EuRBPDB

Basic Information
Cancer Related Information

Description

RBPome

Literatures

Expression

Transcripts

Gene Model

Pathways

Phenotypes

GWAS

PPI

Orthologs

Gene Ontology

Description

Ensembl ID: ENSG00000177885 (Gene tree)
Gene ID: 2885
Gene Symbol: GRB2
Alias: NCKAP2
Full Name: growth factor receptor bound protein 2
Gene Type: protein_coding
Species: Homo_sapiens
Status: confidence
Strand: Minus strand
Length: 87,634 bases
Position: chr17:75,318,076-75,405,709
Accession: 4566
RBP type: non-canonical RBP
Summary: 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]

RNA binding proteome (RBPome)

PID	Title	Method	Time	Author	Doi
30607034	Comprehensive identification of RNA protein interactions in any organism using orthogonal organic phase separation (OOPS)	OOPS & HEK293	2019 Jan 3	Queiroz RML	DOI: 10.1038/s41587-018-0001-2
22658674	Insights into RNA biology from an atlas of mammalian mRNA-binding proteins	RIC & Hela	2012 May 31	Castello A	DOI: 10.1016/j.cell.2012.04.031

Literatures on RNA binding capacity

PID	Title	Article	Time	Author	Doi
15635092	Growth factor receptor binding protein 2-mediated recruitment of the RING domain of Cbl to the epidermal growth factor receptor is essential and sufficient to support receptor endocytosis.	Mol Biol Cell	2005 Mar	Huang F	-
8994826	Cell cycle-dependent activation of Ras.	Curr Biol	1996 Dec 1	Taylor SJ	-
22090132	GRB2 interaction with the ecotropic murine leukemia virus receptor, mCAT-1, controls virus entry and is stimulated by virus binding.	J Virol	2012 Feb	Chen Z	doi: 10.1128/JVI.05993-11
21930784	A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism.	Mol Cell Biol	2011 Nov	Kantonen S	doi: 10.1128/MCB.05684-11
21508312	GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration.	Mol Biol Cell	2011 Jun 15	Zhang JS	doi: 10.1091/mbc.E10-12-0969
21233203	Direct recruitment of ERK cascade components to inducible genes is regulated by heterogeneous nuclear ribonucleoprotein (hnRNP) K.	J Biol Chem	2011 Mar 18	Mikula M	doi: 10.1074/jbc.M110.213330
26251007	Endocytosis of Ubiquitylation-Deficient EGFR Mutants via Clathrin-Coated Pits is Mediated by Ubiquitylation.	Traffic	2015 Nov	Fortian A	doi: 10.1111/tra.12314

Expression

Transcripts

Transcript ID	Name	Length	RefSeq ID	Protein ID	Length	RefSeq ID	UniportKB ID
ENST00000392564	GRB2-205	3182	-	ENSP00000376347	217 (aa)	-	P62993
ENST00000392562	GRB2-203	3729	-	ENSP00000376345	217 (aa)	-	P62993
ENST00000392563	GRB2-204	2851	-	ENSP00000376346	176 (aa)	-	P62993
ENST00000577711	GRB2-207	555	-	-	- (aa)	-	-
ENST00000462266	GRB2-206	601	-	-	- (aa)	-	-
ENST00000581959	GRB2-209	359	-	ENSP00000463525	42 (aa)	-	J3QLF6
ENST00000316804	GRB2-202	3248	-	ENSP00000339007	217 (aa)	-	P62993
ENST00000316615	GRB2-201	3181	-	ENSP00000317360	176 (aa)	-	P62993
ENST00000648046	GRB2-212	1711	-	ENSP00000496913	217 (aa)	-	B0LPF3
ENST00000582582	GRB2-210	584	-	ENSP00000462785	110 (aa)	-	J3KT38
ENST00000583912	GRB2-211	561	-	-	- (aa)	-	-
ENST00000578961	GRB2-208	687	-	ENSP00000464279	156 (aa)	-	J3QRL5

Gene Model

Click here to download ENSG00000177885's gene model file

Pathways

Pathway ID	Pathway Name	Source
hsa01521	EGFR tyrosine kinase inhibitor resistance	KEGG
hsa01522	Endocrine resistance	KEGG
hsa04010	MAPK signaling pathway	KEGG
hsa04012	ErbB signaling pathway	KEGG
hsa04014	Ras signaling pathway	KEGG
hsa04062	Chemokine signaling pathway	KEGG
hsa04068	FoxO signaling pathway	KEGG
hsa04072	Phospholipase D signaling pathway	KEGG
hsa04150	mTOR signaling pathway	KEGG
hsa04151	PI3K-Akt signaling pathway	KEGG
hsa04380	Osteoclast differentiation	KEGG
hsa04510	Focal adhesion	KEGG
hsa04540	Gap junction	KEGG
hsa04550	Signaling pathways regulating pluripotency of stem cells	KEGG
hsa04630	JAK-STAT signaling pathway	KEGG
hsa04650	Natural killer cell mediated cytotoxicity	KEGG
hsa04660	T cell receptor signaling pathway	KEGG
hsa04662	B cell receptor signaling pathway	KEGG
hsa04664	Fc epsilon RI signaling pathway	KEGG
hsa04714	Thermogenesis	KEGG
hsa04722	Neurotrophin signaling pathway	KEGG
hsa04910	Insulin signaling pathway	KEGG
hsa04912	GnRH signaling pathway	KEGG
hsa04915	Estrogen signaling pathway	KEGG
hsa04917	Prolactin signaling pathway	KEGG
hsa04926	Relaxin signaling pathway	KEGG
hsa05034	Alcoholism	KEGG
hsa05160	Hepatitis C	KEGG
hsa05161	Hepatitis B	KEGG
hsa05163	Human cytomegalovirus infection	KEGG
hsa05165	Human papillomavirus infection	KEGG
hsa05200	Pathways in cancer	KEGG
hsa05203	Viral carcinogenesis	KEGG
hsa05205	Proteoglycans in cancer	KEGG
hsa05206	MicroRNAs in cancer	KEGG
hsa05210	Colorectal cancer	KEGG
hsa05211	Renal cell carcinoma	KEGG
hsa05213	Endometrial cancer	KEGG
hsa05214	Glioma	KEGG
hsa05215	Prostate cancer	KEGG
hsa05220	Chronic myeloid leukemia	KEGG
hsa05221	Acute myeloid leukemia	KEGG
hsa05223	Non-small cell lung cancer	KEGG
hsa05224	Breast cancer	KEGG
hsa05225	Hepatocellular carcinoma	KEGG
hsa05226	Gastric cancer	KEGG
hsa05231	Choline metabolism in cancer	KEGG

Phenotypes

ensgID	Trait	pValue	Pubmed ID
ENSG00000177885	Neuroblastoma	1.1E-6	18463370
ENSG00000177885	Lupus Erythematosus, Systemic	3E-6	26502338

GWAS

ensgID	SNP	Chromosome	Position	SNP-risk	Trait	PubmedID	95% CI	Or or BEAT	EFO ID
ENSG00000177885	rs9894206	17	75364073	?	Systemic lupus erythematosus	28714469	[1.15-1.39]	1.25	EFO_0002690
ENSG00000177885	rs36023980	17	75345203	C	Systemic lupus erythematosus	29848360	[1.13-1.24]	1.18	EFO_0002690
ENSG00000177885	rs2385263	17	75325036	?	Waist-hip ratio	30595370			EFO_0004343

Protein-Protein Interaction (PPI)

Clik here to download ENSG00000177885's network

* RBP PPI network refers to all genes directly bind to RBP

Orthologs identified by RBPome

Ensembl ID	Gene Symbol	Coverage	Identiy	Ortholog	Gene Symbol	Coverage	Identiy	Species
ENSG00000177885	GRB2	100	100.000	ENSMUSG00000059923	Grb2	100	100.000	Mus_musculus

Gene Ontology

Go ID	Go_term	PubmedID	Evidence	Category
GO:0000165	MAPK cascade	-	TAS	Process
GO:0001784	phosphotyrosine residue binding	20624904.	IPI	Function
GO:0003723	RNA binding	22658674.	HDA	Function
GO:0005070	SH3/SH2 adaptor activity	8253073.	TAS	Function
GO:0005154	epidermal growth factor receptor binding	12577067.	IPI	Function
GO:0005168	neurotrophin TRKA receptor binding	15488758.	IPI	Function
GO:0005515	protein binding	7504175.7518560.7518772.7522233.7523381.7527391.7537265.7629138.7773779.8112292.8491186.8663178.8798570.8816475.8887653.8892607.8939605.8940013.8955135.8959326.8995379.9020117.9045636.9148935.9174058.9175774.9178760.9178913.9254595.9346925.9447984.9489702.9544989.9569023.9788432.10026169.10206341.10229072.10318918.10377264.10660596.10660620.10811803.10887132.10980613.11278465.11432792.11684012.11741929.11827484.11882361.11896612.11923305.12091307.12213123.12359715.12577067.14679214.14722116.14993658.15467741.15558030.15657067.15784897.15929943.16253990.16273093.16374509.16407827.16520382.16696976.16730941.16799092.16893902.16899217.16912232.16938345.17094785.17235283.17276458.17474147.18273061.18624398.18647389.18654987.18692475.19172738.19323566.19380743.19509291.19615732.19798056.19914172.20933011.20936779.21179510.21189249.21278786.21278788.21706016.21725282.21725358.21822214.21900206.21930792.21988832.22323290.22536782.22726438.23178716.23460737.23799367.24189400.24658140.24728074.25036637.25092874.25416956.25535246.25814554.25819436.27059931.27107012.28046066.28330616.29997244.	IPI	Function
GO:0005634	nucleus	21179510.	IDA	Component
GO:0005654	nucleoplasm	-	IDA	Component
GO:0005730	nucleolus	-	IDA	Component
GO:0005737	cytoplasm	21179510.	IDA	Component
GO:0005768	endosome	21179510.	IDA	Component
GO:0005794	Golgi apparatus	-	IEA	Component
GO:0005829	cytosol	14722116.	TAS	Component
GO:0005886	plasma membrane	-	TAS	Component
GO:0005911	cell-cell junction	-	IEA	Component
GO:0007173	epidermal growth factor receptor signaling pathway	1322798.	TAS	Process
GO:0007265	Ras protein signal transduction	8253073.	TAS	Process
GO:0007267	cell-cell signaling	8253073.	TAS	Process
GO:0007411	axon guidance	-	TAS	Process
GO:0007568	aging	-	IEA	Process
GO:0008180	COP9 signalosome	22561606.	IDA	Component
GO:0008286	insulin receptor signaling pathway	8388384.	IPI	Process
GO:0008286	insulin receptor signaling pathway	-	TAS	Process
GO:0008543	fibroblast growth factor receptor signaling pathway	-	TAS	Process
GO:0012506	vesicle membrane	-	IEA	Component
GO:0016032	viral process	-	IEA	Process
GO:0017124	SH3 domain binding	19509291.	IDA	Function
GO:0019221	cytokine-mediated signaling pathway	-	TAS	Process
GO:0019901	protein kinase binding	20086093.	IPI	Function
GO:0019903	protein phosphatase binding	-	IEA	Function
GO:0030838	positive regulation of actin filament polymerization	-	IEA	Process
GO:0031295	T cell costimulation	-	TAS	Process
GO:0031623	receptor internalization	14985334.	IMP	Process
GO:0035635	entry of bacterium into host cell	-	TAS	Process
GO:0035723	interleukin-15-mediated signaling pathway	-	TAS	Process
GO:0038095	Fc-epsilon receptor signaling pathway	-	TAS	Process
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis	-	TAS	Process
GO:0038128	ERBB2 signaling pathway	-	TAS	Process
GO:0042059	negative regulation of epidermal growth factor receptor signaling pathway	-	TAS	Process
GO:0042770	signal transduction in response to DNA damage	20160708.	IMP	Process
GO:0042802	identical protein binding	12577067.22536782.22726438.	IPI	Function
GO:0043408	regulation of MAPK cascade	-	IEA	Process
GO:0043560	insulin receptor substrate binding	8388384.	IPI	Function
GO:0046579	positive regulation of Ras protein signal transduction	-	TAS	Process
GO:0046875	ephrin receptor binding	12925710.	IPI	Function
GO:0048011	neurotrophin TRK receptor signaling pathway	-	TAS	Process
GO:0048646	anatomical structure formation involved in morphogenesis	-	IEA	Process
GO:0050900	leukocyte migration	-	TAS	Process
GO:0051291	protein heterooligomerization	-	IEA	Process
GO:0051897	positive regulation of protein kinase B signaling	-	TAS	Process
GO:0060670	branching involved in labyrinthine layer morphogenesis	-	IEA	Process
GO:0061024	membrane organization	-	TAS	Process
GO:0070062	extracellular exosome	19056867.20458337.23533145.	HDA	Component
GO:0070436	Grb2-EGFR complex	20086093.	IDA	Component
GO:0071479	cellular response to ionizing radiation	20160708.	IMP	Process
GO:2000379	positive regulation of reactive oxygen species metabolic process	20160708.	IMP	Process

Cancer associated literatures

PID	Title	Article	Time	Author	Doi
18425376	New insight into the key proteins and pathways involved in the metastasis of colorectal carcinoma.	Oncol Rep	2008 May	Yu GZ	-
15182856	Catalase binds Grb2 in tumor cells when stimulated with serum or ligands for integrin receptors.	Free Radic Biol Med	2004 Jun 15	Yano S	-
24391994	Identification of GRB2 and GAB1 coexpression as an unfavorable prognostic factor for hepatocellular carcinoma by a combination of expression profile and network analysis.	PLoS One	2013 Dec 31	Zhang Y	doi: 10.1371/journal.pone.0085170
30054970	Circulating Candidate Biomarkers in Giant Cell Tumors of Bone.	Proteomics Clin Appl	2018 Nov	Conti A	doi: 10.1002/prca.201800041
26885689	mir-329 restricts tumor growth by targeting grb2 in pancreatic cancer.	Oncotarget	2016 Apr 19	Wang X	doi: 10.18632/oncotarget.7375.
24407288	The adaptor proteins p66Shc and Grb2 regulate the activation of the GTPases ARF1 and ARF6 in invasive breast cancer cells.	J Biol Chem	2014 Feb 28	Haines E	doi: 10.1074/jbc.M113.516047
25688510	Dynamic expression changes between non-muscle-invasive bladder cancer and muscle-invasive bladder cancer.	Tumori	2014 Nov-Dec	Zhao YG	doi: 10.1700/1778.19294.
24708867	Met receptor-induced Grb2 or Shc signals both promote transformation of intestinal epithelial cells, albeit they are required for distinct oncogenic functions.	BMC Cancer	2014 Apr 4	Pomerleau V	doi: 10.1186/1471-2407-14-240.
19337752	Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance.	J Cancer Res Clin Oncol	2009 Oct	Yu GZ	doi: 10.1007/s00432-009-0574-8
26103942	Grb2 monomer-dimer equilibrium determines normal versus oncogenic function.	Nat Commun	2015 Jun 24	Ahmed Z	doi: 10.1038/ncomms8354.
27264952	miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2.	Biochem Biophys Res Commun	2016 Aug 5	Zhang Y	doi: 10.1016/j.bbrc.2016.06.006
23826330	A Novel Phosphopeptide Microarray Based Interactome Map in Breast Cancer Cells Reveals Phosphoprotein-GRB2 Cell Signaling Networks.	PLoS One	2013 Jun 27	Krishnamoorthy S	doi: 10.1371/journal.pone.0067634

Expression in 33 cancers

Mutations

Cancer	Chr	Position	Mutation Type	dbSNP	Protein-change	Allele Freq
BLCA	chr17	75320449	Silent	NA	P191P	0.22
BLCA	chr17	75325924	Silent	novel	A91A	0.13
BLCA	chr17	75393635	5'UTR	rs374102478		0.4
BLCA	chr17	75325912	Missense_Mutation	novel	F95L	0.12
BLCA	chr17	75320467	Silent	NA	V185V	0.06
BRCA	chr17	75332755	Missense_Mutation	novel	L41I	0.12
BRCA	chr17	75320378	Missense_Mutation	rs371871562	R215Q	0.47
CESC	chr17	75393572	Silent	novel	F19F	0.1
COAD	chr17	75321781	Missense_Mutation	NA	G116R	0.32
COAD	chr17	75393677	5'UTR	novel		0.37
COAD	chr17	75320488	Silent	novel	R178R	0.12
COAD	chr17	75393646	5'UTR	novel		0.29
COAD	chr17	75393680	5'UTR	novel		0.55
COAD	chr17	75321660	Missense_Mutation	NA	Q156R	0.17
DLBC	chr17	75325899	Missense_Mutation	novel	K100E	0.28
ESCA	chr17	75320325	3'UTR	novel		0.42
GBM	chr17	75320477	Missense_Mutation	novel	F182S	0.13
GBM	chr17	75321709	Missense_Mutation	novel	V140L	0.05
GBM	chr17	75320238	3'UTR	novel		0.09
GBM	chr17	75320434	Silent	novel	G196G	0.05
GBM	chr17	75320490	Missense_Mutation	novel	R178S	0.06
GBM	chr17	75321704	Silent	novel	S141S	0.07
GBM	chr17	75320317	3'UTR	novel		0.13
HNSC	chr17	75393630	5'UTR	novel		0.27
HNSC	chr17	75320532	Nonsense_Mutation	novel	*L164Ffs3**	0.07
KIRC	chr17	75332781	Nonsense_Mutation	novel	C32*	0.04
KIRC	chr17	75320339	3'UTR	novel		0.31
LAML	chr17	75393717	5'UTR	novel		0.09
LAML	chr17	75393719	5'UTR	novel		0.09
LGG	chr17	75393698	5'UTR	novel		0.31
LGG	chr17	75320532	Nonsense_Mutation	novel	*L164Ffs3**	0.08
LIHC	chr17	75320360	3'UTR	novel		0.62
LUAD	chr17	75321698	Missense_Mutation	novel	N143K	0.25
LUAD	chr17	75321667	Missense_Mutation	NA	V154L	0.11
LUAD	chr17	75320541	Missense_Mutation	NA	V161F	0.17
LUAD	chr17	75320420	Missense_Mutation	NA	Q201L	0.22
LUAD	chr17	75321674	Missense_Mutation	NA	I151M	0.2
LUAD	chr17	75332718	Missense_Mutation	NA	I53R	0.15
LUSC	chr17	75393738	5'UTR	novel		0.11
OV	chr17	75393621	Missense_Mutation	novel	A3V	0.07
OV	chr17	75320452	Silent	novel	D190D	0.85
OV	chr17	75321737	Missense_Mutation	NA	E130D	0.31
OV	chr17	75320393	Missense_Mutation	novel	V210D	0.04
OV	chr17	75393673	5'UTR	novel		0.16
READ	chr17	75321747	Missense_Mutation	novel	S127Y	0.48
SKCM	chr17	75326001	Missense_Mutation	rs779784380	P66S	0.3
SKCM	chr17	75320387	Missense_Mutation	novel	P212L	0.36
SKCM	chr17	75393610	Frame_Shift_Del	novel	*Y7Mfs11**	0.4
STAD	chr17	75320373	Missense_Mutation	rs767371260	V217I	0.39
STAD	chr17	75320386	Frame_Shift_Del	NA	V213*	0.18
STAD	chr17	75393664	5'UTR	NA		0.2
STAD	chr17	75393610	Missense_Mutation	NA	Y7D	0.83
STAD	chr17	75320285	3'UTR	novel		0.09
THCA	chr17	75320532	Frame_Shift_Ins	novel	*F165Tfs3**	0.05
THCA	chr17	75320533	Frame_Shift_Ins	novel	*L164Sfs51**	0.03
UCEC	chr17	75325959	Missense_Mutation	NA	D80N	0.13
UCEC	chr17	75319282	3'UTR	novel		0.36
UCEC	chr17	75325962	Missense_Mutation	novel	H79Y	0.36
UCEC	chr17	75320314	3'UTR	novel		0.17
UCEC	chr17	75325953	Missense_Mutation	NA	A82T	0.25
UCEC	chr17	75320138	3'UTR	novel		0.5
UCEC	chr17	75318954	3'UTR	novel		0.4
UCEC	chr17	75321777	Missense_Mutation	NA	K117R	0.29
UCEC	chr17	75318129	3'UTR	novel		0.37
UCEC	chr17	75319317	3'UTR	novel		0.76
UCEC	chr17	75320424	Missense_Mutation	novel	G200W	0.17
UCEC	chr17	75318135	3'UTR	novel		0.41
UCEC	chr17	75321747	Missense_Mutation	novel	S127Y	0.36
UCEC	chr17	75320341	3'UTR	novel		0.24
UCEC	chr17	75319317	3'UTR	novel		0.8
UCEC	chr17	75319553	3'UTR	novel		0.28
UCEC	chr17	75321747	Missense_Mutation	novel	S127Y	0.18
UCEC	chr17	75318959	3'UTR	novel		0.21
UCEC	chr17	75318995	3'UTR	novel		0.39
UCEC	chr17	75320101	3'UTR	novel		0.35
UCEC	chr17	75320520	Missense_Mutation	novel	D168Y	0.35
UCEC	chr17	75319091	3'UTR	novel		0.36
UCEC	chr17	75393591	Missense_Mutation	novel	A13V	0.36

Copy Number Variations (CNVs)

Cancer	Type	Freq	Q-value
BLCA	AMP	0.3922	0.00012456
CESC	AMP	0.1966	2.0209e-05
GBM	AMP	0.0953	0.0035457
KIRP	AMP	0.6701	0.14801
LGG	AMP	0.0721	1.52e-05
LUSC	AMP	0.3513	0.001059
SARC	AMP	0.2412	0.032181
SKCM	AMP	0.297	7.0388e-08
THCA	DEL	0.002	0.221
UVM	AMP	0.1625	0.054583

Survival Analysis

Cancer	P-value	Q-value
THYM	0.018	Kaplan-Meier Survival Analysis
STAD	0.01	Kaplan-Meier Survival Analysis
SARC	0.035	Kaplan-Meier Survival Analysis
SKCM	0.00011	Kaplan-Meier Survival Analysis
PRAD	0.036	Kaplan-Meier Survival Analysis
TGCT	0.046	Kaplan-Meier Survival Analysis
COAD	0.034	Kaplan-Meier Survival Analysis
PAAD	0.021	Kaplan-Meier Survival Analysis
KICH	0.039	Kaplan-Meier Survival Analysis
UCEC	0.004	Kaplan-Meier Survival Analysis
LIHC	0.00011	Kaplan-Meier Survival Analysis
UVM	0.013	Kaplan-Meier Survival Analysis
OV	0.033	Kaplan-Meier Survival Analysis

Drugs

EuRBPDB

Description

RBPome

Literatures

Expression

Transcripts

Gene Model

Pathways

Phenotypes

GWAS

PPI

Orthologs

Gene Ontology

Select Dataset :

Input Drug :

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Eesembl ID

Cell lines and drugs in GSE70138 or GSE92742