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    SHC4 SHC adaptor protein 4 [ Homo sapiens (human) ]

    Gene ID: 399694, updated on 11-Apr-2024

    Summary

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    Official Symbol
    SHC4provided by HGNC
    Official Full Name
    SHC adaptor protein 4provided by HGNC
    Primary source
    HGNC:HGNC:16743
    See related
    Ensembl:ENSG00000185634 MIM:617372; AllianceGenome:HGNC:16743
    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
    RaLP; SHCD
    Summary
    Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in testis (RPKM 6.4), brain (RPKM 2.8) and 5 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    15q21.1
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (48823741..48963919, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (46631939..46772161, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (49115938..49256116, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene oxidation resistance 1 pseudogene Neighboring gene centrosomal protein 152 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9377 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:49090426-49090965 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:49099693-49100193 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:49102416-49102977 Neighboring gene uncharacterized LOC124903487 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:49103270-49103460 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9378 Neighboring gene MPRA-validated peak2329 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr15:49136024-49136191 Neighboring gene Sharpr-MPRA regulatory region 4235 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:49166520-49166841 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9379 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9380 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:49180996-49181177 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:49204976-49206175 Neighboring gene EP300 interacting inhibitor of differentiation 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:49237854-49239053 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:49254590-49255092 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:49255093-49255594 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9381 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:49267886-49268121 Neighboring gene keratin 8 pseudogene 24 Neighboring gene SECIS binding protein 2 like Neighboring gene MPRA-validated peak2330 silencer Neighboring gene MPRA-validated peak2331 silencer Neighboring gene Sharpr-MPRA regulatory region 10237 Neighboring gene RNA, 7SL, cytoplasmic 577, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. A nuclear export signal and oxidative stress regulate ShcD subcellular localisation: a potential role for ShcD in the nucleus. Ahmed SB, et al. Cell Signal, 2014 Jan. PMID 24036217
    2. ShcD interacts with TrkB via its PTB and SH2 domains and regulates BDNF-induced MAPK activation. You Y, et al. BMB Rep, 2010 Jul. PMID 20663410
    3. Adaptor Protein ShcD/SHC4 Interacts with Tie2 Receptor to Synergistically Promote Glioma Cell Invasion. Tilak M, et al. Mol Cancer Res, 2021 May. PMID 33495401, Free PMC Article
    4. [ShcD interacts with TrkC through its PTB and SH2 domains]. You YG, et al. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2009 Dec. PMID 20078941
    5. The ShcD phosphotyrosine adaptor subverts canonical EGF receptor trafficking. Wills MKB, et al. J Cell Sci, 2017 Sep 1. PMID 28724758

    See all (23) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SHC4 orchestrates beta-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.
      Title: SHC4 orchestrates β-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.
    2. Adaptor Protein ShcD/SHC4 Interacts with Tie2 Receptor to Synergistically Promote Glioma Cell Invasion.
      Title: Adaptor Protein ShcD/SHC4 Interacts with Tie2 Receptor to Synergistically Promote Glioma Cell Invasion.
    3. ShcD appears to possess several molecular permutations that actively govern the EGFR, which may have implications in development and disease.
      Title: The ShcD phosphotyrosine adaptor subverts canonical EGF receptor trafficking.
    4. ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine-binding (PTB) domain.
      Title: Signaling adaptor ShcD suppresses extracellular signal-regulated kinase (Erk) phosphorylation distal to the Ret and Trk neurotrophic receptors.
    5. The ShcD signaling adaptor facilitates ligand-independent phosphorylation of the EGF receptor.
      Title: The ShcD signaling adaptor facilitates ligand-independent phosphorylation of the EGF receptor.
    6. ShcD can exist within the nucleus, and its CH2 domain has a critical role in nuclear export of ShcD.
      Title: A nuclear export signal and oxidative stress regulate ShcD subcellular localisation: a potential role for ShcD in the nucleus.
    7. ShcD binds to TrkC in a kinase-activity-dependent manner through its PTB and SH2 domains.
      Title: [ShcD interacts with TrkC through its PTB and SH2 domains].
    8. ShcD interacts with TrkB in a kinase-activity-dependent manner.
      Title: ShcD interacts with TrkB via its PTB and SH2 domains and regulates BDNF-induced MAPK activation.
    9. 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.
    10. A new member of the Shc family of docking proteins is characterised, which may mediate a specific aspect of signaling downstream of the MuSK receptor.
      Title: Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits.
    EBI GWAS Catalog
    Genome-wide association analysis of gender differences in major depressive disorder in the Netherlands NESDA and NTR population-based samples.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC34023

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein domain specific binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables receptor tyrosine kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell surface receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in stem cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in postsynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    SHC-transforming protein 4
    Names
    SH2 domain protein C4
    SHC (Src homology 2 domain containing) family, member 4
    SHC-transforming protein D
    hShcD
    rai-like protein
    src homology 2 domain-containing-transforming protein C4

    NCBI Reference Sequences (RefSeq)

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    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_203349.4 → NP_976224.3  SHC-transforming protein 4

      See identical proteins and their annotated locations for NP_976224.3

      Status: VALIDATED

      Source sequence(s)
      AC012379, AC091073, AY464565
      Consensus CDS
      CCDS10130.1
      UniProtKB/Swiss-Prot
      Q6S5L8, Q6UXQ3, Q8IYW3
      Related
      ENSP00000329668.4, ENST00000332408.9
      Conserved Domains (2) summary
      cd09925
      Location:518 → 618
      SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
      cd01209
      Location:176 → 347
      PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      48823741..48963919 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005254375.4 → XP_005254432.1  SHC-transforming protein 4 isoform X1

      UniProtKB/TrEMBL
      B3KWT2
      Conserved Domains (2) summary
      cd09925
      Location:335 → 435
      SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
      cd01209
      Location:13 → 164
      PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain

    2. XM_047432493.1 → XP_047288449.1  SHC-transforming protein 4 isoform X2

      UniProtKB/TrEMBL
      F5H5M1
      Related
      ENSP00000443300.1, ENST00000537958.5

    3. XM_047432492.1 → XP_047288448.1  SHC-transforming protein 4 isoform X2

      UniProtKB/TrEMBL
      F5H5M1
      Related
      ENSP00000379786.3, ENST00000396535.7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      46631939..46772161 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377896.1 → XP_054233871.1  SHC-transforming protein 4 isoform X1

    2. XM_054377897.1 → XP_054233872.1  SHC-transforming protein 4 isoform X2

      UniProtKB/TrEMBL
      F5H5M1
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6S5L8.1 GenPept UniProtKB/Swiss-Prot:Q6S5L8

    Gene LinkOut

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

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