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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: Transcription factor p65

UniprotKB/SwissProt ID: Q04206 (Q04206)

Gene Name: RELA

Organism: Homo sapiens (Human)

Function: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148)

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Nucleus. Cytoplasm

Graphical Visualization of S-nitrosylation Sites:
InterPro ID Domain Name
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR002909 IPT_dom
IPR033926 IPT_NFkappaB
IPR000451 NFkB/Dor
IPR008967 p53-like_TF_DNA-bd_sf
IPR030495 RelA_RHD_N
IPR030492 RHD_CS
IPR032397 RHD_dimer
IPR011539 RHD_DNA_bind_dom
IPR037059 RHD_DNA_bind_dom_sf

The S-nitrosylation sites of Q04206

No. Position S-nitrosylated Peptide Secondary Structure of S-nitrosylated Peptide Solvent Accessibility of nitrosylated Site PubMed ID
1 105 CRDGFYEAEL C PDRCIHSFQN  CCCCCCCEEC C CHHHCCCCCE  2.19%
2 109 FYEAELCPDR C IHSFQNLGIQ  CCCCCCCEEC C CHHHCCCCCE  4.24%
3 120 IHSFQNLGIQ C VKKRDLEQAI  CCCCCCCEEC C CHHHCCCCCE  4.59%
4 160 GDYDLNAVRL C FQVTVRDPSG  CCCCCCCEEC C CHHHCCCCCE  1.25%
5 206 ICRVNRNSGS C LGGDEIFLLC  CCCCCCCEEC C CHHHCCCCCE  4.7%
6 216 CLGGDEIFLL C DKVQKEDIEV  CCCCCCCEEC C CHHHCCCCCE  5.31%
7 38 KQRGMRFRYK C EGRSAGSIPG  CCCCCCCEEC C CHHHCCCCCE  5.06% 22178444
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