製品: SHC Mouse Monoclonal Antibody
カタログ: BF8370
タンパク質の説明: Mouse monoclonal antibody to SHC
アプリケーション: WB
反応性: Human, Mouse, Rat, Monkey
予測: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
分子量: 46,52,66kDa; 63kD(Calculated).
ユニプロット: P29353

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製品説明

ソース:
Mouse
アプリケーション:
WB 1:500-1:3000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat,Monkey
クローナリティ:
Monoclonal [AFfirm8370]
特異性:
SHC Mouse Monoclonal Antibody detects endogenous levels of total SHC
コンジュゲート:
Unconjugated.
精製:
Affinity-chromatography.
保存:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

FLJ26504; p66; p66SHC; SH2 domain protein C1; SHC (Src homology 2 domain containing) transforming protein 1; SHC 1; SHC A; SHC adaptor protein 1; Shc; SHC transforming protein 1; SHC transforming protein; SHC-transforming protein 1; SHC-transforming protein 3; SHC-transforming protein A; SHC1; SHC1_HUMAN; SHCA; Src homology 2 domain-containing-transforming protein C1;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
発現特異性:
P29353 SHC1_HUMAN:

Widely expressed. Expressed in neural stem cells but absent in mature neurons.

タンパク質の説明:
Shc1 IS an adaptor protein containing a SH2 domain and a PID domain within a PH domain-like fold. Three isoforms(p66, p52 and p46), produced by alternative initiation, variously regulate growth factor signaling, oncogenesis and apoptosis.
タンパク質配列:
MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCSFFPRMSNLRLANPAGGRPGSKGEPGRAADDGEGIVGAAMPDSGPLPLLQDMNKLSGGGGRRTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAAPGAARPTAPNAQTPSHLGATLPVGQPVGGDPEVRKQMPPPPPCPGRELFDDPSYVNVQNLDKARQAVGGAGPPNPAINGSAPRDLFDMKPFEDALRVPPPPQSVSMAEQLRGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVERKL

PTMs - P29353 基板として

Site PTM Type Enzyme
Phosphorylation
M1 Acetylation
S28 Phosphorylation Q05655 (PRKCD)
S36 Phosphorylation P45984 (MAPK9) , P53779 (MAPK10) , P05771 (PRKCB) , Q16539 (MAPK14) , P27361 (MAPK3) , P45983 (MAPK8)
S54 Phosphorylation Q16539 (MAPK14)
T56 Phosphorylation Q16539 (MAPK14)
S115 Phosphorylation
S139 Phosphorylation Q05655 (PRKCD)
K143 Ubiquitination
T145 Phosphorylation
K154 Ubiquitination
Y162 Phosphorylation
K203 Ubiquitination
T206 Phosphorylation
S213 Phosphorylation
K226 Ubiquitination
K313 Ubiquitination
Y315 Phosphorylation Q05397 (PTK2)
K321 Ubiquitination
T324 Phosphorylation
S335 Phosphorylation
Y349 Phosphorylation P12931 (SRC) , P06241 (FYN) , P35916 (FLT4) , P43405 (SYK) , P43403 (ZAP70) , P36888 (FLT3)
Y350 Phosphorylation P12931 (SRC) , P06241 (FYN) , P35916 (FLT4) , P36888 (FLT3) , P43405 (SYK) , P43403 (ZAP70)
T386 Phosphorylation Q16539 (MAPK14)
S426 Phosphorylation
Y427 Phosphorylation P43403 (ZAP70) , P08581 (MET) , P06239 (LCK) , P36888 (FLT3) , P35916 (FLT4) , P06241 (FYN) , P12931 (SRC) , P43405 (SYK)
K435 Ubiquitination
S453 Phosphorylation
K462 Ubiquitination
S494 Phosphorylation
S513 Phosphorylation
Y520 Phosphorylation

PTMs - P29353 酵素として

Substrate Site Source
P43403-2 (ZAP70) Y167 Uniprot

研究背景

機能:

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.

PTMs:

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.

細胞の位置付け:

Cytoplasm.

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.

Mitochondrion.
Note: In case of oxidative conditions, phosphorylation at 'Ser-36' of isoform p66Shc, leads to mitochondrial accumulation.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Widely expressed. Expressed in neural stem cells but absent in mature neurons.

サブユニット構造:

Interacts with CPNE3; this interaction may mediate the binding of CPNE3 with ERBB2. 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 CEACAM1; this interaction is CEACAM1-phosphorylation-dependent and mediates interaction with EGFR or INSR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Interacts (via PID domain) with PEAK1 (when phosphorylated at 'Tyr-1188'). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1.

(Microbial infection) Interacts with herpes simplex virus 1 UL46.

タンパク質ファミリー:

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).

研究領域

· Cellular Processes > Cellular community - eukaryotes > Focal adhesion.   (View pathway)

· Environmental Information Processing > Signal transduction > ErbB signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Ras signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Phospholipase D signaling pathway.   (View pathway)

· Human Diseases > Drug resistance: Antineoplastic > EGFR tyrosine kinase inhibitor resistance.

· Human Diseases > Drug resistance: Antineoplastic > Endocrine resistance.

· Human Diseases > Substance dependence > Alcoholism.

· Human Diseases > Infectious diseases: Bacterial > Bacterial invasion of epithelial cells.

· Human Diseases > Cancers: Overview > MicroRNAs in cancer.

· Human Diseases > Cancers: Specific types > Glioma.   (View pathway)

· Human Diseases > Cancers: Specific types > Chronic myeloid leukemia.   (View pathway)

· Human Diseases > Cancers: Specific types > Breast cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

· Organismal Systems > Immune system > Chemokine signaling pathway.   (View pathway)

· Organismal Systems > Immune system > Natural killer cell mediated cytotoxicity.   (View pathway)

· Organismal Systems > Nervous system > Neurotrophin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Insulin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Estrogen signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Prolactin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Relaxin signaling pathway.

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