Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P62994

- GRB2_RAT

UniProt

P62994 - GRB2_RAT

Protein

Growth factor receptor-bound protein 2

Gene

Grb2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (31 Aug 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.By similarity

    GO - Molecular functioni

    1. epidermal growth factor receptor binding Source: UniProtKB
    2. insulin receptor substrate binding Source: RGD
    3. phosphoprotein binding Source: RGD
    4. phosphotyrosine binding Source: RGD
    5. protein binding Source: IntAct
    6. protein domain specific binding Source: RGD
    7. SH3 domain binding Source: UniProtKB

    GO - Biological processi

    1. aging Source: RGD
    2. anatomical structure formation involved in morphogenesis Source: Ensembl
    3. branching involved in labyrinthine layer morphogenesis Source: Ensembl
    4. cell differentiation Source: Ensembl
    5. cellular response to ionizing radiation Source: Ensembl
    6. insulin receptor signaling pathway Source: Ensembl
    7. positive regulation of actin filament polymerization Source: Ensembl
    8. positive regulation of reactive oxygen species metabolic process Source: Ensembl
    9. positive regulation of signal transduction Source: GOC
    10. protein heterooligomerization Source: RGD
    11. Ras protein signal transduction Source: RGD
    12. receptor internalization Source: Ensembl
    13. regulation of MAPK cascade Source: Ensembl
    14. signal transduction in response to DNA damage Source: Ensembl

    Enzyme and pathway databases

    ReactomeiREACT_195025. Signaling by SCF-KIT.
    REACT_195026. SHC1 events in ERBB4 signaling.
    REACT_195029. SHC1 events in ERBB2 signaling.
    REACT_195202. FCERI mediated MAPK activation.
    REACT_195203. GRB2 events in ERBB2 signaling.
    REACT_196225. Regulation of signaling by CBL.
    REACT_196755. Regulation of actin dynamics for phagocytic cup formation.
    REACT_196848. EGFR Transactivation by Gastrin.
    REACT_197451. Regulation of KIT signaling.
    REACT_197527. PI3K events in ERBB2 signaling.
    REACT_197531. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_198628. Signaling by FGFR1 fusion mutants.
    REACT_198665. Signaling by FGFR mutants.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198995. Negative regulation of FGFR signaling.
    REACT_199007. Spry regulation of FGF signaling.
    REACT_199249. Signaling by constitutively active EGFR.
    REACT_203734. FCERI mediated Ca+2 mobilization.
    REACT_204559. SOS-mediated signalling.
    REACT_206819. Downstream signal transduction.
    REACT_211910. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_212418. DAP12 signaling.
    REACT_79133. SHC-mediated cascade.

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi619758. Grb2.

    Subcellular locationi

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

    GO - Cellular componenti

    1. COP9 signalosome Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Reactome
    4. endosome Source: UniProtKB
    5. Golgi apparatus Source: UniProtKB-SubCell
    6. Grb2-EGFR complex Source: Ensembl
    7. nucleus Source: UniProtKB
    8. protein complex Source: RGD
    9. vesicle membrane Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Endosome, Golgi apparatus, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 217217Growth factor receptor-bound protein 2PRO_0000088201Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei6 – 61N6-acetyllysineBy similarity
    Modified residuei50 – 501N6-acetyllysineBy similarity
    Modified residuei109 – 1091N6-acetyllysineBy similarity
    Modified residuei211 – 2111PhosphothreonineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP62994.
    PRIDEiP62994.

    PTM databases

    PhosphoSiteiP62994.

    Expressioni

    Tissue specificityi

    Wide tissue distribution.1 Publication

    Gene expression databases

    GenevestigatoriP62994.

    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, 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 PTPNS1, REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains. Interacts with CBL and CBLB. Interacts with AJUBA By similarity. Interacts with SHB, INPP5D/SHIP1, SKAP1, SKAP2 and CLNK By similarity. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains SH2 domain with phosphorylated MUC1. Interacts with PRNP By similarity. Interacts with NISCH, RALGPS1 and with HCST By similarity. Interacts with GAPT, THEMIS and PTPRE By similarity. Interacts (via SH3 2) with GAB2 By similarity. Interacts with ADAM15. Interacts with PTPRJ and BCR By similarity. Interacts with THEMIS2. Interacts (via SH2 domain) with AXL and KIT (phosphorylated). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) By similarity. Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PTPN23 By similarity. Interacts with FLT1, KDR and FLT4 (tyrosine phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL, in which GRB2 promotes RTK recruitment by TNK2 By similarity. Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect By similarity. Interacts with PTPN11. Interacts with NTRK1 (phosphorylated upon ligand-binding) By similarity. Interacts with ERBB4. Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts with SCIMP By similarity. Interacts with PLCG1, LAT, THEMIS and TESPA1 upon TCR activation in thymocytes. Interacts with DAB2 By similarity. Interacts (via SH3 domains) with GAREM (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation By similarity. 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 similarity. Interacts (via SH2 domain) with CSF1R and IRS1 (tyrosine phosphorylated).By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Dnm1P215753EBI-401775,EBI-80070
    Ntrk1P357396EBI-401775,EBI-976667
    PDE6GP185452EBI-401775,EBI-2622029From a different organism.
    PTPN1P180313EBI-401775,EBI-968788From a different organism.

    Protein-protein interaction databases

    BioGridi249501. 10 interactions.
    IntActiP62994. 14 interactions.
    MINTiMINT-93691.

    Structurei

    3D structure databases

    ProteinModelPortaliP62994.
    SMRiP62994. Positions 1-217.
    ModBaseiSearch...
    MobiDBiSearch...

    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.By similarity

    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.
    GeneTreeiENSGT00550000074482.
    HOGENOMiHOG000251625.
    HOVERGENiHBG005404.
    InParanoidiP62994.
    KOiK04364.
    OMAiVETKFVQ.
    OrthoDBiEOG75F4F6.
    PhylomeDBiP62994.
    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 (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P62994-1) [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: P62994-2) [UniParc] [UniParc]FASTAAdd to Basket

    Also known as: Ash-M

    The sequence of this isoform differs from the canonical sequence as follows:
         157-170: Missing.

    Show »
    Length:203
    Mass (Da):23,556
    Checksum:i8FB4869BE35F6CF5
    GO
    Isoform 3 (identifier: P62994-3) [UniParc] [UniParc]FASTAAdd to Basket

    Also known as: Ash-S

    The sequence of this isoform differs from the canonical sequence as follows:
         60-217: Missing.

    Show »
    Length:59
    Mass (Da):6,880
    Checksum:i61EC429649FEBFF0
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei60 – 217158Missing in isoform 3. 1 PublicationVSP_001838Add
    BLAST
    Alternative sequencei157 – 17014Missing in isoform 2. 1 PublicationVSP_001840Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X62853 mRNA. Translation: CAA44665.1.
    D49846 mRNA. Translation: BAA08645.1.
    D49847 mRNA. Translation: BAA08646.1.
    BC091144 mRNA. Translation: AAH91144.1.
    PIRiS26050.
    RefSeqiNP_110473.2. NM_030846.2. [P62994-1]
    UniGeneiRn.3360.

    Genome annotation databases

    EnsembliENSRNOT00000005347; ENSRNOP00000005347; ENSRNOG00000003990. [P62994-1]
    GeneIDi81504.
    KEGGirno:81504.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X62853 mRNA. Translation: CAA44665.1 .
    D49846 mRNA. Translation: BAA08645.1 .
    D49847 mRNA. Translation: BAA08646.1 .
    BC091144 mRNA. Translation: AAH91144.1 .
    PIRi S26050.
    RefSeqi NP_110473.2. NM_030846.2. [P62994-1 ]
    UniGenei Rn.3360.

    3D structure databases

    ProteinModelPortali P62994.
    SMRi P62994. Positions 1-217.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249501. 10 interactions.
    IntActi P62994. 14 interactions.
    MINTi MINT-93691.

    Chemistry

    BindingDBi P62994.

    PTM databases

    PhosphoSitei P62994.

    Proteomic databases

    PaxDbi P62994.
    PRIDEi P62994.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000005347 ; ENSRNOP00000005347 ; ENSRNOG00000003990 . [P62994-1 ]
    GeneIDi 81504.
    KEGGi rno:81504.

    Organism-specific databases

    CTDi 2885.
    RGDi 619758. Grb2.

    Phylogenomic databases

    eggNOGi NOG298780.
    GeneTreei ENSGT00550000074482.
    HOGENOMi HOG000251625.
    HOVERGENi HBG005404.
    InParanoidi P62994.
    KOi K04364.
    OMAi VETKFVQ.
    OrthoDBi EOG75F4F6.
    PhylomeDBi P62994.
    TreeFami TF354288.

    Enzyme and pathway databases

    Reactomei REACT_195025. Signaling by SCF-KIT.
    REACT_195026. SHC1 events in ERBB4 signaling.
    REACT_195029. SHC1 events in ERBB2 signaling.
    REACT_195202. FCERI mediated MAPK activation.
    REACT_195203. GRB2 events in ERBB2 signaling.
    REACT_196225. Regulation of signaling by CBL.
    REACT_196755. Regulation of actin dynamics for phagocytic cup formation.
    REACT_196848. EGFR Transactivation by Gastrin.
    REACT_197451. Regulation of KIT signaling.
    REACT_197527. PI3K events in ERBB2 signaling.
    REACT_197531. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_198628. Signaling by FGFR1 fusion mutants.
    REACT_198665. Signaling by FGFR mutants.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198995. Negative regulation of FGFR signaling.
    REACT_199007. Spry regulation of FGF signaling.
    REACT_199249. Signaling by constitutively active EGFR.
    REACT_203734. FCERI mediated Ca+2 mobilization.
    REACT_204559. SOS-mediated signalling.
    REACT_206819. Downstream signal transduction.
    REACT_211910. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_212418. DAP12 signaling.
    REACT_79133. SHC-mediated cascade.

    Miscellaneous databases

    NextBioi 614959.

    Gene expression databases

    Genevestigatori P62994.

    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. "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 SPECIFICITY.
      Strain: Fischer 344.
      Tissue: Brain.
    2. "Splicing isoforms of rat Ash/Grb2. Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms."
      Watanabe K., Fukuchi T., Hosoya H., Shirasawa T., Matsuoka K., Miki H., Takenawa T.
      J. Biol. Chem. 270:13733-13739(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION.
      Strain: Wistar.
      Tissue: Brain.
    3. "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: Thymus.
    4. Lubec G., Afjehi-Sadat L., Chen W.-Q.
      Submitted (APR-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 11-21; 77-86; 101-109; 125-136; 143-149 AND 208-215, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: Sprague-Dawley.
      Tissue: Hippocampus and Spinal cord.
    5. "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.
    6. "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.

    Entry informationi

    Entry nameiGRB2_RAT
    AccessioniPrimary (citable) accession number: P62994
    Secondary accession number(s): P29354
    , Q14450, Q5BKA7, 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 105 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3