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P62993

- GRB2_HUMAN

UniProt

P62993 - GRB2_HUMAN

Protein

Growth factor receptor-bound protein 2

Gene

GRB2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 1 (31 Aug 2004)
      Previous versions | rss
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    Functioni

    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. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.

    GO - Molecular functioni

    1. ephrin receptor binding Source: UniProtKB
    2. epidermal growth factor receptor binding Source: UniProtKB
    3. identical protein binding Source: IntAct
    4. insulin receptor substrate binding Source: UniProtKB
    5. neurotrophin TRKA receptor binding Source: UniProtKB
    6. poly(A) RNA binding Source: UniProtKB
    7. protein binding Source: UniProtKB
    8. protein kinase binding Source: BHF-UCL
    9. SH3/SH2 adaptor activity Source: UniProtKB
    10. SH3 domain binding Source: UniProtKB

    GO - Biological processi

    1. aging Source: Ensembl
    2. anatomical structure formation involved in morphogenesis Source: Ensembl
    3. axon guidance Source: Reactome
    4. blood coagulation Source: Reactome
    5. branching involved in labyrinthine layer morphogenesis Source: Ensembl
    6. cell-cell signaling Source: UniProtKB
    7. cellular response to ionizing radiation Source: BHF-UCL
    8. epidermal growth factor receptor signaling pathway Source: UniProtKB
    9. Fc-epsilon receptor signaling pathway Source: Reactome
    10. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
    11. fibroblast growth factor receptor signaling pathway Source: Reactome
    12. innate immune response Source: Reactome
    13. insulin receptor signaling pathway Source: UniProtKB
    14. leukocyte migration Source: Reactome
    15. negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
    16. neurotrophin TRK receptor signaling pathway Source: Reactome
    17. phosphatidylinositol-mediated signaling Source: Reactome
    18. platelet activation Source: Reactome
    19. positive regulation of actin filament polymerization Source: Ensembl
    20. positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
    21. positive regulation of signal transduction Source: GOC
    22. protein heterooligomerization Source: Ensembl
    23. Ras protein signal transduction Source: UniProtKB
    24. receptor internalization Source: BHF-UCL
    25. regulation of MAPK cascade Source: Ensembl
    26. signal transduction in response to DNA damage Source: BHF-UCL
    27. T cell costimulation Source: Reactome
    28. viral process Source: UniProtKB-KW

    Keywords - Biological processi

    Host-virus interaction

    Enzyme and pathway databases

    ReactomeiREACT_111040. Signaling by SCF-KIT.
    REACT_111080. Spry regulation of FGF signaling.
    REACT_111184. Negative regulation of FGFR signaling.
    REACT_111225. Regulation of KIT signaling.
    REACT_115852. Signaling by constitutively active EGFR.
    REACT_115854. GRB2 events in ERBB2 signaling.
    REACT_115993. SHC1 events in ERBB2 signaling.
    REACT_116005. SHC1 events in ERBB4 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_12033. Signalling to RAS.
    REACT_121096. EGFR Transactivation by Gastrin.
    REACT_121141. Signaling by FGFR1 fusion mutants.
    REACT_121398. Signaling by FGFR mutants.
    REACT_12484. EGFR downregulation.
    REACT_12578. GAB1 signalosome.
    REACT_12579. SHC1 events in EGFR signaling.
    REACT_12606. GRB2 events in EGFR signaling.
    REACT_12621. Tie2 Signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147814. DAP12 signaling.
    REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
    REACT_163701. FCERI mediated MAPK activation.
    REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_163834. FCERI mediated Ca+2 mobilization.
    REACT_17025. Downstream signal transduction.
    REACT_18334. NCAM signaling for neurite out-growth.
    REACT_19238. CD28 dependent Vav1 pathway.
    REACT_19344. Costimulation by the CD28 family.
    REACT_21247. FRS2-mediated cascade.
    REACT_21270. PI-3K cascade.
    REACT_21374. SHC-mediated cascade.
    REACT_23787. Regulation of signaling by CBL.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_23916. Signal regulatory protein (SIRP) family interactions.
    REACT_508. Signal attenuation.
    REACT_524. SOS-mediated signalling.
    REACT_661. SHC-mediated signalling.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_976. PI3K Cascade.
    SignaLinkiP62993.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Growth factor receptor-bound protein 2
    Alternative name(s):
    Adapter protein GRB2
    Protein Ash
    SH2/SH3 adapter GRB2
    Gene namesi
    Name:GRB2
    Synonyms:ASH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:4566. GRB2.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication. Endosome 1 Publication. Golgi apparatus By similarity

    GO - Cellular componenti

    1. COP9 signalosome Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: HGNC
    4. endosome Source: UniProtKB
    5. extracellular vesicular exosome Source: UniProt
    6. Golgi apparatus Source: UniProtKB-SubCell
    7. Grb2-EGFR complex Source: BHF-UCL
    8. nucleus Source: UniProtKB
    9. plasma membrane Source: Reactome
    10. vesicle membrane Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Endosome, Golgi apparatus, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi49 – 491P → L: Ineffective in DNA synthesis. Abolishes interaction with SHB; when associated with L-206. 2 Publications
    Mutagenesisi203 – 2031G → R: Ineffective in DNA synthesis. 1 Publication
    Mutagenesisi206 – 2061P → L: Abolishes interaction with SHB; when associated with L-49. 1 Publication

    Organism-specific databases

    PharmGKBiPA28962.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 217217Growth factor receptor-bound protein 2PRO_0000088198Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine2 Publications
    Modified residuei6 – 61N6-acetyllysine1 Publication
    Modified residuei50 – 501N6-acetyllysine1 Publication
    Modified residuei109 – 1091N6-acetyllysine1 Publication
    Modified residuei211 – 2111Phosphothreonine1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP62993.
    PaxDbiP62993.
    PRIDEiP62993.

    2D gel databases

    OGPiP62993.
    SWISS-2DPAGEP62993.

    PTM databases

    PhosphoSiteiP62993.

    Expressioni

    Gene expression databases

    ArrayExpressiP62993.
    BgeeiP62993.
    CleanExiHS_GRB2.
    GenevestigatoriP62993.

    Organism-specific databases

    HPAiCAB002589.

    Interactioni

    Subunit structurei

    Associates with activated Tyr-phosphorylated EGF receptor/EGFR and PDGF receptors via its SH2 domain. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS. Interacts with phosphorylated TOM1L1 and MET. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1, REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains By similarity. Interacts with HCV NS5A via its SH3 domains. Interacts with CBL and CBLB. Interacts with AJUBA and CLNK By similarity. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with PTPN11. Interacts with PRNP and THEMIS By similarity. Interacts with FLT1 (tyrosine phosphorylated) and KDR. Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect By similarity. Interacts with RALGPS1 and with HCST. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with GAPT and PTPRE. Interacts (via SH2 domain) with KIF26A. Interacts (via SH3 2) with GAB2. Interacts with ADAM15. Interacts with THEMIS2. Interacts (via SH2 domain) with AXL and KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with FLT4 (tyrosine phosphorylated). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PTPN23. Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL, in which GRB2 promotes RTK recruitment by TNK2. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with ERBB4. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts with PTK2B/PYK2 (tyrosine phosphorylated). Isoform 1 interacts with SCIMP. Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes By similarity. Interacts with TESPA1 and DAB2. Interacts (via SH3 domains) with GAREM isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts with ASAP3 (phosphorylated form). Interacts with CD28.By similarity52 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself5EBI-401755,EBI-401755
    O929722EBI-401755,EBI-710506From a different organism.
    P266623EBI-401755,EBI-9099462From a different organism.
    P279583EBI-401755,EBI-706378From a different organism.
    ABL2P426842EBI-401755,EBI-1102694
    ADAM15Q134443EBI-401755,EBI-77818
    AGERQ151092EBI-401755,EBI-1646426
    ANK2Q014842EBI-401755,EBI-941975
    ARHGEF5Q127744EBI-401755,EBI-602199
    ASAP1Q9ULH17EBI-401755,EBI-346622
    ASAP2O431503EBI-401755,EBI-310968
    AXLP305303EBI-401755,EBI-2850927
    BCRP112748EBI-401755,EBI-712838
    BLNKQ8WV284EBI-401755,EBI-2623522
    BRD4O608852EBI-401755,EBI-723869
    CBLP226818EBI-401755,EBI-518228
    CBLBQ131915EBI-401755,EBI-744027
    CD2APQ9Y5K63EBI-401755,EBI-298152
    DAB2P980822EBI-401755,EBI-1171238
    Dab2P980784EBI-401755,EBI-1391846From a different organism.
    DARSP148682EBI-401755,EBI-358730
    DLGAP1O144903EBI-401755,EBI-1753207
    DLGAP2Q9P1A62EBI-401755,EBI-1753397
    DLGAP4Q9Y2H02EBI-401755,EBI-722139
    DNM1Q051933EBI-401755,EBI-713135
    DNM2P505704EBI-401755,EBI-346547
    DOCK1Q141852EBI-401755,EBI-446740
    EGFRP0053329EBI-401755,EBI-297353
    EPHB1P547622EBI-401755,EBI-80252
    ERBB2P046263EBI-401755,EBI-641062
    ERRFI1Q9UJM38EBI-401755,EBI-2941912
    FANCAO153602EBI-401755,EBI-81570
    FGFR2P218025EBI-401755,EBI-1028658
    FLNAP213332EBI-401755,EBI-350432
    FLNBO753692EBI-401755,EBI-352089
    FLNCQ143152EBI-401755,EBI-489954
    GAB1Q134805EBI-401755,EBI-517684
    GAB2Q9UQC214EBI-401755,EBI-975200
    GAREMQ9H7063EBI-401755,EBI-3440103
    Irs1P355705EBI-401755,EBI-520230From a different organism.
    KHDRBS1Q076668EBI-401755,EBI-1364
    KITP107216EBI-401755,EBI-1379503
    KRT8P057873EBI-401755,EBI-297852
    LATO4356112EBI-401755,EBI-1222766
    LCP2Q130947EBI-401755,EBI-346946
    LEPRP483573EBI-401755,EBI-518596
    MAP2K5Q131632EBI-401755,EBI-307294
    MAP4K1Q929188EBI-401755,EBI-881
    MAP4K3Q8IVH82EBI-401755,EBI-1758170
    MAP4K5Q9Y4K44EBI-401755,EBI-1279
    MED28Q9H2043EBI-401755,EBI-514199
    MYH9P355793EBI-401755,EBI-350338
    NELFBQ8WX922EBI-401755,EBI-347721
    PAK2Q131772EBI-401755,EBI-1045887
    PIK3C2BO007502EBI-401755,EBI-641107
    PIK3R1P279863EBI-401755,EBI-79464
    PIK3R2O004594EBI-401755,EBI-346930
    PLCG1P191742EBI-401755,EBI-79387
    PLD2O149394EBI-401755,EBI-1053996
    PPP3CAQ082093EBI-401755,EBI-352922
    PRKAB1Q9Y4782EBI-401755,EBI-719769
    Ptk2P341523EBI-401755,EBI-77070From a different organism.
    PTPN1P180312EBI-401755,EBI-968788
    PTPN11Q061246EBI-401755,EBI-297779
    Ptpn11P352357EBI-401755,EBI-397236From a different organism.
    PTPN22Q9Y2R22EBI-401755,EBI-1211241
    PTPN23Q9H3S76EBI-401755,EBI-724478
    PTPRAP184338EBI-401755,EBI-2609645
    PTPRTO145222EBI-401755,EBI-728180
    REPS2Q8NFH8-28EBI-401755,EBI-8029141
    SF3B4Q154272EBI-401755,EBI-348469
    SHANK2Q9UPX82EBI-401755,EBI-1570571
    SHANK3Q9BYB02EBI-401755,EBI-1752330
    SHC1P2935322EBI-401755,EBI-78835
    SHC1P29353-13EBI-401755,EBI-8160716
    SOS1Q0788922EBI-401755,EBI-297487
    Sos1Q6224511EBI-401755,EBI-1693From a different organism.
    SOS2Q078908EBI-401755,EBI-298181
    SPRY2O435973EBI-401755,EBI-742487
    STAMBPO956303EBI-401755,EBI-396676
    SYNJ2O150562EBI-401755,EBI-310513
    TNPO1Q929732EBI-401755,EBI-286693
    TOM1L1O756742EBI-401755,EBI-712991
    TPX2Q9ULW02EBI-401755,EBI-1037322
    UGP2Q168512EBI-401755,EBI-743729
    VAV1P154982EBI-401755,EBI-625518
    VAV3Q9UKW45EBI-401755,EBI-297568
    WASLO004013EBI-401755,EBI-957615
    WIPF1O435163EBI-401755,EBI-346356
    WIPF2Q8TF743EBI-401755,EBI-2850112

    Protein-protein interaction databases

    BioGridi109142. 456 interactions.
    DIPiDIP-29229N.
    IntActiP62993. 695 interactions.
    MINTiMINT-91952.
    STRINGi9606.ENSP00000339007.

    Structurei

    Secondary structure

    1
    217
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi2 – 54
    Beta strandi13 – 153
    Beta strandi24 – 263
    Beta strandi36 – 438
    Beta strandi45 – 495
    Helixi50 – 523
    Beta strandi61 – 644
    Helixi67 – 759
    Beta strandi78 – 803
    Beta strandi82 – 876
    Turni89 – 935
    Beta strandi95 – 1017
    Beta strandi104 – 1129
    Beta strandi114 – 1163
    Beta strandi118 – 1225
    Beta strandi124 – 1274
    Helixi128 – 1347
    Turni135 – 1373
    Beta strandi142 – 1443
    Beta strandi149 – 1524
    Beta strandi155 – 1573
    Beta strandi160 – 1656
    Beta strandi171 – 1744
    Beta strandi182 – 1876
    Beta strandi190 – 1989
    Beta strandi201 – 2066
    Helixi207 – 2093
    Beta strandi210 – 2123

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AZENMR-A1-56[»]
    1BM2X-ray2.10A49-163[»]
    1BMBX-ray1.80A49-168[»]
    1CJ1X-ray3.00A/B/C/D/E/F/G/H/I/J/K/L57-152[»]
    1FHSNMR-A53-163[»]
    1FYRX-ray2.40A/B/C/D50-161[»]
    1GCQX-ray1.68A/B159-217[»]
    1GFCNMR-A159-215[»]
    1GFDNMR-A159-215[»]
    1GHUNMR-A60-158[»]
    1GRIX-ray3.10A/B1-217[»]
    1IO6NMR-A159-215[»]
    1JYQX-ray2.00A/B60-151[»]
    1JYRX-ray1.55A60-151[»]
    1JYUX-ray2.75A60-151[»]
    1QG1NMR-E58-159[»]
    1TZEX-ray2.10E55-152[»]
    1X0NNMR-A58-159[»]
    1ZFPX-ray1.80E56-153[»]
    2AOAX-ray1.99A/B55-153[»]
    2AOBX-ray1.80A/B/C/D55-153[»]
    2H46X-ray1.90E53-162[»]
    2H5KX-ray3.25A/B53-162[»]
    2HUWX-ray1.90A/B53-162[»]
    2VVKX-ray1.60A161-214[»]
    2VWFX-ray1.58A159-214[»]
    2W0ZX-ray1.70A159-214[»]
    3C7IX-ray1.70A53-162[»]
    3IMDX-ray2.00A/B53-163[»]
    3IMJX-ray2.02A/B53-163[»]
    3IN7X-ray2.00A/C53-163[»]
    3IN8X-ray1.70A53-163[»]
    3KFJX-ray2.02A53-163[»]
    3MXCX-ray2.00A55-152[»]
    3MXYX-ray2.30A55-152[»]
    3N7YX-ray2.02A/B/C55-152[»]
    3N84X-ray2.00A/B/C/D/E/F53-163[»]
    3N8MX-ray2.00A53-163[»]
    3OV1X-ray1.60A53-163[»]
    3OVEX-ray1.82A53-163[»]
    3S8LX-ray1.71A53-163[»]
    3S8NX-ray1.71A53-163[»]
    3S8OX-ray1.85A53-163[»]
    3WA4X-ray1.35A60-152[»]
    4P9VX-ray1.64A53-163[»]
    4P9ZX-ray1.80A53-163[»]
    DisProtiDP00210.
    ProteinModelPortaliP62993.
    SMRiP62993. Positions 1-217.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP62993.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 5858SH3 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini60 – 15293SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini156 – 21560SH3 2PROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The SH3 domains mediate interaction with RALGPS1 and SHB.

    Sequence similaritiesi

    Belongs to the GRB2/sem-5/DRK family.Curated
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 2 SH3 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH2 domain, SH3 domain

    Phylogenomic databases

    eggNOGiNOG298780.
    HOGENOMiHOG000251625.
    HOVERGENiHBG005404.
    InParanoidiP62993.
    KOiK04364.
    OMAiVETKFVQ.
    OrthoDBiEOG75F4F6.
    PhylomeDBiP62993.
    TreeFamiTF354288.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00017. SH2. 1 hit.
    PF00018. SH3_1. 2 hits.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    SMARTiSM00252. SH2. 1 hit.
    SM00326. SH3. 2 hits.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 2 hits.
    SSF55550. SSF55550. 2 hits.
    PROSITEiPS50001. SH2. 1 hit.
    PS50002. SH3. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P62993-1) [UniParc]FASTAAdd to Basket

    Also known as: Ash-L

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK    50
    NYIEMKPHPW FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK 100
    FGNDVQHFKV LRDGAGKYFL WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD 150
    IEQVPQQPTY VQALFDFDPQ EDGELGFRRG DFIHVMDNSD PNWWKGACHG 200
    QTGMFPRNYV TPVNRNV 217
    Length:217
    Mass (Da):25,206
    Last modified:August 31, 2004 - v1
    Checksum:i83A4B0BA1B248DC4
    GO
    Isoform 2 (identifier: P62993-2) [UniParc] [UniParc]FASTAAdd to Basket

    Also known as: GRB3-3

    The sequence of this isoform differs from the canonical sequence as follows:
         60-100: Missing.

    Show »
    Length:176
    Mass (Da):20,557
    Checksum:i70622BED0FE940DE
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei60 – 10041Missing in isoform 2. 1 PublicationVSP_001839Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M96995 mRNA. Translation: AAA58448.1.
    X62852 mRNA. Translation: CAA44664.1.
    L29511 mRNA. Translation: AAC37549.1.
    AF063618
    , AF063614, AF063615, AF063616, AF063617 Genomic DNA. Translation: AAC72075.1.
    AF498925 mRNA. Translation: AAM21073.1.
    CR541942 mRNA. Translation: CAG46740.1.
    AC011933 Genomic DNA. No translation available.
    BC000631 mRNA. Translation: AAH00631.1.
    CCDSiCCDS11721.1.
    CCDS11722.1. [P62993-2]
    PIRiA43321.
    RefSeqiNP_002077.1. NM_002086.4. [P62993-1]
    NP_987102.1. NM_203506.2. [P62993-2]
    UniGeneiHs.444356.

    Genome annotation databases

    EnsembliENST00000316615; ENSP00000317360; ENSG00000177885. [P62993-2]
    ENST00000316804; ENSP00000339007; ENSG00000177885. [P62993-1]
    ENST00000392562; ENSP00000376345; ENSG00000177885. [P62993-1]
    ENST00000392563; ENSP00000376346; ENSG00000177885. [P62993-2]
    ENST00000392564; ENSP00000376347; ENSG00000177885. [P62993-1]
    GeneIDi2885.
    KEGGihsa:2885.
    UCSCiuc002jnx.4. human.
    uc002jny.4. human. [P62993-2]

    Polymorphism databases

    DMDMi51702266.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M96995 mRNA. Translation: AAA58448.1 .
    X62852 mRNA. Translation: CAA44664.1 .
    L29511 mRNA. Translation: AAC37549.1 .
    AF063618
    , AF063614 , AF063615 , AF063616 , AF063617 Genomic DNA. Translation: AAC72075.1 .
    AF498925 mRNA. Translation: AAM21073.1 .
    CR541942 mRNA. Translation: CAG46740.1 .
    AC011933 Genomic DNA. No translation available.
    BC000631 mRNA. Translation: AAH00631.1 .
    CCDSi CCDS11721.1.
    CCDS11722.1. [P62993-2 ]
    PIRi A43321.
    RefSeqi NP_002077.1. NM_002086.4. [P62993-1 ]
    NP_987102.1. NM_203506.2. [P62993-2 ]
    UniGenei Hs.444356.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AZE NMR - A 1-56 [» ]
    1BM2 X-ray 2.10 A 49-163 [» ]
    1BMB X-ray 1.80 A 49-168 [» ]
    1CJ1 X-ray 3.00 A/B/C/D/E/F/G/H/I/J/K/L 57-152 [» ]
    1FHS NMR - A 53-163 [» ]
    1FYR X-ray 2.40 A/B/C/D 50-161 [» ]
    1GCQ X-ray 1.68 A/B 159-217 [» ]
    1GFC NMR - A 159-215 [» ]
    1GFD NMR - A 159-215 [» ]
    1GHU NMR - A 60-158 [» ]
    1GRI X-ray 3.10 A/B 1-217 [» ]
    1IO6 NMR - A 159-215 [» ]
    1JYQ X-ray 2.00 A/B 60-151 [» ]
    1JYR X-ray 1.55 A 60-151 [» ]
    1JYU X-ray 2.75 A 60-151 [» ]
    1QG1 NMR - E 58-159 [» ]
    1TZE X-ray 2.10 E 55-152 [» ]
    1X0N NMR - A 58-159 [» ]
    1ZFP X-ray 1.80 E 56-153 [» ]
    2AOA X-ray 1.99 A/B 55-153 [» ]
    2AOB X-ray 1.80 A/B/C/D 55-153 [» ]
    2H46 X-ray 1.90 E 53-162 [» ]
    2H5K X-ray 3.25 A/B 53-162 [» ]
    2HUW X-ray 1.90 A/B 53-162 [» ]
    2VVK X-ray 1.60 A 161-214 [» ]
    2VWF X-ray 1.58 A 159-214 [» ]
    2W0Z X-ray 1.70 A 159-214 [» ]
    3C7I X-ray 1.70 A 53-162 [» ]
    3IMD X-ray 2.00 A/B 53-163 [» ]
    3IMJ X-ray 2.02 A/B 53-163 [» ]
    3IN7 X-ray 2.00 A/C 53-163 [» ]
    3IN8 X-ray 1.70 A 53-163 [» ]
    3KFJ X-ray 2.02 A 53-163 [» ]
    3MXC X-ray 2.00 A 55-152 [» ]
    3MXY X-ray 2.30 A 55-152 [» ]
    3N7Y X-ray 2.02 A/B/C 55-152 [» ]
    3N84 X-ray 2.00 A/B/C/D/E/F 53-163 [» ]
    3N8M X-ray 2.00 A 53-163 [» ]
    3OV1 X-ray 1.60 A 53-163 [» ]
    3OVE X-ray 1.82 A 53-163 [» ]
    3S8L X-ray 1.71 A 53-163 [» ]
    3S8N X-ray 1.71 A 53-163 [» ]
    3S8O X-ray 1.85 A 53-163 [» ]
    3WA4 X-ray 1.35 A 60-152 [» ]
    4P9V X-ray 1.64 A 53-163 [» ]
    4P9Z X-ray 1.80 A 53-163 [» ]
    DisProti DP00210.
    ProteinModelPortali P62993.
    SMRi P62993. Positions 1-217.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109142. 456 interactions.
    DIPi DIP-29229N.
    IntActi P62993. 695 interactions.
    MINTi MINT-91952.
    STRINGi 9606.ENSP00000339007.

    Chemistry

    BindingDBi P62993.
    ChEMBLi CHEMBL3663.
    DrugBanki DB00061. Pegademase bovine.

    PTM databases

    PhosphoSitei P62993.

    Polymorphism databases

    DMDMi 51702266.

    2D gel databases

    OGPi P62993.
    SWISS-2DPAGE P62993.

    Proteomic databases

    MaxQBi P62993.
    PaxDbi P62993.
    PRIDEi P62993.

    Protocols and materials databases

    DNASUi 2885.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000316615 ; ENSP00000317360 ; ENSG00000177885 . [P62993-2 ]
    ENST00000316804 ; ENSP00000339007 ; ENSG00000177885 . [P62993-1 ]
    ENST00000392562 ; ENSP00000376345 ; ENSG00000177885 . [P62993-1 ]
    ENST00000392563 ; ENSP00000376346 ; ENSG00000177885 . [P62993-2 ]
    ENST00000392564 ; ENSP00000376347 ; ENSG00000177885 . [P62993-1 ]
    GeneIDi 2885.
    KEGGi hsa:2885.
    UCSCi uc002jnx.4. human.
    uc002jny.4. human. [P62993-2 ]

    Organism-specific databases

    CTDi 2885.
    GeneCardsi GC17M073313.
    HGNCi HGNC:4566. GRB2.
    HPAi CAB002589.
    MIMi 108355. gene.
    neXtProti NX_P62993.
    PharmGKBi PA28962.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG298780.
    HOGENOMi HOG000251625.
    HOVERGENi HBG005404.
    InParanoidi P62993.
    KOi K04364.
    OMAi VETKFVQ.
    OrthoDBi EOG75F4F6.
    PhylomeDBi P62993.
    TreeFami TF354288.

    Enzyme and pathway databases

    Reactomei REACT_111040. Signaling by SCF-KIT.
    REACT_111080. Spry regulation of FGF signaling.
    REACT_111184. Negative regulation of FGFR signaling.
    REACT_111225. Regulation of KIT signaling.
    REACT_115852. Signaling by constitutively active EGFR.
    REACT_115854. GRB2 events in ERBB2 signaling.
    REACT_115993. SHC1 events in ERBB2 signaling.
    REACT_116005. SHC1 events in ERBB4 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_12033. Signalling to RAS.
    REACT_121096. EGFR Transactivation by Gastrin.
    REACT_121141. Signaling by FGFR1 fusion mutants.
    REACT_121398. Signaling by FGFR mutants.
    REACT_12484. EGFR downregulation.
    REACT_12578. GAB1 signalosome.
    REACT_12579. SHC1 events in EGFR signaling.
    REACT_12606. GRB2 events in EGFR signaling.
    REACT_12621. Tie2 Signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147814. DAP12 signaling.
    REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
    REACT_163701. FCERI mediated MAPK activation.
    REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_163834. FCERI mediated Ca+2 mobilization.
    REACT_17025. Downstream signal transduction.
    REACT_18334. NCAM signaling for neurite out-growth.
    REACT_19238. CD28 dependent Vav1 pathway.
    REACT_19344. Costimulation by the CD28 family.
    REACT_21247. FRS2-mediated cascade.
    REACT_21270. PI-3K cascade.
    REACT_21374. SHC-mediated cascade.
    REACT_23787. Regulation of signaling by CBL.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_23916. Signal regulatory protein (SIRP) family interactions.
    REACT_508. Signal attenuation.
    REACT_524. SOS-mediated signalling.
    REACT_661. SHC-mediated signalling.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_976. PI3K Cascade.
    SignaLinki P62993.

    Miscellaneous databases

    ChiTaRSi GRB2. human.
    EvolutionaryTracei P62993.
    GeneWikii GRB2.
    GenomeRNAii 2885.
    NextBioi 11389.
    PROi P62993.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P62993.
    Bgeei P62993.
    CleanExi HS_GRB2.
    Genevestigatori P62993.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF00017. SH2. 1 hit.
    PF00018. SH3_1. 2 hits.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 2 hits.
    SSF55550. SSF55550. 2 hits.
    PROSITEi PS50001. SH2. 1 hit.
    PS50002. SH3. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling."
      Lowenstein E.J., Daly R.J., Batzer A.G., Li W., Margolis B., Lammers R., Ullrich A., Skolnik E.Y., Bar-Sagi D., Schlessinger J.
      Cell 70:431-442(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF PRO-49 AND GLY-203.
      Tissue: Brain.
    2. "Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries."
      Matuoka K., Yamakawa A., Shibata M., Takenawa T.
      Proc. Natl. Acad. Sci. U.S.A. 89:9015-9019(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Fetal lung.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
      Tissue: Placenta.
    4. "The gene structure of the human growth factor bound protein GRB2."
      Bochmann H., Gehrisch S., Jaross W.
      Genomics 56:203-207(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Epidermis.
    5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
      Puhl H.L. III, Ikeda S.R., Aronstam R.S.
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    6. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    7. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lymph.
    9. Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
      Submitted (DEC-2008) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 11-20; 27-38; 77-109; 118-136; 143-149 AND 179-195, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
    10. "Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts."
      van der Geer P., Hunter T.
      EMBO J. 12:5161-5172(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CSF1R.
    11. "Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2."
      Tobe K., Matuoka K., Tamemoto H., Ueki K., Kaburagi Y., Asai S., Noguchi T., Matsuda M., Tanaka S., Hattori S., Fukui Y., Akanuma Y., Yazaki Y., Takenawa T., Kadowaki T.
      J. Biol. Chem. 268:11167-11171(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS1.
    12. "The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling."
      Skolnik E.Y., Lee C.-H., Batzer A.G., Vicentini L.M., Zhou M., Daly R.J., Myers M.J. Jr., Backer J.M., Ullrich A., White M.F., Schlessinger J.
      EMBO J. 12:1929-1936(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS1 AND SHC.
    13. "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein."
      Pandey P., Kharbanda S., Kufe D.
      Cancer Res. 55:4000-4003(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH MUC1 AND SOS1, INTERACTION WITH MUC1 AND SOS1.
    14. "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2."
      Kavanaugh W.M., Pot D.A., Chin S.M., Deuter-Reinhard M., Jefferson A.B., Norris F.A., Masiarz F.R., Cousens L.S., Majerus P.W., Williams L.T.
      Curr. Biol. 6:438-445(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INPP5D.
    15. "Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells."
      Stein E., Cerretti D.P., Daniel T.O.
      J. Biol. Chem. 271:23588-23593(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPHB1.
    16. "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."
      Odai H., Sasaki K., Iwamatsu A., Nakamoto T., Ueno H., Yamagata T., Mitani K., Yazaki Y., Hirai H.
      Blood 89:2745-2756(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INPP5D.
    17. "Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src."
      Schlaepfer D.D., Hunter T.
      J. Biol. Chem. 272:13189-13195(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTK2/FAK1.
    18. "A family of proteins that inhibit signalling through tyrosine kinase receptors."
      Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A.
      Nature 386:181-186(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPNS1.
    19. "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site."
      Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W.
      Oncogene 14:2619-2631(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXL.
    20. "Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation."
      Yokouchi M., Suzuki R., Masuhara M., Komiya S., Inoue A., Yoshimura A.
      Oncogene 15:7-15(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SH2B2.
    21. "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation."
      Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.
      Cell 92:83-92(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LAT.
    22. "Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral."
      Ikeda M., Ishida O., Hinoi T., Kishida S., Kikuchi A.
      J. Biol. Chem. 273:814-821(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH REPS2.
    23. "Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells."
      Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E., Lavan B.E.
      J. Biol. Chem. 273:10726-10732(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS4.
    24. "Stimulation through the T cell receptor leads to interactions between SHB and several signaling proteins."
      Welsh M., Songyang Z., Frantz J.D., Trueb T., Reedquist K.A., Karlsson T., Miyazaki M., Cantley L.C., Band H., Shoelson S.E.
      Oncogene 16:891-901(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SHB, MUTAGENESIS OF PRO-49 AND PRO-206.
    25. "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck."
      Braverman L.E., Quilliam L.A.
      J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EGFR.
    26. "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation."
      Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.
      Oncogene 18:1147-1156(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBLB.
    27. Cited for: INTERACTION WITH CBL AND CBLB.
    28. "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."
      Tan S.-L., Nakao H., He Y., Vijaysri S., Neddermann P., Jacobs B.L., Mayer B.J., Katze M.G.
      Proc. Natl. Acad. Sci. U.S.A. 96:5533-5538(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCV NS5A.
    29. "Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral."
      Rebhun J.F., Chen H., Quilliam L.A.
      J. Biol. Chem. 275:13406-13410(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RALGPS1.
    30. "Ligand discrimination in signaling through an ErbB4 receptor homodimer."
      Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C., Carraway K.L. III
      J. Biol. Chem. 275:19803-19807(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ERBB4.
    31. "Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin."
      Asazuma N., Wilde J.I., Berlanga O., Leduc M., Leo A., Schweighoffer E., Tybulewicz V., Bon C., Liu S.K., McGlade C.J., Schraven B., Watson S.P.
      J. Biol. Chem. 275:33427-33434(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SKAP2.
    32. "Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control."
      Gil-Henn H., Volohonsky G., Toledano-Katchalski H., Gandre S., Elson A.
      Oncogene 19:4375-4384(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPRE.
    33. "Structural and functional dissection of the cytoplasmic domain of the transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor protein)."
      Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A., Spicka J., Hilgert I., Scherer J., Schraven B.
      Eur. J. Immunol. 31:1825-1836(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIT1.
    34. "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK."
      Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.
      J. Biol. Chem. 276:42389-42400(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
    35. "Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2."
      Wheeler M., Domin J.
      Mol. Cell. Biol. 21:6660-6667(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND EGFR, INTERACTION WITH PIK3C2B.
    36. "Insulin receptor substrate 4 associates with the protein IRAS."
      Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.
      J. Biol. Chem. 277:19439-19447(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NISCH.
    37. "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation."
      Wu L., Yu Z., Shen S.-H.
      J. Biol. Chem. 277:40420-40427(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SKAP1.
    38. "Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling."
      Zhu M., Janssen E., Leung K., Zhang W.
      J. Biol. Chem. 277:46151-46158(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LAX1.
    39. Cited for: INTERACTION WITH LAT2.
    40. "Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1."
      Palka H.L., Park M., Tonks N.K.
      J. Biol. Chem. 278:5728-5735(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPRJ.
    41. "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis."
      Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.
      J. Cell Biol. 162:661-671(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPHB1 AND SHC1.
    42. "LAB: a new membrane-associated adaptor molecule in B cell activation."
      Janssen E., Zhu M., Zhang W., Koonpaew S., Zhang W.
      Nat. Immunol. 4:117-123(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LAT2.
    43. Cited for: INTERACTION WITH NTRK1.
    44. "Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress."
      Wang J.F., Zhang X., Groopman J.E.
      J. Biol. Chem. 279:27088-27097(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FLT4.
    45. "Signal transduction via the stem cell factor receptor/c-Kit."
      Ronnstrand L.
      Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
    46. "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner."
      Laurent C.E., Smithgall T.E.
      Exp. Cell Res. 299:188-198(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BCR.
    47. "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
      Roskoski R. Jr.
      Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN KIT SIGNALING.
    48. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    49. "NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells."
      Upshaw J.L., Arneson L.N., Schoon R.A., Dick C.J., Billadeau D.D., Leibson P.J.
      Nat. Immunol. 7:524-532(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCST.
    50. "Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells."
      Liu Y., Zhang W.
      J. Leukoc. Biol. 84:842-851(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GAPT.
    51. "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma."
      Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M., Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C., Edwards D.R.
      Mol. Cancer Res. 6:383-394(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ADAM15.
    52. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-211, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    53. "An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis."
      Tarcic G., Boguslavsky S.K., Wakim J., Kiuchi T., Liu A., Reinitz F., Nathanson D., Takahashi T., Mischel P.S., Ng T., Yarden Y.
      Curr. Biol. 19:1788-1798(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EGFR.
    54. "Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling."
      Pao-Chun L., Chan P.M., Chan W., Manser E.
      J. Biol. Chem. 284:34954-34963(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXL; LTK; PDGFRL AND TNK2, FUNCTION.
    55. "KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development."
      Zhou R., Niwa S., Homma N., Takei Y., Hirokawa N.
      Cell 139:802-813(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KIF26A.
    56. "GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling."
      Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E., Taniguchi H., Konishi H.
      J. Biol. Chem. 284:20206-20214(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GAREM.
    57. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    58. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-6; LYS-50 AND LYS-109, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    59. "Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells."
      Shen X., Xi G., Radhakrishnan Y., Clemmons D.R.
      Cell. Mol. Life Sci. 67:3893-3903(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTK2B/PYK2.
    60. "Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL."
      Tanase C.A.
      PLoS ONE 5:E14339-E14339(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPN23, SUBCELLULAR LOCATION.
    61. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    62. "ACAP4 protein cooperates with Grb2 protein to orchestrate epidermal growth factor-stimulated integrin beta1 recycling in cell migration."
      Yu X., Wang F., Liu H., Adams G., Aikhionbare F., Liu D., Cao X., Fan L., Hu G., Chen Y., Frost A., Partridge E., Ding X., Yao X.
      J. Biol. Chem. 286:43735-43747(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ASAP3.
    63. "SCIMP, a transmembrane adapter protein involved in major histocompatibility complex class II signaling."
      Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.
      Mol. Cell. Biol. 31:4550-4562(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SCIMP.
    64. "Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling."
      Wang D., Zheng M., Lei L., Ji J., Yao Y., Qiu Y., Ma L., Lou J., Ouyang C., Zhang X., He Y., Chi J., Wang L., Kuang Y., Wang J., Cao X., Lu L.
      Nat. Immunol. 13:560-568(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TESPA1.
      Tissue: Thymocyte.
    65. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    66. "Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain."
      Thornton K.H., Mueller W.T., McConnell P., Zhu G., Saltiel A.R., Thanabal V.
      Biochemistry 35:11852-11864(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 58-164.
    67. "The three-dimensional solution structure of the Src homology domain-2 of the growth factor receptor-bound protein-2."
      Senior M.M., Frederick A.F., Black S., Murgolo N.J., Perkins L.M., Wilson O., Snow M.E., Wang Y.-S.
      J. Biomol. NMR 11:153-164(1998)
      Cited for: STRUCTURE BY NMR OF 52-163.
    68. "Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2."
      Kohda D., Terasawa H., Ichikawa S., Ogura K., Hatanaka H., Mandiyan V., Ullrich A., Schlessinger J., Inagaki F.
      Structure 2:1029-1040(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 157-215.
    69. Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
    70. "Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide ligands."
      Rahuel J., Garcia-Echeverria C., Furet P., Strauss A., Caravatti G., Fretz H., Schoepfer J., Gay B.
      J. Mol. Biol. 279:1013-1022(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 56-153.
    71. "Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1)."
      Ettmayer P., France D., Gounarides J., Jarosinski M., Martin M.-S., Rondeau J.-M., Sabio M., Topiol S., Weidmann B., Zurini M., Bair K.W.
      J. Med. Chem. 42:971-980(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-163.
    72. "Structure-based design, synthesis, and X-ray crystallography of a high- affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic."
      Furet P., Garcia-Echeverria C., Gay B., Schoepfer J., Zeller M., Rahuel J.
      J. Med. Chem. 42:2358-2363(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 57-152.
    73. "Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex."
      Schiering N., Casale E., Caccia P., Giordano P., Battistini C.
      Biochemistry 39:13376-13382(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 52-160 IN COMPLEX WITH MET.
    74. "Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor."
      Nioche P., Liu W.-Q., Broutin I., Charbonnier F., Latreille M.-T., Vidal M., Roques B., Garbay C., Ducruix A.
      J. Mol. Biol. 315:1167-1177(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-151 IN COMPLEX WITH THE TYROSINE PHOSPHORYLATED PEPTIDE TYR-VAL-ASN-VAL-GLN-ASN AND IN COMPLEX WITH A PEPTIDE INHIBITOR.
    75. "Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2."
      Harkiolaki M., Tsirka T., Lewitzky M., Simister P.C., Joshi D., Bird L.E., Jones E.Y., O'Reilly N., Feller S.M.
      Structure 17:809-822(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 158-211 IN COMPLEX WITH GAB2.
    76. "High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28."
      Higo K., Ikura T., Oda M., Morii H., Takahashi J., Abe R., Ito N.
      PLoS ONE 8:E74482-E74482(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 60-152 IN COMPLEX WITH CD28, INTERACTION WITH CD28.

    Entry informationi

    Entry nameiGRB2_HUMAN
    AccessioniPrimary (citable) accession number: P62993
    Secondary accession number(s): P29354
    , Q14450, Q63057, Q63059
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 31, 2004
    Last sequence update: August 31, 2004
    Last modified: October 1, 2014
    This is version 140 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3