SHC1

Summary

SHC1 (SHC adaptor protein 1, HGNC:10840) is a protein-coding gene on chromosome 1q21.3, encoding SHC-transforming protein 1 (P29353). Signaling adapter that couples activated growth factor receptors to signaling pathways. It is a selective cancer dependency (DepMap: 10.3% of cell lines).

This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6464 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 94 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.3% of screened cell lines
• MANE Select transcript: NM_001130040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10840
Approved symbol	SHC1
Name	SHC adaptor protein 1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	p66, ShcA
Ensembl gene	ENSG00000160691
Ensembl biotype	protein_coding
OMIM	600560
Entrez	6464

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 28 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000366442, ENST00000368445, ENST00000368449, ENST00000368450, ENST00000368453, ENST00000412170, ENST00000414115, ENST00000444179, ENST00000444664, ENST00000448116, ENST00000490667, ENST00000875560, ENST00000875561, ENST00000875562, ENST00000875563, ENST00000875564, ENST00000875565, ENST00000875566, ENST00000875567, ENST00000916209, ENST00000916210, ENST00000916211, ENST00000916212, ENST00000916213, ENST00000916214, ENST00000916215, ENST00000955108, ENST00000955109, ENST00000955110

RefSeq mRNA: 5 — MANE Select: NM_001130040 NM_001130040, NM_001130041, NM_001202859, NM_003029, NM_183001

CCDS: CCDS1076, CCDS30881, CCDS44233, CCDS44234

Canonical transcript exons

ENST00000448116 — 12 exons

Exon	Start	End
ENSE00001175025	154966162	154966231
ENSE00001512188	154970032	154970747
ENSE00001613293	154966319	154966517
ENSE00001622454	154968204	154968257
ENSE00001697799	154965543	154965781
ENSE00001710842	154968771	154968834
ENSE00001760528	154967980	154968031
ENSE00001766651	154967671	154967797
ENSE00001775206	154969378	154969448
ENSE00002201196	154965946	154966080
ENSE00003500828	154968495	154968614
ENSE00003899993	154962298	154963931

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.1324 / max 540.0324, expressed in 1819 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14881	38.4478	1499
14888	18.6781	1814
14879	5.6194	1205
14882	4.6177	1251
14880	4.4711	1106
14887	3.5494	1454
14883	0.6641	411
14889	0.3402	142
14878	0.3038	176
14877	0.1634	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.71	gold quality
gall bladder	UBERON:0002110	97.85	gold quality
omental fat pad	UBERON:0010414	97.85	gold quality
smooth muscle tissue	UBERON:0001135	97.83	gold quality
peritoneum	UBERON:0002358	97.83	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.79	gold quality
descending thoracic aorta	UBERON:0002345	97.56	gold quality
mucosa of stomach	UBERON:0001199	97.54	gold quality
adenohypophysis	UBERON:0002196	97.54	gold quality
left uterine tube	UBERON:0001303	97.53	gold quality
cartilage tissue	UBERON:0002418	97.40	gold quality
right lobe of thyroid gland	UBERON:0001119	97.27	gold quality
endocervix	UBERON:0000458	97.26	gold quality
right coronary artery	UBERON:0001625	97.24	gold quality
pituitary gland	UBERON:0000007	97.20	gold quality
thoracic aorta	UBERON:0001515	97.20	gold quality
ascending aorta	UBERON:0001496	97.17	gold quality
upper lobe of left lung	UBERON:0008952	97.17	gold quality
pericardium	UBERON:0002407	97.15	gold quality
left coronary artery	UBERON:0001626	97.12	gold quality
right adrenal gland	UBERON:0001233	97.10	gold quality
left adrenal gland	UBERON:0001234	97.07	gold quality
left adrenal gland cortex	UBERON:0035825	97.06	gold quality
coronary artery	UBERON:0001621	97.04	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.04	gold quality
upper lobe of lung	UBERON:0008948	97.03	gold quality
secondary oocyte	CL:0000655	97.02	gold quality
ectocervix	UBERON:0012249	97.02	gold quality
adipose tissue	UBERON:0001013	96.96	gold quality
adrenal gland	UBERON:0002369	96.88	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	60.99
E-HCAD-1	yes	18.25
E-ANND-3	yes	16.88
E-MTAB-8271	yes	14.98
E-MTAB-6678	yes	12.79
E-GEOD-135922	yes	10.06
E-MTAB-8410	yes	9.04
E-MTAB-9067	yes	7.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATAD2B, KLF2, MEF2A, NFE2L2, SIRT1, STAT5A, TP53

miRNA regulators (miRDB)

90 targeting SHC1, 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-9-5P	100.00	72.28	2361
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4755-5P	99.71	70.34	2716

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. (PMID:11877420)
• Isoform-specific knockdown and expression of adaptor protein ShcA using small interfering RNA (PMID:11903040)
• The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter (PMID:11948181)
• Among ten hepatocellular carcinoma cases with amplicon 1q21-q22, significant gene expression level of JTB, SHC1, CCT3 and COPA in the tumors than the paired adjacent non-malignant liver tissues. (PMID:12586295)
• shc phosphorylation is regulated by protein kinase C-dependent phosphorylations of Lck in T-lymphocytes (PMID:12589038)
• Single nucleotide polymorphisms in SHC1 have no impact on longevity for Japanese centenarians. (PMID:14530863)
• there is a novel interaction between Tie2 with the adapter molecule ShcA that may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1 (PMID:14665640)
• novel interplay between p66Shc and p52Shc in the control of T-cell fate (PMID:14749389)
• Shc and IGF-1R serve as key elements in the translocation of ERalpha to the cell membrane and in the facilitation of ERalpha-mediated rapid E2 action (PMID:14764897)
• Shc is a critical angiogenic switch for VEGF production downstream from the HGF and ErbB2 RTKs. (PMID:14983012)
• Y317 of p52(Shc) serves as an important regulatory site that allows tyrosine phosphorylation pathways to moderate androgen sensitivity in human prostate cancer cells. (PMID:14990987)
• MK2 is activated with p66(ShcA) co-expression and p66(ShcA) is an in vitro substrate for MK2, further demonstrating their association and suggesting a biological role for p66(Shc) in MK2 activation (PMID:15094067)
• CD9 activates the p46 Shc isoform in tumor cells and leads to apoptosis (PMID:15226408)
• polymorphisms in SHC1 is associated with breast cancer (PMID:15308584)
• insulin receptor substrate-4 and ShcA have roles in signaling by the fibroblast growth factor receptor (PMID:15316024)
• NCAM activates FGFR signaling in a manner distinct from FGF2 stimulation, and regulates ShcA phosphorylation by the concerted efforts of the NCAM/FGFR as well as the NCAM/Fyn signaling pathway. (PMID:15485499)
• Type 2 diabetes induces p66(shc) gene expression in circulating peripheral blood mononuclear cells. (PMID:15562031)
• p52Shc couples tyrosine kinase receptors to Ras by recruiting Grb2. (PMID:15688026)
• conclude that the expression of p66Shc protein is regulated by signaling through the thyrotropin receptor in proliferating thyroid cells (PMID:15705774)
• p46 Shc expressed in the nucleus may play an important role in gastric carcinogenesis (PMID:15753984)
• SHPS-1 functions as an anchor protein that recruits both Shc and SHP-2, whose recruitment is necessary for IGF-I-dependent Shc phosphorylation (PMID:15888547)
• p66shc may have a complex role in mammalian longevity: it is highly expressed in fibroblasts from centenarians (PMID:15992607)
• Expression of p66SHC protein correlates with proliferation of prostate cancer cells. (PMID:16170380)
• DDR2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of DDR2 cytosolic domain-Shc signaling complexes. (PMID:16186108)
• The data show that Shc is connected to the activated TCR via direct interaction with Lck. (PMID:16257509)
• p66(shc) regulates mitochondrial oxidative capacity and may extend life span by repartitioning metabolic energy conversion away from oxidative and toward glycolytic pathways (PMID:16481327)
• p66Shc overexpression plays a pro-apoptotic role in human cell lines that is independent from the presence of a functional form of p53. (PMID:16487929)
• Important variations in the p66Shc gene may be extremely rare and probably this gene is not involved in the genetic susceptibility to coronary artery disease. (PMID:16519809)
• present study identifies ShcA as a mediator of the anti-apoptotic activity of venous malformation -mutant Tie2 (PMID:16756945)
• Upon IGF-I stimulation, a complex assembles on SHPS-1 that contains SHP-2, c-Src, and Shc wherein Src phosphorylates Shc, a signaling step that is necessary for an optimal mitogenic response (PMID:16825188)
• CpG methylation has a role in the control of p66Shc gene expression and Ca2+ signaling may lead to epigenetic modifications in nondividing cells (PMID:16934220)
• report novel investigations into the role of the mitochondrial import machinery on p66(Shc) activation, which highlight the energetic status of mitochondria as a crucial determinant of p66(Shc) function (PMID:17081113)
• Since p66Shc is an aging-regulating gene, we envision that these data may help in understanding the relationship among aging, cancer, and stem cells. (PMID:17158237)
• p66Shc may play an important role in downstream hypoxic signaling, involving HIF-1alpha protein accumulation and cell death in T lymphocytes. (PMID:17167775)
• PTX3 and p66((ShcA)) mRNA levels are significantly more elevated in WBCs and in adipose tissue samples of patients with high levels of LDL compared to those with low levels. (PMID:17380301)
• the adaptors Nck and ShcA influenced adherence of S. Typhimurium to non-phagocytic cells. (PMID:17906149)
• p66 Shc may have a role in progression of colon cancer (PMID:17908971)
• IL-15 but not IL-21 caused an increased phosphorylation of Shc and ERK1/2. (PMID:17938255)
• Up-regulation of muscle p66(ShcA) relates to proteolysis rate, suggesting an involvement of this gene in muscle catabolic response in hypercatabolic traumatized patients. (PMID:17998013)
• Suggest new pathway for the induction of oxidative stress by AGEs involving FKHRL1 inactivation and MnSOD suppression via Ser-36 phosphorylation of p66(shc) in human kidney cells. (PMID:18032526)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	shc1	ENSDARG00000075437
mus_musculus	Shc1	ENSMUSG00000042626
rattus_norvegicus	Shc1	ENSRNOG00000020657

Paralogs (3): CEP152 (ENSG00000103995), SHC3 (ENSG00000148082), SHC4 (ENSG00000185634)

Protein

Protein identifiers

SHC-transforming protein 1 — P29353 (reviewed: P29353)

Alternative names: SHC-transforming protein 3, SHC-transforming protein A, Src homology 2 domain-containing-transforming protein C1

All UniProt accessions (7): P29353, H0Y539, Q5T181, Q5T182, Q5T187, Q5T188, X6R6D0

UniProt curated annotations — full annotation on UniProt →

Function. Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span. Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.

Subunit / interactions. Interacts with CPNE3; this interaction may mediate the binding of CPNE3 with ERBB2. Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain. Once activated, binds to GRB2. Interacts with tyrosine-phosphorylated CD3T and DDR2. Interacts with the N-terminal region of SH2B2. Interacts with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with TRIM31. Interacts with PTPN6/SHP (tyrosine phosphorylated). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTT. Interacts with ALK, GAB2, GRB7 and KIT. Interacts with FLT4 (tyrosine-phosphorylated). Interacts with EPHB1 and GRB2; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PDGFRB (tyrosine-phosphorylated). Interacts with ERBB4. Interacts with TEK/TIE2 (tyrosine-phosphorylated). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. Interacts with PTK2/FAK1. Interacts with CEACAM1; this interaction is CEACAM1-phosphorylation-dependent and mediates interaction with EGFR or INSR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway. Interacts (via PID domain) with PEAK1 (when phosphorylated at ‘Tyr-1188’). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1. (Microbial infection) Interacts with herpes simplex virus 1 UL46.

Subcellular location. Cytoplasm. Cell junction. Focal adhesion Mitochondrion matrix Mitochondrion.

Tissue specificity. Widely expressed. Expressed in neural stem cells but absent in mature neurons.

Post-translational modifications. Phosphorylated by activated epidermal growth factor receptor. Phosphorylated in response to FLT4 and KIT signaling. Isoform p46Shc and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-rich domain. Isoform p66Shc is phosphorylated on Ser-36 by PRKCB upon treatment with insulin, hydrogen peroxide or irradiation with ultraviolet light. Tyrosine phosphorylated in response to FLT3 signaling. Tyrosine phosphorylated by activated PTK2B/PYK2. Tyrosine phosphorylated by ligand-activated ALK. Tyrosine phosphorylated by ligand-activated PDGFRB. Tyrosine phosphorylated by TEK/TIE2. May be tyrosine phosphorylated by activated PTK2/FAK1; tyrosine phosphorylation was seen in an astrocytoma biopsy, where PTK2/FAK1 kinase activity is high, but not in normal brain tissue. Isoform p52Shc dephosphorylation by PTPN2 may regulate interaction with GRB2.

Domain organisation. In response to a variety of growth factors, isoform p46Shc and isoform p52Shc bind to phosphorylated Trk receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif of the Trk receptors. Isoform p46Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation.

Miscellaneous. Regulated by epigenetic modifications of its promoter region. Produced by alternative splicing. Produced by alternative splicing. Produced by alternative splicing.

Isoforms (6)

UniProt ID	Names	Canonical?
P29353-1	p66Shc	yes
P29353-2	p52Shc
P29353-3	p46Shc
P29353-5	5
P29353-6	6
P29353-7	7

RefSeq proteins (5): NP_001123512, NP_001123513, NP_001189788, NP_003020, NP_892113 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR006019	PID_Shc-like	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035676	SHC_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051235	CEP152/SHC-Transforming	Family

Pfam: PF00017, PF00640

UniProt features (71 total): strand 24, modified residue 10, helix 9, sequence conflict 6, splice variant 5, turn 5, region of interest 3, domain 2, sequence variant 2, mutagenesis site 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
4XWX	X-RAY DIFFRACTION	1.87
6DM4	X-RAY DIFFRACTION	1.9
4JMH	X-RAY DIFFRACTION	2.41
5CZI	X-RAY DIFFRACTION	2.6
1MIL	X-RAY DIFFRACTION	2.7
1N3H	SOLUTION NMR
1OY2	SOLUTION NMR
1QG1	SOLUTION NMR
1SHC	SOLUTION NMR
1TCE	SOLUTION NMR
2L1C	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29353-F1	63.24	0.17

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 (10): 139, 154, 349, 350, 427, 453, 1, 1, 1, 36

Mutagenesis-validated functional residues (2):

Position	Phenotype
349	alters interaction with grb2; isoform p52shc (in vitro).
427	no effect on interaction with grb2; isoform p52shc (in vitro).

Function

Pathways and Gene Ontology

Reactome pathways

74 pathways

ID	Pathway
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-167044	Signalling to RAS
R-HSA-180336	SHC1 events in EGFR signaling
R-HSA-210993	Tie2 Signaling
R-HSA-354192	Integrin signaling
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5637810	Constitutive Signaling by EGFRvIII
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-74749	Signal attenuation
R-HSA-74751	Insulin receptor signalling cascade
R-HSA-8853659	RET signaling
R-HSA-8983432	Interleukin-15 signaling
R-HSA-9020558	Interleukin-2 signaling
R-HSA-9027284	Erythropoietin activates RAS
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-9634285	Constitutive Signaling by Overexpressed ERBB2
R-HSA-9664565	Signaling by ERBB2 KD Mutants
R-HSA-9665348	Signaling by ERBB2 ECD mutants
R-HSA-9665686	Signaling by ERBB2 TMD/JMD mutants
R-HSA-9674555	Signaling by CSF3 (G-CSF)
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells
R-HSA-201556	Signaling by ALK
R-HSA-2424491	DAP12 signaling
R-HSA-2428933	SHC-related events triggered by IGF1R
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-2871809	FCERI mediated Ca+2 mobilization

MSigDB gene sets: 518 (showing top): PID_BCR_5PATHWAY, PID_SHP2_PATHWAY, AHRARNT_01, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, BIOCARTA_PTEN_PATHWAY, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, REACTOME_INNATE_IMMUNE_SYSTEM, CCAWYNNGAAR_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GAANYNYGACNY_UNKNOWN, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION

GO Biological Process (20): angiogenesis (GO:0001525), epidermal growth factor receptor signaling pathway (GO:0007173), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), insulin receptor signaling pathway (GO:0008286), negative regulation of angiogenesis (GO:0016525), actin cytoskeleton organization (GO:0030036), intracellular signal transduction (GO:0035556), defense response to bacterium (GO:0042742), negative regulation of apoptotic process (GO:0043066), positive regulation of MAPK cascade (GO:0043410), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), insulin-like growth factor receptor signaling pathway (GO:0048009), cellular response to growth factor stimulus (GO:0071363), positive regulation of cell proliferation in bone marrow (GO:0071864), regulation of superoxide metabolic process (GO:0090322), cell-cell adhesion (GO:0098609), regulation of cell population proliferation (GO:0042127), positive regulation of ERK1 and ERK2 cascade (GO:0070374)

GO Molecular Function (11): phosphotyrosine residue binding (GO:0001784), transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068), epidermal growth factor receptor binding (GO:0005154), insulin receptor binding (GO:0005158), insulin-like growth factor receptor binding (GO:0005159), neurotrophin TRKA receptor binding (GO:0005168), phospholipid binding (GO:0005543), receptor tyrosine kinase binding (GO:0030971), ephrin receptor binding (GO:0046875), epidermal growth factor binding (GO:0048408), protein binding (GO:0005515)

GO Cellular Component (8): mitochondrial matrix (GO:0005759), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), Shc-EGFR complex (GO:0070435), cytoplasm (GO:0005737), mitochondrion (GO:0005739), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Interleukin-2 family signaling	3
Signaling by ERBB2 in Cancer	2
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Signaling by ERBB2	1
Signaling by ERBB4	1
Signalling to ERKs	1
Signaling by EGFR	1
Cell surface interactions at the vascular wall	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
IRE1alpha activates chaperones	1
Signaling by Interleukins	1
Signaling by EGFRvIII in Cancer	1
MAPK1/MAPK3 signaling	1
Insulin receptor signalling cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor binding	4
cell surface receptor protein tyrosine kinase signaling pathway	3
cell population proliferation	2
intracellular anatomical structure	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
cytoplasm	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
ERBB signaling pathway	1
animal organ development	1
circulatory system development	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to insulin stimulus	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cytoskeleton organization	1
actin filament-based process	1
signal transduction	1
defense response	1
response to bacterium	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
response to growth factor	1
cellular response to endogenous stimulus	1
positive regulation of cell population proliferation	1
cell proliferation in bone marrow	1
regulation of cell proliferation in bone marrow	1
superoxide metabolic process	1
regulation of reactive oxygen species metabolic process	1
cell adhesion	1

Protein interactions and networks

STRING

2920 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHC1	GRB2	P29354	999
SHC1	SOS1	Q07889	996
SHC1	SOS2	Q07890	995
SHC1	EGFR	P00533	994
SHC1	NTRK2	Q16620	993
SHC1	IGF1R	P08069	993
SHC1	ERBB2	P04626	992
SHC1	IRS1	P35568	991
SHC1	SRC	P12931	990
SHC1	PTPN11	Q06124	982
SHC1	ERBB3	P21860	976
SHC1	NTRK1	P04629	971
SHC1	NCK1	P16333	969
SHC1	GZMB	P10144	964
SHC1	ESR1	P03372	962

IntAct

346 interactions, top by confidence:

A	B	Type	Score
GRB2	SHC1	psi-mi:“MI:0915”(physical association)	0.980
EGFR	SHC1	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
EGFR	SHC1	psi-mi:“MI:0407”(direct interaction)	0.980
EGFR	SHC1	psi-mi:“MI:0915”(physical association)	0.980
SHC1	EGFR	psi-mi:“MI:0915”(physical association)	0.980
EGFR	SHC1	psi-mi:“MI:0914”(association)	0.980
GRB2	SHC1	psi-mi:“MI:0407”(direct interaction)	0.980
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
SHC1	GRB2	psi-mi:“MI:0915”(physical association)	0.980
SHC1	EGFR	psi-mi:“MI:0407”(direct interaction)	0.980
ERBB2	EGFR	psi-mi:“MI:0914”(association)	0.950
GRB2	PTPRA	psi-mi:“MI:0914”(association)	0.940
DDX19B	MIF4GD	psi-mi:“MI:0914”(association)	0.870
PTPN12	SHC1	psi-mi:“MI:0914”(association)	0.860

BioGRID (727): GRB2 (Affinity Capture-Western), SHC1 (Affinity Capture-Western), SHC1 (Affinity Capture-RNA), SHC1 (Affinity Capture-RNA), SHC1 (Two-hybrid), SHC1 (Two-hybrid), SHC1 (Affinity Capture-MS), CALCOCO2 (Two-hybrid), SHC1 (Affinity Capture-MS), CLIC4 (Co-fractionation), MAT1A (Co-fractionation), PLS3 (Co-fractionation), PSPH (Co-fractionation), SHC1 (Co-fractionation), SHC1 (Co-fractionation)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, B1AVH7, B5DFA1, D2H0G5, D7PF45, O00750, O15357, O70143, P29353, P97573, P98083, Q00IB7, Q0IIE2, Q15678, Q16825, Q17R13, Q2I6J0, Q2I6J1, Q2V2M9, Q5JV73, Q5M824, Q5R7W7, Q5U2X5, Q61120, Q62130, Q62136, Q62728, Q62925, Q69Z98, Q6P4S2, Q6P549, Q80TI1, Q8AY68, Q8BMC3, Q8BYW1, Q8IWQ3, Q8K245, Q92529, Q92835

Diamond homologs: A0A8I3NFE2, A5PMU4, D3ZAR1, O09127, O15357, O70143, P0C6S7, P29321, P29353, P54753, P54754, P54755, P54756, P54758, P59672, P98083, Q03145, Q07498, Q09YL6, Q0IIE2, Q2I6J1, Q32PV0, Q3V1H9, Q5M824, Q5PQS4, Q5R7W7, Q5SW96, Q5TGI4, Q60629, Q61120, Q62413, Q6DD51, Q6P549, Q6P9K8, Q6S5L9, Q7Z6G8, Q801G1, Q8BIZ1, Q8C142, Q8K2A1

SIGNOR signaling

64 interactions.

A	Effect	B	Mechanism
EGFR	“up-regulates activity”	SHC1	binding
DDR2	up-regulates	SHC1	binding
PRKCD	up-regulates	SHC1	phosphorylation
PRKCD	unknown	SHC1	phosphorylation
IL2RB	up-regulates	SHC1	binding
SHC1	up-regulates	GRB2	binding
TEK	“up-regulates activity”	SHC1	binding
PTPN2	“down-regulates activity”	SHC1	dephosphorylation
IL6ST	up-regulates	SHC1	binding
FLT3	“up-regulates activity”	SHC1	phosphorylation
LCK	“up-regulates activity”	SHC1	phosphorylation
ELE1-RET	“up-regulates activity”	SHC1	binding
CCDC6-RET	“up-regulates activity”	SHC1	binding
PTK2	“up-regulates activity”	SHC1	phosphorylation
RET	up-regulates	SHC1	binding
PDGFRB	up-regulates	SHC1	phosphorylation
PTPN12	down-regulates	SHC1	dephosphorylation
SRC	“up-regulates activity”	SHC1	phosphorylation
SHC1	up-regulates	GRAP	binding
LTK	up-regulates	SHC1	phosphorylation
FYN	up-regulates	SHC1	phosphorylation
SYK	up-regulates	SHC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
PI3K events in ERBB2 signaling	6	43.8×	3e-07
Spry regulation of FGF signaling	5	38.8×	6e-06
Constitutive Signaling by EGFRvIII	5	38.8×	6e-06
Signaling by ERBB2 ECD mutants	5	36.5×	7e-06
Signaling by ERBB2 KD Mutants	7	32.2×	2e-07
Interleukin-3, Interleukin-5 and GM-CSF signaling	9	31.0×	1e-09
Interleukin receptor SHC signaling	7	31.0×	2e-07
SHC1 events in ERBB2 signaling	6	31.0×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	12	27.3×	2e-11
cellular response to epidermal growth factor stimulus	8	23.3×	4e-07
peptidyl-tyrosine phosphorylation	6	23.2×	3e-05
insulin-like growth factor receptor signaling pathway	5	22.7×	3e-04
cellular response to nerve growth factor stimulus	5	21.5×	3e-04
phosphatidylinositol 3-kinase/protein kinase B signal transduction	10	19.3×	5e-08
cell surface receptor protein tyrosine kinase signaling pathway	10	15.9×	2e-07
substrate adhesion-dependent cell spreading	5	15.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2033 predictions. Top by Δscore:

Variant	Effect	Δscore
1:154963930:ACC:A	acceptor_loss	1.0000
1:154963932:CTGG:C	acceptor_loss	1.0000
1:154965608:A:AC	donor_gain	1.0000
1:154965609:C:CC	donor_gain	1.0000
1:154965781:TC:T	acceptor_loss	1.0000
1:154965782:C:CA	acceptor_loss	1.0000
1:154965788:G:C	acceptor_gain	1.0000
1:154965942:TCACT:T	donor_loss	1.0000
1:154965943:CACT:C	donor_loss	1.0000
1:154965944:A:AC	donor_gain	1.0000
1:154965944:ACT:A	donor_gain	1.0000
1:154965945:C:CC	donor_gain	1.0000
1:154965945:CT:C	donor_gain	1.0000
1:154965945:CTC:C	donor_gain	1.0000
1:154965945:CTCA:C	donor_gain	1.0000
1:154965945:CTCAT:C	donor_gain	1.0000
1:154966156:TCATA:T	donor_loss	1.0000
1:154966157:CATAC:C	donor_loss	1.0000
1:154966158:ATACC:A	donor_loss	1.0000
1:154966159:TA:T	donor_loss	1.0000
1:154966160:ACCT:A	donor_loss	1.0000
1:154966227:ACAGG:A	acceptor_gain	1.0000
1:154966228:CAGG:C	acceptor_gain	1.0000
1:154966228:CAGGC:C	acceptor_gain	1.0000
1:154966229:AGG:A	acceptor_gain	1.0000
1:154966230:GG:G	acceptor_gain	1.0000
1:154966232:C:CC	acceptor_gain	1.0000
1:154966233:T:G	acceptor_loss	1.0000
1:154966235:C:CT	acceptor_gain	1.0000
1:154967666:CTCA:C	donor_loss	1.0000

AlphaMissense

3794 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154963858:A:C	I566S	1.000
1:154963858:A:G	I566T	1.000
1:154963858:A:T	I566N	1.000
1:154963880:G:C	H559D	1.000
1:154963891:A:G	L555P	1.000
1:154963891:A:T	L555H	1.000
1:154963900:A:T	V552D	1.000
1:154963908:A:C	F549L	1.000
1:154963908:A:T	F549L	1.000
1:154963909:A:G	F549S	1.000
1:154963910:A:G	F549L	1.000
1:154963910:A:T	F549I	1.000
1:154963920:C:A	K545N	1.000
1:154963920:C:G	K545N	1.000
1:154963924:G:A	T544I	1.000
1:154963927:C:G	R543P	1.000
1:154963930:A:T	V542D	1.000
1:154965562:A:C	L535R	1.000
1:154965562:A:G	L535P	1.000
1:154965562:A:T	L535Q	1.000
1:154965565:A:G	L534P	1.000
1:154965565:A:T	L534Q	1.000
1:154965568:A:G	L533S	1.000
1:154965570:A:C	H532Q	1.000
1:154965570:A:T	H532Q	1.000
1:154965571:T:C	H532R	1.000
1:154965572:G:C	H532D	1.000
1:154965595:C:T	G524D	1.000
1:154965596:C:G	G524R	1.000
1:154965601:A:C	L522R	1.000

dbSNP variants (sampled 300 via entrez): RS1000051262 (1:154963298 T>C), RS1000103307 (1:154963488 C>G), RS1000398873 (1:154969717 G>A), RS1000839962 (1:154972045 C>T), RS1001507137 (1:154971794 A>C), RS1001555057 (1:154974540 C>A), RS1001665264 (1:154968400 C>A,T), RS1001677258 (1:154972147 A>G), RS1001725976 (1:154962347 G>C), RS1001778390 (1:154962488 G>T), RS1001890531 (1:154973197 C>T), RS1001946504 (1:154966599 CTAT>C), RS1002400384 (1:154966926 G>A), RS1002482900 (1:154961981 C>T), RS1003158683 (1:154969116 C>G,T)

Disease associations

OMIM: gene MIM:600560 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001942_19	Prostate cancer	2.000000e-08
GCST003602_3	Inflammatory bowel disease	2.000000e-09
GCST005975_5	Eosinophil count	4.000000e-37
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST008103_81	Bipolar disorder	1.000000e-06
GCST010083_89	Hemoglobin levels	4.000000e-23
GCST90020025_1218	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90020027_1803	Waist-hip index	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0004341	body fat distribution
EFO:0004509	hemoglobin measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5626 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3766920	PYGO2, SHC1		0.00	0

ChEMBL bioactivities

18 potent at pChembl≥5 of 50 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.46	Kd	350	nM	CHEMBL505574
6.30	Kd	500	nM	CHEMBL527088
6.11	Kd	770	nM	CHEMBL508118
5.96	Kd	1090	nM	CHEMBL505392
5.33	Kd	4700	nM	CHEMBL526904
5.30	Kd	5000	nM	CHEMBL499590
5.28	Kd	5300	nM	CHEMBL501622
5.22	IC50	6000	nM	CHEMBL448828
5.14	Kd	7200	nM	CHEMBL500998
5.12	Kd	7600	nM	CHEMBL508609
5.10	IC50	8000	nM	CHEMBL449283
5.07	Kd	8600	nM	CHEMBL505136
5.07	Kd	8600	nM	CHEMBL449680
5.05	Kd	9000	nM	CHEMBL509824
5.05	Kd	8900	nM	CHEMBL499931
5.05	IC50	8900	nM	CHEMBL462247
5.02	Kd	9500	nM	CHEMBL501435
5.00	IC50	1e+04	nM	CHEMBL505984

PubChem BioAssay actives

18 with measured affinity, of 70 total; 18 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
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[5-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]pentanoylamino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	0.3500	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[4-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]cyclohexanecarbonyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	0.5000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[2-[3-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]phenyl]acetyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	0.7700	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[3-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]propanoylamino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	1.0900	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[6-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]hexanoylamino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	4.7000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[3-[[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]methyl]benzoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	5.0000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[1-[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]azetidine-3-carbonyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	5.3000	uM
[4-[(2S)-2-acetamido-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]-but-3-enylamino]-1,5-dioxopentan-2-yl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394379: Displacement of FITC-tagged NH-(CH2)4-CO-phospho-tyrosine-glutamine-glycine-leucine-serine-amide from Shc Src homology 2 domain by fluorescence anisotropy competition assay	ic50	6.0000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[4-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]butanoylamino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	7.2000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[(2S)-2-[3-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]propanoylamino]-4-methylpentanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	7.6000	uM
[4-[(2S)-2-acetamido-3-[[(2S)-5-amino-1-[but-3-enyl-[2-[[(2S)-1-[[(2S)-1-(but-3-enylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394379: Displacement of FITC-tagged NH-(CH2)4-CO-phospho-tyrosine-glutamine-glycine-leucine-serine-amide from Shc Src homology 2 domain by fluorescence anisotropy competition assay	ic50	8.0000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[(2S)-2-[4-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]butanoylamino]-4-methylpentanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	8.6000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[3-hydroxy-4-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]butanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	8.6000	uM
[4-[(2S)-2-acetamido-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]-butylamino]-1,5-dioxopentan-2-yl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394379: Displacement of FITC-tagged NH-(CH2)4-CO-phospho-tyrosine-glutamine-glycine-leucine-serine-amide from Shc Src homology 2 domain by fluorescence anisotropy competition assay	ic50	8.9000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[(2S)-2-[5-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]pentanoylamino]-4-methylpentanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	8.9000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[(2R)-2-hydroxy-4-[[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]amino]butanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	9.0000	uM
[4-[(2S)-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-2-[[4-[2-(3-hydroxy-6-oxoxanthen-9-yl)-5-isothiocyanatobenzoyl]piperazine-2-carbonyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394378: Binding affinity to Shc Src homology 2 domain by fluorescence anisotropy	kd	9.5000	uM
[4-[(2S)-2-acetamido-3-[[(2S)-5-amino-1-[[2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]-pentylamino]-1,5-dioxopentan-2-yl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate	394379: Displacement of FITC-tagged NH-(CH2)4-CO-phospho-tyrosine-glutamine-glycine-leucine-serine-amide from Shc Src homology 2 domain by fluorescence anisotropy competition assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Hydrogen Peroxide	decreases reaction, increases expression, increases phosphorylation	5
methylmercuric chloride	increases expression, affects cotreatment	4
Aflatoxin B1	affects expression, decreases methylation, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	increases expression, increases phosphorylation, affects reaction, decreases expression, affects splicing (+3 more)	3
Valproic Acid	affects expression, decreases expression, increases expression	3
diallyl trisulfide	affects response to substance, decreases phosphorylation, decreases response to substance, increases phosphorylation, decreases reaction (+2 more)	2
pyrazolanthrone	decreases reaction, increases phosphorylation	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Bortezomib	decreases expression, affects cotreatment	2
Arsenic Trioxide	affects cotreatment, decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	increases expression	2
Cisplatin	increases response to substance, decreases response to substance	2
Estradiol	affects binding, increases phosphorylation, increases reaction, decreases reaction	2
Folic Acid	decreases reaction, increases expression, increases phosphorylation	2
Glucose	increases expression, decreases reaction, increases reaction	2
Nickel	increases expression	2
Niacinamide	affects cotreatment, increases expression, increases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Asbestos, Crocidolite	increases expression, affects expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction, increases phosphorylation	1
decamethrin	affects localization, increases expression, increases phosphorylation, affects response to substance	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004654	Binding	Binding affinity to streptavidin-coupled biotin-labeled Shc-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

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B6AP	HepaRG P66SHC KO	Cancer cell line	Female
CVCL_TK99	HAP1 SHC1 (-) 1	Cancer cell line	Male
CVCL_XS78	HAP1 SHC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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