Reviewed,
UniProtKB/Swiss-Prot Q04206 (TF65_HUMAN)
Last modified
November 25, 2008.
Version 107.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Transcription factor p65 Alternative name(s): Nuclear factor NF-kappa-B p65 subunit | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 551 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence 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. 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 By similarity.Interacts with NFKBID By similarity. Interacts with NFKBIA. Interacts with GSK3B. Interacts with NFKBIB By similarity. Interacts with NFKBIE. Interacts with NFKBIZ By similarity. 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 UXT. |
| 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. Phosphorylation on 'Ser-536' stimulates acetylation on 'Lys-310' and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity. 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. |
| Sequence similarities | Contains 1 RHD (Rel-like) domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 3 | EBI-73886,EBI-73886 | ||
| AATF | Q9NY61 | 2 | EBI-73886,EBI-372428 | |
| ATF3 | P18847 | 1 | EBI-73886,EBI-712767 | |
| CDK5RAP3 | Q96JB5 | 3 | EBI-73886,EBI-718818 | |
| CHUK | O15111 | 1 | EBI-73886,EBI-81249 | |
| COMMD1 | Q8N668 | 2 | EBI-73886,EBI-1550112 | |
| CREBBP | Q92793 | 1 | EBI-73886,EBI-81215 | |
| DHX9 | Q08211 | 3 | EBI-73886,EBI-352022 | |
| HDAC1 | Q13547 | 2 | EBI-73886,EBI-301834 | |
| MTDH | Q86UE4 | 1 | EBI-73886,EBI-1046588 | |
| NFKB1 | P19838 | 2 | EBI-73886,EBI-300010 | |
| NFKBIA | P25963 | 3 | EBI-73886,EBI-307386 | |
| NFKBIB | Q15653 | 3 | EBI-73886,EBI-352889 | |
| PDCD11 | Q14690 | 1 | EBI-73886,EBI-300028 | |
| REL | Q04864 | 2 | EBI-73886,EBI-307352 | |
| RPS3 | P23396 | 5 | EBI-73886,EBI-351193 | |
| RPS6KA5 | O75582 | 1 | EBI-73886,EBI-73869 | |
| TGM2 | P21980 | 2 | EBI-73886,EBI-727668 | |
| TP53BP2 | Q13625-2 | 5 | EBI-73886,EBI-287091 | |
| UXT | Q9UBK9 | 3 | EBI-73886,EBI-357355 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q04206-1) Also known as: p65; 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 2 (identifier: Q04206-2) Also known as: p65 delta 2; The sequence of this isoform differs from the canonical sequence as follows: 13-25: Missing. 506-506: Missing. | ||||||
| Isoform 3 (identifier: Q04206-3) Also known as: p65 delta; The sequence of this isoform differs from the canonical sequence as follows: 222-231: Missing. | ||||||
| Isoform 4 (identifier: Q04206-4) The sequence of this isoform differs from the canonical sequence as follows: 143-145: Missing. | ||||||
| Notes: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 551 | 551 | Transcription factor p65 | PRO_0000205169 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 19 – 306 | 288 | RHD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Region | 415 – 459 | 45 | Activation domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motif | 301 – 304 | 4 | Nuclear localization signal Potential | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 122 | 1 | N6-acetyllysine; by PCAF and EP300 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 123 | 1 | N6-acetyllysine; by PCAF and EP300 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 254 | 1 | Phosphothreonine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 276 | 1 | Phosphoserine; by RPS6KA4 and RPS6KA5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 281 | 1 | Phosphoserine Probable | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 310 | 1 | N6-acetyllysine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 311 | 1 | Phosphoserine; by PKC/PRKCZ By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 435 | 1 | Phosphothreonine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 468 | 1 | Phosphoserine; by IKKB and IKKE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 505 | 1 | Phosphothreonine; by CHK1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 529 | 1 | Phosphoserine; by CK2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 536 | 1 | Phosphoserine; by IKKB | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 13 – 25 | 13 | Missing in isoform 2. | VSP_005587 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 143 – 145 | 3 | Missing in isoform 4. | VSP_031245 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 222 – 231 | 10 | Missing in isoform 3. | VSP_012031 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 506 | 1 | Missing in isoform 2. | VSP_005588 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 254 | 1 | T → A: Abolishes interaction with PIN1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 276 | 1 | S → C: Loss of phosphorylation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 49 | 1 | E → R in CAA80524. Ref.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 180 | 1 | S → P in AAA36408. Ref.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 372 – 380 | 9 | QISQASALA → RSARPRLG in CAA80524. Ref.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 21 – 25 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 30 – 32 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 39 – 41 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 53 – 55 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 60 – 63 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 68 – 80 | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 87 – 92 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 97 – 104 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 117 – 119 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 126 – 129 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 130 – 137 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 156 – 166 | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 168 – 173 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 183 – 188 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 196 – 200 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 202 – 205 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 211 – 217 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 225 – 230 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 233 – 238 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 241 – 243 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 246 – 248 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 249 – 253 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 266 – 273 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 275 – 277 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 284 – 289 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 294 – 302 | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 306 – 312 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B." Ruben S.M., Dillon P.J., Schreck R., Henkel T., Chen C.-H., Maher M., Baeuerle P.A., Rosen C.A. Science 251:1490-1493(1991) [PubMed: 2006423] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "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], ALTERNATIVE SPLICING. |
| [3] | "An alternatively spliced transcript, p65 delta 2, of the gene encoding the p65 subunit of the transcription factor NF-kappa B." Lyle R., Valleley E.M., Sharpe P.T., Hewitt J.E. Gene 138:265-266(1994) [PubMed: 7907305] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Bone. |
| [4] | "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 4). Tissue: Colon. |
| [5] | SeattleSNPs program for genomic applications Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 4-551. |
| [6] | "Functional characterization of the NF-kappa B p65 transcriptional activator and an alternatively spliced derivative." Ruben S.M., Narayanan R., Klement J.F., Chen C.-H., Rosen C.A. Mol. Cell. Biol. 12:444-454(1992) [PubMed: 1732726] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 214-239 (ISOFORMS 1/2 AND 3), ACTIVATION DOMAIN. |
| [7] | "A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene." Hansen S.K., Nerlov C., Zabel U., Verde P., Johnsen M., Baeuerle P.A., Blasi F. EMBO J. 11:205-213(1992) [PubMed: 1740106] [Abstract] Cited for: IDENTIFICAT |

Clusters with