CEBPB

Summary

CEBPB (CCAAT enhancer binding protein beta, HGNC:1834) is a protein-coding gene on chromosome 20q13.13, encoding CCAAT/enhancer-binding protein beta (P17676). Important transcription factor regulating the expression of genes involved in immune and inflammatory responses.

This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain. The encoded protein functions as a homodimer but can also form heterodimers with CCAAT/enhancer-binding proteins alpha, delta, and gamma. Activity of this protein is important in the regulation of genes involved in immune and inflammatory responses, among other processes. The use of alternative in-frame AUG start codons results in multiple protein isoforms, each with distinct biological functions.

Source: NCBI Gene 1051 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 48 total
• Transcription factor: yes — 469 downstream targets (CollecTRI)
• MANE Select transcript: NM_005194

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1834
Approved symbol	CEBPB
Name	CCAAT enhancer binding protein beta
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	LAP, CRP2, NFIL6, IL6DBP, C/EBP-beta
Ensembl gene	ENSG00000172216
Ensembl biotype	protein_coding
OMIM	189965
Entrez	1051

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000303004, ENST00000718336

RefSeq mRNA: 3 — MANE Select: NM_005194 NM_001285878, NM_001285879, NM_005194

CCDS: CCDS13429

Canonical transcript exons

ENST00000303004 — 1 exons

Exon	Start	End
ENSE00004034812	50190830	50192668

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 205.0277 / max 6576.2984, expressed in 1826 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185208	162.8662	1819
185216	26.0654	1809
185207	2.2396	1012
185210	2.1682	844
185218	1.9128	1056
185205	1.6505	1067
185213	1.5648	697
185214	1.0832	561
185209	1.0719	516
185215	1.0600	645

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.84	gold quality
pericardium	UBERON:0002407	99.67	gold quality
periodontal ligament	UBERON:0008266	99.55	gold quality
vena cava	UBERON:0004087	99.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.34	gold quality
nipple	UBERON:0002030	99.32	gold quality
mammary duct	UBERON:0001765	99.31	gold quality
upper leg skin	UBERON:0004262	99.27	gold quality
tibialis anterior	UBERON:0001385	99.25	gold quality
upper arm skin	UBERON:0004263	99.24	gold quality
mammalian vulva	UBERON:0000997	99.23	gold quality
trachea	UBERON:0003126	99.23	gold quality
cartilage tissue	UBERON:0002418	99.20	gold quality
decidua	UBERON:0002450	99.16	gold quality
palpebral conjunctiva	UBERON:0001812	99.15	gold quality
nasal cavity epithelium	UBERON:0005384	99.08	gold quality
epithelium of mammary gland	UBERON:0003244	99.06	gold quality
mucosa of urinary bladder	UBERON:0001259	99.00	gold quality
epithelium of bronchus	UBERON:0002031	98.97	gold quality
bronchus	UBERON:0002185	98.97	gold quality
body of tongue	UBERON:0011876	98.94	gold quality
quadriceps femoris	UBERON:0001377	98.93	gold quality
bronchial epithelial cell	CL:0002328	98.91	gold quality
caput epididymis	UBERON:0004358	98.91	gold quality
cauda epididymis	UBERON:0004360	98.90	gold quality
diaphragm	UBERON:0001103	98.85	gold quality
vastus lateralis	UBERON:0001379	98.85	gold quality
skin of hip	UBERON:0001554	98.84	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.80	gold quality
blood	UBERON:0000178	98.77	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	192.02
E-HCAD-1	yes	96.54
E-CURD-122	yes	66.01
E-GEOD-135922	yes	47.07
E-MTAB-9221	yes	33.78
E-CURD-46	yes	29.92
E-CURD-88	yes	19.44
E-MTAB-9467	yes	18.87
E-MTAB-8498	yes	10.20
E-GEOD-134144	yes	8.64
E-MTAB-10553	yes	6.59
E-MTAB-9801	yes	4.68
E-GEOD-149689	no	2850.12
E-HCAD-11	no	887.77
E-MTAB-10287	no	39.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

469 targets.

Target	Regulation
A2M
ABCB1	Activation
ABCC2	Activation
ABCC3
ABCC8
ACACA
ACHE
ACTA2
ACTG2
ADAM2
ADAMTS5	Activation
ADH1A	Activation
ADH1B	Activation
ADH1C	Activation
ADIPOQ
ADM	Activation
ADRA1D
AFP	Unknown
AKR1A1
AKT1
ALB	Unknown
ALDH1A1	Activation
ALDH2
ALK
ALOX5AP
AMELX
ANXA5
AP1	Unknown
AP3B1
APCS	Unknown

JASPAR motifs

Motif	Name	Family
MA0466.1	CEBPB	CEBP-related
MA0466.2	CEBPB	CEBP-related
MA0466.3	CEBPB	CEBP-related
MA0466.4	CEBPB	CEBP-related

JASPAR matrix evidence (PMIDs): PMID:8380454, PMID:8632009

Upstream regulators (CollecTRI, top): ATF1, ATF2, ATF4, ATF5, CEBPA, CEBPB, CEBPD, CREB1, DDIT3, EGR1, EGR2, ESR1, FLT3, FOS, FOSL2, FOXO1, GATA2, GATA4, GLI2, IRF6, JUN, KLF4, KLF9, MYB, NR3C1, PAWR, PDX1, PPARD, SMARCA1, SOX9, SREBF1, STAT3

miRNA regulators (miRDB)

44 targeting CEBPB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-410-3P	99.27	69.98	2457

Literature-anchored findings (GeneRIF, showing 40)

• mutational studies of the rat and chick orthologs demonstrating alternative translational initiation (PMID:10921906)
• mutational studies of mouse ortholog demonstrating alternative translational initiation (PMID:11452034)
• The activities of several functional C/EBPbeta responsive elements in the promoter region and in the intron of CCR5 suggest regulatory roles for C/EBPbeta in CCR5 gene expression and in the pathogenesis of HIV disease. (PMID:11466389)
• These findings provide new insight into the regulation of cyclooxygenase-2 promoter by an interplay between two opposite beta isoforms and p300 co-activator. (PMID:11741938)
• PGE(2) induces HIV-1 LTR activity in t cells through a complex interplay between C/EBPbeta and CREB (PMID:11751971)
• CCAAT/enhancer binding protein-beta is a mediator ofkeratinocyte survival and skin tumorigenesis involving oncogenic Ras signaling. (PMID:11756662)
• C/EBP beta binding to the C/EBP site, which is in part mediated via activation of RSK, can primarily explain the TPA responsiveness of the IGF-I gene promoter (PMID:11825899)
• cooperation with cyclic AMP-induced forkhead transcription factor in differentiating human endometrial stromal cells (PMID:11893744)
• Conserved amino acids regulationregulate phosphoenolpyruvate carboxykinase (PEPCK) gene expression. (PMID:11997389)
• Conditional expression of C/EBP alpha induced the C/EBP family members C/EBP beta and C/EBP epsilon and subsequent granulocyte differentiation. (PMID:12036869)
• Decreased activity and enhanced nuclear export of CCAAT-enhancer-binding protein beta during inhibition of adipogenesis by ceramide. (PMID:12071851)
• Organization of the promoter regions involved in transcriptional activation of the human NF-IL6 gene (PMID:12151100)
• both phosphorylation and dephosphorylation of C/EBPbeta in response to growth hormone coordinately modulate its ability to activate transcription by modulating its DNA binding activity and its transactivation capacity (PMID:12213825)
• Calreticulin interacts with C/EBPalpha and C/EBPbeta mRNAs and represses translation of C/EBP proteins. (PMID:12242300)
• Regulates HIV-1 transcription in activated Jurkat T cells (PMID:12367750)
• IL-1 induces CRP expression through 2 overlapping response elements, the binding sites for CCAAT-box/enhancer-binding protein-beta (C/EBP-beta) and p50-nuclear factor-kappaB (p50-NFkappaB). (PMID:12393563)
• 5’-region from -252 to -175, containing a consensus site for CCAAT/enhancer binding proteins alpha,beta (C/EBPalpha,beta), was essential for SAA1 induction in HASMCs. (PMID:12410800)
• IRF-1-CEBPbeta complex activate the promoter of IL-18 binding protein. (PMID:12482935)
• the level of basal as well as cAMP-stimulated IL-10 transcription depends on the expression of C/EBP alpha and beta and their binding to three motifs in the promoter/enhancer region (PMID:12493739)
• A C/EBP beta element in the FasL promoter, identified by a functionally significant single-nucleotide polymorphism, affects FasL expression in vitro and ex vivo and is associated with systemic lupus erythematosus in African American patients. (PMID:12496392)
• MEK2 and p38 in IFN-gamma-mediated signal transduction and induction of C/EBP beta expression and activity associated with interleukin-6 (IL-6) secretion in colon epithelial cells. (PMID:12505790)
• Positively functioning NF-IL6 (C/EBPbeta)is not constitutively multiubiquinated by the proteasome. Deletion of leucine zipper domain in NF-IL6 caused the loss of its homodimerization activity & its degradation by the ubiquitin-proteasome system. (PMID:12618752)
• C/EBP-beta may have a role in promoting tumor invasiveness (PMID:12631601)
• HMGI-Y physically interacts with Sp1 and C/EBP beta and facilitates the binding of both factors to the insulin receptor promoter (PMID:12665574)
• There are high levels of FGF-BP expression in invasive human breast cancer, relative to normal breast and in situ carcinoma, and in MDA-MB-468 human breast cancer cells. (PMID:12670924)
• Papillomavirus E2 protein binds to C/EBP factors and may contribute to enhancing keratinocyte differentiation, which is suppressed by the viral oncoproteins E6 and E7 in HPV-induced lesions (PMID:12692227)
• Pretreatment of monocytic cells with low TNF doses inhibited TNF-induced (restimulation with a high dose) IL-8 promoter-dependent transcription as well as IL-8 production, which was prevented by overexpression of C/EBPbeta, but not p65 or Oct-1. (PMID:12707271)
• transcriptional activation of the interleukin-8 promoter by bradykinin involves the prostanoid-independent activation of nuclear factor-kappaB, and prostanoid-dependent activation of activating protein-1 and nuclear factor-interleukin-6 (PMID:12748173)
• Expression levels of C/EBPbeta isoforms in breast tumors were correlated with clinicopathological tumor parameters, expression of estrogen and progesterone receptors (ER, PR), Ki67 immunostaining, and expression of 7 cell-cycle regulatory proteins. (PMID:12825852)
• These results suggest that CSF-induced and HIV-1-mediated regulation of Hck and C/EBPbeta represent the heterogeneous susceptibility of tissue macrophages to HIV-1 infection. (PMID:12900520)
• study provides strong evidence that early growth response 1 regulates low density lipoprotein receptor transcription via a novel mechanism of protein-protein interaction with CCAAT enhancer-binding protein beta (PMID:12947119)
• We conclude that C/EBPalpha and C/EBPbeta contribute to the deregulated expression of Bcl-2 in t(14;18) lymphoma cells (PMID:12970736)
• isoform LAP* is the primary isoform of C/EBP beta that regulates, through a redox switch, the LPS-induced expression of the IL-6 gene. (PMID:14530280)
• Overexpression of C/EBP beta was sufficient to increase basal expression of a Dlx3 reporter gene in a dose-dependent manner. (PMID:14670999)
• Transfection of NF-IL63’UTR nduced tumor suppression in a human hepatoma cell line. (PMID:14728809)
• Calcitrio may signal cell differentiation of HL 60 cells which in turn regulates expresson of CEBPB (PMID:14729647)
• Ras-induced structural alteration of C/EBPbeta determines differential gene activation through selective interaction with distinct Mediator complexes (PMID:14759369)
• CEBPbeta could be an important gene in acute promyelocytic leukemia pathogenesis (PMID:14976428)
• mechanisms of MDR1 activation by C/EBPbeta include C/EBPbeta binding of the chromatin of the MDR1 gene and interactions of C/EBPbeta with the Y box and Y box-associated proteins. (PMID:15044620)
• Data show that epidermal growth factor receptor signaling results in phosphorylation of CUG-BP1, and leads to increased binding of CUG-BP1 to CCAAT/enhancer binding protein beta (C/EBP beta) mRNA and elevated expression of the C/EBPbeta LIP isoform. (PMID:15082764)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cebpb	ENSDARG00000042725
mus_musculus	Cebpb	ENSMUSG00000056501
rattus_norvegicus	Cebpb	ENSRNOG00000078148
drosophila_melanogaster	slbo	FBGN0005638
caenorhabditis_elegans		WBGENE00016997
caenorhabditis_elegans	zip-4	WBGENE00021552

Paralogs (4): CEBPE (ENSG00000092067), CEBPG (ENSG00000153879), CEBPD (ENSG00000221869), CEBPA (ENSG00000245848)

Protein

Protein identifiers

CCAAT/enhancer-binding protein beta — P17676 (reviewed: P17676)

Alternative names: Liver activator protein, Liver-enriched inhibitory protein, Nuclear factor NF-IL6, Transcription factor 5

All UniProt accessions (1): P17676

UniProt curated annotations — full annotation on UniProt →

Function. Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5’-T[TG]NNGNAA[TG]-3’. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant roles with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage. Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Also plays a role in intracellular bacteria killing. During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation. Essential for female reproduction because of a critical role in ovarian follicle development. Restricts osteoclastogenesis: together with NFE2L1; represses expression of DSPP during odontoblast differentiation. Essential for gene expression induction in activated macrophages. Plays a major role in immune responses such as CD4(+) T-cell response, granuloma formation and endotoxin shock. Not essential for intracellular bacteria killing. Acts as a dominant negative through heterodimerization with isoform 2. Promotes osteoblast differentiation and osteoclastogenesis.

Subunit / interactions. Binds DNA as a homodimer and as a heterodimer. Interacts with ATF4. Binds DNA as a heterodimer with ATF4. Interacts with MYB; within the complex, MYB and CEBPB bind to different promoter regions. Can form stable heterodimers with CEBPD. Can form stable heterodimers with CEBPA and CEBPE. Interacts with SIX1. Isoform 2 and isoform 3 also form heterodimers. Interacts with TRIM28 and PTGES2. Interacts with PRDM16. Interacts with CCDC85B. Forms a complex with THOC5. Interacts with ZNF638; this interaction increases transcriptional activation. Interacts with CIDEA and CIDEC; these interactions increase transcriptional activation of a subset of CEBPB downstream target genes. Interacts with DDIT3/CHOP. Interacts with EP300; recruits EP300 to chromatin. Interacts with RORA; the interaction disrupts interaction with EP300. Interacts (not methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1. Interacts with KAT2A and KAT2B. Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding. Interacts with NFE2L1; the heterodimer represses expression of DSPP during odontoblast differentiation.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed at low levels in the lung, kidney and spleen.

Post-translational modifications. Methylated. Methylation at Arg-3 by CARM1 and at Lys-43 by EHMT2 inhibit transactivation activity. Methylation is probably inhibited by phosphorylation at Thr-235. Sumoylated by polymeric chains of SUMO2 or SUMO3. Sumoylation at Lys-174 is required for inhibition of T-cells proliferation. In adipocytes, sumoylation at Lys-174 by PIAS1 leads to ubiquitination and subsequent proteasomal degradation. Desumoylated by SENP2, which abolishes ubiquitination and stabilizes protein levels. Ubiquitinated, leading to proteasomal degradation. Phosphorylated at Thr-235 by MAPK and CDK2, serves to prime phosphorylation at Thr-226 and Ser-231 by GSK3B and acquire DNA-binding as well as transactivation activities, required to induce adipogenesis. MAPK and CDK2 act sequentially to maintain Thr-235 in the primed phosphorylated state during mitotical cloning expansion and thereby progression of terminal differentiation. Phosphorylation at Thr-266 enhances transactivation activity. Phosphorylation at Ser-325 in response to calcium increases transactivation activity. Phosphorylated at Thr-235 by RPS6KA1. O-glycosylated, glycosylation at Ser-227 and Ser-228 prevents phosphorylation on Thr-235, Ser-231 and Thr-226 and DNA binding activity which delays the adipocyte differentiation program. Acetylated. Acetylation at Lys-43 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function. Deacetylation by HDAC1 represses its transactivation activity. Acetylated by KAT2A and KAT2B within a cluster of lysine residues between amino acids 129-133, this acetylation is strongly induced by glucocorticoid treatment and enhances transactivation activity.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Induction. By ER stress.

Similarity. Belongs to the bZIP family. C/EBP subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P17676-1	1, C/EBPbeta-FL	yes
P17676-2	2, C/EBPbeta-LAP
P17676-3	3, C/EBPbeta-LIP

RefSeq proteins (3): NP_001272807, NP_001272808, NP_005185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR016468	C/EBP_chordates	Family
IPR031106	C/EBP	Family
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF07716

UniProt features (47 total): modified residue 12, region of interest 8, cross-link 8, compositionally biased region 4, glycosylation site 2, splice variant 2, mutagenesis site 2, sequence conflict 2, chain 1, domain 1, short sequence motif 1, sequence variant 1, strand 1, helix 1, turn 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
6MG1	X-RAY DIFFRACTION	1.75
7L4V	X-RAY DIFFRACTION	1.75
1GU4	X-RAY DIFFRACTION	1.8
2E42	X-RAY DIFFRACTION	1.8
1GTW	X-RAY DIFFRACTION	1.85
6MG2	X-RAY DIFFRACTION	1.93
6MG3	X-RAY DIFFRACTION	2.05
1GU5	X-RAY DIFFRACTION	2.1
2E43	X-RAY DIFFRACTION	2.1
8K8D	X-RAY DIFFRACTION	2.2
1H8A	X-RAY DIFFRACTION	2.23
1H89	X-RAY DIFFRACTION	2.45
7UPZ	X-RAY DIFFRACTION	2.49
1H88	X-RAY DIFFRACTION	2.8
1HJB	X-RAY DIFFRACTION	3
1IO4	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17676-F1	61.55	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (20): 3, 43, 43, 129, 132, 133, 226, 231, 235, 266, 288, 325, 133, 174, 174, 185, 187, 260, 262, 332

Glycosylation sites (2): 227, 228

Mutagenesis-validated functional residues (2):

Position	Phenotype
235	loss of transactivation activity in response to ifng.
288	loss of nuclear translocation.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648895	Response of EIF2AK1 (HRI) to heme deficiency
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer
R-HSA-1266738	Developmental Biology
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-381042	PERK regulates gene expression
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9700206	Signaling by ALK in cancer
R-HSA-9711097	Cellular response to starvation
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 601 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION

GO Biological Process (49): negative regulation of transcription by RNA polymerase II (GO:0000122), ovarian follicle development (GO:0001541), embryonic placenta development (GO:0001892), granuloma formation (GO:0002432), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), acute-phase response (GO:0006953), inflammatory response (GO:0006954), immune response (GO:0006955), memory (GO:0007613), neuron differentiation (GO:0030182), regulation of interleukin-6 production (GO:0032675), positive regulation of interleukin-4 production (GO:0032753), mammary gland epithelial cell proliferation (GO:0033598), response to endoplasmic reticulum stress (GO:0034976), T-helper 1 cell activation (GO:0035711), negative regulation of T cell proliferation (GO:0042130), defense response to bacterium (GO:0042742), negative regulation of neuron apoptotic process (GO:0043524), regulation of cell differentiation (GO:0045595), positive regulation of fat cell differentiation (GO:0045600), positive regulation of osteoblast differentiation (GO:0045669), regulation of osteoclast differentiation (GO:0045670), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of inflammatory response (GO:0050729), brown fat cell differentiation (GO:0050873), mammary gland epithelial cell differentiation (GO:0060644), myeloid cell development (GO:0061515), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), positive regulation of biomineral tissue development (GO:0070169), cellular response to lipopolysaccharide (GO:0071222), cellular response to amino acid stimulus (GO:0071230), cellular response to interleukin-1 (GO:0071347), hepatocyte proliferation (GO:0072574), liver regeneration (GO:0097421), positive regulation of cold-induced thermogenesis (GO:0120162), integrated stress response signaling (GO:0140467), regulation of odontoblast differentiation (GO:1901329)

GO Molecular Function (24): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), kinase binding (GO:0019900), chromatin DNA binding (GO:0031490), histone acetyltransferase binding (GO:0035035), nuclear glucocorticoid receptor binding (GO:0035259), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), ubiquitin-like protein ligase binding (GO:0044389), protein heterodimerization activity (GO:0046982), sequence-specific double-stranded DNA binding (GO:1990837), chromatin binding (GO:0003682), protein binding (GO:0005515), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA-binding transcription factor binding (GO:0140297)

GO Cellular Component (9): condensed chromosome, centromeric region (GO:0000779), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear matrix (GO:0016363), CHOP-C/EBP complex (GO:0036488), RNA polymerase II transcription regulator complex (GO:0090575), C/EBP complex (GO:1990647)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cellular responses to stress	3
Cellular Senescence	1
PERK regulates gene expression	1
Adipogenesis	1
Generic Transcription Pathway	1
Developmental Biology	1
Cellular response to starvation	1
Signaling by ALK fusions and activated point mutants	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Disease	1
Gene expression (Transcription)	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	5
enzyme binding	4
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
defense response	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
protein dimerization activity	2
binding	2
nuclear lumen	2
RNA polymerase II transcription regulator complex	2
negative regulation of DNA-templated transcription	1
female gonad development	1
anatomical structure development	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
immune effector process	1
chronic inflammatory response	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
acute inflammatory response	1
immune system process	1
response to stimulus	1
learning or memory	1
cell differentiation	1
generation of neurons	1
regulation of cytokine production	1
interleukin-6 production	1
positive regulation of cytokine production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
epithelial cell proliferation	1
mammary gland epithelium development	1
cellular response to stress	1
CD4-positive, alpha-beta T cell activation	1
T cell proliferation	1

Protein interactions and networks

STRING

4652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEBPB	PRDM16	Q9HAZ2	995
CEBPB	HDAC1	Q13547	981
CEBPB	EP300	Q09472	976
CEBPB	CEBPD	P49716	965
CEBPB	DDIT3	P35638	944
CEBPB	CEBPA	P49715	942
CEBPB	RUNX2	Q13950	940
CEBPB	ATF6	P18850	927
CEBPB	PPARG	P37231	924
CEBPB	FOXO1	Q12778	922
CEBPB	STAT3	P40763	920
CEBPB	SMAD3	P84022	919
CEBPB	PPARGC1A	Q9UBK2	910
CEBPB	JUN	P05412	900
CEBPB	CREB1	P16220	900

IntAct

120 interactions, top by confidence:

A	B	Type	Score
RELA		psi-mi:“MI:0914”(association)	0.790
SMAD4	CEBPB	psi-mi:“MI:0915”(physical association)	0.610
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
CEBPB	SMAD4	psi-mi:“MI:0407”(direct interaction)	0.610
E2	CEBPB	psi-mi:“MI:0915”(physical association)	0.600
E2	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.600
CEBPB	E2	psi-mi:“MI:0407”(direct interaction)	0.600
CEBPB	CEBPA	psi-mi:“MI:0407”(direct interaction)	0.590
CEBPA	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.590
CEBPD	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.590
DDIT3	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.590
ATF3	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.590
CEBPB	DDIT3	psi-mi:“MI:0407”(direct interaction)	0.590
CEBPB	ESR1	psi-mi:“MI:0407”(direct interaction)	0.590
TP53	CEBPB	psi-mi:“MI:0915”(physical association)	0.560
CEBPB	TP53	psi-mi:“MI:0403”(colocalization)	0.560
HMGA1	CEBPB	psi-mi:“MI:0915”(physical association)	0.540
CEBPB	HMGA1	psi-mi:“MI:0407”(direct interaction)	0.540
CEBPB	E2	psi-mi:“MI:0915”(physical association)	0.540
E2	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.540
CEBPB	E2	psi-mi:“MI:0407”(direct interaction)	0.540

BioGRID (1572): CEBPB (Reconstituted Complex), CEBPB (Affinity Capture-MS), CEBPB (Affinity Capture-Western), CEBPB (Affinity Capture-Western), KLF5 (Two-hybrid), CEBPB (Affinity Capture-Western), KLF5 (Affinity Capture-Western), CEBPB (Affinity Capture-MS), EP300 (Affinity Capture-Western), CEBPB (Affinity Capture-RNA), ZC3H12A (Protein-RNA), CEBPB (Affinity Capture-RNA), CEBPB (Affinity Capture-RNA), CEBPB (Affinity Capture-MS), MED23 (Affinity Capture-Western)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

Diamond homologs: O02754, O02755, O02756, O77728, P05554, P17676, P21272, P26801, P28033, P49715, P49716, P53566, P53567, P53568, P56261, Q00322, Q02638, Q03484, Q05826, Q15744, Q3T0B9, Q6PZD9, Q9N0J3, Q8IG69, Q02637

SIGNOR signaling

68 interactions.

A	Effect	B	Mechanism
dexamethasone	up-regulates	CEBPB
3-isobutyl-1-methylxanthine	up-regulates	CEBPB
EGR2	“up-regulates quantity by expression”	CEBPB	“transcriptional regulation”
CDK2	up-regulates	CEBPB	phosphorylation
GSK3B	up-regulates	CEBPB	phosphorylation
SOX9	“down-regulates quantity by repression”	CEBPB	“transcriptional regulation”
MAPK3	up-regulates	CEBPB	phosphorylation
ABL1	up-regulates	CEBPB	phosphorylation
ABL2	up-regulates	CEBPB	phosphorylation
MAPK1	up-regulates	CEBPB	phosphorylation
3-isobutyl-1-methyl-7H-xanthine	up-regulates	CEBPB
SOX9	down-regulates	CEBPB	“transcriptional regulation”
CyclinA2/CDK2	up-regulates	CEBPB	phosphorylation
ERK1/2	“up-regulates activity”	CEBPB	phosphorylation
SMAD3/SMAD4	“down-regulates activity”	CEBPB	“transcriptional regulation”
SMAD1/4	“up-regulates activity”	CEBPB	binding
CEBPB	“up-regulates quantity by expression”	ABCB1	“transcriptional regulation”
CEBPB	“down-regulates quantity by repression”	GFER	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	PCK2	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	S100A9	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	SFTPD	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	CSRP1	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	GDF15	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	SLC19A1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Response of EIF2AK1 (HRI) to heme deficiency	5	87.0×	4e-07
Adipogenesis	5	19.1×	3e-04
Signaling by Interleukins	10	15.7×	2e-07
Interleukin-4 and Interleukin-13 signaling	6	15.1×	2e-04
Response of EIF2AK4 (GCN2) to amino acid deficiency	5	13.5×	8e-04
Cytokine Signaling in Immune system	10	9.9×	5e-06
Chromatin organization	5	9.9×	1e-03
Chromatin modifying enzymes	5	8.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	8	117.0×	7e-13
positive regulation of miRNA transcription	7	42.4×	4e-08
positive regulation of neuron apoptotic process	5	28.3×	5e-05
liver development	6	27.7×	6e-06
transforming growth factor beta receptor signaling pathway	5	16.6×	6e-04
positive regulation of gene expression	11	8.9×	3e-06
negative regulation of cell population proliferation	10	8.8×	1e-05
chromatin remodeling	5	7.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

48 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

116 predictions. Top by Δscore:

Variant	Effect	Δscore
20:50192024:TTC:T	donor_gain	0.8800
20:50192202:GCCC:G	donor_gain	0.8500
20:50192210:G:GG	donor_gain	0.8300
20:50192033:C:G	donor_gain	0.8200
20:50192206:GTCG:G	donor_gain	0.8200
20:50192003:C:G	donor_gain	0.8100
20:50192355:T:TA	acceptor_gain	0.8100
20:50192205:CGTCG:C	donor_loss	0.8000
20:50192207:TCGG:T	donor_loss	0.8000
20:50192210:GTA:G	donor_loss	0.8000
20:50192211:T:G	donor_loss	0.8000
20:50192362:CTCCA:C	acceptor_loss	0.7900
20:50192363:TCCA:T	acceptor_loss	0.7900
20:50192364:CCAGG:C	acceptor_loss	0.7900
20:50192365:CAGG:C	acceptor_loss	0.7900
20:50192366:A:AG	acceptor_gain	0.7900
20:50192366:A:C	acceptor_loss	0.7900
20:50192367:G:GG	acceptor_gain	0.7900
20:50192212:A:C	donor_loss	0.7300
20:50192367:GGC:G	acceptor_gain	0.7000
20:50192017:G:GT	donor_gain	0.6900
20:50191983:TG:T	donor_gain	0.6800
20:50191984:GG:G	donor_gain	0.6800
20:50192387:TTTCG:T	acceptor_loss	0.6800
20:50191941:TCCTG:T	donor_gain	0.6200
20:50191978:G:GT	donor_gain	0.6100
20:50192018:A:T	donor_gain	0.6100
20:50191985:GA:G	donor_gain	0.6000
20:50192205:C:G	donor_gain	0.6000
20:50192199:G:GT	donor_gain	0.5200

AlphaMissense

2218 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:50191251:T:A	I73N	1.000
20:50191844:A:C	S271R	1.000
20:50191846:C:A	S271R	1.000
20:50191846:C:G	S271R	1.000
20:50191853:T:C	Y274H	1.000
20:50191853:T:G	Y274D	1.000
20:50191854:A:C	Y274S	1.000
20:50191854:A:G	Y274C	1.000
20:50191862:C:G	R277G	1.000
20:50191863:G:C	R277P	1.000
20:50191865:C:A	R278S	1.000
20:50191865:C:G	R278G	1.000
20:50191865:C:T	R278C	1.000
20:50191866:G:A	R278H	1.000
20:50191866:G:C	R278P	1.000
20:50191866:G:T	R278L	1.000
20:50191871:C:A	R280S	1.000
20:50191871:C:T	R280C	1.000
20:50191872:G:C	R280P	1.000
20:50191874:A:C	N281H	1.000
20:50191874:A:G	N281D	1.000
20:50191875:A:C	N281T	1.000
20:50191875:A:G	N281S	1.000
20:50191875:A:T	N281I	1.000
20:50191876:C:A	N281K	1.000
20:50191876:C:G	N281K	1.000
20:50191877:A:C	N282H	1.000
20:50191877:A:G	N282D	1.000
20:50191878:A:C	N282T	1.000
20:50191878:A:T	N282I	1.000

dbSNP variants (sampled 300 via entrez): RS1000008468 (20:50191091 G>T), RS1000467250 (20:50190593 G>A,C,T), RS1001174583 (20:50192700 G>T), RS1001637314 (20:50189920 T>A,G), RS1001870613 (20:50189604 C>T), RS1002087980 (20:50190108 C>A), RS1004430008 (20:50188801 C>T), RS1004713578 (20:50189880 T>C), RS1006695163 (20:50192998 A>C,G), RS1006987847 (20:50190279 C>T), RS1007209716 (20:50189287 C>G,T), RS1007262958 (20:50190117 G>C), RS1007707663 (20:50192255 A>C), RS1007935912 (20:50188877 C>G), RS1008404302 (20:50189257 A>C)

Disease associations

OMIM: gene MIM:189965 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001725_66	Inflammatory bowel disease	5.000000e-08
GCST002796_1	Bronchodilator response in asthma	2.000000e-10
GCST003854_1	Gut microbiota (functional units)	3.000000e-09
GCST003854_28	Gut microbiota (functional units)	1.000000e-08
GCST007367_3	Meconium ileus in cystic fibrosis	5.000000e-07
GCST007847_71	Type 2 diabetes	4.000000e-06
GCST009379_299	Type 2 diabetes	2.000000e-11
GCST010118_78	Type 2 diabetes	2.000000e-14
GCST90016675_5	Pancreas fat	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

227 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases activity, increases expression, increases reaction, affects localization (+2 more)	10
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
bisphenol A	decreases expression, affects cotreatment, affects expression, increases expression	6
Arsenic Trioxide	decreases methylation, increases expression, affects cotreatment, affects binding, decreases reaction (+1 more)	6
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	5
Tunicamycin	increases expression	5
trichostatin A	affects cotreatment, increases expression, decreases reaction	4
sodium arsenite	increases expression, affects activity, affects expression, affects cotreatment, increases abundance	4
Benzo(a)pyrene	increases expression, increases methylation, decreases expression	4
Calcitriol	decreases reaction, increases expression, increases reaction, affects localization, affects reaction (+1 more)	4
Ozone	increases abundance, affects cotreatment, increases expression, increases activity, affects expression	4
Quercetin	increases localization, affects cotreatment, affects binding, decreases reaction, increases expression	4
Arsenic	decreases expression, increases abundance, increases reaction, increases expression, affects cotreatment (+2 more)	3
Vehicle Emissions	affects expression, increases reaction, increases expression, affects cotreatment, decreases expression	3
Cisplatin	affects expression, increases expression, increases reaction	3
Doxorubicin	increases expression, increases reaction, increases response to substance, affects cotreatment, affects localization	3
Estradiol	affects reaction, increases expression, affects cotreatment, affects binding, increases reaction	3
Fluorouracil	increases expression	3
Silicon Dioxide	decreases expression, increases expression	3
Tamoxifen	affects expression, affects cotreatment, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	increases activity, increases expression	3
Cyclosporine	increases expression	3
Thapsigargin	affects binding, increases reaction, increases expression	3
Raloxifene Hydrochloride	decreases expression, increases expression, affects expression, affects cotreatment	3
cobaltous chloride	decreases expression, increases expression	2
sulindac sulfide	increases expression	2
ochratoxin A	decreases expression	2
S-(1,2-dichlorovinyl)cysteine	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2

Cellosaurus cell lines

14 cell lines: 11 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0P3	SEES3-1V human CEBPB, clone1	Embryonic stem cell	Male
CVCL_A0P4	SEES3-1V human CEBPB, clone2	Embryonic stem cell	Male
CVCL_A0P5	SEES3-1V human CEBPB, clone3	Embryonic stem cell	Male
CVCL_AW15	K562 eGFP-CEBPB	Cancer cell line	Female
CVCL_B1N9	Abcam HeLa CEBPB KO	Cancer cell line	Female
CVCL_D3XF	HepG2/8F_HS	Cancer cell line	Male
CVCL_DI39	Hep3BLAP-I	Cancer cell line	Male
CVCL_DI40	Hep3BLAP-II	Cancer cell line	Male
CVCL_DI41	Hep3BLIP-I	Cancer cell line	Male
CVCL_DI42	Hep3BLIP-II	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.