CEBPZ

Summary

CEBPZ (CCAAT enhancer binding protein zeta, HGNC:24218) is a protein-coding gene on chromosome 2p22.2, encoding CCAAT/enhancer-binding protein zeta (Q03701). Stimulates transcription from the HSP70 promoter. It is a common-essential gene (DepMap: required in 93.3% of cancer cell lines).

This gene belongs to the CBF/Mak21 family. The encoded protein plays a role in cellular response to environmental stimuli through a transcriptional process that involves heat shock factors, conserved DNA elements (heat shock elements or HSEs) and CCAAT boxes. The protein acts as a DNA-binding transcriptional activator and regulates the heat-shock protein 70 (HSP70) promoter in a CCAAT-dependent manner. The protein is also involved in cell growth and differentiation, particularly, hematopoietic differentiation.

Source: NCBI Gene 10153 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 194 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 93.3% of screened cell lines (common-essential)
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_005760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24218
Approved symbol	CEBPZ
Name	CCAAT enhancer binding protein zeta
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Aliases	CBF2, CTF2, HSP-CBF
Ensembl gene	ENSG00000115816
Ensembl biotype	protein_coding
OMIM	612828
Entrez	10153

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000234170, ENST00000446769, ENST00000489306, ENST00000898578, ENST00000898579, ENST00000938546, ENST00000938547, ENST00000938548

RefSeq mRNA: 1 — MANE Select: NM_005760 NM_005760

CCDS: CCDS1787

Canonical transcript exons

ENST00000234170 — 16 exons

Exon	Start	End
ENSE00000747278	37211843	37212039
ENSE00000747280	37212335	37212392
ENSE00000747281	37213864	37213961
ENSE00000747282	37214886	37214952
ENSE00000747283	37216140	37216208
ENSE00000747285	37216316	37216418
ENSE00000747287	37216984	37217037
ENSE00000747288	37220385	37220473
ENSE00000747289	37222380	37222563
ENSE00000747290	37223170	37223401
ENSE00000747292	37227544	37229036
ENSE00001282630	37231412	37231596
ENSE00001390774	37201612	37201903
ENSE00003502984	37202950	37203008
ENSE00003616242	37202784	37202865
ENSE00003671204	37210999	37211082

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.1153 / max 997.1908, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27773	40.1153	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.56	gold quality
tendon	UBERON:0000043	97.38	gold quality
tendon of biceps brachii	UBERON:0008188	97.28	gold quality
ventricular zone	UBERON:0003053	95.32	gold quality
adrenal tissue	UBERON:0018303	95.24	gold quality
medial globus pallidus	UBERON:0002477	94.79	gold quality
left testis	UBERON:0004533	94.12	gold quality
gastrocnemius	UBERON:0001388	94.02	gold quality
testis	UBERON:0000473	93.97	gold quality
right testis	UBERON:0004534	93.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.72	gold quality
colonic epithelium	UBERON:0000397	93.63	gold quality
pericardium	UBERON:0002407	93.40	gold quality
ganglionic eminence	UBERON:0004023	93.38	gold quality
body of pancreas	UBERON:0001150	93.32	gold quality
islet of Langerhans	UBERON:0000006	93.29	gold quality
muscle of leg	UBERON:0001383	93.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.25	gold quality
parietal pleura	UBERON:0002400	93.11	gold quality
cervix squamous epithelium	UBERON:0006922	93.04	gold quality
right adrenal gland cortex	UBERON:0035827	93.01	gold quality
endothelial cell	CL:0000115	92.97	gold quality
adrenal cortex	UBERON:0001235	92.89	gold quality
cranial nerve II	UBERON:0000941	92.85	gold quality
adrenal gland	UBERON:0002369	92.85	gold quality
globus pallidus	UBERON:0001875	92.83	gold quality
pancreas	UBERON:0001264	92.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.80	gold quality
left adrenal gland	UBERON:0001234	92.77	gold quality
mucosa of transverse colon	UBERON:0004991	92.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.20
E-MTAB-4850	no	673.52
E-CURD-135	no	480.50

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
ALOX12
APC	Activation
CDKN1A
COL10A1
COL11A1	Repression
COL1A2	Unknown
COL5A3	Activation
CP	Unknown
CYBB
ERVW-1
FAS
GZMB	Unknown
HSPA4	Activation
IL3
MLH1	Repression
PDLIM7	Activation
SOX9	Unknown
THBS1
TP73
TPM1

Upstream regulators (CollecTRI, top): JUND, RBPJ, TCF3

miRNA regulators (miRDB)

18 targeting CEBPZ, 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-3613-3P	100.00	76.36	7965
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-758-5P	93.99	64.46	534

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• Mouse and Human CCAAT binding factors are discussed in this citation. (PMID:8604343)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cebpz	ENSDARG00000045857
danio_rerio	si:ch1073-412h12.3	ENSDARG00000094486
mus_musculus	Cebpz	ENSMUSG00000024081
rattus_norvegicus	Cebpz	ENSRNOG00000005087
drosophila_melanogaster	Noc1	FBGN0036124
caenorhabditis_elegans		WBGENE00009084

Protein

Protein identifiers

CCAAT/enhancer-binding protein zeta — Q03701 (reviewed: Q03701)

Alternative names: CCAAT-box-binding transcription factor

All UniProt accessions (2): Q03701, C9J9W7

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates transcription from the HSP70 promoter.

Subcellular location. Nucleus.

Similarity. Belongs to the CBF/MAK21 family.

RefSeq proteins (1): NP_005751* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005612	CCAAT-binding_factor	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR040155	CEBPZ/Mak21-like	Family

Pfam: PF03914

UniProt features (24 total): modified residue 7, compositionally biased region 6, region of interest 5, sequence variant 4, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03701-F1	67.34	0.15

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 (7): 113, 629, 695, 835, 959, 973, 978

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_255, MODULE_317, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, SCHUHMACHER_MYC_TARGETS_UP, MUELLER_PLURINET, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MORF_RFC4, ACATTCC_MIR1_MIR206, MORF_PRKDC, GARY_CD5_TARGETS_DN

GO Biological Process (1): positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), CCAAT-binding factor complex (GO:0016602)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
transcription coregulator activity	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

2424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEBPZ	PDCD11	Q14690	959
CEBPZ	NFYC	Q13952	827
CEBPZ	CTF1	Q16619	805
CEBPZ	NFYA	P23511	779
CEBPZ	NFYB	P25208	771
CEBPZ	CREBBP	Q92793	660
CEBPZ	RPH3AL	Q9UNE2	655
CEBPZ	UTP20	O75691	613
CEBPZ	RBPJ	Q06330	608
CEBPZ	GNL2	Q13823	606
CEBPZ	NFIX	Q14938	593
CEBPZ	WDR74	Q6RFH5	584
CEBPZ	WDR12	Q9GZL7	573
CEBPZ	NSA2	O95478	556
CEBPZ	BYSL	Q13895	548

IntAct

209 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
SRP68	SRP72	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
MECP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
RPL18	RRP8	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
CEBPZ	GSK3B	psi-mi:“MI:0915”(physical association)	0.550
CEBPZ	PRKRA	psi-mi:“MI:0915”(physical association)	0.550
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530

BioGRID (327): CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Affinity Capture-MS), CEBPZ (Co-fractionation), CEBPZ (Co-fractionation), CEBPZ (Co-fractionation), CEBPZ (Co-fractionation)

ESM2 similar proteins: A0A8I3P7X4, A7S641, A8WG88, A9ULY7, B0R034, B0W6N3, B5DFC8, B5ME19, D6WIX5, E7EXT2, F7AEX0, O60308, O95202, P0C204, P45433, P53569, Q03701, Q0VA06, Q173M7, Q1L987, Q28HX4, Q3SYW6, Q3ZC50, Q4QR58, Q5RAT8, Q5RCI4, Q5U2X6, Q5XGZ8, Q5XIN6, Q5ZK33, Q66I12, Q6AZI2, Q6IVW0, Q6P1V4, Q6PFQ2, Q6PGY6, Q7PGE8, Q7SYB2, Q8BZN6, Q8R1B4

Diamond homologs: F4IDC2, O36021, P53569, Q03701, G0SEQ5, Q12176, Q19753, Q9VTE6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 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
Peptide chain elongation	23	22.8×	3e-23
Viral mRNA Translation	23	22.8×	3e-23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	22.6×	3e-23
Selenocysteine synthesis	23	21.6×	6e-23
Eukaryotic Translation Termination	23	21.6×	6e-23
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	21.1×	9e-23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	23	21.1×	9e-23
Formation of a pool of free 40S subunits	24	21.0×	3e-23

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	24	25.7×	1e-24
ribosomal large subunit biogenesis	10	25.6×	1e-09
translation	26	15.4×	6e-21
rRNA processing	18	14.7×	9e-14
ribosomal small subunit biogenesis	10	13.2×	9e-07
negative regulation of viral genome replication	6	13.0×	8e-04
negative regulation of translation	8	9.1×	5e-04
RNA processing	7	8.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	161
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2500 predictions. Top by Δscore:

Variant	Effect	Δscore
2:37201640:A:AG	acceptor_gain	1.0000
2:37201641:G:GG	acceptor_gain	1.0000
2:37202780:TTA:T	donor_loss	1.0000
2:37202781:TAC:T	donor_loss	1.0000
2:37202782:A:AC	donor_gain	1.0000
2:37202782:ACTT:A	donor_loss	1.0000
2:37202782:ACTTG:A	donor_gain	1.0000
2:37202783:C:CG	donor_gain	1.0000
2:37202783:CTT:C	donor_gain	1.0000
2:37202783:CTTG:C	donor_gain	1.0000
2:37202783:CTTGC:C	donor_gain	1.0000
2:37202861:CCAAA:C	acceptor_gain	1.0000
2:37202862:CAAA:C	acceptor_gain	1.0000
2:37202862:CAAAC:C	acceptor_gain	1.0000
2:37202863:AAA:A	acceptor_gain	1.0000
2:37202863:AAAC:A	acceptor_loss	1.0000
2:37202864:AA:A	acceptor_gain	1.0000
2:37202864:AAC:A	acceptor_loss	1.0000
2:37202866:C:CA	acceptor_loss	1.0000
2:37202866:C:CC	acceptor_gain	1.0000
2:37202867:T:C	acceptor_gain	1.0000
2:37202868:T:TC	acceptor_gain	1.0000
2:37202869:T:C	acceptor_gain	1.0000
2:37202869:T:TC	acceptor_gain	1.0000
2:37202943:GCCTT:G	donor_loss	1.0000
2:37202944:CCTTA:C	donor_loss	1.0000
2:37202945:CTTA:C	donor_loss	1.0000
2:37202946:TTACC:T	donor_loss	1.0000
2:37202947:TACC:T	donor_loss	1.0000
2:37202948:A:AG	donor_loss	1.0000

AlphaMissense

7109 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:37216354:C:G	R758P	0.998
2:37216362:A:C	F755L	0.998
2:37216362:A:T	F755L	0.998
2:37216364:A:G	F755L	0.998
2:37227716:C:G	A493P	0.997
2:37227727:C:T	G489D	0.997
2:37227997:G:T	A399D	0.997
2:37228444:G:T	A250D	0.997
2:37223345:A:G	L569P	0.996
2:37227733:A:G	L487S	0.996
2:37217001:C:G	A731P	0.995
2:37217022:G:C	H724D	0.995
2:37227607:A:G	L529S	0.995
2:37227820:G:T	A458D	0.995
2:37228445:C:G	A250P	0.995
2:37201873:C:G	R1019P	0.994
2:37216350:A:C	F759L	0.994
2:37216350:A:T	F759L	0.994
2:37216352:A:G	F759L	0.994
2:37216360:A:G	L756S	0.994
2:37216363:A:G	F755S	0.994
2:37223284:C:A	R589S	0.994
2:37223284:C:G	R589S	0.994
2:37223297:G:T	A585D	0.994
2:37223330:A:G	L574P	0.994
2:37227728:C:G	G489R	0.994
2:37227872:C:G	A441P	0.994
2:37201884:C:A	W1015C	0.993
2:37201884:C:G	W1015C	0.993
2:37216342:C:G	R762P	0.993

dbSNP variants (sampled 300 via entrez): RS1000055694 (2:37204976 A>C), RS1000098043 (2:37213654 T>A,C), RS1000179814 (2:37229330 C>A,T), RS1000347166 (2:37232661 C>G), RS1000465723 (2:37226895 C>A,T), RS1000586709 (2:37233587 A>G), RS1000944028 (2:37221814 G>A), RS1001182216 (2:37216175 C>A,T), RS1001199992 (2:37205410 G>A), RS1001349534 (2:37209884 T>A,C), RS1001405372 (2:37232939 G>A), RS1001777658 (2:37231748 G>A,T), RS1001876418 (2:37205761 C>A,G), RS1001939760 (2:37204383 T>C), RS1002140671 (2:37233301 G>A,C)

Disease associations

OMIM: gene MIM:612828 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002149_12	Schizophrenia	7.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067231 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.49	Kd	3243	nM	CHEMBL3752910
5.49	ED50	3243	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149838: Binding affinity to human CEBPZ incubated for 45 mins by Kinobead based pull down assay	kd	3.2431	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Camptothecin	decreases expression	1
Daunorubicin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Bucladesine	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	affects binding	1
Etoposide	decreases expression	1
Ivermectin	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Ribonucleotides	affects binding	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin M1	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652880	Binding	Binding affinity to human CEBPZ incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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