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P62994

- GRB2_RAT

UniProt

P62994 - GRB2_RAT

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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

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. poly(A) RNA binding Source: Ensembl
  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: Ensembl
  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
Complete GO annotation...

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. cell-cell junction Source: Ensembl
  2. COP9 signalosome Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: Reactome
  5. endosome Source: UniProtKB
  6. extracellular vesicular exosome Source: Ensembl
  7. Golgi apparatus Source: UniProtKB-KW
  8. Grb2-EGFR complex Source: Ensembl
  9. nucleus Source: UniProtKB
  10. protein complex Source: RGD
  11. vesicle membrane Source: Ensembl
Complete GO annotation...

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

        10         20         30         40         50
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK
60 70 80 90 100
NYIEMKPHPW FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK
110 120 130 140 150
FGNDVQHFKV LRDGAGKYFL WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD
160 170 180 190 200
IEQVPQQPTY VQALFDFDPQ EDGELGFRRG DFIHVMDNSD PNWWKGACHG
210
QTGMFPRNYV TPVNRNV
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

« Hide 'large scale' publications
  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 29, 2014
This is version 106 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