UBA3

Summary

UBA3 (ubiquitin like modifier activating enzyme 3, HGNC:12470) is a protein-coding gene on chromosome 3p14.1, encoding NEDD8-activating enzyme E1 catalytic subunit (Q8TBC4). Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. It is a selective cancer dependency (DepMap: 83.9% of 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 E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 9039 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 78 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 83.9% of screened cell lines
• MANE Select transcript: NM_003968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12470
Approved symbol	UBA3
Name	ubiquitin like modifier activating enzyme 3
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	hUba3, NAE2
Ensembl gene	ENSG00000144744
Ensembl biotype	protein_coding
OMIM	603172
Entrez	9039

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 22 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000349511, ENST00000361055, ENST00000415609, ENST00000461522, ENST00000461934, ENST00000464605, ENST00000465108, ENST00000465627, ENST00000466763, ENST00000485424, ENST00000493957, ENST00000630585, ENST00000854659, ENST00000854660, ENST00000854661, ENST00000854662, ENST00000854663, ENST00000854664, ENST00000854665, ENST00000854666, ENST00000854667, ENST00000854668, ENST00000931269, ENST00000968747, ENST00000968748, ENST00000968749, ENST00000968750, ENST00000968751, ENST00000968752, ENST00000968753

RefSeq mRNA: 3 — MANE Select: NM_003968 NM_001363861, NM_003968, NM_198195

CCDS: CCDS2909, CCDS2910, CCDS87106

Canonical transcript exons

ENST00000361055 — 18 exons

Exon	Start	End
ENSE00000966872	69067928	69068008
ENSE00000966873	69064068	69064111
ENSE00001376644	69071535	69071617
ENSE00001518240	69054730	69055525
ENSE00003460896	69056000	69056063
ENSE00003489907	69075430	69075510
ENSE00003502454	69055851	69055905
ENSE00003508973	69056183	69056283
ENSE00003525143	69061814	69061927
ENSE00003534643	69063439	69063503
ENSE00003538340	69077798	69077918
ENSE00003563643	69056612	69056693
ENSE00003657960	69062077	69062179
ENSE00003661106	69062982	69063137
ENSE00003685682	69056779	69056815
ENSE00003686622	69080112	69080153
ENSE00003688550	69057256	69057309
ENSE00003846957	69080334	69080365

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8626 / max 1329.5877, expressed in 1798 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42955	26.8626	1798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	97.75	gold quality
monocyte	CL:0000576	97.63	gold quality
mononuclear cell	CL:0000842	97.59	gold quality
leukocyte	CL:0000738	97.31	gold quality
secondary oocyte	CL:0000655	97.10	gold quality
epithelium of nasopharynx	UBERON:0001951	97.05	gold quality
upper leg skin	UBERON:0004262	96.92	gold quality
germinal epithelium of ovary	UBERON:0001304	96.88	gold quality
esophagus squamous epithelium	UBERON:0006920	96.81	gold quality
gingival epithelium	UBERON:0001949	96.59	gold quality
heart right ventricle	UBERON:0002080	96.55	gold quality
skin of hip	UBERON:0001554	96.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.05	gold quality
gingiva	UBERON:0001828	95.97	gold quality
visceral pleura	UBERON:0002401	95.91	gold quality
calcaneal tendon	UBERON:0003701	95.82	gold quality
myocardium	UBERON:0002349	95.61	gold quality
endothelial cell	CL:0000115	95.59	gold quality
parietal pleura	UBERON:0002400	95.55	gold quality
tibia	UBERON:0000979	95.53	gold quality
corpus callosum	UBERON:0002336	95.53	gold quality
squamous epithelium	UBERON:0006914	95.38	gold quality
left ventricle myocardium	UBERON:0006566	95.27	gold quality
pleura	UBERON:0000977	95.26	gold quality
endometrium	UBERON:0001295	95.20	gold quality
superficial temporal artery	UBERON:0001614	95.03	gold quality
tonsil	UBERON:0002372	95.02	gold quality
vermiform appendix	UBERON:0001154	94.96	gold quality
corpus epididymis	UBERON:0004359	94.95	gold quality
epithelium of esophagus	UBERON:0001976	94.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.94
E-GEOD-100618	no	617.84
E-GEOD-124858	no	451.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

66 targeting UBA3, 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-126-5P	100.00	72.71	3180
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-664B-3P	99.84	71.65	3590

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• structure and mutational analysis of human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8 (PMID:12646924)
• Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. (PMID:12740388)
• Data report the structure of the quaternary complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP. (PMID:14690597)
• 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)
• X-ray crystallographic analysis of APPBP1-UBA3-NEDD8 shows that APPBP1-UBA3’s preference for NEDD8’s Ala72 appears to be indirect, due to proper positioning of UBA3’s Arg190. (PMID:18652489)
• Demonstrated that Uba3-betaGD is an independently folded domain in solution and that residues involved in E2 binding are absent from the NMR spectrum, indicating that the E2-binding surface on Uba3-betaGD interconverts between multiple conformations. (PMID:22821745)
• Report role for neddylation via Nedd8-activating enzyme in the regulation of tumor angiogenesis. (PMID:24525735)
• The study demonstrated that two mutations in UBA3 which were not previously reported confer MLN4924 resistance to MLN4924, a selective NEDD8-activating enzyme inhibitor. (PMID:24691136)
• 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)
• The NEDD8-activating enzyme E1 UBA3 orchestrates the immunosuppressive microenvironment in lung adenocarcinoma via the NF-small ka, CyrillicB pathway. (PMID:37656220)
• UBE1C is upregulated and promotes neddylation of p53 in lung cancer. (PMID:37668436)
• UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway. (PMID:38298057)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	uba3	ENSDARG00000057987
mus_musculus	Uba3	ENSMUSG00000030061
rattus_norvegicus	Uba3	ENSRNOG00000006221
drosophila_melanogaster	Uba3	FBGN0263697
caenorhabditis_elegans		WBGENE00004341

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), MOCS3 (ENSG00000124217), UBA2 (ENSG00000126261), UBA1 (ENSG00000130985), SAE1 (ENSG00000142230), NAE1 (ENSG00000159593), UBA7 (ENSG00000182179), ATG7 (ENSG00000197548)

Protein

Protein identifiers

NEDD8-activating enzyme E1 catalytic subunit — Q8TBC4 (reviewed: Q8TBC4)

Alternative names: NEDD8-activating enzyme E1C, Ubiquitin-activating enzyme E1C, Ubiquitin-like modifier-activating enzyme 3

All UniProt accessions (4): Q8TBC4, F8W8D4, F8WAT6, F8WF86

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.

Subunit / interactions. Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand. Interacts with TBATA.

Tissue specificity. Ubiquitously expressed.

Activity regulation. Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.

Pathway. Protein modification; protein neddylation.

Miscellaneous. Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex.

Similarity. Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TBC4-1	1	yes
Q8TBC4-2	2

RefSeq proteins (3): NP_001350790, NP_003959, NP_937838 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR014929	E2-binding	Domain
IPR023318	Ub_act_enz_dom_a_sf	Homologous_superfamily
IPR030468	Uba3_N	Domain
IPR033127	UBQ-activ_enz_E1_Cys_AS	Active_site
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00899, PF08825

Enzyme classification (BRENDA):

• EC 2.3.2.23 — E2 ubiquitin-conjugating enzyme (BRENDA: 20 organisms, 93 substrates, 28 inhibitors, 12 Km, 8 kcat entries)
• EC 6.2.1.64 — E1 NEDD8-activating enzyme (BRENDA: 5 organisms, 13 substrates, 51 inhibitors, 16 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0045–0.175	9
[UBIQUITIN-CARRIER-PROTEIN UBC2B]-L-CYSTEINE	0.0001	5
DIPHOSPHATE	0.005–0.0511	4
UBIQUITIN	0.0006–0.0012	3
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.2203–0.3014	2
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1

UniProt features (89 total): mutagenesis site 24, helix 21, strand 19, region of interest 9, turn 5, binding site 2, sequence conflict 2, initiator methionine 1, chain 1, active site 1, site 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
5JJM	X-RAY DIFFRACTION	2.15
1Y8X	X-RAY DIFFRACTION	2.4
3FN1	X-RAY DIFFRACTION	2.5
1TT5	X-RAY DIFFRACTION	2.6
1YOV	X-RAY DIFFRACTION	2.6
2NVU	X-RAY DIFFRACTION	2.8
3DBH	X-RAY DIFFRACTION	2.85
3DBL	X-RAY DIFFRACTION	2.9
1R4M	X-RAY DIFFRACTION	3
3GZN	X-RAY DIFFRACTION	3
3DBR	X-RAY DIFFRACTION	3.05
1R4N	X-RAY DIFFRACTION	3.6
2LQ7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBC4-F1	93.20	0.89

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 (2): 237 (glycyl thioester intermediate); 211 (determines specificity for nedd8)

Ligand- & substrate-binding residues (2): 100–124; 148–171

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (24):

Position	Phenotype
65	reduces affinity for ube2m.
148	no effect on nedd8 adenylation.
160–161	reduces affinity for ube2m.
167	abolishes nedd8 adenylation.
192	reduces affinity for ube2m; when associated with a-195 and a-197.
195	reduces affinity for ube2m; when associated with a-192 and a-197.
197	reduces affinity for ube2m; when associated with a-192 and a-195.
211	abolishes specificity for nedd8.
214	reduces affinity for ube2m; when associated with a-217.
217	reduces affinity for ube2m; when associated with a-214.
227–228	strongly reduces nedd8 adenylation.
237	abolishes thioester intermediate formation.
238	no effect on nedd8 adenylation; impairs thioester intermediate formation.
310	no effect on nedd8 adenylation or thioester intermediate formation; impairs nedd8 transfer to ube2m.
331	reduces affinity for ube2m.
352–357	abolishes nedd8 adenylation.
368	impairs nedd8 transfer to ube2m.
369	no effect on nedd8 transfer to ube2m.
370	impairs nedd8 transfer to ube2m.
412	impairs nedd8 transfer to ube2m.
415	impairs nedd8 transfer to ube2m.
418	impairs nedd8 transfer to ube2m.
421	impairs nedd8 transfer to ube2m.
424	no effect on nedd8 transfer to ube2m.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
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
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 177 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_PROTEIN_NEDDYLATION, WONG_PROTEASOME_GENE_MODULE, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, PID_ERB_GENOMIC_PATHWAY, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, TGCTGAY_UNKNOWN

GO Biological Process (8): proteolysis (GO:0006508), endomitotic cell cycle (GO:0007113), protein modification process (GO:0036211), post-translational protein modification (GO:0043687), protein neddylation (GO:0045116), regulation of cell cycle (GO:0051726), mitotic cell cycle (GO:0000278), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (9): ATP binding (GO:0005524), NEDD8 activating enzyme activity (GO:0019781), NEDD8 transferase activity (GO:0019788), identical protein binding (GO:0042802), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641), ligase activity (GO:0016874)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
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
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cell cycle	2
cellular anatomical structure	2
mitotic cell cycle	1
macromolecule modification	1
protein modification process	1
protein modification by small protein conjugation	1
regulation of cellular process	1
mitotic nuclear division	1
protein modification by small protein conjugation or removal	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like modifier activating enzyme activity	1
ubiquitin-like protein transferase activity	1
protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
ligase activity, forming carbon-sulfur bonds	1
catalytic activity, acting on a protein	1
ATP-dependent activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cellular_component	1

Protein interactions and networks

STRING

2596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBA3	UBE2M	P61081	999
UBA3	NAE1	Q13564	999
UBA3	NEDD8	Q15843	998
UBA3	UBE2F	Q969M7	922
UBA3	RBX1	P62877	893
UBA3	CUL1	Q13616	877
UBA3	CUL7	Q14999	813
UBA3	UBA5	Q9GZZ9	808
UBA3	SENP8	Q96LD8	792
UBA3	DCUN1D1	Q96GG9	778
UBA3	SKP1	P34991	756
UBA3	RNF7	Q9UBF6	744
UBA3	FBXW8	Q8N3Y1	732
UBA3	COPS5	Q92905	730
UBA3	FBXW11	Q9UKB1	717

IntAct

68 interactions, top by confidence:

A	B	Type	Score
NEDD8	UBE2M	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
CUL1	UBE2M	psi-mi:“MI:0567”(neddylation reaction)	0.790
UBA3	IMPA2	psi-mi:“MI:0915”(physical association)	0.720
CPNE2	UBA3	psi-mi:“MI:0915”(physical association)	0.720
UBA3	CPNE2	psi-mi:“MI:0915”(physical association)	0.720
IMPA2	UBA3	psi-mi:“MI:0915”(physical association)	0.720
NEDD8	NAE1	psi-mi:“MI:0915”(physical association)	0.670
UBA3	UBA3	psi-mi:“MI:0915”(physical association)	0.670
NEDD8	NAE1	psi-mi:“MI:0914”(association)	0.670
FBXO11	TP53	psi-mi:“MI:0567”(neddylation reaction)	0.650
UBA3	DUSP23	psi-mi:“MI:0915”(physical association)	0.560
NAE1	UBA3	psi-mi:“MI:0915”(physical association)	0.560
UBA3	APOE	psi-mi:“MI:0915”(physical association)	0.560
APP	UBA3	psi-mi:“MI:0915”(physical association)	0.560
UBE2M	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
APIP	VSIG8	psi-mi:“MI:0914”(association)	0.530
CUL5	UBE2M	psi-mi:“MI:0567”(neddylation reaction)	0.440
	DENR	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (144): UBA3 (Two-hybrid), UBA3 (Two-hybrid), CPNE2 (Two-hybrid), UBA3 (Reconstituted Complex), UBE2M (Biochemical Activity), UBE2F (Biochemical Activity), UBA3 (Biochemical Activity), UBE2M (Biochemical Activity), NAE1 (Reconstituted Complex), UBA3 (Affinity Capture-MS), UBA3 (Affinity Capture-MS), ATG7 (Co-fractionation), UBA3 (Co-fractionation), UBA3 (Affinity Capture-MS), UBA3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4Q2, A6NEY8, A6QP05, O80526, P11172, P12081, P13439, P31754, P37111, P38918, P47897, Q02053, Q16798, Q28EX9, Q2KI84, Q2KJD7, Q32LQ4, Q3MHH4, Q502H1, Q53JY8, Q5FWT7, Q5R4A0, Q5R4C4, Q5R4R2, Q5R514, Q5R8R4, Q5RGJ5, Q5U300, Q5ZJJ8, Q61035, Q641F1, Q66H61, Q6DI37, Q6DIJ1, Q6IQS6, Q6NRL0, Q7ZVX6, Q8BGR9, Q8BML9, Q8C878

Diamond homologs: A0AVT1, A2VE14, A3KMV5, O31619, O42939, O65041, O94609, P20973, P22314, P22515, P31251, P31252, P31254, P31255, P41226, P52495, P92974, P93028, Q02053, Q06624, Q09765, Q18217, Q19360, Q29504, Q54QG9, Q54WI4, Q55C16, Q5R4A0, Q5U300, Q7ZVX6, Q8C7R4, Q8C878, Q8TBC4, Q99344, Q99MI7, Q9DBK7, Q9V6U8, Q9VTE9, A1A4L8, A1CAZ7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBA3	“form complex”	NAE	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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	9	11.5×	2e-05
Antigen processing: Ubiquitination & Proteasome degradation	7	7.0×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	5	76.3×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2560 predictions. Top by Δscore:

Variant	Effect	Δscore
3:69055521:CAATT:C	acceptor_gain	1.0000
3:69055524:TT:T	acceptor_gain	1.0000
3:69055525:TC:T	acceptor_loss	1.0000
3:69055526:C:CC	acceptor_gain	1.0000
3:69055902:CCGA:C	acceptor_gain	1.0000
3:69055903:CGA:C	acceptor_gain	1.0000
3:69055903:CGAC:C	acceptor_gain	1.0000
3:69055906:C:CC	acceptor_gain	1.0000
3:69056181:A:AC	donor_gain	1.0000
3:69056182:C:CC	donor_gain	1.0000
3:69056182:CA:C	donor_gain	1.0000
3:69056692:CA:C	acceptor_gain	1.0000
3:69056694:C:CC	acceptor_gain	1.0000
3:69075511:C:CC	acceptor_gain	1.0000
3:69077796:A:AC	donor_gain	1.0000
3:69077797:C:CC	donor_gain	1.0000
3:69077797:CTT:C	donor_gain	1.0000
3:69077799:T:TA	donor_gain	1.0000
3:69080097:C:A	donor_gain	1.0000
3:69080110:A:AC	donor_gain	1.0000
3:69080111:C:CC	donor_gain	1.0000
3:69080111:CTT:C	donor_gain	1.0000
3:69080113:T:TA	donor_gain	1.0000
3:69080328:A:AC	donor_gain	1.0000
3:69080329:C:CC	donor_gain	1.0000
3:69080331:TACGG:T	donor_loss	1.0000
3:69080332:A:AC	donor_gain	1.0000
3:69080332:ACGG:A	donor_gain	1.0000
3:69080332:ACGGC:A	donor_loss	1.0000
3:69080333:C:CT	donor_gain	1.0000

AlphaMissense

3041 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:69071550:C:A	R111M	1.000
3:69055492:A:T	V446D	0.999
3:69057268:C:G	A318P	0.999
3:69057300:T:A	K307I	0.999
3:69062164:A:G	C237R	0.999
3:69063043:C:G	R211P	0.999
3:69063461:C:G	R172T	0.999
3:69063476:T:A	D167V	0.999
3:69063476:T:G	D167A	0.999
3:69067984:C:A	K124N	0.999
3:69067984:C:G	K124N	0.999
3:69071549:C:A	R111S	0.999
3:69071549:C:G	R111S	0.999
3:69071550:C:G	R111T	0.999
3:69071558:A:C	N108K	0.999
3:69071558:A:T	N108K	0.999
3:69071571:A:T	I104K	0.999
3:69056785:G:T	A332D	0.998
3:69056808:A:C	C324W	0.998
3:69062145:G:T	P243H	0.998
3:69062162:G:C	C237W	0.998
3:69062163:C:G	C237S	0.998
3:69062164:A:T	C237S	0.998
3:69063008:A:G	C223R	0.998
3:69063052:C:T	G208E	0.998
3:69063053:C:G	G208R	0.998
3:69063053:C:T	G208R	0.998
3:69063073:C:T	G201E	0.998
3:69063074:C:A	G201W	0.998
3:69063460:T:A	R172S	0.998

dbSNP variants (sampled 300 via entrez): RS1000137675 (3:69065542 A>C), RS1000258666 (3:69075809 G>A), RS1000421654 (3:69058091 T>C), RS1000489022 (3:69063213 C>T), RS1000749576 (3:69077589 T>C), RS1000831760 (3:69054593 T>C,G), RS1000993958 (3:69056431 T>C), RS1001022104 (3:69057033 A>G), RS1001164468 (3:69059339 T>G), RS1001192476 (3:69073823 T>G), RS1001222020 (3:69074095 T>C), RS1001531378 (3:69061447 G>A,C), RS1001593228 (3:69054670 A>G,T), RS1001670175 (3:69067723 A>G), RS1001712601 (3:69064850 T>C)

Disease associations

OMIM: gene MIM:603172 | 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
GCST010143_29	Meat-related diet	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2016430 (SINGLE PROTEIN), CHEMBL3831283 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 168,358 (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
CHEMBL58	MITOXANTRONE	4	166,878
CHEMBL1231160	PEVONEDISTAT	3	1,480

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

Binding affinities (BindingDB)

5 measured of 22 human assays (22 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[4-[4-(2,3-dihydro-1H-inden-1-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate	IC50	12 nM	US-9963456: Pyrrolopyrimidine compound or salt thereof and compositions containing the pyrrolopyrimidine compound or salt thereof
[2-hydroxy-4-[7-(2-thiophen-2-ylethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof
[2-hydroxy-4-[7-(3-phenylpropylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof
[2-hydroxy-4-[7-[[(1R,2S)-2-[(2-methoxyacetyl)amino]-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof
[2-hydroxy-4-[7-[[(1S)-1’-methylspiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof

ChEMBL bioactivities

171 potent at pChembl≥5 of 173 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL5170838
9.68	IC50	0.21	nM	CHEMBL5182746
9.59	IC50	0.26	nM	PEVONEDISTAT
9.26	IC50	0.55	nM	CHEMBL5177755
9.24	IC50	0.57	nM	CHEMBL5206652
9.22	IC50	0.6	nM	CHEMBL4569826
9.05	IC50	0.9	nM	CHEMBL4582044
9.02	IC50	0.955	nM	CHEMBL5175806
9.00	IC50	1	nM	CHEMBL5181979
8.65	IC50	2.23	nM	CHEMBL5173723
8.64	IC50	2.28	nM	CHEMBL5192493
8.45	IC50	3.56	nM	CHEMBL5197178
8.40	IC50	4	nM	PEVONEDISTAT
8.38	IC50	4.2	nM	CHEMBL5209054
8.30	IC50	5	nM	PEVONEDISTAT
8.30	IC50	5	nM	CHEMBL4577730
8.24	IC50	5.77	nM	CHEMBL5188530
8.22	IC50	6	nM	CHEMBL5193236
8.21	IC50	6.11	nM	CHEMBL5177700
8.10	IC50	8	nM	CHEMBL4585101
8.10	IC50	8	nM	CHEMBL5181979
8.01	IC50	9.76	nM	CHEMBL5178136
8.00	IC50	10	nM	CHEMBL4573232
8.00	IC50	10	nM	CHEMBL4847817
8.00	IC50	9.98	nM	CHEMBL5192527
8.00	IC50	10	nM	CHEMBL2017005
7.92	IC50	12	nM	CHEMBL4514025
7.89	IC50	13	nM	CHEMBL4580824
7.82	IC50	15	nM	CHEMBL4558498
7.80	IC50	15.9	nM	CHEMBL5169743
7.72	IC50	19	nM	CHEMBL4566409
7.70	IC50	20	nM	CHEMBL4570552
7.68	IC50	21.1	nM	CHEMBL5170141
7.68	IC50	21.1	nM	CHEMBL5179467
7.66	IC50	22	nM	CHEMBL4521457
7.64	IC50	23	nM	CHEMBL4860740
7.54	IC50	29	nM	CHEMBL4878088
7.52	EC50	30	nM	PEVONEDISTAT
7.51	IC50	31	nM	CHEMBL4878832
7.51	IC50	30.6	nM	CHEMBL5207989
7.50	IC50	32	nM	CHEMBL4852015
7.50	IC50	32	nM	CHEMBL4860960
7.43	IC50	37	nM	CHEMBL4561991
7.19	IC50	64	nM	CHEMBL4853360
7.19	IC50	64	nM	CHEMBL4848442
7.17	IC50	66.9	nM	CHEMBL5201960
7.09	IC50	81.8	nM	CHEMBL5206633
7.09	IC50	80.9	nM	CHEMBL5206263
7.06	IC50	87	nM	CHEMBL4856793
7.04	IC50	91	nM	CHEMBL4537144

PubChem BioAssay actives

90 with measured affinity, of 171 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
[(1S,2S,4R)-4-[7-[[(1S)-1’-(tert-butylcarbamoyl)spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	<0.0001	uM
[(1S,2S,4R)-4-[7-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0002	uM
[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0003	uM
methyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0006	uM
[(3R)-oxolan-3-yl] (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0006	uM
4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine	1872481: Inhibition of recombinant human APPBP1/UBA3 expressed in Escherichia coli assessed as Ub/Ubl thioester transfer	ic50	0.0010	uM
[(2R,3S,4R,5R)-5-[4-amino-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1894758: Inhibition of NAE (unknown origin)	ic50	0.0010	uM
ethyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0022	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0023	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1R,2S)-2-(2-methoxyethoxy)-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0036	uM
propan-2-yl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0042	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1S)-1’-(2-methoxyacetyl)spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0058	uM
2-fluoroethyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0060	uM
[(1S,2S,4R)-4-[7-[(2-fluorophenyl)methylamino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0061	uM
tert-butyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0098	uM
[(2R,3S,4R,5R)-5-[6-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1894758: Inhibition of NAE (unknown origin)	ic50	0.0100	uM
[(1R,2S,4R)-4-[[5-[1-[(3-bromophenyl)methyl]pyrrole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0100	uM
2-morpholin-4-ylethyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0100	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(thiophen-2-ylmethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0159	uM
[(1S,2S,4R)-4-[7-(hexylamino)triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0211	uM
1,1,1,3,3,3-hexafluoropropan-2-yl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0211	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrrole-3-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0230	uM
[(1R,2R,3S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-2,3-dihydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0290	uM
[(1S,2S,4R)-4-[7-(furan-2-ylmethylamino)triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0306	uM
[(1R,2R,3S,4R)-4-[[5-[4-[1-(6-bromo-2-pyridinyl)-1-hydroxyethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2,3-dihydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0310	uM
[(1R,2S,4R)-2-hydroxy-4-[[5-(1-phenylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]cyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0320	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0320	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-hydroxymethyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0640	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0640	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1S)-spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0669	uM
methyl (1R,4S)-4-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopent-2-ene-1-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0809	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(2-phenylethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0818	uM
[(1R,2S,4R)-4-[[5-[4-(7-chloro-3,4-dihydro-1H-isochromen-1-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0870	uM
[(1R,2S,4R)-4-[[5-[4-[(3-bromophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0910	uM
[(1R,2S,4R)-4-[[5-[4-(3,4-dihydro-1H-isochromen-1-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1020	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(2-thiophen-2-ylethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1070	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-hydroxymethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1140	uM
1,3-dihydroxypropan-2-yl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1200	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrazole-4-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1220	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(3-phenylpropylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1490	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1R,2S)-2-[(2-methoxyacetyl)amino]-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1700	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1S)-1’-methylspiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1870	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1900	uM
[(1R,2S,4R)-4-[[5-[4-[(1R)-3,4-dihydro-1H-isochromen-1-yl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1980	uM
[(1R,2S,4R)-4-[[5-[4-(2-chloro-6,8-dihydro-5H-pyrano[3,4-b]pyridin-8-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.2030	uM
[(1S,2S,4R)-4-[7-[[(1R,2S)-2-(dimethylamino)-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.2070	uM
[(1R,2S,4R)-4-[[5-[1-[(2-chlorophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.2150	uM
[(1S,2S,4R)-4-[[6-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.2190	uM
[(1R,2S,4R)-4-[[5-[1-[(3-bromophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.2280	uM
[(1R,2S,4R)-4-[[5-[4-[amino-(3-chlorophenyl)methyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.2350	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
afimoxifene	affects response to substance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
deguelin	decreases expression	1
calfactant	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Copper Sulfate	decreases expression	1
Nanotubes, Carbon	increases expression, affects cotreatment	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

67 unique, capped per target: 67 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2019640	Binding	Inhibition of UBA3-mediated NEDD8 activation at 10 mM after 1.5 hrs by Western blot analysis	Identification of NAE Inhibitors Exhibiting Potent Activity in Leukemia Cells: Exploring the Structural Determinants of NAE Specificity. — ACS Med Chem Lett

Clinical trials (associated diseases)

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