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SHC1 SHC (Src homology 2 domain containing) transforming protein 1 [ Homo sapiens (human) ]

Gene ID: 6464, updated on 1-Sep-2014
Official Symbol
SHC1provided by HGNC
Official Full Name
SHC (Src homology 2 domain containing) transforming protein 1provided by HGNC
Primary source
HGNC:10840
Locus tag
RP11-307C12.1
See related
Ensembl:ENSG00000160691; HPRD:02780; MIM:600560; Vega:OTTHUMG00000037295
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SHC; SHCA
Summary
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]
See SHC1 in Epigenomics, MapViewer
Location:
1q21
Exon count:
13
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 1 NC_000001.11 (154962298..154974483, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (154934774..154946959, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene pre-B-cell leukemia homeobox interacting protein 1 Neighboring gene collagen alpha-1(III) chain-like Neighboring gene pygopus family PHD finger 2 Neighboring gene microRNA 4258 Neighboring gene CDC28 protein kinase regulatory subunit 1B Neighboring gene flavin adenine dinucleotide synthetase 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Tat tat SHC (Src homology 2 domain containing) transforming protein 1 is upregulated in HIV-1 Tat and NC cotransfection of HEK 293T 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
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
nucleocapsid gag SHC (Src homology 2 domain containing) transforming protein 1 is upregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells PubMed

Go to the HIV-1, Human Protein Interaction Database

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  • SHC activation, organism-specific biosystem (from REACTOME)
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  • SHC-mediated cascade, organism-specific biosystem (from REACTOME)
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  • SHC-mediated signalling, organism-specific biosystem (from REACTOME)
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    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.
  • SHC-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
    SHC-related events triggered by IGF1R, organism-specific biosystemPhosphorylated IGF1R binds and phosphorylates SHC1 (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parrella et al. 2010, Siddle et al. 2012). Phosphorylated SHC then binds GR...
  • SHC1 events in EGFR signaling, organism-specific biosystem (from REACTOME)
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    SHC1 events in ERBB2 signaling, organism-specific biosystemAll ERBB2 heterodimers, ERBB2:EGFR, ERBB2:ERBB3 and ERBB2:ERBB4, are able to activate RAF/MAP kinase cascade by recruiting SHC1 (Pinkas-Kramarski et al. 1996, Sepp-Lorenzino et al. 1996) to phosphory...
  • SHC1 events in ERBB4 signaling, organism-specific biosystem (from REACTOME)
    SHC1 events in ERBB4 signaling, organism-specific biosystemAll splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SHC1 (Kaushansky et al. 2008, Pinkas-Kramarski et al. 1996, Cohen et al. 1996). Once bound t...
  • 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 EGFR, organism-specific biosystem (from REACTOME)
    Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
  • Signaling by EGFR in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows "Signaling by constitutively active EGFR" in parallel with "Signaling by EGFR". This allows users to compare signaling by constitutively active EGFR ca...
  • Signaling by ERBB2, organism-specific biosystem (from REACTOME)
    Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
  • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
    Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
  • Signaling by FGFR, organism-specific biosystem (from REACTOME)
    Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by FGFR in disease, organism-specific biosystem (from REACTOME)
    Signaling by FGFR in disease, organism-specific biosystemThe pathway 'Signaling by FGFR in disease' shows 'Signaling by FGFR mutants' in parallel with the wild-type pathway 'Signaling by FGFR', allowing users to compare disease and normal events. FGFR mut...
  • 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...
  • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
    Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
  • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
    Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
  • Signaling by constitutively active EGFR, organism-specific biosystem (from REACTOME)
    Signaling by constitutively active EGFR, organism-specific biosystemSignaling by EGFR is frequently activated in cancer through either genomic amplification of the EGFR locus, resulting in over-expression of the wild-type protein, or through activating mutations in t...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by PTP1B, organism-specific biosystem
    Signaling events mediated by PTP1B
  • Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
    Signaling events mediated by Stem cell factor receptor (c-Kit)
  • Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem
    Signaling events mediated by VEGFR1 and VEGFR2
  • Signaling events regulated by Ret tyrosine kinase, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events regulated by Ret tyrosine kinase, organism-specific biosystem
    Signaling events regulated by Ret tyrosine kinase
  • 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...
  • TCR Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TCR Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
  • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD4+ T cells, organism-specific biosystem
    TCR signaling in naive CD4+ T cells
  • TGF-beta receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
    TGF-beta receptor signaling, organism-specific biosystem
    TGF-beta receptor signaling
  • Tie2 Signaling, organism-specific biosystem (from REACTOME)
    Tie2 Signaling, organism-specific biosystemThe Tie2/Tek receptor tyrosine kinase plays a pivotal role in vascular and hematopoietic development and is expressed exclusively on endothelial lineage. Tie2 interacts with a group of ligands belong...
  • Trk receptor signaling mediated by PI3K and PLC-gamma, organism-specific biosystem (from Pathway Interaction Database)
    Trk receptor signaling mediated by PI3K and PLC-gamma, organism-specific biosystem
    Trk receptor signaling mediated by PI3K and PLC-gamma
  • Unfolded Protein Response (UPR), organism-specific biosystem (from REACTOME)
    Unfolded Protein Response (UPR), organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...
  • XBP1(S) activates chaperone genes, organism-specific biosystem (from REACTOME)
    XBP1(S) activates chaperone genes, organism-specific biosystemXbp-1 (S) binds the sequence CCACG in ER Stress Responsive Elements (ERSE, consensus sequence CCAAT (N)9 CCACG) located upstream from many genes. The ubiquitous transcription factor NF-Y, a heterotri...
  • a6b1 and a6b4 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    a6b1 and a6b4 Integrin signaling, organism-specific biosystem
    a6b1 and a6b4 Integrin signaling
  • p38 MAPK Signaling Pathway, organism-specific biosystem (from WikiPathways)
    p38 MAPK Signaling Pathway, organism-specific biosystemp38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases...
  • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
    p75(NTR)-mediated signaling, organism-specific biosystem
    p75(NTR)-mediated signaling
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ26504

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ephrin receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
epidermal growth factor receptor binding ISS
Inferred from Sequence or Structural Similarity
more info
 
insulin receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
insulin-like growth factor receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
neurotrophin TRKA receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
phospholipid binding TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein tyrosine kinase activity TAS
Traceable Author Statement
more info
 
transmembrane receptor protein tyrosine kinase adaptor activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
Ras protein signal transduction TAS
Traceable Author Statement
more info
 
actin cytoskeleton reorganization IEA
Inferred from Electronic Annotation
more info
 
activation of MAPK activity IDA
Inferred from Direct Assay
more info
PubMed 
activation of signaling protein activity involved in unfolded protein response TAS
Traceable Author Statement
more info
 
angiogenesis IEA
Inferred from Electronic Annotation
more info
 
blood coagulation TAS
Traceable Author Statement
more info
 
cellular protein metabolic process TAS
Traceable Author Statement
more info
 
endoplasmic reticulum unfolded protein response TAS
Traceable Author Statement
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
fibroblast growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
heart development IEA
Inferred from Electronic Annotation
more info
 
innate immune response TAS
Traceable Author Statement
more info
 
insulin receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
insulin receptor signaling pathway TAS
Traceable Author Statement
more info
 
leukocyte migration TAS
Traceable Author Statement
more info
 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
more info
 
peptidyl-tyrosine phosphorylation TAS
Traceable Author Statement
more info
 
platelet activation TAS
Traceable Author Statement
more info
 
positive regulation of DNA replication ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cell proliferation NAS
Non-traceable Author Statement
more info
PubMed 
regulation of epidermal growth factor-activated receptor activity TAS
Traceable Author Statement
more info
PubMed 
regulation of growth IEA
Inferred from Electronic Annotation
more info
 
single organismal cell-cell adhesion IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Shc-EGFR complex ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol TAS
Traceable Author Statement
more info
 
mitochondrial matrix IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
SHC-transforming protein 1
Names
SHC-transforming protein 1
SH2 domain protein C1
SHC-transforming protein 3
SHC-transforming protein A
SHC (Src homology 2 domain-containing) transforming protein 1

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.

Genomic

  1. NG_029028.1 

    Range
    5001..17186
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001130040.1NP_001123512.1  SHC-transforming protein 1 isoform 3

    See proteins identical to NP_001123512.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) encodes the longest isoform (3).
    Source sequence(s)
    BX647149
    Consensus CDS
    CCDS44233.1
    UniProtKB/Swiss-Prot
    P29353
    Related
    ENSP00000401303, OTTHUMP00000035407, ENST00000448116, OTTHUMT00000090779
    Conserved Domains (2) summary
    cd09925
    Location:481584
    Blast Score: 576
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:146317
    Blast Score: 921
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  2. NM_001130041.1NP_001123513.1  SHC-transforming protein 1 isoform 4

    See proteins identical to NP_001123513.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an alternate 5' sequence and an alternate splice site in the CDS, as compared to variant 3. The resulting isoform (4), also known as p52Shc, has a shorter N-terminus and lacks an internal amino acid, as compared to isoform 3.
    Source sequence(s)
    AK292143, BC014158, X68148
    Consensus CDS
    CCDS44234.1
    UniProtKB/Swiss-Prot
    P29353
    Related
    ENSP00000357435, OTTHUMP00000035472, ENST00000368450, OTTHUMT00000090928
    Conserved Domains (2) summary
    cd09925
    Location:370473
    Blast Score: 574
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:36207
    Blast Score: 917
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  3. NM_001202859.1NP_001189788.1  SHC-transforming protein 1 isoform 5 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) has an alternate 5' sequence and an alternate splice site in the CDS, as compared to variant 3. The resulting isoform (5), also known as p46Shc, has a shorter N-terminus and lacks an internal amino acid, as compared to isoform 3. Variants 4 and 5 have the same nucleotide sequence, but variant 5 represents use of a downstream AUG compared to variant 4.
    Source sequence(s)
    AK292143, BC014158
    UniProtKB/Swiss-Prot
    P29353
    Conserved Domains (2) summary
    cd09925
    Location:325428
    Blast Score: 577
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:1162
    Blast Score: 868
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  4. NM_003029.4NP_003020.2  SHC-transforming protein 1 isoform 2

    See proteins identical to NP_003020.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an alternate 5' sequence, as compared to variant 3. The resulting isoform (2) has a shorter N-terminus, as compared to isoform 3.
    Source sequence(s)
    AK292143, BC014158
    Consensus CDS
    CCDS1076.1
    UniProtKB/Swiss-Prot
    P29353
    Related
    ENSP00000357438, OTTHUMP00000035471, ENST00000368453, OTTHUMT00000090927
    Conserved Domains (2) summary
    cd09925
    Location:371474
    Blast Score: 574
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:36207
    Blast Score: 917
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  5. NM_183001.4NP_892113.4  SHC-transforming protein 1 isoform 1

    See proteins identical to NP_892113.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) has an alternate splice site in the CDS, as compared to variant 3. The resulting isoform (1), also known as p66Shc, lacks an internal amino acid, as compared to isoform 3.
    Source sequence(s)
    BX647149
    Consensus CDS
    CCDS30881.1
    UniProtKB/Swiss-Prot
    P29353
    Related
    ENSP00000357430, OTTHUMP00000035409, ENST00000368445, OTTHUMT00000090781
    Conserved Domains (2) summary
    cd09925
    Location:480583
    Blast Score: 575
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:146317
    Blast Score: 921
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000001.11 

    Range
    154962298..154974483
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005245452.1XP_005245509.1  

    Conserved Domains (2) summary
    cd09925
    Location:353456
    Blast Score: 574
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:36189
    Blast Score: 770
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  2. XM_005245450.2XP_005245507.1  

    Conserved Domains (2) summary
    cd09925
    Location:463566
    Blast Score: 576
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:146299
    Blast Score: 772
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  3. XM_005245449.2XP_005245506.1  

    Conserved Domains (2) summary
    cd09925
    Location:480583
    Blast Score: 421
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:146317
    Blast Score: 921
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
  4. XM_005245451.2XP_005245508.1  

    See proteins identical to XP_005245508.1

    Conserved Domains (2) summary
    cd09925
    Location:370473
    Blast Score: 420
    SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)
    cd01209
    Location:36207
    Blast Score: 919
    PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain

Alternate HuRef

Genomic

  1. AC_000133.1 

    Range
    126296519..126308704
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 

    Range
    156331148..156343332
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)