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Protein

Growth factor receptor-bound protein 2

Gene

Grb2

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

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-RNO-109704 PI3K Cascade
R-RNO-112412 SOS-mediated signalling
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 family interactions
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-8983432 Interleukin-15 signaling
R-RNO-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-RNO-9032759 NTRK2 activates RAC1
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi619758 Grb2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
SwissPalmiP62994

Expressioni

Tissue specificityi

Wide tissue distribution.1 Publication

Gene expression databases

BgeeiENSRNOG00000003990 Expressed in 10 organ(s), highest expression level in spleen
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). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (By similarity).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249501, 12 interactors
CORUMiP62994
IntActiP62994, 15 interactors
MINTiP62994
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

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

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

Family and domain databases

CDDicd11949 SH3_GRB2_C, 1 hit
cd11946 SH3_GRB2_N, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR030219 Grb2
IPR035643 GRB2_C_SH3
IPR035641 GRB2_N_SH3
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR24418:SF290 PTHR24418:SF290, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF00018 SH3_1, 2 hits
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 2 hits
SUPFAMiSSF50044 SSF50044, 2 hits
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits

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

Similar proteinsi

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, 12 interactors
CORUMiP62994
IntActiP62994, 15 interactors
MINTiP62994
STRINGi10116.ENSRNOP00000005347

PTM databases

iPTMnetiP62994
PhosphoSitePlusiP62994
SwissPalmiP62994

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
OMAiHWWHGEI
OrthoDBiEOG091G0HWS
PhylomeDBiP62994
TreeFamiTF354288

Enzyme and pathway databases

ReactomeiR-RNO-109704 PI3K Cascade
R-RNO-112412 SOS-mediated signalling
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 family interactions
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-8983432 Interleukin-15 signaling
R-RNO-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-RNO-9032759 NTRK2 activates RAC1
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

PROiPR:P62994

Gene expression databases

BgeeiENSRNOG00000003990 Expressed in 10 organ(s), highest expression level in spleen
GenevisibleiP62994 RN

Family and domain databases

CDDicd11949 SH3_GRB2_C, 1 hit
cd11946 SH3_GRB2_N, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR030219 Grb2
IPR035643 GRB2_C_SH3
IPR035641 GRB2_N_SH3
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR24418:SF290 PTHR24418:SF290, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF00018 SH3_1, 2 hits
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 2 hits
SUPFAMiSSF50044 SSF50044, 2 hits
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiGRB2_RAT
AccessioniPrimary (citable) accession number: P62994
Secondary accession number(s): P29354
, Q14450, Q5BKA7, Q63057, Q63059
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: August 31, 2004
Last modified: November 7, 2018
This is version 143 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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