UBE2M

Summary

UBE2M (ubiquitin conjugating enzyme E2 M, HGNC:12491) is a protein-coding gene on chromosome 19q13.43, encoding NEDD8-conjugating enzyme Ubc12 (P61081). Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. It is a common-essential gene (DepMap: required in 96.9% of cancer cell lines).

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin.

Source: NCBI Gene 9040 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 19 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 96.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_003969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12491
Approved symbol	UBE2M
Name	ubiquitin conjugating enzyme E2 M
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	hUbc12, UBC12
Ensembl gene	ENSG00000130725
Ensembl biotype	protein_coding
OMIM	603173
Entrez	9040

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000253023, ENST00000593801, ENST00000595957, ENST00000596985, ENST00000599829, ENST00000940562

RefSeq mRNA: 1 — MANE Select: NM_003969 NM_003969

CCDS: CCDS12987

Canonical transcript exons

ENST00000253023 — 6 exons

Exon	Start	End
ENSE00000655807	58556316	58556379
ENSE00000892667	58558273	58558611
ENSE00000892668	58555712	58556229
ENSE00003463954	58556892	58556930
ENSE00003543684	58556687	58556790
ENSE00003657102	58557063	58557157

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.9989 / max 509.2398, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182973	24.1137	1814
182976	23.0244	1810
182972	2.8607	1470

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.65	gold quality
cingulate cortex	UBERON:0003027	98.53	gold quality
anterior cingulate cortex	UBERON:0009835	98.53	gold quality
prefrontal cortex	UBERON:0000451	98.35	gold quality
left testis	UBERON:0004533	97.90	gold quality
apex of heart	UBERON:0002098	97.89	gold quality
adenohypophysis	UBERON:0002196	97.80	gold quality
amygdala	UBERON:0001876	97.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.77	gold quality
right testis	UBERON:0004534	97.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.68	gold quality
lower esophagus mucosa	UBERON:0035834	97.51	gold quality
gastrocnemius	UBERON:0001388	97.48	gold quality
cerebellar hemisphere	UBERON:0002245	97.45	gold quality
cerebellar cortex	UBERON:0002129	97.42	gold quality
nucleus accumbens	UBERON:0001882	97.30	gold quality
right atrium auricular region	UBERON:0006631	97.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.21	gold quality
lower esophagus	UBERON:0013473	97.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.20	gold quality
ganglionic eminence	UBERON:0004023	97.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.14	gold quality
caudate nucleus	UBERON:0001873	97.07	gold quality
right adrenal gland	UBERON:0001233	96.99	gold quality
right adrenal gland cortex	UBERON:0035827	96.95	gold quality
frontal cortex	UBERON:0001870	96.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.91	gold quality
left adrenal gland cortex	UBERON:0035825	96.91	gold quality
left adrenal gland	UBERON:0001234	96.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	342.54
E-ANND-3	yes	9.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting UBE2M, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 23)

• crystal structure of a complex between the C-terminal domain from NEDD8’s heterodimeric E1 (APPBP1-UBA3) and the catalytic core domain of NEDD8’s E2 (Ubc12) (PMID:15694336)
• SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation (PMID:18826954)
• Our results demonstrate a role for UBE2M in mediating cytotoxicity of gemcitabine in human urothelial carcinoma cells. (PMID:21477582)
• Distinct preferences of UBC12 and UBE2F peptides for inhibiting different DCNLs, including the oncogenic DCNL1. (PMID:23201271)
• UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle. (PMID:25025768)
• E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human intrahepatic cholangiocarcinoma (PMID:25229838)
• Polymorphisms in the UBE2M gene are associated with cetuximab efficacy in colorectal cancer. (PMID:26206335)
• GlyRS preferentially binds and protects Ubc12. (PMID:27348078)
• Furthermore, the authors characterized SENP8/DEN1 as the protease that counteracts Ubc12 auto-neddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components in SENP8-deficient cells. (PMID:28475037)
• Impairment of NEDDylation by Ubc12 knockout enhances PCNA ubiquitination and promotes PCNA-poleta interaction, while up-regulation of NEDDylation by NEDD8 overexpression or NEDP1 deletion reduces the excessive accumulation of ubiquitinated PCNA. Moreover, Ubc12 knockout decreases cell sensitivity to H2O2-induced oxidative stress, but NEDP1 deletion aggravates this sensitivity (PMID:28831681)
• the DCN1-UBC12 interaction is inhibited by DI-591, a high-affinity, cell-permeable small-molecule inhibitor that binds to purified recombinant human DCN1 and DCN2 proteins with K i values of 10-12 nM (PMID:29074978)
• Study establishes a negative regulatory axis between two neddylation E2s with UBE2M ubiquitylating UBE2F, and two CRLs with CRL3 inactivating CRL5. (PMID:29932898)
• In this study, we found that UBC12 was overexpressed in human lung cancer, increased with disease deterioration, and positively correlated with NEDD8 expression. Moreover, targeting UBC12 effectively suppressed the malignant phenotypes of lung cancer both in vitro and in vivo (PMID:31208947)
• The present study was designed to assess the effects of Nedd8conjugating enzyme UBE2M knockdown on intrahepatic cholangiocarcinoma cells, and to determine the potential underlying mechanisms. UBE2M and associated protein expression levels were determined via immunohistochemistry and western blotting (PMID:31545502)
• All reported DCN1 inhibitors are able to induce remarkable accumulation of cullin 3 and its substrate NRF2, indicating therapeutic potential of DCN1 inhibitors for human diseases that may benefit from upregulation of cullin 3 and NRF2 (PMID:31668094)
• REVIEW: Targeting DCN1-UBC12 Protein-Protein Interaction for Regulation of Neddylation Pathway (PMID:31898237)
• UBE2M promotes cell proliferation via the beta-catenin/cyclin D1 signaling in hepatocellular carcinoma. (PMID:32012120)
• UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis. (PMID:32449166)
• NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma. (PMID:32651357)
• Ubiquitin conjugating enzyme E2 M promotes apoptosis in osteoarthritis chondrocytes via Wnt/beta-catenin signaling. (PMID:32819607)
• NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation. (PMID:33905671)
• NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins. (PMID:38126621)
• UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance. (PMID:39138151)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	UBE2M	ENSDARG00000101521
mus_musculus	Ube2m	ENSMUSG00000005575
rattus_norvegicus	Chmp2a	ENSRNOG00000043328

Protein

Protein identifiers

NEDD8-conjugating enzyme Ubc12 — P61081 (reviewed: P61081)

Alternative names: NEDD8 carrier protein, Ubiquitin-conjugating enzyme E2 M

All UniProt accessions (4): P61081, A0A024R4T4, M0QX69, M0QYI6

UniProt curated annotations — full annotation on UniProt →

Function. Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation.

Subunit / interactions. Interacts with UBA3 and RBX1. Interacts (N-terminally acetylated form) with (via DCUN1 domain) DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5.

Post-translational modifications. The acetylation of Met-1 increases affinity for DCUN1D1 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins.

Domain organisation. Both the N-terminal docking peptide and the catalytic core domain must bind the UBA3-NAE1 complex simultaneously for optimal transfer of NEDD8.

Pathway. Protein modification; protein neddylation.

Similarity. Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P61081-1	1	yes
P61081-2	2

RefSeq proteins (1): NP_003960* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site
IPR050113	Ub_conjugating_enzyme-E2-like	Family

Pfam: PF00179

Enzyme classification (BRENDA):

• EC 2.3.2.34 — E2 NEDD8-conjugating enzyme (BRENDA: 3 organisms, 20 substrates, 2 inhibitors, 0 Km, 0 kcat entries)

UniProt features (49 total): mutagenesis site 19, strand 8, helix 6, modified residue 6, turn 3, region of interest 2, chain 1, domain 1, splice variant 1, active site 1, initiator methionine 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3TDU	X-RAY DIFFRACTION	1.5
3TDZ	X-RAY DIFFRACTION	2
1Y8X	X-RAY DIFFRACTION	2.4
1TT5	X-RAY DIFFRACTION	2.6
2NVU	X-RAY DIFFRACTION	2.8
4P5O	X-RAY DIFFRACTION	3.11
4GAO	X-RAY DIFFRACTION	3.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61081-F1	91.87	0.86

Functional residue map

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

Catalytic / active sites (1): 111 (glycyl thioester intermediate)

Post-translational modifications (6): 2, 1, 3, 50, 169, 169

Mutagenesis-validated functional residues (19):

Position	Phenotype
1	no effect on thioester intermediate formation.
4	impairs thioester intermediate formation.
5	strongly impairs thioester intermediate formation.
6	slightly impairs thioester intermediate formation.
7	strongly impairs thioester intermediate formation.
9	impairs thioester intermediate formation.
10	no effect on thioester intermediate formation.
11	no effect on thioester intermediate formation.
12	impairs thioester intermediate formation.
32	strongly impairs thioester intermediate formation.
35	strongly impairs thioester intermediate formation.
36	strongly impairs thioester intermediate formation.
38	strongly impairs thioester intermediate formation.
39	no effect on thioester intermediate formation.
41	strongly impairs thioester intermediate formation.
51	strongly impairs thioester intermediate formation.
55	strongly impairs thioester intermediate formation.
57	strongly impairs thioester intermediate formation.
111	forms a stable complex with nedd8, which prevents subsequent nedd8 conjugation to cullins.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5676590	NIK–>noncanonical NF-kB signaling
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 193 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_SYNAPSE_ASSEMBLY, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, PAL_PRMT5_TARGETS_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, CMYB_01, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_PROTEIN_NEDDYLATION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

GO Biological Process (6): protein modification process (GO:0036211), post-translational protein modification (GO:0043687), protein neddylation (GO:0045116), regulation of postsynapse assembly (GO:0150052), protein polyubiquitination (GO:0000209), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (8): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), NEDD8 transferase activity (GO:0019788), NEDD8 conjugating enzyme activity (GO:0061654), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by TGF-beta Receptor Complex	1
CLEC7A (Dectin-1) signaling	1
TNFR2 non-canonical NF-kB pathway	1
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	3
ubiquitin-like protein transferase activity	2
protein metabolic process	1
macromolecule modification	1
protein modification process	1
protein modification by small protein conjugation	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
protein ubiquitination	1
protein modification by small protein conjugation or removal	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
NEDD8 transferase activity	1
ubiquitin-like protein conjugating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

2514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2M	NAE1	Q13564	999
UBE2M	UBA3	Q8TBC4	999
UBE2M	DCUN1D1	Q96GG9	997
UBE2M	NEDD8	Q15843	995
UBE2M	RBX1	P62877	977
UBE2M	UBA1	P22314	952
UBE2M	CUL1	Q13616	904
UBE2M	UFC1	Q9Y3C8	857
UBE2M	UFM1	P61960	797
UBE2M	UBA5	Q9GZZ9	793
UBE2M	CUL4A	Q13619	787
UBE2M	COPS5	Q92905	776
UBE2M	SENP8	Q96LD8	774
UBE2M	RNF7	Q9UBF6	772
UBE2M	CAND1	Q86VP6	717

IntAct

145 interactions, top by confidence:

A	B	Type	Score
UBE2M	NEDD8	psi-mi:“MI:0915”(physical association)	0.940
UBE2M	NEDD8	psi-mi:“MI:0407”(direct interaction)	0.940
NEDD8	UBE2M	psi-mi:“MI:0407”(direct interaction)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
UBE2M	UBA3	psi-mi:“MI:0407”(direct interaction)	0.820
UBE2M	UBA3	psi-mi:“MI:0915”(physical association)	0.820
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
CUL1	UBE2M	psi-mi:“MI:0567”(neddylation reaction)	0.790
UBE2M	CUL1	psi-mi:“MI:0567”(neddylation reaction)	0.790
CUL1	UBE2M	psi-mi:“MI:0915”(physical association)	0.790
RBX1	UBE2M	psi-mi:“MI:0407”(direct interaction)	0.750
UBE2M	RBX1	psi-mi:“MI:0915”(physical association)	0.750
DCUN1D1	UBE2M	psi-mi:“MI:0915”(physical association)	0.740
FBXO11	TP53	psi-mi:“MI:0567”(neddylation reaction)	0.650
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
CUL1		psi-mi:“MI:0220”(ubiquitination reaction)	0.620
UBE2M	GNB2	psi-mi:“MI:0915”(physical association)	0.560
UBE2M	PRKN	psi-mi:“MI:0915”(physical association)	0.560
UBE2M	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530

BioGRID (874): RBX1 (Two-hybrid), DCUN1D1 (Co-crystal Structure), UBE2M (Affinity Capture-Western), UBE2M (Reconstituted Complex), UBE2M (Reconstituted Complex), UBE2M (Affinity Capture-Western), UBE2M (Reconstituted Complex), UBE2M (Reconstituted Complex), CUL1 (Biochemical Activity), UBE2M (Reconstituted Complex), UBE2M (Reconstituted Complex), UBE2M (Biochemical Activity), UBE2M (Biochemical Activity), UBE2M (Reconstituted Complex), UBE2M (Reconstituted Complex)

ESM2 similar proteins: A3KN22, O74549, P0C8G3, P21734, P25869, P27949, P49427, P51965, P52482, P52491, P61081, P61082, P62253, P62254, P62255, Q08BH7, Q1RMW1, Q29503, Q3UWQ3, Q42540, Q42541, Q54TI6, Q55EY8, Q5M8Y2, Q5U203, Q5ZKX6, Q6C9W0, Q6CSW8, Q6DCZ9, Q6FVQ8, Q6IRC7, Q6NY82, Q6P8D9, Q6ZWZ2, Q712K3, Q75AF2, Q7ZY08, Q8CFI2, Q91W82, Q95017

Diamond homologs: A0A1B0GUS4, A3KN22, A5PKP9, D3ZDK2, O00103, O00762, O13685, O74196, O74549, P0CS16, P0CS17, P15731, P15732, P21734, P25867, P35128, P35129, P35130, P35131, P35132, P35133, P35134, P35135, P42746, P43102, P46595, P49459, P51668, P52478, P52490, P52491, P52492, P61077, P61078, P61079, P61080, P61081, P61082, P62837, P62838

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2M	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2M	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
Neddylation	16	6.7×	1e-06
mRNA Splicing - Major Pathway	12	5.8×	4e-04
Antigen processing: Ubiquitination & Proteasome degradation	13	4.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	8	42.6×	1e-08
intrinsic apoptotic signaling pathway	5	13.6×	5e-03
negative regulation of translation	7	10.4×	1e-03
mRNA splicing, via spliceosome	10	6.9×	8e-04
ubiquitin-dependent protein catabolic process	11	6.2×	8e-04
protein phosphorylation	11	5.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

748 predictions. Top by Δscore:

Variant	Effect	Δscore
19:58556227:CTC:C	acceptor_gain	1.0000
19:58556229:CCTGT:C	acceptor_loss	1.0000
19:58556230:C:CC	acceptor_gain	1.0000
19:58556237:CAG:C	acceptor_gain	1.0000
19:58556238:A:T	acceptor_gain	1.0000
19:58556310:ACT:A	donor_loss	1.0000
19:58556312:TCAC:T	donor_loss	1.0000
19:58556313:CA:C	donor_loss	1.0000
19:58556314:A:AC	donor_gain	1.0000
19:58556315:C:CC	donor_gain	1.0000
19:58556376:CTCT:C	acceptor_gain	1.0000
19:58556378:CT:C	acceptor_gain	1.0000
19:58556380:C:A	acceptor_loss	1.0000
19:58556380:C:CC	acceptor_gain	1.0000
19:58556381:T:A	acceptor_loss	1.0000
19:58556681:CCTCA:C	donor_loss	1.0000
19:58556682:CTCA:C	donor_loss	1.0000
19:58556683:TCACC:T	donor_loss	1.0000
19:58556684:CACCT:C	donor_loss	1.0000
19:58556685:A:AC	donor_gain	1.0000
19:58556686:C:CC	donor_gain	1.0000
19:58556686:C:CG	donor_loss	1.0000
19:58556789:ACCT:A	acceptor_loss	1.0000
19:58556790:CCT:C	acceptor_loss	1.0000
19:58556798:C:CT	acceptor_gain	1.0000
19:58556798:C:T	acceptor_gain	1.0000
19:58556799:A:T	acceptor_gain	1.0000
19:58556888:TCA:T	donor_loss	1.0000
19:58556890:A:AT	donor_loss	1.0000
19:58556891:C:CA	donor_loss	1.0000

AlphaMissense

1214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:58556161:A:C	F160L	1.000
19:58556161:A:T	F160L	1.000
19:58556163:A:G	F160L	1.000
19:58556183:A:G	L153P	1.000
19:58556193:C:G	A150P	1.000
19:58556195:G:T	A149D	1.000
19:58556207:A:G	L145P	1.000
19:58556213:T:C	D143G	1.000
19:58556323:A:G	L135P	1.000
19:58556332:A:G	L132P	1.000
19:58556335:C:T	G131D	1.000
19:58556336:C:G	G131R	1.000
19:58556344:A:T	I128K	1.000
19:58556359:A:G	L123P	1.000
19:58556362:A:T	V122D	1.000
19:58556365:G:T	P121Q	1.000
19:58556370:C:A	W119C	1.000
19:58556370:C:G	W119C	1.000
19:58556371:C:G	W119S	1.000
19:58556372:A:G	W119R	1.000
19:58556372:A:T	W119R	1.000
19:58556379:T:A	R116S	1.000
19:58556379:T:G	R116S	1.000
19:58556687:C:A	R116I	1.000
19:58556687:C:G	R116T	1.000
19:58556690:A:G	L115P	1.000
19:58556690:A:T	L115H	1.000
19:58556699:A:G	L112P	1.000
19:58556699:A:T	L112H	1.000
19:58556701:G:C	C111W	1.000

dbSNP variants (sampled 300 via entrez): RS1000133837 (19:58555279 C>A), RS1001524540 (19:58559789 G>A,C), RS1002285561 (19:58555552 T>A), RS1002316712 (19:58555386 T>C), RS1002934396 (19:58558783 C>T), RS1003015512 (19:58555924 A>T), RS1003161727 (19:58558903 G>A), RS1004152273 (19:58555756 T>G), RS1004245591 (19:58555876 C>A,T), RS1004870845 (19:58557210 G>A,C), RS1006060054 (19:58560334 G>C), RS1006287317 (19:58555696 T>A,G), RS1006512221 (19:58555886 G>A,T), RS1006673685 (19:58559117 G>A), RS1007785569 (19:58558911 G>A,C)

Disease associations

OMIM: gene MIM:603173 | 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
GCST90002390_664	Mean corpuscular hemoglobin	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4295787 (SINGLE PROTEIN), CHEMBL4523603 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523656 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 120 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL457547	MICAFUNGIN	4	120

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

ChEMBL bioactivities

388 potent at pChembl≥5 of 483 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.59	Ki	2.57	nM	CHEMBL6160376
8.53	IC50	2.96	nM	CHEMBL6160376
8.37	IC50	4.3	nM	CHEMBL5908146
8.27	IC50	5.41	nM	CHEMBL6147339
8.17	IC50	6.8	nM	CHEMBL5994790
8.11	IC50	7.85	nM	CHEMBL6159903
8.08	Ki	8.26	nM	CHEMBL5085822
8.06	IC50	8.77	nM	CHEMBL6159780
8.03	IC50	9.42	nM	CHEMBL6169886
8.03	IC50	9.39	nM	CHEMBL6152670
7.98	IC50	10.57	nM	CHEMBL6148513
7.96	IC50	11	nM	CHEMBL5268493
7.91	IC50	12.31	nM	CHEMBL6151309
7.89	IC50	12.82	nM	CHEMBL6160640
7.87	Ki	13.66	nM	CHEMBL4592844
7.85	IC50	14.06	nM	CHEMBL6147763
7.82	IC50	15	nM	CHEMBL5276248
7.82	IC50	15.27	nM	CHEMBL6091989
7.80	IC50	16	nM	CHEMBL5267017
7.80	IC50	15.65	nM	CHEMBL6149459
7.77	IC50	17	nM	CHEMBL5279467
7.75	IC50	18	nM	CHEMBL5801181
7.74	IC50	18.31	nM	CHEMBL4592844
7.72	IC50	19	nM	CHEMBL4517307
7.72	IC50	18.91	nM	CHEMBL6148881
7.70	IC50	19.92	nM	CHEMBL6168999
7.66	IC50	22	nM	CHEMBL5278571
7.66	IC50	22	nM	CHEMBL5271740
7.65	IC50	22.17	nM	CHEMBL6102730
7.62	IC50	24	nM	CHEMBL5288681
7.60	IC50	24.87	nM	CHEMBL6102329
7.59	IC50	25.65	nM	CHEMBL6109007
7.56	IC50	27.42	nM	CHEMBL6160603
7.55	IC50	28	nM	CHEMBL4440896
7.55	IC50	28	nM	CHEMBL5288518
7.54	IC50	28.84	nM	CHEMBL6133122
7.46	IC50	35	nM	CHEMBL4077431
7.41	IC50	39	nM	CHEMBL5280708
7.37	IC50	43.06	nM	CHEMBL6152462
7.34	IC50	46.17	nM	CHEMBL6145788
7.34	IC50	45.16	nM	CHEMBL6120490
7.30	IC50	50.51	nM	CHEMBL6150583
7.29	IC50	51	nM	CHEMBL5287179
7.28	IC50	53	nM	CHEMBL4099097
7.25	IC50	55.9	nM	CHEMBL4094517
7.24	IC50	58	nM	CHEMBL5268005
7.24	IC50	58	nM	CHEMBL4077759
7.23	IC50	59	nM	CHEMBL5277278
7.22	IC50	60	nM	CHEMBL4864963
7.22	IC50	60	nM	CHEMBL4074213

PubChem BioAssay actives

113 with measured affinity, of 269 total; 50 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
2-[5-[[2-[(4-chlorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0110	uM
2-[5-[[2-[(4-bromophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0150	uM
2-[5-[[2-[(4-fluorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0160	uM
2-[5-[[2-[(4-chloro-3-fluorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0170	uM
(2S)-N-[(1S)-1-cyclohexyl-2-(3-morpholin-4-ylpropanoylamino)ethyl]-2-(propanoylamino)-3-(6-propan-2-yl-1,3-benzothiazol-2-yl)propanamide	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0190	uM
2-[5-[(2-benzylsulfanyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0220	uM
2-[5-[[2-[(3-chloro-4-fluorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0220	uM
N,N-dimethyl-2-[5-[[5-methyl-2-[(2-nitrophenyl)methylsulfanyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0240	uM
N-[2-[[(1-pentan-2-ylpiperidin-4-yl)-[[3-(trifluoromethyl)phenyl]carbamoyl]amino]methyl]phenyl]prop-2-enamide	1960618: Inhibition of biotinylated DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by TR-FRET analysis	ic50	0.0280	uM
2-[5-[[2-[(4-methoxyphenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0280	uM
N,N-dimethyl-2-[5-[[5-methyl-2-[(4-nitrophenyl)methylsulfanyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0390	uM
N,N-dimethyl-2-[5-[(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0510	uM
2-[5-[[2-(cyclohexylmethylsulfanyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0580	uM
2-[5-[[2-(cyclopropylmethylsulfanyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0590	uM
1-benzyl-1-(1-butylpiperidin-4-yl)-3-(3,4-dichlorophenyl)urea	1960618: Inhibition of biotinylated DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by TR-FRET analysis	ic50	0.0600	uM
N-[3-(aminomethyl)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.0600	uM
N,N-dimethyl-2-[5-(1,8,10,12-tetrazatricyclo[7.3.0.03,7]dodeca-2,7,9,11-tetraen-2-ylsulfanyl)tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0610	uM
N,N-dimethyl-2-[5-[(5-methyl-2-prop-2-ynylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0670	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-3-(piperidin-1-ylmethyl)-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.0700	uM
N-[(4S,5S)-3-[(ethenylsulfonylamino)methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.0700	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-[(4-methylpiperazin-1-yl)methyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.0700	uM
N,N-dimethyl-2-[5-[[5-methyl-2-[(4-methylphenyl)methylsulfanyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0780	uM
N,N-dimethyl-2-[5-[(5-phenyl-2-prop-2-ynylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0790	uM
N-[(4S,5S)-3-(acetamidomethyl)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.0900	uM
tert-butyl N-[3-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylamino]propyl]carbamate	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.1000	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-(morpholin-4-ylmethyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.1000	uM
N-[(4S,5S)-3-(aminomethyl)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.1000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149710: Binding affinity to human UBE2M incubated for 45 mins by Kinobead based pull down assay	kd	0.1079	uM
2-[5-[(5-cyclopropyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.1270	uM
N,N-dimethyl-2-[5-[(5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.1300	uM
N,N-dimethyl-2-[5-[(5-methyl-2-prop-2-enylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.1370	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-(hydroxymethyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.1700	uM
N,N-dimethyl-2-[5-[[5-methyl-2-[[4-(trifluoromethyl)phenyl]methylsulfanyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.1860	uM
2-[5-[[2-[(2,6-dichlorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.1920	uM
2-[5-[[2-[(3-bromophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.1950	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-methylbenzamide	1579906: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.2000	uM
N-[(4S,5S)-1-cyclopropyl-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-methylbenzamide	1579906: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.2000	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-1-propyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-methylbenzamide	1579906: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.2000	uM
N,N-dimethyl-2-[5-[[5-methyl-2-(naphthalen-1-ylmethylsulfanyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.2090	uM
N,N-dimethyl-2-[5-[(5-methyl-2-propylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.2140	uM
N-[(4S,5S)-7-ethyl-4-(6-fluoro-3-pyridinyl)-3-methyl-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.2400	uM
N,N-dimethyl-2-[5-[(5-methyl-2-propan-2-ylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.2680	uM
2-[5-[(2-benzylsulfanyl-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.2900	uM
N-[(4S,5S)-1-cyclopentyl-4-(4-fluorophenyl)-3-methyl-6-oxo-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-5-yl]-3-methylbenzamide	1579906: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.3000	uM
4-[[7-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]sulfanylmethyl]benzo[h]chromen-2-one;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.3090	uM
N-[(4S,5S)-7-ethyl-4-(4-fluoro-3-nitrophenyl)-3-methyl-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.3100	uM
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.3200	uM
N-[(4S,5S)-4-(4-fluorophenyl)-7-(2-hydroxyethyl)-3-methyl-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.3400	uM
2-[5-[(2-benzylsulfanyl-5-ethyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.3520	uM
N-[(4R,5S)-7-ethyl-3-methyl-6-oxo-1-phenyl-4-(1,2-thiazol-4-yl)-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	1776608: Inhibition of biotinylated DCN1 (unknown origin) - AlexaFluor488 labelled UBE2M (unknown origin) protein-protein interaction after 1 hr by TR-FRET assay	ic50	0.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	3
sodium arsenite	affects binding, increases reaction, decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, affects expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Smoke	decreases expression, increases abundance	2
Cyclosporine	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
trichostatin A	affects expression	1
cobaltous chloride	increases expression	1
nickel sulfate	increases expression	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arbutin	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Cocaine	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1

ChEMBL screening assays

83 unique, capped per target: 83 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4222567	Binding	Binding affinity to N-terminally acetylated human UBE2M	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.