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Protein Page:
Shc1 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
Shc1 an adaptor protein containing a SH2 domain and a PID domain within a PH domain-like fold. Couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Six human isoforms are produced by alternative promoter usage and alternative splicing. Isoforms p66, p52 and p46 (P29353-1, -2, and -3), produced by alternative initiation, variously regulate growth factor signaling, oncogenesis, intracellular oxidant levels, and apoptosis. Isoforms p46 and p52, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex, thus initiating the cytoplasmic proliferative Ras signaling cascade in various non-neuronal systems. Isoform p66 does not mediate Ras activation, but associates with mitochondria where it controls intracellular redox status, mitochondrial permeability, life span, and stress-induced apoptosis. p66 acts as a downstream target of the tumor suppressor p53 and is required for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. P66 deletion in mice decreases the incidence of aging-associated diseases, such as atherosclerosis, and significantly prolongs life span. Participates in signaling downstream of TIE2, the tyrosine kinase receptor for angiopoietin, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. Interacts with tyrosine-phosphorylated CD3T, DDR2, LRP1, IRS4, SHP, FLT4, PDGFRB, TIE2, TrkA, -B and -C. Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain. p66Shc is known to be activated by the mutant SOD1 associated with familial forms of amyotrophic lateral sclerosis (ALS), causing a decrease in the activity of Rac1 through a redox-sensitive regulation. In case of oxidative conditions, phosphorylation at S36 of isoform p66Shc, leads to mitochondrial accumulation p66 plays a role in mediating mitophagy and determining neuronal cell fate following acute oxygen glucose deprivation. Isoform p46 is 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. Note: This description may include information from UniProtKB.
Protein type: Mitochondrial; Adaptor/scaffold; Motility/polarity/chemotaxis; Apoptosis
Cellular Component: mitochondrial matrix; plasma membrane; cytosol
Molecular Function: insulin-like growth factor receptor binding; protein binding; ephrin receptor binding; protein-tyrosine kinase activity; neurotrophin TRKA receptor binding; phospholipid binding; transmembrane receptor protein tyrosine kinase adaptor protein activity; insulin receptor binding; epidermal growth factor receptor binding
Biological Process: epidermal growth factor receptor signaling pathway; platelet activation; peptidyl-tyrosine phosphorylation; fibroblast growth factor receptor signaling pathway; nerve growth factor receptor signaling pathway; unfolded protein response; activation of MAPK activity; heart development; regulation of epidermal growth factor receptor activity; MAPKKK cascade; cell-cell adhesion; cellular protein metabolic process; unfolded protein response, activation of signaling protein activity; regulation of growth; positive regulation of cell proliferation; actin cytoskeleton reorganization; Ras protein signal transduction; insulin receptor signaling pathway; innate immune response; angiogenesis; blood coagulation; leukocyte migration; positive regulation of DNA replication
Reference #:  P29353 (UniProtKB)
Alt. Names/Synonyms: FLJ26504; SH2 domain protein C1; SHC; SHC (Src homology 2 domain containing) transforming protein 1; SHC (Src homology 2 domain-containing) transforming protein 1; SHC-transforming protein 1; SHC-transforming protein 3; SHC-transforming protein A; SHC1; SHCA; Src homology 2 domain-containing-transforming protein C1
Gene Symbols: SHC1
Molecular weight: 62,822 Da
Basal Isoelectric point: 6.01  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  Growth And Differentiation Control by MAPKs  |  IL6 Signaling  |  Insulin Receptor Signaling  |  SAPK/JNK Signaling Cascades  |  TGF-├č Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

Shc1

Protein Structure Not Found.


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Sites Implicated In
apoptosis, altered: Y349‑p, Y350‑p, Y427‑p
apoptosis, induced: S36‑p, S54‑p, T386‑p
apoptosis, inhibited: Y349‑p, Y350‑p
cell growth, altered: Y427‑p
cell motility, altered: Y427‑p
molecular association, regulation: S36‑p, Y349‑p, Y350‑p, Y427‑p
phosphorylation: S36‑p
protein stabilization: S54‑p, T386‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
16 0 S36-p TPPEELPsPSASSLG
1 0 S54-p PPLPGDDsPTTLCSF
0 3 S115-p LQDMNKLsGGGGRRT
2 31 S139-p EEWTRHGsFVNKPTR
0 1 T145 GsFVNKPTRGWLHPN
0 6 K154-ub GWLHPNDkVMGPGVS
0 3 K203-ub CEAVPGAkGATRRRK
0 5 K226-ub ILGRSNLkFAGMPIT
1 3 Y315-p FELRFKQyLRNPPkL
0 3 K321-ub QyLRNPPkLVtPHDR
0 1 T324-p RNPPkLVtPHDRMAG
0 3 S335-p RMAGFDGsAWDEEEE
29 955 Y349-p EEPPDHQyyNDFPGK
26 950 Y350-p EPPDHQyyNDFPGKE
1 2 T386-p PTAPNAQtPSHLGAT
0 89 S426-p RELFDDPsyVNVQNL
41 2002 Y427-p ELFDDPsyVNVQNLD
0 1 R437 VQNLDKARQAVGGAG
0 3 S453-p PNPAINGsAPRDLFD
0 4 K462-ub PRDLFDMkPFEDALR
0 1 S494-p PWFHGKLsRREAEAL
0 1 S513-p GDFLVREsTTTPGQy
1 4 Y520-p sTTTPGQyVLTGLQS
1 0 Y558 SVSHLISYHMDNHLP
2434 : Phospho-Shc (Tyr239/240) Antibody
2434 : Phospho-Shc (Tyr239/240) Antibody
2431 : Phospho-Shc (Tyr317) Antibody
  Shc1 iso2  
- gap
- gap
S5 ___MNKLSGGGGRRT
S29-p EEWTRHGsFVNKPTR
T35 GsFVNKPTRGWLHPN
K44 GWLHPNDKVMGPGVS
K93 CEAVPGAKGATRRRK
K116 ILGRSNLKFAGMPIT
Y205 FELRFKQYLRNPPKL
K211 QYLRNPPKLVTPHDR
T214 RNPPKLVTPHDRMAG
S225 RMAGFDGSAWDEEEE
Y239-p EEPPDHQyyNDFPGK
Y240-p EPPDHQyyNDFPGKE
T276 PTAPNAQTPSHLGAT
S316 RELFDDPSyVNVQNL
Y317-p ELFDDPSyVNVQNLD
R327 VQNLDKARQAVGGAG
S343 PNPAINGSAPRDLFD
K352 PRDLFDMKPFEDALR
S384 PWFHGKLSRREAEAL
S403 GDFLVRESTTTPGQy
Y410-p STTTPGQyVLTGLQS
Y448-p SVSHLISyHMDNHLP
  Shc1 iso3  
- gap
- gap
- gap
- gap
- gap
- gap
K48 CEAVPGAKGATRRRK
K71 ILGRSNLKFAGMPIT
Y160 FELRFKQYLRNPPKL
K166 QYLRNPPKLVTPHDR
T169 RNPPKLVTPHDRMAG
S180 RMAGFDGSAWDEEEE
Y194-p EEPPDHQyyNDFPGK
Y195-p EPPDHQyyNDFPGKE
T231 PTAPNAQTPSHLGAT
S271 RELFDDPSyVNVQNL
Y272-p ELFDDPSyVNVQNLD
R282 VQNLDKARQAVGGAG
S298 PNPAINGSAPRDLFD
K307 PRDLFDMKPFEDALR
S339 PWFHGKLSRREAEAL
S358 GDFLVRESTTTPGQY
Y365 STTTPGQYVLTGLQS
Y403 SVSHLISYHMDNHLP
  Shc1 iso6  
- gap
- gap
S115 LQDMNKLSGGGGRRT
S139 EEWTRHGSFVNKPTR
T145 GSFVNKPTRGWLHPN
K154 GWLHPNDKVMGPGVS
K203 CEAVPGAKGATRRRK
K226 ILGRSNLKFAGMPIT
Y315 FELRFKQYLRNPPKL
K321 QYLRNPPKLVTPHDR
T324 RNPPKLVTPHDRMAG
S335 RMAGFDGSAWDEEEE
Y349 EEPPDHQYYNDFPGK
Y350 EPPDHQYYNDFPGKE
T386 PTAPNAQTPSHLGAT
S427 RELFDDPSyVNVQNL
Y428-p ELFDDPSyVNVQNLD
R438 VQNLDKARQAVGGAG
S454 PNPAINGSAPRDLFD
K463 PRDLFDMKPFEDALR
S495 PWFHGKLSRREAEAL
S514 GDFLVRESTTTPGQY
Y521 STTTPGQYVLTGLQS
Y559 SVSHLISYHMDNHLP
  Shc1 iso7  
- gap
- gap
S5 ___MNKLSGGGGRRT
S29 EEWTRHGSFVNKPTR
T35 GSFVNKPTRGWLHPN
K44 GWLHPNDKVMGPGVS
K93 CEAVPGAKGATRRRK
K116 ILGRSNLKFAGMPIT
Y205 FELRFKQYLRNPPKL
K211 QYLRNPPKLVTPHDR
T214 RNPPKLVTPHDRMAG
S225 RMAGFDGSAWDEEEE
Y239 EEPPDHQYYNDFPGK
Y240 EPPDHQYYNDFPGKE
T276 PTAPNAQTPSHLGAT
S317 RELFDDPSyVNVQNL
Y318-p ELFDDPSyVNVQNLD
R328 VQNLDKARQAVGGAG
S344 PNPAINGSAPRDLFD
K353 PRDLFDMKPFEDALR
S385 PWFHGKLSRREAEAL
S404 GDFLVRESTTTPGQY
Y411 STTTPGQYVLTGLQS
Y449 SVSHLISYHMDNHLP
  mouse

► Hide Isoforms
 
S36-p TPPEELPsPSASSLG
S54 PPLPGDDSPTTLCSF
S115 LQDMNKLSGGGGRRT
S139-p EEWTRHGsFVNKPtR
T145-p GsFVNKPtRGWLHPN
K154 GWLHPNDKVMGPGVS
K203 CEAVPGAKGATRRRK
K226 ILGRSNLKFAGMPIT
Y315-p FELRFKQyLRNPPKL
K321 QyLRNPPKLVTPHDR
T324 RNPPKLVTPHDRMAG
S335 RMAGFDGSAWDEEEE
Y349-p EEPPDHQyyNDFPGK
Y350-p EPPDHQyyNDFPGKE
M382 PTLPSAQMSSHLGAT
S422-p RELFDDPsyVNIQNL
Y423-p ELFDDPsyVNIQNLD
R433-m2 IQNLDKArQAGGGAG
S449 PNPSLNGSAPRDLFD
K458 PRDLFDMKPFEDALR
S490 PWFHGKLSRREAEAL
S509 GDFLVRESTTTPGQY
Y516 STTTPGQYVLTGLQS
Y554 SVSHLISYHMDNHLP
2434 : Phospho-Shc (Tyr239/240) Antibody
2434 : Phospho-Shc (Tyr239/240) Antibody
2431 : Phospho-Shc (Tyr317) Antibody
  Shc1 iso2  
- gap
- gap
S5 ___MNKLSGGGGRRT
S29-p EEWTRHGsFVNKPTR
T35 GsFVNKPTRGWLHPN
K44 GWLHPNDKVMGPGVS
K93 CEAVPGAKGATRRRK
K116 ILGRSNLKFAGMPIT
Y205-p FELRFKQyLRNPPKL
K211 QyLRNPPKLVTPHDR
T214 RNPPKLVTPHDRMAG
S225 RMAGFDGSAWDEEEE
Y239-p EEPPDHQyyNDFPGK
Y240-p EPPDHQyyNDFPGKE
M272 PTLPSAQMSSHLGAT
S312 RELFDDPSyVNIQNL
Y313-p ELFDDPSyVNIQNLD
R323 IQNLDKARQAGGGAG
S339 PNPSLNGSAPRDLFD
K348 PRDLFDMKPFEDALR
S380 PWFHGKLSRREAEAL
S399 GDFLVRESTTTPGQY
Y406 STTTPGQYVLTGLQS
Y444 SVSHLISYHMDNHLP
  Shc1 iso3  
- gap
- gap
- gap
- gap
- gap
- gap
K48 CEAVPGAKGATRRRK
K71 ILGRSNLKFAGMPIT
Y160-p FELRFKQyLRNPPKL
K166 QyLRNPPKLVTPHDR
T169 RNPPKLVTPHDRMAG
S180 RMAGFDGSAWDEEEE
Y194-p EEPPDHQyyNDFPGK
Y195-p EPPDHQyyNDFPGKE
M227 PTLPSAQMSSHLGAT
S267 RELFDDPSyVNIQNL
Y268-p ELFDDPSyVNIQNLD
R278 IQNLDKARQAGGGAG
S294 PNPSLNGSAPRDLFD
K303 PRDLFDMKPFEDALR
S335 PWFHGKLSRREAEAL
S354 GDFLVRESTTTPGQY
Y361 STTTPGQYVLTGLQS
Y399 SVSHLISYHMDNHLP
  rat

► Hide Isoforms
 
S36-p TPPEELPsPSASSLG
S54 PPLPGDDSPTTLCSF
S115 LQDMNKLSGGGGRRT
S139 EEWTRHGSFVNKPTR
T145 GSFVNKPTRGWLHPN
K154 GWLHPNDKVMGPGVS
K203 CEAVPGAKGAMRRRK
K226 ILGRSNLKFAGMPIT
Y315 FELRFKQYLRNPPKL
K321 QYLRNPPKLVTPHDR
T324 RNPPKLVTPHDRMAG
S335 RMAGFDGSAWDEEEE
Y349-p EEPPDHQyyNDFPGK
Y350-p EPPDHQyyNDFPGKE
M382 PTLPSTQMPSHLGAT
S422 RELFDDPSyVNIQNL
Y423-p ELFDDPSyVNIQNLD
R433 IQNLDKARQAGGGAG
S449 PNPSVNGSAPRDLFD
K458 PRDLFDMKPFEDALR
S490 SWFHGKLSRREAEAL
S509 GDFLVRESTTTPGQY
Y516 STTTPGQYVLTGLQS
Y554 SVSHLISYHMDNHLP
  Shc1 iso2  
- gap
- gap
S5 ___MNKLSGGGGRRT
S29 EEWTRHGSFVNKPTR
T35 GSFVNKPTRGWLHPN
K44 GWLHPNDKVMGPGVS
K93 CEAVPGAKGAMRRRK
K116 ILGRSNLKFAGMPIT
Y205 FELRFKQYLRNPPKL
K211 QYLRNPPKLVTPHDR
T214 RNPPKLVTPHDRMAG
S225 RMAGFDGSAWDEEEE
Y239-p EELPDHQyyNDFPGK
Y240-p ELPDHQyyNDFPGKE
M272 PTLPSTQMPSHLGAT
S312 RELFDDPSyVNIQNL
Y313-p ELFDDPSyVNIQNLD
R323 IQNLDKARQAGGGAG
S339 PNPSVNGSAPRDLFD
K348 PRDLFDMKPFEDALR
S380 SWFHGKLSRREAEAL
S399 GDFLVRESTTTPGQY
Y406 STTTPGQYVLTGLQS
Y444 SVSHLISYHMDNHLP
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