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Symbol SHC1 contributors: mct/npt/pgu - updated : 13-03-2020
HGNC name SHC (Src homology 2 domain containing) transforming protein 1
HGNC id 10840
Location 1q21.3      Physical location : 154.934.774 - 154.946.959
Synonym name
  • Src homology collagen-like) adaptor protein
  • SH2 domain protein C1
  • Synonym symbol(s) SHCA, FLJ26504, SHC, p52SHC, p66SHC, p66
    TYPE functioning gene
    STRUCTURE 12.18 kb     12 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    TRANSCRIPTS type messenger
    text three isoforms (p46, p52, p66)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 3195 52 474 - 2019 31202267
  • p52SHC or variant 2
  • interacting with TRIM31
  • p52SHC is the oncogenic isoform of SHC1 gene products in breast cancer
  • 12 - 3493 62.8 583 - 2018 30109811
  • genetic determinant of life span implicated in the regulation of receptor signaling and various mitochondrial functions
  • inducing mitochondrial DNA replication
  • p66SHC or variant 1
  • is a novel regulator of autophagy and mitophagy in B cells and p66SHC-mediated coordination of autophagy and apoptosis is implicated in B cell survival and differentiation
  • 12 - 3496 - 584 - 2008 18279888
    13 - 3192 - 473 - 2008 18279888
    13 - 3059 - 428 . mitochondrially localized 2016 27059956
  • p46Shc
  • major mitochondrial partner of p46Shc is the lipid oxidation enzyme 3-ketoacylCoA thiolase ACAA2, to which p46Shc binds directly and with a strong affinity
  • potential negative mitochondrial thiolase activity regulator
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Reproductivemale systemprostate  highly
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    Text neural stem cells
  • a N terminal phosphotyrosine binding domain
  • a central collagen homologous region (CH1), with three tyrosine residues that are known to become phosphorylated
  • a proline-rich region (binding SHS) motifs
  • a SH2 C terminal motif, lacking a catalytic unit
    CATEGORY adaptor , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • transduction adaptor protein SHC
  • signaling adapter that couples activated growth factor receptors to signaling pathway
  • plays a crucial role in linking stimulated receptors to mitogen-activated protein kinase activation through the formation of dynamic signalling complexes
  • play a non-redundant role in cytoskeletal reorganization-induced Erk activation by cytochalasin D
  • role of SHC1 in the assembly and/or maintenance of the subventricular zone (SVZ) neural stem cells (NSCs) niche in the adult brain
  • SHC1 might play a pivotal role in mediating immunogenic and tolerogenic properties of Dendritic cells
  • is required for integrin-mediated spreading and migration specifically on fibronectin, as well as endothelial cell survival in response to VEGFA
  • is the key effector driving vascular hyperglycemic memory in diabetes
  • SHC1 scaffold therefore directs the temporal flow of signalling information after EGF stimulation
  • is a critical regulator of actin dynamics in mast cells, providing a basis for understanding the molecular mechanisms involved in vesicle-mediated secretion in these cells
  • negative regulator of B-cell chemotaxis, suggesting a role for this adaptor in the control of B-cell homing (pMID: 24556683)
  • has a pro-oxidant and pro-apoptotic activity and is implicated in the aging process
  • hypercholesterolemia stimulates p66Shc expression in platelets, promoting platelet oxidative stress, hyperreactivity and hyperaggregation via p66Shc
  • important role for the adapter protein SHC1 in later stages of thymic T cell development and in peripheral T cell-dependent events
  • is a determinant of the epithelial phenotype by repressing TGFB1-induced SMAD activation through differential partitioning of receptor complexes at the cell surface
  • involved in in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy
  • is a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy
  • SHC1 scaffold, a central regulator of tyrosine kinase signalling, is essential for promoting breast cancer immune suppression
  • is a cytoplasmic signaling protein that supports signal transduction by receptor protein-tyrosine kinases by providing auxiliary tyrosine phosphorylation sites that engage additional signaling proteins
  • SHC1 is a key validated downstream effector of DDR2 signalling and is essential for multiple biological functions such as axon regeneration
  • SHC1 is dispensable for the regulation of DDR2 receptor localisation and phosphorylation dynamics
  • plays a role in insulin signaling, stress resistance and energy metabolism
    signaling signal transduction
  • SYK/SHC1 pathway that regulates the plasma membrane levels of CFTR channels, contributing to a better understanding of how CFTR-mediated chloride secretion is regulated
  • a component
  • component of multimeric complexes with EGFR, SOS, GRB2
  • GRB2/GAB2/SHC1/LRRK1 signal integrator complex is functionally involved in the balance of cellular stress responses
    small molecule
  • interacting with GRB2 independently of IRS1
  • bind the tyrosine-phosphorylated CD247 chain of the receptor via its src homology 2 (SH2) domain, delivering signals that control T cell development and activation
  • GADD45GIP1 knockdown partially induces endothelial activation via increased ROS production and phosphorylation of SHC1
  • interaction between UBASH3B and SHC1 is regulated in response to EGF receptor activation
  • OSMR activates a non-redundant signaling pathway by recruitment of the adapter SHC1
  • cell & other
    Other tyrosine-phosphorylated during insulin and EGFR stimulation
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance
    Variant & Polymorphism
    Candidate gene
  • ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic factors of overall survival of clear cell renal cell carcinoma
  • might act as a new biomarker and a diagnostic tool to identify membranous lupus nephritis with other membranous nephropathy (MN)
  • Therapy target
  • p66Shc (-/-) diabetic mice show significantly less cognitive dysfunction and decreased levels of oxidative stress (OS) and the numbers of microglia