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Entry version 209 (13 Nov 2019)
Sequence version 1 (01 Nov 1996)
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Protein

Growth factor receptor-bound protein 2

Gene

Grb2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 (By similarity).By similarity

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-109704 PI3K Cascade
R-MMU-112412 SOS-mediated signalling
R-MMU-1250347 SHC1 events in ERBB4 signaling
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1295596 Spry regulation of FGF signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-1433559 Regulation of KIT signaling
R-MMU-167044 Signalling to RAS
R-MMU-179812 GRB2 events in EGFR signaling
R-MMU-180292 GAB1 signalosome
R-MMU-180336 SHC1 events in EGFR signaling
R-MMU-182971 EGFR downregulation
R-MMU-186763 Downstream signal transduction
R-MMU-1963640 GRB2 events in ERBB2 signaling
R-MMU-1963642 PI3K events in ERBB2 signaling
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-210993 Tie2 Signaling
R-MMU-2179392 EGFR Transactivation by Gastrin
R-MMU-2424491 DAP12 signaling
R-MMU-2428933 SHC-related events triggered by IGF1R
R-MMU-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-MMU-2871796 FCERI mediated MAPK activation
R-MMU-2871809 FCERI mediated Ca+2 mobilization
R-MMU-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-MMU-375165 NCAM signaling for neurite out-growth
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389359 CD28 dependent Vav1 pathway
R-MMU-391160 Signal regulatory protein family interactions
R-MMU-5654688 SHC-mediated cascade:FGFR1
R-MMU-5654689 PI-3K cascade:FGFR1
R-MMU-5654693 FRS-mediated FGFR1 signaling
R-MMU-5654695 PI-3K cascade:FGFR2
R-MMU-5654699 SHC-mediated cascade:FGFR2
R-MMU-5654700 FRS-mediated FGFR2 signaling
R-MMU-5654704 SHC-mediated cascade:FGFR3
R-MMU-5654706 FRS-mediated FGFR3 signaling
R-MMU-5654710 PI-3K cascade:FGFR3
R-MMU-5654712 FRS-mediated FGFR4 signaling
R-MMU-5654719 SHC-mediated cascade:FGFR4
R-MMU-5654720 PI-3K cascade:FGFR4
R-MMU-5654726 Negative regulation of FGFR1 signaling
R-MMU-5654727 Negative regulation of FGFR2 signaling
R-MMU-5654732 Negative regulation of FGFR3 signaling
R-MMU-5654733 Negative regulation of FGFR4 signaling
R-MMU-5663213 RHO GTPases Activate WASPs and WAVEs
R-MMU-5673001 RAF/MAP kinase cascade
R-MMU-6807004 Negative regulation of MET activity
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-74749 Signal attenuation
R-MMU-74751 Insulin receptor signalling cascade
R-MMU-8851805 MET activates RAS signaling
R-MMU-8851907 MET activates PI3K/AKT signaling
R-MMU-8853659 RET signaling
R-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis
R-MMU-8865999 MET activates PTPN11
R-MMU-8875555 MET activates RAP1 and RAC1
R-MMU-8875656 MET receptor recycling
R-MMU-8983432 Interleukin-15 signaling
R-MMU-9027284 Erythropoietin activates RAS
R-MMU-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912631 Regulation of signaling by CBL
R-MMU-9607240 FLT3 Signaling
R-MMU-9645139 Stat5 Activation
R-MMU-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Growth factor receptor-bound protein 2
Alternative name(s):
Adapter protein GRB2
SH2/SH3 adapter GRB2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Grb2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:95805 Grb2

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Cellular componenti

Cytoplasm, Endosome, Golgi apparatus, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL4830

DrugCentral

More...
DrugCentrali
Q60631

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000881991 – 217Growth factor receptor-bound protein 2Add BLAST217

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

More...
EPDi
Q60631

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q60631

PeptideAtlas

More...
PeptideAtlasi
Q60631

PRoteomics IDEntifications database

More...
PRIDEi
Q60631

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q60631

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q60631

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
Q60631

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in macrophages.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000059923 Expressed in 296 organ(s), highest expression level in brain

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
Q60631 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q60631 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (By similarity).

Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (PubMed:8943348).

Interacts with IRS4 (when Tyr-phosphorylated) (PubMed:11113178). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains (By similarity). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis.

Interacts with SOS1 (By similarity).

Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (By similarity).

Interacts with phosphorylated MET (By similarity).

Interacts with phosphorylated TOM1L1 (PubMed:11711534).

Interacts with the phosphorylated C-terminus of SH2B2 (By similarity).

Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:16249387, PubMed:14610044, PubMed:15477350, PubMed:15477348, PubMed:22561606).

Interacts with NISCH, PTPNS1 and REPS2 (By similarity).

Interacts with syntrophin SNTA1 (PubMed:11551227).

Interacts (via SH3 domains) with REPS1 (PubMed:9395447).

Interacts (via SH3 domains) with PIK3C2B (By similarity).

Interacts with CBL and CBLB (By similarity).

Interacts with AJUBA and CLNK (PubMed:10330178, PubMed:11463797).

Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (PubMed:10521483).

Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (By similarity).

Interacts with PTPN11 (PubMed:8943348).

Interacts with PRNP (PubMed:11571277).

Interacts with RALGPS1 (By similarity).

Interacts also with HCST (PubMed:16582911).

Interacts with KDR (PubMed:16966330).

Interacts with FLT1 (tyrosine-phosphorylated) (PubMed:9722576).

Interacts with GAPT and PTPRE (By similarity).

Interacts (via SH2 domain) with KIF26A (By similarity).

Interacts (via SH3 2) with GAB2 (PubMed:10068651).

Interacts with ADAM15 (By similarity).

Interacts with THEMIS2 (PubMed:20644716).

Interacts (via SH2 domain) with AXL (phosphorylated) (By similarity).

Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:10377264).

Interacts with PTPRJ and BCR (By similarity).

Interacts with PTPN23 (By similarity).

Interacts with FLT4 (tyrosine phosphorylated) (By similarity).

Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:12925710).

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 (By similarity).

Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046).

Interacts with ERBB4 (By similarity).

Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity).

Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:7997267).

Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (By similarity).

Interacts (via SH2-domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-58' (PubMed:21930792, PubMed:28098138, PubMed:28290451).

Interacts (via SH3 domains) with GAREM1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (By similarity).

Interacts with DAB2 (PubMed:9569023).

Interacts with TESPA1 (By similarity).

Interacts with THEMIS (PubMed:19597498, PubMed:19597497, PubMed:19805304, PubMed:22561606).

Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (PubMed:22561606).

Interacts with CD28 (By similarity).

Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (PubMed:21543326).

Interacts with ASAP3 (phosphorylated form) (By similarity).

Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064).

Interacts with PTPRO (phosphorylated form) (PubMed:20398064).

Interacts with PTPRB (phosphorylated form) (PubMed:20398064).

Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (By similarity).

Interacts with ST5 (By similarity).

Interacts (via SH3 domain) with ZDHHC19 (via SH3-binding motif); leading to recruit STAT3 (By similarity).

By similarity32 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
200046, 46 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q60631

Database of interacting proteins

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DIPi
DIP-259N

Protein interaction database and analysis system

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IntActi
Q60631, 77 interactors

Molecular INTeraction database

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MINTi
Q60631

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000021090

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q60631

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1217
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q60631

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q60631

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1 – 58SH3 1PROSITE-ProRule annotationAdd BLAST58
Domaini60 – 152SH2PROSITE-ProRule annotationAdd BLAST93
Domaini156 – 215SH3 2PROSITE-ProRule annotationAdd BLAST60

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The SH3 domains mediate interaction with RALGPS1 and SHB.By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the GRB2/sem-5/DRK family.Curated

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG3601 Eukaryota
ENOG410XR1G LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000155738

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000251625

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q60631

KEGG Orthology (KO)

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KOi
K04364

Identification of Orthologs from Complete Genome Data

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OMAi
YHRSASV

Database of Orthologous Groups

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OrthoDBi
1091250at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q60631

TreeFam database of animal gene trees

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TreeFami
TF354288

Family and domain databases

Conserved Domains Database

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CDDi
cd11949 SH3_GRB2_C, 1 hit
cd11946 SH3_GRB2_N, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.30.505.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View 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

The PANTHER Classification System

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PANTHERi
PTHR46037:SF4 PTHR46037:SF4, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00017 SH2, 1 hit
PF00018 SH3_1, 2 hits

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00401 SH2DOMAIN
PR00452 SH3DOMAIN

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 2 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q60631-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
IEQMPQQPTY VQALFDFDPQ EDGELGFRRG DFIHVMDNSD PNWWKGACHG
210
QTGMFPRNYV TPVNRNV
Length:217
Mass (Da):25,238
Last modified:November 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i97F4A4FE4B248DDF
GO
Isoform 2 (identifier: Q60631-2) [UniParc]FASTAAdd to basket
Also known as: GRB3-3

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

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Length:176
Mass (Da):20,589
Checksum:i64323FA95FE940C5
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1AT92B1AT92_MOUSE
Growth factor receptor-bound protei...
Grb2
203Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B1AT95B1AT95_MOUSE
Growth factor receptor-bound protei...
Grb2
71Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_00184160 – 100Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
U07617 mRNA Translation: AAB40022.1
D85748 mRNA Translation: BAA12862.1
BC052377 mRNA Translation: AAH52377.1
BC085254 mRNA Translation: AAH85254.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS25645.1 [Q60631-1]

Protein sequence database of the Protein Information Resource

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PIRi
A54688

NCBI Reference Sequences

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RefSeqi
NP_001300865.1, NM_001313936.1 [Q60631-1]
NP_001300866.1, NM_001313937.1 [Q60631-1]
NP_032189.1, NM_008163.4 [Q60631-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENSMUST00000021090; ENSMUSP00000021090; ENSMUSG00000059923 [Q60631-1]
ENSMUST00000106497; ENSMUSP00000102106; ENSMUSG00000059923 [Q60631-1]
ENSMUST00000106499; ENSMUSP00000102108; ENSMUSG00000059923 [Q60631-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
14784

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:14784

UCSC genome browser

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UCSCi
uc007mii.1 mouse [Q60631-2]
uc007mij.1 mouse [Q60631-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

Grb2 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07617 mRNA Translation: AAB40022.1
D85748 mRNA Translation: BAA12862.1
BC052377 mRNA Translation: AAH52377.1
BC085254 mRNA Translation: AAH85254.1
CCDSiCCDS25645.1 [Q60631-1]
PIRiA54688
RefSeqiNP_001300865.1, NM_001313936.1 [Q60631-1]
NP_001300866.1, NM_001313937.1 [Q60631-1]
NP_032189.1, NM_008163.4 [Q60631-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GBQNMR-A1-61[»]
1GBRNMR-A1-59[»]
2GBQNMR-A1-59[»]
3GBQNMR-A1-59[»]
4GBQNMR-A1-59[»]
SMRiQ60631
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi200046, 46 interactors
CORUMiQ60631
DIPiDIP-259N
IntActiQ60631, 77 interactors
MINTiQ60631
STRINGi10090.ENSMUSP00000021090

Chemistry databases

BindingDBiQ60631
ChEMBLiCHEMBL4830
DrugCentraliQ60631

PTM databases

iPTMnetiQ60631
PhosphoSitePlusiQ60631
SwissPalmiQ60631

Proteomic databases

EPDiQ60631
PaxDbiQ60631
PeptideAtlasiQ60631
PRIDEiQ60631

Genome annotation databases

EnsembliENSMUST00000021090; ENSMUSP00000021090; ENSMUSG00000059923 [Q60631-1]
ENSMUST00000106497; ENSMUSP00000102106; ENSMUSG00000059923 [Q60631-1]
ENSMUST00000106499; ENSMUSP00000102108; ENSMUSG00000059923 [Q60631-2]
GeneIDi14784
KEGGimmu:14784
UCSCiuc007mii.1 mouse [Q60631-2]
uc007mij.1 mouse [Q60631-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
2885
MGIiMGI:95805 Grb2

Phylogenomic databases

eggNOGiKOG3601 Eukaryota
ENOG410XR1G LUCA
GeneTreeiENSGT00940000155738
HOGENOMiHOG000251625
InParanoidiQ60631
KOiK04364
OMAiYHRSASV
OrthoDBi1091250at2759
PhylomeDBiQ60631
TreeFamiTF354288

Enzyme and pathway databases

ReactomeiR-MMU-109704 PI3K Cascade
R-MMU-112412 SOS-mediated signalling
R-MMU-1250347 SHC1 events in ERBB4 signaling
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1295596 Spry regulation of FGF signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-1433559 Regulation of KIT signaling
R-MMU-167044 Signalling to RAS
R-MMU-179812 GRB2 events in EGFR signaling
R-MMU-180292 GAB1 signalosome
R-MMU-180336 SHC1 events in EGFR signaling
R-MMU-182971 EGFR downregulation
R-MMU-186763 Downstream signal transduction
R-MMU-1963640 GRB2 events in ERBB2 signaling
R-MMU-1963642 PI3K events in ERBB2 signaling
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-210993 Tie2 Signaling
R-MMU-2179392 EGFR Transactivation by Gastrin
R-MMU-2424491 DAP12 signaling
R-MMU-2428933 SHC-related events triggered by IGF1R
R-MMU-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-MMU-2871796 FCERI mediated MAPK activation
R-MMU-2871809 FCERI mediated Ca+2 mobilization
R-MMU-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-MMU-375165 NCAM signaling for neurite out-growth
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389359 CD28 dependent Vav1 pathway
R-MMU-391160 Signal regulatory protein family interactions
R-MMU-5654688 SHC-mediated cascade:FGFR1
R-MMU-5654689 PI-3K cascade:FGFR1
R-MMU-5654693 FRS-mediated FGFR1 signaling
R-MMU-5654695 PI-3K cascade:FGFR2
R-MMU-5654699 SHC-mediated cascade:FGFR2
R-MMU-5654700 FRS-mediated FGFR2 signaling
R-MMU-5654704 SHC-mediated cascade:FGFR3
R-MMU-5654706 FRS-mediated FGFR3 signaling
R-MMU-5654710 PI-3K cascade:FGFR3
R-MMU-5654712 FRS-mediated FGFR4 signaling
R-MMU-5654719 SHC-mediated cascade:FGFR4
R-MMU-5654720 PI-3K cascade:FGFR4
R-MMU-5654726 Negative regulation of FGFR1 signaling
R-MMU-5654727 Negative regulation of FGFR2 signaling
R-MMU-5654732 Negative regulation of FGFR3 signaling
R-MMU-5654733 Negative regulation of FGFR4 signaling
R-MMU-5663213 RHO GTPases Activate WASPs and WAVEs
R-MMU-5673001 RAF/MAP kinase cascade
R-MMU-6807004 Negative regulation of MET activity
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-74749 Signal attenuation
R-MMU-74751 Insulin receptor signalling cascade
R-MMU-8851805 MET activates RAS signaling
R-MMU-8851907 MET activates PI3K/AKT signaling
R-MMU-8853659 RET signaling
R-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis
R-MMU-8865999 MET activates PTPN11
R-MMU-8875555 MET activates RAP1 and RAC1
R-MMU-8875656 MET receptor recycling
R-MMU-8983432 Interleukin-15 signaling
R-MMU-9027284 Erythropoietin activates RAS
R-MMU-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912631 Regulation of signaling by CBL
R-MMU-9607240 FLT3 Signaling
R-MMU-9645139 Stat5 Activation
R-MMU-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
Grb2 mouse
EvolutionaryTraceiQ60631

Protein Ontology

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PROi
PR:Q60631

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000059923 Expressed in 296 organ(s), highest expression level in brain
ExpressionAtlasiQ60631 baseline and differential
GenevisibleiQ60631 MM

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
PANTHERiPTHR46037:SF4 PTHR46037:SF4, 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, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiGRB2_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q60631
Secondary accession number(s): Q61240
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 13, 2019
This is version 209 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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