Reviewed, UniProtKB/Swiss-Prot Q04864 (REL_HUMAN)

Names and origin

Protein names

Recommended name:
    C-Rel proto-oncogene protein
      Short name=C-Rel protein

Gene names

Name:

REL

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	619 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Proto-oncogene that may play a role in differentiation and lymphopoiesis. 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. 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. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.
Subunit structure	Component of the NF-kappa-B p65-c-Rel complex. Component of the NF-kappa-B p50-c-Rel complex. Component of the NF-kappa-B p52-c-Rel complex. Homodimer; component of the NF-kappa-B c-Rel-c-Rel complex By similarity. Interacts with NKIRAS1. Interacts with NFKBIB By similarity. Interacts with NFKBIE. Ref.7 Ref.10
Subcellular location	Nucleus By similarity.
Sequence similarities	Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct transcription factor activity Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COMMD1	Q8N668	1	EBI-307352,EBI-1550112
RELA	Q04206	2	EBI-307352,EBI-73886

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 619	619	C-Rel proto-oncogene protein		PRO_0000205165
Regions
	Region	8 – 297	290	RHD
	Motif	290 – 295	6	Nuclear localization signal Potential
Amino acid modifications
	Modified residue	267	1	Phosphoserine; by PKA Potential
	Modified residue	503	1	Phosphoserine Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q04864-1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 03E1033BDF7B1B30	FASTA	619	68,520
	10 20 30 40 50 60 MASGAYNPYI EIIEQPRQRG MRFRYKCEGR SAGSIPGEHS TDNNRTYPSI QIMNYYGKGK 70 80 90 100 110 120 VRITLVTKND PYKPHPHDLV GKDCRDGYYE AEFGQERRPL FFQNLGIRCV KKKEVKEAII 130 140 150 160 170 180 TRIKAGINPF NVPEKQLNDI EDCDLNVVRL CFQVFLPDEH GNLTTALPPV VSNPIYDNRA 190 200 210 220 230 240 PNTAELRICR VNKNCGSVRG GDEIFLLCDK VQKDDIEVRF VLNDWEAKGI FSQADVHRQV 250 260 270 280 290 300 AIVFKTPPYC KAITEPVTVK MQLRRPSDQE VSESMDFRYL PDEKDTYGNK AKKQKTTLLF 310 320 330 340 350 360 QKLCQDHVET GFRHVDQDGL ELLTSGDPPT LASQSAGITV NFPERPRPGL LGSIGEGRYF 370 380 390 400 410 420 KKEPNLFSHD AVVREMPTGV SSQAESYYPS PGPISSGLSH HASMAPLPSS SWSSVAHPTP 430 440 450 460 470 480 RSGNTNPLSS FSTRTLPSNS QGIPPFLRIP VGNDLNASNA CIYNNADDIV GMEASSMPSA 490 500 510 520 530 540 DLYGISDPNM LSNCSVNMMT TSSDSMGETD NPRLLSMNLE NPSCNSVLDP RDLRQLHQMS 550 560 570 580 590 600 SSSMSAGANS NTTVFVSQSD AFEGSDFSCA DNSMINESGP SNSTNPNSHG FVQDSQYSGI 610 GSMQNEQLSD SFPYEFFQV

References

[1]	"A human rel proto-oncogene cDNA containing an Alu fragment as a potential coding exon." Brownell E., Mittereder N., Rice N.R. Oncogene 4:935-942(1989) [PubMed: 2666912] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Genetic characterization of human c-rel sequences." Brownell E., O'Brien S.J., Nash W.G., Rice N.R. Mol. Cell. Biol. 5:2826-2831(1985) [PubMed: 3016517] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 180-284.
[4]	"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-C-REL COMPLEX.
[5]	"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 P50-C-REL COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P52-C-REL COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P65-C-REL COMPLEX.
[6]	"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-C-REL COMPLEX.
[7]	"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.
[8]	"Tumor necrosis factor-alpha activation of NF-kappa B requires the phosphorylation of Ser-471 in the transactivation domain of c-Rel." Martin A.G., Fresno M. J. Biol. Chem. 275:24383-24391(2000) [PubMed: 10823840] [Abstract] Cited for: PHOSPHORYLATION AT SER-503.
[9]	"Leishmania major amastigotes induce p50/c-Rel NF-kappa B transcription factor in human macrophages: involvement in cytokine synthesis." Guizani-Tabbane L., Ben-Aissa K., Belghith M., Sassi A., Dellagi K. Infect. Immun. 72:2582-2589(2004) [PubMed: 15102766] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX.
[10]	"Inhibition of NF-kappaB activity by IkappaBbeta in association with kappaB-Ras." Chen Y., Vallee S., Wu J., Vu D., Sondek J., Ghosh G. Mol. Cell. Biol. 24:3048-3056(2004) [PubMed: 15024091] [Abstract] Cited for: INTERACTION WITH NKIRAS1.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	X75042 mRNA. Translation: CAA52954.1. DQ314888 Genomic DNA. Translation: ABC40747.1. M11595 Genomic DNA. Translation: AAA52073.1.
IPI	IPI00029773.
PIR	A60646.
RefSeq	NP_002899.1.
UniGene	Hs.631886
3D structure databases
SMR	Q04864. Positions 8-282.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-301N.
IntAct	Q04864. 31 interactions.
STRING	Q04864.
Proteomic databases
PRIDE	Q04864.
Genome annotation databases
Ensembl	ENST00000295025; ENSP00000295025; ENSG00000162924; Homo sapiens. [Genome view]
GeneID	5966.
KEGG	hsa:5966.
UCSC	uc002sam.1. human.
Organism-specific databases
CTD	5966.
GeneCards	GC02P061020.
H-InvDB	HIX0029962.
HGNC	HGNC:9954. REL.
HPA	CAB004404.
MIM	164910. gene.
PharmGKB	PA30126.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18542.
HOGENOM	HBG282218.
HOVERGEN	Q04864.
InParanoid	Q04864.
OMA	CADNSMI.
OrthoDB	EOG9SR0GB.
PhylomeDB	Q04864.
Enzyme and pathway databases
Pathway_Interaction_DB	nfkappabatypicalpathway. Atypical NF-kappaB pathway. ar_tf_pathway. Regulation of Androgen receptor activity.
Gene expression databases
ArrayExpress	Q04864.
Bgee	Q04864.
CleanEx	HS_REL.
Genevestigator	Q04864.
GermOnline	ENSG00000162924. 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	23226.
SOURCE	Search...

Entry information

Entry name

REL_HUMAN

Accession

Primary (citable) accession number: Q04864
Secondary accession number(s): Q2PNZ7, Q6LDY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	January 19, 2010
This is version 92 of the entry and version 1 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.