SHC1 Gene: Adaptor Protein in Cell Signaling and Cancer
Comprehensive genomic, expression, and mutation analysis of SHC1 (SHC adaptor protein 1), a key mediator of receptor tyrosine kinase signaling.
Gene Information Card
| Symbol | SHC1 |
|---|---|
| Full Name | SHC adaptor protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 6464 ncbi.nlm.nih.gov/gene/6464 |
| Ensembl ID | ENSG00000160691 |
| UniProt ID | P29353 |
| OMIM ID | 600560 |
| HGNC ID | 10840 |
| Aliases | SHC, SHCA, SHC-transforming protein 1 |
Description
The SHC1 gene encodes the SHC adaptor protein 1, a cytoplasmic signaling molecule that links activated receptor tyrosine kinases (RTKs) to downstream pathways such as RAS/MAPK and PI3K/AKT. It contains a phosphotyrosine-binding (PTB) domain, a Src homology 2 (SH2) domain, and a collagen-homology (CH1) region. SHC1 is involved in cell proliferation, differentiation, and survival, and its dysregulation is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | SHC1 overexpression or phosphorylation enhances mitogenic signaling, promoting tumor growth and metastasis. | COSMIC; PMID: 12379205 |
| Alzheimer's disease | SHC1 is involved in amyloid-beta toxicity and oxidative stress signaling in neurons. | PMID: 14517220 |
| Insulin resistance / Type 2 diabetes | SHC1 competes with IRS-1 for insulin receptor binding, affecting insulin signaling. | PMID: 10944110 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.4 | Medium |
| Lung | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.5 | Medium |
| Testis | 15.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line; high expression |
| A549 | 10.1 | Lung carcinoma; moderate expression |
| MCF7 | 12.8 | Breast cancer; high expression |
| HepG2 | 8.5 | Liver cancer; moderate expression |
| K562 | 7.9 | Leukemia; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.392A>G (p.Tyr131Cys) | Missense | 0.01% (COSMIC) | Altered PTB domain; potential impact on phosphotyrosine binding |
| c.1045C>T (p.Pro349Ser) | Missense | 0.02% (COSMIC) | Located in CH1 region; may affect phosphorylation sites |
| c.1270G>A (p.Val424Met) | Missense | 0.005% (COSMIC) | In SH2 domain; possible effect on downstream signaling |
Mutation functional classification
Loss of Function (LOF)
Rare truncating mutations (e.g., frameshift) that reduce SHC1 protein levels or disrupt key domains, leading to impaired RTK signaling and potentially altered cellular responses.
Gain of Function (GOF)
Overexpression or phosphorylation-enhancing mutations (e.g., Y239/240 phosphorylation) that increase MAPK activation, contributing to oncogenic transformation.
Dominant Negative (DN)
Mutations in the PTB or SH2 domains that retain binding but fail to recruit downstream effectors, thereby blocking normal signaling.
View complete mutation data：
Gene Ontology (GO)
| • signal transducer activity | • protein binding |
| • phosphotyrosine binding | • SH2 domain binding |
| • PTB domain binding | • cell surface receptor signaling pathway |
| • positive regulation of MAPK cascade | • positive regulation of cell proliferation |
| • insulin receptor signaling pathway | • apoptotic process |
Pathways
• RAS/MAPK signaling
• PI3K/AKT signaling
• ErbB signaling
• Insulin signaling
• Fc epsilon receptor signaling
• Neurotrophin signaling
Protein Summary
SHC1 is a 473-amino acid adaptor protein with a molecular weight of ~52 kDa (isoform p52). It contains an N-terminal PTB domain, a central CH1 region with multiple tyrosine phosphorylation sites (Y239, Y240, Y313, Y427), and a C-terminal SH2 domain. Upon RTK activation, SHC1 is phosphorylated and recruits GRB2/SOS to activate RAS, leading to MAPK signaling. It also interacts with other partners to modulate cell survival and differentiation. Alternative splicing produces p46, p52, and p66 isoforms, with p66 involved in oxidative stress response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHC1 Knockout HEK293 Cell Line | EDJ-KQ659 | Human | 6464 | Details Get a Quote |
| WASHC1 Knockout HEK293 Cell Line | EDJ-KQ16125 | Human | 100287171 | Details Get a Quote |
| SHC1 Knockout A-549 Cell Line | EDJ-KQ20524 | Human | 6464 | Details Get a Quote |
| SHC1 Knockout HCT 116 Cell Line | EDJ-KQ20526 | Human | 6464 | Details Get a Quote |
| SHC1 Knockout HeLa Cell Line | EDJ-KQ20527 | Human | 6464 | Details Get a Quote |
| WASHC1 Knockout A-549 Cell Line | EDJ-KQ47293 | Human | 100287171 | Details Get a Quote |
| WASHC1 Knockout HCT 116 Cell Line | EDJ-KQ47294 | Human | 100287171 | Details Get a Quote |
| WASHC1 Knockout HeLa Cell Line | EDJ-KQ47295 | Human | 100287171 | Details Get a Quote |
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