26701625
MIRT739093	hsa-miR-22-3p	PAR-CLIP	26701625
MIRT739955	hsa-miR-3120-3p	PAR-CLIP	26701625
MIRT740432	hsa-miR-3155a	PAR-CLIP	26701625
MIRT740443	hsa-miR-3155b	PAR-CLIP	26701625
MIRT741049	hsa-miR-3194-3p	PAR-CLIP	26701625
MIRT741230	hsa-miR-324-3p	PAR-CLIP	26701625
MIRT744502	hsa-miR-4438	PAR-CLIP	26701625
MIRT746255	hsa-miR-4632-3p	PAR-CLIP	26701625
MIRT749047	hsa-miR-484	PAR-CLIP	26701625
MIRT750085	hsa-miR-5197-3p	PAR-CLIP	26701625
MIRT750452	hsa-miR-545-3p	PAR-CLIP	26701625
MIRT751045	hsa-miR-558	PAR-CLIP	26701625
MIRT753537	hsa-miR-660-3p	PAR-CLIP	26701625
MIRT756034	hsa-miR-6791-3p	PAR-CLIP	26701625
MIRT757088	hsa-miR-6829-3p	PAR-CLIP	26701625
MIRT759451	hsa-miR-760	PAR-CLIP	26701625
MIRT760122	hsa-miR-8073	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0001784	Function	Phosphotyrosine residue binding	IPI	20624904
GO:0003723	Function	RNA binding	HDA	22658674
GO:0005154	Function	Epidermal growth factor receptor binding	IPI	12577067
GO:0005168	Function	Neurotrophin TRKA receptor binding	IPI	15488758
GO:0005515	Function	Protein binding	IPI	7504175, 7518560, 7518772, 7522233, 7523381, 7527391, 7537265, 7597091, 7629138, 7773779, 7929073, 8112292, 8491186, 8663178, 8798570, 8816475, 8887653, 8892607, 8939605, 8940013, 8955135, 8959326, 8995379, 9020117, 9045636, 9148935, 9174058, 9175774, 9178760, 9178913, 9254595, 9346925
GO:0005634	Component	Nucleus	IDA	21179510
GO:0005654	Component	Nucleoplasm	IDA
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IDA	21179510
GO:0005768	Component	Endosome	IDA	21179510
GO:0005794	Component	Golgi apparatus	IEA
GO:0005829	Component	Cytosol	TAS	14722116
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	IMP	8253073
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	TAS	1322798
GO:0007265	Process	Ras protein signal transduction	TAS	8253073
GO:0007411	Process	Axon guidance	TAS
GO:0007568	Process	Aging	IEA
GO:0008180	Component	COP9 signalosome	IDA	22561606
GO:0008286	Process	Insulin receptor signaling pathway	IPI	8388384
GO:0008286	Process	Insulin receptor signaling pathway	TAS
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	TAS
GO:0012506	Component	Vesicle membrane	IEA
GO:0016032	Process	Viral process	IEA
GO:0017124	Function	SH3 domain binding	IDA	19509291
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019901	Function	Protein kinase binding	IPI	20086093
GO:0019903	Function	Protein phosphatase binding	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	IEA
GO:0030838	Process	Positive regulation of actin filament polymerization	IEA
GO:0031295	Process	T cell costimulation	TAS
GO:0031532	Process	Actin cytoskeleton reorganization	IMP	8253073
GO:0031623	Process	Receptor internalization	IMP	14985334
GO:0035635	Process	Entry of bacterium into host cell	TAS
GO:0035723	Process	Interleukin-15-mediated signaling pathway	TAS
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0038128	Process	ERBB2 signaling pathway	TAS
GO:0042059	Process	Negative regulation of epidermal growth factor receptor signaling pathway	TAS
GO:0042770	Process	Signal transduction in response to DNA damage	IMP	20160708
GO:0042802	Function	Identical protein binding	IPI	12577067, 22536782, 22726438
GO:0043408	Process	Regulation of MAPK cascade	IEA
GO:0043560	Function	Insulin receptor substrate binding	IPI	8388384
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0046579	Process	Positive regulation of Ras protein signal transduction	TAS
GO:0046875	Function	Ephrin receptor binding	IPI	12925710
GO:0048011	Process	Neurotrophin TRK receptor signaling pathway	TAS
GO:0048646	Process	Anatomical structure formation involved in morphogenesis	IEA
GO:0050900	Process	Leukocyte migration	TAS
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0060670	Process	Branching involved in labyrinthine layer morphogenesis	IEA
GO:0061024	Process	Membrane organization	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337, 23533145
GO:0070436	Component	Grb2-EGFR complex	IDA	20086093
GO:0071479	Process	Cellular response to ionizing radiation	IMP	20160708
GO:2000379	Process	Positive regulation of reactive oxygen species metabolic process	IMP	20160708

Other IDs

• MIM: 108355
• HGNC: 4566
• e!Ensembl: ENSG00000177885

Protein

• UniProt ID: P62993
• Protein name: Growth factor receptor-bound protein 2 (Adapter protein GRB2) (Protein Ash) (SH2/SH3 adapter GRB2)
• Protein function: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. ; [Isoform 2]: Does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.
• PDB: 1AZE, 1BM2, 1BMB, 1CJ1, 1FHS, 1FYR, 1GCQ, 1GFC, 1GFD, 1GHU, 1GRI, 1IO6, 1JYQ, 1JYR, 1JYU, 1QG1, 1TZE, 1X0N, 1ZFP, 2AOA, 2AOB, 2H46, 2H5K, 2HUW, 2VVK, 2VWF, 2W0Z, 3C7I, 3IMD, 3IMJ, 3IN7, 3IN8, 3KFJ, 3MXC, 3MXY, 3N7Y, 3N84, 3N8M, 3OV1, 3OVE, 3S8L, 3S8N, 3S8O, 3WA4, 4P9V, 4P9Z, 5CDW, 6ICG, 6ICH, 6SDF, 6VK2
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00018	SH3_1	4 → 50	SH3 domain	Domain
  PF00017	SH2	60 → 135	SH2 domain	Domain
  PF00018	SH3_1	162 → 207	SH3 domain	Domain

• Sequence:

  MEAIAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIEMKPHPW
  FFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFL
  WVVKFNSLNELVDYHRSTSVSRNQQIFLRDIEQVPQQPTYVQALFDFDPQEDGELGFRRG
  DFIHVMDNSDPNWWKGACHGQTGMFPRNYVTPVNRNV

• Sequence length: 217