EAF2

Summary

EAF2 (ELL associated factor 2, HGNC:23115) is a protein-coding gene on chromosome 3q13.33, encoding ELL-associated factor 2 (Q96CJ1). Acts as a transcriptional transactivator of TCEA1 elongation activity.

Enables transcription elongation factor activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription elongation by RNA polymerase II. Part of transcription elongation factor complex. Biomarker of prostate cancer.

Source: NCBI Gene 55840 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_018456

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23115
Approved symbol	EAF2
Name	ELL associated factor 2
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	BM040, TRAITS, U19
Ensembl gene	ENSG00000145088
Ensembl biotype	protein_coding
OMIM	607659
Entrez	55840

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 nonsense_mediated_decay

ENST00000273668, ENST00000451944, ENST00000465664, ENST00000490434, ENST00000490477, ENST00000858957

RefSeq mRNA: 2 — MANE Select: NM_018456 NM_001320041, NM_018456

CCDS: CCDS3006

Canonical transcript exons

ENST00000273668 — 6 exons

Exon	Start	End
ENSE00001217946	121886342	121886526
ENSE00001936051	121835209	121835391
ENSE00003493704	121872537	121872788
ENSE00003538388	121854687	121854823
ENSE00003589003	121844453	121844547
ENSE00003612712	121857011	121857156

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2101 / max 614.3212, expressed in 1296 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38200	11.9934	1196
38199	1.2166	595

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	96.66	gold quality
monocyte	CL:0000576	94.58	gold quality
mononuclear cell	CL:0000842	94.50	gold quality
bone marrow	UBERON:0002371	94.40	gold quality
leukocyte	CL:0000738	93.83	gold quality
bone element	UBERON:0001474	90.97	gold quality
lymph node	UBERON:0000029	89.23	gold quality
trabecular bone tissue	UBERON:0002483	89.04	gold quality
granulocyte	CL:0000094	88.89	gold quality
vermiform appendix	UBERON:0001154	88.77	gold quality
nephron tubule	UBERON:0001231	88.23	gold quality
epithelium of nasopharynx	UBERON:0001951	87.62	gold quality
rectum	UBERON:0001052	85.85	gold quality
spleen	UBERON:0002106	85.22	gold quality
caecum	UBERON:0001153	85.04	gold quality
kidney epithelium	UBERON:0004819	84.39	gold quality
tonsil	UBERON:0002372	84.16	gold quality
seminal vesicle	UBERON:0000998	83.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.81	gold quality
adult mammalian kidney	UBERON:0000082	82.27	gold quality
prostate gland	UBERON:0002367	80.91	gold quality
kidney	UBERON:0002113	80.08	gold quality
superficial temporal artery	UBERON:0001614	79.52	gold quality
diaphragm	UBERON:0001103	79.32	gold quality
renal glomerulus	UBERON:0000074	79.18	gold quality
metanephric glomerulus	UBERON:0004736	78.70	gold quality
islet of Langerhans	UBERON:0000006	78.61	gold quality
mucosa of transverse colon	UBERON:0004991	77.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	77.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.22	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	91.16
E-MTAB-9467	yes	57.40
E-HCAD-1	yes	40.37
E-CURD-122	yes	37.48
E-CURD-46	yes	37.11
E-MTAB-8410	yes	35.45
E-HCAD-11	yes	27.79
E-MTAB-9801	yes	3.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
ELL
FABP2
THBS1
WNT4

Upstream regulators (CollecTRI, top): PML, TFPT

miRNA regulators (miRDB)

12 targeting EAF2, 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-548AT-5P	99.96	70.83	2666
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-136-3P	93.27	66.31	131

Literature-anchored findings (GeneRIF, showing 21)

• U19 is growth inhibitory and tumor suppressive and that the disruption of androgen-dependent growth inhibition via U19 down-regulation is commonly associated with prostate cancer progression. (PMID:12907652)
• ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL. (PMID:16006523)
• ELL may be an important factor required for U19/Eaf2 function because U19/Eaf2 nuclear localization and transactivation activity are essential for its function as a transcription factor. (PMID:16114057)
• FB1 is an important binding partner and a functional regulator of U19/EAF2, EAF1, and/or ELL. (PMID:17395368)
• Data suggest that U19/EAF2 regulates the expression of TSP-1 via blocking p53 repression of the TSP-1 promoter. (PMID:19826414)
• Findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo. (PMID:20161747)
• the role of the EAF2 in response to simvastatin and lovastatin in HCT-116 colon cancer cells (PMID:21483694)
• EAF2 bound to and suppressed HIF-1alpha. (PMID:24421387)
• Together these findings identify a novel physical and functional interaction between EAF2 and the Rb pathway. (PMID:24727455)
• Findings suggest that regulation of the AR signaling pathway, cell proliferation, and migration through FOXA1 represents an important mechanism of EAF2 suppression of prostate carcinogenesis. (PMID:25808853)
• EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation (PMID:26370086)
• EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1alpha signaling axis. (PMID:27259264)
• analysis showed that EAF2 and EAF1 are required for the recruitment and retention of Ku70/Ku80 to DNA damage sites and play a functional role in nonhomologous end-joining DNA repair. Findings provide evidence for EAF2 as a key factor mediating androgen protection of DNA damage via Ku70/Ku80 in prostate cancer cells. (PMID:27721405)
• Concurrent p53 nuclear staining and EAF2 downregulation was associated with high Gleason score In human prostate cancer specimens. (PMID:29029019)
• The results indicated that Eaf2 was able to effectively suppress H2O2induced apoptosis of HLE cells via inhibition of caspase 3 production and activation of Wnt3a signaling. (PMID:29257273)
• Simultaneous inactivation of EAF2 and p53 can act to activate STAT3 and drive prostate tumorigenesis. (PMID:29518696)
• Findings provide further evidence that ELL2 is a potential tumor suppressor frequently down-regulated in clinical prostate cancer specimens and provides new insights into regulation of ELL2 protein level by polyubiquitination and EAF2 binding. (PMID:30009504)
• EAF2 frameshift mutation is associated with Colorectal Cancer. (PMID:30088132)
• Systematic expression analysis of EAF family reveals the importance of EAF2 in melanoma. (PMID:33182068)
• CircEAF2 counteracts Epstein-Barr virus-positive diffuse large B-cell lymphoma progression via miR-BART19-3p/APC/beta-catenin axis. (PMID:34852843)
• Mechanism of ELL-associated factor 2 and vasohibin 1 regulating invasion, migration, and angiogenesis in colorectal cancer. (PMID:37426316)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eaf2	ENSDARG00000010432
mus_musculus	Eaf2	ENSMUSG00000022838
rattus_norvegicus	Eaf2	ENSRNOG00000002350
drosophila_melanogaster	Eaf	FBGN0033166
caenorhabditis_elegans	eaf-1	WBGENE00017011

Paralogs (1): EAF1 (ENSG00000144597)

Protein

Protein identifiers

ELL-associated factor 2 — Q96CJ1 (reviewed: Q96CJ1)

Alternative names: Testosterone-regulated apoptosis inducer and tumor suppressor protein

All UniProt accessions (4): B4DWJ3, Q96CJ1, F8WCI9, F8WF04

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional transactivator of TCEA1 elongation activity. Acts as a transcriptional transactivator of ELL and ELL2 elongation activities. Potent inducer of apoptosis in prostatic and non-prostatic cell lines. Inhibits prostate tumor growth in vivo.

Subunit / interactions. Isoform 1 and isoform 2 interact with TCEA1. Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with ELL and ELL2.

Subcellular location. Nucleus speckle.

Tissue specificity. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, spleen, prostate, testis, small intestine, colon, adrenal, bone marrow, lymph node, spinal gland, stomach, thyroid, trachea, thymus, liver and leukocytes.

Induction. By androgen.

Similarity. Belongs to the EAF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96CJ1-1	1	yes
Q96CJ1-2	2

RefSeq proteins (2): NP_001306970, NP_060926* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019194	Tscrpt_elong_fac_Eaf_N	Domain
IPR027093	EAF_fam	Family

Pfam: PF09816

UniProt features (13 total): region of interest 5, modified residue 3, compositionally biased region 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CJ1-F1	70.75	0.34

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 (3): 151, 154, 146

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-75955	RNA Polymerase II Transcription Elongation

MSigDB gene sets: 187 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, FISCHER_G1_S_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, MODULE_511, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_UROGENITAL_SYSTEM_DEVELOPMENT, FISCHER_DREAM_TARGETS

GO Biological Process (8): transcription elongation by RNA polymerase II (GO:0006368), apoptotic process (GO:0006915), negative regulation of cell growth (GO:0030308), regulation of transcription elongation by RNA polymerase II (GO:0034243), positive regulation of transcription by RNA polymerase II (GO:0045944), epithelial cell proliferation involved in prostate gland development (GO:0060767), negative regulation of epithelial cell proliferation involved in prostate gland development (GO:0060770), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): transcription elongation factor activity (GO:0003711), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), transcription elongation factor complex (GO:0008023), nuclear speck (GO:0016607), super elongation complex (GO:0032783), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
DNA-templated transcription elongation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
transcription elongation by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
prostate gland development	1
epithelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
epithelial cell proliferation involved in prostate gland development	1
regulation of epithelial cell proliferation involved in prostate gland development	1
negative regulation of reproductive process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription regulator activity	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
nuclear protein-containing complex	1
nuclear ribonucleoprotein granule	1
transcription elongation factor complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EAF2	ELL	P55199	967
EAF2	VHL	P40337	590
EAF2	ELL2	O00472	553
EAF2	MED26	O95402	472
EAF2	ICE2	Q659A1	457
EAF2	ELL3	Q9HB65	363
EAF2	SPINK7	P58062	337
EAF2	HEPHL1	Q6MZM0	298
EAF2	DISP3	Q9P2K9	291
EAF2	SH3GL1	Q99961	288
EAF2	MPV17	P39210	286
EAF2	CSRNP3	Q8WYN3	286
EAF2	ELOA2	Q8IYF1	284
EAF2	TRIM47	Q96LD4	276
EAF2	SLITRK4	Q8IW52	274

IntAct

66 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
AFF4	ELL2	psi-mi:“MI:0914”(association)	0.730
BEND7	EAF2	psi-mi:“MI:0915”(physical association)	0.700
EAF2	BEND7	psi-mi:“MI:0915”(physical association)	0.700
ELL3	CCNT1	psi-mi:“MI:0914”(association)	0.640
EAF2	PSME3	psi-mi:“MI:0915”(physical association)	0.620
PSME3	EAF2	psi-mi:“MI:0915”(physical association)	0.620
EAF2	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
BIRC2	EAF2	psi-mi:“MI:0915”(physical association)	0.560
EAF2	BIRC2	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	EAF2	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	EAF2	psi-mi:“MI:0915”(physical association)	0.560
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
HIF1A	EAF2	psi-mi:“MI:0915”(physical association)	0.520
EAF2	TFPT	psi-mi:“MI:0915”(physical association)	0.510
TFPT	EAF2	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (59): EAF2 (Two-hybrid), EAF2 (Two-hybrid), BEND7 (Two-hybrid), EAF2 (Affinity Capture-MS), EAF2 (Affinity Capture-MS), EAF2 (Affinity Capture-MS), EAF2 (Affinity Capture-Western), EAF2 (Reconstituted Complex), RBBP4 (Affinity Capture-Western), RBBP7 (Affinity Capture-Western), EAF2 (Two-hybrid), EAF2 (Two-hybrid), EAF2 (Affinity Capture-MS), EAF2 (Affinity Capture-Western), EAF2 (Affinity Capture-Western)

ESM2 similar proteins: A2BD83, F4HQA1, F4HRV8, F4ICK8, O43290, P21675, P35269, Q04870, Q13435, Q15545, Q1RMR0, Q2HJG8, Q2KJ14, Q3THK3, Q3UJB0, Q4R5A5, Q4U0S5, Q4V886, Q52KV5, Q53F19, Q5EA53, Q5HZB6, Q5R4D6, Q5R7L9, Q5RAX0, Q5XIW8, Q5XJE5, Q5ZHP7, Q5ZIH9, Q5ZIM6, Q5ZM19, Q641X2, Q6AY96, Q6NYV9, Q6P2Y1, Q6R1L1, Q80UV9, Q811X5, Q8BZR9, Q8CFC7

Diamond homologs: B3MI72, B3NA01, B4GCP2, B4HQT6, B4J6N6, B4KND9, B4LMA2, B4MR74, B4P1N5, B5E1I4, Q5RAM8, Q5ZHP7, Q7JRJ1, Q811X5, Q91ZD6, Q96CJ1, Q96JC9, Q9D4C5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EAF2	up-regulates	ELL	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1728 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:121844458:T:C	F38L	1.000
3:121844460:C:A	F38L	1.000
3:121844460:C:G	F38L	1.000
3:121844459:T:C	F38S	0.999
3:121844528:T:A	I61K	0.999
3:121854712:T:C	F76S	0.999
3:121844459:T:G	F38C	0.998
3:121844528:T:G	I61R	0.998
3:121844534:T:C	L63P	0.998
3:121854717:G:C	G78R	0.998
3:121854815:A:C	K110N	0.998
3:121854815:A:T	K110N	0.998
3:121835389:G:C	R35P	0.997
3:121844498:T:C	L51P	0.997
3:121854711:T:C	F76L	0.997
3:121854713:C:A	F76L	0.997
3:121854713:C:G	F76L	0.997
3:121854744:T:C	C87R	0.997
3:121854751:T:C	L89S	0.997
3:121854784:T:C	L100P	0.997
3:121854811:T:A	V109E	0.997
3:121854814:A:T	K110I	0.997
3:121844463:A:C	K39N	0.996
3:121844463:A:T	K39N	0.996
3:121854718:G:A	G78D	0.996
3:121854793:T:A	L103H	0.996
3:121854793:T:C	L103P	0.996
3:121854813:A:G	K110E	0.996
3:121835376:T:C	F31L	0.995
3:121835378:C:A	F31L	0.995

dbSNP variants (sampled 300 via entrez): RS1000000916 (3:121886467 G>C), RS1000028550 (3:121850205 A>G), RS1000057119 (3:121862489 C>A,T), RS1000104639 (3:121849925 T>C), RS1000142339 (3:121874177 A>G), RS1000220654 (3:121841647 T>G), RS1000264465 (3:121866393 C>T), RS1000357888 (3:121856187 T>C), RS1000418903 (3:121853687 A>C), RS1000463371 (3:121861025 T>G), RS1000658844 (3:121866181 C>T), RS1000700919 (3:121865918 C>T), RS1000708659 (3:121836725 G>A,C,T), RS1000739288 (3:121880464 G>A,T), RS1000752967 (3:121853910 G>A,C)

Disease associations

OMIM: gene MIM:607659 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Cyclosporine	increases expression	3
mercuric bromide	affects cotreatment, increases expression	2
entinostat	affects cotreatment, increases expression	2
Vorinostat	increases expression	2
Nickel	increases expression	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
methylmercuric chloride	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
cinnamaldehyde	decreases expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
oxamflatin	increases expression	1
apicidin	increases expression	1
2-palmitoylglycerol	increases expression	1
scriptaid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
belinostat	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
suberoyl bis-hydroxamic acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Dutasteride	decreases expression, increases expression, increases reaction	1
Docetaxel	decreases expression	1
Panobinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1

Clinical trials (associated diseases)

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