GRB2

Summary

GRB2 (growth factor receptor bound protein 2, HGNC:4566) is a protein-coding gene on chromosome 17q25.1, encoding Growth factor receptor-bound protein 2 (P62993). Non-enzymatic adapter protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression. It is a selective cancer dependency (DepMap: 74.3% of cell lines).

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.

Source: NCBI Gene 2885 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 17 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 74.3% of screened cell lines
• MANE Select transcript: NM_002086

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4566
Approved symbol	GRB2
Name	growth factor receptor bound protein 2
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	NCKAP2
Ensembl gene	ENSG00000177885
Ensembl biotype	protein_coding
OMIM	108355
Entrez	2885

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000316615, ENST00000316804, ENST00000392562, ENST00000392563, ENST00000392564, ENST00000462266, ENST00000577711, ENST00000578961, ENST00000581959, ENST00000582582, ENST00000583912, ENST00000648046, ENST00000904768, ENST00000904769, ENST00000904770, ENST00000932796, ENST00000932797, ENST00000932798, ENST00000970150, ENST00000970151, ENST00000970153, ENST00000970154, ENST00000970155

RefSeq mRNA: 2 — MANE Select: NM_002086 NM_002086, NM_203506

CCDS: CCDS11721, CCDS11722

Canonical transcript exons

ENST00000316804 — 6 exons

Exon	Start	End
ENSE00000387085	75332700	75332797
ENSE00001292179	75393551	75393765
ENSE00001361284	75405489	75405678
ENSE00001512383	75318076	75320553
ENSE00003564272	75325898	75326020
ENSE00003569357	75321659	75321827

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.5295 / max 1993.2245, expressed in 1826 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168075	100.1258	1826
168073	6.8510	1459
168074	5.1052	1241
168072	2.1930	880
168069	0.4635	249
168063	0.4163	206
168071	0.2004	82
168070	0.1741	74

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.56	gold quality
leukocyte	CL:0000738	98.17	gold quality
mononuclear cell	CL:0000842	98.15	gold quality
blood	UBERON:0000178	98.13	gold quality
cortical plate	UBERON:0005343	97.89	gold quality
superficial temporal artery	UBERON:0001614	97.67	gold quality
granulocyte	CL:0000094	97.62	gold quality
lymph node	UBERON:0000029	97.35	gold quality
lower lobe of lung	UBERON:0008949	97.30	gold quality
epithelium of nasopharynx	UBERON:0001951	96.62	gold quality
ganglionic eminence	UBERON:0004023	96.53	gold quality
spleen	UBERON:0002106	96.41	gold quality
tonsil	UBERON:0002372	96.40	gold quality
prefrontal cortex	UBERON:0000451	96.15	gold quality
stromal cell of endometrium	CL:0002255	96.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.02	gold quality
gingival epithelium	UBERON:0001949	96.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.92	silver quality
rectum	UBERON:0001052	95.76	gold quality
nucleus accumbens	UBERON:0001882	95.72	gold quality
adult organism	UBERON:0007023	95.64	gold quality
spinal cord	UBERON:0002240	95.55	gold quality
bone marrow	UBERON:0002371	95.55	gold quality
endothelial cell	CL:0000115	95.52	gold quality
gall bladder	UBERON:0002110	95.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.49	gold quality
amniotic fluid	UBERON:0000173	95.48	gold quality
gingiva	UBERON:0001828	95.44	gold quality
right frontal lobe	UBERON:0002810	95.31	gold quality
caecum	UBERON:0001153	95.29	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	22.96
E-CURD-88	yes	4.11
E-MTAB-7051	no	913.39
E-ENAD-20	no	172.13
E-MTAB-5061	no	3.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ELF1, HOXA1

miRNA regulators (miRDB)

134 targeting GRB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Investigation of the GRB2, GRB7, and CSH1 genes as candidates for the Silver-Russell syndrome (SRS) on chromosome 17q. (PMID:11897833)
• Results indicate that leptin, after binding its receptor, leads to activation of Grb2 and several pathways for signal transduction that might lead to mitogenic effects. (PMID:11997181)
• Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis (PMID:12006650)
• Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus (PMID:12007418)
• grb2 tyrosine phosphorylation was decreased in Couzon syndrome. (PMID:12162872)
• results suggest a model in which hepatitis C virus NS5A interacts with Grb2 to inhibit mitogenic signaling while simultaneously promoting the PI3K-AKT cell survival pathway by interaction with p85 PI3K (PMID:12186904)
• mediates recruitment of the Rab5 GTPase-activating protein RN-tre in endocyosis of EGFR (PMID:12399475)
• p21-activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple to growth factor signaling (PMID:12522133)
• Results demonstrate that p27(Kip1) can inhibit growth factor receptor-bound protein 2 function by blocking its association with the guanine nucleotide exchange factor SOS. (PMID:12748278)
• PNRC and Grb2, by interacting with each other, can suppress nuclear receptor-mediated regulation and growth factor-mediated regulation in human breast tissue (PMID:15122321)
• catalase (447)Tyr-Val-Asn-Val binds Grb2 upon phosphorylation in tumor cells when stimulated with serum or ligands for integrin receptors (PMID:15182856)
• Results suggest that MUC20 is a novel regulator of the Met signaling cascade which has a role in suppression of the Grb2-Ras pathway. (PMID:15314156)
• GRB2 is necessary for RET-mediated branching of MDCK cells (PMID:15326489)
• Peptides with very high affinity for Grb2 were rationally designed as possible antitumor agents (review) (PMID:15368963)
• demonstrate an interaction between Grb2 and magicin (PMID:15467741)
• Grb2-mediated recruitment of the functional RING domain of Cbl to the EGFR is essential and sufficient to support receptor endocytosis (PMID:15635092)
• p52Shc couples tyrosine kinase receptors to Ras by recruiting Grb2. (PMID:15688026)
• Src homology 2 domain of Grb2 and the tyrosine residue tyrosine606 in CD229 are required for CD229-Grb2 complex formation. (PMID:15879090)
• Grb2, in addition to its key function in signaling through Ras, may have a negatively regulatory role on EGF-induced PLC-gamma1 activation. (PMID:16038803)
• EGFR-induced signaling and Grb2 are essential for formation of clathrin-coated pits accommodating the EGFR, while activation of MAPK and PI3K is not required. (PMID:16382132)
• Y(169) and Y(179) are located within two consensus sites in PLD2 that mediate an SH2 interaction with Grb2. Y(169) and Y(179) are located within two consensus sites in PLD2 that mediate an SH2 interaction with Grb2. (PMID:16407827)
• EGFR has six binding sites for the adapter protein Grb2, and ErbB4 has five. (PMID:16729043)
• The full-length Grb2 proteins mediate negative regulation of the intrinsic Ras guanine-nucleotide exchange activity of hSos1. (PMID:16760435)
• Grb2 is not essential for CD28-mediated NF-kappa B activation. The interaction between the YMNM motif of CD28 and the SH2 domain is sufficient for Grb2 binding. (PMID:16818765)
• In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL. (PMID:16906159)
• By lysing primary hemopoietic cells at high pH, BCR-ABL1 protein-degradative activity was inhibited & association between BCR-ABL1 protein in complexes with adaptor proteins CBL, CRKL & GRB2 in primary chronic myeloid leukaemia material was demonstrated (PMID:16955467)
• biophysical analysis of Grb2-SH2 domain-swapping (PMID:17466257)
• Grb2 Src homology-2 domain-mediated interactions have a critical role in metastatic spread of primary solid tumors and Grb2 is inhibited by C90 (PMID:17616655)
• These results are evidence that the Sprouty2 mechanism of ERK inhibition is independent of Grb2 binding. (PMID:17689925)
• Grb2 functions as a factor which mediates phosphorylation of AMPK at Thr172. (PMID:17849173)
• examination of rate of association reactions between Grb2 and epidermal growth factor receptor (PMID:17991782)
• These results suggest that coupling of Grb2 to Gab1 mediates the hepatocyte growth factor-induced strong activation of the ERK pathway, which is required for the inhibition of HepG2 cell proliferation. (PMID:18003605)
• tumors expressing Grb2- and Shc-recruiting Met receptors demonstrated a marked loss in Grb2-associated adaptor protein 1 (Gab1) protein levels, which was not observed in the cell lines, consistent with a post-translationally regulated process (PMID:18192688)
• In human uterine leiomyomas, GRB2 were also overexpressed. (PMID:18231572)
• Neph1 but not nephrin specifically binds to adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner. (PMID:18258597)
• Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease. (PMID:18307981)
• in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration (PMID:18420583)
• Grb2 may have a role in tumor growth, invasiveness and metastasis (PMID:18425376)
• tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases are regulated by phosphorylation (PMID:18467332)
• Structural basis of the differential binding of the SH3 domains of GRB2 to SOS1 are reported. (PMID:18778683)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grb2a	ENSDARG00000105276
mus_musculus	Grb2	ENSMUSG00000059923
rattus_norvegicus	Grb2	ENSRNOG00000003990
drosophila_melanogaster	drk	FBGN0004638
caenorhabditis_elegans		WBGENE00004774

Paralogs (9): DAPP1 (ENSG00000070190), NCK2 (ENSG00000071051), GRAP2 (ENSG00000100351), SLA2 (ENSG00000101082), GRAP (ENSG00000154016), SLA (ENSG00000155926), NCK1 (ENSG00000158092), GRAPL (ENSG00000189152), SH2D5 (ENSG00000189410)

Protein

Protein identifiers

Growth factor receptor-bound protein 2 — P62993 (reviewed: P62993)

Alternative names: Adapter protein GRB2, Protein Ash, SH2/SH3 adapter GRB2

All UniProt accessions (5): P62993, B0LPF3, J3KT38, J3QLF6, J3QRL5

UniProt curated annotations — full annotation on UniProt →

Function. Non-enzymatic adapter protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression. Thus, participates in many biological processes including regulation of innate and adaptive immunity, autophagy, DNA repair or necroptosis. Controls signaling complexes at the T-cell antigen receptor to facilitate the activation, differentiation, and function of T-cells. Mechanistically, engagement of the TCR leads to phosphorylation of the adapter protein LAT, which serves as docking site for GRB2. In turn, GRB2 establishes a a connection with SOS1 that acts as a guanine nucleotide exchange factor and serves as a critical regulator of KRAS/RAF1 leading to MAPKs translocation to the nucleus and activation. Functions also a role in B-cell activation by amplifying Ca(2+) mobilization and activation of the ERK MAP kinase pathway upon recruitment to the phosphorylated B-cell antigen receptor (BCR). Plays a role in switching between autophagy and programmed necrosis upstream of EGFR by interacting with components of necrosomes including RIPK1 and with autophagy regulators SQSTM1 and BECN1. Regulates miRNA biogenesis by forming a functional ternary complex with AGO2 and DICER1. Functions in the replication stress response by protecting DNA at stalled replication forks from MRE11-mediated degradation. Mechanistically, inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks. Additionally, directly recruits and later releases MRE11 at DNA damage sites during the homology-directed repair (HDR) process. Does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Mechanistically, inhibits RAS-ERK signaling and downstream cell proliferation by competing with GRB2 for SOS1 binding and thus by regulating SOS1 membrane recruitment.

Subunit / interactions. Homodimer. Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS2, 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. Interacts with SOS1. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with phosphorylated MET. Interacts with phosphorylated TOM1L1. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1 and REPS2. Interacts (via SH3 domains) with syntrophin SNTA1. Interacts (via SH2 domains) with tyrosine-phosphorylated syntrophin SNTA1. Interacts (via SH3 domains) with REPS1. Interacts (via SH3 domains) with PIK3C2B. Interacts with CBL and CBLB. Interacts with AJUBA and CLNK. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Interacts with PTPN11. Interacts with PRNP. Interacts with RALGPS1. Interacts with HCST. Interacts with KDR. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with GAPT and PTPRE. Interacts (via SH2 domain) with KIF26A. Interacts (via SH3 2) with GAB2. Interacts with ADAM15. Interacts with THEMIS2. Interacts (via SH2 domain) with AXL (phosphorylated). Interacts (via SH2 domain) with KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with PTPN23. Interacts with FLT4 (tyrosine phosphorylated). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Part of a complex including TNK2, GRB2, LTK and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, 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). Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation. Interacts with DAB2. Interacts with TESPA1. Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1. Interacts with CD28. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts with ASAP3 (phosphorylated form). Interacts (via SH2 domain) with PTPRH (phosphorylated form). Interacts with PTPRO (phosphorylated form). Interacts with PTPRB (phosphorylated form). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region). Interacts with FCRL6 (tyrosine phosphorylated form). Interacts with RHEX (via tyrosine-phosphorylated form). Interacts with DENND2B. Interacts with SPRY2. Interacts with LRRC8A. Interacts with PEAK1. Interacts with CD28. Interacts with FCRL1. Interacts with PCNA. Interacts with CD19. Interacts with BECN1. Interacts with RAD51; the interaction inhibits RAD51 ATPase to stabilize RAD51-DNA complex at stalled replication forks. Interacts with MRE11; this interaction recruits MRE11 to the DNA damage sites. Interacts with RIPK1 and SQSTM1; these interactions play a critical role in regulating programmed necrosis. Interacts with AGO2; this interaction is important for the formation of a ternary complex containing GRB2, AGO2 and DICER1. Interacts with TIGIT; this interaction inhibits PI3K and MAPK signaling cascades. Interacts with CD226; this interaction leads to activation of VAV1, PI3K and PLCG1. Interacts (via SH2-domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP ‘Tyr-69’. Interacts with SOS1; this interaction competes with GRB2 to bind SOS1 via its N-terminal SH3 domain. (Microbial infection) Interacts (via SH3 domain) with hepatitis E virus/HEV ORF3 protein. (Microbial infection) Interacts with hepatitis C virus/HCV protein NS5A via its SH3 domains. (Microbial infection) Interacts with herpes simplex virus 1 protein UL46. (Microbial infection) Interacts with B19 parvovirus protein 11K.

Subcellular location. Nucleus. Cytoplasm. Endosome. Golgi apparatus.

Post-translational modifications. Phosphorylation of Tyr-209 in the C-terminal SH3 domain reduces its binding to SOS1. Ubiquitinated by RNF173, leading to proteasomal degradation and inhibition of the RAF/MEK/ERK pathway. In the nucleus, polyubiquitinated by RBBP6 at Lys-109 at DNA damage sites.

Domain organisation. The SH3 domains mediate interaction with RALGPS1 and SHB.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P62993-1	1, Ash-L	yes
P62993-2	2, GRB3-3

RefSeq proteins (2): NP_002077, NP_987102 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001452	SH3_domain	Domain
IPR035641	GRB2_N_SH3	Domain
IPR035643	GRB2_C_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR043539	Grb2-like	Family

Pfam: PF00017, PF00018

UniProt features (49 total): strand 24, mutagenesis site 9, modified residue 6, helix 4, domain 3, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

58 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6ICG	X-RAY DIFFRACTION	1.15
3WA4	X-RAY DIFFRACTION	1.35
1JYR	X-RAY DIFFRACTION	1.55
2VWF	X-RAY DIFFRACTION	1.58
2VVK	X-RAY DIFFRACTION	1.6
3OV1	X-RAY DIFFRACTION	1.6
4P9V	X-RAY DIFFRACTION	1.64
1GCQ	X-RAY DIFFRACTION	1.68
2W0Z	X-RAY DIFFRACTION	1.7
3C7I	X-RAY DIFFRACTION	1.7
3IN8	X-RAY DIFFRACTION	1.7
3S8L	X-RAY DIFFRACTION	1.71
3S8N	X-RAY DIFFRACTION	1.71
1BMB	X-RAY DIFFRACTION	1.8
1ZFP	X-RAY DIFFRACTION	1.8
2AOB	X-RAY DIFFRACTION	1.8
4P9Z	X-RAY DIFFRACTION	1.8
6WM1	X-RAY DIFFRACTION	1.8
3OVE	X-RAY DIFFRACTION	1.82
3S8O	X-RAY DIFFRACTION	1.85
2H46	X-RAY DIFFRACTION	1.9
2HUW	X-RAY DIFFRACTION	1.9
2AOA	X-RAY DIFFRACTION	1.99
1JYQ	X-RAY DIFFRACTION	2
3IMD	X-RAY DIFFRACTION	2
3IN7	X-RAY DIFFRACTION	2
3MXC	X-RAY DIFFRACTION	2
3N84	X-RAY DIFFRACTION	2
3N8M	X-RAY DIFFRACTION	2
6ICH	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62993-F1	88.89	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 109, 1, 6, 50, 109, 209, 211

Mutagenesis-validated functional residues (9):

Position	Phenotype
36	loss of binding to ago2.
49	ineffective in dna synthesis. abolishes interaction with shb; when associated with l-206. abolishes interaction with sos
89	no effect on the interaction with sos1.
90	no effect on the interaction with sos1.
109	loss of polyubiquitination.
123	strong loss of clustering of phospho-lat at the t-cell plasma membrane.
193	loss of binding to ago2.
203	ineffective in dna synthesis. abolishes interaction with sos1.
206	abolishes interaction with shb; when associated with l-49.

Function

Pathways and Gene Ontology

Reactome pathways

97 pathways

ID	Pathway
R-HSA-8983432	Interleukin-15 signaling
R-HSA-9674555	Signaling by CSF3 (G-CSF)
R-HSA-9702518	STAT5 activation downstream of FLT3 ITD mutants
R-HSA-9703648	Signaling by FLT3 ITD and TKD mutants
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9842663	Signaling by LTK
R-HSA-109704	PI3K Cascade
R-HSA-112412	SOS-mediated signalling
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1250347	SHC1 events in ERBB4 signaling
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1295596	Spry regulation of FGF signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1433559	Regulation of KIT signaling
R-HSA-167044	Signalling to RAS
R-HSA-179812	GRB2 events in EGFR signaling
R-HSA-180292	GAB1 signalosome
R-HSA-180336	SHC1 events in EGFR signaling
R-HSA-182971	EGFR downregulation
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
R-HSA-186763	Downstream signal transduction
R-HSA-1963640	GRB2 events in ERBB2 signaling
R-HSA-1963642	PI3K events in ERBB2 signaling
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-210993	Tie2 Signaling
R-HSA-2179392	EGFR Transactivation by Gastrin
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491	DAP12 signaling
R-HSA-2428933	SHC-related events triggered by IGF1R

MSigDB gene sets: 814 (showing top): PID_BCR_5PATHWAY, PID_SHP2_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, BIOCARTA_PTEN_PATHWAY, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, TSENG_IRS1_TARGETS_UP

GO Biological Process (25): signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), Ras protein signal transduction (GO:0007265), insulin receptor signaling pathway (GO:0008286), fibroblast growth factor receptor signaling pathway (GO:0008543), Schwann cell development (GO:0014044), actin cytoskeleton organization (GO:0030036), positive regulation of actin filament polymerization (GO:0030838), receptor internalization (GO:0031623), positive regulation of Rac protein signal transduction (GO:0035022), endodermal cell differentiation (GO:0035987), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), T cell activation (GO:0042110), natural killer cell mediated cytotoxicity (GO:0042267), myelination (GO:0042552), signal transduction in response to DNA damage (GO:0042770), regulation of MAPK cascade (GO:0043408), negative regulation of natural killer cell mediated cytotoxicity (GO:0045953), insulin-like growth factor receptor signaling pathway (GO:0048009), B cell receptor signaling pathway (GO:0050853), branching involved in labyrinthine layer morphogenesis (GO:0060670), cellular response to ionizing radiation (GO:0071479), positive regulation of reactive oxygen species metabolic process (GO:2000379), T cell costimulation (GO:0031295), anatomical structure formation involved in morphogenesis (GO:0048646)

GO Molecular Function (15): phosphotyrosine residue binding (GO:0001784), RNA binding (GO:0003723), transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068), guanyl-nucleotide exchange factor adaptor activity (GO:0005091), epidermal growth factor receptor binding (GO:0005154), neurotrophin TRKA receptor binding (GO:0005168), SH3 domain binding (GO:0017124), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), insulin receptor substrate binding (GO:0043560), ephrin receptor binding (GO:0046875), protein binding (GO:0005515), protein domain specific binding (GO:0019904)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endosome (GO:0005768), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), cell cortex (GO:0005938), COP9 signalosome (GO:0008180), vesicle membrane (GO:0012506), extracellular exosome (GO:0070062), Grb2-EGFR complex (GO:0070436), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Signaling by EGFR	4
Signaling by Receptor Tyrosine Kinases	2
IRS-mediated signalling	2
Interleukin-2 family signaling	1
Cytokine Signaling in Immune system	1
Signaling by FLT3 ITD and TKD mutants	1
FLT3 signaling in disease	1
Signaling by ALK in cancer	1
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Signaling by ERBB2	1
Signaling by ERBB4	1
Intracellular signaling by second messengers	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell surface receptor protein tyrosine kinase signaling pathway	4
protein binding	4
cellular anatomical structure	4
cytoplasm	3
intracellular membrane-bounded organelle	2
endomembrane system	2
cell periphery	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ERBB signaling pathway	1
small GTPase-mediated signal transduction	1
cellular response to insulin stimulus	1
cellular response to fibroblast growth factor stimulus	1
Schwann cell differentiation	1
glial cell development	1
cytoskeleton organization	1
actin filament-based process	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
receptor-mediated endocytosis	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
endoderm formation	1
cell differentiation	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
lymphocyte activation	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
axon ensheathment	1
DNA damage response	1
intracellular signal transduction	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1342 interactions, top by confidence:

A	B	Type	Score
GRB2	SHC1	psi-mi:“MI:0915”(physical association)	0.980
EGFR	GRB2	psi-mi:“MI:0915”(physical association)	0.980
CBLB	GRB2	psi-mi:“MI:0915”(physical association)	0.970
GRB2	CBLB	psi-mi:“MI:0915”(physical association)	0.970
GAB2	GRB2	psi-mi:“MI:0915”(physical association)	0.960
CBL	GRB2	psi-mi:“MI:0915”(physical association)	0.960
GRB2	CBL	psi-mi:“MI:0915”(physical association)	0.960
WASL	GRB2	psi-mi:“MI:0915”(physical association)	0.940
GAREM1	GRB2	psi-mi:“MI:0915”(physical association)	0.940
GRB2	WASL	psi-mi:“MI:0915”(physical association)	0.940
GRB2	GAREM1	psi-mi:“MI:0915”(physical association)	0.940
STAMBP	GRB2	psi-mi:“MI:0915”(physical association)	0.930
GRB2	STAMBP	psi-mi:“MI:0915”(physical association)	0.930
GRB2	DNM2	psi-mi:“MI:0915”(physical association)	0.930
DNM2	GRB2	psi-mi:“MI:0915”(physical association)	0.930
GRB2	LCP2	psi-mi:“MI:0915”(physical association)	0.920

BioGRID (1739): GRB2 (Reconstituted Complex), GRB2 (Reconstituted Complex), GRB2 (Affinity Capture-Western), GRB2 (Affinity Capture-Western), SHC1 (Affinity Capture-Western), EGFR (Affinity Capture-Western), GRB2 (Two-hybrid), GRB2 (Two-hybrid), GRB2 (Two-hybrid), HNRNPK (Two-hybrid), LCP2 (Two-hybrid), LMO2 (Two-hybrid), REL (Two-hybrid), TRIM27 (Two-hybrid), TP53BP2 (Two-hybrid)

ESM2 similar proteins: A6QLK6, O14508, O35717, O70277, O75382, O88582, O95057, P09851, P20936, P49138, P50904, P57790, P62993, P62994, P87379, Q05B84, Q07883, Q08012, Q13588, Q14145, Q16644, Q2T9Z7, Q3SYZ2, Q5PR73, Q5R4J7, Q5R6S2, Q5R774, Q5RKN4, Q5ZLD3, Q60631, Q66H84, Q66II3, Q684M4, Q6GPJ9, Q6TDP3, Q6YKA8, Q6ZPT1, Q7YRV6, Q861R0, Q8TC17

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

59 interactions.

A	Effect	B	Mechanism
BCR-ABL	down-regulates	GRB2	phosphorylation
GRB2	up-regulates	CBL	relocalization
ERBB2	up-regulates	GRB2	relocalization
ERBB3	up-regulates	GRB2	binding
ERBB4	up-regulates	GRB2	binding
SHC3	up-regulates	GRB2	relocalization
GRB2	down-regulates	KIT
GRB2	up-regulates	SOS2	binding
FGFR2	up-regulates	GRB2	phosphorylation
CD28	up-regulates	GRB2	binding
GRB2	up-regulates	GAB2	binding
EGFR	unknown	GRB2	phosphorylation
SHC1	up-regulates	GRB2	binding
GRB2	up-regulates	GAB1	binding
CBLB	“up-regulates activity”	GRB2	binding
IRS1	“up-regulates activity”	GRB2	binding
GRB2	“up-regulates activity”	SOS1	relocalization
BCR-ABL	“down-regulates activity”	GRB2	phosphorylation
SRC	unknown	GRB2	phosphorylation
ALK	unknown	GRB2	phosphorylation
BCR-ABL	unknown	GRB2	phosphorylation
KIT	“up-regulates activity”	GRB2	binding
LAT	up-regulates	GRB2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Clathrin-mediated endocytosis	5	9.3×	4e-03
RAC1 GTPase cycle	6	8.0×	3e-03
CDC42 GTPase cycle	5	7.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

17 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1761 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75321653:GCTTA:G	donor_loss	1.0000
17:75321656:TA:T	donor_loss	1.0000
17:75321657:A:AC	donor_gain	1.0000
17:75321657:AC:A	donor_loss	1.0000
17:75321658:C:CC	donor_gain	1.0000
17:75321658:C:CT	donor_loss	1.0000
17:75321823:CAAAC:C	acceptor_gain	1.0000
17:75321824:AAAC:A	acceptor_gain	1.0000
17:75321825:AAC:A	acceptor_gain	1.0000
17:75321825:AACC:A	acceptor_loss	1.0000
17:75321826:AC:A	acceptor_gain	1.0000
17:75321827:CC:C	acceptor_gain	1.0000
17:75321827:CCTGG:C	acceptor_loss	1.0000
17:75321828:C:CC	acceptor_gain	1.0000
17:75321828:CTGGG:C	acceptor_loss	1.0000
17:75321829:T:A	acceptor_loss	1.0000
17:75325892:ACTT:A	donor_loss	1.0000
17:75325894:TTACT:T	donor_loss	1.0000
17:75325895:TACT:T	donor_loss	1.0000
17:75325896:A:AC	donor_gain	1.0000
17:75325896:ACTTG:A	donor_loss	1.0000
17:75325897:C:CT	donor_gain	1.0000
17:75325897:CT:C	donor_gain	1.0000
17:75325897:CTT:C	donor_gain	1.0000
17:75325897:CTTG:C	donor_gain	1.0000
17:75325897:CTTGA:C	donor_gain	1.0000
17:75326017:CCAC:C	acceptor_gain	1.0000
17:75326018:CAC:C	acceptor_gain	1.0000
17:75326018:CACC:C	acceptor_gain	1.0000
17:75326021:C:CC	acceptor_gain	1.0000

AlphaMissense

1462 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75320393:A:T	V210D	1.000
17:75320405:G:T	P206H	1.000
17:75320406:G:A	P206S	1.000
17:75320406:G:T	P206T	1.000
17:75320408:A:G	F205S	1.000
17:75320414:C:T	G203D	1.000
17:75320415:C:G	G203R	1.000
17:75320435:C:T	G196E	1.000
17:75320436:C:G	G196R	1.000
17:75320436:C:T	G196R	1.000
17:75320442:A:G	W194R	1.000
17:75320442:A:T	W194R	1.000
17:75320443:C:A	W193C	1.000
17:75320443:C:G	W193C	1.000
17:75320444:C:G	W193S	1.000
17:75320445:A:G	W193R	1.000
17:75320445:A:T	W193R	1.000
17:75320492:A:G	F177S	1.000
17:75320498:A:G	L175P	1.000
17:75320521:A:C	F167L	1.000
17:75320521:A:T	F167L	1.000
17:75320522:A:G	F167S	1.000
17:75320523:A:G	F167L	1.000
17:75320527:A:C	F165L	1.000
17:75320527:A:T	F165L	1.000
17:75320529:A:G	F165L	1.000
17:75320534:G:T	A163D	1.000
17:75321684:A:G	L148P	1.000
17:75321684:A:T	L148Q	1.000
17:75321701:T:A	R142S	1.000

dbSNP variants (sampled 300 via entrez): RS1000028237 (17:75377736 G>C), RS1000032693 (17:75383618 C>G,T), RS1000048987 (17:75383386 G>A), RS1000062288 (17:75370396 A>G), RS1000063433 (17:75393974 G>A), RS1000116225 (17:75363776 C>T), RS1000123485 (17:75369679 A>G), RS1000139801 (17:75329162 A>C,G), RS1000163281 (17:75360093 G>A,T), RS1000193741 (17:75403259 G>A), RS1000231958 (17:75335191 G>A), RS1000264099 (17:75353645 A>T), RS1000320397 (17:75382031 T>C), RS1000326168 (17:75396852 G>T), RS1000339878 (17:75327226 C>T)

Disease associations

OMIM: gene MIM:108355 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003155_33	Systemic lupus erythematosus	3.000000e-06
GCST005752_11	Systemic lupus erythematosus	1.000000e-11
GCST005752_44	Systemic lupus erythematosus	2.000000e-06
GCST005831_5	Systemic lupus erythematosus	5.000000e-09
GCST007400_24	Systemic lupus erythematosus	1.000000e-07
GCST009131_22	Systemic sclerosis	2.000000e-08
GCST009597_159	Multiple sclerosis	5.000000e-08
GCST010244_201	Triglyceride levels	1.000000e-08
GCST010727_37	Deep white matter hyperintensities	4.000000e-07
GCST012226_814	Waist circumference adjusted for body mass index	7.000000e-12
GCST012228_593	Waist-hip index	2.000000e-08
GCST90011899_101	Aspartate aminotransferase levels	2.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3663 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 175,245 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1554	DACTINOMYCIN	4	175,245

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

8 measured of 16 human assays (16 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
cyclic ((N-AC)Gla Leu Tyr BCH Asn Val Gly Met Tyr Cys NH2)	IC50	730 nM
4-[(2S)-2-{[(1S)-1-{3-[(3,4-dichlorophenyl)methyl]-1,2,4-oxadiazol-5-yl}-2-hydroxyethyl]carbamoyl}-2-(1-phenylacetamido)ethyl]phenoxyphosphonic acid	IC50	263000 nM
4-[(2S)-2-{[(1S)-3-carbamoyl-1-[3-(naphthalen-2-ylmethyl)-1,2,4-oxadiazol-5-yl]propyl]carbamoyl}-2-acetamidoethyl]phenoxyphosphonic acid	IC50	327000 nM
4-[(2S)-2-{[(1S)-1-{3-[(3,4-dichlorophenyl)methyl]-1,2,4-oxadiazol-5-yl}-3-phenylpropyl]carbamoyl}-2-acetamidoethyl]phenoxyphosphonic acid	IC50	340000 nM
4-[(2S)-2-{[(1S)-2-hydroxy-1-[3-(naphthalen-2-ylmethyl)-1,2,4-oxadiazol-5-yl]ethyl]carbamoyl}-2-(1-phenylacetamido)ethyl]phenoxyphosphonic acid	IC50	368000 nM
4-[(2S)-2-{[(1S)-3-carbamoyl-1-{3-[(3,4-dichlorophenyl)methyl]-1,2,4-oxadiazol-5-yl}propyl]carbamoyl}-2-acetamidoethyl]phenoxyphosphonic acid	IC50	441000 nM
4-[(2S)-2-{[(1S)-1-(3-benzyl-1,2,4-oxadiazol-5-yl)-3-carbamoylpropyl]carbamoyl}-2-acetamidoethyl]phenoxyphosphonic acid	IC50	456000 nM
4-[(2S)-2-acetamido-2-{[(1S)-2-hydroxy-1-[3-(naphthalen-2-ylmethyl)-1,2,4-oxadiazol-5-yl]ethyl]carbamoyl}ethyl]phenoxyphosphonic acid	IC50	479000 nM

ChEMBL bioactivities

289 potent at pChembl≥5 of 343 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.12	Kd	0.075	nM	CHEMBL423988
10.12	Kd	0.075	nM	CHEMBL349373
10.03	Kd	0.093	nM	CHEMBL349373
10.01	Kd	0.097	nM	CHEMBL175456
9.52	IC50	0.3	nM	CHEMBL73003
9.40	IC50	0.4	nM	CHEMBL72036
9.05	IC50	0.9	nM	CHEMBL72694
9.00	IC50	1	nM	CHEMBL3144403
9.00	IC50	1	nM	CHEMBL77689
8.96	Kd	1.1	nM	CHEMBL427641
8.92	IC50	1.2	nM	CHEMBL431982
8.85	IC50	1.4	nM	CHEMBL306657
8.83	Kd	1.47	nM	CHEMBL349373
8.80	IC50	1.6	nM	CHEMBL1160046
8.80	IC50	1.6	nM	CHEMBL307890
8.78	IC50	1.68	nM	CHEMBL439878
8.74	Kd	1.8	nM	CHEMBL437910
8.70	IC50	2	nM	CHEMBL306657
8.70	IC50	2	nM	CHEMBL84798
8.70	IC50	2	nM	CHEMBL367037
8.64	Kd	2.28	nM	CHEMBL175456
8.52	Kd	3	nM	CHEMBL3142999
8.48	IC50	3.3	nM	CHEMBL191728
8.47	IC50	3.4	nM	CHEMBL72525
8.44	Kd	3.62	nM	CHEMBL191728
8.42	IC50	3.77	nM	CHEMBL2371612
8.40	IC50	4	nM	CHEMBL72036
8.37	IC50	4.3	nM	CHEMBL70024
8.37	Kd	4.3	nM	CHEMBL175456
8.37	IC50	4.3	nM	CHEMBL1205233
8.20	Kd	6.3	nM	CHEMBL2296610
8.20	IC50	6.3	nM	CHEMBL424823
8.15	IC50	7	nM	CHEMBL332862
8.12	IC50	7.65	nM	CHEMBL2371617
8.10	IC50	8	nM	CHEMBL93367
8.10	IC50	8	nM	CHEMBL279961
8.10	IC50	8	nM	CHEMBL1672710
8.10	IC50	8	nM	CHEMBL312875
8.08	IC50	8.4	nM	CHEMBL193281
8.08	IC50	8.26	nM	CHEMBL216415
8.06	IC50	8.8	nM	CHEMBL263328
8.05	IC50	9	nM	CHEMBL55627
8.04	IC50	9.2	nM	CHEMBL72996
8.00	IC50	10	nM	CHEMBL55627
7.96	IC50	11	nM	CHEMBL3142999
7.96	IC50	11	nM	CHEMBL331463
7.96	IC50	11	nM	CHEMBL582892
7.96	IC50	11.1	nM	CHEMBL19378
7.92	IC50	12.1	nM	CHEMBL70024
7.92	IC50	12.1	nM	CHEMBL306657

PubChem BioAssay actives

287 with measured affinity, of 676 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[2-amino-4-[(2S)-2-amino-3-[[1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	75188: Inhibition of binding to Growth factor receptor bound protein 2 (Grb2) SH2 domain	ic50	<0.0001	uM
2-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methylindol-1-yl)methyl]-8,17,20-trioxo-10-[4-(phosphonomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetic acid	711516: Binding affinity to SH2 domain of GRB2	kd	0.0001	uM
trisodium;2-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methylindol-1-yl)methyl]-8,17,20-trioxo-10-[4-(phosphonatomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetate	75330: In vitro binding affinity for Grb2 SH2 domain	kd	0.0001	uM
[4-[[(2S,5S,9S,11E)-5-(2-amino-2-oxoethyl)-2-methyl-9-(naphthalen-1-ylmethyl)-3,6,15-trioxo-13-[4-(phosphonomethyl)phenyl]-1,4,7-triazacyclopentadec-11-en-2-yl]methyl]phenyl]phosphonic acid	238078: In vitro binding affinity for growth factor receptor bound protein 2 SH2 domain from human breast cancer cells	kd	0.0001	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(5-hydroxyindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0003	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(5-methylindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0004	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(5-methoxyindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0009	uM
(3-aminophenyl)methyl N-[(2S)-1-[[1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]carbamate	1224126: Binding affinity to Grb2 SH2 domain (unknown origin)	ic50	0.0010	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-[1-[2-[[(2S)-1-[[1-[[(2S)-4-amino-1,4-dioxo-1-(pentylamino)butan-2-yl]carbamoyl]cyclohexyl]amino]-1-oxo-3-[4-(phosphonomethyl)phenyl]propan-2-yl]amino]-2-oxoethyl]triazol-4-yl]propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	274120: Binding affinity to Grb2-SH2 domain	kd	0.0011	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-(3-indol-1-ylpropylamino)-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0012	uM
2-[(9S,10S,11E,14S,18S)-18-(2-amino-2-oxoethyl)-14-(naphthalen-1-ylmethyl)-8,17,20-trioxo-10-[4-(phosphonomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetic acid	75183: In vitro Growth factor receptor bound protein 2-binding affinity in in surface plasmon resonance (SPR) method	ic50	0.0014	uM
(3-aminophenyl)methyl N-[(2S)-1-[[1-[[(6S)-6-carbamoylcyclohex-2-en-1-yl]carbamoyl]cyclohexyl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]carbamate	155663: Inhibition of Grb2-SH2 domain binding to phospho-EGF receptor intracellular C-terminal domain	ic50	0.0016	uM
(3-aminophenyl)methyl N-[(2S)-1-[[1-[[(1R,6S)-6-carbamoylcyclohex-2-en-1-yl]carbamoyl]cyclohexyl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]carbamate	75010: Inhibition of Grb2-SH2 domain binding to phospho-EGF receptor intracellular C-terminal domain	ic50	0.0016	uM
[4-[[(9S,12S,15S,21R,24S,27S,33S,36S)-36-(2-amino-2-oxoethyl)-12-benzyl-21-carbamoyl-27-(2,2-dimethylpropyl)-24-[(4-hydroxyphenyl)methyl]-15-methyl-8,11,14,17,23,26,29,32,35,38-decaoxo-33-propan-2-yl-19-thia-7,10,13,16,22,25,28,31,34,37-decazaspiro[5.32]octatriacontan-9-yl]methyl]phenyl] dihydrogen phosphate	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0017	uM
44418277	274120: Binding affinity to Grb2-SH2 domain	kd	0.0018	uM
2-[(9S,10S,11E,14S,18S)-18-(2-amino-2-oxoethyl)-14-(2,3-dihydronaphthalen-1-ylmethyl)-8,17,20-trioxo-10-[4-(phosphonomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetic acid	75184: Inhibition against Growth factor receptor bound protein 2 binding using ELISA technique	ic50	0.0020	uM
2-[[(2S)-1-[[1-[[(2S)-4-amino-1-[3-(5-methylindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-1-oxo-3-[4-(phosphonomethyl)phenyl]propan-2-yl]amino]-2-oxoacetic acid	75186: Inhibition of Growth factor receptor bound protein 2 binding by ELISA assay method	ic50	0.0020	uM
(3-aminophenyl)methyl N-[(2S)-1-[[(2S)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-2-methyl-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]carbamate	75313: The compound was tested on a LS250B Perkin-Elmer fluorimeter for Growth factor receptor bound protein 2 equilibrium constant(Kd) by the Michaelis-Menten type curve-fitting equation	kd	0.0030	uM
2-[4-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-9-(carboxymethyl)-14-[(5-methylindol-1-yl)methyl]-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl]phenyl]propanedioic acid	241368: Inhibitory concentration against growth factor receptor bound protein 2	ic50	0.0033	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-[5-(dimethylamino)indol-1-yl]propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0034	uM
[4-[[(9S,12S,15S,21R,24S,27S,33S,36S)-36-(2-amino-2-oxoethyl)-21-carbamoyl-24-[(4-hydroxyphenyl)methyl]-15-methyl-12-(2-methylpropyl)-27-(2-methylsulfanylethyl)-8,11,14,17,23,26,29,32,35,38-decaoxo-33-propan-2-yl-19-thia-7,10,13,16,22,25,28,31,34,37-decazaspiro[5.32]octatriacontan-9-yl]methyl]phenyl] dihydrogen phosphate	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0038	uM
2-[4-[(9S,10S,11E,14S,18S)-18-(2-amino-2-oxoethyl)-9-(carboxymethyl)-14-(naphthalen-1-ylmethyl)-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl]phenyl]propanedioic acid	1811150: Binding affinity to Grb2-SH2 domain (unknown origin) by ELISA	ic50	0.0043	uM
disodium;2-[4-[(9S,10S,11E,14S,18S)-18-(2-amino-2-oxoethyl)-9-(carboxymethyl)-14-(naphthalen-1-ylmethyl)-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl]phenyl]propanedioate	75182: In vitro Growth factor receptor bound protein 2-binding affinity in ELISA method	ic50	0.0043	uM
2-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-10-[4-[[hydroxy(methyl)phosphoryl]methyl]phenyl]-14-[(5-methylindol-1-yl)methyl]-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetic acid	241368: Inhibitory concentration against growth factor receptor bound protein 2	ic50	0.0063	uM
[4-[(2R)-2-acetamido-3-[[1-[[(2S)-4-amino-1-(3-naphthalen-1-ylpropylamino)-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	75175: Inhibitory concentration against Growth factor receptor bound protein 2 in MDA-MB-453 cells	ic50	0.0070	uM
[4-[[(6R,9S,12S,18S,21S,27S,30S,33S)-21-(2-amino-2-oxoethyl)-6-carbamoyl-12-(2,2-dimethylpropyl)-9-[(4-hydroxyphenyl)methyl]-30-(2-methylpropyl)-2,8,11,14,17,20,23,26,29,32-decaoxo-18-propan-2-ylspiro[4-thia-1,7,10,13,16,19,22,25,28,31-decazabicyclo[31.3.0]hexatriacontane-24,1’-cyclohexane]-27-yl]methyl]phenyl] dihydrogen phosphate	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0076	uM
2-[(3S,9S,10S,11E,14S)-3-(2-amino-2-oxoethyl)-14-(2,3-dihydronaphthalen-1-ylmethyl)-6,6-dimethyl-2,5,8-trioxo-10-[4-(phosphonomethyl)phenyl]-1,4,7-triazacyclopentadec-11-en-9-yl]acetic acid	75184: Inhibition against Growth factor receptor bound protein 2 binding using ELISA technique	ic50	0.0080	uM
(3R)-4-[[1-[[(2S)-3-carboxy-1-(3-naphthalen-1-ylpropylamino)-1-oxopropan-2-yl]carbamoyl]cyclohexyl]amino]-4-oxo-3-[[4-(phosphonomethyl)phenyl]methyl]butanoic acid	574408: Displacement of biotin-Ahx-PSpYVNVQN from Grb2-SH2 by competition binding assay	ic50	0.0080	uM
2-[4-[(2S)-3-[[1-[[(2S)-4-amino-1-[3-(5-methylindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-2-(oxaloamino)-3-oxopropyl]phenyl]propanedioic acid	75186: Inhibition of Growth factor receptor bound protein 2 binding by ELISA assay method	ic50	0.0080	uM
(3R)-4-[[1-[[(2S)-4-amino-1-(3-naphthalen-1-ylpropylamino)-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-4-oxo-3-[[4-(phosphonomethyl)phenyl]methyl]butanoic acid	75181: Binding affinity for Growth factor receptor bound protein 2 SH2 domain	ic50	0.0080	uM
3-[(3R,6S,9S,15S,18S,21S,24S,27S)-18-(2-amino-2-oxoethyl)-3-carbamoyl-6-[(4-hydroxyphenyl)methyl]-27-(2-methylpropyl)-9-(2-methylsulfanylethyl)-5,8,11,14,17,20,23,26,29,33-decaoxo-24-[(4-phosphonooxyphenyl)methyl]-15-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,32-decazacyclotetratriacont-21-yl]propanoic acid	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0083	uM
2-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-10-[4-[[benzyl(hydroxy)phosphoryl]methyl]phenyl]-14-[(5-methylindol-1-yl)methyl]-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-9-yl]acetic acid	241368: Inhibitory concentration against growth factor receptor bound protein 2	ic50	0.0084	uM
2-[4-[(9S,10S,11E,14R,18S)-18-(2-amino-2-oxoethyl)-9-(carboxymethyl)-14-[(5-methylindol-1-yl)methyl]-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl]anilino]-2-oxoacetic acid	241368: Inhibitory concentration against growth factor receptor bound protein 2	ic50	0.0088	uM
2-[[(2S)-1-[[1-[[(2S)-4-amino-1-(3-naphthalen-1-ylpropylamino)-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-1-oxo-3-[4-(phosphonomethyl)phenyl]propan-2-yl]amino]-2-oxoacetic acid	75181: Binding affinity for Growth factor receptor bound protein 2 SH2 domain	ic50	0.0090	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(1-methylindol-3-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0092	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(2-hydroxynaphthalen-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	75011: Inhibition of Grb2 SH2 domain binding	ic50	0.0110	uM
[4-[(2S)-3-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-2-methyl-2-[[(2S)-2-[[2-methyl-2-(4-methyl-2-phenyldiazenylphenoxy)propanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	442238: Inhibition of Grb2 by ELISA	ic50	0.0110	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(8-hydroxynaphthalen-2-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	75192: Inhibitory concentration required against Src homology (SH2) domain of Growth factor receptor bound protein 2 by ELISA binding assay	ic50	0.0111	uM
2-[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(5-methylindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]propanedioic acid	75186: Inhibition of Growth factor receptor bound protein 2 binding by ELISA assay method	ic50	0.0120	uM
(3-aminophenyl)methyl N-[(2S)-1-[[(2R)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxo-2-(4-phosphonooxyphenyl)propan-2-yl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]carbamate	1224125: Binding affinity to Grb2 SH2 domain (60 to 151) (unknown origin) expressed in Escherichia coli BL21(DE3) after overnight incubation by ELISA	ic50	0.0130	uM
[4-[[(9S,12S,15S,21R,24S,27S,33S,36S)-36-(2-amino-2-oxoethyl)-21-carbamoyl-24-[(4-hydroxyphenyl)methyl]-15,27-dimethyl-12-(2-methylpropyl)-8,11,14,17,23,26,29,32,35,38-decaoxo-33-propan-2-yl-19-thia-7,10,13,16,22,25,28,31,34,37-decazaspiro[5.32]octatriacontan-9-yl]methyl]phenyl] dihydrogen phosphate	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0133	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(6-methoxy-1H-indol-3-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0140	uM
3-[(5S,8S,11S,14S,17S,20S,26S,29S,32R)-17-(2-amino-2-oxoethyl)-32-carbamoyl-26-(2,2-dimethylpropyl)-29-[(4-hydroxyphenyl)methyl]-5-methyl-8-(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30-decaoxo-11-[(4-phosphonooxyphenyl)methyl]-20-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-14-yl]propanoic acid	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0145	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-[3-(2-methylindol-1-yl)propylamino]-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	69737: Inhibition of Grb-SH2 domain binding to phosphorylated carboxy-terminal intracellular domain of epidermal growth factor receptor	ic50	0.0147	uM
(3R)-4-[[5-[[(2S)-4-amino-1-(3-naphthalen-1-ylpropylamino)-1,4-dioxobutan-2-yl]amino]-5-oxopentyl]amino]-4-oxo-3-[[4-(phosphonomethyl)phenyl]methyl]butanoic acid	238079: In vitro binding affinity for growth factor receptor bound protein 2 SH2 domain from human breast cancer cells	kd	0.0148	uM
[4-[(10R,11E,14S,18S)-18-(2-amino-2-oxoethyl)-14-(naphthalen-1-ylmethyl)-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl]phenyl]methylphosphonic acid	1811153: Displacement of FITC-Ahx-PVPePYINQSVPKRK-NH2 from N-terminal His6-tagged human full length GRB2 (1 to 217 residues) expressed in Escherichia coli assessed as inhibition constant by fluorescence anisotropy assay	ki	0.0160	uM
(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-hydroxy-2-[[(2S)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoic acid	75326: Dissociation constant of compound was determined from affinity of compound towards Growth factor receptor bound protein 2 measured by fluorescence	kd	0.0180	uM
[4-[(2S)-2-acetamido-3-[[1-[[(2S)-4-amino-1-(3-naphthalen-1-ylpropylamino)-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]amino]-3-oxopropyl]phenyl]methylphosphonic acid	75186: Inhibition of Growth factor receptor bound protein 2 binding by ELISA assay method	ic50	0.0200	uM
[4-[(10R,11E,14S,18S)-18-(2-amino-2-oxoethyl)-14-(2,3-dihydronaphthalen-1-ylmethyl)-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl]phenyl]methylphosphonic acid	75184: Inhibition against Growth factor receptor bound protein 2 binding using ELISA technique	ic50	0.0200	uM
[4-[[(9S,12S,22R,25S,28S,34S,37S)-37-(2-amino-2-oxoethyl)-22-carbamoyl-25-[(4-hydroxyphenyl)methyl]-12-(2-methylpropyl)-28-(2-methylsulfanylethyl)-8,11,14,18,24,27,30,33,36,39-decaoxo-34-propan-2-yl-20-thia-7,10,13,17,23,26,29,32,35,38-decazaspiro[5.33]nonatriacontan-9-yl]methyl]phenyl] dihydrogen phosphate	75191: Inhibition of Growth factor receptor-bound protein 2 (Grb2) SH2 domain binding by ELISA	ic50	0.0210	uM

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
bisphenol A	increases expression, affects reaction	2
Resveratrol	affects binding, affects localization, increases reaction, decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases methylation, increases expression	2
Cannabidiol	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Ozone	affects expression, increases abundance, affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Sodium Selenite	decreases expression, increases expression	2
Genistein	decreases expression, increases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
moringin	affects cotreatment, increases expression	1
Baizhu	decreases expression	1
Fangfeng	decreases expression	1
allyl isothiocyanate	decreases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
tetrandrine	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, decreases expression, affects localization	1
Nonidet P-40	decreases expression	1
arsenite	affects binding, increases reaction	1
cypermethrin	decreases expression	1
cobaltous chloride	increases expression	1
bufalin	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
arsenic acid	affects binding, increases reaction	1
benzo(e)pyrene	decreases methylation	1

ChEMBL screening assays

134 unique, capped per target: 132 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004653	Binding	Binding affinity to streptavidin-coupled biotin-labeled Grb2-SH2 by surface plasmon resonance spectrophotometry	Selectivity and mechanism of action of a growth factor receptor-bound protein 2 SRC homology 2 domain binding antagonist. — J Med Chem
CHEMBL685525	Functional	Inhibition of binding to Growth factor receptor bound protein 2 SH2 domain	L-O-(2-malonyl)tyrosine: a new phosphotyrosyl mimetic for the preparation of Src homology 2 domain inhibitory peptides. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1C6	Abcam A-431 GRB2 KO	Cancer cell line	Female
CVCL_B1DM	Abcam HCT 116 GRB2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.