P17676 (CEBPB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CCAAT/enhancer-binding protein beta
Short name=C/EBP beta

Alternative name(s):
Liver activator protein
Nuclear factor NF-IL6
Transcription factor 5
Short name=TCF-5

Gene names

Name:	CEBPB
Synonyms:	LAP, TCF5
ORF Names:	PP9092

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

General annotation (Comments)

Function	Important transcriptional activator in the regulation of genes involved in immune and inflammatory responses. Specifically binds to an IL-1 response element in the IL-6 gene. NF-IL6 also binds to regulatory regions of several acute-phase and cytokines genes. It probably plays a role in the regulation of acute-phase reaction, inflammation and hemopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Functions in brown adipose tissue (BAT) differentiation By similarity. Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG). Ref.12
Subunit structure	Binds DNA as a dimer and can form stable heterodimers with C/EBP alpha, delta and gamma. Interacts with TRIM28 and PTGES2. Interacts with PRDM16. Interacts with CCDC85B. Forms a complex with THOC5 By similarity. Interacts with ZNF638; this interaction increases transcriptional activation By similarity. Interacts with CIDEA and CIDEC; these interactions increase transcriptional activation of a subset of CEBPB downstream target genes By similarity. Interacts with DDIT3/CHOP. Ref.12
Subcellular location	Nucleus Ref.12.
Tissue specificity	Expressed at low levels in the lung, kidney and spleen.
Induction	By ER stress. Ref.12
Domain	the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. Ref.11
Post-translational modification	Sumoylated by polymeric chains of SUMO2 or SUMO3. Ref.10 Phosphorylated at Thr-235 by RPS6KA1. Ref.9
Sequence similarities	Belongs to the bZIP family. C/EBP subfamily. Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute-phase response Traceable author statement Ref.1. Source: ProtInc brown fat cell differentiation Inferred from electronic annotation. Source: Compara cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara embryonic placenta development Inferred from electronic annotation. Source: Compara immune response Traceable author statement Ref.1. Source: ProtInc induction of apoptosis Inferred from electronic annotation. Source: Compara mammary gland epithelial cell differentiation Inferred from electronic annotation. Source: Compara mammary gland epithelial cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara regulation of interleukin-6 biosynthetic process Inferred from electronic annotation. Source: Compara response to endoplasmic reticulum stress Inferred from direct assay Ref.12. Source: UniProtKB response to lipopolysaccharide Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from electronic annotation. Source: Compara nuclear matrix Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	DNA binding Traceable author statement PubMed 10821850. Source: ProtInc RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TP53	P04637	4	EBI-969696,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

CCAAT/enhancer-binding protein beta

PRO_0000076617

Regions

Domain

271 – 334

64

bZIP

Region

1 – 24

24

Required for Lys-174 sumoylation

Region

275 – 295

21

Basic motif By similarity

Region

297 – 304

8

Leucine-zipper By similarity

Motif

116 – 124

9

9aaTAD

Compositional bias

162 – 170

9

Poly-Pro

Amino acid modifications

Modified residue

235

1

Phosphothreonine; by RPS6KA1 Ref.9

Cross-link

174

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.10

Natural variations

Natural variant

195

1

G → S. Ref.3
Corresponds to variant rs4253440 [ dbSNP | Ensembl ].

VAR_016300

Experimental info

Sequence conflict

241

1

A → P no nucleotide entry Ref.8

Sequence conflict

253

1

A → G in CAA36794. Ref.1

Secondary structure

1

.

.

.

.

.

345

Helix Strand Turn

Details...

Beta strand

269 – 271

3

Helix

272 – 328

57

Turn

329 – 331

3

Sequences

	Sequence		Length	Mass (Da)
	P17676 [UniParc]. Last modified August 22, 2003. Version 2. Checksum: 9B725BD6CCAA771D	FASTA	345	36,106
	10 20 30 40 50 60 MQRLVAWDPA CLPLPPPPPA FKSMEVANFY YEADCLAAAY GGKAAPAAPP AARPGPRPPA 70 80 90 100 110 120 GELGSIGDHE RAIDFSPYLE PLGAPQAPAP ATATDTFEAA PPAPAPAPAS SGQHHDFLSD 130 140 150 160 170 180 LFSDDYGGKN CKKPAEYGYV SLGRLGAAKG ALHPGCFAPL HPPPPPPPPP AELKAEPGFE 190 200 210 220 230 240 PADCKRKEEA GAPGGGAGMA AGFPYALRAY LGYQAVPSGS SGSLSTSSSS SPPGTPSPAD 250 260 270 280 290 300 AKAPPTACYA GAAPAPSQVK SKAKKTVDKH SDEYKIRRER NNIAVRKSRD KAKMRNLETQ 310 320 330 340 HKVLELTAEN ERLQKKVEQL SRELSTLRNL FKQLPEPLLA SSGHC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family." Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. EMBO J. 9:1897-1906(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[2]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	SeattleSNPs variation discovery resource Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-195.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle and Skin.
[8]	"Identification of a transcriptional regulatory factor for human aromatase cytochrome P450 gene expression as nuclear factor interleukin-6 (NF-IL6), a member of the CCAAT/enhancer-binding protein family." Toda K., Akira S., Kishimoto T., Sasaki H., Hashimoto K., Yamamoto Y., Sagara Y., Shizuta Y. Eur. J. Biochem. 231:292-299(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 241-323.
[9]	"C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival." Buck M., Poli V., Hunter T., Chojkier M. Mol. Cell 8:807-816(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-235.
[10]	"Modification of CCAAT/enhancer-binding protein-beta by the small ubiquitin-like modifier (SUMO) family members, SUMO-2 and SUMO-3." Eaton E.M., Sealy L. J. Biol. Chem. 278:33416-33421(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-174.
[11]	"Nine-amino-acid transactivation domain: establishment and prediction utilities." Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M. Genomics 89:756-768(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN.
[12]	"Endoplasmic reticulum stress-activated C/EBP homologous protein enhances nuclear factor-kappaB signals via repression of peroxisome proliferator-activated receptor gamma." Park S.H., Choi H.J., Yang H., Do K.H., Kim J., Lee D.W., Moon Y. J. Biol. Chem. 285:35330-35339(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DDIT3, SUBCELLULAR LOCATION, INDUCTION.
[13]	"Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta." Tahirov T.H., Inoue-Bungo T., Morii H., Fujikawa A., Sasaki M., Kimura K., Shiina M., Sato K., Kumasaka T., Yamamoto M., Ishii S., Ogata K. Cell 104:755-767(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 259-336 IN COMPLEX WITH RUNX1; CBFB AND DNA.
[14]	"Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter." Tahirov T.H., Sato K., Ichikawa-Iwata E., Sasaki M., Inoue-Bungo T., Shiina M., Kimura K., Takata S., Fujikawa A., Morii H., Kumasaka T., Yamamoto M., Ishii S., Ogata K. Cell 108:57-70(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 259-345 IN COMPLEX WITH MOUSE MYB.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52560 Genomic DNA. Translation: CAA36794.1.
AF289608 mRNA. Translation: AAL55792.1.
AY193834 Genomic DNA. Translation: AAN86350.1.
AK291536 mRNA. Translation: BAF84225.1.
AL161937 Genomic DNA. Translation: CAC14276.1.
CH471077 Genomic DNA. Translation: EAW75629.1.
BC007538 mRNA. Translation: AAH07538.1.
BC021931 mRNA. Translation: AAH21931.1.

IPI

IPI00289773.

PIR

S12788.
S66246.

RefSeq

NP_005185.2. NM_005194.3.

UniGene

Hs.517106.
Hs.719041.
Hs.720603.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GTW	X-ray	1.85	A/B	259-336	[»]
1GU4	X-ray	1.80	A/B	259-336	[»]
1GU5	X-ray	2.10	A/B	259-336	[»]
1H88	X-ray	2.80	A/B	259-336	[»]
1H89	X-ray	2.45	A/B	273-336	[»]
1H8A	X-ray	2.23	A/B	259-336	[»]
1HJB	X-ray	3.00	A/B/D/E	259-345	[»]
1IO4	X-ray	3.00	A/B	259-336	[»]
2E42	X-ray	1.80	A/B	259-336	[»]
2E43	X-ray	2.10	A/B	259-336	[»]

ProteinModelPortal

P17676.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35345N.

IntAct

P17676. 3 interactions.

MINT

MINT-230873.

STRING

9606.ENSP00000305422.

PTM databases

PhosphoSite

P17676.

Polymorphism databases

DMDM

34223718.

Proteomic databases

PaxDb

P17676.

PeptideAtlas

P17676.

PRIDE

P17676.

Protocols and materials databases

DNASU

1051.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000303004; ENSP00000305422; ENSG00000172216.

GeneID

1051.

KEGG

hsa:1051.

UCSC

uc002xvi.2. human.

Organism-specific databases

CTD

1051.

GeneCards

GC20P048807.

H-InvDB

HIX0174729.

HGNC

HGNC:1834. CEBPB.

HPA

CAB004213.

MIM

189965. gene.

neXtProt

NX_P17676.

PharmGKB

PA26377.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG299311.

HOGENOM

HOG000013112.

HOVERGEN

HBG050879.

InParanoid

P17676.

KO

K10048.

OMA

CKKPAEY.

OrthoDB

EOG4M65JR.

PhylomeDB

P17676.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3apathway. FOXA1 transcription factor network.
hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
ifngpathway. IFN-gamma pathway.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

P17676.

Bgee

P17676.

CleanEx

HS_CEBPB.

Genevestigator

P17676.

GermOnline

ENSG00000172216. Homo sapiens.

Family and domain databases

InterPro

IPR004827. bZIP.
IPR016468. CCAAT/enhancer-binding.
[Graphical view]

Pfam

PF07716. bZIP_2. 1 hit.
[Graphical view]

PIRSF

PIRSF005879. CCAAT/enhancer-binding. 1 hit.

SMART

SM00338. BRLZ. 1 hit.
[Graphical view]

PROSITE

PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P17676.

GenomeRNAi

1051.

NextBio

4401.

SOURCE

Search...

Entry information

Entry name

CEBPB_HUMAN

Accession

Primary (citable) accession number: P17676
Secondary accession number(s): A8K671, Q96IH2, Q9H4Z5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 22, 2003
Last modified:	May 1, 2013
This is version 152 of the entry and version 2 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.