UBA1

Summary

UBA1 (ubiquitin like modifier activating enzyme 1, HGNC:12469) is a protein-coding gene on chromosome Xp11.3, encoding Ubiquitin-like modifier-activating enzyme 1 (P22314). Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

The protein encoded by this gene catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. This gene complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. It is part of a gene cluster on chromosome Xp11.23. Alternatively spliced transcript variants that encode the same protein have been described.

Source: NCBI Gene 7317 — RefSeq curated summary.

At a glance

• Gene–disease (curated): infantile-onset X-linked spinal muscular atrophy (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 732 total — 1 likely-pathogenic
• Phenotypes (HPO): 83
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_003334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12469
Approved symbol	UBA1
Name	ubiquitin like modifier activating enzyme 1
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	UBE1X, POC20, CFAP124
Ensembl gene	ENSG00000130985
Ensembl biotype	protein_coding
OMIM	314370
Entrez	7317

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 79 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000335972, ENST00000377269, ENST00000377351, ENST00000412206, ENST00000427561, ENST00000442035, ENST00000451702, ENST00000457753, ENST00000490869, ENST00000880170, ENST00000880171, ENST00000880172, ENST00000880173, ENST00000880174, ENST00000880175, ENST00000880176, ENST00000880177, ENST00000880178, ENST00000880179, ENST00000880180, ENST00000880181, ENST00000880182, ENST00000880183, ENST00000880184, ENST00000880185, ENST00000880186, ENST00000880187, ENST00000880188, ENST00000880189, ENST00000880190, ENST00000880191, ENST00000880192, ENST00000880193, ENST00000880194, ENST00000880195, ENST00000880196, ENST00000880197, ENST00000880198, ENST00000880199, ENST00000940362, ENST00000940363, ENST00000940364, ENST00000940365, ENST00000940366, ENST00000940367, ENST00000940368, ENST00000940369, ENST00000940370, ENST00000940371, ENST00000940372, ENST00000940373, ENST00000940374, ENST00000940375, ENST00000940376, ENST00000940377, ENST00000940378, ENST00000940379, ENST00000940380, ENST00000940381, ENST00000940382, ENST00000940383, ENST00000940384, ENST00000940385, ENST00000940386, ENST00000940387, ENST00000940388, ENST00000940389, ENST00000954376, ENST00000954377, ENST00000954378, ENST00000954379, ENST00000954380, ENST00000954381, ENST00000954382, ENST00000954383, ENST00000954384, ENST00000954385, ENST00000954386, ENST00000954387, ENST00000954388

RefSeq mRNA: 2 — MANE Select: NM_003334 NM_003334, NM_153280

CCDS: CCDS14275

Canonical transcript exons

ENST00000335972 — 26 exons

Exon	Start	End
ENSE00000896879	47199480	47199614
ENSE00000896881	47199209	47199377
ENSE00000896883	47199048	47199106
ENSE00001609845	47209928	47210123
ENSE00001615447	47212424	47212512
ENSE00001617049	47205948	47206113
ENSE00001625306	47214537	47214637
ENSE00001655149	47209623	47209687
ENSE00001659133	47210842	47210916
ENSE00001663824	47202156	47202253
ENSE00001671960	47212990	47213181
ENSE00001687972	47202638	47202814
ENSE00001727072	47212771	47212863
ENSE00001728673	47206248	47206444
ENSE00001731193	47193829	47194024
ENSE00001758857	47202358	47202504
ENSE00001763851	47211036	47211225
ENSE00001770737	47214327	47214428
ENSE00001802011	47201276	47201366
ENSE00001897739	47214794	47215128
ENSE00002208618	47200894	47201000
ENSE00003497509	47202943	47203047
ENSE00003587071	47203541	47203696
ENSE00003641993	47203134	47203214
ENSE00003758789	47198803	47198919
ENSE00003787175	47201478	47201610

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 140.0454 / max 1185.1083, expressed in 1828 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196170	111.0516	1828
196162	17.1203	1753
196169	5.5328	1740
196161	4.3940	1628
196164	1.6561	1141
196163	0.2550	95
196166	0.0270	11
196165	0.0086	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.17	gold quality
renal medulla	UBERON:0000362	99.15	gold quality
pharyngeal mucosa	UBERON:0000355	98.83	gold quality
ventricular zone	UBERON:0003053	98.83	gold quality
right lobe of thyroid gland	UBERON:0001119	98.80	gold quality
ganglionic eminence	UBERON:0004023	98.80	gold quality
nipple	UBERON:0002030	98.77	gold quality
postcentral gyrus	UBERON:0002581	98.76	gold quality
right uterine tube	UBERON:0001302	98.73	gold quality
cortical plate	UBERON:0005343	98.73	gold quality
parietal lobe	UBERON:0001872	98.72	gold quality
dorsal root ganglion	UBERON:0000044	98.69	gold quality
left lobe of thyroid gland	UBERON:0001120	98.66	gold quality
trigeminal ganglion	UBERON:0001675	98.66	gold quality
ileal mucosa	UBERON:0000331	98.62	gold quality
thyroid gland	UBERON:0002046	98.53	gold quality
superior surface of tongue	UBERON:0007371	98.52	gold quality
stromal cell of endometrium	CL:0002255	98.51	gold quality
pylorus	UBERON:0001166	98.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.47	gold quality
right adrenal gland cortex	UBERON:0035827	98.46	gold quality
right adrenal gland	UBERON:0001233	98.43	gold quality
embryo	UBERON:0000922	98.42	gold quality
inferior vagus X ganglion	UBERON:0005363	98.42	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.39	gold quality
ventral tegmental area	UBERON:0002691	98.33	gold quality
metanephros cortex	UBERON:0010533	98.33	gold quality
pituitary gland	UBERON:0000007	98.32	gold quality
adrenal cortex	UBERON:0001235	98.32	gold quality
left adrenal gland	UBERON:0001234	98.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting UBA1, 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-607	99.97	73.62	5593
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-1914-3P	95.07	63.37	762

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• In conclusion, nUBE1L is a novel human E1 like gene highly expressed in adult testis, which plays key role in ubiquitin system, and accordingly influences spermatogenesis and male fertility. (PMID:15202508)
• analysis of ATP.Mg2+ binding in the catalytic cycle of ubiquitin-activating enzyme (PMID:16595681)
• unusual type of regulation at the level of the E1 enzyme is likely to affect numerous cellular processes and may represent a strategy to coordinate multiple phenotypic changes upon differentiation by using E1 as a “master switch.” (PMID:17060614)
• Human Uba6 and Ube1 have distinct preferences for E2 charging in vitro, and their specificity depends in part on their C-terminal ubiquitin-fold domains, which recruit E2s (PMID:17597759)
• Large-scale mutation analysis in genes resulted in detection of 3 rare novel variants in exon 15 of UBE1 that segregate with X-linked infantile spinal muscular atrophy. (PMID:18179898)
• high-level expression of UBE1 was seen inextranodal NK/T cell lymphoma, nasal type; there was no significant difference between UBE1 expression and patients’ outcome (PMID:18661401)
• Ubiquitin and UBE1 are upregulated in tic epilepsy. (PMID:20653130)
• Data show that largazole and ester/keto analogs inhibit ubiquitin E1 activation. (PMID:22279528)
• Decrease in free ubiquitin levels under stress allows NEDD8 to be conjugated through Ube1. (PMID:22370482)
• UBA1 knockdown impairs formation of ubiquitin conjugates at DNA double-strand breaks. (PMID:22456334)
• Diminished ubiquitylation phenotype observed in enteropathogenic Escherichia coli infected cells corresponds to a strong reduction in the abundance of both Ube1 and Uba6. (PMID:22999844)
• Ubiquitin-activating enzyme is necessary for 17beta-estradiol-induced breast cancer cell proliferation and migration. (PMID:25138535)
• A ubiquitin shuttle DC-UbP reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes. (PMID:25207809)
• We expressed and purified the N-terminal domains of human E1 and determined their crystal structures, which contain inactive adenylation domain (IAD) and the first catalytic cysteine half-domain (FCCH) (PMID:25209502)
• Conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation (PMID:25768649)
• Results from a study on gene expression variability markers in early-stage human embryos shows that UBA1 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• recent findings put UBA1 at the center of cellular homeostasis and neurodegeneration [review] (PMID:26432019)
• Polyubiquitination and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1, and that Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. These data suggest that distinctive substrate pools exist for Uba1 and Uba6 that reflect non-redundant biological roles for Uba6. (PMID:28134249)
• hUBA1 shares a conserved overall structure and mechanism with previously characterized yeast orthologs, but displays subtle structural differences, particularly within the active site. (PMID:30279270)
• Differential Inhibition of Human and Trypanosome Ubiquitin E1S by TAK-243 Offers Possibilities for Parasite Selective Inhibitors. (PMID:31700050)
• Ubiquitination-activating enzymes UBE1 and UBA6 regulate ubiquitination and expression of cardiac sodium channel Nav1.5. (PMID:32315024)
• Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. (PMID:33108101)
• Herpes simplex virus 1 infection induces ubiquitination of UBE1a. (PMID:33355669)
• Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS. (PMID:33779074)
• Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. (PMID:33789873)
• Acetylated Ubiquitin Modulates the Catalytic Activity of the E1 Enzyme Uba1. (PMID:33848125)
• Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS. (PMID:34048852)
• Somatic Mutation in UBA1 and ANCA-associated Vasculitis. (PMID:34074684)
• Atypical splice-site mutations causing VEXAS syndrome. (PMID:34213531)
• Prevalence of UBA1 mutations in MDS/CMML patients with systemic inflammatory and auto-immune disease. (PMID:34344988)
• Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: fevers, myalgia, arthralgia, auricular chondritis, and erythema nodosum. (PMID:34391501)
• Looking for somatic mutations in UBA1 in patients with chronic myelomonocytic leukemia associated with systemic inflammation and autoimmune diseases. (PMID:34474632)
• UBA1 gene mutation in giant cell arteritis. (PMID:35094194)
• Absence of NLRP3 somatic mutations and VEXAS-related UBA1 mutations in a large cohort of patients with Schnitzler syndrome. (PMID:35713654)
• Identification of UBA1 as the causative gene of an X-linked non-Kennedy spinal-bulbar muscular atrophy. (PMID:35996994)
• Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study. (PMID:36002395)
• An update on VEXAS syndrome. (PMID:36537591)
• Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome. (PMID:37062784)
• Clonal haematopoiesis and UBA1 mutations in individuals with biopsy-proven giant cell arteritis and population-based controls. (PMID:37632778)
• Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis. (PMID:38167209)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	uba7	ENSDARG00000061222
mus_musculus	Uba1	ENSMUSG00000001924
rattus_norvegicus	Uba1	ENSRNOG00000019164

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), MOCS3 (ENSG00000124217), UBA2 (ENSG00000126261), SAE1 (ENSG00000142230), UBA3 (ENSG00000144744), NAE1 (ENSG00000159593), UBA7 (ENSG00000182179), ATG7 (ENSG00000197548)

Protein

Protein identifiers

Ubiquitin-like modifier-activating enzyme 1 — P22314 (reviewed: P22314)

Alternative names: Protein A1S9, Ubiquitin-activating enzyme E1

All UniProt accessions (8): P22314, A0A024R1A3, Q5JRR6, Q5JRR9, Q5JRS0, Q5JRS1, Q5JRS2, Q5JRS3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.

Subunit / interactions. Monomer. Interacts with GAN (via BTB domain).

Subcellular location. Cytoplasm. Mitochondrion. Nucleus Nucleus Cytoplasm.

Tissue specificity. Detected in erythrocytes (at protein level). Ubiquitous.

Post-translational modifications. ISGylated.

Disease relevance. Spinal muscular atrophy X-linked 2 (SMAX2) [MIM:301830] A lethal infantile form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Clinical features include hypotonia, areflexia, and multiple congenital contractures. The disease is caused by variants affecting the gene represented in this entry. VEXAS syndrome (VEXAS) [MIM:301054] A sporadic, often fatal, treatment-refractory inflammatory syndrome that develops in late adulthood. Clinical features include fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. The disease affects only males and is associated with de novo somatic mutations. The disease is caused by variants affecting the gene represented in this entry. Somatic variants affecting the initiator methionine of isoform 2 are recurrently found in VEXAS patients. These variants cause loss of isoform 2 and production of a shorter isoform with strongly reduced enzymatic activity from a downstream methionine (Met-67).

Domain organisation. The first 11 amino acids are essential for phosphorylation and exclusive nuclear localization.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.

Similarity. Belongs to the ubiquitin-activating E1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P22314-1	1, E1a	yes
P22314-2	2, E1b

RefSeq proteins (2): NP_003325, NP_695012 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000011	UBQ/SUMO-activ_enz_E1-like	Family
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR018074	UBQ-activ_enz_E1_CS	Conserved_site
IPR018075	UBQ-activ_enz_E1	Family
IPR018965	Ub-activating_enz_E1_C	Domain
IPR019572	UBA_E1_SCCH	Domain
IPR032418	E1_FCCH	Domain
IPR032420	E1_4HB	Domain
IPR033127	UBQ-activ_enz_E1_Cys_AS	Active_site
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR038252	UBA_E1_C_sf	Homologous_superfamily
IPR042063	Ubi_acti_E1_SCCH	Homologous_superfamily
IPR042302	E1_FCCH_sf	Homologous_superfamily
IPR042449	Ub-E1_IAD_1	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00899, PF09358, PF10585, PF16190, PF16191

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 6.2.1.45 — E1 ubiquitin-activating enzyme (BRENDA: 12 organisms, 35 substrates, 23 inhibitors, 28 Km, 30 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)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0047–0.208	11
UBIQUITIN	0.0002–0.029	11
ATP	0.0045–0.175	9
[UBIQUITIN-CARRIER-PROTEIN UBC2B]-L-CYSTEINE	0.0001	5
UBIQUITIN CARRIER PROTEIN E2	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
OREGON GREEN-LABELED UBIQUITIN	0.0002	1

UniProt features (138 total): helix 42, strand 38, modified residue 16, turn 11, sequence variant 7, mutagenesis site 6, binding site 5, initiator methionine 2, repeat 2, region of interest 2, sequence conflict 2, chain 1, splice variant 1, short sequence motif 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4P22	X-RAY DIFFRACTION	2.75
6DC6	X-RAY DIFFRACTION	3.14
7PYV	X-RAY DIFFRACTION	3.27
9MC5	ELECTRON MICROSCOPY	3.29
9MC4	ELECTRON MICROSCOPY	3.32
9MC6	ELECTRON MICROSCOPY	3.32
9MC7	ELECTRON MICROSCOPY	3.34
9MC9	ELECTRON MICROSCOPY	3.37
9MCB	ELECTRON MICROSCOPY	3.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22314-F1	92.71	0.86

Functional residue map

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

Catalytic / active sites (1): 632 (glycyl thioester intermediate)

Ligand- & substrate-binding residues (5): 504; 515; 528; 576–577; 478

Post-translational modifications (16): 2, 2, 4, 13, 21, 24, 46, 55, 528, 671, 800, 810, 816, 820, 835, 980

Mutagenesis-validated functional residues (6):

Position	Phenotype
1–66	localizes to the cytoplasm.
1–40	localizes to the cytoplasm; when associated with a-67.
4	reduces phosphorylation.
8–11	loss of nuclear localization and a 90-95% decrease in the phosphorylation.
41	localizes to the nucleus; when associated with a-67.
67	localizes to the nucleus; when associated with a-41. localizes to the cytoplasm; when associated with 1-m–g-40 del.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 388 (showing top): MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_VACUOLAR_MEMBRANE, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, MATTIOLI_MGUS_VS_PCL, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, HSIAO_HOUSEKEEPING_GENES, TGACCTY_ERR1_Q2, KAUFFMANN_DNA_REPAIR_GENES, GGGTGGRR_PAX4_03, USF_C

GO Biological Process (5): ubiquitin-dependent protein catabolic process (GO:0006511), DNA damage response (GO:0006974), protein ubiquitination (GO:0016567), protein modification by small protein conjugation (GO:0032446), protein modification process (GO:0036211)

GO Molecular Function (7): RNA binding (GO:0003723), ubiquitin activating enzyme activity (GO:0004839), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641), ligase activity (GO:0016874)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062), heterochromatin (GO:0000792), lysosomal membrane (GO:0005765), endosome membrane (GO:0010008), desmosome (GO:0030057), rough endoplasmic reticulum membrane (GO:0030867)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein ubiquitination	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
cellular anatomical structure	3
protein ubiquitination	2
intracellular membrane-bounded organelle	2
cytoplasm	2
bounding membrane of organelle	2
modification-dependent protein catabolic process	1
cellular response to stress	1
protein modification by small protein conjugation	1
protein modification by small protein conjugation or removal	1
protein metabolic process	1
macromolecule modification	1
nucleic acid binding	1
ubiquitin-like modifier activating enzyme activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	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
nuclear lumen	1
intracellular anatomical structure	1
extracellular vesicle	1
chromatin	1
lysosome	1
lytic vacuole membrane	1
endosome	1
cytoplasmic vesicle membrane	1
cell-cell junction	1
endoplasmic reticulum membrane	1
rough endoplasmic reticulum	1

Protein interactions and networks

STRING

3876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBA1	UBE2D2	P51669	988
UBA1	UBE2D1	P51668	957
UBA1	UBE2M	P61081	952
UBA1	NEDD8	Q15843	936
UBA1	A0A087WY85	A0A087WY85	926
UBA1	UBE2S	Q16763	922
UBA1	CDC34	P49427	900
UBA1	UBE2K	P27924	890
UBA1	UBE2N	P61088	889
UBA1	UBE2H	P37286	885
UBA1	UBE2A	P49459	884
UBA1	GAN	Q9H2C0	830
UBA1	UBE3A	P78355	815
UBA1	ARIH1	Q9Y4X5	813
UBA1	RAD23A	P54725	809

IntAct

320 interactions, top by confidence:

A	B	Type	Score
MDM4	TP53	psi-mi:“MI:0220”(ubiquitination reaction)	0.970
RNF20	RNF40	psi-mi:“MI:0220”(ubiquitination reaction)	0.820
STUB1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.730
SUN2	LMNA	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
	UBA1	psi-mi:“MI:0407”(direct interaction)	0.670
	UBA1	psi-mi:“MI:0195”(covalent binding)	0.670
OTUB1	UBA1	psi-mi:“MI:0915”(physical association)	0.670
UBE2N	UBA1	psi-mi:“MI:0914”(association)	0.640
	UBA6	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
HEMGN	NPM1	psi-mi:“MI:0914”(association)	0.600
MAGEC2	TP53	psi-mi:“MI:0914”(association)	0.590
TRAF4	UBA1	psi-mi:“MI:0915”(physical association)	0.560
WWP2	UBA1	psi-mi:“MI:0915”(physical association)	0.560
UBA1	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (674): UBA1 (Affinity Capture-MS), UBA1 (Affinity Capture-Western), UBA1 (Co-crystal Structure), UBA1 (Reconstituted Complex), UBA1 (Affinity Capture-Western), UBA1 (Affinity Capture-MS), FUS (Affinity Capture-Western), UBA1 (Affinity Capture-MS), UBE2D2 (Biochemical Activity), UBE2E1 (Biochemical Activity), UBE2L3 (Biochemical Activity), UBA1 (Biochemical Activity), UBE2K (Biochemical Activity), UBE2K (Biochemical Activity), UBA1 (Affinity Capture-MS)

ESM2 similar proteins: A2VE39, A2X0Q3, A3KMV5, A4IG62, A7YW45, A8BQB4, D2HRF1, F4JVN6, O14744, O23617, O80585, O80738, O95352, P22314, P35573, P42898, P45437, Q02053, Q0WUI9, Q29504, Q295E6, Q29G21, Q2PQH8, Q4R5M3, Q5I598, Q5R698, Q5R981, Q5RGJ5, Q5U300, Q5ZJT0, Q60HE5, Q641Y5, Q6ESI7, Q6NUA1, Q6YXZ7, Q75HE6, Q8AVL0, Q8CIG8, Q8GWT4, Q8IYB8

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

4 interactions.

A	Effect	B	Mechanism
UBA1	“form complex”	“Ub:E1 (UBA1 substrate)”	binding
CDK1	up-regulates	UBA1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 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
NOD1/2 Signaling Pathway	7	15.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	12.7×	2e-03
cellular senescence	6	10.5×	4e-03
learning or memory	7	10.0×	2e-03
protein polyubiquitination	11	7.5×	4e-04
ubiquitin-dependent protein catabolic process	13	5.7×	4e-04
negative regulation of gene expression	11	4.5×	6e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	14	4.3×	2e-03
negative regulation of apoptotic process	18	3.7×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	265
Likely benign	233
Benign	67

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1318544	NM_003334.4(UBA1):c.1660C>T (p.Pro554Ser)	Likely pathogenic

SpliceAI

3345 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47190922:G:GT	donor_gain	1.0000
X:47198920:G:GG	donor_gain	1.0000
X:47199044:CTAGG:C	acceptor_loss	1.0000
X:47199045:TA:T	acceptor_loss	1.0000
X:47199046:A:AG	acceptor_gain	1.0000
X:47199046:AG:A	acceptor_gain	1.0000
X:47199046:AGG:A	acceptor_gain	1.0000
X:47199046:AGGGA:A	acceptor_loss	1.0000
X:47199047:G:GT	acceptor_gain	1.0000
X:47199047:GG:G	acceptor_gain	1.0000
X:47199047:GGG:G	acceptor_gain	1.0000
X:47199047:GGGA:G	acceptor_gain	1.0000
X:47199047:GGGAA:G	acceptor_gain	1.0000
X:47199102:CAGCT:C	donor_gain	1.0000
X:47199103:AGCT:A	donor_gain	1.0000
X:47199104:GCT:G	donor_gain	1.0000
X:47199104:GCTG:G	donor_gain	1.0000
X:47199105:CT:C	donor_gain	1.0000
X:47199107:G:GG	donor_gain	1.0000
X:47199108:T:G	donor_loss	1.0000
X:47199111:G:GG	donor_gain	1.0000
X:47199463:A:AG	acceptor_gain	1.0000
X:47199463:ACT:A	acceptor_gain	1.0000
X:47199464:C:G	acceptor_gain	1.0000
X:47199465:T:A	acceptor_gain	1.0000
X:47199468:A:AG	acceptor_gain	1.0000
X:47199469:C:G	acceptor_gain	1.0000
X:47199470:A:AG	acceptor_gain	1.0000
X:47199471:C:G	acceptor_gain	1.0000
X:47199475:TACA:T	acceptor_loss	1.0000

AlphaMissense

6942 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47199099:C:G	R57G	1.000
X:47201494:T:A	V232D	1.000
X:47201542:T:A	V248D	1.000
X:47203631:G:C	D504H	1.000
X:47203632:A:T	D504V	1.000
X:47203637:G:C	D506H	1.000
X:47203638:A:T	D506V	1.000
X:47203644:T:A	I508N	1.000
X:47203657:T:A	N512K	1.000
X:47203657:T:G	N512K	1.000
X:47203659:T:C	L513P	1.000
X:47203676:T:C	F519L	1.000
X:47203678:C:A	F519L	1.000
X:47203678:C:G	F519L	1.000
X:47205956:G:C	K528N	1.000
X:47205956:G:T	K528N	1.000
X:47206096:T:C	L575P	1.000
X:47206098:G:C	D576H	1.000
X:47206099:A:C	D576A	1.000
X:47206099:A:G	D576G	1.000
X:47206099:A:T	D576V	1.000
X:47206100:C:A	D576E	1.000
X:47206100:C:G	D576E	1.000
X:47206400:T:C	C632R	1.000
X:47206401:G:A	C632Y	1.000
X:47206402:T:G	C632W	1.000
X:47206415:T:C	F637L	1.000
X:47206416:T:C	F637S	1.000
X:47206416:T:G	F637C	1.000
X:47206417:C:A	F637L	1.000

dbSNP variants (sampled 300 via entrez): RS1000465453 (X:47193611 C>T), RS1000538311 (X:47211461 T>C), RS1000648503 (X:47202057 T>C), RS1000732044 (X:47193081 T>G), RS1001335967 (X:47195164 T>A), RS1001617354 (X:47204596 T>C), RS1001649864 (X:47204190 G>T), RS1001870431 (X:47195399 A>C,G), RS1001950795 (X:47213523 C>T), RS1002289023 (X:47197229 C>T), RS1002475028 (X:47197732 G>A), RS1003176394 (X:47190170 G>A), RS1003929288 (X:47207902 T>C), RS1004313920 (X:47201203 T>A,C), RS1004321067 (X:47192783 G>A)

Disease associations

OMIM: gene MIM:314370 | disease phenotypes: MIM:301830, MIM:301054

GenCC curated gene-disease

Disease	Classification	Inheritance
infantile-onset X-linked spinal muscular atrophy	Strong	X-linked
inflammatory disease	No Known Disease Relationship	Unknown

Mondo (4): infantile-onset X-linked spinal muscular atrophy (MONDO:0010532), VEXAS syndrome (MONDO:0026777), congenital portosystemic shunt (MONDO:0018811), inflammatory disease (MONDO:0021166)

Orphanet (3): Infantile-onset X-linked spinal muscular atrophy (Orphanet:1145), VEXAS syndrome (Orphanet:596753), Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

83 total (30 of 83 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000218	High palate
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000773	Short ribs
HP:0000887	Cupped ribs
HP:0001220	Interphalangeal joint contracture of finger
HP:0001252	Hypotonia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001308	Tongue fasciculations
HP:0001369	Arthritis
HP:0001371	Flexion contracture
HP:0001419	X-linked recessive inheritance
HP:0001442	Typified by somatic mosaicism
HP:0001558	Decreased fetal movement
HP:0001612	Weak cry
HP:0001873	Thrombocytopenia
HP:0001907	Thromboembolism
HP:0001939	Abnormality of metabolism/homeostasis
HP:0001954	Recurrent fever
HP:0001972	Macrocytic anemia
HP:0002009	Potter facies
HP:0002033	Poor suck
HP:0002058	Myopathic facies
HP:0002093	Respiratory insufficiency

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535380	Arthrogryposis multiplex congenita, distal, X-linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5924 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

28 measured of 121 human assays (121 total across all organisms); most potent 28 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Compound I	IC50	10.2 nM
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-phenylpyrazolo[1,5-a]pyrimidin-7-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-[(1R,2R,3S,4R)-2,3-dihydroxy-4-{[2-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-[(1R,2R,3S,4R)-4-{[2-(2,4-dichlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(2-(3,3-dimethyl-2,3-dihydrobenzofuran-7-yl)pyrazolo[1,5-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-7-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-Dihydroxy-4-((2-(3-phenoxyphenyl)pyrazolo[1,5-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(2-(trifluoromethyl)pyridin-4-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-Dihydroxy-4-((2-(5-(trifluoromethyl)thiophen-2-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(6-(trifluoromethyl)pyridin-2-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(2-phenoxyphenyl)pyrazolo[1,5-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(2-(3-benzylpenyl)pyrazolo[1,5-a]pyrimidin-7-ylamino)-2,3-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(2-(3-benzoylphenyl)pyrazolo[1,5-a]pyrimidin-7-ylamino)-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-[(1R,2R,3S,4R)-2,3-dihydroxy-4-{[2-(1H-indol-5-yl)pyrazolo[1,5-a]pyrimidin-7-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(2-(trifluoromethylthio)phenyl)pyrazolo[1,5-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(4-(trifluoromethylthio)phenyl)pyrazolo[1,5-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(2-(6-chlorobenzo[b]thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(2-(5-ethylbenzo[b]thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-7-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(s.e.)-((1R,2R,3S,4R)-4-(2-(2,4-dichloronaphthalen-1-yl)pyrazolo[1,5-a]pyrimidin-7-	IC50	55 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-{(1R,2R,3S,4R)-2,3-dihydroxy-4-[(5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-{(1R,2R,3S,4R)-4-[(5-chloro-2-phenylpyrazolo[1,5-a]pyrimidin-7-yl)amino]-2,3-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(2-(4-bromophenyl)-5-chloropyrazolo[1,5-a]pyrimidin-7-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-{[5-chloro-2-(1-naphthyl)pyrazolo[1,5-a]pyrimidin-7-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-((1R,2R,3S,4R)-4-(5-chloro-2-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-[(1R,2R,3S,4R)-4-{[5-chloro-2-(4-methoxyphenyl)pyrazolo[1,5-a]-pyrimidin-7-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(rac)-{(1R,2R,3S,4R)-2,3-dihydroxy-4-[(6-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(s.e.)-{(1R,2R,3S,4R)-4-[(3,6-dichloro-2-{3-	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme
(s.e.)-{(1R,2R,3S,4R)-4-[(6-chloro-2-{3-[(trifluoromethyl)sulfanyl]phenyl}pyrazolo[1,	IC50	550 nM	US-9796725: Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme

ChEMBL bioactivities

34 potent at pChembl≥5 of 37 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.26	IC50	55	nM	CHEMBL5759269
7.26	IC50	55	nM	CHEMBL5864078
7.26	IC50	55	nM	CHEMBL5780833
7.26	IC50	55	nM	CHEMBL5887314
7.26	IC50	55	nM	CHEMBL5768102
7.26	IC50	55	nM	CHEMBL6003529
7.26	IC50	55	nM	CHEMBL5803994
7.26	IC50	55	nM	CHEMBL5954380
7.26	IC50	55	nM	CHEMBL5918592
7.26	IC50	55	nM	CHEMBL5958476
7.26	IC50	55	nM	CHEMBL5940945
7.26	IC50	55	nM	CHEMBL5747752
7.26	IC50	55	nM	CHEMBL5971124
7.26	IC50	55	nM	CHEMBL5832385
7.26	IC50	55	nM	CHEMBL5828810
7.26	IC50	55	nM	CHEMBL5997651
7.26	IC50	55	nM	CHEMBL6065415
7.26	IC50	55	nM	CHEMBL6053122
7.18	IC50	66	nM	CHEMBL5177755
7.03	Kd	92.91	nM	CHEMBL5653589
7.03	ED50	92.91	nM	CHEMBL5653589
6.35	IC50	449	nM	CHEMBL5175806
6.26	IC50	550	nM	CHEMBL5793677
6.26	IC50	550	nM	CHEMBL5743820
6.26	IC50	550	nM	CHEMBL5866556
6.26	IC50	550	nM	CHEMBL5799754
6.26	IC50	550	nM	CHEMBL6054356
6.26	IC50	550	nM	CHEMBL5762899
6.26	IC50	550	nM	CHEMBL5929395
6.26	IC50	550	nM	CHEMBL5960054
6.26	IC50	550	nM	CHEMBL5769060
6.20	Kd	630	nM	CHEMBL5440318
6.14	Kd	720	nM	CHEMBL5433769
5.62	IC50	2400	nM	HYRTIORETICULIN A

PubChem BioAssay actives

9 with measured affinity, of 55 total; 7 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
[(2R,3S,4R,5R)-5-[6-(2,3-dihydro-1H-inden-1-ylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1799781: Ubiquitin Thioester Inhibtion Assay from Article 10.1074/jbc.M111.279984: “Mechanistic studies of substrate-assisted inhibition of ubiquitin-activating enzyme by adenosine sulfamate analogues.”	ic50	0.0102	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	1872488: Inhibition of UAE (unknown origin)	ic50	0.0660	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149701: Binding affinity to human UBA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0929	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	1872482: Inhibition of recombinant C-terminal His-tagged human full length UAE1 expressed in Escherichia coli BL21 (lambdaDE3) assessed as reduction in transfer of Ub to UBE2C enzyme	ic50	0.4490	uM
N-[(2R)-6-amino-1-[[2-[[(2R)-6-amino-1-[[2-[[(2R)-6-amino-1-[[2-[[(8R,14R,20R)-8-[[[2-[[(2R)-6-amino-1-[[2-[[(2R)-1-[2-aminoethylsulfonyl-(2-amino-2-oxoethyl)amino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]hexan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]methyl]-14-(4-aminobutyl)-12-(methyl-methylidene-oxo-lambda6-sulfanyl)-18-methylsulfonyl-2,10,16,26-tetraoxo-3,9,12,15,18,25-hexazabicyclo[25.2.2]hentriaconta-1(29),27,30-trien-20-yl]amino]-2-oxoethyl]-(2-aminoethylsulfonyl)amino]hexan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]hexan-2-yl]amino]-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]hexan-2-yl]-3-[(2’,7’-dihydroxy-3-oxospiro[2-benzofuran-1,10’-9H-anthracene]-5-yl)carbamothioylamino]propanamide	1965065: Binding affinity to Uba1 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by fluorescence polarisation assay	kd	0.6300	uM
N-[(2R)-6-amino-1-[[2-[[(8R,14R,20R)-8-[[[2-[[(2R)-6-amino-1-[[2-[[(2R)-1-[[2-[[(2R)-6-amino-1-[[2-[[(2R)-1-[2-aminoethylsulfonyl-(2-amino-2-oxoethyl)amino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]hexan-2-yl]amino]-2-oxoethyl]-(2-methylpropylsulfonyl)amino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-(methyl-methylidene-oxo-lambda6-sulfanyl)amino]hexan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]methyl]-14-(4-aminobutyl)-12-(2-aminoethylsulfonyl)-18-methylsulfonyl-2,10,16,26-tetraoxo-3,9,12,15,18,25-hexazabicyclo[25.2.2]hentriaconta-1(29),27,30-trien-20-yl]amino]-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]hexan-2-yl]-3-[(2’,7’-dihydroxy-3-oxospiro[2-benzofuran-1,10’-9H-anthracene]-5-yl)carbamothioylamino]propanamide	1965065: Binding affinity to Uba1 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by fluorescence polarisation assay	kd	0.7200	uM
(1R,3S)-6-hydroxy-1-(1H-imidazol-5-ylmethyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid	670510: Inhibition of FLAG-tagged ubiquitin-activating enzyme E1 assessed as inhibition of GST-ubiquitin/FLAG-E1 intermediate formation by Western blot analysis	ic50	2.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, affects expression	2
ochratoxin A	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Caffeine	increases expression, affects phosphorylation	2
Tobacco Smoke Pollution	affects expression, increases metabolic processing	2
Ziram	decreases activity, decreases reaction, decreases ubiquitination	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
methyldithiocarbamate	increases activity, increases ubiquitination	1
molinate	increases activity, increases ubiquitination	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
zinc chloride	decreases ubiquitination, increases reaction, decreases activity	1
sodium arsenite	increases expression, increases abundance	1
cobaltous chloride	decreases expression	1
pyrrolidine dithiocarbamic acid	decreases activity, decreases ubiquitination	1
manganese chloride	decreases activity, decreases ubiquitination	1
4-hydroxy-2-nonenal	increases activity, increases ubiquitination	1
cupric chloride	decreases activity, decreases ubiquitination, increases reaction	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
epigallocatechin gallate	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

38 unique, capped per target: 38 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1014022	Binding	Inhibition of human recombinant E1-ubiquitin complex formation	Panepophenanthrin, from a mushroom strain, a novel inhibitor of the ubiquitin-activating enzyme. — J Nat Prod

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8A8	Abcam Raji UBA1 KO	Cancer cell line	Male
CVCL_C0B2	Abcam THP-1 UBA1 KO	Cancer cell line	Male
CVCL_C7CQ	Abcam PC-3 UBA1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00958620	PHASE4	COMPLETED	Shockwave Therapy of Chronic Achilles Tendinopathy
NCT03153527	PHASE4	RECRUITING	Taper Or Abrupt Steroid Stop: TOASSTtrial
NCT04297592	PHASE4	ENROLLING_BY_INVITATION	Antibiotic Prophylaxis in High-Risk Arthroplasty Patients
NCT02266433	PHASE3	TERMINATED	Dexamethasone Versus Ketorolac Injection for the Treatment of Local Inflammatory Hand and Upper Extremity Disorders
NCT06059989	PHASE3	RECRUITING	InDuctIon TREatment with SubCuTaneous Infliximab for Crohn’s Disease
NCT01364389	PHASE2	TERMINATED	A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica
NCT03604406	PHASE2	COMPLETED	The Immunogenicity and Safety of Zostavax® and Shingrix® in Rheumatoid Arthritis Patients Using Abatacept
NCT03651518	PHASE2	COMPLETED	Personalized Therapies in Inflammatory Complex Disease
NCT06782373	PHASE2	RECRUITING	A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS)
NCT00734240	PHASE1	COMPLETED	Safety and Tolerability of Single and Multiple Doses of ISIS 353512 in Healthy Volunteers
NCT01398475	PHASE1	COMPLETED	A Relative Bioavailability and Food Effect Study of New Formulations
NCT01695876	PHASE1	COMPLETED	A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), Food Effect of AMG 357 in Healthy Subjects
NCT02959138	PHASE1	COMPLETED	Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function
NCT03044873	PHASE1	COMPLETED	Effect of BMS-986165 on the Pharmacokinetics of Rosuvastatin
NCT04987333	PHASE1	COMPLETED	Study of Efavaleukin Alfa in Healthy Chinese, Japanese, and Caucasian Participants
NCT05323110	PHASE1	TERMINATED	Study of Intravenously Administered Anti-LIGHT Monoclonal Antibody CBS001 in Healthy Volunteers
NCT05546788	PHASE1	UNKNOWN	Hydroxylated Polymethoxy Flavones Solid Dispersion in Treatment of Periodontitis
NCT05662033	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, and Pharmacokinetics (PK) of Oral AZD6793 in Healthy and Chronic Obstructive Pulmonary Disease Participants, to Assess the Relative Oral Bioavailability Between Two Formulations, and the Food Effect on the PK of AZD6793 Compared to Fasting State.
NCT05857215	PHASE1	COMPLETED	A First-in-Human Study of Single and Multiple Doses of Amilo-5MER in Healthy Subjects
NCT06065592	PHASE1	UNKNOWN	Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms
NCT06670274	PHASE1	COMPLETED	A Dose Escalating Study of HC002 in Healthy Adult Volunteers
NCT06538181	PHASE1	RECRUITING	Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
NCT06448052	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Umbilical Cord Mesenchymal Stem Cell for Aging-related Low-grade Inflammation
NCT02925351	EARLY_PHASE1	COMPLETED	Fluorine F 18 Clofarabine PET/CT in Imaging Patients With Autoimmune or Inflammatory Diseases
NCT00968084	Not specified	COMPLETED	Screening Protocol for Subjects Being Evaluated for Center for Human Immunology, Autoimmunity, and Inflammatory Diseases (CHI) Protocols
NCT01143454	Not specified	RECRUITING	Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System
NCT01280825	Not specified	RECRUITING	The 1200 Patients Project: Studying the Implementation of Clinical Pharmacogenomic Testing
NCT01460082	Not specified	COMPLETED	Endothelial Dysfunction in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT01567553	Not specified	TERMINATED	The Inflammatory Process and the Medical Imaging in Patients With an Inflammatory Disease of the Central Nervous System.
NCT01903642	Not specified	TERMINATED	Study of the Proteome and Cytokines During Inflammatory Syndromes of Different Etiologies.
NCT01981785	Not specified	UNKNOWN	Investigation of Immune Disorders and Deficiencies
NCT02084147	Not specified	COMPLETED	PET-MRI in Diagnosing Patients With Cancer, Cardiac Diseases, or Neurologic Diseases
NCT02122575	Not specified	COMPLETED	Effect of Fasting on the NLRP3 Inflammasome
NCT02332460	Not specified	UNKNOWN	Infusion Related Reactions in Patients Receiving Infliximab
NCT02408874	Not specified	WITHDRAWN	Inhaled Nanosilver Study
NCT02552004	Not specified	COMPLETED	Assessment of Intraoperative Probe-based Confocal Laser Endomicroscopy in Digestive and Endocrine Surgery: a Pilot Study
NCT02653079	Not specified	RECRUITING	Immunophenotyping From Blood of Patients Suffering From Chronic Degenerating Joint Diseases and Receiving LDRT
NCT03076866	Not specified	UNKNOWN	Prospective Follow-up of Patients With Chronic Inflammatory Rheumatism
NCT03112785	Not specified	ACTIVE_NOT_RECRUITING	Fitmore Versus CLS Stem in Total Hip Arthroplasty. Bilateral One-stage Operations
NCT03221127	Not specified	ACTIVE_NOT_RECRUITING	Kuopio Ischaemic Heart Disease Risk Factor Study (Nutrition Component)