Q04864 (REL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proto-oncogene c-Rel

Gene names

Name:

REL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.4 Ref.5 Ref.6 Ref.7 Ref.9 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 Reference proteome
Gene Ontology (GO)
Biological_process	cytokine production Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern PubMed 12761501. Source: UniProtKB positive regulation of interleukin-12 biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Non-traceable author statement PubMed 8423996. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COMMD1	Q8N668	3	EBI-307352,EBI-1550112

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 619	619	Proto-oncogene c-Rel		PRO_0000205165
Regions
	Domain	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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. NM_002908.2.
UniGene	Hs.631886.
3D structure databases
ProteinModelPortal	Q04864.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-301N.
IntAct	Q04864. 7 interactions.
MINT	MINT-1137552.
STRING	9606.ENSP00000295025.
PTM databases
PhosphoSite	Q04864.
Polymorphism databases
DMDM	548720.
Proteomic databases
PaxDb	Q04864.
PRIDE	Q04864.
Protocols and materials databases
DNASU	5966.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295025; ENSP00000295025; ENSG00000162924.
GeneID	5966.
KEGG	hsa:5966.
UCSC	uc002sam.1. human.
Organism-specific databases
CTD	5966.
GeneCards	GC02P061108.
HGNC	HGNC:9954. REL.
HPA	CAB004404.
MIM	164910. gene.
neXtProt	NX_Q04864.
PharmGKB	PA34321.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG119056.
HOGENOM	HOG000264257.
HOVERGEN	HBG017916.
InParanoid	Q04864.
KO	K09254.
OMA	GRFIKKE.
OrthoDB	EOG4NVZK2.
Enzyme and pathway databases
Pathway_Interaction_DB	nfkappabatypicalpathway. Atypical NF-kappaB pathway. ar_tf_pathway. Regulation of Androgen receptor activity.
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q04864.
Bgee	Q04864.
CleanEx	HS_REL.
Genevestigator	Q04864.
GermOnline	ENSG00000162924. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit. 2.60.40.340. 1 hit.
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]
Pfam	PF00554. RHD. 1 hit. [Graphical view]
PRINTS	PR00057. NFKBTNSCPFCT.
SMART	SM00429. IPT. 1 hit. [Graphical view]
SUPFAM	SSF81296. Ig_E-set. 1 hit. SSF49417. P53_like_DNA_bnd. 1 hit.
PROSITE	PS01204. REL_1. 1 hit. PS50254. REL_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5966.
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:	May 1, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.