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Reviewed, UniProtKB/Swiss-Prot Q04207 (TF65_MOUSE)

Last modified January 19, 2010. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Transcription factor p65
Alternative name(s):
    Nuclear factor NF-kappa-B p65 subunit
Gene names
Name: Rela
Synonyms: Nfkb3
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMus

Protein attributes

Sequence length549 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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.

Subunit structure

Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-c-Rel complex. Homodimer; component of the NF-kappa-B p65-p65 complex. Component of the NF-kappa-B p65-p52 complex. May interact with ETHE1. Binds AES and TLE1. Interacts with TP53BP2. Binds to and is phosphorylated by the activated form of either RPS6KA4 or RPS6KA5. Interacts with ING4 and this interaction may be indirect. Interacts with CARM1, USP48 and UNC5CL. Interacts with IRAK1BP1. Interacts with NFKBIA. Interacts with GSK3B. Interacts with NFKBIB. Interacts with NFKBIE. Interacts with NFKBIZ. Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Interacts with HDAC3; HDAC3 mediates the deacetylation of RELA. Interacts with HDAC1; the interaction requires non-phosphorylated RELA. Interacts with CBP; the interaction requires phosphorylated RELA. Interacts (phosphorylated at 'Thr-254') with PIN1; the interaction inhibits p65 binding to NFKBIA. Interacts with SOCS1. Interacts with MTDH and PHF11 By similarity. Interacts with NFKBID. Interacts with ARRB2 By similarity. Ref.5 Ref.6 Ref.10 Ref.11

Subcellular location

Nucleus. Cytoplasm. Note: Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).

Post-translational modification

Ubiquitinated, leading to its proteosomal degradation. Degradation is required for termination of NF-kappa-B response By similarity.

Phosphorylation on 'Ser-534' stimulates acetylation on 'Lys-310' and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity By similarity. Ref.7

Reversibly acetylated; the acetylation seems to be mediated by CBP, the deacetylation by HDAC3. Acetylation at 'Lys-122' enhances DNA binding and impairs association with NFKBIA. Acetylation at 'Lys-310' is required for full transcriptional activity in the absence of effects on DNA binding and NFKBIA association. Acetylation can also lower DNA-binding and results in nuclear export By similarity.

Sequence similarities

Contains 1 RHD (Rel-like) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform p65 (identifier: Q04207-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform p65 delta (identifier: Q04207-2)

The sequence of this isoform differs from the canonical sequence as follows:
     222-231: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 549549Transcription factor p65
PRO_0000205170

Regions

Domain19 – 306288RHD
Motif301 – 3044Nuclear localization signal Potential

Amino acid modifications

Modified residue1221N6-acetyllysine; by PCAF and EP300 By similarity
Modified residue1231N6-acetyllysine; by PCAF and EP300 By similarity
Modified residue2541Phosphothreonine By similarity
Modified residue2761Phosphoserine; by RPS6KA4 and RPS6KA5 By similarity
Modified residue2811Phosphoserine By similarity
Modified residue3101N6-acetyllysine By similarity
Modified residue3111Phosphoserine; by PKC/PRKCZ Ref.7
Modified residue4331Phosphothreonine By similarity
Modified residue4671Phosphoserine; by IKKB and IKKE By similarity
Modified residue5041Phosphothreonine; by CHK1 By similarity
Modified residue5271Phosphoserine; by CK2 By similarity
Modified residue5341Phosphoserine; by IKKB By similarity

Natural variations

Alternative sequence222 – 23110Missing in isoform p65 delta.
VSP_005589

Experimental info

Mutagenesis2811S → A or E: Abolishes DNA-binding and transcriptional activity. Ref.8
Sequence conflict281K → N in AAB00795. Ref.3
Sequence conflict611I → IQKD in AAB00795. Ref.3

Secondary structure

............................................... 549
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform p65 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: BDF1673D2FE398B9

FASTA54960,212
        10         20         30         40         50         60 
MDDLFPLIFP SEPAQASGPY VEIIEQPKQR GMRFRYKCEG RSAGSIPGER STDTTKTHPT 

        70         80         90        100        110        120 
IKINGYTGPG TVRISLVTKD PPHRPHPHEL VGKDCRDGYY EADLCPDRSI HSFQNLGIQC 

       130        140        150        160        170        180 
VKKRDLEQAI SQRIQTNNNP FHVPIEEQRG DYDLNAVRLC FQVTVRDPAG RPLLLTPVLS 

       190        200        210        220        230        240 
HPIFDNRAPN TAELKICRVN RNSGSCLGGD EIFLLCDKVQ KEDIEVYFTG PGWEARGSFS 

       250        260        270        280        290        300 
QADVHRQVAI VFRTPPYADP SLQAPVRVSM QLRRPSDREL SEPMEFQYLP DTDDRHRIEE 

       310        320        330        340        350        360 
KRKRTYETFK SIMKKSPFNG PTEPRPPTRR IAVPTRNSTS VPKPAPQPYT FPASLSTINF 

       370        380        390        400        410        420 
DEFSPMLLPS GQISNQALAL APSSAPVLAQ TMVPSSAMVP LAQPPAPAPV LTPGPPQSLS 

       430        440        450        460        470        480 
APVPKSTQAG EGTLSEALLH LQFDADEDLG ALLGNSTDPG VFTDLASVDN SEFQQLLNQG 

       490        500        510        520        530        540 
VSMSHSTAEP MLMEYPEAIT RLVTGSQRPP DPAPTPLGTS GLPNGLSGDE DFSSIADMDF 


SALLSQISS 

« Hide

Isoform p65 delta.

Checksum: F834FD0302D351BD
Show »

FASTA53959,061

References

« Hide 'large scale' references
[1]"DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide."
Nolan G.P., Ghosh S., Liou H.C., Tempst P., Baltimore D.
Cell 64:961-969(1991) [PubMed: 2001591] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P65).
Strain: C57BL/6J.
Tissue: Mammary gland.
[3]"Cloning of the murine relA (p65 NF-kappa B) gene and comparison to the human gene reveals a distinct first intron."
Linker R.A., Baeuerle P.A., Kaltschmidt C.
Gene 176:119-124(1996) [PubMed: 8918242] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
Strain: BALB/c.
[4]"Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing."
Deloukas P., van Loon A.P.G.M.
Hum. Mol. Genet. 2:1895-1900(1993) [PubMed: 8281153] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 188-252, ALTERNATIVE SPLICING.
Strain: BALB/c.
[5]"Role of unphosphorylated, newly synthesized IkappaB beta in persistent activation of NF-kappaB."
Suyang H., Phillips R.J., Douglas I., Ghosh S.
Mol. Cell. Biol. 16:5444-5449(1996) [PubMed: 8816457] [Abstract]
Cited for: INTERACTION WITH NFKBIB.
[6]"Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor."
Fiorini E., Schmitz I., Marissen W.E., Osborn S.L., Touma M., Sasada T., Reche P.A., Tibaldi E.V., Hussey R.E., Kruisbeek A.M., Reinherz E.L., Clayton L.K.
Mol. Cell 9:637-648(2002) [PubMed: 11931770] [Abstract]
Cited for: INTERACTION WITH NFKBID.
[7]"Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-kappaB transcriptional activation."
Duran A., Diaz-Meco M.T., Moscat J.
EMBO J. 22:3910-3918(2003) [PubMed: 12881425] [Abstract]
Cited for: PHOSPHORYLATION AT SER-311.
[8]"Critical role of RelB serine 368 for dimerization and p100 stabilization."
Maier H.J., Marienfeld R., Wirth T., Baumann B.
J. Biol. Chem. 278:39242-39250(2003) [PubMed: 12874295] [Abstract]
Cited for: MUTAGENESIS OF SER-281.
[9]"A defect in nucleosome remodeling prevents IL-12(p35) gene transcription in neonatal dendritic cells."
Goriely S., Van Lint C., Dadkhah R., Libin M., De Wit D., Demonte D., Willems F., Goldman M.
J. Exp. Med. 199:1011-1016(2004) [PubMed: 15051764] [Abstract]
Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-P50 COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P65-P65 COMPLEX.
[10]"Tumor necrosis factor alpha induction of NF-kappaB requires the novel coactivator SIMPL."
Kwon H.-J., Breese E.H., Vig-Varga E., Luo Y., Lee Y., Goebl M.G., Harrington M.A.
Mol. Cell. Biol. 24:9317-9326(2004) [PubMed: 15485901] [Abstract]
Cited for: INTERACTION WITH IRAK1BP1.
[11]"Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-kappaB-dependent gene expression."
Covic M., Hassa P.O., Saccani S., Buerki C., Meier N.I., Lombardi C., Imhof R., Bedford M.T., Natoli G., Hottiger M.O.
EMBO J. 24:85-96(2005) [PubMed: 15616592] [Abstract]
Cited for: INTERACTION WITH CARM1.
[12]"The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation."
Huxford T., Huang D.B., Malek S., Ghosh G.
Cell 95:759-770(1998) [PubMed: 9865694] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 19-291.
[13]"A novel DNA recognition mode by the NF-kappa B p65 homodimer."
Chen Y.Q., Ghosh S., Ghosh G.
Nat. Struct. Biol. 5:67-73(1998) [PubMed: 9437432] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 19-291.
[14]"Crystal structure of p50/p65 heterodimer of transcription factor NF-kappaB bound to DNA."
Chen F.E., Huang D.B., Chen Y.Q., Ghosh G.
Nature 391:410-413(1998) [PubMed: 9450761] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M61909 mRNA. Translation: AAA39811.1.
BC003818 mRNA. Translation: AAH03818.1.
L77155 Genomic DNA. Translation: AAB00795.1.
Z22952 Genomic DNA. Translation: CAA80528.1.
IPIIPI00134188.
IPI00229014.
PIRA37932.
PC4233.
S48113.
RefSeqNP_033071.1.
UniGeneMm.249966

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BFTX-ray2.00A/B191-291[»]
1IKNX-ray2.30A19-304[»]
1K3ZX-ray2.50A/B191-326[»]
1LE5X-ray2.75A/E20-291[»]
1LE9X-ray3.00A/E20-291[»]
1LEIX-ray2.70A20-291[»]
1MY5X-ray1.80A/B191-304[»]
1MY7X-ray1.49A/B191-304[»]
1OY3X-ray2.05B/C191-326[»]
1RAMX-ray2.70A/B19-291[»]
1VKXX-ray2.90A20-291[»]
2I9TX-ray2.80A19-291[»]
2RAMX-ray2.40A/B19-291[»]
SMRQ04207. Positions 20-319.
DisProtDP00129.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-6219N.
IntActQ04207. 14 interactions.
STRINGQ04207.

PTM databases

PhosphoSiteQ04207.

Proteomic databases

PRIDEQ04207.

Genome annotation databases

EnsemblENSMUST00000025867; ENSMUSP00000025867; ENSMUSG00000024927; Mus musculus. [Genome view]
GeneID19697.
KEGGmmu:19697.
UCSCuc008gee.1. mouse.

Organism-specific databases

CTD19697.
MGIMGI:103290. Rela.

Phylogenomic databases

HOGENOMHBG268789.
HOVERGENQ04207.
InParanoidQ04207.
OMAKPAPQPY.
OrthoDBEOG9SR0GB.
PhylomeDBQ04207.

Gene expression databases

ArrayExpressQ04207.
BgeeQ04207.
GenevestigatorQ04207.
GermOnlineENSMUSG00000024927. Mus musculus.

Family and domain databases

InterProIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT_TIG_rcpt.
IPR000451. NF_Rel_dor.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.60.40.340. RHD. 1 hit.
PfamPF00554. RHD. 1 hit.
[Graphical view]
PRINTSPR00057. NFKBTNSCPFCT.
SMARTSM00429. IPT. 1 hit.
[Graphical view]
PROSITEPS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio297048.
SOURCESearch...

Entry information

Entry nameTF65_MOUSE
AccessionPrimary (citable) accession number: Q04207
Secondary accession number(s): Q62025
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: January 19, 2010
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents