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Protein

Growth factor receptor-bound protein 2

Gene

Grb2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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 similarity1 Publication

GO - Molecular functioni

  • enzyme binding Source: RGD
  • epidermal growth factor receptor binding Source: UniProtKB
  • insulin receptor substrate binding Source: RGD
  • phosphoprotein binding Source: RGD
  • phosphotyrosine binding Source: RGD
  • poly(A) RNA binding Source: Ensembl
  • protein domain specific binding Source: RGD
  • SH3 domain binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-109704. PI3K Cascade.
R-RNO-112412. SOS-mediated signalling.
R-RNO-114604. GPVI-mediated activation cascade.
R-RNO-1250347. SHC1 events in ERBB4 signaling.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1295596. Spry regulation of FGF signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-1433559. Regulation of KIT signaling.
R-RNO-167044. Signalling to RAS.
R-RNO-179812. GRB2 events in EGFR signaling.
R-RNO-180292. GAB1 signalosome.
R-RNO-180336. SHC1 events in EGFR signaling.
R-RNO-182971. EGFR downregulation.
R-RNO-186763. Downstream signal transduction.
R-RNO-1963640. GRB2 events in ERBB2 signaling.
R-RNO-1963642. PI3K events in ERBB2 signaling.
R-RNO-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-RNO-210993. Tie2 Signaling.
R-RNO-2179392. EGFR Transactivation by Gastrin.
R-RNO-2424491. DAP12 signaling.
R-RNO-2428933. SHC-related events triggered by IGF1R.
R-RNO-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-2871809. FCERI mediated Ca+2 mobilization.
R-RNO-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-388841. Costimulation by the CD28 family.
R-RNO-389359. CD28 dependent Vav1 pathway.
R-RNO-391160. Signal regulatory protein (SIRP) family interactions.
R-RNO-392451. G beta:gamma signalling through PI3Kgamma.
R-RNO-5654688. SHC-mediated cascade:FGFR1.
R-RNO-5654689. PI-3K cascade:FGFR1.
R-RNO-5654693. FRS-mediated FGFR1 signaling.
R-RNO-5654695. PI-3K cascade:FGFR2.
R-RNO-5654699. SHC-mediated cascade:FGFR2.
R-RNO-5654700. FRS-mediated FGFR2 signaling.
R-RNO-5654704. SHC-mediated cascade:FGFR3.
R-RNO-5654706. FRS-mediated FGFR3 signaling.
R-RNO-5654710. PI-3K cascade:FGFR3.
R-RNO-5654712. FRS-mediated FGFR4 signaling.
R-RNO-5654719. SHC-mediated cascade:FGFR4.
R-RNO-5654720. PI-3K cascade:FGFR4.
R-RNO-5654726. Negative regulation of FGFR1 signaling.
R-RNO-5654727. Negative regulation of FGFR2 signaling.
R-RNO-5654732. Negative regulation of FGFR3 signaling.
R-RNO-5654733. Negative regulation of FGFR4 signaling.
R-RNO-5663213. RHO GTPases Activate WASPs and WAVEs.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-6807004. Negative regulation of MET activity.
R-RNO-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-RNO-74749. Signal attenuation.
R-RNO-74751. Insulin receptor signalling cascade.
R-RNO-8851805. MET activates RAS signaling.
R-RNO-8851907. MET activates PI3K/AKT signaling.
R-RNO-8853659. RET signaling.
R-RNO-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-RNO-8856828. Clathrin-mediated endocytosis.
R-RNO-8865999. MET activates PTPN11.
R-RNO-8875555. MET activates RAP1 and RAC1.
R-RNO-8875656. MET receptor recycling.
R-RNO-912526. Interleukin receptor SHC signaling.
R-RNO-912631. Regulation of signaling by CBL.
R-RNO-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

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
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi619758. Grb2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Golgi apparatus, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000882011 – 217Growth factor receptor-bound protein 2Add BLAST217

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei6N6-acetyllysineBy similarity1
Modified residuei50N6-acetyllysineBy similarity1
Modified residuei109N6-acetyllysineBy similarity1
Modified residuei211PhosphothreonineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP62994.
PRIDEiP62994.

PTM databases

iPTMnetiP62994.
PhosphoSitePlusiP62994.

Expressioni

Tissue specificityi

Wide tissue distribution.1 Publication

Gene expression databases

BgeeiENSRNOG00000003990.
GenevisibleiP62994. RN.

Interactioni

Subunit structurei

Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect. Interacts with IRS4 (when Tyr-phosphorylated). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, 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. Interacts with SOS1. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with phosphorylated MET. Interacts with phosphorylated TOM1L1. 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 and REPS2. Interacts with syntrophin SNTA1. Interacts (via SH3 domains) with REPS1. Interacts (via SH3 domains) with PIK3C2B. Interacts with CBL and CBLB. Interacts with AJUBA and CLNK. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Interacts with PTPN11. Interacts with PRNP. Interacts with RALGPS1. Interacts also with HCST. Interacts with KDR. Interacts with FLT1 (tyrosine-phosphorylated). 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 (phosphorylated). Interacts (via SH2 domain) with KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with PTPN23. Interacts with FLT4 (tyrosine phosphorylated). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2. Interacts with ERBB4. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts with PTK2B/PYK2 (tyrosine phosphorylated). Interacts with SCIMP. Interacts (via SH3 domains) with GAREM1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation. Interacts with DAB2. Interacts with TESPA1. Interacts with THEMIS. Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1. Interacts with CD28. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts with ASAP3 (phosphorylated form) (By similarity). Interacts (via SH2 domain) with CSF1R and IRS1 (tyrosine phosphorylated) (PubMed:8262059, PubMed:8388384). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity).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.

GO - Molecular functioni

  • enzyme binding Source: RGD
  • epidermal growth factor receptor binding Source: UniProtKB
  • insulin receptor substrate binding Source: RGD
  • phosphoprotein binding Source: RGD
  • phosphotyrosine binding Source: RGD
  • protein domain specific binding Source: RGD
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi249501. 10 interactors.
IntActiP62994. 15 interactors.
MINTiMINT-93691.
STRINGi10116.ENSRNOP00000005347.

Structurei

3D structure databases

ProteinModelPortaliP62994.
SMRiP62994.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 58SH3 1PROSITE-ProRule annotationAdd BLAST58
Domaini60 – 152SH2PROSITE-ProRule annotationAdd BLAST93
Domaini156 – 215SH3 2PROSITE-ProRule annotationAdd BLAST60

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

eggNOGiKOG3601. Eukaryota.
ENOG410XR1G. LUCA.
GeneTreeiENSGT00820000126999.
HOGENOMiHOG000251625.
HOVERGENiHBG005404.
InParanoidiP62994.
KOiK04364.
OMAiYDFTPQE.
OrthoDBiEOG091G0HWS.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00183860 – 217Missing in isoform 3. 1 PublicationAdd BLAST158
Alternative sequenceiVSP_001840157 – 170Missing in isoform 2. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP62994.
SMRiP62994.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249501. 10 interactors.
IntActiP62994. 15 interactors.
MINTiMINT-93691.
STRINGi10116.ENSRNOP00000005347.

PTM databases

iPTMnetiP62994.
PhosphoSitePlusiP62994.

Proteomic databases

PaxDbiP62994.
PRIDEiP62994.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2885.
RGDi619758. Grb2.

Phylogenomic databases

eggNOGiKOG3601. Eukaryota.
ENOG410XR1G. LUCA.
GeneTreeiENSGT00820000126999.
HOGENOMiHOG000251625.
HOVERGENiHBG005404.
InParanoidiP62994.
KOiK04364.
OMAiYDFTPQE.
OrthoDBiEOG091G0HWS.
PhylomeDBiP62994.
TreeFamiTF354288.

Enzyme and pathway databases

ReactomeiR-RNO-109704. PI3K Cascade.
R-RNO-112412. SOS-mediated signalling.
R-RNO-114604. GPVI-mediated activation cascade.
R-RNO-1250347. SHC1 events in ERBB4 signaling.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1295596. Spry regulation of FGF signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-1433559. Regulation of KIT signaling.
R-RNO-167044. Signalling to RAS.
R-RNO-179812. GRB2 events in EGFR signaling.
R-RNO-180292. GAB1 signalosome.
R-RNO-180336. SHC1 events in EGFR signaling.
R-RNO-182971. EGFR downregulation.
R-RNO-186763. Downstream signal transduction.
R-RNO-1963640. GRB2 events in ERBB2 signaling.
R-RNO-1963642. PI3K events in ERBB2 signaling.
R-RNO-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-RNO-210993. Tie2 Signaling.
R-RNO-2179392. EGFR Transactivation by Gastrin.
R-RNO-2424491. DAP12 signaling.
R-RNO-2428933. SHC-related events triggered by IGF1R.
R-RNO-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-2871809. FCERI mediated Ca+2 mobilization.
R-RNO-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-388841. Costimulation by the CD28 family.
R-RNO-389359. CD28 dependent Vav1 pathway.
R-RNO-391160. Signal regulatory protein (SIRP) family interactions.
R-RNO-392451. G beta:gamma signalling through PI3Kgamma.
R-RNO-5654688. SHC-mediated cascade:FGFR1.
R-RNO-5654689. PI-3K cascade:FGFR1.
R-RNO-5654693. FRS-mediated FGFR1 signaling.
R-RNO-5654695. PI-3K cascade:FGFR2.
R-RNO-5654699. SHC-mediated cascade:FGFR2.
R-RNO-5654700. FRS-mediated FGFR2 signaling.
R-RNO-5654704. SHC-mediated cascade:FGFR3.
R-RNO-5654706. FRS-mediated FGFR3 signaling.
R-RNO-5654710. PI-3K cascade:FGFR3.
R-RNO-5654712. FRS-mediated FGFR4 signaling.
R-RNO-5654719. SHC-mediated cascade:FGFR4.
R-RNO-5654720. PI-3K cascade:FGFR4.
R-RNO-5654726. Negative regulation of FGFR1 signaling.
R-RNO-5654727. Negative regulation of FGFR2 signaling.
R-RNO-5654732. Negative regulation of FGFR3 signaling.
R-RNO-5654733. Negative regulation of FGFR4 signaling.
R-RNO-5663213. RHO GTPases Activate WASPs and WAVEs.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-6807004. Negative regulation of MET activity.
R-RNO-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-RNO-74749. Signal attenuation.
R-RNO-74751. Insulin receptor signalling cascade.
R-RNO-8851805. MET activates RAS signaling.
R-RNO-8851907. MET activates PI3K/AKT signaling.
R-RNO-8853659. RET signaling.
R-RNO-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-RNO-8856828. Clathrin-mediated endocytosis.
R-RNO-8865999. MET activates PTPN11.
R-RNO-8875555. MET activates RAP1 and RAC1.
R-RNO-8875656. MET receptor recycling.
R-RNO-912526. Interleukin receptor SHC signaling.
R-RNO-912631. Regulation of signaling by CBL.
R-RNO-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Miscellaneous databases

PROiP62994.

Gene expression databases

BgeeiENSRNOG00000003990.
GenevisibleiP62994. RN.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 127 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.