UBE2V1

Summary

UBE2V1 (ubiquitin conjugating enzyme E2 V1, HGNC:12494) is a protein-coding gene on chromosome 20q13.13, encoding Ubiquitin-conjugating enzyme E2 variant 1 (Q13404). Has no ubiquitin ligase activity on its own. It is a selective cancer dependency (DepMap: 51.5% of cell lines).

Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein encoded by this gene is located in the nucleus and can cause transcriptional activation of the human FOS proto-oncogene. It is thought to be involved in the control of differentiation by altering cell cycle behavior. Alternatively spliced transcript variants encoding multiple isoforms have been described for this gene, and multiple pseudogenes of this gene have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (Kua-UEV), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product.

Source: NCBI Gene 7335 — RefSeq curated summary.

At a glance

• Druggable target: yes
• Cancer dependency (DepMap): dependent in 51.5% of screened cell lines
• MANE Select transcript: NM_001032288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12494
Approved symbol	UBE2V1
Name	ubiquitin conjugating enzyme E2 V1
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	UEV-1, CROC-1, UEV1A, CROC1
Ensembl gene	ENSG00000244687
Ensembl biotype	protein_coding
OMIM	602995
Entrez	7335

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 13 protein_coding, 11 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000340309, ENST00000371657, ENST00000371674, ENST00000371677, ENST00000396059, ENST00000415862, ENST00000432266, ENST00000461960, ENST00000462217, ENST00000467839, ENST00000468926, ENST00000470565, ENST00000472923, ENST00000473860, ENST00000483534, ENST00000486653, ENST00000490289, ENST00000490555, ENST00000492371, ENST00000493090, ENST00000557021, ENST00000617119, ENST00000625172, ENST00000866194, ENST00000866195, ENST00000936103, ENST00000936104, ENST00000936105

RefSeq mRNA: 16 — MANE Select: NM_001032288 NM_001032288, NM_001257393, NM_001257394, NM_001257395, NM_001257396, NM_001257397, NM_001257398, NM_001257399, NM_001282575, NM_001282576, NM_001282577, NM_001282578, NM_001282579, NM_021988, NM_022442, NM_199144

CCDS: CCDS13426, CCDS13427, CCDS33483, CCDS58775, CCDS74740

Canonical transcript exons

ENST00000371674 — 4 exons

Exon	Start	End
ENSE00001433094	50113107	50113150
ENSE00003678668	50096672	50096820
ENSE00003746646	50084129	50084254
ENSE00003900090	50081124	50082914

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.8802 / max 2703.4951, expressed in 1820 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187813	90.7780	1818
187814	13.9229	1783
187815	3.9597	1470
187810	3.8997	1529
187809	0.7816	432
187811	0.5382	273

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	98.88	gold quality
superior frontal gyrus	UBERON:0002661	98.25	gold quality
cortical plate	UBERON:0005343	98.23	gold quality
tonsil	UBERON:0002372	98.00	gold quality
smooth muscle tissue	UBERON:0001135	97.76	gold quality
lower esophagus mucosa	UBERON:0035834	97.66	gold quality
placenta	UBERON:0001987	97.63	gold quality
ganglionic eminence	UBERON:0004023	97.63	gold quality
primary visual cortex	UBERON:0002436	97.62	gold quality
lower esophagus	UBERON:0013473	97.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.60	gold quality
bone marrow cell	CL:0002092	97.56	gold quality
skin of leg	UBERON:0001511	97.55	gold quality
monocyte	CL:0000576	97.54	gold quality
leukocyte	CL:0000738	97.53	gold quality
anterior cingulate cortex	UBERON:0009835	97.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.44	gold quality
zone of skin	UBERON:0000014	97.43	gold quality
islet of Langerhans	UBERON:0000006	97.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.42	gold quality
body of pancreas	UBERON:0001150	97.41	gold quality
pancreas	UBERON:0001264	97.41	gold quality
esophagus	UBERON:0001043	97.37	gold quality
mucosa of stomach	UBERON:0001199	97.35	gold quality
endometrium	UBERON:0001295	97.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.33	gold quality
lymph node	UBERON:0000029	97.29	gold quality
right frontal lobe	UBERON:0002810	97.29	gold quality
cerebral cortex	UBERON:0000956	97.24	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.93
E-GEOD-110499	no	1097.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting UBE2V1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6870-5P	99.99	68.55	2115
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-5696	99.98	72.36	4487
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 51.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• Data demonstrate that divergent activities of Ubc13 rely on its pairing with either of two Uevs, Uev1A or Mms2. (PMID:16129784)
• A structural model for the Ub-hUev1a-hUbc13-Ub tetramer was developed to gain chemical insight into the synthesis of Lys(63)-linked Ubiquitin chains. (PMID:16893187)
• These data provide evidence that Uev1A is a critical regulatory component in the NF-kappaB signaling pathway in response to environmental stresses and identify UEV1A as a potential proto-oncogene. (PMID:17041755)
• 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)
• Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-small ka, CyrillicB mediated matrix metalloproteinase-1 gene regulation. (PMID:25022892)
• Gene and protein expression of UBE2v1, a ubiquitin-conjugating E2-enzyme variant that mediates Lys63-linked ubiquitination, and Lys63-ubiquitinated proteins increased in HK2 tubular cells under high glucose; immunohistochemistry on diabtic kidney samples revealed an increase in UBE2v1- and Lys63-ubiquitinated proteins, particularly in kidneys of patients with diabetic nephropathy. (PMID:27881486)
• Uev1A appears to be involved in the BMP signaling pathway in which it collaborates with a ubiquitin E3 ligase Smurf1 to promote Smad1 degradation in a Ubc13-independent manner. (PMID:28771228)
• Uev1A-Ubc13 complex catalyzes lysine63-linked ubiquitination of RHBDF2 to promote TACE maturation. (PMID:29069608)
• variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1 (PMID:29108000)
• Ube2v1suppressed autophagy program and promoted epithelial mesenchymal transition (EMT) and metastasis of CRC cells in an autophagy-dependent pattern in vitro and in vivo. (PMID:30016968)
• Ube2v1 Positively Regulates Protein Aggregation by Modulating Ubiquitin Proteasome System Performance Partially Through K63 Ubiquitination. (PMID:32081062)
• Uev1A amino terminus stimulates poly-ubiquitin chain assembly and is required for NF-kappaB activation. (PMID:32659264)
• Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler. (PMID:33288957)
• Uev1A promotes breast cancer cell migration by up-regulating CT45A expression via the AKT pathway. (PMID:34503444)
• Ubiquitin-conjugating enzyme V variant 1 enables cellular responses toward fibroblast growth factor signaling in endothelium. (PMID:34921695)
• Hypoxia-induced long non-coding RNA LINC00460 promotes p53 mediated proliferation and metastasis of pancreatic cancer by regulating the miR-4689/UBE2V1 axis and sequestering USP10. (PMID:37786443)
• Role of Ubiquitin-conjugating enzyme E2 (UBE2) in two immune-mediated inflammatory skin diseases: a mendelian randomization analysis. (PMID:38795139)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ube2v1	ENSMUSG00000078923
rattus_norvegicus		ENSRNOG00000067007
rattus_norvegicus		ENSRNOG00000081040

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), UBE2N (ENSG00000177889), UBE2F (ENSG00000184182), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 variant 1 — Q13404 (reviewed: Q13404)

Alternative names: CROC-1, TRAF6-regulated IKK activator 1 beta Uev1A

All UniProt accessions (3): D6RG00, Q13404, G3V2F7

UniProt curated annotations — full annotation on UniProt →

Function. Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. 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. 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 UBE2N, 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 UBE2N. 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 TRAF6.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in thyroid, pancreas, spinal cord, lymph node, trachea, adrenal gland, bone marrow and pancreas. Detected at low levels in heart, breast, placenta, brain, liver, kidney, stomach and lung.

Induction. Down-regulated during differentiation of cultured colon adenocarcinoma cells.

Miscellaneous. In human, PESD1/KUA and UBE2V1/UEV1 are adjacent genes which can produce independent proteins and can also be fused to form a PESD1-UBE2V1 hybrid protein.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q13404-4	3, Isoform 2	yes
Q13404-1	1, CROC-1B, UEV-1B, Isoform 4
Q13404-2	2, CROC-1A, UEV-1A
Q13404-6	4, UEV-1As
Q13404-7	5, Isoform 3
Q13404-8	6

RefSeq proteins (16): NP_001027459, NP_001244322, NP_001244323, NP_001244324, NP_001244325, NP_001244326, NP_001244327, NP_001244328, NP_001269504, NP_001269505, NP_001269506, NP_001269507, NP_001269508, NP_068823, NP_071887, NP_954595 (=MANE)

Domains & families (InterPro)

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

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 (25 total): strand 6, splice variant 6, helix 4, turn 4, initiator methionine 1, chain 1, domain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2A4D	X-RAY DIFFRACTION	1.69
6D6I	X-RAY DIFFRACTION	2.55
2C2V	X-RAY DIFFRACTION	2.9
2HLW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13404-F1	94.68	0.91

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
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-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: 230 (showing top): REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, AGGAAGC_MIR5163P, RRAGTTGT_UNKNOWN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, 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, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, PID_IL1_PATHWAY, GOBP_DNA_DAMAGE_TOLERANCE, CACCAGC_MIR138

GO Biological Process (11): protein polyubiquitination (GO:0000209), regulation of DNA repair (GO:0006282), DNA damage tolerance (GO:0006301), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154), error-free postreplication DNA repair (GO:0042275), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of DNA-templated transcription (GO:0045893), protein K63-linked ubiquitination (GO:0070534), positive regulation of protein K63-linked ubiquitination (GO:1902523), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (3): ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin conjugating enzyme activity (GO:0061631), protein binding (GO:0005515)

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-17 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
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	2
MyD88 cascade initiated on plasma membrane	2
MAP kinase activation	2
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
Mitophagy	1
C-type lectin receptors (CLRs)	1
Interleukin-1 family signaling	1
Selective autophagy	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
intracellular protein-containing complex	2
transferase complex	2
protein ubiquitination	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
DNA metabolic process	1
DNA replication	1
DNA damage response	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
DNA damage tolerance	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
protein polyubiquitination	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
ubiquitin-like protein conjugating enzyme binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein conjugating enzyme activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
ubiquitin conjugating enzyme complex	1
cellular_component	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

259 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:0220”(ubiquitination reaction)	0.850
UBQLN1	UBE2V1	psi-mi:“MI:0915”(physical association)	0.810
UBE2V1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.810
RNF11	UBE2N	psi-mi:“MI:0220”(ubiquitination reaction)	0.730
UBE2V1	RNF11	psi-mi:“MI:0915”(physical association)	0.680
UBE2V1	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
FAM168A	UBE2V1	psi-mi:“MI:0915”(physical association)	0.670
XIAP	UBE2V1	psi-mi:“MI:0915”(physical association)	0.670
UBE2V1	TRIM32	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (235): UBE2V1 (Reconstituted Complex), STUB1 (Affinity Capture-MS), UBE2V1 (Reconstituted Complex), ube2nb (Two-hybrid), ube2nb (Reconstituted Complex), UBE2V1 (Reconstituted Complex), UBE2V1 (Reconstituted Complex), FAM168A (Two-hybrid), UBQLN1 (Two-hybrid), UBE2V1 (Reconstituted Complex), UBE2V1 (Reconstituted Complex), UBE2V1 (Reconstituted Complex), UBE2N (Reconstituted Complex), UBE2V1 (Reconstituted Complex), UBE2V1 (Affinity Capture-Western)

ESM2 similar proteins: A6H795, B3RTL9, B5DEI4, B5X1G6, B9EM04, C1BKD1, C1BZU2, C3ZDX5, O23239, P42743, Q02384, Q07889, Q07890, Q13404, Q15819, Q1JPX4, Q28FC1, Q28IA3, Q32L27, Q3SZ43, Q3SZ52, Q498F8, Q4R5E1, Q4VBH4, Q5E953, Q5F3Z3, Q5R4Z6, Q5R6C9, Q5RE48, Q5XGV8, Q5ZJJ5, Q6BBI8, Q6DEN0, Q6DJ78, Q6PEH5, Q7M767, Q7ZYX1, Q8VDW4, Q90879, Q96B02

Diamond homologs: A5PJC4, A5PKP9, C4R826, D3ZDK2, O45495, O60015, O74196, O74983, P0CS16, P0CS17, P15731, P15732, P23566, P25153, P25866, P25867, P25868, P35129, P35134, P42747, P43102, P46595, P49428, P51668, P51965, P52482, P52483, P52485, P52486, P52493, P53152, P61077, P61078, P61079, P61080, P61085, P61086, P61087, P62837, P62838

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
UBE2N	“up-regulates activity”	UBE2V1	binding
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2V1	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2V1	ubiquitination
UBE2V1	“up-regulates activity”	TRAF6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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
TICAM1, RIP1-mediated IKK complex recruitment	6	39.6×	8e-07
Regulation of necroptotic cell death	7	33.8×	3e-07
IKK complex recruitment mediated by RIP1	6	32.7×	2e-06
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	5	20.2×	3e-04
Regulation of TNFR1 signaling	8	19.7×	8e-07
PINK1-PRKN Mediated Mitophagy	5	19.6×	3e-04
Negative regulators of DDX58/IFIH1 signaling	5	17.9×	4e-04
NOD1/2 Signaling Pathway	5	17.4×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein K6-linked ubiquitination	6	49.6×	1e-07
suppression of viral release by host	5	41.3×	7e-06
positive regulation of ERAD pathway	5	37.0×	1e-05
protein K63-linked ubiquitination	16	35.7×	5e-18
protein autoubiquitination	15	29.3×	5e-16
host-mediated suppression of symbiont invasion	5	29.3×	4e-05
positive regulation of protein ubiquitination	13	23.1×	2e-12
protein monoubiquitination	8	22.9×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1088 predictions. Top by Δscore:

Variant	Effect	Δscore
20:50096659:G:C	donor_gain	1.0000
20:50096670:A:AC	donor_gain	1.0000
20:50096671:C:CC	donor_gain	1.0000
20:50096671:CT:C	donor_gain	1.0000
20:50082911:CCAC:C	acceptor_gain	0.9900
20:50082912:CACC:C	acceptor_gain	0.9900
20:50082912:CACCT:C	acceptor_loss	0.9900
20:50082913:ACCTA:A	acceptor_loss	0.9900
20:50082914:CCTAC:C	acceptor_loss	0.9900
20:50082915:C:CA	acceptor_loss	0.9900
20:50082915:CTACA:C	acceptor_loss	0.9900
20:50082916:T:C	acceptor_loss	0.9900
20:50082916:T:G	acceptor_loss	0.9900
20:50084128:CCA:C	donor_gain	0.9900
20:50084128:CCACT:C	donor_gain	0.9900
20:50084251:TTGT:T	acceptor_gain	0.9900
20:50084251:TTGTC:T	acceptor_loss	0.9900
20:50084252:TGTC:T	acceptor_loss	0.9900
20:50084252:TGTCT:T	acceptor_loss	0.9900
20:50084253:GT:G	acceptor_gain	0.9900
20:50084253:GTC:G	acceptor_loss	0.9900
20:50084253:GTCTG:G	acceptor_loss	0.9900
20:50084254:TC:T	acceptor_loss	0.9900
20:50084254:TCTGG:T	acceptor_loss	0.9900
20:50084255:C:CC	acceptor_gain	0.9900
20:50084255:CTGGA:C	acceptor_loss	0.9900
20:50084256:T:A	acceptor_loss	0.9900
20:50084256:T:C	acceptor_loss	0.9900
20:50085511:C:A	donor_gain	0.9900
20:50096650:ATAG:A	donor_gain	0.9900

AlphaMissense

955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:50082881:A:G	W111R	1.000
20:50082881:A:T	W111R	1.000
20:50084133:C:A	G98V	1.000
20:50084133:C:T	G98E	1.000
20:50084213:A:C	C71W	1.000
20:50084226:A:G	L67P	1.000
20:50084238:C:G	R63P	1.000
20:50096682:C:A	G54V	1.000
20:50096682:C:T	G54E	1.000
20:50096683:C:A	G54W	1.000
20:50096683:C:G	G54R	1.000
20:50096683:C:T	G54R	1.000
20:50096688:A:C	I52R	1.000
20:50096688:A:T	I52K	1.000
20:50096694:C:T	G50E	1.000
20:50096695:C:A	G50W	1.000
20:50096695:C:G	G50R	1.000
20:50096695:C:T	G50R	1.000
20:50096699:C:A	W48C	1.000
20:50096699:C:G	W48C	1.000
20:50096700:C:G	W48S	1.000
20:50096701:A:G	W48R	1.000
20:50096701:A:T	W48R	1.000
20:50096709:A:G	L45P	1.000
20:50096737:C:G	G36R	1.000
20:50096740:A:G	W35R	1.000
20:50096740:A:T	W35R	1.000
20:50096741:G:C	S34R	1.000
20:50096741:G:T	S34R	1.000
20:50096743:T:G	S34R	1.000

dbSNP variants (sampled 300 via entrez): RS1000139210 (20:50103234 T>A), RS1000172044 (20:50084886 G>C), RS1000174731 (20:50117944 G>A), RS1000191814 (20:50102829 G>T), RS1000470892 (20:50104678 T>A), RS1000474251 (20:50097606 C>T), RS1000676715 (20:50104699 A>T), RS1000678070 (20:50110545 G>T), RS1000730045 (20:50099695 G>T), RS1000769058 (20:50084616 C>T), RS1000816005 (20:50091192 G>A), RS1000837819 (20:50114328 C>T), RS1000929397 (20:50109842 A>G), RS1000964791 (20:50085252 C>A), RS1001063663 (20:50110162 G>A)

Disease associations

OMIM: gene MIM:602995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3883289 (PROTEIN-PROTEIN INTERACTION), CHEMBL5234 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 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

PubChem BioAssay actives

4 with measured affinity, of 26 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

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

Chemical	Actions (top 5)	PubMed papers
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	3
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	affects expression, affects cotreatment, decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenite	decreases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
bisphenol S	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, decreases reaction	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects splicing	1
Phthalic Acids	increases methylation	1
Potassium Dichromate	increases expression	1
Selenium	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	affects expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XU85	HAP1 UBE2V1 (-) 1	Cancer cell line	Male
CVCL_XU86	HAP1 UBE2V1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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