UniProt Accession

 TF65_MOUSE; Q04207; Q62025 

Genbank Protein ID

 M61909; BC003818; L77155; Z22952 

Genbank Nucleotide ID

 AAA39811.1; AAH03818.1; AAB00795.1; CAA80528.1 

Protein Name

 Transcription factor p65 

Protein Synonyms/Alias

 Nuclear factor NF-kappa-B p65 subunit; Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 

Gene Name

 Rela 

Gene Synonyms/Alias

 Nfkb3 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
123	LGIQCVKKRDLEQAI	ubiquitination	[1]
310	KRTYETFKSIMKKSP	acetylation	[2, 3, 4]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [3] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [4] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337] 

Functional Description

 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 and the heterodimeric p65-p50 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. 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. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity). The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA- binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. 

Sequence Annotation

 DOMAIN 19 306 RHD.
 MOTIF 301 304 Nuclear localization signal (Potential).
 MOD_RES 38 38 Cysteine persulfide; alternate.
 MOD_RES 38 38 S-nitrosocysteine; alternate.
 MOD_RES 122 122 N6-acetyllysine; by PCAF and EP300;
 MOD_RES 123 123 N6-acetyllysine; by PCAF and EP300;
 MOD_RES 254 254 Phosphothreonine (By similarity).
 MOD_RES 276 276 Phosphoserine; by RPS6KA4 and RPS6KA5 (By
 MOD_RES 310 310 N6-acetyllysine; alternate (By
 MOD_RES 310 310 N6-methyllysine; by SETD6; alternate.
 MOD_RES 311 311 Phosphoserine; by PKC/PRKCZ.
 MOD_RES 433 433 Phosphothreonine (By similarity).
 MOD_RES 467 467 Phosphoserine; by IKKB and IKKE (By
 MOD_RES 504 504 Phosphothreonine; by CHEK1 (By
 MOD_RES 527 527 Phosphoserine; by CK2 (By similarity).
 MOD_RES 534 534 Phosphoserine; by IKKB (By similarity).
 CROSSLNK 37 37 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 122 122 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 123 123 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Activator; Alternative splicing; Complete proteome; Cytoplasm; DNA-binding; Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Reference proteome; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 549 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:MGI.
 GO:0071159; C:NF-kappaB complex; TAS:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005667; C:transcription factor complex; IEA:Compara.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IDA:MGI.
 GO:0042301; F:phosphate ion binding; IEA:Compara.
 GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
 GO:0043565; F:sequence-specific DNA binding; IEA:Compara.
 GO:0044212; F:transcription regulatory region DNA binding; IEA:Compara.
 GO:0006117; P:acetaldehyde metabolic process; IEA:Compara.
 GO:0007568; P:aging; IEA:Compara.
 GO:0071347; P:cellular response to interleukin-1; IEA:Compara.
 GO:0071222; P:cellular response to lipopolysaccharide; IEP:UniProtKB.
 GO:0071356; P:cellular response to tumor necrosis factor; IEA:Compara.
 GO:0019221; P:cytokine-mediated signaling pathway; IEA:Compara.
 GO:0006952; P:defense response; IMP:MGI.
 GO:0001942; P:hair follicle development; IMP:MGI.
 GO:0006954; P:inflammatory response; IEA:Compara.
 GO:0001889; P:liver development; IMP:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Compara.
 GO:0042177; P:negative regulation of protein catabolic process; IMP:MGI.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IEA:Compara.
 GO:0009887; P:organ morphogenesis; IMP:MGI.
 GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
 GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0045084; P:positive regulation of interleukin-12 biosynthetic process; IDA:MGI.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0014040; P:positive regulation of Schwann cell differentiation; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0050727; P:regulation of inflammatory response; IDA:UniProtKB.
 GO:0043200; P:response to amino acid stimulus; IEA:Compara.
 GO:0051591; P:response to cAMP; IEA:Compara.
 GO:0033590; P:response to cobalamin; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0042542; P:response to hydrogen peroxide; IEA:Compara.
 GO:0032868; P:response to insulin stimulus; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0043278; P:response to morphine; IEA:Compara.
 GO:0032495; P:response to muramyl dipeptide; IDA:MGI.
 GO:0032570; P:response to progesterone stimulus; IEA:Compara.
 GO:0010224; P:response to UV-B; IEA:Compara. 

Interpro

 IPR013783; Ig-like_fold.
 IPR014756; Ig_E-set.
 IPR002909; IPT_TIG_rcpt.
 IPR000451; NF_Rel_Dor.
 IPR008967; p53-like_TF_DNA-bd.
 IPR011539; RHD. 

Pfam

 PF00554; RHD 

SMART

 SM00429; IPT 

PROSITE

 PS01204; REL_1
 PS50254; REL_2 

PRINTS

 PR00057; NFKBTNSCPFCT.