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
• GTEx eGene: eQTL in 12 tissues, sQTL in 1 (q < 0.05)
• Drug target: yes — 1 via a complex or family; 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 83.9% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.46 (moderately constrained)
• MANE Select transcript: NM_003968
• Notable: 78 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 53 — 25 protein_coding, 22 nonsense_mediated_decay, 6 retained_intron

MANE Select: ENST00000361055

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 8, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000361055, ENST00000349511, 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, ENST00000977790, ENST00000977791, ENST00000977792, ENST00000977793, ENST00000977794, ENST00000977795, ENST00000977796, ENST00000977797, ENST00001035832, ENST00001035833, ENST00001035834, ENST00001035835, ENST00001035836, ENST00001035837, ENST00001035839, ENST00001086054, ENST00001086055, ENST00001086056, ENST00001086057, ENST00001086058, ENST00001086059, ENST00001102135, ENST00001139165

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.

Highest expression (Bgee): palpebral conjunctiva, monocyte, mononuclear cell, leukocyte, secondary oocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

UBA3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	1.3e-52	-0.40	3:69079592:A:G
Skin Sun Exposed Lower leg	eqtl	8.9e-45	-0.34	3:69079592:A:G
Colon Sigmoid	sqtl	6.3e-03	-1.51	3:69649986:G:A
Brain Cerebellum	eqtl	8.2e-03	+0.89	3:69400425:T:C
Adipose Subcutaneous	eqtl	1.1e-02	+0.16	3:69138746:T:C
Muscle Skeletal	eqtl	1.3e-02	+0.15	3:69138384:C:T
Whole Blood	eqtl	1.6e-02	-0.05	3:69078638:C:T
Esophagus Gastroesophageal Junction	eqtl	1.7e-02	+0.32	3:69322064:C:T
Brain Anterior cingulate cortex BA24	eqtl	1.9e-02	-0.29	3:69089525:A:T
Heart Left Ventricle	eqtl	2.0e-02	+0.10	3:69138746:T:C
Artery Tibial	eqtl	3.3e-02	-0.11	3:69072692:T:C
Thyroid	eqtl	3.4e-02	+0.38	3:69392135:A:G
Stomach	eqtl	3.4e-02	+0.13	3:69337711:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
42955	26.8626	1798

Top tissues by expression

showing 100 of 295 tissues 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
cortical plate	UBERON:0005343	94.90	gold quality
pigmented layer of retina	UBERON:0001782	94.83	gold quality
parotid gland	UBERON:0001831	94.83	gold quality
trabecular bone tissue	UBERON:0002483	94.83	gold quality
oral cavity	UBERON:0000167	94.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.72	gold quality
amniotic fluid	UBERON:0000173	94.53	gold quality
blood vessel layer	UBERON:0004797	94.52	gold quality
seminal vesicle	UBERON:0000998	94.50	gold quality
cardiac ventricle	UBERON:0002082	94.50	gold quality
heart left ventricle	UBERON:0002084	94.47	gold quality
rectum	UBERON:0001052	94.46	gold quality
oocyte	CL:0000023	94.40	gold quality
bronchial epithelial cell	CL:0002328	94.39	gold quality
lymph node	UBERON:0000029	94.39	gold quality
placenta	UBERON:0001987	94.28	gold quality
saliva-secreting gland	UBERON:0001044	94.20	gold quality
cauda epididymis	UBERON:0004360	94.15	gold quality
caput epididymis	UBERON:0004358	94.11	gold quality
mouth mucosa	UBERON:0003729	94.10	gold quality
minor salivary gland	UBERON:0001830	94.09	gold quality
choroid plexus epithelium	UBERON:0003911	94.07	gold quality
pons	UBERON:0000988	94.05	gold quality
granulocyte	CL:0000094	93.95	gold quality
heart	UBERON:0000948	93.92	gold quality
adrenal tissue	UBERON:0018303	93.89	gold quality
jejunal mucosa	UBERON:0000399	93.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.72	gold quality
caecum	UBERON:0001153	93.70	gold quality
uterus	UBERON:0000995	93.58	gold quality
jejunum	UBERON:0002115	93.48	gold quality
spinal cord	UBERON:0002240	93.46	gold quality
ventricular zone	UBERON:0003053	93.38	gold quality
stromal cell of endometrium	CL:0002255	93.37	gold quality
islet of Langerhans	UBERON:0000006	93.37	gold quality
ganglionic eminence	UBERON:0004023	93.36	gold quality
nasal cavity mucosa	UBERON:0001826	93.33	gold quality
primary visual cortex	UBERON:0002436	93.32	gold quality
right adrenal gland	UBERON:0001233	93.30	gold quality
female reproductive system	UBERON:0000474	93.24	gold quality
right adrenal gland cortex	UBERON:0035827	93.24	gold quality
skin of abdomen	UBERON:0001416	93.23	gold quality
blood	UBERON:0000178	93.19	gold quality
gall bladder	UBERON:0002110	93.16	gold quality
esophagus mucosa	UBERON:0002469	93.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.13	gold quality
spleen	UBERON:0002106	93.09	gold quality
zone of skin	UBERON:0000014	93.06	gold quality
cardiac atrium	UBERON:0002081	93.01	gold quality
left adrenal gland	UBERON:0001234	93.00	gold quality
hair follicle	UBERON:0002073	92.98	gold quality
descending thoracic aorta	UBERON:0002345	92.96	gold quality
substantia nigra	UBERON:0002038	92.93	gold quality
right atrium auricular region	UBERON:0006631	92.93	gold quality
body of uterus	UBERON:0009853	92.93	gold quality
esophagus	UBERON:0001043	92.91	gold quality
left uterine tube	UBERON:0001303	92.90	gold quality
ectocervix	UBERON:0012249	92.89	gold quality
left adrenal gland cortex	UBERON:0035825	92.87	gold quality
bone marrow	UBERON:0002371	92.79	gold quality
adrenal gland	UBERON:0002369	92.78	gold quality
midbrain	UBERON:0001891	92.77	gold quality
inferior vagus X ganglion	UBERON:0005363	92.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.77	gold quality
cerebellar hemisphere	UBERON:0002245	92.76	gold quality
urinary bladder	UBERON:0001255	92.75	gold quality
cerebellar cortex	UBERON:0002129	92.75	gold quality
colonic mucosa	UBERON:0000317	92.74	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	251.8
Locus coeruleus	tissue	229.2
Hippocampus	tissue	209.2	medium
Choroid plexus	tissue	136.2
Postcentral gyrus	tissue	126.2
Pons	tissue	64.6
Frontal cortex	tissue	62.9
Thalamus	tissue	62.6
Heart muscle	tissue	62.3	medium
Cerebral cortex	tissue	57.9	medium
Caudate putamen	tissue	57.9
Somatosensory cortex	tissue	57.9
Midbrain	tissue	57.6
Superior colliculi	tissue	57.6
Retina	tissue	57.0
Putamen	tissue	56.5
Hippocampal formation	tissue	54.9
Occipital cortex	tissue	54.4
Motor cortex	tissue	53.7
Medulla oblongata	tissue	53.6
Retrosplenial and cingulate cortex	tissue	52.5
Spinal cord	tissue	51.2
Septum	tissue	51.1
Substantia nigra	tissue	49.7
Entorhinal cortex	tissue	49.6
Prefrontal cortex	tissue	49.5
Temporal cortex	tissue	49.1
Hypothalamus	tissue	47.9
Ventral forebrain	tissue	47.2
Retrosplenial cortex	tissue	47.2
Tonsil	tissue	46.5	medium
Lymph node	tissue	46.4	medium
Corpus callosum	tissue	46.2
Basal ganglia	tissue	45.8	medium
Cerebellum	tissue	45.8	medium
Periaqueductal gray	tissue	45.4
Olfactory bulb	tissue	43.4
Parathyroid gland	tissue	42.8	medium
Insular cortex	tissue	42.7
Skin 1	tissue	42.5	medium
Salivary gland	tissue	42.3	medium
Thymus	tissue	41.8
Amygdala	tissue	41.0
Breast	tissue	40.7	medium
Placenta	tissue	39.2	medium
Skeletal muscle	tissue	38.9	low
Epididymis	tissue	38.7	medium
Smooth muscle	tissue	37.2	low
Appendix	tissue	37.2	medium
Urinary bladder	tissue	36.8	medium
Spleen	tissue	36.6	medium
Bone marrow	tissue	35.1	medium
Prostate	tissue	34.2	medium
Rectum	tissue	33.7	medium
Ovary	tissue	33.3	not detected
Endometrium 1	tissue	33.1	low
Tongue	tissue	32.5
Colon	tissue	32.3	low
Adipose tissue	tissue	32.2	medium
Esophagus	tissue	31.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (872.3), Temporal white matter (814.1), Corpus callosum, genu (white matter) (761.6), Corpus callosum, splenium (white matter) (712.1), Nucleus raphe obscurus (605.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

Targeting UBA3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 66 miRNAs:

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

gnomAD constraint: pLI 0.996, LOEUF 0.463, missense Z 0.835 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000361055 — one region, missense o/e 0.89. DepMap (CRISPR cell-line fitness): dependent in 83.9% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): MHH-ES-1 (-1.448), NCI-H1694 (-1.371), VMRC-RCW (-1.35), RD-ES (-1.255), RERF-LC-AI (-1.253), SCC-25 (-1.244), HEL 92.1.7 (-1.229), TE-10 (-1.178), YAPC (-1.176), SNU-46 (-1.154), OCI-AML3 (-1.13), CAL-33 (-1.118), RERF-LC-Sq1 (-1.103), HT-1080 (-1.1), JM1 (-1.095).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1341217) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal embryonic tissue morphology	1
abnormal inner cell mass morphology	1
abnormal cell cycle	1
abnormal blastocyst hatching	1
disorganized embryonic tissue	1
abnormal inner cell mass apoptosis	1
embryonic lethality between implantation and placentation, complete penetrance	1
embryonic lethality between implantation and somite formation, complete penetrance	1
embryonic lethality before implantation, incomplete penetrance	1
absent embryonic epiblast	1
abnormal blastocyst formation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharomyces cerevisiae RM11-1a	B3LSM6	100.0%	Diamond
Saccharomyces cerevisiae AWRI1631	B5VK45	100.0%	Diamond
Saccharomyces cerevisiae S288C	P38820	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WMN6	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WMN7	100.0%	Diamond
Pongo abelii	Q5NVN7	100.0%	Diamond
Saccharomyces cerevisiae YJM789	A6ZT19	99.8%	Diamond
Aspergillus fumigatus A1163	B0Y0P7	99.8%	Diamond
Aspergillus fumigatus Af293	Q4WV19	99.8%	Diamond
Xenopus laevis	Q642Q1	99.8%	Diamond
Triticum aestivum	P20973	99.2%	Diamond
Oryctolagus cuniculus	Q29504	96.7%	Diamond
Bos taurus	A3KMV5	96.6%	Diamond
Sordaria macrospora k-hell	F7W4M2	96.1%	Diamond
Neurospora crassa OR74A	Q871U2	96.1%	Diamond
Xenopus tropicalis	Q28GH3	95.3%	Diamond
Osphranter rufus	P31255	92.1%	Diamond
Aspergillus fischeri NRRL 181	A1DED8	91.7%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	Q56067	88.8%	Diamond
Gallus gallus	Q5ZKY2	84.4%	Diamond
Aspergillus clavatus NRRL 1	A1CAZ7	83.3%	Diamond
Arabidopsis thaliana	P92974	81.0%	Diamond
Aspergillus niger CBS 513.88	A2R3H4	76.3%	Diamond
Aspergillus oryzae RIB40	Q2TWN3	76.3%	Diamond
Aspergillus terreus NIH2624	Q0CFD4	76.2%	Diamond
Aspergillus nidulans FGSC A4	O59954	73.8%	Diamond
Kluyveromyces marxianus DMKU3-1042	W0TA05	73.4%	Diamond
Vanderwaltozyma polyspora DSM 70294	A7THV5	68.9%	Diamond
Nakaseomyces glabratus CBS 138	Q6FR35	68.0%	Diamond
Candida albicans WO-1	P52495	67.2%	Diamond
Scheffersomyces stipitis CBS 6054	A3LQF9	65.7%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CMC2	64.3%	Diamond
Eremothecium gossypii ATCC 10895	Q756K6	63.7%	Diamond
Candida albicans SC5314	Q59WH7	63.0%	Diamond
Porphyra purpurea	P51335	62.3%	Diamond
Pyropia yezoensis	Q1XDF1	62.3%	Diamond
Schizosaccharomyces pombe 972h-	O94609	61.6%	Diamond
Dictyostelium discoideum	Q55C16	61.6%	Diamond
Meyerozyma guilliermondii ATCC 6260	A5DMB6	58.1%	Diamond
Escherichia coli K-12	Q46927	57.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ARL6IP5	protein-coding	10550
FRMD4B	protein-coding	23150
MITF	protein-coding	4286
LMOD3	protein-coding	56203
EOGT-DT	ncRNA	121676928
TAFA4	protein-coding	151647
EOGT	protein-coding	285203
TMF1	protein-coding	7110
MIR3136	ncRNA	100422859
SAMMSON	ncRNA	101927152

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 (96 total): helix 27, mutagenesis site 24, strand 20, 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 by resolution:

PDB	Title	Method	Resolution (Å)
5JJM	Crystal Structure of Homodimeric Androgen Receptor Ligand-Binding Domain bound to DHT and …	X-RAY DIFFRACTION	2.15
1Y8X	Structural basis for recruitment of Ubc12 by an E2-binding domain in NEDD8’s E1	X-RAY DIFFRACTION	2.4
3FN1	E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification.	X-RAY DIFFRACTION	2.5
1TT5	Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal …	X-RAY DIFFRACTION	2.6
1YOV	Insights into the Ubiquitin Transfer Cascade from the refined structure of the activating …	X-RAY DIFFRACTION	2.6
2NVU	Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein …	X-RAY DIFFRACTION	2.8
3DBH	Structural Dissection of a Gating Mechanism Preventing Misactivation of Ubiquitin by …	X-RAY DIFFRACTION	2.85
3DBL	Structural Dissection of a Gating Mechanism Preventing Misactivation of Ubiquitin by …	X-RAY DIFFRACTION	2.9
1R4M	APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex	X-RAY DIFFRACTION	3
3GZN	Structure of NEDD8-activating enzyme in complex with NEDD8 and MLN4924	X-RAY DIFFRACTION	3
3DBR	Structural Dissection of a Gating Mechanism Preventing Misactivation of Ubiquitin by …	X-RAY DIFFRACTION	3.05
1R4N	APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex with ATP	X-RAY DIFFRACTION	3.6
2LQ7	E2 binding surface on Uba3 beta-grasp domain undergoes a conformational transition	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane; centrosome; nucleoplasm

Antibody reliability (HPA): IH supported · IF approved

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)

Position	Role
237	glycyl thioester intermediate
211	determines specificity for nedd8

Ligand- & substrate-binding residues (2)

Position	Role
100–124	ATP
148–171	ATP

Post-translational modifications (1)

Type	Positions
N-acetylalanine	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 curated (TAS) of 15; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

15 pathways:

ID	Pathway	Evidence
R-HSA-9918485	Dengue Virus Attachment and Entry ⚕	curated
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	curated
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling	curated
R-HSA-5676590	NIK–>noncanonical NF-kB signaling	curated
R-HSA-8951664	Neddylation	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-5621481	C-type lectin receptors (CLRs)	—
R-HSA-5607764	CLEC7A (Dectin-1) signaling	—
R-HSA-983169	Class I MHC mediated antigen processing & presentation	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway	—

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 (5): proteolysis (GO:0006508), protein modification process (GO:0036211), post-translational protein modification (GO:0043687), protein neddylation (GO:0045116), 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

11 top-level categories:

Category	Pathways
Immune System	3
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
C-type lectin receptors (CLRs)	1
Innate Immune System	1
Cytokine Signaling in Immune system	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

24 GO namespaces:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
macromolecule modification	1
protein modification process	1
protein modification by small protein conjugation	1
protein modification by small protein conjugation or removal	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
protein neddylation	BP	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
NEDD8 activating enzyme activity	MF	direct assay
identical protein binding	MF	physical interaction
protein heterodimerization activity	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,526 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBA3	NAE1	Q13564	985
UBA3	UBE2M	P61081	982
UBA3	NEDD8	Q15843	972
UBA3	RBX1	P62877	892
UBA3	CUL1	Q13616	859
UBA3	UBE2F	Q969M7	841
UBA3	CUL7	Q14999	813
UBA3	UBA5	Q9GZZ9	778
UBA3	SENP8	Q96LD8	776
UBA3	DCUN1D1	Q96GG9	744
UBA3	RNF7	Q9UBF6	741
UBA3	SKP1	P34991	740
UBA3	FBXW8	Q8N3Y1	736
UBA3	COPS5	Q92905	729
UBA3	FBXW11	Q9UKB1	718

IntAct

Human interaction partners of UBA3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
UBE2M	direct interaction	0.820	3
CPNE2	physical association	0.720	6
IMPA2	physical association	0.720	6
APOE	physical association	0.560	3
APP	physical association	0.560	3
DUSP23	physical association	0.560	3
NAE1	physical association	0.560	3
RAD23B	physical association	0.400	2
RAD23A	physical association	0.400	1
KDM1A	physical association	0.370	1
UBE2F	physical association	0.370	1
CHD3	physical association	0.000	1
DSCAM	physical association	0.000	1

BioGRID (145 interactions; top human partners by supporting records): UBE2M (Biochemical Activity; 20 records), NAE1 (Reconstituted Complex; 16 records), NEDD8 (Biochemical Activity; 5 records), UBE2F (Biochemical Activity; 4 records), APIP (Affinity Capture-MS; 3 records), CPNE2 (Two-hybrid; 2 records), IMPA2 (Two-hybrid; 2 records), PARK2 (Affinity Capture-MS; 2 records), ZBTB44 (Affinity Capture-MS; 2 records), ACAT2 (Co-fractionation), AHCY (Co-fractionation), AMBRA1 (Proximity Label-MS), ANAPC13 (Negative Genetic), ANKRD39 (Affinity Capture-MS), ARL2 (Negative Genetic)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
UBA3	“form complex”	NAE	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
APPBP1-UBA3 complex	2	NAE1, UBA3

Disease & clinical

Genetic variants

Variant evidence for UBA3: 78 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,691):

Position(s)	Effect	Δscore	Sites
3:69080097	donor_gain	1.0000
3:69080110	donor_gain	1.0000
3:69080332–69080333	donor_loss	1.0000	3
3:69055526–69055527	acceptor_loss	0.9900	4
3:69055849–69055850	donor_loss	0.9900	6
3:69056178	donor_loss	0.9900
3:69056181–69056182	donor_loss	0.9900	5
3:69056284–69056285	acceptor_loss	0.9900	6
3:69056610–69056611	donor_loss	0.9900	5
3:69056694–69056695	acceptor_loss	0.9900	6

AlphaMissense

1,212 missense substitutions predicted likely pathogenic (of 3,041 scored), across 300 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D167	8	0.997	0.999
D100	8	0.994	0.997
D102	8	0.992	0.997
D200	8	0.989	0.996
F115	8	0.975	0.998
H248	8	0.974	0.995
F113	8	0.965	0.997
D448	8	0.956	0.988
N108	8	0.952	0.999
D273	8	0.910	0.976
F206	8	0.899	0.983
F93	8	0.877	0.996
D119	8	0.837	0.965
F329	8	0.794	0.979
C237	7	0.997	0.999
R111	7	0.994	1.000
C223	7	0.992	0.998
F159	7	0.982	0.998
C220	7	0.982	0.997
C364	7	0.981	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (TCGA)	favorable	0.00083

Disease associations

OMIM: gene MIM:603172 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST010143_13	Meat-related diet	5e-9

EFO canonical traits (from GWAS)

1 canonical traits:

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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes UBA3 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
PEVONEDISTAT	NEDD8 activating enzyme	2	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 170,278 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL58	MITOXANTRONE	4	168,731
CHEMBL1231160	PEVONEDISTAT	3	1,547

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

87 measured of 123 human assays (123 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5170838	IC50	0.02 nM
CHEMBL5182746	IC50	0.21 nM
CHEMBL5177755	IC50	0.55 nM
CHEMBL5206652	IC50	0.57 nM
CHEMBL5181979	IC50	1 nM
CHEMBL5173723	IC50	2.2 nM
CHEMBL5192493	IC50	2.3 nM
CHEMBL5197178	IC50	3.6 nM
CHEMBL5209054	IC50	4.2 nM
MLN-4924	IC50	4.7 nM
CHEMBL5188530	IC50	5.8 nM
CHEMBL5193236	IC50	6 nM
CHEMBL5177700	IC50	6.1 nM
CHEMBL5178136	IC50	9.8 nM
CHEMBL2017005	IC50	10 nM
CHEMBL4847817	IC50	10 nM
CHEMBL5192527	IC50	10 nM
[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
CHEMBL5169743	IC50	16 nM
CHEMBL5170141	IC50	21 nM
CHEMBL5179467	IC50	21 nM
CHEMBL4860740	IC50	23 nM
CHEMBL4878832	IC50	31 nM
CHEMBL5207989	IC50	31 nM
{(1R,2S,4R)-4-[(5-{[4-(3-chlorobenzyl)-5-methyl-2-thienyl]carbonyl}pyrimidin-4- yl)amino]-2-hydroxycyclopentyl}methyl sulfamate	IC50	32 nM
CHEMBL4852015	IC50	32 nM
CHEMBL4870385	IC50	50 nM
CHEMBL4856793	IC50	50 nM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	IC50	64 nM	US-10780090: Heteroaryl compounds useful as inhibitors of SUMO activating enzyme
CHEMBL4848442	IC50	64 nM
CHEMBL5201960	IC50	67 nM
CHEMBL5206263	IC50	81 nM
CHEMBL5206633	IC50	82 nM
[(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2- thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate	IC50	90 nM
[(1R,2S,4R)-4-[[5-[4-[(3-bromophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	IC50	91 nM	US-10780090: Heteroaryl compounds useful as inhibitors of SUMO activating enzyme
CHEMBL4848140	IC50	102 nM
CHEMBL5190183	IC50	107 nM
CHEMBL4860263	IC50	114 nM
CHEMBL5188300	IC50	120 nM
CHEMBL4847843	IC50	122 nM
CHEMBL5200375	IC50	149 nM
CHEMBL5173277	IC50	170 nM
CHEMBL5188093	IC50	187 nM
CHEMBL4865086	IC50	190 nM
CHEMBL4848114	IC50	198 nM
CHEMBL4858933	IC50	203 nM
CHEMBL5189807	IC50	207 nM
CHEMBL4866833	IC50	215 nM
CHEMBL5197934	IC50	219 nM
CHEMBL4854038	IC50	235 nM

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	increases expression, affects cotreatment	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	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for UBA3 across ~30M SureChEMBL compounds — explore on Sugi Predict.