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Sep. 10, 2014:
A total of 174 experimentally verified S-nitrosylation sites on 94 S-nitrosylated proteins from individualized human colorectal cancer tissues using a label-free quantitation strategy.

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Protein Name: Epidermal growth factor receptor

UniprotKB/SwissProt ID: P00533 (P00533)

Gene Name: EGFR

Organism: Homo sapiens (Human)

Function: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity) Isoform 2 may act as an antagonist of EGF action (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Nucleus membrane. Endosome. Endosome membrane. Nucleus. Secreted

Graphical Visualization of S-nitrosylation Sites:
InterPro ID Domain Name
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR050122 RTK
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR049328 TM_ErbB1
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016245 Tyr_kinase_EGF/ERB/XmrK_rcpt

The S-nitrosylation sites of P00533

No. Position S-nitrosylated Peptide Secondary Structure of S-nitrosylated Peptide Solvent Accessibility of nitrosylated Site PubMed ID
1 157 AVRFSNNPAL C NVESIQWRDI  CCCCHHHHHH H HHHHHHHCHH  6.11%
2 190 FQNHLGSCQK C DPSCPNGSCW  CCCCHHHHHH H HHHHHHHCHH  3.71% 22178444
19056486
3 215 ENCQKLTKII C AQQCSGRCRG  CCCCHHHHHH H HHHHHHHCHH  2.97%
4 291 PEGKYSFGAT C VKKCPRNYVV  CCCCHHHHHH H HHHHHHHCHH  4.13% 22178444
20140087
5 311 VTDHGSCVRA C GADSYEMEED  CCCCHHHHHH H HHHHHHHCHH  3.02% 22178444
20140087
6 329 EEDGVRKCKK C EGPCRKVCNG  CCCCHHHHHH H HHHHHHHCHH  4.46% 22178444
19056486
7 470 DVIISGNKNL C YANTINWKKL  CCCCHHHHHH H HHHHHHHCHH  4.16% 22178444
20140087