CPEB2

Summary

CPEB2 (cytoplasmic polyadenylation element binding protein 2, HGNC:21745) is a protein-coding gene on chromosome 4p15.32, encoding Cytoplasmic polyadenylation element-binding protein 2 (Q7Z5Q1). May play a role in translational regulation of stored mRNAs in transcriptionally inactive haploid spermatids.

The protein encoded by this gene is highly similar to cytoplasmic polyadenylation element binding protein (CPEB), an mRNA-binding protein that regulates cytoplasmic polyadenylation of mRNA as a trans factor in oogenesis and spermatogenesis. Studies of the similar gene in mice suggested a possible role of this protein in transcriptionally inactive haploid spermatids. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 132864 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 170 total
• MANE Select transcript: NM_001177382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21745
Approved symbol	CPEB2
Name	cytoplasmic polyadenylation element binding protein 2
Location	4p15.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137449
Ensembl biotype	protein_coding
OMIM	610605
Entrez	132864

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000345451, ENST00000382395, ENST00000382401, ENST00000442003, ENST00000503926, ENST00000507071, ENST00000509684, ENST00000538197

RefSeq mRNA: 6 — MANE Select: NM_001177382 NM_001177381, NM_001177382, NM_001177383, NM_001177384, NM_182485, NM_182646

CCDS: CCDS56325, CCDS56326, CCDS93479, CCDS93480

Canonical transcript exons

ENST00000538197 — 12 exons

Exon	Start	End
ENSE00000927352	15062079	15062260
ENSE00001293264	15052414	15052584
ENSE00001312682	15017188	15017278
ENSE00001318425	15054128	15054217
ENSE00001338033	15008338	15008427
ENSE00001338035	15033161	15033211
ENSE00001338038	15007305	15007586
ENSE00001491992	15040464	15040487
ENSE00001692146	15058421	15058539
ENSE00001718573	15059187	15059301
ENSE00002040018	15066153	15070151
ENSE00003908489	15002481	15004335

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5769 / max 670.7050, expressed in 1803 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46967	21.5741	1753
46960	5.0416	1388
46963	3.8394	1239
46971	3.4597	1364
46966	1.3408	677
46964	1.2686	584
46962	0.3589	188
46965	0.2727	124
46961	0.2399	125
46970	0.1814	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.68	gold quality
upper arm skin	UBERON:0004263	97.90	gold quality
buccal mucosa cell	CL:0002336	97.55	gold quality
endothelial cell	CL:0000115	97.42	gold quality
upper leg skin	UBERON:0004262	97.29	gold quality
gingival epithelium	UBERON:0001949	97.28	gold quality
epithelial cell of pancreas	CL:0000083	96.91	gold quality
gingiva	UBERON:0001828	96.80	gold quality
oviduct epithelium	UBERON:0004804	96.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.26	gold quality
inferior vagus X ganglion	UBERON:0005363	95.87	gold quality
subthalamic nucleus	UBERON:0001906	95.75	gold quality
corpus callosum	UBERON:0002336	95.51	gold quality
medulla oblongata	UBERON:0001896	95.37	gold quality
adult organism	UBERON:0007023	95.35	gold quality
saphenous vein	UBERON:0007318	95.34	gold quality
palpebral conjunctiva	UBERON:0001812	95.28	gold quality
penis	UBERON:0000989	95.11	gold quality
trigeminal ganglion	UBERON:0001675	95.09	gold quality
lateral globus pallidus	UBERON:0002476	95.03	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.95	gold quality
skin of hip	UBERON:0001554	94.85	gold quality
entorhinal cortex	UBERON:0002728	94.81	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.75	gold quality
superior vestibular nucleus	UBERON:0007227	94.75	gold quality
cauda epididymis	UBERON:0004360	94.71	gold quality
mammalian vulva	UBERON:0000997	94.62	gold quality
substantia nigra pars compacta	UBERON:0001965	94.38	gold quality
amniotic fluid	UBERON:0000173	94.15	gold quality
left ventricle myocardium	UBERON:0006566	94.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	9.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

399 targeting CPEB2, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 13)

• Functional studies of the mouse homolog (PMID:12672660)
• findings demonstrate that the regulation of CPEB2 mRNA splicing is a key mechanism in AnR and a driving force in TNBC metastasis (PMID:26304115)
• CPEB1, 2, and 4, are essential to successful mitotic cell division. (PMID:26398195)
• Long non-coding RNA TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis. (PMID:28302487)
• Our findings demonstrated the overexpression of miR-885-5p in liver metastasis and its roles in inducing CRC metastasis, potentiating development of miR-885-5p inhibitor to treat advanced CRC in the future. (PMID:28460469)
• Data demonstrated an increased occurrence of both SRSF3 and the CPEB2B isoform in triple negative breast cancer (TNBC), and identified a consensus binding motif for SRSF3 in the exon promoting the CPEB2B isoform. The study also suggests that the splicing event, which promotes the expression of CPEB2B, is driven by SRSF3 as well as linked to aggressive growth in metastatic TNBC. (PMID:31138601)
• CPEB2, presumably the isoform A, plays a key role in suppressing tumorigenesis in mammary epithelial cells by repressing EMT, migration, invasion, proliferation and stem-like cells phenotype, via multiple targets, including a newly-identified translational target p53. (PMID:31185986)
• A positive feedback self-regulatory loop between miR-210 and HIF-1alpha mediated by CPEB2 is involved in trophoblast syncytialization: implication of trophoblast malfunction in preeclampsiadagger. (PMID:31616934)
• The RNA binding protein CPEB2 regulates hormone sensing in mammary gland development and luminal breast cancer. (PMID:32440535)
• A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration. (PMID:34362680)
• CPEB2 m6A methylation regulates blood-tumor barrier permeability by regulating splicing factor SRSF5 stability. (PMID:36064747)
• CPEB2 enhances cell growth and angiogenesis by upregulating ARPC5 mRNA stability in multiple myeloma. (PMID:37231521)
• CPEB2 inhibit cell proliferation through upregulating p21 mRNA stability in glioma. (PMID:38158431)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpeb2	ENSDARG00000052604
mus_musculus	Cpeb2	ENSMUSG00000039782
rattus_norvegicus	Cpeb2	ENSRNOG00000005043
drosophila_melanogaster	orb2	FBGN0264307
caenorhabditis_elegans		WBGENE00000770
caenorhabditis_elegans		WBGENE00000771

Paralogs (3): CPEB3 (ENSG00000107864), CPEB4 (ENSG00000113742), CPEB1 (ENSG00000214575)

Protein

Protein identifiers

Cytoplasmic polyadenylation element-binding protein 2 — Q7Z5Q1 (reviewed: Q7Z5Q1)

All UniProt accessions (6): Q7Z5Q1, A0A5K1VW61, A0A5K1VW71, A0A5K1VW79, A0A5K1VW93, H0Y9D9

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in translational regulation of stored mRNAs in transcriptionally inactive haploid spermatids. Binds to poly(U) RNA oligomers. Required for cell cycle progression, specifically for the transition from metaphase to anaphase.

Subunit / interactions. Interacts with TENT2/GLD2.

Subcellular location. Cytoplasm.

Similarity. Belongs to the RRM CPEB family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q7Z5Q1-2	1	yes
Q7Z5Q1-3	2
Q7Z5Q1-4	3
Q7Z5Q1-5	4, CPEB2b
Q7Z5Q1-6	5
Q7Z5Q1-7	6
Q7Z5Q1-8	7
Q7Z5Q1-9	8

RefSeq proteins (6): NP_001170852, NP_001170853, NP_001170854, NP_001170855, NP_872291, NP_872587 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR032296	CEBP_ZZ	Domain
IPR034819	CPEB	Family
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR038446	CEBP_ZZ_sf	Homologous_superfamily

Pfam: PF16366, PF16367

UniProt features (17 total): splice variant 5, compositionally biased region 5, domain 2, region of interest 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5Q1-F1	61.86	0.37

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 (1): 89

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 399 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, ATACCTC_MIR202, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GTTAAAG_MIR302B, GOBP_REGULATION_OF_TRANSLATIONAL_ELONGATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, AATGGAG_MIR136, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION

GO Biological Process (6): cellular response to insulin stimulus (GO:0032869), cellular response to hypoxia (GO:0071456), negative regulation of cytoplasmic translational elongation (GO:1900248), negative regulation of cytoplasmic translation (GO:2000766), translation (GO:0006412), regulation of translation (GO:0006417)

GO Molecular Function (11): mRNA regulatory element binding translation repressor activity (GO:0000900), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), GTPase inhibitor activity (GO:0005095), translation factor activity, RNA binding (GO:0008135), mRNA 3’-UTR AU-rich region binding (GO:0035925), ribosome binding (GO:0043022), ribosomal large subunit binding (GO:0043023), ribosomal small subunit binding (GO:0043024), nucleic acid binding (GO:0003676), translation regulator activity (GO:0045182)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), neuron projection (GO:0043005), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
mRNA binding	2
ribosome binding	2
response to insulin	1
cellular response to peptide hormone stimulus	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
cytoplasmic translational elongation	1
negative regulation of translational elongation	1
regulation of cytoplasmic translational elongation	1
negative regulation of cytoplasmic translation	1
cytoplasmic translation	1
negative regulation of translation	1
regulation of cytoplasmic translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
translation repressor activity	1
nucleic acid binding	1
GTPase activity	1
enzyme inhibitor activity	1
GTPase regulator activity	1
RNA binding	1
translation factor activity	1
mRNA 3’-UTR binding	1
ribonucleoprotein complex binding	1
binding	1
molecular_function	1
regulation of translation	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPEB2	EEF2	P13639	757
CPEB2	FXR1	P51114	731
CPEB2	FMR1	Q06787	721
CPEB2	EIF4E	P06730	717
CPEB2	FXR2	P51116	707
CPEB2	DDX6	P26196	698
CPEB2	NGDN	Q8NEJ9	649
CPEB2	SYMPK	Q92797	647
CPEB2	TENT2	Q6PIY7	608
CPEB2	CAMK2A	Q9UQM7	553
CPEB2	RBFOX2	O43251	546
CPEB2	HNRNPA2B1	P22626	538
CPEB2	IGF2BP1	Q9NZI8	530
CPEB2	CDH1	P12830	511
CPEB2	PAPOLB	Q9NRJ5	505

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CPEB4	CPEB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): CPEB2 (Affinity Capture-MS), CPEB2 (Affinity Capture-MS), CPEB2 (Affinity Capture-MS), ATG2A (Two-hybrid), ATP6 (Two-hybrid), COPS7A (Two-hybrid), EEF2 (Two-hybrid), GABBR1 (Two-hybrid), GAA (Two-hybrid), KEAP1 (Two-hybrid), ATP1B2 (Two-hybrid), NECAB2 (Two-hybrid), OTUB1 (Two-hybrid), PIGS (Two-hybrid), PUF60 (Two-hybrid)

ESM2 similar proteins: A1A6K6, B9DFV2, F4HWF9, F4JCU0, F4JP52, F4KDN0, G7ID19, O22812, O80567, O80678, Q08A72, Q0D3J9, Q0P5D2, Q0VBL3, Q10M00, Q16630, Q3MHY8, Q5NVH8, Q5XI29, Q5ZL34, Q6ATR0, Q6DDW4, Q6JB11, Q6NWC6, Q6ZK57, Q7KMJ6, Q7Z5Q1, Q812E0, Q8BTV2, Q8H0P8, Q8LPQ9, Q8N684, Q8W4I9, Q940D0, Q94CJ8, Q96T37, Q9CQT2, Q9LES2, Q9LKA4, Q9LKA5

Diamond homologs: O01835, P0C279, P70166, Q03571, Q17RY0, Q28CH2, Q52KN7, Q5R733, Q6E3C9, Q6E3D2, Q6E3D4, Q6E3D5, Q7SXN4, Q7TN98, Q7TN99, Q7Z5Q1, Q812E0, Q8NE35, Q91572, Q967R6, Q9BZB8, Q9DED5, Q9VSR3, Q9YGX5, Q6E3C7, Q6E3D0, Q6E3F0, O14979, Q18317, Q3SWU3, Q5ZI72, Q6E3F2, Q6E3F3, Q9Z130, F4JHI7, Q96EP5, Q98SJ2, Q9JII5, Q9SJA6, P48809

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	164
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2629 predictions. Top by Δscore:

Variant	Effect	Δscore
4:15007582:TACAG:T	donor_loss	1.0000
4:15007583:ACAG:A	donor_loss	1.0000
4:15007584:CAGGT:C	donor_loss	1.0000
4:15007585:AGGTA:A	donor_loss	1.0000
4:15007586:GG:G	donor_loss	1.0000
4:15017183:TCCA:T	acceptor_loss	1.0000
4:15017185:CA:C	acceptor_loss	1.0000
4:15017186:A:AG	acceptor_gain	1.0000
4:15017186:AG:A	acceptor_gain	1.0000
4:15017186:AGGAT:A	acceptor_loss	1.0000
4:15017187:G:A	acceptor_gain	1.0000
4:15017187:G:GA	acceptor_gain	1.0000
4:15017187:GGA:G	acceptor_gain	1.0000
4:15017187:GGAT:G	acceptor_gain	1.0000
4:15017187:GGATC:G	acceptor_gain	1.0000
4:15017277:GG:G	donor_gain	1.0000
4:15017278:GG:G	donor_gain	1.0000
4:15017279:G:GG	donor_gain	1.0000
4:15017279:GTAG:G	donor_loss	1.0000
4:15052560:G:GA	donor_gain	1.0000
4:15052581:GAAGG:G	donor_loss	1.0000
4:15052582:A:T	donor_gain	1.0000
4:15052583:AGGT:A	donor_loss	1.0000
4:15052585:G:T	donor_loss	1.0000
4:15052586:T:G	donor_loss	1.0000
4:15054125:AAGAT:A	acceptor_gain	1.0000
4:15054126:A:G	acceptor_gain	1.0000
4:15054127:GAT:G	acceptor_gain	1.0000
4:15058407:AAT:A	acceptor_gain	1.0000
4:15058409:T:TA	acceptor_gain	1.0000

AlphaMissense

6724 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000140067 (4:15060325 G>A,C), RS1000149028 (4:15003759 A>AGGAGGCGGAGGG), RS1000176224 (4:15064603 A>C), RS1000197408 (4:15011693 G>A), RS1000253885 (4:15005533 T>A,C), RS1000312893 (4:15053870 T>C), RS1000328073 (4:15068332 T>G), RS1000374757 (4:15040190 C>T), RS1000428380 (4:15059962 A>T), RS1000446932 (4:15031045 A>C), RS1000469063 (4:15040523 C>T), RS1000483311 (4:15061580 A>G,T), RS1000610671 (4:15070227 A>C), RS1000620251 (4:15024270 C>T), RS1000661625 (4:15070610 G>A)

Disease associations

OMIM: gene MIM:610605 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006406_3	Cognitive flexibility	3.000000e-07
GCST010244_212	Triglyceride levels	2.000000e-08
GCST012042_1	Type 2 diabetes	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009332	executive function measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
Estradiol	affects cotreatment, increases expression	3
trichostatin A	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	affects cotreatment, increases expression	2
chromium hexavalent ion	decreases expression, increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1

Clinical trials (associated diseases)

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