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Symbol GRB2 contributors: mct - updated : 23-02-2015
HGNC name growth factor receptor-bound protein 2
HGNC id 4566
Location 17q25.1      Physical location : 73.314.157 - 73.401.790
Synonym name
  • abundant SRC homology
  • epidermal growth factor receptor-binding protein GRB2
  • growth factor receptor-bound protein 3
  • adapter protein GRB2
  • Synonym symbol(s) ASH, EGFRBP-GRB2, Grb3-3, MST084, MSTP084, HT027
    TYPE functioning gene
    STRUCTURE 87.63 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    DKFZP564C103 17q25.2 DKFZP564C103 protein FLJ20255 17q25.2 hypothetical protein FLJ20255 GRIN2C 17q25 glutamate receptor, ionotropic, N-methyl D-aspartate 2C FDXR 17q24-q25 ferredoxin reductase LOC283985 17q25.2 similar to delta 5 fatty acid desaturase USH1G 17q25.2 Usher syndrome 1G (autosomal recessive) OTOP2 17q25.2 otopetrin 2 OTOP3 17q25.2 otopetrin 3 C17orf28 17q25.1 chromosome 17 open reading frame 28 HUMPPA 17q25.2 paraneoplastic antigen ICT1 17q25.2 immature colon carcinoma transcript 1 ATP5H 12q13 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d LOC390814 17 similar to Hypothetical protein KIAA0176 SLC16A5 17q25.3 solute carrier family 16 (monocarboxylic acid transporters), member 5 FLJ22160 17q25.2 hypothetical protein FLJ22160 NT5C 17q25.3 5', 3'-nucleotidase, cytosolic HN1 17q25.2 hematological and neurological expressed 1 SMT3H2 17q25.3 SMT3 suppressor of mif two 3 homolog 2 (yeast) PCNT1 17q25 pericentrin 1 GGA3 17q25.3 golgi associated, gamma adaptin ear containing, ARF binding protein 3 MRPS7 17q23-25 mitochondrial ribosomal protein S7 AD023 17q25.2 AD023 protein SLC25A19 17q25.3 solute carrier family 25 (mitochondrial deoxynucleotide carrier), member 19 GRB2 17q24.3-q25 growth factor receptor-bound protein 2 KIAA0195 17q25.3 growth factor receptor-bound protein 2 CASKIN2 17q25.3 CASK interacting protein 2 LOC283989 17q25.3 hypothetical protein LOC283989 LLGL2 17q24-q25 lethal giant larvae homolog 2 (Drosophila) MYO15B 17q25 myosin XVB, pseudogene LOC390815 17 similar to Myosin XV (Unconventional myosin-15) RECQL5 17q25 RecQ protein-like 5 HCNGP 17q25.3 transcriptional regulator protein ITGB4 17q24.3 integrin, beta 4 GALK1 17q24 galactokinase 1 H3F3B 17q25 H3 histone, family 3B (H3.3B) KIAA1753 17q25.3 KIAA1753 protein UNC13D 17q25.3 unc-13 homolog D (C. elegans) WBP2 17q25 WW domain binding protein 2
    TRANSCRIPTS type messenger
    text several transcripts resulting from alternative splicing
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 3303 - 217 - 2008 18789888
    deletion in the SH2 domain
    5 - 3181 - 176 - 2008 18789888
    dominant negative over GRB2 triggering apoptosis
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
    Nervousbrain   highly
    cell lineage
    cell lines
    at STAGE
  • one SH2 binding PGDFRs, EGFR, IRS1, SHC1 (one central SH2 domain flanked by two SH3 domains), SH2 domain having the potential to be used as a binding component of a probe to detect activated-RTK and to evaluate the effect of kinase inhibitors on RTK activation
  • two SH3 domains binding SOS (signal transduction), C-SH3 domain binds to a proline-rich sequence at the very C terminus of FGFR2 prior to growth factor stimulation
  • one K homology (KH) motif bound to a QUA2 motif (RNA binding), lacking a catalytic domain
    interspecies homolog to C.elegans Sem5 gene
    homolog to Drosophila Drk
  • GRB2/sem-5/DRK family
  • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • linking the insulin receptor to Ras signaling pathway through the formation of a complex with SOS1
  • mitogenic RAS signaling through interaction with SHC1
  • may act as an adaptor protein to simultaneously regulate both cell surface localization and reverse signaling of FASLG in Schwann cells
  • major mediator in Ras-MAPK activation induced by numerous receptors because of its association with son of sevenless, a GDP-GTP exchange factor for Ras
  • adaptor molecule that mediates Ras-MAPK activation induced by various receptors
  • plays a pivotal role in both thymic positive and negative selection and amplifies TCR signaling at the top end of the tyrosine phosphorylation cascade via a scaffolding function
  • nonredundant regulator that controls lymphoid follicle organization and germinal center reaction (executes this function by connecting the CXCR5 signaling pathway to lymphotoxin expression but not to chemotaxis)
  • involved in the regulation of CD22 tyrosine phosphorylation, suggesting that it may control BCR signaling by integrating the CD22-SHP-1 negative-feedback loop in B cells
  • GRB2-mediated signaling is critical for lymphotoxin expression in naive B cells
  • plays an important role in B cells via integrating various signaling transduction pathways of the BCR and CXCR5
  • RASGRP1 and GRB2/SOS1 are insulators of signals that lead to RAS activation induced by different stimuli, rather than cooperating downstream of the TCRA
  • GRB2 is strongly implicated in controlling FGFR2 kinase activity prior to growth factor stimulation
  • exerts constitutive control over the mutually dependent activities of FGFR2 and PTPN11
  • SOS1 and its adaptor GRB2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the Ras-Erk pathway during development and drive embryonic stem cells toward the primitive endoderm (PrE) lineage
  • GRB2 is a negative regulator of myogenesis and reduces myogenic differentiation by inhibiting actin polymerization/remodeling through its C-terminal SH3 domain
    signaling signal transduction
    a component
  • major component of CBL associated protein
  • GRB2/GAB2/SHC1/LRRK1 signal integrator complex is functionally involved in the balance of cellular stress responses
  • DOK3/GRB2 modulates the balance between activatory and inhibitory LYN functions with the aim to adjust BCR signaling efficiency
    small molecule
  • GRB2/SOS1 binding to activated tyrosine-phosphorylated
  • EGFR and PDGFR and other cellular tyrosine phosphorylated proteins receptors to signaling for mitogenesis and cytoskeletal reorganization
  • IRS1 and SHC1 in the INSR to RAS signaling pathway
  • binding to GRF2
  • DISC1-interacting molecule
  • binds to the proline-rich domain of FASLG and regulates its cell surface expression (acting as an adaptor for FASLG to interact with adaptin beta, a molecule known to regulate trafficking)
  • interacting with CLEC17A
  • phosphorylating PRKAB1 at Thr172
  • interaction with both LY6G6F and GRB7 is mediated through its Src homology 2 domains and is dependent on the phosphorylation of LY6G6F
  • interaction of PTPN23 with two adapters of the GRB2 family, essential for numerous signaling pathways, suggesting that PTPN23 might be important for signaling through a plethora of receptors
  • interaction with LRRK1
  • interacting with CXCR5 (specifically controls a branch of CXCR5 signaling in B cells that induces lymphotoxin beta transcription but not chemotaxis)
  • interaction with RHOU (GRB2 couples RHOU to epidermal growth factor receptor signaling and cell migration)
  • ASAP3 regulates ITGB1 dynamics during EGF-stimulated cell migration by interaction with GRB2
  • GRB2 mediates the interaction of TNK2 with EGFR through binding to the EBD and activates TNK2 by releasing the auto-inhibition
  • role for GRB2 as an active regulator of RTK signaling
  • ATXN2 modulates the levels of GRB2 and SRC but not ras signaling
  • controls FGFR2 signaling by regulating receptor kinase and PTPN11 phosphatase activity in the absence of extracellular stimulation
  • scaffold function of SOS1 depended on its ability to bind to the adaptor protein GRB2
  • GRB2 is a new PTK2 activator awith an essential role in coordinating PTPRA tyrosine phosphorylation to enable downstream integrin signaling and migration
  • upon T cell activation, LAT is phosphorylated and associates with GRB2, GRAP2, and PLCG1 through its four distal tyrosine residues
  • GRB2 N-terminal and C-terminal SH3 domains bind to proline rich proteins such as WASL
  • cell & other
    Phosphorylated by FGFR2 (upon stimulation, FGFR2 phosphorylates tyrosine residues on GRB2, promoting dissociation from the receptor and allowing full activation of downstream signaling)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    Variant & Polymorphism
    Candidate gene
    Therapy target