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GRB2 Gene

protein-coding GIFtS: 67

GC17M068724

growth factor receptor-bound protein 2
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database

		Products

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

Aliases & Descriptions
growth factor receptor-bound protein 2¹ ²		MST084²
NCKAP2¹ ²		growth factor receptor-bound protein 3²
Protein Ash² ³		OTTHUMP00000166097²
Adapter protein GRB2² ³		EGFRBP-GRB2²
SH2/SH3 adapter GRB2² ³		MSTP084²
ASH² ³		abundant SRC homology²
epidermal growth factor receptor-binding protein GRB2²		HT027²
OTTHUMP00000166098²		Grb3-3²

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

Export aliases for GRB2 gene to outside databases

Previous GC identifers: GC17M073313 GC17M076374 GC17M073779 GC17M073911 GC17M070825

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki,
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)

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 GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits

EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2

and by suppressing proliferative signals, may trigger active programmed cell death

Gene Wiki entry for GRB2 (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 60), Regulatory elements and Epigenetics data according to Qiagen and/or SABiosciences)
About This Section

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the GRB2 gene promoter:
         p53   c-Myc   Max   Max1   STAT1beta   STAT1alpha   STAT1   Elk-1   GATA-2   Sp1
         Other transcription factors

Search SABiosciences Chromatin IP Primers for GRB2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays

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 gene densities for chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M068724: view genomic region (about GC identifiers)

Start:	68,724,752 bp from pter
End:	68,824,731 bp from pter
Size:	99,980 bases
Orientation:	minus strand

1 alternative location:

Chr17- 73,314,157-73,401,790

RefSeq DNA sequence:

NC_000017.10 NT_010783.15

(According to ¹UniProtKB, neXtProt, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Millipore, Sigma-Aldrich, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, and/or ProSpec,
Biochemical Assays by Millipore, Sigma-Aldrich, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Dec 2010 and Entrez Gene, Antibodies by Millipore, Sigma-Aldrich, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, and/or Epitomics)
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 receptors 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 JUB and CLNK (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 PRNP and THEMIS (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 (By similarity)

Subcellular location: Golgi apparatus (By similarity)

PDB structures from and Proteopedia :

1AZE (3D)

1BM2 (3D)

1BMB (3D)

1CJ1 (3D)

1FHS (3D)

1FYR (3D)

1GCQ (3D)

1GFC (3D)

1GFD (3D)

1GHU (3D)

1GRI (3D)

1IO6 (3D)

1JYQ (3D)

1JYR (3D)

1JYU (3D)

1QG1 (3D)

1TZE (3D)

1X0N (3D)

1ZFP (3D)

2AOA (3D)

2AOB (3D)

2H46 (3D)

2H5K (3D)

2HUW (3D)

2VVK (3D)

2VWF (3D)

2W0Z (3D)

3C7I (3D)

3IMD (3D)

3IMJ (3D)

3IN7 (3D)

3IN8 (3D)

3KFJ (3D)

Secondary accessions: P29354 Q14450 Q63057 Q63059

Alternative splicing: 2 isoforms: P62993-1, P29354-1 P62993-2, P29354-2 (Additional isoforms seem to exist)

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

Post-translational modifications:

View phosphorylation sites using PhosphoSite²

REFSEQ proteins (2 alternative transcripts):

NP_002077.1 NP_987102.1

ENSEMBL proteins:

ENSP00000339007 ENSP00000376345 ENSP00000376346 ENSP00000376347 ENSP00000317360

Human Recombinant Proteins

	Millipore Purified and/or Recombinant GRB2 Protein
	Sigma-Aldrich Proteins for GRB2
	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: GRB2
	GenScript Custom Purified and Recombinant Proteins Services for GRB2
	Novus Biologicals Proteins for GRB2
	Novus Biologicals Lysate for GRB2
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for GRB2

5/6 Gene Ontology (GO) cellular component terms (GO ID links to tree view) (see all 6):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IEA	--
GO:0005794	Golgi apparatus	IEA	--
GO:0005829	cytosol	TAS	--
GO:0012506	vesicle membrane	IEA	--
GO:0016020	membrane	IEA	--

About this table

GRB2 for ontologies About GeneDecksing

Antibodies for GRB2:

	Millipore Mono- and Polyclonal Antibodies for the study of GRB2
	Sigma-Aldrich Antibody Arrays and Antibodies for GRB2
	R&D Systems Antibodies for GRB2
	Cell Signaling Technology (CST) Antibodies for GRB2
	OriGene Antibodies (see all 4): GRB2
	GenScript Custom Superior Antibodies Services for GRB2
	Novus Biologicals Antibodies for GRB2
	Epitomics antibodies for GRB2

Assays for GRB2:

	Browse Kits and Assays available from Millipore
	Browse ELISAs at Sigma-Aldrich
	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 UniProtKB, IUBMB,and/or Genatlas, Animal models from MGI Dec 24 2010,
shRNA from OriGene, Sigma-Aldrich, RNAi from Millipore, siRNAs from Sigma-Aldrich, OriGene, Qiagen, Super-pooled esiRNAs from Sigma-Aldrich, microRNA from Sigma-Aldrich, Qiagen, SABiosciences, Clones from Millipore, Sigma-Aldrich, OriGene, GenScript, Sino Biological, Cell Lines from GenScript, Ontologies according to Gene Ontology Consortium 01 Dec 2010 via Entrez Gene.)
About This Section

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 GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits

EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2

and by suppressing proliferative signals, may trigger active programmed cell death

Inhib. RNA:		Browse for Gene Knock-down Tools from Millipore
		Browse Nano Scale siRNA at Sigma-Aldrich Sigma-Aldrich esiRNA and siRNA for GRB2 Sigma-Aldrich shRNA Panels and shRNA for GRB2
		OriGene 29mer shRNA kits in GFP-retroviral vector (see all 2): GRB2 OriGene shRNA RFP (see all 2): GRB2 OriGene basic RS shRNA (see all 2): GRB2 OriGene siRNA (see all 2): GRB2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing of GRB2

miRNA:		Sigma-Aldrich microRNA Mimics for GRB2 Browse microRNA target validation systems at Sigma-Aldrich
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of GRB2
		8/16 SABiosciences Assays for microRNAs that regulate GRB2 (see all 16):
		hsa-miR-362-3p hsa-miR-1288 hsa-miR-513a-5p hsa-miR-200a hsa-miR-105 hsa-miR-141 hsa-miR-124 hsa-miR-506

Gene
Editing:

Browse CompoZr Knockout ZFN at Sigma-Aldrich

Clones:		Browse Clones for the Expression of Recombinant Proteins Available from Millipore
		Browse iPSC Reprogramming Factors at Sigma-Aldrich
		OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): GRB2 OriGene Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): GRB2 OriGene untagged cDNA clones in CMV expression vector (see all 2): GRB2 OriGene 3'-UTR clone (see all 2): GRB2 Browse MicroRNA Expression Plasmids
		GenScript Custom cDNA clone Services for GRB2
		Browse Sino Biological Human cDNA Clones

Cell
Lines:

GenScript Custom overexpressing Cell Line Services for GRB2

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

5/7 Gene Ontology (GO) molecular function terms (GO ID links to tree view) (see all 7):

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:0005515	protein binding	IPI	7523381
GO:0019904	protein domain specific binding	IEA	--

About this table

GRB2 for ontologies About GeneDecksing

Animal Models: 15 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Grb2):

behavior/neurological	cardiovascular system	craniofacial	digestive/alimentary	embryogenesis
growth/size	hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism	immune system
lethality-prenatal/perinatal	nervous system	normal	skeleton	tumorigenesis

GRB2 for phenotypes About GeneDecksing

(Pathways according to Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB, Sets of similar genes according to GeneDecks, PCR Arrays from SABiosciences, Proteins Network according to SABiosciences, Sigma-Aldrich, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Dec 2010 via Entrez Gene).
About This Section

GRB2 for pathways About GeneDecksing

5/80 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

5/86 Sigma-Aldrich "Your Favorite Gene" (powered by Ingenuity) Pathways for GRB2 (see all 86)

	TGF-β Signaling
	Regulation of eIF4 and p70S6K Signaling
	Acute Myeloid Leukemia Signaling
	Glucocorticoid Receptor Signaling
	Cardiac Hypertrophy Signaling

5/6 Cell Signaling Technology (CST) Pathways for GRB2 (see all 6)

	Jak/Stat Signaling: IL-6 Receptor Family
	Insulin Receptor Signaling
	T Cell Receptor Signaling
	B Cell Receptor Signaling
	MAPK/Erk in Growth and Differentiation

5/23 Kegg Pathways (Kegg details for GRB2) (see all 23):

	hsa04010 MAPK signaling pathway
	hsa04012 ErbB signaling pathway
	hsa04062 Chemokine signaling pathway
	hsa04320 Dorso-ventral axis formation
	hsa04510 Focal adhesion

SABiosciences Pathway-Focused PCR Arrays including GRB2 (see all 6): PAHS-030A PAHS-040A

Sigma-Aldrich "Your Favorite Gene" (powered by Ingenuity) Molecular Interaction Network for GRB2

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

5/469 Interacting proteins for GRB2 (P62993^{1, 2} ENSP00000339007³) via UniProtKB, MINT, and/or STRING (see all 469)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
EGFR	P00533¹^,², ENSP00000275493³	EBI-401755,EBI-297353 MINT-8029342 MINT-8029357 MINT-74541 MINT-61494 MINT-8029326 MINT-58642 MINT-8029310 MINT-1793777 MINT-61502 MINT-8029261 MINT-61540 MINT-8038388 MINT-6169986 MINT-8038373 MINT-61498 MINT-61500 MINT-58641 MINT-61496 MINT-8029372 MINT-58640 MINT-61497 MINT-8029231 STRING: ENSP00000275493
SOS1	Q07889¹^,², ENSP00000263879³	EBI-401755,EBI-297487 MINT-1782504 MINT-7217748 MINT-7135453 MINT-6173175 MINT-6170102 MINT-1782591 MINT-7217714 MINT-7217731 MINT-7217692 MINT-7253710 MINT-7217665 MINT-7135473 MINT-6170081 MINT-61539 MINT-6170118 MINT-65980 STRING: ENSP00000263879
MAP4K1	Q92918¹^,², ENSP00000221409³	EBI-401755,EBI-881 MINT-7212988 MINT-7213002 MINT-7213078 MINT-7213120 MINT-7212968 MINT-7213066 MINT-7253194 STRING: ENSP00000221409
PTPN11	Q06124¹^,², ENSP00000340944³	EBI-401755,EBI-297779 MINT-7300447 MINT-61552 STRING: ENSP00000340944
DNM1	Q05193¹^,², ENSP00000362014³	EBI-401755,EBI-713135 MINT-65952 MINT-65951 STRING: ENSP00000362014

About this table

5/24 Gene Ontology (GO) biological process terms (GO ID links to tree view) (see all 24):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007173	epidermal growth factor receptor signaling pathway	TAS	1322798
GO:0007265	Ras protein signal transduction	TAS	8253073
GO:0007267	cell-cell signaling	TAS	8253073
GO:0007411	axon guidance	TAS	--
GO:0007568	aging	IEA	--

About this table

GRB2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

GRB2 for compounds About GeneDecksing

Browse Small Molecules at Sigma-Aldrich

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for GRB2
10/52 Novoseek chemical compound relationships for GRB2 gene (see all 52)

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)

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 228 Homo sapiens; Dec 8 2010) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Millipore,
siRNAs from Sigma-Aldrich, OriGene, Qiagen, Super-pooled esiRNAs from Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene, microRNA from Sigma-Aldrich, Qiagen, SABiosciences,
Tagged/untagged cDNA clones from OriGene, Sigma-Aldrich, GenScript, Primers from OriGene and/or SABiosciences)
About This Section

Inhib. RNA:		Browse for Gene Knock-down Tools from Millipore
		Browse Nano Scale siRNA at Sigma-Aldrich Sigma-Aldrich esiRNA and siRNA for GRB2 Sigma-Aldrich shRNA Panels and shRNA for GRB2
		OriGene 29mer shRNA kits in GFP-retroviral vector (see all 2): GRB2 OriGene shRNA RFP (see all 2): GRB2 OriGene basic RS shRNA (see all 2): GRB2 OriGene siRNA (see all 2): GRB2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing of GRB2

miRNA:		Sigma-Aldrich microRNA Mimics for GRB2 Browse microRNA target validation systems at Sigma-Aldrich
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of GRB2
		8/16 SABiosciences Assays for microRNAs that regulate GRB2 (see all 16):
		hsa-miR-362-3p hsa-miR-1288 hsa-miR-513a-5p hsa-miR-200a hsa-miR-105 hsa-miR-141 hsa-miR-124 hsa-miR-506

Clones:		Browse FLAG tag genes at Sigma-Aldrich
		OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): GRB2 OriGene Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): GRB2 OriGene untagged cDNA clones in CMV expression vector (see all 2): GRB2 OriGene 3'-UTR Clone (see all 2): GRB2 Browse OriGene MicroRNA Expression Plasmids
		GenScript Custom cDNA clone Services for GRB2

Primers:		OriGene genome-wide validated SYBR primer pairs: GRB2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay for GRB2: PPH00714A

REFSEQ mRNAs for GRB2 gene (2 alternative transcripts):

NM_002086.4 NM_203506.2

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 BC127778.1 CR450363.1 CR541942.1 L29511.1

M96995.1 X62852.1

24/27 DOTS entries (see all 27):

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

DT.100827630 DT.121008073 DT.121008099 DT.97776617 DT.100039623 DT.92454820 DT.121008170 DT.95197812

DT.121008094 DT.100827635 DT.100827636 DT.121008122 DT.65285546 DT.100827634 DT.121008141 DT.91710775

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

AI364084 CA435956 BU730769 BM695652 BQ879498 AF498925 BP339140 AI446232

AU142798 H13810 BU521520 AW302611 F02165 BU195750 AI355116 BX353450

BQ012409 BE221139 BF446179 AI073688 BU687777 AI682636 AA373713 CA306094

highest scoring ESTs for GRB2:

AA313802 AI439688 AI815684 AL134982 AU142798 AW161184 AW674664 BC000631 BE387478 BE396668

Unigene Cluster for GRB2:

Growth factor receptor-bound protein 2

Hs.444356 [show with all ESTs]

Unigene Representative Sequence: NM_002086

GeneLoc Exon Structure

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

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

About this scheme

ECgene alternative splicing isoforms for GRB2
6 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000316804(uc002jnx.3) ENST00000392562 ENST00000392563 ENST00000392564

ENST00000462266 ENST00000316615(uc002jny.3)

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 228 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Primers from OriGene and/or SABiosciences )
About This Section

GRB2 expression in normal and diseased human tissues

¹ / ² / ³

7 probe-sets matching GRB2 gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
46217_at²^{, 3}	U95-B	1	1.00	1.00	0.85	1.35	AI439688	0.80	1.00	0.91	1
1565_s_at²^{, 3}	U95-A	1	0.81	1.00	0.48	0.82	M96995	0.80	1.00	0.91	1
33855_at²^{, 3}	U95-A	1	0.50	1.00	0.66	0.84	M96995	0.80	1.00	0.91	1
223049_at²^{, 3}	U133-B	1	1.00	1.00	--	--	AF246238	0.60	1.00	0.82	1
215075_s_at²^{, 3}	U133-A	1	0.46	1.00	--	--	L29511	0.60	1.00	0.82	1
223049_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
215075_s_at²	U133Plus2	1	0.46	1.00	--	--	--	--	--	--	--

About this table

GRB2 for expression About GeneDecksing

Data from Genenote (Publications) and GNF BioGPS
About these images

GRB2 gene electronic northern expression

About these images

CGAP SAGE TAG: AAGCCTTGCT

SOURCE GeneReport for Unigene cluster: Hs.444356

Expression variation in blood from EXPOLDB for GRB2

Primers:		OriGene genome-wide validated SYBR primer pairs: GRB2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay for GRB2: PPH00714A

SABiosciences Expression via Pathway-Focused PCR Arrays including GRB2 (see all 6): PAHS-030A PAHS-040A

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Dec 24 2010, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
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Orthologs for GRB2 gene from 5/13 species (see all 13)

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	GRB2¹	--	growth factor receptor-bound protein 2	94.78(n) 100(a)	483312 XM_540431.2 XP_540431.2
chimpanzee (Pan troglodytes)	GRB2¹	--	growth factor receptor-bound protein 2	100(n) 100(a)	737245 XM_001141640.1 XP_001141640.1
cow (Bos taurus)	GRB2¹	--	growth factor receptor-bound protein 2	93.86(n) 100(a)	535298 NM_001034630.1 NP_001029802.1
rat (Rattus norvegicus)	Grb2¹	--	growth factor receptor bound protein 2	92.01(n) 100(a)	81504 NM_030846.2 NP_110473.2
mouse (Mus musculus)	Grb2^{1 , 5}	11 (80.91 cM)⁵	growth factor receptor bound protein 2^{1, 5}	92.17(n)¹ 99.54(a)¹	14784¹ NM_008163.3¹ NP_032189.1¹ AA408164⁵ AI323718⁵ (see all 26)

About this table Species with no ortholog for GRB2

ENSEMBL Gene Tree for GRB2 (if available)

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
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Paralogs for GRB2 gene

GRAP² GRAPL² NCK1² NCK2² GRAP2²

GRB2 for paralogs About GeneDecksing

(SNPs according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Resequencing Primers from Qiagen)
About This Section

SNP ID	Valid	Chr 17 pos	Sequence	Recs	AA Chg	Type	More	Recs	Allele freq	Pop	Total sample	More
Genomic Data				Transcription Related Data				Allele Frequencies
			--	--	--		--	--
rs7219^1,2	C,F,A,H,	73315368(-)	`TAAAGA/GCAGTC`	2	--	ut3¹ ese³		14		MN NS EA NA	856
rs755968^1,2	--	73365277(-)	`TTTATA/GTACCA`	2	--	int¹		0	--	--	--	--
rs892768^1,2	C,A,H,	73366602(-)	`AGGGAC/TGCGTT`	2	--	int¹		10		NA PA WA	266
rs959260^1,2	C,F,O,H,	73369422(-)	`TTGACA/GTTCTG`	2	--	int¹		39		NA EA NS	3794
rs1043617^1,2	--	73314441(-)	`CTCTTC/TTGGGC`	2	--	ut3¹ ese³		1		MN	184
rs1043824^1,2	--	73389838(-)	`GGCATT/CGTGTG`	2	--	ut5¹ ese³		1		MN	184
rs1076094^1,2	C,F,O,A,	73344711(+)	`GGAAAC/TTGCTG`	2	--	int¹		28		NA EA NS	2095
rs1108355^1,2	C,F,O,H,	73383913(-)	`CTAAGA/TTGTTG`	2	--	int¹		15		NS EA NA	730
rs1109033^1,2	C,F,H,	73333569(+)	`GCTGCG/ACCTAC`	2	--	int¹		17		NA EA NS	2322
rs1369299^1,2	C,F,A,H,	73347325(+)	`CCCTCC/TCAAAA`	2	--	int¹ trp³		25		NS EA NA	4214

About this table

HapMap Linkage Disequilibrium images for GRB2 (up to first 250kb)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 2 variations for GRB2
2 CNVs: 5030 5881

QIAGEN SeqTarget long-range PCR primers for resequencing GRB2

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, LSDB, HGMD, GAD, HuGE Navigator, and/or TGDB.)
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GRB2 for disorders About GeneDecksing

OMIM: 108355

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

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)

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Human Genome Epidemiology (HuGE) Navigator: GRB2 (10 documents)
Tumor Gene Database (TGDB): GRB2

Export disorders and mutations for GRB2 gene to outside databases

(Possibly Related Articles in Doctor's Guide)
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(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶UniProtKB/TrEMBL, and/or ⁷Novoseek)
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10/1099 PubMed articles for GRB2 gene, integrated from 7 sources (see all 1099):
(articles sorted by number of sources associating them with GRB2)

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, 7} 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, 7} 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, 7} 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, 7} 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, 7} Wheeler M. and Domin J. (2001)
Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. (PubMed id 7881903)^{1, 2, 7} Kohda D.... Inagaki F. (1994)
Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. (PubMed id 19523899)^{1, 2, 7} Harkiolaki M.... Feller S.M. (2009)
Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin. (PubMed id 10942756)^{1, 2, 7} Asazuma N.... Watson S.P. (2000)
Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. (PubMed id 10022120)^{1, 2, 7} Elly C....Liu Y.-C. (1999)
Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1). (PubMed id 10090780)^{1, 2, 7} Ettmayer P.... Bair K.W. (1999)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 2885	HGNC: 4566	AceView: GRB2	Ensembl:ENSG00000177885	euGenes: HUgn2885
ECgene: GRB2	Kegg: 2885	H-InvDB: GRB2

(According to HUGE)
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(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
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 XenneX, Inc.)

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

GeneCards and IP:
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