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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

GRB2 Gene

protein-coding GIFtS: 72
GCID: GC17M073313

growth factor receptor-bound protein 2

Explore 65 diseases affiliated with
GRB2 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Growth Factor Receptor-Bound Protein 2¹ ²		HT027²
NCKAP2¹ ²		MST084²
Protein Ash² ³		MSTP084²
ASH² ³		Abundant SRC Homology²
SH2/SH3 Adapter GRB2² ³		Epidermal Growth Factor Receptor-Binding Protein GRB2²
EGFRBP-GRB2²		Growth Factor Receptor-Bound Protein 3²
Grb3-3²		Adapter Protein GRB2³

External Ids:	HGNC: 4566¹	Entrez Gene: 2885²	Ensembl: ENSG00000177885⁷	OMIM: 108355⁵	UniProtKB: P62993³

Export aliases for GRB2 gene to outside databases

Previous GC identifers: GC17M076374 GC17M073779 GC17M073911 GC17M070825 GC17M068724

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for GRB2:

The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3

domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain

binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the

signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found

for this gene. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993

Function: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras

signaling pathway

Function: 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

Gene Wiki entry for GRB2

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010783.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the GRB2 gene promoter:
p53 Sp1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: GRB2 promoter sequence

Search SABiosciences Chromatin IP Primers for GRB2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat GRB2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q24-q25 Ensembl cytogenetic band: 17q25.1 HGNC cytogenetic band: 17q24-q25

GRB2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GRB2 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M073313: view genomic region (about GC identifiers)

Start:	73,314,157 bp from pter	End:	73,401,790 bp from pter
Size:	87,634 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993 (See protein sequence)

Recommended Name: Growth factor receptor-bound protein 2

Size: 217 amino acids; 25206 Da

Subunit: 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, IRS1, 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 NISCH, PTPNS1, REPS2 and the syntrophin SNTA1. Interacts

with REPS1 and PIK3C2B via its SH3 domains (By similarity). Interacts with HCV NS5A via its SH3 domains. Interacts

with CBL and CBLB. Interacts with AJUBA and CLNK (By similarity). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine

phosphorylated) (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Forms a complex with MUC1 and

SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with

PTPN11. Interacts with PRNP and THEMIS (By similarity). Interacts with FLT1 (tyrosine phosphorylated) and KDR.

Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By similarity). Interacts with

RALGPS1 and with HCST. Interacts (via SH3 domain) with HEV ORF3 protein. 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 and KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with FLT4 (tyrosine

phosphorylated). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Interacts

with PTPN23. Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL, in which GRB2

promotes RTK recruitment by TNK2. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with

ERBB4. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated).

Interacts with PTK2B/PYK2 (tyrosine phosphorylated). Isoform 1 interacts with SCIMP. Interacts with PLCG1, LAT and

THEMIS upon TCR activation in thymocytes (By similarity). Interacts with TESPA1 and DAB2. Interacts (via SH3 domains)

with GAREM isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF

stimulation

Subcellular location: Nucleus. Cytoplasm. Endosome. Golgi apparatus (By similarity)

6/43 PDB 3D structures from and Proteopedia for GRB2 (see all 43):

1AZE (3D)

1BM2 (3D)

1BMB (3D)

1CJ1 (3D)

1FHS (3D)

1FYR (3D)

Secondary accessions: P29354 Q14450 Q63057 Q63059

Alternative splicing: 2 isoforms: P62993-1, P29354-1 P62993-2, P29354-2

Explore the universe of human proteins at neXtProt for GRB2: NX_P62993

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P62993

GRB2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_002077.1 NP_987102.1

ENSEMBL proteins:

ENSP00000463525 ENSP00000376346 ENSP00000376347 ENSP00000376345 ENSP00000339007

ENSP00000464279 ENSP00000462785 ENSP00000317360

Reactome Protein details: P62993
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant GRB2 Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: GRB2 OriGene Protein Over-expression Lysate (see all 3): GRB2 OriGene Custom Protein Services for GRB2
	GenScript Custom Purified and Recombinant Proteins Services for GRB2
	Novus Biologicals GRB2 Proteins Novus Biologicals GRB2 Lysate
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for GRB2
	Browse Proteins at Uscn

Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005737	cytoplasm	IDA	--
GO:0005768	endosome	IDA	--
GO:0005794	Golgi apparatus	IEA	--
GO:0005829	cytosol	TAS	--

GRB2 for ontologies About GeneDecksing

GRB2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of GRB2
	R&D Systems Antibodies for GRB2
	Cell Signaling Technology (CST) Antibodies for GRB2
	OriGene Antibodies (see all 4): GRB2 OriGene Custom Antibody Services for GRB2
	GenScript Custom Superior Antibodies Services for GRB2
	Novus Biologicals GRB2 Antibodies
	Abcam antibodies for GRB2
	Browse Antibodies at Uscn
	ThermoFisher Antibody for GRB2

Assay Products for GRB2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for GRB2
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

GRB2 for domains About GeneDecksing

3 InterPro domains/families:

IPR000108 p67phox

IPR001452 SH3_domain

IPR000980 SH2

Graphical View of Domain Structure for InterPro Entry P62993

ProtoNet protein and cluster: P62993

UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993

Domain: The SH3 domains mediate interaction with RALGPS1 and SHB

Similarity: Belongs to the GRB2/sem-5/DRK family

Similarity: Contains 1 SH2 domain

Similarity: Contains 2 SH3 domains

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993

Function: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras

signaling pathway

Function: 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

Genatlas biochemistry entry for GRB2:

growth factor receptor bound protein 2,major CBL associated protein,homolog to Caenorhabditis elegans Sem5 gene and

Drosophila Drk,STAR playing a key role in insulin signal transduction through connecting with IRS1 and IGFR5,and in

mitogenic RAS signalic through interaction with SHC1

miRNA Products:		miRTarBase miRNAs that target GRB2: hsa-mir-433 (MIRT001201)

		OriGene 3'-UTR Clone (see all 2): GRB2 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat GRB2
		8/61 QIAGEN miScript miRNA Assays for microRNAs that regulate GRB2 (see all 61):
		hsa-miR-4291 hsa-miR-1224-3p hsa-miR-513a-5p hsa-miR-128 hsa-miR-200a hsa-miR-1260b hsa-miR-507 hsa-miR-105

		SwitchGear 3'UTR luciferase reporter plasmid: GRB2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for GRB2 (see all 7) OriGene shRNA RFP: GRB2 OriGene siRNA: GRB2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat GRB2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for GRB2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for GRB2 (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for GRB2 (see all 2) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): GRB2 (NM_002086)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for GRB2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat GRB2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for GRB2
		Search LifeMap BioReagents cell lines for GRB2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GRB2

Gene Ontology (GO): 5/13 molecular function terms (GO ID links to tree view) (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001784	phosphotyrosine binding	IEA	--
GO:0005070	SH3/SH2 adaptor activity	TAS	8253073
GO:0005154	epidermal growth factor receptor binding	IPI	12577067
GO:0005168	neurotrophin TRKA receptor binding	IPI	15488758
GO:0005515	protein binding	IPI	--

GRB2 for ontologies About GeneDecksing

3 GenomeRNAi human phenotypes for GRB2:

Decreased focal adhesion (FA)

Increased cell death HMECs cel

Upregulation of Wnt/beta-caten

Animal Models:
Mouse knock-out Grb2^tm1Paw for GRB2
15/16 MGI mutant phenotypes (inferred from 5 alleles) (MGI details for Grb2) (see all 16):

behavior/neurological	cardiovascular system	cellular	craniofacial	digestive/alimentary
embryogenesis	growth/size	hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism
immune system	mortality/aging	nervous system	normal	skeleton

GRB2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/165 super-pathways (see all 165) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Development_CNTF receptor signaling

8/22 pathways (see all 22)
Development_CNTF receptor signaling	1.00	Development Growth hormone signaling via PI3K/AKT and MAPK cascades	0.34
Development CNTF receptor signaling	1.00	Translation _Regulation of EIF4F activity	0.32
Transcription Receptor-mediated HIF regulation	0.43	Translation Regulation activity of EIF4F	0.32
Transcription_Receptor-mediated HIF regulation	0.43	ErbB2/ErbB3 signaling events	0.31

Development HGF signaling pathway

8/15 pathways (see all 15)
Development HGF signaling pathway	1.00	Signaling of Hepatocyte Growth Factor Receptor	0.35
Development_HGF signaling pathway	0.78	Development EGFR signaling via PIP3	0.26
Development_Neurotrophin family signaling	0.45	Development_EGFR signaling via PIP3	0.26
Development Neurotrophin family signaling	0.45	Apoptosis and survival_NGF signaling pathway	0.25

IL-9 Signaling Pathways

8/14 pathways (see all 14)
IL-9 Signaling Pathways	1.00	IL-9 Signaling Pathway	0.42
IL-21 Signaling Pathways	0.90	Immune response_IL-9 signaling pathway	0.42
IL-7 Signaling Pathways	0.90	Immune response IL-9 signaling pathway	0.42
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways	0.90	IL-7 Signaling Pathway	0.38

Signaling by FGFR

8/12 pathways (see all 12)
Signaling by FGFR	1.00	DAP12 signaling	0.83
Downstream signaling of activated FGFR	0.92	Signaling by EGFR in Cancer	0.83
Signaling by FGFR in disease	0.91	DAP12 interactions	0.76
Signaling by ERBB2	0.89	Signaling by PDGF	0.72

PIP3 activates AKT signaling

8/10 pathways (see all 10)
PI-3K cascade	1.00	PI3K/AKT activation	0.97
PIP3 activates AKT signaling	1.00	GAB1 signalosome	0.96
PI3K/AKT Signaling in Cancer	1.00	Constitutive PI3K/AKT Signaling in Cancer	0.88
PI3K events in ERBB2 signaling	1.00	Signaling by SCF-KIT	0.72

Pathway sources
See GeneCards unified pathways
Show all pathways

5/80 EMD Millipore Pathways for GRB2 (see all 80)

	Chemotaxis CXCR4 signaling pathway
	Immune response CD16 signaling in NK cells
	Cytoskeleton remodeling FAK signaling
	Cell adhesion Integrin-mediated cell adhesion and migration
	G-protein signaling G-Protein beta/gamma signaling cascades

5/9 R&D Systems Pathways for GRB2 (see all 9)

	IL-21 Signaling Pathways
	IL-2 Signaling Pathways
	IL-4 Signaling Pathways
	Adipocytokines & Insulin Signaling
	IL-7 Signaling Pathways

5/83 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for GRB2 (see all 83)

	Molecular Mechanisms of Cancer
	eIF2 Pathway
	JNK Pathway
	ITK and TCR Signaling
	ErbB Family Pathway

1 Cell Signaling Technology (CST) Pathway for GRB2

Tyrosine Kinases / Adaptors

5/82 GeneGo (Thomson Reuters) Pathways for GRB2 (see all 82)

	G-protein signaling H-RAS regulation pathway
	Development CNTF receptor signaling
	Development EGFR signaling pathway
	Immune response IL-9 signaling pathway
	Transcription PPAR Pathway

5/67 BioSystems Pathways for GRB2 (see all 67)

	DNA damage response (only ATM dependent)
	Signaling Pathways in Glioblastoma
	MAPK signaling pathway
	ErbB signaling pathway
	Focal Adhesion

5/94 Reactome Pathways for GRB2 (see all 94)

	SHC-related events
	EGFR Transactivation by Gastrin
	SHC1 mediates cytokine-induced phosphorylation of GAB2
	SHC-mediated signalling
	IRS-mediated signalling

1 PharmGKB Pathway for GRB2

EGFR Inhibitor Pathway, Pharmacodynamics

5/24 Kegg Pathways (Kegg details for GRB2) (see all 24):

	MAPK signaling pathway
	ErbB signaling pathway
	Chemokine signaling pathway
	Dorso-ventral axis formation
	Osteoclast differentiation

GRB2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for GRB2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/1214 Interacting proteins for GRB2 (P62993^{1, 2, 3} ENSP00000339007⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 1214)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
SHC1	P29353¹^,²^,³, ENSP00000401303⁴	EBI-401755,EBI-78835 MINT-6169992 MINT-8032691 MINT-8032762 MINT-8028762 MINT-7135507 MINT-8032822 MINT-8032838 MINT-61537 MINT-8032721 MINT-60983 MINT-1782399 MINT-8401377 MINT-7135483 MINT-8032777 MINT-49658 MINT-60982 MINT-8401389 MINT-7135494 I2D: score=15 STRING: ENSP00000401303
GAB2	Q9UQC2¹^,²^,³	EBI-401755,EBI-975200 MINT-7219506 MINT-7219550 MINT-7220613 MINT-7219528 MINT-7221243 MINT-7300447 MINT-7219679 MINT-58401 MINT-7219571 MINT-7219602 MINT-7219698 I2D: score=9
LAT	O43561²^,³, ENSP00000354119⁴	MINT-3382392 MINT-3382320 MINT-8032277 MINT-3382363 MINT-3382436 MINT-8032322 MINT-8034048 MINT-8032337 MINT-8033992 MINT-3382412 MINT-8034033 I2D: score=7 STRING: ENSP00000354119
HIST1H3A	P68431²^,³	MINT-61561 I2D: score=2
HIST1H3C	P68431²^,³	MINT-61561 I2D: score=2

About this table

Gene Ontology (GO): 5/25 biological process terms (GO ID links to tree view) (see all 25): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007173	epidermal growth factor receptor signaling pathway	TAS	--
GO:0007265	Ras protein signal transduction	TAS	--
GO:0007267	cell-cell signaling	TAS	8253073
GO:0007411	axon guidance	TAS	--
GO:0007568	aging	IEA	--

GRB2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

GRB2 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for GRB2

3 HMDB Compounds for GRB2 About this table

Compound	Synonyms	CAS #	PubMed Ids
Guanosine diphosphate	5'-GDP (see all 10)	146-91-8	--
Guanosine monophosphate	5'-GMP (see all 14)	85-32-5	--
Guanosine triphosphate	5'-GTP (see all 10)	86-01-1	--

2 DrugBank Compounds for GRB2 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
4-[(10s,14s,18s)-18-(2-Amino-2-Oxoethyl)-14-(1-Naphthylmethyl)-8,17,20-Trioxo-7,16,19-Triazaspiro[5.14]Icos-11-En-10-Yl]Benzylphosphonic Acid	--	--	target	--	17139284 17016423 10592235
Pegademase bovine	Adenosine aminohydrolase (see all 2)	9026-93-1	target	binder	9299436

10/52 Novoseek chemical compound relationships for GRB2 gene (see all 52) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tyrosine	89.5	626	8910422 (5), 8388384 (5), 8491186 (4), 11726515 (4) (see all 99)
phosphotyrosine	84.4	50	10356320 (2), 8391166 (1), 9183666 (1), 11689444 (1) (see all 34)
phosphatidylinositol	80.1	91	7961682 (3), 7791764 (3), 7692230 (2), 9565634 (2) (see all 72)
pp36	79.1	5	9541596 (2), 9529333 (2), 7544353 (1)
ag 1478	55.7	1	9722539 (1)
phosphoinositide	49	17	10330169 (1), 12220227 (1), 19438505 (1), 15579470 (1) (see all 13)
letrozole	45.7	8	15958587 (2), 15967659 (1), 17113978 (1), 19250202 (1) (see all 6)
wortmannin	45.6	1	16267404 (1)
phosphatidylinositol-3,4,5-trisphosphate	45.4	2	17923698 (1)
phenylalanine	44.9	9	11002419 (1), 16407827 (1), 7559570 (1), 8959326 (1) (see all 9)

Search CenterWatch for drugs/clinical trials and news about GRB2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for GRB2 gene (2 alternative transcripts):

NM_002086.4 NM_203506.2

Unigene Cluster for GRB2:

Growth factor receptor-bound protein 2

Hs.444356 [show with all ESTs]

Unigene Representative Sequence: NM_002086

11 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000581959 ENST00000392563 ENST00000392564 ENST00000392562 ENST00000316804(uc002jnx.4)

ENST00000578961 ENST00000462266 ENST00000582582 ENST00000583912 ENST00000577711

ENST00000316615(uc002jny.4)

miRNA Products:		OriGene 3'-UTR Clone (see all 2): GRB2 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat GRB2
		8/61 QIAGEN miScript miRNA Assays for microRNAs that regulate GRB2 (see all 61):
		hsa-miR-4291 hsa-miR-1224-3p hsa-miR-513a-5p hsa-miR-128 hsa-miR-200a hsa-miR-1260b hsa-miR-507 hsa-miR-105

		SwitchGear 3'UTR luciferase reporter plasmid: GRB2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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Additional cDNA sequence:

AF171699.1 AF246238.1 AF302079.1 AF498925.1 AK024539.1 AK091010.1 AK315565.1 BC000631.2

BC019082.2 BC033644.1 BC039827.1 BC043007.1 CR450363.1 CR541942.1 L29511.1 M96995.1

X62852.1

24 DOTS entries:

DT.91786336 DT.101985106 DT.455862 DT.95197797 DT.100833847 DT.100827631 DT.97788620 DT.91768193

DT.100827630 DT.121008073 DT.121008099 DT.95197812 DT.100039623 DT.100827635 DT.121008094 DT.100827636

DT.65285546 DT.100827634 DT.121008122 DT.121008141 DT.91710775 DT.95177922 DT.92454820 DT.97778180

24/631 AceView cDNA sequences (see all 631):

CD369353 BP339140 F02165 AI298612 BU615796 BQ921559 BI862246 BU619642

AI885859 NM_002086 AI572432 BM708461 BQ065151 AI355116 BU733359 CB117837

BE396668 AI084012 BU521520 BM968429 CB136581 CA411871 CA307217 BU608476

GeneLoc Exon Structure

5/7 Alternative Splicing Database (ASD) splice patterns (SP) for GRB2 (see all 7) About this scheme

ExUns:	1	^	2	^	3a	·	3b	·	3c	·	3d	·	3e	^	4	^	5a	·	5b	^	6	^	7	^	8a	·	8b	·	8c	·	8d
SP1:			-		-		-						-		-
SP2:													-		-
SP3:													-		-								-
SP4:													-		-						-
SP5:			-		-		-						-

ECgene alternative splicing isoforms for GRB2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

GRB2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AAGCCTTGCT

About this image

GRB2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Hypoblast

Hypoblast Cells

Extraembryonic Tissues

Inner Cell Mass

Inner Cell Mass Cells

Early Embryo

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See GRB2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for GRB2

SOURCE GeneReport for Unigene cluster: Hs.444356

SABiosciences Expression via Pathway-Focused PCR Arrays including GRB2 (see all 16):

Insulin Signaling Pathway in human mouse rat

Multiple Sclerosis in human mouse rat

Leukemia in human mouse rat

VEGF Signaling in human mouse rat

JAK / STAT Signaling Pathway in human mouse rat

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GRB2

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for GRB2 gene from 6/21 species (see all 21) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	GRB2¹	growth factor receptor-bound protein 2	87.86(n) 96.31(a)		386572 NM_204411.1 NP_989742.1
lizard (Anolis carolinensis)	Reptilia	GRB2⁶	--	89(a)	1 ↔ 1	2(114598470-114612186)
African clawed frog (Xenopus laevis)	Amphibia	U89775.1²	--	84.11(n)		U89775.1
zebrafish (Danio rerio)	Actinopterygii	wufb18e12²	Danio rerio cDNA clone MGC73077 IMAGE4146196, complete more	81.67(n)		BC059450.1
fruit fly (Drosophila melanogaster)	Insecta	drk^{1 , 3}	RAS protein signal transduction SH3/SH2 adaptor more³ downstream of receptor kinase¹	65(a)³ 61.7(n)¹ 66.83(a)¹		2 50A13³ 36497¹ NM_165998.1¹ NP_725306.1¹
worm (Caenorhabditis elegans)	Secernentea	sem-5^{1 , 3}	C. elegans sem-5³ Protein SEM-5¹	58(a)³ 60.88(n)¹ 59.15(a)¹		X(7995288-7996908)³ 181055¹ NM_076941.4¹ NP_509342.1¹

ENSEMBL Gene Tree for GRB2 (if available)
TreeFam Gene Tree for GRB2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for GRB2 gene

GRAP² GRAPL² NCK1² NCK2² GRAP2²

18/26 SIMAP similar genes for GRB2 using alignment to 6 protein entries: GRB2_HUMAN (see all proteins) (see all similar genes):

ITSN2 GRAPL GRAP ARHGEF7 NCK1 SORBS3

SH3GL2 PTPN11 SH3GL1 ABL2 YES1 FYN

ABL1 BCR-ABL1 e19a2 FGR PTK6 BCR-ABL1 BCR/ABL fusion

GRB2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs74493141^1,2	C,F,	--	68724263(+)	`GCCAAC/TGTGTG`	2	--	ds500¹		1		NA	120
rs17490675^1,2	C,F,H,	--	68724380(+)	`TTCTTG/CTTTAA`	2	--	ds500¹		21		NA NS EA WA	3436
rs55960830^1,2		--	68724630(+)	`GCCCCA/GCATGC`	2	--	ds500¹		0	--	--	--	--
rs61757955^1,2	C,F,	--	68724762(-)	`CACAAT/CGAATT`	2	--	ut3¹		4		NS NA	214
rs61757954^1,2	C,F,	--	68724813(-)	`AACTCT/-GCGGA`	2	--	ut3¹		2		NS	92
rs3211129^1,2	C,H	--	68725201(-)	`CCCAAA/CCCCCT`	2	--	ut3¹ ese³		6		MN NS EA NA	582
rs61757952^1,2	C,F,	--	68726280(-)	`TTAGCC/AGGGTG`	2	--	ut3¹		2		NS	92
rs61757951^1,2	C,F,	--	68726405(-)	`GGCGCG/AGTGGC`	2	--	ut3¹		4		NS WA	214
rs61757950^1,2	C,F,	--	68726866(-)	`GATTTA/GAAAAT`	2	--	ut3¹		2		NS	94
rs59083128^1,2	C,F,	--	68726923(+)	`CACAGG/AGTGAC`	2	--	ut3¹		4		NS WA	214

HapMap Linkage Disequilibrium report for GRB2 (73314157 - 73401790 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 2 variations for GRB2
2 CNVs: 5030 5881

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

GRB2 for disorders           About GeneDecksing

OMIM gene information: 108355    OMIM disorders: --

20/65 diseases for GRB2 (see all 65):    About MalaCards

wiskott-aldrich syndrome silver-russell syndrome severe combined immunodeficiency combined immunodeficiency

multiple endocrine neoplasia myeloproliferative disorder b-cell lymphomas myeloid leukemia

anorexia nervosa oculocerebrorenal syndrome hydrocele adrenal adenoma

hepatitis e chronic lymphocytic leukemia hepatitis c chronic myeloid leukemia

acute myeloid leukemia herpes simplex fanconi's anemia lymphocytic leukemia

3 diseases from the University of Copenhagen DISEASES database for GRB2:

Hydrocele Leukemia Hypertrophic cardiomyopathy

10/31 Novoseek disease relationships for GRB2 gene (see all 31) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
myeloid leukemia chronic	37.9	1	15143164 (1)
wiskott-aldrich syndrome	37.3	3	9307968 (2), 15579908 (1)
breast cancer	36.4	33	11175341 (5), 10022814 (5), 8058337 (3), 9390033 (2) (see all 16)
neoplastic transformation	32.3	2	8084588 (1), 8662827 (1)
leukemia	21.4	9	9096689 (1), 15143164 (1), 15050920 (1), 10887132 (1) (see all 8)
leukemogenesis	20.2	2	15143164 (2)
tumors	17.9	35	11606575 (2), 16309242 (2), 15958587 (2), 12850474 (1) (see all 27)
cancer	16.7	20	18620523 (2), 9009162 (1), 18216394 (1), 12878216 (1) (see all 14)
myeloproliferative disorders	6.3	1	10887132 (1)
melanoma	5.33	1	10091608 (1)

Human Genome Epidemiology (HuGE) Navigator: GRB2 (14 documents)
Tumor Gene Database (TGDB): GRB2

Export disorders for GRB2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for GRB2 gene, integrated from 9 sources (see all 1208):
(articles sorted by number of sources associating them with GRB2)

Utopia: connect your pdf to the dynamic
world of online information

The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine- phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. (PubMed id 8491186)^{1, 2, 9} Skolnik E.Y....Schlessinger J. (1993)
Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. (PubMed id 8388384)^{1, 2, 9} Tobe K.... Kadowaki T. (1993)
Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2. (PubMed id 8723348)^{1, 2, 9} Kavanaugh W.M....Williams L.T. (1996)
Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor. (PubMed id 11827484)^{1, 2, 9} Nioche P.... Ducruix A. (2002)
Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2. (PubMed id 11533253)^{1, 2, 9} Wheeler M. and Domin J. (2001)
Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells. (PubMed id 8798570)^{1, 2, 9} Stein E.... Daniel T.O. (1996)
Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. (PubMed id 7881903)^{1, 2, 9} Kohda D.... Inagaki F. (1994)
Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. (PubMed id 9178760)^{1, 2, 9} Braunger J....Janssen J.W. (1997)
Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. (PubMed id 19523899)^{1, 2, 9} Harkiolaki M.... Feller S.M. (2009)
Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src. (PubMed id 9148935)^{1, 2, 9} Schlaepfer D.D. and Hunter T. (1997)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 2885	HGNC: 4566	AceView: GRB2	Ensembl:ENSG00000177885	euGenes: HUgn2885
ECgene: GRB2	Kegg: 2885	H-InvDB: GRB2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for GRB2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for GRB2	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for GRB2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for GRB2 gene:
Search GeneIP for patents involving GRB2

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section

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growth factor receptor-bound protein 2

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growth factor receptor-bound protein 2

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