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    SHC3 SHC (Src homology 2 domain containing) transforming protein 3 [ Homo sapiens ]

    Gene ID: 53358, updated on 19-May-2012
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    Summary

    Official Symbol
    SHC3provided by HGNC
    Official Full Name
    SHC (Src homology 2 domain containing) transforming protein 3provided by HGNC
    Primary source
    HGNC:18181
    Locus tag
    RP11-82L18.3
    See related
    Ensembl:ENSG00000148082; HPRD:12005; MIM:605263; Vega:OTTHUMG00000020179
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RAI; NSHC; SHCC; N-Shc; FLJ45325; DKFZp686H1544
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    Genomic context

    Location :
    9q22.1
    Sequence :
    Chromosome: 9; NC_000009.11 (91620686..91793682, complement)
    See SHC3 in Epigenomics, MapViewer

    Chromosome 9 - NC_000009.11Genomic Context describing neighboring genes Neighboring gene PEST containing nuclear protein pseudogene 2 Neighboring gene uncharacterized LOC100131540 Neighboring gene chromosome 9 open reading frame 47 Neighboring gene sphingosine-1-phosphate receptor 3 Neighboring gene uncharacterized LOC100507009 Neighboring gene microRNA 3153 Neighboring gene SECIS binding protein 2 Neighboring gene CDC28 protein kinase regulatory subunit 2

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    2. The importance of a sub-region on chromosome 19q13.3 for prognosis of multiple myeloma patients after high-dose treatment and stem cell support: a linkage disequilibrium mapping in RAI and CD3EAP. Vangsted AJ, et al. Ann Hematol, 2011 Jun. PMID 21046104.
    3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Rose JE, et al. Mol Med, 2010 Jul-Aug. PMID 20379614.
    4. EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas. Magrassi L, et al. Cancer Lett, 2010 Apr 1. PMID 19748727.
    5. Distinct role of ShcC docking protein in the differentiation of neuroblastoma. Miyake I, et al. Oncogene, 2009 Feb 5. PMID 18997821.

    See all (30) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Polymorphism in RAI and CD3EAP are associated with outcome of myeloma patients treated with high dose treatment.
      Title: The importance of a sub-region on chromosome 19q13.3 for prognosis of multiple myeloma patients after high-dose treatment and stem cell support: a linkage disequilibrium mapping in RAI and CD3EAP.
    2. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    3. amplification of SHC3 and EDG3 genes suggests that the two proteins co-operate and are important for ependymomas in vivo.
      Title: EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas.
    4. ShcC is a therapeutic target that might induce differentiation in the aggressive type of neuroblastomas.
      Title: Distinct role of ShcC docking protein in the differentiation of neuroblastoma.
    5. shcc is expressed in the human gut, especially in the enteric glial cells
      Title: Expression of the Rai (Shc C) adaptor protein in the human enteric nervous system.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence.
    7. ShcC has phosphotyrosine-dependent and -independent functions in neuroblastoma cells
      Title: Domain-specific function of ShcC docking protein in neuroblastoma cells.
    8. data suggest that RAI (ShcC/H-Shc)is a critical substrate for RET oncoproteins in thyroid carcinomas
      Title: RAI(ShcC/N-Shc)-dependent recruitment of GAB 1 to RET oncoproteins potentiates PI 3-K signalling in thyroid tumors.
    9. The inappropriate in vivo expression of Shc3 in high-grade glioma may contribute to the survival of the cancer cells.
      Title: Shc3 affects human high-grade astrocytomas survival.
    10. Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc.
      Title: Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc.
    Submit: New GeneRIF Correction See all (14)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat-induced small GTPase Ras activation is mediated by tyrosine phosphorylation of Shc and recruitment of Grb2 in human endothelial cells PubMed
    tat HIV-1 Tat activates the MAPK signaling pathway leading to the phosphorylation of Shc, a protein involved in signal transduction downstream of receptor tyrosine kinase activation PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_058544.2 GRB2    BIND  PubMed An unspecified isoform of GRB2 interacts with SHC3 (ShcC). 
    Q92529 Q9UM73 ALK    HPRD  PubMed  
    Q92529 P05067 APP    HPRD  PubMed  
    Q92529 RICS ARHGAP32    HPRD  PubMed  
    Q92529 P30530 AXL    HPRD  PubMed  
    Q92529 P00533 EGFR    HPRD  PubMed  
    Q92529 P35916 FLT4    HPRD  PubMed  
    Q92529 P62993 GRB2    HPRD  PubMed  
    Q92529 P04629 NTRK1    HPRD  PubMed  
    Q92529 Q16620 NTRK2    HPRD  PubMed  
    Q92529 P07949 RET    HPRD  PubMed  
    BioGRID:119752 BioGRID:106739 ALK    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:119752 BioGRID:115091 ARHGAP32    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:119752 BioGRID:108276 EGFR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:119752 BioGRID:110969 NTRK1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:119752 BioGRID:110970 NTRK2    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:119752 BioGRID:112354 SH3GL3    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Alcoholism, organism-specific biosystem (from KEGG)
      Alcoholism, organism-specific biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
    • Alcoholism, conserved biosystem (from KEGG)
      Alcoholism, conserved biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
    • Bacterial invasion of epithelial cells, organism-specific biosystem (from KEGG)
      Bacterial invasion of epithelial cells, organism-specific biosystemMany pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-ph...
    • Bacterial invasion of epithelial cells, conserved biosystem (from KEGG)
      Bacterial invasion of epithelial cells, conserved biosystemMany pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-ph...
    • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
      Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
    • Chemokine signaling pathway, conserved biosystem (from KEGG)
      Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
    • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
      Chronic myeloid leukemia, organism-specific biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • Chronic myeloid leukemia, conserved biosystem (from KEGG)
      Chronic myeloid leukemia, conserved biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • ErbB signaling pathway, organism-specific biosystem (from KEGG)
      ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • ErbB signaling pathway, conserved biosystem (from KEGG)
      ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • Focal Adhesion, organism-specific biosystem (from WikiPathways)
      Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, organism-specific biosystem (from KEGG)
      Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, conserved biosystem (from KEGG)
      Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Glioma, organism-specific biosystem (from KEGG)
      Glioma, organism-specific biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • Glioma, conserved biosystem (from KEGG)
      Glioma, conserved biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • Insulin Signaling, organism-specific biosystem (from WikiPathways)
      Insulin Signaling, organism-specific biosystem
      Insulin Signaling
    • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
      Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
    • Insulin signaling pathway, organism-specific biosystem (from KEGG)
      Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Insulin signaling pathway, conserved biosystem (from KEGG)
      Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Integrin-mediated cell adhesion, organism-specific biosystem (from WikiPathways)
      Integrin-mediated cell adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Neurotrophic factor-mediated Trk receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
      Neurotrophic factor-mediated Trk receptor signaling, organism-specific biosystem
      Neurotrophic factor-mediated Trk receptor signaling
    • Neurotrophin signaling pathway, organism-specific biosystem (from KEGG)
      Neurotrophin signaling pathway, organism-specific biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Neurotrophin signaling pathway, conserved biosystem (from KEGG)
      Neurotrophin signaling pathway, conserved biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • SHC-mediated signalling, organism-specific biosystem (from REACTOME)
      SHC-mediated signalling, organism-specific biosystemRelease of phospho-SHC from the insulin receptor triggers a cascade of signalling events via SOS, RAF and the MAP kinases.
    • SHC-related events, organism-specific biosystem (from REACTOME)
      SHC-related events, organism-specific biosystemSHC is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving SOS, RAF and the MAP kinases.
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signal attenuation, organism-specific biosystem (from REACTOME)
      Signal attenuation, organism-specific biosystemNow with the complete receptor-ligand dissociation and subsequent degradation of insulin in the endosomal lumen, the endosomally associated protein tyrosine phosphatases (PTPs) complete the receptor ...
    • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
      Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Signalling to ERKs, organism-specific biosystem (from REACTOME)
      Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
    • Signalling to RAS, organism-specific biosystem (from REACTOME)
      Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    signal transducer activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    Ras protein signal transduction TAS
    Traceable Author Statement
    more info
    		  
    central nervous system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    epidermal growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    insulin receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    intracellular signal transduction NAS
    Non-traceable Author Statement
    more info
    		  
    learning or memory IEA
    Inferred from Electronic Annotation
    more info
    		  
    nerve growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    synaptic transmission, glutamatergic IEA
    Inferred from Electronic Annotation
    more info
    		  
    transmembrane receptor protein tyrosine kinase signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cellular_component ND
    No biological Data available
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    intracellular NAS
    Non-traceable Author Statement
    more info
    		  
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    General protein information

    Preferred Names
    SHC-transforming protein 3
    Names
    SHC-transforming protein 3
    protein Rai
    neuronal Shc
    SH2 domain protein C3
    SHC-transforming protein C
    src homology 2 domain-containing transforming protein C3
    src homology 2 domain-containing-transforming protein C3
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_016848.5 → NP_058544.3  SHC-transforming protein 3

      Status: VALIDATED

      Source sequence(s)
      AL353150, AL772202, BC026314, D84361
      Consensus CDS
      CCDS6681.1
      UniProtKB/Swiss-Prot
      Q92529
      Related
      ENSP00000364995, OTTHUMP00000021614, ENST00000375835, OTTHUMT00000052986
      Conserved Domains (2) summary
      cd01209
      Location:143 – 308
      Blast Score: 594
      SHC; SHC phosphotyrosine-binding (PTB) domain
      cd09925
      Location:492 – 594
      Blast Score: 479
      SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000009.11 Reference GRCh37.p5 Primary Assembly

      Range
      91620686..91793682, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000141.1 Alternate HuRef

      Range
      61453127..61626017, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL160054.14 CAI41366.1
    genomic AL353150.25 CAI16864.1
      CAI16865.1
    genomic AL772202.14 (52793..55955) None
    genomic CH471089.1 EAW62759.1
      EAW62760.1
    mRNA AK127258.1 None
    mRNA BC026314.1 AAH26314.1
    mRNA BC042431.1 None
    mRNA BX538228.1 None
    mRNA BX641139.1 None
    mRNA D84361.1 BAA12322.1
      BAA12323.1
    other-genetic DQ896663.2 ABM87662.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5T7I8 GenPept UniProtKB/TrEMBL:Q5T7I8
    Q92529.1 GenPept UniProtKB/Swiss-Prot:Q92529
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

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