Reviewed, UniProtKB/Swiss-Prot Q04206 (TF65_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor p65
Alternative name(s):
    Nuclear factor NF-kappa-B p65 subunit

Gene names

Name:	RELA
Synonyms:	NFKB3

Organism

Homo sapiens (Human) [Complete proteome]

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.
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. Ref.15 Ref.41
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. Interacts with MTDH and PHF11. Interacts with ARRB2. Interacts with human respiratory syncytial virus (HRSV) protein M2-1. Ref.41 Ref.8 Ref.11 Ref.14 Ref.16 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.29 Ref.30 Ref.35 Ref.36 Ref.37 Ref.39 Ref.42
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. Ref.28 Phosphorylation on 'Ser-536' stimulates acetylation on 'Lys-310' and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity. Ref.21 Ref.22 Ref.25 Ref.13 Ref.17 Ref.27 Ref.31 Ref.32 Ref.33 Ref.38 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

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: UniProtKB cellular defense response Non-traceable author statement. Source: UniProtKB cytokine-mediated signaling pathway Inferred from direct assay. Source: UniProtKB defense response to virus Non-traceable author statement. Source: UniProtKB inflammatory response Inferred from direct assay. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW membrane protein intracellular domain proteolysis Inferred from Experiment. Source: Reactome nucleotide-binding oligomerization domain containing 2 signaling pathway Inferred from direct assay. Source: MGI positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from direct assay. Source: MGI positive regulation of transcription from RNA polymerase II promoter Ref.16 Inferred from mutant phenotype. Source: UniProtKB response to UV-B Inferred from direct assay. Source: UniProtKB response to interleukin-1 Inferred from genetic interaction. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome transcription factor complex Inferred from direct assay. Source: UniProtKB
Molecular function	NF-kappaB binding Inferred from physical interaction. Source: UniProtKB RNA polymerase II transcription factor activity, enhancer binding Inferred from direct assay. Source: UniProtKB identical protein binding Ref.14 Inferred from direct assay. Source: UniProtKB phosphate binding Ref.13 Inferred from direct assay. Source: UniProtKB protein N-terminus binding Inferred from physical interaction. Source: UniProtKB protein kinase binding Ref.13 Inferred from physical interaction. Source: UniProtKB transcription activator binding Inferred from physical interaction. Source: UniProtKB transcription repressor binding Ref.16 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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
SIRT6	Q8N6T7	3	EBI-73886,EBI-712415
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.

Note: 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 Ref.23

Modified residue

123

1

N6-acetyllysine; by PCAF and EP300 Ref.23

Modified residue

254

1

Phosphothreonine Ref.25

Modified residue

276

1

Phosphoserine; by RPS6KA4 and RPS6KA5 Ref.22

Modified residue

281

1

Phosphoserine Probable

Modified residue

310

1

N6-acetyllysine Ref.20 Ref.34 Ref.43

Modified residue

311

1

Phosphoserine; by PKC/PRKCZ By similarity

Modified residue

435

1

Phosphothreonine Ref.27

Modified residue

468

1

Phosphoserine; by IKKB and IKKE Ref.32 Ref.38

Modified residue

505

1

Phosphothreonine; by CHK1 Ref.31

Modified residue

529

1

Phosphoserine; by CK2 Ref.17

Modified residue

536

1

Phosphoserine; by IKKB Ref.13

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. Ref.25

Mutagenesis

276

1

S → C: Loss of phosphorylation. Ref.22

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

1

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551

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform 1 (p65) [UniParc]. Last modified April 26, 2005. Version 2. Checksum: 8147A6AF9F2445C6	FASTA	551	60,219
	10 20 30 40 50 60 MDELFPLIFP AEPAQASGPY VEIIEQPKQR GMRFRYKCEG RSAGSIPGER STDTTKTHPT 70 80 90 100 110 120 IKINGYTGPG TVRISLVTKD PPHRPHPHEL VGKDCRDGFY EAELCPDRCI HSFQNLGIQC 130 140 150 160 170 180 VKKRDLEQAI SQRIQTNNNP FQVPIEEQRG DYDLNAVRLC FQVTVRDPSG RPLRLPPVLS 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 SIMKKSPFSG PTDPRPPPRR IAVPSRSSAS VPKPAPQPYP FTSSLSTINY 370 380 390 400 410 420 DEFPTMVFPS GQISQASALA PAPPQVLPQA PAPAPAPAMV SALAQAPAPV PVLAPGPPQA 430 440 450 460 470 480 VAPPAPKPTQ AGEGTLSEAL LQLQFDDEDL GALLGNSTDP AVFTDLASVD NSEFQQLLNQ 490 500 510 520 530 540 GIPVAPHTTE PMLMEYPEAI TRLVTGAQRP PDPAPAPLGA PGLPNGLLSG DEDFSSIADM 550 DFSALLSQIS S
	Isoform 2 (p65 delta 2). Checksum: A1F26DF2F53E662E	FASTA	537	58,807
	10 20 30 40 50 60 MDELFPLIFP AEQPKQRGMR FRYKCEGRSA GSIPGERSTD TTKTHPTIKI NGYTGPGTVR 70 80 90 100 110 120 ISLVTKDPPH RPHPHELVGK DCRDGFYEAE LCPDRCIHSF QNLGIQCVKK RDLEQAISQR 130 140 150 160 170 180 IQTNNNPFQV PIEEQRGDYD LNAVRLCFQV TVRDPSGRPL RLPPVLSHPI FDNRAPNTAE 190 200 210 220 230 240 LKICRVNRNS GSCLGGDEIF LLCDKVQKED IEVYFTGPGW EARGSFSQAD VHRQVAIVFR 250 260 270 280 290 300 TPPYADPSLQ APVRVSMQLR RPSDRELSEP MEFQYLPDTD DRHRIEEKRK RTYETFKSIM 310 320 330 340 350 360 KKSPFSGPTD PRPPPRRIAV PSRSSASVPK PAPQPYPFTS SLSTINYDEF PTMVFPSGQI 370 380 390 400 410 420 SQASALAPAP PQVLPQAPAP APAPAMVSAL AQAPAPVPVL APGPPQAVAP PAPKPTQAGE 430 440 450 460 470 480 GTLSEALLQL QFDDEDLGAL LGNSTDPAVF TDLASVDNSE FQQLLNQGIP VAPHTTEPML 490 500 510 520 530 MEYPEAITRL VTAQRPPDPA PAPLGAPGLP NGLLSGDEDF SSIADMDFSA LLSQISS
	Isoform 3 (p65 delta). Checksum: 49F0493E19798AD1	FASTA	541	59,068
	10 20 30 40 50 60 MDELFPLIFP AEPAQASGPY VEIIEQPKQR GMRFRYKCEG RSAGSIPGER STDTTKTHPT 70 80 90 100 110 120 IKINGYTGPG TVRISLVTKD PPHRPHPHEL VGKDCRDGFY EAELCPDRCI HSFQNLGIQC 130 140 150 160 170 180 VKKRDLEQAI SQRIQTNNNP FQVPIEEQRG DYDLNAVRLC FQVTVRDPSG RPLRLPPVLS 190 200 210 220 230 240 HPIFDNRAPN TAELKICRVN RNSGSCLGGD EIFLLCDKVQ KGWEARGSFS QADVHRQVAI 250 260 270 280 290 300 VFRTPPYADP SLQAPVRVSM QLRRPSDREL SEPMEFQYLP DTDDRHRIEE KRKRTYETFK 310 320 330 340 350 360 SIMKKSPFSG PTDPRPPPRR IAVPSRSSAS VPKPAPQPYP FTSSLSTINY DEFPTMVFPS 370 380 390 400 410 420 GQISQASALA PAPPQVLPQA PAPAPAPAMV SALAQAPAPV PVLAPGPPQA VAPPAPKPTQ 430 440 450 460 470 480 AGEGTLSEAL LQLQFDDEDL GALLGNSTDP AVFTDLASVD NSEFQQLLNQ GIPVAPHTTE 490 500 510 520 530 540 PMLMEYPEAI TRLVTGAQRP PDPAPAPLGA PGLPNGLLSG DEDFSSIADM DFSALLSQIS S
	Isoform 4. Checksum: ED40EF8B91F0A19A	FASTA	548	59,910
	10 20 30 40 50 60 MDELFPLIFP AEPAQASGPY VEIIEQPKQR GMRFRYKCEG RSAGSIPGER STDTTKTHPT 70 80 90 100 110 120 IKINGYTGPG TVRISLVTKD PPHRPHPHEL VGKDCRDGFY EAELCPDRCI HSFQNLGIQC 130 140 150 160 170 180 VKKRDLEQAI SQRIQTNNNP FQEEQRGDYD LNAVRLCFQV TVRDPSGRPL RLPPVLSHPI 190 200 210 220 230 240 FDNRAPNTAE LKICRVNRNS GSCLGGDEIF LLCDKVQKED IEVYFTGPGW EARGSFSQAD 250 260 270 280 290 300 VHRQVAIVFR TPPYADPSLQ APVRVSMQLR RPSDRELSEP MEFQYLPDTD DRHRIEEKRK 310 320 330 340 350 360 RTYETFKSIM KKSPFSGPTD PRPPPRRIAV PSRSSASVPK PAPQPYPFTS SLSTINYDEF 370 380 390 400 410 420 PTMVFPSGQI SQASALAPAP PQVLPQAPAP APAPAMVSAL AQAPAPVPVL APGPPQAVAP 430 440 450 460 470 480 PAPKPTQAGE GTLSEALLQL QFDDEDLGAL LGNSTDPAVF TDLASVDNSE FQQLLNQGIP 490 500 510 520 530 540 VAPHTTEPML MEYPEAITRL VTGAQRPPDP APAPLGAPGL PNGLLSGDED FSSIADMDFS ALLSQISS

References

	« Hide 'large scale' referencesShow '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 variation discovery resource 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: IDENTIFICATION IN THE NF-KAPPA-B P65-P50 COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P65-C-REL COMPLEX.
[8]	"I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding." Ganchi P.A., Sun S.C., Greene W.C., Ballard D.W. Mol. Biol. Cell 3:1339-1352(1992) [PubMed: 1493333] [Abstract] Cited for: INTERACTION WITH NFKBIA.
[9]	"Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor." Beg A.A., Baldwin A.S. Jr. Oncogene 9:1487-1492(1994) [PubMed: 8152812] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-C-REL COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P65-P52 COMPLEX.
[10]	"Regulation of intercellular adhesion molecule-1 gene by tumor necrosis factor-alpha is mediated by the nuclear factor-kappaB heterodimers p65/p65 and p65/c-Rel in the absence of p50." Aoudjit F., Brochu N., Belanger B., Stratowa C., Hiscott J., Audette M. Cell Growth Differ. 8:335-342(1997) [PubMed: 9056676] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-P65 COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P65-C-REL COMPLEX.
[11]	"A new member of the IkappaB protein family, IkappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription." Li Z., Nabel G.J. Mol. Cell. Biol. 17:6184-6190(1997) [PubMed: 9315679] [Abstract] Cited for: INTERACTION WITH NFKBIE.
[12]	"IKAP is a scaffold protein of the IkappaB kinase complex." Cohen L., Henzel W.J., Baeuerle P.A. Nature 395:292-296(1998) [PubMed: 9751059] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CHUK; IKBKB; NFKBIA; IKBKAP AND MAP3K14.
[13]	"IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain." Sakurai H., Chiba H., Miyoshi H., Sugita T., Toriumi W. J. Biol. Chem. 274:30353-30356(1999) [PubMed: 10521409] [Abstract] Cited for: PHOSPHORYLATION AT SER-536.
[14]	"NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2." Yang J.-P., Hori M., Takahashi N., Kawabe T., Kato H., Okamoto T. Oncogene 18:5177-5186(1999) [PubMed: 10498867] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH TP53BP2.
[15]	"Yersinia enterocolitica invasin protein triggers IL-8 production in epithelial cells via activation of Rel p65-p65 homodimers." Schulte R., Grassl G.A., Preger S., Fessele S., Jacobi C.A., Schaller M., Nelson P.J., Autenrieth I.B. FASEB J. 14:1471-1484(2000) [PubMed: 10928981] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE NF-KAPPA-B P65-P65 COMPLEX.
[16]	"Inhibition of nuclear factor-kappaB-mediated transcription by association with the amino-terminal enhancer of split, a Groucho-related protein lacking WD40 repeats." Tetsuka T., Uranishi H., Imai H., Ono T., Sonta S., Takahashi N., Asamitsu K., Okamoto T. J. Biol. Chem. 275:4383-4390(2000) [PubMed: 10660609] [Abstract] Cited for: INTERACTION WITH AES AND TLE1.
[17]	"Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II." Wang D., Westerheide S.D., Hanson J.L., Baldwin A.S. Jr. J. Biol. Chem. 275:32592-32597(2000) [PubMed: 10938077] [Abstract] Cited for: PHOSPHORYLATION AT SER-529.
[18]	"Duration of nuclear NF-kappaB action regulated by reversible acetylation." Chen L.F., Fischle W., Verdin E., Greene W.C. Science 293:1653-1657(2001) [PubMed: 11533489] [Abstract] Cited for: ACETYLATION, INTERACTION WITH HDAC3.
[19]	"A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis." Higashitsuji H., Higashitsuji H., Nagao T., Nonoguchi K., Fujii S., Itoh K., Fujita J. Cancer Cell 2:335-346(2002) [PubMed: 12398897] [Abstract] Cited for: INTERACTION WITH ETHE1.
[20]	"Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB." Chen L.F., Mu Y., Greene W.C. EMBO J. 21:6539-6548(2002) [PubMed: 12456660] [Abstract] Cited for: ACETYLATION AT LYS-218; LYS-221 AND LYS-310.
[21]	"The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1." Zhong H., May M.J., Jimi E., Ghosh S. Mol. Cell 9:625-636(2002) [PubMed: 11931769] [Abstract] Cited for: INTERACTION WITH CBP AND HDAC1, PHOSPHORYLATION.
[22]	"Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)." Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G. EMBO J. 22:1313-1324(2003) [PubMed: 12628924] [Abstract] Cited for: INTERACTION WITH RPS6KA5, MUTAGENESIS OF SER-276, PHOSPHORYLATION AT SER-276.
[23]	"Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65." Kiernan R., Bres V., Ng R.W., Coudart M.-P., El Messaoudi S., Sardet C., Jin D.-Y., Emiliani S., Benkirane M. J. Biol. Chem. 278:2758-2766(2003) [PubMed: 12419806] [Abstract] Cited for: ACETYLATION AT LYS-122 AND LYS-123.
[24]	"Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability." Demarchi F., Bertoli C., Sandy P., Schneider C. J. Biol. Chem. 278:39583-39590(2003) [PubMed: 12871932] [Abstract] Cited for: INTERACTION WITH GSK3B.
[25]	"Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA." Ryo A., Suizu F., Yoshida Y., Perrem K., Liou Y.C., Wulf G., Rottapel R., Yamaoka S., Lu K.P. Mol. Cell 12:1413-1426(2003) [PubMed: 14690596] [Abstract] Cited for: PHOSPHORYLATION AT THR-254, INTERACTION WITH PIN1 AND SOCS1, MUTAGENESIS OF THR-254.
[26]	"Identification of a ZU5 and death domain-containing inhibitor of NF-kappaB." Zhang J., Xu L.-G., Han K.-J., Shu H.-B. J. Biol. Chem. 279:17819-17825(2004) [PubMed: 14769797] [Abstract] Cited for: INTERACTION WITH UNC5CL.
[27]	"Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation." Yeh P.Y., Yeh K.H., Chuang S.E., Song Y.C., Cheng A.L. J. Biol. Chem. 279:26143-26148(2004) [PubMed: 15073167] [Abstract] Cited for: PHOSPHORYLATION AT THR-435.
[28]	"Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor kappaB response." Saccani S., Marazzi I., Beg A.A., Natoli G. J. Exp. Med. 200:107-113(2004) [PubMed: 15226358] [Abstract] Cited for: UBIQUITINATION.
[29]	"Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways." Gao H., Sun Y., Wu Y., Luan B., Wang Y., Qu B., Pei G. Mol. Cell 14:303-317(2004) [PubMed: 15125834] [Abstract] Cited for: INTERACTION WITH ARRB2.
[30]	"The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis." Garkavtsev I., Kozin S.V., Chernova O., Xu L., Winkler F., Brown E., Barnett G.H., Jain R.K. Nature 428:328-332(2004) [PubMed: 15029197] [Abstract] Cited for: INTERACTION WITH ING4.
[31]	"Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor." Rocha S., Garrett M.D., Campbell K.J., Schumm K., Perkins N.D. EMBO J. 24:1157-1169(2005) [PubMed: 15775976] [Abstract] Cited for: PHOSPHORYLATION AT THR-505.
[32]	"IKKbeta phosphorylates p65 at S468 in transactivaton domain 2." Schwabe R.F., Sakurai H. FASEB J. 19:1758-1760(2005) [PubMed: 16046471] [Abstract] Cited for: PHOSPHORYLATION AT SER-468.
[33]	"cis-acting, element-specific transcriptional activity of differentially phosphorylated nuclear factor-kappa B." Anrather J., Racchumi G., Iadecola C. J. Biol. Chem. 280:244-252(2005) [PubMed: 15516339] [Abstract] Cited for: PHOSPHORYLATION AT SER-281.
[34]	"NF-kappaB RelA phosphorylation regulates RelA acetylation." Chen L.F., Williams S.A., Mu Y., Nakano H., Duerr J.M., Buckbinder L., Greene W.C. Mol. Cell. Biol. 25:7966-7975(2005) [PubMed: 16135789] [Abstract] Cited for: ACETYLATION AT LYS-310.
[35]	"Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B." Reimers K., Buchholz K., Werchau H. Virology 331:260-268(2005) [PubMed: 15629770] [Abstract] Cited for: INTERACTION WITH HRSV PROTEIN M2-1.
[36]	"Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis." Emdad L., Sarkar D., Su Z.-Z., Randolph A., Boukerche H., Valerie K., Fisher P.B. Cancer Res. 66:1509-1516(2006) [PubMed: 16452207] [Abstract] Cited for: INTERACTION WITH MTDH.
[37]	"Human ubiquitin specific protease 31 is a deubiquitinating enzyme implicated in activation of nuclear factor-kappaB." Tzimas C., Michailidou G., Arsenakis M., Kieff E., Mosialos G., Hatzivassiliou E.G. Cell. Signal. 18:83-92(2006) [PubMed: 16214042] [Abstract] Cited for: INTERACTION WITH USP48.
[38]	"Inducible phosphorylation of NF-kappa B p65 at serine 468 by T cell costimulation is mediated by IKK epsilon." Mattioli I., Geng H., Sebald A., Hodel M., Bucher C., Kracht M., Schmitz M.L. J. Biol. Chem. 281:6175-6183(2006) [PubMed: 16407239] [Abstract] Cited for: PHOSPHORYLATION AT SER-468.
[39]	"Coactivator-associated arginine methyltransferase-1 enhances nuclear factor-kappaB-mediated gene transcription through methylation of histone H3 at arginine 17." Miao F., Li S., Chavez V., Lanting L., Natarajan R. Mol. Endocrinol. 20:1562-1573(2006) [PubMed: 16497732] [Abstract] Cited for: INTERACTION WITH CARM1.
[40]	"IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation." Song Y.J., Jen K.Y., Soni V., Kieff E., Cahir-McFarland E. Proc. Natl. Acad. Sci. U.S.A. 103:2689-2694(2006) [PubMed: 16477006] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-P52 COMPLEX.
[41]	"UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome." Sun S., Tang Y., Lou X., Zhu L., Yang K., Zhang B., Shi H., Wang C. J. Cell Biol. 178:231-244(2007) [PubMed: 17620405] [Abstract] Cited for: FUNCTION, INTERACTION WITH UXT.
[42]	"Functional characterization of the atopy-associated gene PHF11." Clarke E., Rahman N., Page N., Rolph M.S., Stewart G.J., Jones G.J. J. Allergy Clin. Immunol. 121:1148-1154(2008) [PubMed: 18405956] [Abstract] Cited for: INTERACTION WITH PHF11.
[43]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-310, MASS SPECTROMETRY.
[44]	"Structure of an IkappaBalpha/NF-kappaB complex." Jacobs M.D., Harrison S.C. Cell 95:749-758(1998) [PubMed: 9865693] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M62399 mRNA. Translation: AAA36408.1.
Z22948 , Z22949, Z22953, Z22950, Z22951 Genomic DNA. Translation: CAA80524.2.
L19067 mRNA. Translation: AAA20946.1.
BC033522 mRNA. Translation: AAH33522.1.
AY455868 Genomic DNA. Translation: AAR13863.1.

IPI

IPI00219084.
IPI00386448.
IPI00479470.
IPI00884950.

PIR

A40851.
I53719.
A42017. S51782.

RefSeq

NP_001138610.1.
NP_068810.3.

UniGene

Hs.502875

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NFI	X-ray	2.70	A/C	20-320	[»]
2O61	X-ray	2.80	A	20-291	[»]
3GUT	X-ray	3.59	A/C/E/G	20-291	[»]

DisProt

DP00085.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24238N.

IntAct

Q04206. 126 interactions.

STRING

Q04206.

PTM databases

PhosphoSite

Q04206.

Proteomic databases

PRIDE

Q04206.

Genome annotation databases

Ensembl

ENST00000406246; ENSP00000384273; ENSG00000173039; Homo sapiens. [Genome view]

GeneID

5970.

KEGG

hsa:5970.

NMPDR

fig|9606.3.peg.6043.

UCSC

uc001ofg.1. human.
uc001ofh.1. human.

Organism-specific databases

CTD

5970.

GeneCards

GC11M065178.

H-InvDB

HIX0009804.

HGNC

HGNC:9955. RELA.

HPA

CAB004264.
CAB005030.

MIM

164014. gene.

PharmGKB

PA296.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05741.

HOGENOM

HBG268789.

HOVERGEN

Q04206.

InParanoid

Q04206.

OMA

KPAPQPY.

PhylomeDB

Q04206.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
ceramidepathway. Ceramide signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il1pathway. IL1-mediated signaling events.
il12_2pathway. IL12-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il23pathway. IL23-mediated signaling events.
lysophospholipid_pathway. LPA receptor mediated events.
avb3_opn_pathway. Osteopontin-mediated events.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_11061. Signalling by NGF.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

Q04206.

Bgee

Q04206.

CleanEx

HS_RELA.

Genevestigator

Q04206.

GermOnline

ENSG00000173039. Homo sapiens.

Family and domain databases

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.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.60.40.340. RHD. 1 hit.

Pfam

PF00554. RHD. 1 hit.
[Graphical view]

PRINTS

PR00057. NFKBTNSCPFCT.

SMART

SM00429. IPT. 1 hit.
[Graphical view]

PROSITE

PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

23241.

SOURCE

Search...

Entry information

Entry name

TF65_HUMAN

Accession

Primary (citable) accession number: Q04206
Secondary accession number(s): Q6GTV1, Q6SLK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	April 26, 2005
Last modified:	January 19, 2010
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.