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FLASH GENE
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
    DNA
    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
    RNA
    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
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Reproductivemale systemprostate  highly
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text neural stem cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY adaptor , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    REGULATION
    Other tyrosine-phosphorylated during insulin and EGFR stimulation
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • 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
    ANIMAL & CELL MODELS
  • p66Shc (-/-) diabetic mice show significantly less cognitive dysfunction and decreased levels of oxidative stress (OS) and the numbers of microglia