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Aliases for SHC1 Gene

Aliases for SHC1 Gene

  • SHC (Src Homology 2 Domain Containing) Transforming Protein 1 2 3
  • SHC (Src Homology 2 Domain-Containing) Transforming Protein 1 2 3
  • SHC-Transforming Protein 3 3 4
  • SHC-Transforming Protein A 3 4
  • SH2 Domain Protein C1 3 4
  • SHCA 3 4
  • SHC 3 4
  • Src Homology 2 Domain-Containing-Transforming Protein C1 4
  • SHC-Transforming Protein 1 3

External Ids for SHC1 Gene

Previous Symbols for SHC1 Gene

  • SHC

Summaries for SHC1 Gene

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 prostate cancer. Among its related pathways are PI-3K cascade and PI-3K cascade. GO annotations related to this gene include phospholipid binding and ephrin receptor binding. An important paralog of this gene is SHC4.

UniProtKB/Swiss-Prot for SHC1 Gene

  • 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SHC1 Gene

Genomics for SHC1 Gene

Genomic Location for SHC1 Gene

Start:
154,962,298 bp from pter
End:
154,974,483 bp from pter
Size:
12,186 bases
Orientation:
Minus strand

Genomic View for SHC1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SHC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SHC1 Gene

Regulatory Elements for SHC1 Gene

Proteins for SHC1 Gene

  • Protein details for SHC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P29353-SHC1_HUMAN
    Recommended name:
    SHC-transforming protein 1
    Protein Accession:
    P29353
    Secondary Accessions:
    • B5BU19
    • D3DV78
    • O15290
    • Q5T180
    • Q5T183
    • Q5T184
    • Q5T185
    • Q5T186
    • Q8N4K5
    • Q96CL1

    Protein attributes for SHC1 Gene

    Size:
    583 amino acids
    Molecular mass:
    62822 Da
    Quaternary structure:
    • 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. Interacts with herpes simplex virus 1 UL46.
    SequenceCaution:
    • Sequence=CAI13254.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SHC1 Gene

    Alternative splice isoforms for SHC1 Gene

neXtProt entry for SHC1 Gene

Proteomics data for SHC1 Gene at MOPED

Post-translational modifications for SHC1 Gene

  • 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 GRB2.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for SHC1 Gene

Domains for SHC1 Gene

Gene Families for SHC1 Gene

HGNC:
  • SH2D :SH2 domain containing

Graphical View of Domain Structure for InterPro Entry

P29353

UniProtKB/Swiss-Prot:

SHC1_HUMAN
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).:
    • P29353
  • Contains 1 PID domain.:
    • P29353
  • Contains 1 SH2 domain.:
    • P29353
genes like me logo Genes that share domains with SHC1: view

Function for SHC1 Gene

Molecular function for SHC1 Gene

GENATLAS Biochemistry: transduction adaptor protein SHC,tyrosine-phosphorylated during insulin and EGFR stimulation,interacting with GRB2,independently of IRS1,forming multimeric complexes with EGFR,SOS,GRB2
UniProtKB/Swiss-Prot 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 Ontology (GO) - Molecular Function for SHC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004713 protein tyrosine kinase activity TAS --
GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity TAS 14676841
GO:0005154 epidermal growth factor receptor binding ISS --
GO:0005158 insulin receptor binding IPI 7537849
GO:0005159 insulin-like growth factor receptor binding IPI 7541045
genes like me logo Genes that share ontologies with SHC1: view
genes like me logo Genes that share phenotypes with SHC1: view

Animal Models for SHC1 Gene

MGI Knock Outs for SHC1:

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for SHC1 Gene

Localization for SHC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SHC1 Gene

Cytoplasm.
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.
Isoform p66Shc: Mitochondrion. Note=In case of oxidative conditions, phosphorylation at Ser-36 of isoform p66Shc, leads to mitochondrial accumulation. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SHC1 Gene COMPARTMENTS Subcellular localization image for SHC1 gene
Compartment Confidence
mitochondrion 5
cytosol 4
nucleus 3
plasma membrane 3
endoplasmic reticulum 1
extracellular 1

Gene Ontology (GO) - Cellular Components for SHC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion --
GO:0005759 mitochondrial matrix IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
GO:0070435 Shc-EGFR complex ISS --
genes like me logo Genes that share ontologies with SHC1: view

Pathways for SHC1 Gene

SuperPathways for SHC1 Gene

Superpath Contained pathways
1 IL-9 Signaling Pathways
2 Signaling by FGFR
3 Translation Insulin regulation of translation
4 Insulin receptor signalling cascade
5 Development Angiotensin activation of ERK
genes like me logo Genes that share pathways with SHC1: view

Gene Ontology (GO) - Biological Process for SHC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IDA 14676841
GO:0000187 activation of MAPK activity IDA 14676841
GO:0001525 angiogenesis IEA --
GO:0006987 activation of signaling protein activity involved in unfolded protein response --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with SHC1: view

Compounds for SHC1 Gene

(76) Novoseek inferred chemical compound relationships for SHC1 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 90.3 295
phosphotyrosine 86.8 101
phosphatidylinositol 79.4 74
ag 1478 68.3 7
pd 98,059 62.3 2
genes like me logo Genes that share compounds with SHC1: view

Transcripts for SHC1 Gene

Unigene Clusters for SHC1 Gene

SHC (Src homology 2 domain containing) transforming protein 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SHC1 Gene

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: - - - - - - - - - - - - - -
SP6: - - - - - - - -
SP7: - - - - -
SP8:
SP9:
SP10: - - - - - - - - - - - -
SP11: - - - - - - -
SP12: - - - - - -
SP13: - - - -
SP14: - -
SP15: - - - - - - - - - - -
SP16:

ExUns: 13 ^ 14a · 14b · 14c ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19a · 19b · 19c
SP1: -
SP2: -
SP3: -
SP4: -
SP5: -
SP6:
SP7:
SP8:
SP9: - -
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:

Relevant External Links for SHC1 Gene

GeneLoc Exon Structure for
SHC1
ECgene alternative splicing isoforms for
SHC1

Expression for SHC1 Gene

mRNA expression in normal human tissues for SHC1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SHC1 Gene

SOURCE GeneReport for Unigene cluster for SHC1 Gene Hs.433795

mRNA Expression by UniProt/SwissProt for SHC1 Gene

P29353-SHC1_HUMAN
Tissue specificity: Widely expressed. Expressed in neural stem cells but absent in mature neurons
genes like me logo Genes that share expressions with SHC1: view

No data available for mRNA differential expression in normal tissues for SHC1 Gene

Orthologs for SHC1 Gene

This gene was present in the common ancestor of animals.

Orthologs for SHC1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SHC1 35
  • 98.97 (n)
  • 99.14 (a)
SHC1 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SHC1 35
  • 91.94 (n)
  • 95.2 (a)
SHC1 36
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SHC1 35
  • 91.15 (n)
  • 94.97 (a)
SHC1 36
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Shc1 35
  • 89.87 (n)
  • 94.65 (a)
Shc1 16
Shc1 36
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SHC1 36
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Shc1 35
  • 88.89 (n)
  • 94.3 (a)
chicken
(Gallus gallus)
Aves SHC1 35
  • 75.23 (n)
  • 81.34 (a)
SHC1 36
  • 75 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SHC1 36
  • 71 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.3210 35
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100492349 35
  • 74.49 (n)
  • 82.89 (a)
zebrafish
(Danio rerio)
Actinopterygii shc1 35
  • 71.17 (n)
  • 78.83 (a)
shc1 36
  • 71 (a)
OneToOne
wufc10h03 35
fruit fly
(Drosophila melanogaster)
Insecta Shc 36
  • 41 (a)
OneToMany
Shc 37
  • 39 (a)
worm
(Caenorhabditis elegans)
Secernentea shc-1 36
  • 33 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9150 35
Species with no ortholog for SHC1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SHC1 Gene

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

Paralogs for SHC1 Gene

Paralogs for SHC1 Gene

Selected SIMAP similar genes for SHC1 Gene using alignment to 6 proteins:

Pseudogenes.org Pseudogenes for SHC1 Gene

genes like me logo Genes that share paralogs with SHC1: view

Variants for SHC1 Gene

Sequence variations from dbSNP and Humsavar for SHC1 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs1050944 -- 154,965,641(-) ACTTC(C/T)TGGTA reference, synonymous-codon
rs1131397 -- 154,965,759(-) CTTCG(C/G)GTGCC reference, synonymous-codon
rs3215173 -- 154,969,305(+) AGTGA(-/C)CCACT intron-variant
rs3738023 -- 154,971,607(+) CAAAC(C/T)ACCCC upstream-variant-2KB, intron-variant, utr-variant-5-prime
rs3753644 -- 154,970,002(+) TCTGC(A/G)GGGGA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SHC1 Gene

Variant ID Type Subtype PubMed ID
nsv509502 CNV Insertion 20534489
nsv872453 CNV Loss 21882294
nsv872454 CNV Loss 21882294

Relevant External Links for SHC1 Gene

HapMap Linkage Disequilibrium report
SHC1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SHC1 Gene

Disorders for SHC1 Gene

(1) MalaCards Diseases for SHC1 Gene

Search for SHC1 Gene in MalaCards »

(37) Novoseek inferred disease relationships for SHC1 Gene

Disease -log(P) Hits PubMed IDs
men 2a 43.7 3
breast cancer 39.5 33
neoplastic transformation 20.7 1
men 3 16.1 1
prostate carcinoma 11.8 2

Relevant External Links for SHC1

Genetic Association Database (GAD)
SHC1
Human Genome Epidemiology (HuGE) Navigator
SHC1
genes like me logo Genes that share disorders with SHC1: view

No data available for UniProtKB/Swiss-Prot for SHC1 Gene

Publications for SHC1 Gene

  1. Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. (PMID: 7559478) He W. … Gustafson T.A. (J. Biol. Chem. 1995) 3 4 23
  2. Direct interaction between Shc and the platelet-derived growth factor beta-receptor. (PMID: 8195171) Yokote K. … Claesson-Welsh L. (J. Biol. Chem. 1994) 3 4 23
  3. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. (PMID: 8524391) Zhou M.-M. … Fesik S.W. (Nature 1995) 3 4 23
  4. Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors. (PMID: 8940081) Yokote K. … Claesson-Welsh L. (J. Biol. Chem. 1996) 3 4 23
  5. The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein-protein interactions. (PMID: 8939605) van der Geer P. … Pawson T. (Curr. Biol. 1996) 3 4 23

Products for SHC1 Gene

  • Addgene plasmids for SHC1

Sources for SHC1 Gene

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