UBE2N

Summary

UBE2N (ubiquitin conjugating enzyme E2 N, HGNC:12492) is a protein-coding gene on chromosome 12q22, encoding Ubiquitin-conjugating enzyme E2 N (P61088). The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical ‘Lys-63’-linked polyubiquitin chains. It is a common-essential gene (DepMap: required in 90.4% of cancer cell lines).

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Studies in mouse suggest that this protein plays a role in DNA postreplication repair.

Source: NCBI Gene 7334 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 9 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 90.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_003348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12492
Approved symbol	UBE2N
Name	ubiquitin conjugating enzyme E2 N
Location	12q22
Locus type	gene with protein product
Status	Approved
Aliases	UbcH-ben, UBC13, MGC8489
Ensembl gene	ENSG00000177889
Ensembl biotype	protein_coding
OMIM	603679
Entrez	7334

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000318066, ENST00000548946, ENST00000549490, ENST00000549833, ENST00000550657, ENST00000552442, ENST00000889119, ENST00000934316

RefSeq mRNA: 1 — MANE Select: NM_003348 NM_003348

CCDS: CCDS31875

Canonical transcript exons

ENST00000318066 — 4 exons

Exon	Start	End
ENSE00001277525	93441855	93441947
ENSE00001277538	93405684	93410079
ENSE00003551313	93410734	93410874
ENSE00003668633	93411053	93411299

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.1073 / max 1130.1496, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132658	95.7594	1827
132661	1.2391	627
132660	0.4981	271
132659	0.3369	150
132662	0.2738	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.26	gold quality
right testis	UBERON:0004534	99.21	gold quality
sperm	CL:0000019	98.77	gold quality
male germ cell	CL:0000015	98.61	gold quality
testis	UBERON:0000473	98.42	gold quality
adult organism	UBERON:0007023	98.37	gold quality
ganglionic eminence	UBERON:0004023	98.29	gold quality
embryo	UBERON:0000922	98.21	gold quality
islet of Langerhans	UBERON:0000006	98.13	gold quality
cortical plate	UBERON:0005343	98.09	gold quality
ventricular zone	UBERON:0003053	98.00	gold quality
heart right ventricle	UBERON:0002080	97.99	gold quality
pons	UBERON:0000988	97.97	gold quality
penis	UBERON:0000989	97.81	gold quality
myocardium	UBERON:0002349	97.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.68	gold quality
substantia nigra pars compacta	UBERON:0001965	97.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.58	gold quality
secondary oocyte	CL:0000655	97.57	gold quality
pharyngeal mucosa	UBERON:0000355	97.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.54	gold quality
left ventricle myocardium	UBERON:0006566	97.53	gold quality
colonic mucosa	UBERON:0000317	97.52	gold quality
body of tongue	UBERON:0011876	97.50	gold quality
epithelium of nasopharynx	UBERON:0001951	97.40	gold quality
vena cava	UBERON:0004087	97.35	gold quality
superior vestibular nucleus	UBERON:0007227	97.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.16	gold quality
biceps brachii	UBERON:0001507	97.12	gold quality
caecum	UBERON:0001153	97.11	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	3983.51
E-MTAB-4850	yes	394.84
E-CURD-122	yes	16.06
E-CURD-88	yes	4.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting UBE2N, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• This paper describes the function of the mouse protein, but suggests the function of the human protein, since both human and mouse proteins are 100% identical. (PMID:12039045)
• An NMR-based model of the ubiquitin-bound human complex and the structural basis of lysine 63 chain catalysis. (PMID:12569095)
• Ubc13-Mms2 and Lys63-polyubiquitin chains are associated with signaling cellular stress (PMID:14562038)
• The results in this study allowed identification of important residues of the Ubc13-Mms2 interface, determine a correlation between heterodimer formation and function, and conclude why Mms2 forms a specific complex with Ubc13 but not other Ubc proteins. (PMID:15749714)
• ISGylation of Ubc13 disrupts its ability to form thioester bond with ubiquitin (PMID:16122702)
• These data reveal a critical and unexpected role for vertebrate Ubc13 in the initiation of homologous recombination at the level of double-strand break processing. (PMID:17349954)
• modification of proteins with Lys(63)-linked ubiquitin chains occurs through a UEV1A-independent substrate modification and UEV1A-dependent Lys(63)-linked ubiquitin chain synthesis mechanism (PMID:17709375)
• Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax-mediated NF-kappaB activation. (PMID:17942533)
• the human Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage (PMID:18077395)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• RNF5 associates with JAMP in the ER membrane. This association results in Ubc13-dependent RNF5-mediated noncanonical ubiquitination of JAMP. (PMID:19269966)
• crystal structures of TRAF6 and its complex with the ubiquitin-conjugating enzyme (E2) Ubc13 (PMID:19465916)
• regulation of p53 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53. (PMID:19651615)
• UbcH5c approximately Ub conjugate populates an array of extended conformations, and the population of Ubc13 approximately Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13 (PMID:21226485)
• the interation between RAP80 and MDC1 is dependent upon the UBC13 mediated ubiquitination of MDC1 at K-1977 (PMID:21622030)
• entire coding region and splice junctions of RNF8, UBC13 and MMS2 genes were screened for mutations in affected index cases from 123 Northern Finnish breast cancer families (PMID:21774837)
• Data show that growth hormone receptor (GHR) endocytosis requires both ubiquitin-conjugating enzyme Ubc13 and the ubiquitin ligase COOH terminus of Hsp70 interacting protein (CHIP). (PMID:22433856)
• Data show RING finger (RNF) E3 ubiquitin ligase RNF8 dimerizes and binds to E2 ubiquitin-conjugating complex Ubc13/Mms2 with formation of Lys-63 ubiquitin chains, whereas the RNF168 RING domain is a monomer and does not catalyze Lys-6 ubiquitylation. (PMID:22589545)
• the crystal structure of human OTUB1 in complex with human UBC13 and MMS2 (PMID:22679021)
• The structure of the Shigella flexneri OspI and human Ubc13 complex revealed that the interacting surfaces between OspI and Ubc13 are a hydrophobic surface and a complementary charged surface. (PMID:23542009)
• crystal structure of the Shigella flexneri OspI-Ubc13 complex at 2.3 A resolution; study reveals the molecular basis of Ubc13 deamidation by OspI, as well as a convergence of E2 recognition by bacterial and host proteins (PMID:23633953)
• UBE2N inhibition induces neuroblastoma apoptotic cell death via activation of p53 and JNK pathways. (PMID:24556694)
• overexpression of hsa-miR-4516 downregulates STAT3, p-STAT3, CDK6, and UBE2N proteins that are consistently upregulated in psoriasis and induces apoptosis in HaCaT cells. (PMID:24610393)
• together with UBE2L3 and UBE2D2, synergistically contribute to Parkin-mediated mitophagy (PMID:24906799)
• Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-small ka, CyrillicB mediated matrix metalloproteinase-1 gene regulation. (PMID:25022892)
• Ubc13 was dispensable for transforming growth factor beta (TGFbeta)-induced SMAD activation but was required for activation of non-SMAD signaling via TGFbeta-activating kinase 1 (TAK1) and p38 (PMID:25189770)
• MiR-205 inhibits DNA damage repair by targeting ZEB1 and Ubc13. (PMID:25476932)
• Data suggest that ubiquitin-conjugating enzyme E2 variant 2 (Ube2V2) and ring finger protein 4 (RNF4) together induce an active conformation of the ubiquitin-conjugating enzyme Ubc13-ubiquitin (Ubc13~Ub) thioester. (PMID:26148049)
• The malin-laforin complex interacts physically and functionally with the ubiquitin conjugating enzyme E2-N (UBE2N). (PMID:26546463)
• Together with Riplet, Ube2D3 promotes covalent conjugation of polyubiquitin chains to RIG-I, while Ube2N preferentially facilitates production of unanchored chains. In the presence of these chains, RIG-I induces MAVS aggregation directly on the mitochondria. Data thus reveal two essential mechanisms underlying the activation of RIG-I and MAVS for triggering innate immune signaling in response to viral infection in cells. (PMID:28469175)
• Uev1A-Ubc13 complex catalyzes lysine63-linked ubiquitination of RHBDF2 to promote TACE maturation. (PMID:29069608)
• a novel function for UBC13 in regulating paclitaxel sensitivity through a DNMT1-CHFR-Aurora A pathway in ovarian cancer cells, is reported. (PMID:29367628)
• Study identified Ubc13 as a functional E2 for LNX1 and determined the complex structure of LNX1- Ubc13~ubiquitin (Ub). This structure uncovers a new interface between LNX1 and Ub, and unravels the mechanism by which Ub-loaded Ubc13 is recruited for Ub transfer via the E3 ligase activity of LNX1. (PMID:29496391)
• RNF11 may regulate the activity of E3s that rely on Ubc13 for ubiquitin chain assembly by limiting the availability of Ubc13 and its conjugate. (PMID:29537486)
• as a consequence of its high E2 affinity, an excess of ZNRF1 inhibits Ube2N-mediated ubiquitination at concentrations >/=500 nM instead of showing enhanced ubiquitination (PMID:29626159)
• The protein expression of UBE2N was validated in an independent clinical cohort to distinguish euploid from aneuploid colorectal cancers cells. (PMID:31319803)
• Data show that miR-934 binds to a 3’-UTR of ubiquitin-conjugating enzyme 2N (ube2n) mRNA, down-regulated UBE2N protein expression; this, in turn, attenuated cyclin dependent kinase 6 (CDK6) protein degradation and led to CDK6 protein accumulation as well as the promotion of BC tumor growth. (PMID:31373842)
• Study reveals how TRIM21 facilitates ubiquitin transfer and differentiates this E2 from other closely related enzymes. A tri-ionic motif provides optimally distributed anchor points that allow TRIM21 to wrap an Ube2N~Ub complex around its RING domain. The tri-ionic motif is exclusively required for Ube2N but not Ube2D1 activity and provides a generic E2-specific catalysis mechanism for RING E3s. (PMID:31582740)
• Deamidation elicited by Shigella flexneri disrupts native and transient contacts to weaken the interaction between UBC13 and TRAF6 and to silence the host anti-inflammatory response. (PMID:31638574)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2na	ENSDARG00000008748
danio_rerio	ube2nb	ENSDARG00000045877
mus_musculus	Ube2n	ENSMUSG00000074781
drosophila_melanogaster	ben	FBGN0000173
drosophila_melanogaster	CG3473	FBGN0028913
caenorhabditis_elegans		WBGENE00006708

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), UBE2K (ENSG00000078140), CDC34 (ENSG00000099804), UBE2I (ENSG00000103275), UBE2W (ENSG00000104343), UBE2R2 (ENSG00000107341), UBE2S (ENSG00000108106), UBE2B (ENSG00000119048), UBE2G1 (ENSG00000132388), UBE2Z (ENSG00000159202), UBE2J2 (ENSG00000160087), AKTIP (ENSG00000166971), UBE2V2 (ENSG00000169139), UBE2C (ENSG00000175063), UBE2O (ENSG00000175931), UBE2U (ENSG00000177414), UBE2F (ENSG00000184182), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 N — P61088 (reviewed: P61088)

Alternative names: Bendless-like ubiquitin-conjugating enzyme, E2 ubiquitin-conjugating enzyme N, Ubc13, UbcH13, Ubiquitin carrier protein N, Ubiquitin-protein ligase N

All UniProt accessions (6): P61088, F8VQQ8, F8VSD4, F8VV71, F8VZ29, V9HW41

UniProt curated annotations — full annotation on UniProt →

Function. The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical ‘Lys-63’-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the ‘Lys-63’-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the ‘Lys-63’-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate ‘Lys-63’-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UB2V1, catalyzes the viral RNA-dependent ‘Lys-63’-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production. UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate ‘Lys-63’-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway.

Subunit / interactions. Heterodimer with UBE2V2. Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific ‘Lys-63’-linked polyubiquitination activity. Interacts with RNF8 and RNF168. Interacts with RNF11. Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the ‘Lys-63’-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair. Interacts with ARIH2 (via RING-type 2). Interacts with OTUB1; leading to inhibit E2-conjugating activity. Interacts with GPS2; leading to inhibit E2-conjugating activity. Interacts with RIGI and RNF135; involved in RIGI ubiquitination and activation. Interacts with ZNRF1.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.

Activity regulation. Activity is inhibited by binding to OTUB1, which prevents ‘Lys-63’-linked polyubiquitination. Activity is inhibited by GPS2, leading to prevent ‘Lys-63’-linked polyubiquitination.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (1): NP_003339* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site

Pfam: PF00179

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 2.3.2.24 — (E3-independent) E2 ubiquitin-conjugating enzyme (BRENDA: 5 organisms, 56 substrates, 7 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBIQUITIN-CARRIER-PROTEIN UBC2B]-L-CYSTEINE	0.0001	5
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.2203–0.3014	2
[HISTONE H2A]-L-LYSINE	0.0008–0.0028	2
[HISTONE H2B]-L-LYSINE	0.0015–0.012	2
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1
[CYTOCHROME C]-L-LYSINE	0.125	1
[HISTONE H3]-L-LYSINE	0.0013	1

UniProt features (27 total): strand 10, helix 5, turn 3, mutagenesis site 3, chain 1, domain 1, active site 1, modified residue 1, disulfide bond 1, cross-link 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4ONL	X-RAY DIFFRACTION	1.35
4ONM	X-RAY DIFFRACTION	1.35
5YWR	X-RAY DIFFRACTION	1.47
4ONN	X-RAY DIFFRACTION	1.5
9BIV	X-RAY DIFFRACTION	1.68
9LHJ	X-RAY DIFFRACTION	1.68
4DHI	X-RAY DIFFRACTION	1.8
4NR3	X-RAY DIFFRACTION	1.8
1J7D	X-RAY DIFFRACTION	1.85
4NRG	X-RAY DIFFRACTION	1.95
6ULH	X-RAY DIFFRACTION	1.97
4TKP	X-RAY DIFFRACTION	2.08
6P5B	X-RAY DIFFRACTION	2.1
3HCT	X-RAY DIFFRACTION	2.1
9N1F	X-RAY DIFFRACTION	2.1
7BBD	X-RAY DIFFRACTION	2.2
5AIU	X-RAY DIFFRACTION	2.21
4IP3	X-RAY DIFFRACTION	2.3
4NRI	X-RAY DIFFRACTION	2.3
6UMS	X-RAY DIFFRACTION	2.34
4DHJ	X-RAY DIFFRACTION	2.35
6KG6	X-RAY DIFFRACTION	2.39
5EYA	X-RAY DIFFRACTION	2.4
6JKY	X-RAY DIFFRACTION	2.45
6LP2	X-RAY DIFFRACTION	2.48
7BBF	X-RAY DIFFRACTION	2.54
6D6I	X-RAY DIFFRACTION	2.55
3HCU	X-RAY DIFFRACTION	2.6
7BXG	X-RAY DIFFRACTION	2.71
6S53	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61088-F1	95.84	0.95

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): 87 (glycyl thioester intermediate)

Post-translational modifications (2): 82, 92

Disulfide bonds (1): 87

Mutagenesis-validated functional residues (3):

Position	Phenotype
87	loss of polyubiquitination of pcna. impairs interaction with shprh.
92	no isgylation.
94	no effect on isgylation.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-202424	Downstream TCR signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9020702	Interleukin-1 signaling
R-HSA-937039	IRAK1 recruits IKK complex
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-9646399	Aggrephagy
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975110	TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975144	IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 392 (showing top): REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, PID_IL1_PATHWAY, GCM_ZNF198

GO Biological Process (24): protein polyubiquitination (GO:0000209), double-strand break repair via homologous recombination (GO:0000724), DNA double-strand break processing (GO:0000729), regulation of DNA repair (GO:0006282), DNA damage tolerance (GO:0006301), protein monoubiquitination (GO:0006513), protein ubiquitination (GO:0016567), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of DNA repair (GO:0045739), T cell receptor signaling pathway (GO:0050852), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein K63-linked ubiquitination (GO:0070534), antiviral innate immune response (GO:0140374), positive regulation of protein K63-linked ubiquitination (GO:1902523), positive regulation of intracellular signal transduction (GO:1902533), negative regulation of TORC1 signaling (GO:1904262), positive regulation of double-strand break repair (GO:2000781), DNA repair (GO:0006281), ubiquitin-dependent protein catabolic process (GO:0006511), DNA damage response (GO:0006974), cellular response to nutrient levels (GO:0031669), protein modification by small protein conjugation (GO:0032446), TORC1 signaling (GO:0038202)

GO Molecular Function (11): RNA binding (GO:0003723), ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin protein ligase binding (GO:0031625), ubiquitin binding (GO:0043130), ubiquitin conjugating enzyme activity (GO:0061631), ubiquitin-protein transferase activator activity (GO:0097027), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (9): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), ubiquitin conjugating enzyme complex (GO:0031371), UBC13-MMS2 complex (GO:0031372), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
Toll Like Receptor 3 (TLR3) Cascade	2
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	2
TRIF (TICAM1)-mediated TLR4 signaling	2
MyD88 cascade initiated on plasma membrane	2
MAP kinase activation	2
Antimicrobial mechanism of IFN-stimulated genes	1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
Interleukin-1 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
Mitophagy	1
C-type lectin receptors (CLRs)	1
DNA Double Strand Break Response	1
DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
double-strand break repair	3
DNA metabolic process	3
cellular anatomical structure	3
DNA repair	2
DNA damage response	2
ubiquitin-protein transferase activity	2
intracellular protein-containing complex	2
transferase complex	2
recombinational repair	1
5’-3’ DNA exonuclease activity	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
DNA replication	1
protein modification by small protein conjugation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
antigen receptor-mediated signaling pathway	1
protein polyubiquitination	1
innate immune response	1
defense response to virus	1
protein K63-linked ubiquitination	1
regulation of protein K63-linked ubiquitination	1
positive regulation of protein polyubiquitination	1
positive regulation of signal transduction	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
modification-dependent protein catabolic process	1
nucleic acid binding	1

Protein interactions and networks

STRING

4450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2N	G3V2F7	G3V2F7	999
UBE2N	UBE2V2	Q15819	999
UBE2N	OTUB1	Q96FW1	998
UBE2N	RNF8	O76064	997
UBE2N	TRAF6	Q9Y4K3	997
UBE2N	BIRC2	Q13490	996
UBE2N	RNF168	Q8IYW5	990
UBE2N	TAX1BP1	Q86VP1	980
UBE2N	RAD18	Q9NS91	970
UBE2N	HLTF	Q14527	953
UBE2N	STUB1	Q9UNE7	943
UBE2N	IKBKG	Q9Y6K9	942
UBE2N	SHPRH	Q149N8	941
UBE2N	TAB2	Q9NYJ8	936
UBE2N	UBA1	P22314	889

IntAct

363 interactions, top by confidence:

A	B	Type	Score
UBE2V1	UBE2N	psi-mi:“MI:0915”(physical association)	0.910
UBE2N	UBE2V1	psi-mi:“MI:0915”(physical association)	0.910
UBE2V1	UBE2N	psi-mi:“MI:0220”(ubiquitination reaction)	0.910
UBE2N	UBE2V1	psi-mi:“MI:0407”(direct interaction)	0.910
UBE2V1	UBE2N	psi-mi:“MI:0407”(direct interaction)	0.910
UBE2V1	UBE2N	psi-mi:“MI:0914”(association)	0.910
TRAF6	UBE2N	psi-mi:“MI:0407”(direct interaction)	0.850
TRAF6	UBE2N	psi-mi:“MI:0915”(physical association)	0.850
UBE2N	TRAF6	psi-mi:“MI:0915”(physical association)	0.850
UBE2N	TRAF6	psi-mi:“MI:0220”(ubiquitination reaction)	0.850
TRAF6	UBE2N	psi-mi:“MI:0220”(ubiquitination reaction)	0.850
UBE2N	ZNRF1	psi-mi:“MI:0915”(physical association)	0.820
ZNRF1	UBE2N	psi-mi:“MI:0915”(physical association)	0.820
UBE2N	UBE2V2	psi-mi:“MI:0407”(direct interaction)	0.810
UBE2V2	UBE2N	psi-mi:“MI:0915”(physical association)	0.810
UBE2N	UBE2V2	psi-mi:“MI:0915”(physical association)	0.810
OTUB1		psi-mi:“MI:0914”(association)	0.760
UBE2N	STUB1	psi-mi:“MI:0915”(physical association)	0.750
UBE2N	STUB1	psi-mi:“MI:0407”(direct interaction)	0.750
UBE2N	RNF11	psi-mi:“MI:0915”(physical association)	0.730
TRIM32	UBE2N	psi-mi:“MI:0915”(physical association)	0.730
RNF11	UBE2N	psi-mi:“MI:0915”(physical association)	0.730

BioGRID (717): UBE2N (Reconstituted Complex), UBE2N (Reconstituted Complex), SLX5 (Biochemical Activity), SLX8 (Biochemical Activity), RNF168 (Affinity Capture-Western), UBE2N (Reconstituted Complex), UBE2N (Reconstituted Complex), STUB1 (Affinity Capture-MS), UBE2N (Reconstituted Complex), UBE2N (Reconstituted Complex), BFAR (Two-hybrid), UBE2N (Reconstituted Complex), UBE2N (Reconstituted Complex), UBE2N (Reconstituted Complex), UBE2N (Reconstituted Complex)

ESM2 similar proteins: I1RRW0, O00102, O74810, P0CS16, P0CS17, P21734, P25868, P35128, P40984, P52486, P52491, P56616, P61085, P61086, P61087, P61088, P61089, P62253, P62254, P62255, Q02159, Q0P5K3, Q1RMW1, Q28CQ4, Q32LD2, Q32PA5, Q3UWQ3, Q42540, Q4PFA5, Q4R4I1, Q4R5Y8, Q5JXB2, Q5M8Y2, Q5R7J6, Q5U203, Q5ZKX6, Q6IRC7, Q6NY82, Q6Y1Z4, Q75AF2

Diamond homologs: A0A1B0GUS4, A5PJC4, A5PKP9, D3ZDK2, O13685, O14933, O74196, O74810, P0C8G3, P0C8G4, P0C8G5, P15731, P15732, P21734, P25867, P25869, P27949, P35128, P35129, P35131, P35132, P35133, P35134, P35135, P43102, P46595, P49427, P51668, P51965, P52482, P52483, P52485, P52487, P52490, P52492, P61077, P61078, P61079, P61080, P61088

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
UBE2N	“up-regulates activity”	TRAF2	ubiquitination
UBE2N	up-regulates	H2AX	ubiquitination
UBE2N	“up-regulates activity”	UBE2V1	binding
OTUB1	down-regulates	UBE2N	binding
TRAF2	“up-regulates activity”	UBE2N	binding
RNF8	up-regulates	UBE2N	binding
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2N	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2N	ubiquitination
UBE2N	“up-regulates activity”	TRIM63	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 173 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
Extra-nuclear estrogen signaling	7	9.3×	4e-03
Antigen processing: Ubiquitination & Proteasome degradation	18	5.2×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein K63-linked ubiquitination	14	23.4×	3e-13
protein autoubiquitination	14	20.5×	2e-12
protein polyubiquitination	20	14.4×	1e-14
cell surface receptor protein tyrosine kinase signaling pathway	13	14.1×	2e-09
protein monoubiquitination	6	12.9×	6e-04
ubiquitin-dependent protein catabolic process	23	10.7×	1e-14
obsolete positive regulation of NF-kappaB transcription factor activity	8	10.3×	1e-04
protein K48-linked ubiquitination	9	9.5×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

891 predictions. Top by Δscore:

Variant	Effect	Δscore
12:93410870:CTTAT:C	acceptor_gain	1.0000
12:93411124:A:AC	donor_gain	1.0000
12:93411125:C:CC	donor_gain	1.0000
12:93411295:GTTTC:G	acceptor_gain	1.0000
12:93411296:TTTC:T	acceptor_gain	1.0000
12:93411297:TTC:T	acceptor_gain	1.0000
12:93411298:TC:T	acceptor_gain	1.0000
12:93411299:CCTA:C	acceptor_gain	1.0000
12:93411300:C:CA	acceptor_loss	1.0000
12:93411300:C:CC	acceptor_gain	1.0000
12:93411300:C:T	acceptor_gain	1.0000
12:93411302:A:C	acceptor_gain	1.0000
12:93411306:C:CT	acceptor_gain	1.0000
12:93411307:A:T	acceptor_gain	1.0000
12:93441850:GTTAC:G	donor_loss	1.0000
12:93441851:TTAC:T	donor_loss	1.0000
12:93441852:TACCT:T	donor_loss	1.0000
12:93441853:A:AT	donor_loss	1.0000
12:93441854:C:CG	donor_loss	1.0000
12:93410729:GATAC:G	donor_loss	0.9900
12:93410730:ATACC:A	donor_loss	0.9900
12:93410731:TACC:T	donor_loss	0.9900
12:93410732:A:AG	donor_loss	0.9900
12:93410733:C:T	donor_loss	0.9900
12:93411184:C:CA	donor_gain	0.9900
12:93411296:TTTCC:T	acceptor_gain	0.9900
12:93411297:TTCC:T	acceptor_gain	0.9900
12:93411298:TCCT:T	acceptor_gain	0.9900
12:93411299:CCTAT:C	acceptor_gain	0.9900
12:93411300:CTAT:C	acceptor_gain	0.9900

AlphaMissense

993 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:93410867:C:A	W95C	1.000
12:93410867:C:G	W95C	1.000
12:93410869:A:G	W95R	1.000
12:93410869:A:T	W95R	1.000
12:93411079:C:A	G84V	1.000
12:93411079:C:T	G84E	1.000
12:93441865:C:A	R7M	1.000
12:93410856:A:G	L99P	0.999
12:93411055:T:A	K92I	0.999
12:93411058:A:G	L91S	0.999
12:93411064:T:A	D89V	0.999
12:93411065:C:G	D89H	0.999
12:93411069:A:C	C87W	0.999
12:93411070:C:T	C87Y	0.999
12:93411071:A:G	C87R	0.999
12:93411073:A:C	I86R	0.999
12:93411073:A:T	I86K	0.999
12:93411080:C:G	G84R	0.999
12:93411080:C:T	G84R	0.999
12:93411088:T:A	D81V	0.999
12:93411093:A:C	N79K	0.999
12:93411093:A:T	N79K	0.999
12:93411101:G:C	H77D	0.999
12:93411117:G:C	F71L	0.999
12:93411117:G:T	F71L	0.999
12:93411119:A:G	F71L	0.999
12:93411130:G:T	P67H	0.999
12:93411146:A:G	Y62H	0.999
12:93411163:A:G	L56P	0.999
12:93411169:A:T	L54H	0.999

dbSNP variants (sampled 300 via entrez): RS1000158607 (12:93430479 G>A,C), RS1000189765 (12:93413757 A>C), RS1000240703 (12:93413506 T>C), RS1000319837 (12:93407558 G>T), RS1000334437 (12:93414177 T>C), RS1000368933 (12:93405759 T>A,C), RS1000499229 (12:93441495 C>T), RS1000567660 (12:93419789 C>T), RS1000770874 (12:93437061 G>A,C), RS1000823726 (12:93425759 G>A), RS1000976636 (12:93437556 G>A), RS1001020646 (12:93419176 G>A,C), RS1001034713 (12:93419562 A>C), RS1001048666 (12:93437333 T>C), RS1001075025 (12:93431166 G>A,T)

Disease associations

OMIM: gene MIM:603679 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000175_22	Height	2.000000e-07
GCST90002396_532	Mean reticulocyte volume	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3883289 (PROTEIN-PROTEIN INTERACTION), CHEMBL6089 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 138,431 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,574
CHEMBL1200883	THONZONIUM BROMIDE	4	1,098
CHEMBL1516474	TEGASEROD MALEATE	4	1,823
CHEMBL567	PERPHENAZINE	4	21,883
CHEMBL790	CHLORHEXIDINE	4	85,053

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

Binding affinities (BindingDB)

207 measured of 876 human assays (1209 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6-Amino-4-(3-ethoxy-4-hydroxy-phenyl)-3-phenyl-1,4-dihydro-pyrano[2,3-c]pyrazole	EC50	0.00738 nM
METHIOTHEPIN	KI	1 nM
1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-4-methylpiperazine	KI	1.8 nM
4-amino-5-chloro-N-(1-(3-(4-fluorophenoxy)propyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide	KI	10.2 nM
[3H]4-OHT	IC50	21 nM
SMR001230745	KI	63.1 nM
2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;hydrochloride	KI	146 nM
MLS000911514	EC50	340 nM
4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanol	KI	421 nM
MLS000540774	EC50	436 nM
6-(methoxymethyl)-2-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1H-pyrimidin-4-one	EC50	560 nM
2-amino-4-[4-(4-chlorobenzyl)oxy-3-methoxy-phenyl]-6-phenyl-1,4-dihydropyrimidine-5-carboxylic acid ethyl ester	EC50	580 nM
2-[(3-benzamido-4-keto-quinazolin-2-yl)thio]acetic acid ethyl ester	EC50	933 nM
cid_2913535	KI	950 nM
(5E)-2-(4-hydroxyanilino)-5-(4-hydroxy-3,5-dimethoxy-benzylidene)-2-thiazolin-4-one	EC50	974 nM
SMR000391146	EC50	1010 nM
1-Decyloxycarbonylmethyl-3-methyl-2-o-tolyloxymethyl-3H-benzoimidazol-1-ium	EC50	1020 nM
2-[[2-[2-(dimethylamino)ethylamino]-1-oxoethyl]amino]-4-(4-phenylphenyl)-3-thiophenecarboxylic acid ethyl ester;hydrochloride	EC50	1090 nM
4-methoxy-N-[4-oxidanylidene-2-[2-oxidanylidene-2-[(phenylmethyl)amino]ethyl]sulfanyl-quinazolin-3-yl]benzamide	EC50	1290 nM
MLS000028463	KI	1410 nM
LW-LW	EC50	1440 nM
MLS000829932	IC50	1460 nM
(5S)-4-[2-(3,4-dichlorophenyl)ethyl]-1-[(1R)-5-[methyl(p-anisyl)amino]-1-[(p-anisylamino)methyl]pentyl]-5-phenyl-piperazine-2,3-quinone	EC50	1480 nM
2-[2-[4-(2-hydroxy-3-phenoxy-propyl)piperazino]ethyl]benzo[de]isoquinoline-1,3-quinone	EC50	1710 nM
MLS000118108	IC50	1740 nM
2-[[4-(2,4-dichlorobenzyl)oxybenzylidene]amino]guanidine	EC50	1910 nM
1-ethyl-3-[(2-keto-5-nitro-indol-3-yl)amino]thiourea	EC50	1930 nM
(6-bromo-2-methyl-4-quinolyl)-(p-anisylideneamino)amine	EC50	1940 nM
MLS001233767	IC50	1960 nM
(2R,3R)-1-N,3-dimethyl-2-N-[(2R)-3-naphthalen-1-yl-2-[2-[3-(trifluoromethyl)phenyl]ethylamino]propyl]pentane-1,2-diamine	EC50	2030 nM
MLS000591024	IC50	2050 nM
3-bromo-N-[(2S)-1-[(3S,6S)-6-[(4-methoxyphenyl)methyl]-3-propan-2-yl-2,3,5,6-tetrahydroimidazo[1,2-a]imidazol-7-yl]propan-2-yl]-4-methylbenzamide	IC50	2070 nM
MLS001165417	EC50	2240 nM
MLS000034396	EC50	2290 nM
2-amino-4-[4-(4-carbomethoxybenzyl)oxyphenyl]-6-phenyl-1,4-dihydropyrimidine-5-carboxylic acid ethyl ester	EC50	2380 nM
cid_1548953	IC50	2410 nM
3-Benzyl-9-dimethylamino-3H-pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidin-4-one	EC50	2470 nM
2-[3-methyl-2-(phenoxymethyl)-1-benzimidazol-3-iumyl]acetic acid decyl ester;chloride	EC50	2600 nM
1-(2,4-dichlorophenyl)-2-[5-(4-fluorobenzoyl)-2,8-dimethyl-3,4,4a,9b-tetrahydro-1H-pyrido[4,3-b]indol-2-ium-2-yl]ethanone;chloride	IC50	2650 nM
(2E)-2-[(3-methoxyphenyl)methylidene]-3-oxo-N-(2-pyrrolidin-1-ylethyl)-4H-1,4-benzothiazine-6-carboxamide	EC50	2810 nM
cid_16746003	EC50	2860 nM
cid_42600997	IC50	2880 nM
MLS000871726	EC50	2910 nM
cid_5074	KI	2920 nM
methyl (4S)-4-(4-bromophenyl)-6-methyl-1-(phenylmethyl)-2-(2-pyridin-3-ylethylamino)-4H-pyrimidine-5-carboxylate	IC50	3040 nM
SMR001251708	IC50	3310 nM
2-(4-hydroxyphenyl)-3-({4-[2-(piperidin-1-yl)ethoxy]phenyl}carbonyl)-1-benzothiophen-6-ol	IC50	3400 nM
2-[(4-{[5-chloro-2-(propan-2-yloxy)phenyl]amino}-6-(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)amino]ethan-1-ol	IC50	3440 nM
MLS000757047	IC50	3670 nM
2-chloranyl-10-[3-(4-methylpiperazin-1-yl)propyl]phenothiazine;ethane-1,2-disulfonic acid	IC50	3770 nM

ChEMBL bioactivities

379 potent at pChembl≥5 of 656 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	IC50	90	nM	MANADOSTEROL A
6.89	IC50	130	nM	MANADOSTEROL B
6.89	IC50	130	nM	CHEMBL6167644
6.41	IC50	386	nM	CHEMBL3192949
6.32	IC50	477	nM	CHEMBL3192949
6.29	IC50	507	nM	CHEMBL3192124
6.29	IC50	509	nM	CHEMBL1521485
6.26	IC50	548	nM	CHEMBL3192124
6.25	IC50	561	nM	CHEMBL1509569
6.23	IC50	594	nM	CHEMBL1558306
6.18	IC50	664	nM	CHEMBL1326930
6.15	IC50	709	nM	CHEMBL1381940
6.12	IC50	763	nM	CHEMBL1418004
6.11	IC50	781	nM	CHEMBL6148515
6.08	IC50	829	nM	CHEMBL1462994
6.06	IC50	873	nM	AMINODIMETHOXYQUINAZOLINYLPIPERAZINE
6.02	IC50	947	nM	CHEMBL3191507
6.01	IC50	965	nM	CHEMBL3191507
6.01	IC50	982	nM	CHEMBL1511432
6.01	IC50	967	nM	CHEMBL1409350
5.99	IC50	1022	nM	CHEMBL1494737
5.95	IC50	1114	nM	CHEMBL1995152
5.91	IC50	1228	nM	CHEMBL1381940
5.90	IC50	1246	nM	CHEMBL3194432
5.89	IC50	1274	nM	CHEMBL1316978
5.88	IC50	1332	nM	CHEMBL3194432
5.88	IC50	1315	nM	CHEMBL1336154
5.88	IC50	1314	nM	CHEMBL1368012
5.87	IC50	1351	nM	CHEMBL1299925
5.87	IC50	1336	nM	CHEMBL1511432
5.84	IC50	1445	nM	CHEMBL1986183
5.83	IC50	1462	nM	CHEMBL1494737
5.83	IC50	1496	nM	AMINODIMETHOXYQUINAZOLINYLPIPERAZINE
5.83	IC50	1465	nM	CHEMBL1534719
5.83	IC50	1466	nM	CHEMBL1421924
5.82	IC50	1524	nM	CHEMBL1466441
5.81	IC50	1534	nM	CHEMBL1533093
5.81	IC50	1545	nM	CHEMBL1336154
5.80	IC50	1585	nM	CHEMBL1349480
5.78	IC50	1677	nM	CHEMBL3198118
5.78	IC50	1677	nM	CHEMBL1456173
5.77	IC50	1700	nM	CHEMBL1448793
5.76	IC50	1727	nM	CHEMBL1409350
5.76	IC50	1725	nM	ALEXIDINE HYDROCHLORIDE
5.75	IC50	1783	nM	CHEMBL1533093
5.72	IC50	1885	nM	CHEMBL1457602
5.72	IC50	1893	nM	CHEMBL3198118
5.70	IC50	2005	nM	CHEMBL1986183
5.70	IC50	1977	nM	ALEXIDINE HYDROCHLORIDE
5.70	IC50	1987	nM	CHEMBL1537917

PubChem BioAssay actives

2 with measured affinity, of 25 total; 2 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
pentasodium;[(2S,3S,5S,6S,8S,9S,10R,13R,14S,17R)-17-[(Z,2R)-4-[(1S,5R)-5-[(3R)-3-[(2S,3S,5S,6S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-2,3,6-trisulfonatooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butyl]-2,2,4-trimethylcyclopent-3-en-1-yl]but-3-en-2-yl]-3-hydroxy-10,13-dimethyl-2-sulfonatooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl] sulfate	685292: Inhibition of recombinant human Ubc13-Uev1A interaction expressed in Escherichia BL21 after 1.5 hrs by ELISA	ic50	0.0900	uM
tetrasodium;[(3S,5S,6S,8S,9S,10R,13R,14S,17R)-17-[(E,2R)-4-[(1S,5R)-5-[(3S)-3-[(2S,3S,5S,6S,8S,9S,10R,13S,14S,17R)-10,13-dimethyl-2,3,6-trisulfonatooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-hydroxybutyl]-2,2-dimethyl-4-methylidenecyclopentyl]but-3-en-2-yl]-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl] sulfate	685292: Inhibition of recombinant human Ubc13-Uev1A interaction expressed in Escherichia BL21 after 1.5 hrs by ELISA	ic50	0.1300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects reaction, decreases expression	4
bisphenol A	increases expression, affects expression, decreases expression	3
Benzo(a)pyrene	decreases expression, affects cotreatment, increases expression, affects methylation	3
Cisplatin	affects reaction, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
methylmercuric chloride	decreases expression	1
chlorophyllin	decreases expression	1
geraniol	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
CPG-oligonucleotide	increases expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

16 unique, capped per target: 14 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013729	Binding	Inhibition of human Ubc13-Uev1A interaction expressed in Escherichia BL21 after 15 mins by ELISA	Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis. — Bioorg Med Chem Lett
CHEMBL1738239	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID485273, AID485343, AID493182]	PubChem BioAssay data set

Clinical trials (associated diseases)

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