DCUN1D3

Summary

DCUN1D3 (defective in cullin neddylation 1 domain containing 3, HGNC:28734) is a protein-coding gene on chromosome 16p12.3, encoding DCN1-like protein 3 (Q8IWE4). Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes and may play a role in the cell cycle progression by regulating the SCF ubiquitin E3 ligase complex,….

Enables cullin family protein binding activity. Involved in several processes, including negative regulation of G1/S transition of mitotic cell cycle; regulation of protein neddylation; and response to UV-C. Located in several cellular components, including cytosol; nucleoplasm; and perinuclear region of cytoplasm.

Source: NCBI Gene 123879 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 38 total
• Druggable target: yes
• MANE Select transcript: NM_173475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28734
Approved symbol	DCUN1D3
Name	defective in cullin neddylation 1 domain containing 3
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC48972, FLJ41725, DKFZp686O0290, SCCRO3
Ensembl gene	ENSG00000188215
Ensembl biotype	protein_coding
OMIM	616167
Entrez	123879

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000324344, ENST00000563934, ENST00000900856, ENST00000900857, ENST00000917271, ENST00000917272, ENST00000917273, ENST00000917274, ENST00000917275, ENST00000917276, ENST00000947782, ENST00000947783, ENST00000947784, ENST00000947785

RefSeq mRNA: 1 — MANE Select: NM_173475 NM_173475

CCDS: CCDS10592

Canonical transcript exons

ENST00000324344 — 3 exons

Exon	Start	End
ENSE00001246377	20862108	20862643
ENSE00001307758	20854925	20860369
ENSE00001321284	20900204	20900358

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 93.48.

FANTOM5 (CAGE): breadth broad, TPM avg 0.3891 / max 11.0143, expressed in 184 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156705	6.6292	1669
156704	0.3000	135
156703	0.0891	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.48	gold quality
left ventricle myocardium	UBERON:0006566	93.48	gold quality
epithelial cell of pancreas	CL:0000083	90.61	silver quality
oocyte	CL:0000023	88.21	gold quality
pancreatic ductal cell	CL:0002079	87.97	silver quality
tibialis anterior	UBERON:0001385	87.90	silver quality
kidney epithelium	UBERON:0004819	86.20	silver quality
lower lobe of lung	UBERON:0008949	86.04	gold quality
oviduct epithelium	UBERON:0004804	85.84	gold quality
vena cava	UBERON:0004087	85.59	gold quality
omental fat pad	UBERON:0010414	84.91	gold quality
peritoneum	UBERON:0002358	84.88	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.73	gold quality
cartilage tissue	UBERON:0002418	83.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.90	silver quality
calcaneal tendon	UBERON:0003701	83.62	gold quality
adipose tissue	UBERON:0001013	83.56	gold quality
sural nerve	UBERON:0015488	83.42	gold quality
buccal mucosa cell	CL:0002336	83.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.70	gold quality
parietal pleura	UBERON:0002400	82.41	gold quality
stromal cell of endometrium	CL:0002255	82.38	gold quality
deltoid	UBERON:0001476	81.07	silver quality
left adrenal gland	UBERON:0001234	81.06	gold quality
popliteal artery	UBERON:0002250	80.80	gold quality
tibial artery	UBERON:0007610	80.80	gold quality
left adrenal gland cortex	UBERON:0035825	80.79	gold quality
superficial temporal artery	UBERON:0001614	80.77	silver quality
liver	UBERON:0002107	80.76	gold quality
tibial nerve	UBERON:0001323	80.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.31
E-MTAB-7303	no	249.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

302 targeting DCUN1D3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790

Literature-anchored findings (GeneRIF, showing 4)

• DCUN1D3 is a novel UVC-response gene involved in cell cycle regulation and cell survival. (PMID:18823379)
• SCCRO3 functions as a tumor suppressor by antagonizing the neddylation activity of SCCRO (PMID:25349211)
• DCUN1D3 has a role in activating SCFSKP2 ubiquitin E3 ligase activity through cullin-1 neddylation and cell cycle progression in tumor cells with UV damage (PMID:27542266)
• Bladder Cancer Progression Is Suppressed Through the Heart and Neural Crest Derivatives Expressed 2-Antisense RNA 1/microRNA-93-5p/Defective in Cullin Neddylation 1 Domain Containing 3 Axis. (PMID:36656536)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcun1d3	ENSDARG00000011493
mus_musculus	Dcun1d3	ENSMUSG00000048787
rattus_norvegicus	Dcun1d3	ENSRNOG00000014037
rattus_norvegicus	Dcun1d3	ENSRNOG00000066875
drosophila_melanogaster	SCCRO3	FBGN0033784

Paralogs (4): DCUN1D1 (ENSG00000043093), DCUN1D4 (ENSG00000109184), DCUN1D5 (ENSG00000137692), DCUN1D2 (ENSG00000150401)

Protein

Protein identifiers

DCN1-like protein 3 — Q8IWE4 (reviewed: Q8IWE4)

Alternative names: DCUN1 domain-containing protein 3, Defective in cullin neddylation protein 1-like protein 3, Squamous cell carcinoma-related oncogene 3

All UniProt accessions (1): Q8IWE4

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes and may play a role in the cell cycle progression by regulating the SCF ubiquitin E3 ligase complex, after UV damage. At the cell membrane, can promote and as well inhibit cullins neddylation.

Subunit / interactions. Part of a complex containing DCUN1D3, CUL3 and RBX1. Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Interacts preferentially with CUL3; this interaction triggers the relocalization of CUL3 to the cell membrane where CUL3 is neddylated. Interacts (via DCUN1 domain) with RBX1. May also interact with regulators or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these interactions are bridged by cullins. Interacts (via DCUN1 domain) with CAND1; this interaction is bridged by cullins and strongly inhibits cullin neddylation. These CAND-cullin-DCNL complexes can only be neddylated in the presence of a substrate adapter. Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F.

Subcellular location. Cell membrane. Cytoplasm. Nucleus. Perinuclear region.

Tissue specificity. Tends to be down-regulated in different type of cancers, including lung neuroendocrine carcinoma, thyroid Huerthle cell carcinoma and lung squamous cell carcinoma. Mostly expressed in testis and brain. Highly expressed in liver, bladder and renal normal tissue than their tumor tissue counterparts. Palmitoylation stabilizes DCUN1D3 at the cell membrane.

Domain organisation. The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities. This domain is also involved in CAND1-, cullins- and RBX1-binding.

Induction. Increases by UVC treatment.

RefSeq proteins (1): NP_775746* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005176	PONY_dom	Domain
IPR014764	DCN-prot	Family
IPR042460	DCN1-like_PONY	Homologous_superfamily

Pfam: PF03556

UniProt features (31 total): helix 10, mutagenesis site 9, strand 2, turn 2, region of interest 2, sequence variant 2, initiator methionine 1, chain 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4GBA	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWE4-F1	80.97	0.66

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): 2

Mutagenesis-validated functional residues (9):

Position	Phenotype
4	does not affect myristoylation; when associated with a-8. loss of myristoylation; when associated with a-2. loss of palm
8	does not affect myristoylation; when associated with a-4. loss of myristoylation; when associated with a-2. loss of palm
241	loss of interaction with cul1, cul2, cul3, cula4, cula5, cand1 and rbx1; when associated with r-265 and a-271. does not
241	loss of cand1-, cul1-, cul3- and rbx1-binding. loss of function of inhibition of dcun1d1-mediated cul1 neddylation, but
265	loss of cand1-, cul1-, cul3- and rbx1-binding. loss of function of inhibition of dcun1d1-mediated cul1 neddylation, but
271	loss of interaction with cul1, cul2, cul3, cula4, cula5 cald1 and rbx1; when associated with a-241 and r-265. does not a
271	loss of cand1-, cul1-, cul3- and rbx1-binding. loss of function of inhibition of dcun1d1-mediated cul1 neddylation, but
1–26	no effect on cand1-, cul1-, cul3- and rbx1-binding.
2	no effect on cand1-, cul1-, cul3- and rbx1-binding. loss of localization at the cell membrane. loss of function of inhib

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 280 (showing top): GOBP_RESPONSE_TO_UV_C, GOBP_RESPONSE_TO_IONIZING_RADIATION, TAATAAT_MIR126, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH, GOBP_PROTEIN_NEDDYLATION, GGGTGGRR_PAX4_03, AGGCACT_MIR5153P, SRF_C, CATTTCA_MIR203, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN

GO Biological Process (10): response to UV-C (GO:0010225), response to gamma radiation (GO:0010332), regulation of cell cycle process (GO:0010564), negative regulation of cell growth (GO:0030308), positive regulation of apoptotic process (GO:0043065), protein neddylation (GO:0045116), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), regulation of protein neddylation (GO:2000434), negative regulation of protein neddylation (GO:2000435), positive regulation of protein neddylation (GO:2000436)

GO Molecular Function (4): ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin-like protein binding (GO:0032182), cullin family protein binding (GO:0097602), protein binding (GO:0005515)

GO Cellular Component (8): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein neddylation	3
regulation of protein neddylation	2
protein binding	2
cytoplasm	2
response to UV	1
response to ionizing radiation	1
cell cycle process	1
regulation of cell cycle	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
protein modification by small protein conjugation	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
regulation of protein modification by small protein conjugation or removal	1
negative regulation of protein modification by small protein conjugation or removal	1
positive regulation of protein modification by small protein conjugation or removal	1
ubiquitin-like protein conjugating enzyme binding	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

463 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCUN1D3	UBE2M	P61081	677
DCUN1D3	UBE2F	Q969M7	548
DCUN1D3	UBA3	Q8TBC4	531
DCUN1D3	SDAD1	Q9NVU7	503
DCUN1D3	MVB12A	Q96EY5	495
DCUN1D3	NEDD8	Q15843	489
DCUN1D3	RBX1	P62877	470
DCUN1D3	CAND1	Q86VP6	450
DCUN1D3	ZCCHC14	Q8WYQ9	422
DCUN1D3	CUL3	Q13618	421
DCUN1D3	COX10	Q12887	420
DCUN1D3	CUL1	Q13616	416
DCUN1D3	RPS26	P02383	415
DCUN1D3	NAE1	Q13564	414
DCUN1D3	SENP8	Q96LD8	413

IntAct

15 interactions, top by confidence:

A	B	Type	Score
DCUN1D3	CUL3	psi-mi:“MI:0915”(physical association)	0.580
CUL3	DCUN1D3	psi-mi:“MI:0914”(association)	0.580
DCUN1D3	CUL3	psi-mi:“MI:0915”(physical association)	0.500
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
UBE2M	DCUN1D3	psi-mi:“MI:0407”(direct interaction)	0.440
DCUN1D3	H3-4	psi-mi:“MI:0915”(physical association)	0.400
DCUN1D3	CUL1	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ASB2	NFKB2	psi-mi:“MI:0914”(association)	0.350
SPATA7	EEPD1	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (75): CAND1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL3 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), CUL1 (Biochemical Activity), CUL2 (Biochemical Activity), CUL3 (Biochemical Activity), CUL4A (Biochemical Activity), CUL4B (Biochemical Activity), CUL5 (Biochemical Activity), CUL1 (Affinity Capture-MS), CUL2 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CUL4B (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6A2H6, A2VEI2, A4IG32, A4IHK8, A5D7A0, D2HZB0, D4A1F2, E9Q4Z2, F1MF74, O00763, O08874, O14795, O94851, P23092, Q05AA6, Q08BI9, Q13474, Q17QM6, Q3TWN3, Q4FZY0, Q4KUS2, Q4V8B2, Q5E9V1, Q5R9G1, Q5RDI4, Q5U2P1, Q5ZJT0, Q62768, Q62769, Q69ZT9, Q6DFA1, Q86XE3, Q8BHD4, Q8BML1, Q8IWE4, Q8K0V2, Q8WN03, Q96C19, Q9BQI0, Q9BUP0

Diamond homologs: A4IHK8, Q1RMX9, Q4V8B2, Q54GP1, Q5ADL9, Q5E9V1, Q5PPL2, Q5R9G1, Q5RDF9, Q5RHX6, Q5ZKU1, Q60YT5, Q6C0B6, Q6DFA1, Q6PH85, Q86JM4, Q8BZJ7, Q8CCA0, Q8IWE4, Q8K0V2, Q8T8S1, Q92564, Q96GG9, Q9BTE7, Q9CXV9, Q9QZ73, Q9U3C8, Q9VUQ8, Q9VWB1, Q12395, Q6FJR2, Q750Y3, Q5AWS1, Q8WZK4, Q9MBG8, Q4PF67, P0CN06, P0CN07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1041 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20860366:CTTC:C	acceptor_gain	1.0000
16:20860367:TTC:T	acceptor_gain	1.0000
16:20860368:TC:T	acceptor_gain	1.0000
16:20860368:TCC:T	acceptor_loss	1.0000
16:20860369:CC:C	acceptor_gain	1.0000
16:20860370:C:CC	acceptor_gain	1.0000
16:20860374:A:T	acceptor_gain	1.0000
16:20860376:C:CT	acceptor_gain	1.0000
16:20860377:A:T	acceptor_gain	1.0000
16:20897757:T:TA	donor_gain	1.0000
16:20897781:G:C	donor_gain	1.0000
16:20900203:CAG:C	donor_gain	1.0000
16:20860373:C:CT	acceptor_gain	0.9900
16:20862103:CTAA:C	donor_loss	0.9900
16:20862106:A:T	donor_loss	0.9900
16:20862107:CCTGG:C	donor_loss	0.9900
16:20862142:T:TA	donor_gain	0.9900
16:20862213:T:TA	donor_gain	0.9900
16:20897743:T:TA	donor_gain	0.9900
16:20900202:A:AC	donor_gain	0.9900
16:20900203:C:CC	donor_gain	0.9900
16:20860370:C:T	acceptor_gain	0.9800
16:20862102:ACT:A	donor_loss	0.9800
16:20897793:T:C	donor_gain	0.9800
16:20900199:CTCA:C	donor_loss	0.9700
16:20900200:TCA:T	donor_loss	0.9700
16:20900201:CACA:C	donor_loss	0.9700
16:20900202:AC:A	donor_loss	0.9700
16:20900203:C:CG	donor_loss	0.9700
16:20862101:GAC:G	donor_loss	0.9600

AlphaMissense

2013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20859982:A:C	F273L	1.000
16:20859982:A:T	F273L	1.000
16:20859983:A:G	F273S	1.000
16:20859984:A:G	F273L	1.000
16:20859989:T:A	D271V	1.000
16:20859989:T:C	D271G	1.000
16:20859989:T:G	D271A	1.000
16:20860001:G:A	P267L	1.000
16:20860001:G:C	P267R	1.000
16:20860001:G:T	P267Q	1.000
16:20860002:G:A	P267S	1.000
16:20860002:G:T	P267T	1.000
16:20860003:C:A	W266C	1.000
16:20860003:C:G	W266C	1.000
16:20860005:A:G	W266R	1.000
16:20860005:A:T	W266R	1.000
16:20860055:A:G	F249S	1.000
16:20860067:A:G	M245T	1.000
16:20860072:C:A	W243C	1.000
16:20860072:C:G	W243C	1.000
16:20860073:C:G	W243S	1.000
16:20860074:A:G	W243R	1.000
16:20860074:A:T	W243R	1.000
16:20860078:G:C	D241E	1.000
16:20860078:G:T	D241E	1.000
16:20860079:T:A	D241V	1.000
16:20860079:T:C	D241G	1.000
16:20860079:T:G	D241A	1.000
16:20860080:C:A	D241Y	1.000
16:20860080:C:G	D241H	1.000

dbSNP variants (sampled 300 via entrez): RS1000143115 (16:20875681 G>A), RS1000177459 (16:20889290 G>A), RS1000183700 (16:20896657 A>G), RS1000212356 (16:20899735 G>A,C), RS1000247780 (16:20896310 A>C,G), RS1000276723 (16:20896214 T>C), RS1000284262 (16:20875375 C>G,T), RS1000307735 (16:20895714 A>G), RS1000386693 (16:20895443 A>G), RS1000391026 (16:20856633 G>A,T), RS1000452539 (16:20889007 C>T), RS1000510268 (16:20894978 G>A,C), RS1000627863 (16:20893662 T>C), RS1000798202 (16:20887659 G>A), RS1000893225 (16:20902281 G>A)

Disease associations

OMIM: gene MIM:616167 | 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
GCST002589_21	Hippocampal sclerosis	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295894 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.23	Ki	591.7	nM	CHEMBL4592844

PubChem BioAssay actives

1 with measured affinity, of 8 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-(4-methylphenyl)-2-prop-2-ynylsulfanyl-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1599585: Binding affinity to N-terminal GST tagged recombinant DCN3 (unknown origin) (86 to 304 residues) expressed in Escherichia coli BL21(DE3) assessed as reduction in DCN1/FAM-labelled N-terminal acetylated UBE2M (1 to 21 residues) protein-protein interaction after 30 mins by HTRF assay	ki	0.5917	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	5
Dexamethasone	affects cotreatment, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
hydroquinone	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4222550	Binding	Inhibition of human DCN3-mediated cullin neddylation assessed as reduction in transfer of fluorescein-5-maleimide-tagged NEDD8 from N-terminally acetylated human UBE2M to CUL2-CTD at 50 uM measured for 2 mins by pulse-chase assay	Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation. — J Med Chem

Clinical trials (associated diseases)

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