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SHC1 Gene

protein-coding   GIFtS: 70
GCID: GC01M154934

SHC (Src Homology 2 Domain Containing) Transforming Protein...

(Previous name: SHC (Src homology 2 domain-containing) transforming protein...)
(Previous symbol: SHC)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
SHC (Src Homology 2 Domain Containing) Transforming Protein 11 2     SHC-Transforming Protein 32 3
SHC1 2 3     SHC-Transforming Protein A2 3
SHC (Src Homology 2 Domain-Containing) Transforming Protein 11 2     SHC-Transforming Protein 12
SHCA2 3     Src Homology 2 Domain-Containing-Transforming Protein C13
SH2 Domain Protein C12 3     

External Ids:    HGNC: 108401   Entrez Gene: 64642   Ensembl: ENSG000001606917   OMIM: 6005605   UniProtKB: P293533   

Export aliases for SHC1 gene to outside databases

Previous GC identifers: GC01M152750 GC01M150665 GC01M151710 GC01M152151 GC01M151747 GC01M153201 GC01M126296


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for SHC1 Gene:
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. (provided by RefSeq, Feb 2011)

GeneCards Summary for SHC1 Gene:
SHC1 (SHC (Src homology 2 domain containing) transforming protein 1) is a protein-coding gene. Diseases associated with SHC1 include suppurative lymphadenitis, and multiple endocrine neoplasia type 2a. GO annotations related to this gene include ephrin receptor binding and phospholipid binding. An important paralog of this gene is SHC4.

UniProtKB/Swiss-Prot: SHC1_HUMAN, P29353
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 (By similarity).
Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of
endothelial cell migration and sprouting angiogenesis

Gene Wiki entry for SHC1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000001.11  NT_004487.20  NC_018912.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SHC1 gene promoter:
         CREB   AP-1   deltaCREB   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): SHC1 promoter sequence
   Search Chromatin IP Primers for SHC1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SHC1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1q21   Ensembl cytogenetic band:  1q21.3   HGNC cytogenetic band: 1q21

SHC1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SHC1 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M154934:  view genomic region     (about GC identifiers)

Start:
154,934,774 bp from pter      End:
154,946,959 bp from pter
Size:
12,186 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: SHC1_HUMAN, P29353 (See protein sequence)
Recommended Name: SHC-transforming protein 1  
Size: 583 amino acids; 62822 Da
Subunit: 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 APS. 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 (By similarity). 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
Sequence caution: Sequence=CAI13254.1; Type=Erroneous gene model prediction;
Selected PDB 3D structures from and Proteopedia for SHC1 (see all 8):
1MIL (3D)        1N3H (3D)        1OY2 (3D)        1QG1 (3D)        1SHC (3D)        1TCE (3D)    
Secondary accessions: B5BU19 D3DV78 O15290 Q5T180 Q5T183 Q5T184 Q5T185 Q5T186 Q8N4K5 Q96CL1
Alternative promoter usage, Alternative splicing: 6 isoforms:  P29353-1   P29353-2   P29353-3   P29353-5   P29353-6   P29353-7   (Produced by alternative splicing)

Explore the universe of human proteins at neXtProt for SHC1: NX_P29353

Explore proteomics data for SHC1 at MOPED

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 (By similarity). Tyrosine phosphorylated in response to FLT3 signaling (By similarity).
    Tyrosine phosphorylated by activated PTK2B/PYK2 (By similarity). 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 GRB21
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See SHC1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (5 alternative transcripts): 
    NP_001123512.1  NP_001123513.1  NP_001189788.1  NP_003020.2  NP_892113.4  

    ENSEMBL proteins: 
     ENSP00000357430   ENSP00000401303   ENSP00000357434   ENSP00000357438   ENSP00000357435  
     ENSP00000396333   ENSP00000404908   ENSP00000398864   ENSP00000398441   ENSP00000396162  
     ENSP00000475850  
    Reactome Protein details: P29353

    SHC1 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    OriGene Purified Protein for SHC1
    OriGene Protein Over-expression Lysate for SHC1
    OriGene MassSpec for SHC1
    OriGene Custom Protein Services for SHC1
    GenScript Custom Purified and Recombinant Proteins Services for SHC1
    Novus Biologicals SHC1 Proteins
    Novus Biologicals SHC1 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for SHC1
    Cloud-Clone Corp. Proteins for SHC1

    SHC1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of SHC1
    R&D Systems Antibodies for SHC1
    Cell Signaling Technology (CST) Antibodies for SHC1 
    OriGene Antibodies for SHC1
    OriGene Custom Antibody Services for SHC1
    Novus Biologicals SHC1 Antibodies
    Abcam antibodies for SHC1
    Cloud-Clone Corp. Antibodies for SHC1
    ThermoFisher Antibody for SHC1
    LSBio Antibodies in human, mouse, rat for SHC1

    SHC1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for SHC1
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for SHC1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for SHC1
    Cloud-Clone Corp. CLIAs for SHC1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    SH2D: SH2 domain containing

    4 InterPro protein domains:
     IPR011993 PH_like_dom
     IPR006020 PTB/PI_dom
     IPR006019 PID_Shc-like
     IPR000980 SH2

    Graphical View of Domain Structure for InterPro Entry P29353

    ProtoNet protein and cluster: P29353

    2 Blocks protein domains:
    IPB006019 SHC phosphotyrosine interaction domain signature
    IPB006020 Phosphotyrosine interaction domain


    UniProtKB/Swiss-Prot: SHC1_HUMAN, P29353
    Domain: 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 (By similarity)
    Similarity: Contains 1 PID domain
    Similarity: Contains 1 SH2 domain


    SHC1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: SHC1_HUMAN, P29353
    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 (By similarity).
    Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of
    endothelial cell migration and sprouting angiogenesis

         Genatlas biochemistry entry for SHC1:
    transduction adaptor protein SHC,tyrosine-phosphorylated during insulin and EGFR stimulation,interacting with
    GRB2,independently of IRS1,forming multimeric complexes with EGFR,SOS,GRB2

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004713protein tyrosine kinase activity TAS--
    GO:0005068transmembrane receptor protein tyrosine kinase adaptor activity TAS14676841
    GO:0005154epidermal growth factor receptor binding ISS--
    GO:0005158insulin receptor binding IPI7537849
    GO:0005159insulin-like growth factor receptor binding IPI7541045
         
    SHC1 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for SHC1:
     Decreased focal adhesion (FA)  

         Selected MGI mutant phenotypes (inferred from 13 alleles(MGI details for Shc1) (see all 16):
     behavior/neurological  cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland 
     growth/size/body  hematopoietic system  homeostasis/metabolism  immune system  integument 
     mortality/aging  muscle  nervous system  normal  reproductive system 

    SHC1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for SHC1: Shc1tm8Paw Shc1tm1Lex Shc1tm9.1Paw Shc1tm1Paw Shc1tm1Pgp

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SHC1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for SHC1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SHC1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SHC1

    miRNA
    Products:
        
    miRTarBase miRNAs that target SHC1:
    hsa-mir-200a-3p (MIRT020350), hsa-mir-30b-5p (MIRT046156), hsa-mir-141-3p (MIRT021650), hsa-mir-200c-3p (MIRT021079), hsa-mir-200b-3p (MIRT024134), hsa-mir-429 (MIRT016646), hsa-mir-124-3p (MIRT023035)

    Block miRNA regulation of human, mouse, rat SHC1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SHC1 (see all 32):
    hsa-miR-3664-5p hsa-miR-429 hsa-miR-219-5p hsa-miR-650 hsa-miR-3171 hsa-miR-4267 hsa-miR-374c hsa-miR-124
    SwitchGear 3'UTR luciferase reporter plasmidSHC1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for SHC1
    Predesigned siRNA for gene silencing in human, mouse, rat SHC1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for SHC1

    Clone
    Products:
         
    OriGene clones in human, mouse for SHC1 (see all 24)
    OriGene ORF clones in mouse, rat for SHC1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): SHC1 (NM_001130040)
    Sino Biological Human cDNA Clone for SHC1
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for SHC1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SHC1

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for SHC1
    Browse ESI BIO Cell Lines and PureStem Progenitors for SHC1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SHC1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    SHC1_HUMAN, P29353: Cytoplasm
    SHC1_HUMAN, P29353: Isoform p46Shc: Mitochondrion matrix. Note=Localized to the mitochondria matrix. Targeting
    of isoform p46Shc to mitochondria is mediated by its first 32 amino acids, which behave as a bona fide
    mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc, that contain the same sequence but more
    internally located, display a different subcellular localization
    SHC1_HUMAN, P29353: Isoform p66Shc: Mitochondrion (By similarity). Note=In case of oxidative conditions,
    phosphorylation at 'Ser-36' of isoform p66Shc, leads to mitochondrial accumulation (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    cytosol4
    nucleus3
    plasma membrane3
    endoplasmic reticulum1
    extracellular1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005759mitochondrial matrix IEA--
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--
    GO:0070435Shc-EGFR complex ISS--

    SHC1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for SHC1 About   (see all 94)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1IL-9 Signaling Pathways
    IL-9 Signaling Pathways0.90
    IL-4 Signaling Pathways0.84
    IL-7 Signaling Pathways0.90
    IL-9 Signaling Pathway0.42
    IL-21 Signaling Pathways0.90
    Immune response IL 9 signaling pathway0.42
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways0.90
    IL-7 Signaling Pathway0.40
    2Translation Insulin regulation of translation
    Translation Insulin regulation of translation0.59
    Cell adhesion PLAU signaling0.35
    Regulation of lipid metabolism Insulin signaling generic cascades0.59
    Transcription PPAR Pathway0.34
    Transcription Receptor mediated HIF regulation0.51
    Development Growth hormone signaling via PI3K AKT and MAPK cascades0.34
    Translation Regulation activity of EIF20.47
    Insulin signaling pathway0.32
    3Prolactin Signaling Pathway
    Development Prolactin receptor signaling0.39
    Leptin signaling pathway0.35
    Prolactin Signaling Pathway0.39
    Prolactin signaling pathway0.33
    4Development IGF 1 receptor signaling
    Development IGF RI signaling0.49
    Immune response IL 4 signaling pathway0.39
    Development IGF 1 receptor signaling0.48
    5Development EPO induced Jak STAT pathway
    Development EPO induced Jak STAT pathway0.42
    EPO signaling pathway0.34
    EPO Receptor Signaling0.42

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for SHC1 (see all 10)
        IL-21 Signaling Pathways
    IL-2 Signaling Pathways
    IL-4 Signaling Pathways
    Adipocytokines & Insulin Signaling
    IL-7 Signaling Pathways


    1 Cell Signaling Technology (CST) Pathway for SHC1
        Tyrosine Kinases / Adaptors

    Selected GeneGo (Thomson Reuters) Pathways for SHC1 (see all 71)
        G-protein signaling H-RAS regulation pathway
    Development CNTF receptor signaling
    Development EGFR signaling pathway
    Immune response IL-9 signaling pathway
    Transcription PPAR Pathway

    Selected BioSystems Pathways for SHC1 (see all 48)
        Focal Adhesion
    Integrin-mediated cell adhesion
    EGFR1 Signaling Pathway
    Insulin Signaling
    DNA damage response (only ATM dependent)

    2 Sino Biological Pathways for SHC1
        EGFR Signaling Pathway
    VEGF Signaling

    Selected Reactome Pathways for SHC1 (see all 14)
        Signalling to RAS
    Tie2 Signaling
    SHC1 events in ERBB2 signaling
    Interleukin-2 signaling
    Interleukin receptor SHC signaling

    1 PharmGKB Pathway for SHC1
        EGFR Inhibitor Pathway, Pharmacodynamics

    Selected Kegg Pathways  (Kegg details for SHC1) (see all 14):
        ErbB signaling pathway
    Ras signaling pathway
    Chemokine signaling pathway
    Focal adhesion
    Natural killer cell mediated cytotoxicity


    SHC1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SHC1 (see all 6): 
              Insulin Signaling Pathway in human mouse rat
              Cell Cycle in human mouse rat
              Leukemia in human mouse rat
              PI3K-AKT Signaling Pathway in human mouse rat
              EGF / PDGF Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SHC1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for SHC1 (P293531, 2, 3 ENSP000004013034) via UniProtKB, MINT, STRING, and/or I2D (see all 904)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    GRB2P629931, 2, 3, ENSP000003390074EBI-78835,EBI-401755 MINT-6169992 MINT-8032691 MINT-8032762 MINT-8028762 MINT-7135507 MINT-8032822 MINT-8032838 MINT-61537 MINT-8032721 MINT-60983 MINT-1782399 MINT-8401377 MINT-7135483 MINT-8032777 MINT-49658 MINT-60982 MINT-8401389 MINT-7135494 I2D: score=15 STRING: ENSP00000339007
    ERBB2P046261, 2, 3, ENSP000002695714EBI-78835,EBI-641062 MINT-61504 MINT-61511 MINT-61510 MINT-74737 MINT-74736 MINT-74735 MINT-61506 MINT-74734 MINT-74733 MINT-61508 I2D: score=8 STRING: ENSP00000269571
    EGFRP005331, 2, 3, ENSP000002754934EBI-78835,EBI-297353 MINT-74727 MINT-74729 MINT-8038549 MINT-74731 MINT-1782377 MINT-8038504 MINT-61491 MINT-1782352 MINT-74732 MINT-8401401 MINT-61499 MINT-8038534 MINT-61501 MINT-17353 MINT-74730 MINT-8401377 MINT-61495 MINT-61482 MINT-74728 MINT-61503 MINT-61489 MINT-8038489 MINT-8038564 I2D: score=10 STRING: ENSP00000275493
    ENSG00000212866P081073I2D: score=2 
    ENSG00000215328P081073I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade IDA14676841
    GO:0000187activation of MAPK activity IDA14676841
    GO:0001525angiogenesis IEA--
    GO:0006987activation of signaling protein activity involved in unfolded protein response TAS--
    GO:0007173epidermal growth factor receptor signaling pathway TAS--

    SHC1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for SHC1

    Selected Novoseek inferred chemical compound relationships for SHC1 gene (see all 76)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 90.3 983 10570274 (8), 8036006 (7), 7542991 (6), 9710204 (6) (see all 99)
    phosphotyrosine 86.8 137 7542744 (4), 8537373 (4), 7542991 (3), 9271429 (3) (see all 78)
    phosphatidylinositol 79.4 78 8022784 (2), 9761726 (2), 7692230 (2), 11278505 (2) (see all 65)
    ag 1478 68.3 9 9722539 (1), 17956904 (1), 19804820 (1), 10702246 (1) (see all 7)
    pd 98,059 62.3 2 11228049 (1), 19167776 (1)
    inositol 59.7 18 9973396 (2), 9099679 (1), 10570274 (1), 8805618 (1) (see all 15)
    phosphatidylinositol-3,4,5-trisphosphate 59.1 2 10194451 (1), 7650013 (1)
    wortmannin 55 9 11897789 (3), 8660383 (1), 10644984 (1), 18385518 (1) (see all 6)
    phenylalanine 54.7 20 7542991 (1), 8567619 (1), 9388490 (1), 10499514 (1) (see all 18)
    ly294002 46.4 2 11897789 (1), 11228049 (1)



    SHC1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for SHC1 gene (5 alternative transcripts): 
    NM_001130040.1  NM_001130041.1  NM_001202859.1  NM_003029.4  NM_183001.4  

    Unigene Cluster for SHC1:

    SHC (Src homology 2 domain containing) transforming protein 1
    Hs.433795  [show with all ESTs]
    Unigene Representative Sequence: BX647149
    12 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000368445 ENST00000448116(uc001ffw.3 uc001ffv.3) ENST00000368449
    ENST00000368453(uc001ffx.3) ENST00000368450(uc001ffz.1 uc001ffy.3)
    ENST00000490667 ENST00000444664 ENST00000414115 ENST00000444179 ENST00000412170
    ENST00000366442 ENST00000606391
    miRNA
    Products:
         
    Block miRNA regulation of human, mouse, rat SHC1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SHC1 (see all 32):
    hsa-miR-3664-5p hsa-miR-429 hsa-miR-219-5p hsa-miR-650 hsa-miR-3171 hsa-miR-4267 hsa-miR-374c hsa-miR-124
    SwitchGear 3'UTR luciferase reporter plasmidSHC1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat SHC1
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    OriGene clones in human, mouse for SHC1 (see all 24)
    OriGene ORF clones in mouse, rat for SHC1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): SHC1 (NM_001130040)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for SHC1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SHC1
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for SHC1
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      QuantiTect SYBR Green Assays in human, mouse, rat SHC1
      QuantiFast Probe-based Assays in human, mouse, rat SHC1

    Additional mRNA sequence: 

    AB451255.1 AB451379.1 AK096169.1 AK130014.1 AK225332.1 AK292143.1 AK296786.1 AK315842.1 
    BC011813.1 BC014158.2 BC017283.1 BC033925.1 BX647136.1 BX647149.1 X68148.1 

    Selected DOTS entries (see all 39):

    DT.40287869  DT.447555  DT.100846065  DT.121414070  DT.91794052  DT.121413736  DT.100846072  DT.121413914 
    DT.99970890  DT.102835757  DT.91850144  DT.97779549  DT.121413965  DT.121413815  DT.100761500  DT.95212663 
    DT.121413963  DT.100715607  DT.91775292  DT.100719206  DT.100846068  DT.102835755  DT.99952056  DT.100059561 

    Selected AceView cDNA sequences (see all 662):

    AI609334 BQ939807 BC033925 BE302277 AV654127 BX647136 BM914466 BM468518 
    CB105409 AI289037 BM911759 BQ962736 BQ270580 BX395688 BQ953225 CB152347 
    BE887474 BC011813 BC006132 BM843092 CF264840 BQ549734 T50498 CB215134 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for SHC1 (see all 16)    About this scheme

    ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b · 2c · 2d ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c ^ 10a · 10b ^ 11 ^ 12 ^
    SP1:                                -     -     -     -     -     -     -     -     -                                                                           
    SP2:                                -     -     -     -     -     -     -     -     -                                                                           
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                -     -     -     -     -     -     -     -     -           -     -     -     -     -                                       

    ExUns: 13 ^ 14a · 14b · 14c ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19a · 19b · 19c
    SP1:                                                  -                     
    SP2:                                                  -                     
    SP3:                                                  -                     
    SP4:                                                  -                     
    SP5:                                                  -                     


    ECgene alternative splicing isoforms for SHC1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    SHC1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GAGGGGAAAC
    SHC1 Expression
    About this image


    SHC1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 14) fully expand
     
     Ovary (Reproductive System)
             Oviduct
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Pancreas (Endocrine System)
             Islets of Langerhans
    SHC1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SHC1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.433795

    UniProtKB/Swiss-Prot: SHC1_HUMAN, P29353
    Tissue specificity: Widely expressed. Expressed in neural stem cells but absent in mature neurons

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SHC1 (see all 6): 
              Insulin Signaling Pathway in human mouse rat
              Cell Cycle in human mouse rat
              Leukemia in human mouse rat
              PI3K-AKT Signaling Pathway in human mouse rat
              EGF / PDGF Signaling Pathway in human mouse rat

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SHC1

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for SHC1 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Shc11 , 5 src homology 2 domain-containing transforming protein more1, 5 89.87(n)1
    94.65(a)1
      3 (39.11 cM)5
    204161  NM_001113331.21  NP_001106802.11 
     894184435 
    chicken
    (Gallus gallus)
    Aves SHC11 SHC (Src homology 2 domain containing) transforming more 75.23(n)
    81.34(a)
      395934  XM_424373.4  XP_424373.4 
    lizard
    (Anolis carolinensis)
    Reptilia SHC16
    SHC (Src homology 2 domain containing) transformin...
    71(a)
    1 ↔ 1
    GL344009.1(23067-31870)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.32102 Xenopus laevis src homology collagen mRNA, complete more 77.69(n)    AY027793.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufc10h032 Transcribed sequence with weak similarity to protein more 80.57(n)    BM157048.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Shc3 EGF receptor signaling pathway 39(a)   3 67B4   --
    worm
    (Caenorhabditis elegans)
    Secernentea shc-16
    Protein SHC-1, isoform a
    33(a)
    1 → many
    I(969680-973137) WBGene00018788


    ENSEMBL Gene Tree for SHC1 (if available)
    TreeFam Gene Tree for SHC1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SHC1 gene
    SHC42  SHC22  SHC32  
    5 SIMAP similar genes for SHC1 using alignment to 6 protein entries:     SHC1_HUMAN (see all proteins):
    L3MBTL2    SHC4    SHC2    ETFA    SHC3

    SHC1 for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for SHC1
    PGOHUM00000237082 PGOHUM00000241811


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for SHC1 (see all 348)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs563001991,2
    C--126307756(+) AAAAA-/A/GGATAG 3 -- int10--------
    rs32151731,2
    C--154941781(+) AGTGAC/-CCACT 5 -- int11Minor allele frequency- -:0.02NA 48
    rs2000054321,2
    --161436557(+) GGAGC-/AAGGAC 5 -- ds50010--------
    rs75285481,2
    C,F,H--161436916(+) AAACTC/TTGCAG 5 -- ds500112Minor allele frequency- T:0.05NS NA CSA 1638
    rs1852253671,2
    C--161436969(+) TCTGCA/CGCTGA 5 -- ds50010--------
    rs1897599411,2
    --161437076(+) TGAGAA/CCCGTG 5 -- ut310--------
    rs1813379221,2
    --161437153(+) AAAGAG/TGGGGG 5 -- ut310--------
    rs37669201,2
    C,F,H--161437214(+) TAGAAG/AGTACT 5 -- ut3110Minor allele frequency- A:0.05EA NS NA 2372
    rs1418985541,2
    C--161437228(+) GAACTG/TCAGGT 5 -- ut310--------
    rs120361,2
    C--161437242(-) AGGGGA/CAACGC 5 -- ut31 trp32Minor allele frequency- C:0.00MN NA 186

    HapMap Linkage Disequilibrium report for SHC1 (154934774 - 154946959 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for SHC1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv509502CNV Insertion20534489
    nsv872454CNV Loss21882294
    nsv872453CNV Loss21882294

    Site Specific Mutation Identification with PCR Assays
    1 Copy Number PCR Panel containing SHC1:
    Oncogenes & Tumor Suppressor Genes 384HC
    SeqTarget long-range PCR primers for resequencing SHC1
    DNA2.0 Custom Variant and Variant Library Synthesis for SHC1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600560    OMIM disorders: --

    Selected diseases for SHC1 (see all 55):    
    About MalaCards
    suppurative lymphadenitis    multiple endocrine neoplasia type 2a    cancer progression/metastasis    lymphadenitis
    prostate cancer, progression and metastasis of    severe congenital neutropenia    cblc    multiple endocrine neoplasia
    phaeochromocytoma    hyperglycemia    anaplastic astrocytoma    neutropenia
    thyroid cancer    mitochondrial disorders    astrocytoma    pheochromocytoma
    medulloblastoma    endometrial adenocarcinoma    myeloid leukemia    wiskott-aldrich syndrome


    SHC1 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for SHC1 gene (see all 37)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    men 2a 43.7 6 10465268 (2), 9047384 (1)
    breast cancer 39.5 42 8660324 (4), 10741744 (2), 17196107 (2), 14669164 (2) (see all 21)
    neoplastic transformation 20.7 1 8084588 (1)
    men 3 16.1 1 9047384 (1)
    prostate carcinoma 11.8 2 14696093 (1), 11007941 (1)
    pheochromocytoma 9.15 2 8288573 (1), 8156997 (1)
    tumors 8.99 31 9714065 (5), 7675449 (4), 14669164 (2), 14583473 (2) (see all 17)
    metastasis 5.43 10 11896612 (2), 10741744 (1), 17699761 (1), 10527634 (1) (see all 6)
    leukemia 5.34 3 7537361 (1), 9096689 (1), 11016927 (1)
    insulin resistance 4.04 4 10372739 (2), 9267983 (1), 11788655 (1)

    Genetic Association Database (GAD): SHC1
    Human Genome Epidemiology (HuGE) Navigator: SHC1 (6 documents)

    Export disorders for SHC1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for SHC1 gene, integrated from 10 sources (see all 1073):
    (articles sorted by number of sources associating them with SHC1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. (PubMed id 1623525)1, 2, 3 Pelicci G.... Pelicci P.-G. (Cell 1992)
    2. Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. (PubMed id 7559478)1, 2, 9 He W.... Gustafson T.A. (J. Biol. Chem. 1995)
    3. The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein-protein interactions. (PubMed id 8939605)1, 2, 9 van der Geer P.... Pawson T. (Curr. Biol. 1996)
    4. Direct interaction between Shc and the platelet-derived growth factor beta-receptor. (PubMed id 8195171)1, 2, 9 Yokote K....Claesson-Welsh L. (J. Biol. Chem. 1994)
    5. Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation. (PubMed id 9121430)1, 2, 9 Gotoh N.... Shibuya M. (Mol. Cell. Biol. 1997)
    6. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. (PubMed id 8524391)1, 2, 9 Zhou M.-M....Fesik S.W. (Nature 1995)
    7. Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. (PubMed id 14665640)1, 2, 9 Audero E.... Bussolino F. (J. Biol. Chem. 2004)
    8. A cryptic targeting signal induces isoform-specific localization of p46Shc to mitochondria. (PubMed id 14573619)1, 2, 9 Ventura A.... Pelicci P.-G. (J. Biol. Chem. 2004)
    9. EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. (PubMed id 12925710)1, 2, 9 Vindis C.... Huynh-Do U. (J. Cell Biol. 2003)
    10. The Src homology 2 domain containing inositol 5-phosphatase SHIP2 is recruited to the epidermal growth factor (EGF) receptor and dephosphorylates phosphatidylinositol 3,4,5-trisphosphate in EGF- stimulated COS-7 cells. (PubMed id 11349134)1, 2, 9 Pesesse X.... Erneux C. (J. Biol. Chem. 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 6464 HGNC: 10840 AceView: SHC1andPYGO2 Ensembl:ENSG00000160691 euGenes: HUgn6464
    ECgene: SHC1 Kegg: 6464 H-InvDB: SHC1

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for SHC1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for SHC1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for SHC1 gene:
    Search GeneIP for patents involving SHC1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014

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