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

Gene ID: 399694, updated on 2-Nov-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 cell surface 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, Nov 2024]
Expression
Biased expression in testis (RPKM 6.4), brain (RPKM 2.8) and 5 other tissues See more
Orthologs
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Genomic context

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See SHC4 in Genome Data Viewer
Location:
15q21.1
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (48823741..48963919, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (46631939..46772161, complement)
RS_2024_09 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 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. SHC4 orchestrates β-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation. Zhong W, et al. Cancer Lett, 2024 Feb 1. PMID 38052369
  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. 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
  4. 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
  5. [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

See all (25) 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_2024_08

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

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