UBE2I

Summary

UBE2I (ubiquitin conjugating enzyme E2 I, HGNC:12485) is a protein-coding gene on chromosome 16p13.3, encoding SUMO-conjugating enzyme UBC9 (P63279). Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. It is a common-essential gene (DepMap: required in 99.7% 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. Four alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 7329 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_003345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12485
Approved symbol	UBE2I
Name	ubiquitin conjugating enzyme E2 I
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	UBC9
Ensembl gene	ENSG00000103275
Ensembl biotype	protein_coding
OMIM	601661
Entrez	7329

Gene structure

Transcript identifiers

Ensembl transcripts: 91 — 52 protein_coding, 19 nonsense_mediated_decay, 11 retained_intron, 9 protein_coding_CDS_not_defined

ENST00000325437, ENST00000355803, ENST00000397514, ENST00000397515, ENST00000402301, ENST00000403747, ENST00000406620, ENST00000473256, ENST00000562470, ENST00000562482, ENST00000566159, ENST00000566587, ENST00000566775, ENST00000567074, ENST00000567383, ENST00000568209, ENST00000568288, ENST00000568989, ENST00000677314, ENST00000677987, ENST00000678584, ENST00000679082, ENST00000679137, ENST00000711294, ENST00000711295, ENST00000711296, ENST00000711297, ENST00000711298, ENST00000711299, ENST00000711300, ENST00000711301, ENST00000711302, ENST00000711303, ENST00000711304, ENST00000711305, ENST00000711306, ENST00000711307, ENST00000711308, ENST00000711309, ENST00000711310, ENST00000711311, ENST00000711312, ENST00000711313, ENST00000711314, ENST00000711315, ENST00000711316, ENST00000711317, ENST00000711318, ENST00000711319, ENST00000711320, ENST00000711321, ENST00000711322, ENST00000711323, ENST00000711324, ENST00000711330, ENST00000711331, ENST00000711332, ENST00000711333, ENST00000711334, ENST00000711335, ENST00000711336, ENST00000711337, ENST00000711338, ENST00000711339, ENST00000711340, ENST00000711341, ENST00000711342, ENST00000711343, ENST00000711344, ENST00000711345, ENST00000711346, ENST00000711347, ENST00000711348, ENST00000711349, ENST00000711350, ENST00000711351, ENST00000711352, ENST00000711353, ENST00000713916, ENST00000713917, ENST00000713920, ENST00000713921, ENST00000713922, ENST00000852849, ENST00000852850, ENST00000852851, ENST00000852852, ENST00000939696, ENST00000939697, ENST00000939698, ENST00000948372

RefSeq mRNA: 4 — MANE Select: NM_003345 NM_003345, NM_194259, NM_194260, NM_194261

CCDS: CCDS10433

Canonical transcript exons

ENST00000397514 — 7 exons

Exon	Start	End
ENSE00000873575	1315654	1315726
ENSE00003584681	1320174	1320283
ENSE00003608455	1314293	1314376
ENSE00003788207	1320438	1320517
ENSE00004015238	1314020	1314096
ENSE00004015245	1324730	1327017
ENSE00004475477	1309636	1309773

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 146.1948 / max 431.1267, expressed in 1826 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152088	138.4256	1826
152087	4.4037	1589
152092	1.4675	904
152089	0.7362	379
152093	0.4886	265
207702	0.3106	136
152090	0.2010	65
152091	0.1615	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.63	gold quality
ganglionic eminence	UBERON:0004023	98.25	gold quality
embryo	UBERON:0000922	97.93	gold quality
left ovary	UBERON:0002119	97.45	gold quality
ventricular zone	UBERON:0003053	97.23	gold quality
monocyte	CL:0000576	97.18	gold quality
mononuclear cell	CL:0000842	97.15	gold quality
leukocyte	CL:0000738	97.14	gold quality
right ovary	UBERON:0002118	97.13	gold quality
thymus	UBERON:0002370	97.09	gold quality
cortical plate	UBERON:0005343	96.96	gold quality
ovary	UBERON:0000992	96.91	gold quality
stromal cell of endometrium	CL:0002255	96.58	gold quality
left uterine tube	UBERON:0001303	96.51	gold quality
left adrenal gland	UBERON:0001234	96.43	gold quality
lymph node	UBERON:0000029	96.39	gold quality
right coronary artery	UBERON:0001625	96.38	gold quality
right adrenal gland cortex	UBERON:0035827	96.34	gold quality
right adrenal gland	UBERON:0001233	96.31	gold quality
endometrium epithelium	UBERON:0004811	96.31	gold quality
left adrenal gland cortex	UBERON:0035825	96.31	gold quality
body of uterus	UBERON:0009853	96.29	gold quality
secondary oocyte	CL:0000655	96.24	gold quality
adrenal gland	UBERON:0002369	96.21	gold quality
skin of hip	UBERON:0001554	96.13	gold quality
tibial artery	UBERON:0007610	96.12	gold quality
popliteal artery	UBERON:0002250	96.11	gold quality
adrenal cortex	UBERON:0001235	96.07	gold quality
skin of abdomen	UBERON:0001416	96.06	gold quality
skin of leg	UBERON:0001511	96.06	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

Upstream regulators (CollecTRI, top): ESR1, FOXL2, NR2F1, NR3C2, WT1, ZBTB17

miRNA regulators (miRDB)

91 targeting UBE2I, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1283	99.69	72.42	3009

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Identification of a substrate recognition site on Ubc9. (PMID:11877416)
• structure of the protein surfaces involved in UBC9 interaction with Sumo-1 and Smt3 (PMID:12021447)
• binding of proteins SALL1, UBE2I and SUMO-1 (PMID:12200128)
• SUMO-1 overexpression enhances and Ubc9 knockdown reduces levels of intranuclear Smad4, growth inhibitory response, as well as transcriptional responses to TGF-beta. (PMID:12813045)
• interacts with Mason-Pfizer monkey virus Gag in cells. This strengthens the hypothesis that Gag proteins transiently associate with the nuclear compartment during viral replication, and suggest that hUbc9 plays a role in this process (PMID:14517060)
• ubiquitin-conjugating enzyme E2I functions as a novel COUP-TFI corepressor, the function of which is distinct from its SUMO-1 conjugating enzyme activity. (PMID:14765993)
• The interaction of Ubc9 with Daxx and subsequent alteration in the subcellular localization of Daxx may contribute to the increased sensitivity to anticancer drugs in the cells expressing Ubc9-DN. (PMID:15087395)
• It is revealed with an in vitro SUMO-1 and Ad4BP/SF-1 that DNA binding activity and interaction with Sox9 are unaffected. (PMID:15192080)
• SUMO conjugation is a novel regulator of Elk-1 function through the control of its nuclear-cytoplasmic shuttling. (PMID:15210726)
• Ubc9 has a role in inhibition of diadenosine triphosphate hydrolase activity of the putative tumor suppressor protein Fhit (PMID:15246872)
• Ubc9- small ubiquitin-like modifier (SUMO-1) thioester could be recruited to RanBP2 via SUMO-1 in the absence of strong binding between Ubc9 and RanBP2 (PMID:15608651)
• data support a physiological role of Ubc9 and PIAS1 as transcriptional coactivators in COUP-TFI-mediated CYP11B2 transcription (PMID:15611122)
• specific interactions of SUMO-3 with its modifying enzyme, UBC9. (PMID:15723523)
• these results suggest a role for Ubc9 in tumorigenesis at least partially through regulation of bcl-2 expression. (PMID:15735760)
• p14ARF acts through a common modification of diverse binding partners, including Ubc9 (PMID:15876874)
• OZF interacts with UBC9, the E2 enzyme involved in the covalent conjugation of the small ubiquitin-like modifier 1 (SUMO-1). (PMID:15881673)
• Nup358/RanBP2 acts as an E3 by binding both SUMO and Ubc9 to position the SUMO-E2-thioester in an optimal orientation to enhance conjugation (PMID:15931224)
• Findings suggest that the interaction of small ubiquitin-like modifier 1 with N-terminus of ataxin-3 first and the relevant sumoylation probably participate in the post-translation modifying of ataxin-3 and in the pathogenesis of SCA3/MJD. (PMID:15952105)
• Thus, we did not find evidence for uniquely interacting partner proteins using this approach, but did identify four new lamin A/C interactive partners (PMID:16248985)
• SUMO-1 controls the protein stability and the biological function of phosducin. (PMID:16421094)
• In targeting RanGAP1 to nuclear pore complexes, Ubc9 conjugates SUMO to RanGAP1, and is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. (PMID:16469311)
• Results suggest that Ubc9 might regulate bcl-2 expression through the ER signaling pathway, which ultimately contributes to the alterations of drug responsiveness and tumor growth. (PMID:16566921)
• It shows that Ubc9 interacts with SOX4 and represses its transcriptional activity independent of its SUMO-1-conjugating activity. (PMID:16631117)
• This is the first report demonstrating the interaction of hUbc9 with a structural protein of plus-strand RNA viruses, indicating a new drug target for SARS-CoV. (PMID:16998888)
• results indicate that Ubc9 influences herpesvirus 6 immediate-early 2 protein function and provide new information on the complex interactions that occur between herpesviruses and the sumoylation pathway (PMID:17005699)
• the nucleocapsid protein of severe acute respiratory syndrome coronavirus is sumoylated by interaction with Ubc9 (PMID:17037517)
• Ubc9 has a role as a transcriptional MR coactivator, beyond the known SUMO E2-conjugating enzyme (PMID:17105732)
• Expressed at high levels in melanoma-positive lymph nodes; plays a crucial role in preventing advanced-stage melanomas from undergoing chemotherapy-induced apoptosis. (PMID:17297476)
• We show here that TRPS1 is SUMOylated at multiple sites, both in vivo and in vitro, through interaction with UBC9. Overexpression of wild-type UBC9 enhances TRPS1-mediated transcriptional repression. (PMID:17391059)
• analysis of SUMO-Ubc9 interaction (PMID:17466333)
• Ubc9 is an important C/EBPalphap30 target through which C/EBPalphap30 enhances the sumoylation of C/EBPalphap42 to inhibit granulocytic differentiation. (PMID:17671234)
• RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel target for sumoylation (PMID:17698038)
• RSUME increases noncovalent binding of SUMO-1 to Ubc9 and enhances Ubc9 thioester formation and SUMO polymerization. (PMID:17956732)
• Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3) are targets for S-nitrosation (PMID:17987106)
• MEL-18 bound to HSF2 inhibits its sumoylation by binding to and inhibiting the activity of UBC9 enzymes in the vicinity of HSF2. (PMID:18211895)
• Data show that the nuclear accumulation of Smad1 and Smad4 are inhibited by Ubc9 silencing, and thus Ubc9 plays an important role in the up-regulation of the bone morphogenetic protein signaling pathway. (PMID:18321803)
• These data suggests that Ubc9 can function as a co-factor of PLAGL2, uncoupling from its enzymatic activity, to mediate PLAGL2 interactive SP-C promoter activity. (PMID:18655774)
• The crystal structure of sumoylated Ubc9 demonstrates how the newly created binding interface can provide a gain in affinity otherwise provided by E3 ligases. (PMID:18691969)
• BRCA1/1a/1b fine tunes the dynamic complex interplay between SUMO-dependent/independent activities of Ubc9 on E2-induced ERalpha activation/repression and degradation in breast cancer cells (PMID:19287951)
• Tb-SUMO interacts with human Ubc9 through residues located on the beta-sheet of Tb-SUMO, which is also similar to that of SUMO-1 and Smt3 suggesting the evolutionary conservation of SUMO and sumoylation in eukaryotes. (PMID:19343802)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2ia	ENSDARG00000052649
mus_musculus	Ube2i	ENSMUSG00000015120
rattus_norvegicus	Ube2i	ENSRNOG00000066579
drosophila_melanogaster	lwr	FBGN0010602
caenorhabditis_elegans		WBGENE00006706

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), UBE2K (ENSG00000078140), CDC34 (ENSG00000099804), 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), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

SUMO-conjugating enzyme UBC9 — P63279 (reviewed: P63279)

Alternative names: RING-type E3 SUMO transferase UBC9, SUMO-protein ligase, Ubiquitin carrier protein 9, Ubiquitin carrier protein I, Ubiquitin-conjugating enzyme E2 I, Ubiquitin-protein ligase I, p18

All UniProt accessions (15): P63279, A0AAA9YHD0, A0AAA9YHE7, A0AAA9YHF5, A0AAA9YHJ6, A0AAA9YHJ9, A0AAA9YHK4, A0AAA9YHQ4, A0AAA9YHQ8, A0AAA9YHV5, A0AAA9YHW0, A0AAA9YHW2, H3BPC4, H3BQQ9, H3BRD1

UniProt curated annotations — full annotation on UniProt →

Function. Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation. Sumoylates p53/TP53 at ‘Lys-386’. Mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity. Sumoylates SHMT1 at ‘Lys-38’ or ‘Lys-39’ leading to RAN-dependent nuclear import of SHMT1. Also sumoylates TYMS and DHFR.

Subunit / interactions. Forms a complex with SENP6 and UBE2I in response to UV irradiation. Forms a tight complex with RANGAP1 and RANBP2. Identified in a complex with SUMO2 and UBE2I, where one ZNF451 interacts with one UBE2I and two SUMO2 chains, one bound to the UBE2I active site and the other to another region of the same UBE2I molecule. Interacts with SETX. Interacts with HIPK1 and HIPK2. Interacts with PPM1J. Interacts with RASD2. Interacts with TCF3. Interacts with NR2C1; the interaction promotes its sumoylation. Interacts with SIAH1. Interacts with PARP. Interacts with various transcription factors such as TFAP2A, TFAP2B, and TFAP2C. Interacts with AR. Interacts with ETS1. Interacts with SOX4. Interacts with RWDD3; the interaction enhances the sumoylation of a number of proteins such as HIF1A and I-kappa-B. Interacts with FOXL2. Interacts with DNM1l (via its GTPase and B domains); the interaction promotes sumoylation of DNM1L, mainly in its B domain. Interacts with NFATC2IP; this inhibits formation of poly-SUMO chains. Interacts with FHIT. Interacts with PRKRA and p53/TP53. Interacts with UHRF2. Interacts with NR3C1 and this interaction is enhanced in the presence of RWDD3. Interacts with MTA1. Interacts with ZNF451. Interacts with CPEB3. Interacts with SUMO1, SUMO2 and SUMO3. Interacts with IPO13. Interacts with DNMT1. Interacts with SUMO1P1/SUMO5. Interacts with PML-RARA oncoprotein (via the coiled-colied domain); the interaction is required for sumoylation of the PML-RARA oncoprotein. Interacts with ZBED1/hDREF. (Microbial infection) Interacts with human herpesvirus 6 IE2. (Microbial infection) Interacts with human adenovirus early E1A protein; this interaction interferes with polysumoylation. (Microbial infection) Interacts with Epstein-barr virus protein LMP1. (Microbial infection) Interacts with ebolavirus VP35; this interaction mediates the sumoylation of IRF7 and contributes to the viral inhibition of IFN-type I production. (Microbial infection) Interacts with Hantaan hantavirus nucleoprotein. (Microbial infection) Interacts with human cytomegalovirus protein UL44.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in heart, skeletal muscle, pancreas, kidney, liver, lung, placenta and brain. Also expressed in testis and thymus.

Post-translational modifications. Phosphorylation at Ser-71 significantly enhances SUMOylation activity.

Pathway. Protein modification; protein sumoylation.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (4): NP_003336, NP_919235, NP_919236, NP_919237 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site
IPR050113	Ub_conjugating_enzyme-E2-like	Family

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)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. 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
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1

UniProt features (51 total): mutagenesis site 17, cross-link 6, strand 6, helix 5, site 4, modified residue 3, turn 3, sequence conflict 2, initiator methionine 1, chain 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5F6E	X-RAY DIFFRACTION	1.12
5F6Y	X-RAY DIFFRACTION	1.14
2GRR	X-RAY DIFFRACTION	1.3
5F6V	X-RAY DIFFRACTION	1.49
5F6U	X-RAY DIFFRACTION	1.55
5F6D	X-RAY DIFFRACTION	1.55
5F6X	X-RAY DIFFRACTION	1.56
5F6W	X-RAY DIFFRACTION	1.7
2GRO	X-RAY DIFFRACTION	1.7
2GRQ	X-RAY DIFFRACTION	1.7
9GLR	X-RAY DIFFRACTION	1.72
2GRN	X-RAY DIFFRACTION	1.8
6SYF	X-RAY DIFFRACTION	1.9
2GRP	X-RAY DIFFRACTION	2.05
5FQ2	X-RAY DIFFRACTION	2.2
3UIP	X-RAY DIFFRACTION	2.29
2PE6	X-RAY DIFFRACTION	2.4
5D2M	X-RAY DIFFRACTION	2.4
1KPS	X-RAY DIFFRACTION	2.5
4W5V	X-RAY DIFFRACTION	2.5
3UIN	X-RAY DIFFRACTION	2.6
2O25	X-RAY DIFFRACTION	2.6
3UIO	X-RAY DIFFRACTION	2.6
3A4S	X-RAY DIFFRACTION	2.7
4Y1L	X-RAY DIFFRACTION	2.7
9DRJ	ELECTRON MICROSCOPY	2.7
1A3S	X-RAY DIFFRACTION	2.8
2XWU	X-RAY DIFFRACTION	2.8
8ODR	X-RAY DIFFRACTION	2.85
9B62	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63279-F1	97.46	0.98

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 (5): 93 (glycyl thioester intermediate); 4 (interaction with ranbp2); 25 (interaction with ranbp2); 57 (interaction with ranbp2); 100–101 (substrate binding)

Post-translational modifications (9): 65, 71, 18, 18, 48, 49, 49, 101, 2

Mutagenesis-validated functional residues (17):

Position	Phenotype
13–14	impairs binding to sumo1 and catalytic activity.
17–18	impairs binding to sumo1 and catalytic activity.
22	impairs binding to ranbp2.
25	impairs binding to ranbp2.
27	impairs binding to ranbp2.
42	slightly impairs binding to ranbp2.
48	slightly impairs binding to ranbp2.
54	slightly impairs binding to ranbp2.
57	impairs binding to ranbp2.
59	impairs binding to ranbp2.
61	slightly impairs binding to ranbp2.
85	impairs catalytic activity.
87	impairs catalytic activity.
93	loss of enhancement of sumoylation by rwdd3. no effect on rwdd3 protein levels.
100–101	impairs catalytic activity.
127	impairs catalytic activity.
127	no effect on catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-196791	Vitamin D (calciferol) metabolism
R-HSA-3065678	SUMO is transferred from E1 to E2 (UBE2I, UBC9)
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-4655427	SUMOylation of DNA methylation proteins
R-HSA-4755510	SUMOylation of immune response proteins
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-8866904	Negative regulation of activity of TFAP2 (AP-2) family transcription factors
R-HSA-9615933	Postmitotic nuclear pore complex (NPC) reformation
R-HSA-9683610	Maturation of nucleoprotein
R-HSA-9694631	Maturation of nucleoprotein
R-HSA-9735871	SARS-CoV-1 targets host intracellular signalling and regulatory pathways
R-HSA-9793242	SUMOylation of nuclear envelope proteins
R-HSA-9833482	PKR-mediated signaling
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9918432	Maturation of DENV proteins
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9937850	NuRD complex assembly

MSigDB gene sets: 380 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, PID_HDAC_CLASSI_PATHWAY, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_MEMBRANE_BIOGENESIS, MORF_SNRP70, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), ubiquitin-dependent protein catabolic process (GO:0006511), chromosome segregation (GO:0007059), mitotic nuclear membrane reassembly (GO:0007084), protein sumoylation (GO:0016925), positive regulation of cell migration (GO:0030335), protein modification process (GO:0036211), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of DNA-templated transcription (GO:0045892), modulation of chemical synaptic transmission (GO:0050804), nuclear export (GO:0051168), cell division (GO:0051301), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (14): transcription coregulator binding (GO:0001221), RNA binding (GO:0003723), ATP binding (GO:0005524), transcription factor binding (GO:0008134), SUMO transferase activity (GO:0019789), enzyme binding (GO:0019899), HLH domain binding (GO:0043398), small protein activating enzyme binding (GO:0044388), SUMO conjugating enzyme activity (GO:0061656), RING-like zinc finger domain binding (GO:0071535), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (17): synaptonemal complex (GO:0000795), nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), PML body (GO:0016605), perinuclear region of cytoplasm (GO:0048471), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), presynaptic cytosol (GO:0099523), postsynaptic cytosol (GO:0099524), SUMO ligase complex (GO:0106068), transferase complex (GO:1990234), chromosome (GO:0005694), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	11
Meiosis	1
Metabolism of steroids	1
Processing and activation of SUMO	1
DNA Double Strand Break Response	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
Nuclear Envelope (NE) Reassembly	1
Translation of Structural Proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	2
protein domain specific binding	2
cytoplasm	2
synapse	2
cytosol	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
cell cycle process	1
mitotic cell cycle	1
nuclear membrane reassembly	1
mitotic nuclear membrane organization	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
protein metabolic process	1
macromolecule modification	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
nucleocytoplasmic transport	1
intercellular transport	1
cellular process	1
protein modification by small protein conjugation or removal	1
transcription factor binding	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like protein transferase activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

520 interactions, top by confidence:

A	B	Type	Score
UBE2I	SUMO1	psi-mi:“MI:0914”(association)	0.950
PIAS2	UBE2I	psi-mi:“MI:0915”(physical association)	0.850
UBE2I	PIAS2	psi-mi:“MI:0915”(physical association)	0.850
UBE2I	RNF111	psi-mi:“MI:0915”(physical association)	0.740
RNF111	UBE2I	psi-mi:“MI:0915”(physical association)	0.740
GOLGA2	UBE2I	psi-mi:“MI:0915”(physical association)	0.660
UBE2I	GOLGA2	psi-mi:“MI:0915”(physical association)	0.660
UBE2I	RWDD3	psi-mi:“MI:0407”(direct interaction)	0.610
BHLHE40	UBE2I	psi-mi:“MI:0915”(physical association)	0.580
UBE2I	BHLHE40	psi-mi:“MI:0915”(physical association)	0.580
UBE2I	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	ZCCHC7	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
UBE2I		psi-mi:“MI:0915”(physical association)	0.560
ADE4	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	POL30	psi-mi:“MI:0915”(physical association)	0.560
THR1	UBE2I	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1271): UBE2I (Two-hybrid), ZHX1 (Affinity Capture-Western), UBE2I (Affinity Capture-Western), TP53 (Biochemical Activity), PTEN (Affinity Capture-Western), USP25 (Reconstituted Complex), RANGAP1 (Biochemical Activity), SP100 (Biochemical Activity), PARP1 (Biochemical Activity), UBE2I (Reconstituted Complex), CREBBP (Affinity Capture-Western), DAXX (Affinity Capture-Western), ELK1 (Affinity Capture-Western), UBE2I (Reconstituted Complex), UBE2I (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GUS4, A5PJC4, A5PKP9, D3ZDK2, O14933, O74196, P23566, P25867, P34477, P35129, P40984, P42747, P51668, P52487, P60604, P60605, P61080, P62837, P62838, P62839, P62840, P63279, P63280, P63281, P63282, P63283, P68036, P68037, Q1RMW1, Q1RMX2, Q28CQ4, Q2EF73, Q2TA10, Q3MHP1, Q42540, Q42541, Q42551, Q4V8J2, Q553F3, Q5R5I4

Diamond homologs: A5PKP9, D3ZDK2, O00102, O74201, P06104, P0C8G3, P0C8G4, P0C8G5, P0CS16, P0CS17, P14682, P23566, P25153, P25865, P25866, P25867, P25868, P25869, P27949, P34477, P35129, P35130, P35131, P35132, P35133, P35134, P35135, P42745, P42746, P42747, P49427, P49459, P51668, P52478, P52492, P52493, P60604, P60605, P61077, P61078

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
UBE2I	down-regulates	PLAG1	sumoylation
UBE2I	down-regulates	ETV5	sumoylation
UBE2I	up-regulates	FOXL2	sumoylation
PCGF2	“down-regulates activity”	UBE2I	binding
UBE2I	“down-regulates activity”	SOX6	sumoylation
UBE2I	“up-regulates activity”	N	sumoylation
UBE2I	“down-regulates activity”	JUN	sumoylation
UBE2I	“down-regulates activity”	FOS	sumoylation
UBE2I	“up-regulates quantity by stabilization”	ZHX1	sumoylation
UBE2I	“down-regulates activity”	IRF7	sumoylation
LMP1	“up-regulates activity”	UBE2I	binding
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2I	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2I	ubiquitination
UBE2I	“down-regulates quantity by destabilization”	BHLHE40	polyubiquitination
CDK1	“up-regulates activity”	UBE2I	phosphorylation
UBE2I	down-regulates	MITF	ubiquitination
UBE2I	up-regulates	SMAD4	sumoylation
UBE2I	“down-regulates activity”	CEBPA	sumoylation
UBE2I	“up-regulates activity”	MBD4	sumoylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Transport of Ribonucleoproteins into the Host Nucleus	6	71.4×	4e-09
SUMOylation of ubiquitinylation proteins	7	68.3×	3e-10
Postmitotic nuclear pore complex (NPC) reformation	5	68.0×	1e-07
Nuclear import of Rev protein	6	67.2×	5e-09
SUMOylation of DNA replication proteins	8	66.2×	4e-11
SUMOylation of SUMOylation proteins	6	65.3×	5e-09
Rev-mediated nuclear export of HIV RNA	6	63.4×	6e-09
IPs transport between nucleus and cytosol	5	63.4×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	7	63.0×	4e-09
protein import into nucleus	5	20.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1705 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1314070:A:T	donor_gain	1.0000
16:1314082:A:T	donor_gain	1.0000
16:1314174:G:GT	donor_gain	1.0000
16:1314287:TCTCA:T	acceptor_loss	1.0000
16:1314288:CTCAG:C	acceptor_loss	1.0000
16:1314289:TCA:T	acceptor_loss	1.0000
16:1314290:CAG:C	acceptor_loss	1.0000
16:1314291:A:AG	acceptor_gain	1.0000
16:1314291:AG:A	acceptor_gain	1.0000
16:1314291:AGGGT:A	acceptor_loss	1.0000
16:1314292:G:A	acceptor_gain	1.0000
16:1314292:G:GA	acceptor_gain	1.0000
16:1314292:GGGT:G	acceptor_gain	1.0000
16:1314366:G:GT	donor_gain	1.0000
16:1314367:A:T	donor_gain	1.0000
16:1314374:GGG:G	donor_gain	1.0000
16:1314375:GG:G	donor_gain	1.0000
16:1314375:GGG:G	donor_gain	1.0000
16:1314376:GG:G	donor_gain	1.0000
16:1315648:CCACA:C	acceptor_loss	1.0000
16:1315649:CACAG:C	acceptor_loss	1.0000
16:1315650:ACAGA:A	acceptor_loss	1.0000
16:1315651:CA:C	acceptor_loss	1.0000
16:1315652:A:AG	acceptor_gain	1.0000
16:1315652:AG:A	acceptor_loss	1.0000
16:1315653:G:GA	acceptor_gain	1.0000
16:1315653:GA:G	acceptor_gain	1.0000
16:1315723:AAATG:A	donor_loss	1.0000
16:1315725:AT:A	donor_gain	1.0000
16:1315725:ATGT:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000089291 (16:1321158 G>A,C,T), RS1000094979 (16:1315978 A>G), RS1000282388 (16:1319222 G>A), RS1000290145 (16:1310381 G>A), RS1000393207 (16:1323219 G>A), RS1000485647 (16:1323776 C>G), RS1000517919 (16:1323608 G>A), RS1000521848 (16:1326488 G>A,T), RS1000569174 (16:1319302 C>A,G,T), RS1000745923 (16:1326859 C>T), RS1000922391 (16:1313182 G>A), RS1000977487 (16:1326700 T>G), RS1001022180 (16:1320417 G>A,C), RS1001068651 (16:1316614 A>G,T), RS1001183392 (16:1325078 C>G,T)

Disease associations

OMIM: gene MIM:601661 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005588_7	Idiopathic dilated cardiomyopathy	3.000000e-06
GCST006629_3	Pulse pressure	5.000000e-15
GCST007267_86	Systolic blood pressure	5.000000e-10
GCST007269_153	Pulse pressure	1.000000e-14
GCST010002_107	Refractive error	6.000000e-18
GCST90000025_249	Appendicular lean mass	6.000000e-10
GCST90002394_529	Monocyte percentage of white cells	4.000000e-11
GCST90002407_600	White blood cell count	1.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004980	appendicular lean mass
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1741191 (SINGLE PROTEIN), CHEMBL3137290 (PROTEIN COMPLEX)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9597	Efficacy	3	cisplatin;irinotecan	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9597	BAIAP3, RPS20P2, UBE2I	3	3.00	1	cisplatin;irinotecan

Binding affinities (BindingDB)

252 measured of 269 human assays (323 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(6-indolo[3,2-b]quinoxalinyl)acetic acid ethyl ester	EC50	0.00538 nM
cid_1912988	IC50	498 nM
MLS000527128	IC50	540 nM
MLS000591719	EC50	950 nM
(E)-2-cyano-3-[5-(4-nitrophenyl)-2-furanyl]-N-(4-thiophen-2-yl-2-thiazolyl)-2-propenamide	IC50	1180 nM
2-[2,6-bis(chloranyl)-4-[(Z)-[3-[2-[(4-methylphenyl)amino]-2-oxidanylidene-ethyl]-2,4-bis(oxidanylidene)-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	1200 nM
2-{3-[(2-Hydroxy-benzoyl)-hydrazono]-2-oxo-2,3-dihydro-indol-1-yl}-N-o-tolyl-acetamide	IC50	1230 nM
3-[4-[(Z)-(4-keto-2-thioxo-thiazolidin-5-ylidene)methyl]-1-phenyl-pyrazol-3-yl]-N,N-dimethyl-benzenesulfonamide	IC50	1440 nM
(5Z)-3-[[(E)-(6-keto-3-nitro-cyclohexa-2,4-dien-1-ylidene)methyl]amino]-5-[(5-methyl-2-furyl)methylene]-2-thioxo-thiazolidin-4-one	IC50	1530 nM
(5Z)-2-azanylidene-3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one	IC50	1550 nM
4-[5-(5-Cyano-2-hydroxy-4-methyl-6-oxo-6H-pyridin-3-ylidenemethyl)-furan-2-yl]-b	IC50	1590 nM
MLS000588669	IC50	1610 nM
MLS000686315	IC50	1610 nM
3-hydroxy-N-[[5-[4-(2-pyrimidinylsulfamoyl)phenyl]-2-furanyl]methylideneamino]-2-naphthalenecarboxamide	IC50	1630 nM
3-amino-6-(2-furanyl)-N-(2-methoxyphenyl)-2-thieno[2,3-b]pyridinecarboxamide	IC50	1790 nM
3,6,7-trimethoxyphenanthrene-2,5-diol	IC50	1950 nM
4-[(5E)-4-keto-5-p-anisylidene-2-thioxo-thiazolidin-3-yl]-N-thiazol-2-yl-benzenesulfonamide	IC50	1980 nM
cid_5754238	IC50	2000 nM
cid_367783	IC50	2080 nM
MLS001213411	IC50	2170 nM
(E)-4-(1,3-benzothiazol-2-yl)-5-[4-(N-methylanilino)-3-nitro-phenyl]pent-4-enoic acid	IC50	2270 nM
6-(4-fluorobenzyl)-2-(2-furfurylidene)thiazolo[3,2-b][1,2,4]triazine-3,7-quinone	IC50	2350 nM
2-(2-carbomethoxy-4-hydroxy-6-methoxy-phenoxy)-6-hydroxy-4-methyl-benzoic acid	IC50	2420 nM
(3S,4S)-5-[(3S,4S)-4,10-dihydroxy-7,9-dimethoxy-3-methyl-3,4-dihydro-1H-benz[g]isochromen-5-yl]-7,9-dimethoxy-3-methyl-3,4-dihydro-1H-benz[g]isochromene-4,10-diol	IC50	2510 nM
2-{3-[(3-Hydroxy-naphthalene-2-carbonyl)-hydrazono]-2-oxo-2,3-dihydro-indol-1-yl}-N-p-tolyl-acetamide	IC50	2570 nM
3-Amino-6-furan-2-yl-thieno[2,3-b]pyridine-2-carboxylic acid (4-bromo-phenyl)-amide	IC50	2580 nM
4-({[4-(2-fluorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]sulfonyl}amino)benzoic acid	IC50	2580 nM
3-[[(E)-3-[4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl]-2-cyanoprop-2-enoyl]amino]benzoic acid	IC50	2600 nM
MLS000544577	IC50	2630 nM
cid_2851352	IC50	2630 nM
2-hydroxy-N-[(Z)-[1-[2-(2-methoxyanilino)-2-oxoethyl]-2-oxo-3-indolylidene]amino]benzamide	IC50	2740 nM
2-(4-bromoanilino)-6-nitro-1,3-benzothiazin-4-one	IC50	2740 nM
2-amino-3-hydroxy-N’-(2,3,4-trihydroxybenzyl)propionohydrazide;hydrochloride	IC50	3050 nM
4-ethyl-N-(4-keto-1-naphthylidene)benzenesulfonamide	IC50	3110 nM
MLS000716282	IC50	3680 nM
3-[[4-chloranyl-2-oxidanylidene-5-[[(3-oxidanylnaphthalen-2-yl)carbonylhydrazinylidene]methyl]-1,3-thiazol-3-yl]methyl]benzoic acid	IC50	3740 nM
2-[[5-[(4-chlorobenzyl)thio]-1,3,4-thiadiazol-2-yl]thio]-N’-[(Z)-indol-3-ylidenemethyl]acetohydrazide	IC50	3820 nM
SMR000123743	IC50	3840 nM
2-[4-[[6-ethoxycarbonyl-7-methyl-3-oxo-5-(4-propan-2-yloxyphenyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-2-ylidene]methyl]phenoxy]acetic acid	IC50	3850 nM
4-[8-[(3-methoxyphenyl)sulfamoyl]-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl]benzoic acid	EC50	3880 nM
MLS000591126	IC50	3910 nM
5-[[5-(2,5-dichlorophenyl)-1H-pyrrol-2-yl]methylidene]-1,3-diazinane-2,4,6-trione	EC50	4040 nM
(6E)-5-azanylidene-6-[[2,5-dimethyl-1-(phenylmethyl)pyrrol-3-yl]methylidene]-2-(furan-2-yl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one	IC50	4060 nM
2-(1,3-benzoxazol-2-ylamino)-6-methyl-4-(4-methylphenyl)-N-phenyl-1,4-dihydropyrimidine-5-carboxamide	IC50	4070 nM
MLS000537135	IC50	4140 nM
2-azanylidene-3-(4-bromophenyl)sulfonyl-1-(furan-2-ylmethyl)dipyrido[1,2-d:3’,4’-f]pyrimidin-5-one	IC50	4160 nM
5-[[1-(4-hydroxyphenyl)-2-pyrrolyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	4450 nM
3-(4-chlorophenyl)sulfonyl-1-(2-furanylmethyl)-2-imino-5-dipyrido[1,2-d:3’,4’-f]pyrimidinone	IC50	4470 nM
cid_1334850	IC50	4640 nM
MLS000054169	IC50	4690 nM

ChEMBL bioactivities

45 potent at pChembl≥5 of 96 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.54	Kd	290.7	nM	CHEMBL5653589
6.54	ED50	290.7	nM	CHEMBL5653589
5.71	IC50	1930	nM	CHEMBL1518374
5.70	IC50	2010	nM	CHEMBL1535613
5.69	IC50	2060	nM	CHEMBL1713480
5.66	IC50	2180	nM	CHEMBL1719957
5.65	IC50	2230	nM	CHEMBL1736753
5.62	IC50	2410	nM	CHEMBL1721038
5.60	IC50	2510	nM	CHEMBL1703530
5.60	IC50	2490	nM	CHEMBL1736986
5.58	IC50	2610	nM	CHEMBL1727351
5.58	IC50	2660	nM	CHEMBL1399979
5.58	IC50	2630	nM	CHEMBL1507308
5.57	IC50	2710	nM	CHEMBL1530437
5.55	IC50	2840	nM	CHEMBL1731605
5.47	IC50	3370	nM	CHEMBL1703238
5.42	IC50	3760	nM	CHEMBL1711163
5.42	IC50	3830	nM	CHEMBL1722076
5.40	IC50	4000	nM	CHEMBL1706750
5.39	IC50	4070	nM	CHEMBL1518888
5.38	IC50	4120	nM	CHEMBL1518098
5.38	IC50	4200	nM	CHEMBL1405964
5.37	IC50	4290	nM	CHEMBL1612112
5.36	IC50	4330	nM	CHEMBL1704267
5.35	IC50	4460	nM	CHEMBL1731605
5.33	IC50	4640	nM	CHEMBL1720079
5.33	IC50	4630	nM	CHEMBL1722739
5.30	IC50	4980	nM	CHEMBL1446655
5.29	IC50	5120	nM	CHEMBL1714309
5.28	IC50	5240	nM	CHEMBL1328773
5.24	IC50	5800	nM	CHEMBL1361703
5.22	IC50	6000	nM	CHEMBL3410378
5.22	IC50	6040	nM	CHEMBL1732031
5.22	IC50	6000	nM	CHEMBL1727199
5.21	IC50	6110	nM	CHEMBL1562713
5.20	IC50	6320	nM	CHEMBL1402456
5.19	IC50	6500	nM	CHEMBL1728000
5.18	IC50	6590	nM	CHEMBL1308068
5.14	IC50	7160	nM	CHEMBL1706577
5.12	IC50	7680	nM	CHEMBL1706851
5.10	IC50	8000	nM	CHEMBL3410377
5.09	IC50	8060	nM	CHEMBL1704267
5.05	IC50	9000	nM	CHEMBL3410379
5.04	IC50	9070	nM	CHEMBL1706577
5.03	IC50	9450	nM	CHEMBL1727666

PubChem BioAssay actives

4 with measured affinity, of 30 total; 4 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149708: Binding affinity to human UBE2I incubated for 45 mins by Kinobead based pull down assay	kd	0.2907	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-1-[(2S)-2-acetamidopropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]-6-aminohexanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-4-amino-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-5-oxopentanoic acid	1199041: Inhibition of Ubc9 (unknown origin) assessed as reduction in fluorescent peptide FL-AR sumoylation using ATP, SUMO E1 and His-tagged SUMO-1 after 90 mins by competitive sumoylation microfluidic electrophoretic mobility shift biochemical assay	ic50	6.0000	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]-6-aminohexanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-5-oxopentanoic acid	1199041: Inhibition of Ubc9 (unknown origin) assessed as reduction in fluorescent peptide FL-AR sumoylation using ATP, SUMO E1 and His-tagged SUMO-1 after 90 mins by competitive sumoylation microfluidic electrophoretic mobility shift biochemical assay	ic50	8.0000	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]-6-aminohexanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-5-oxopentanoic acid	1199041: Inhibition of Ubc9 (unknown origin) assessed as reduction in fluorescent peptide FL-AR sumoylation using ATP, SUMO E1 and His-tagged SUMO-1 after 90 mins by competitive sumoylation microfluidic electrophoretic mobility shift biochemical assay	ic50	9.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
trichostatin A	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Arsenic Trioxide	affects binding, increases reaction, increases sumoylation, affects reaction, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Valproic Acid	increases expression, increases methylation	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases abundance, increases expression	1
ochratoxin A	increases expression, affects cotreatment	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ON 01910	affects binding, increases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Bilirubin	decreases expression	1
Cholesterol	decreases reaction, increases abundance	1
Citrinin	affects cotreatment, increases expression	1
Cocaine	increases expression	1
Copper	affects binding, decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 7 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3414298	Binding	Inhibition of Ubc9 (unknown origin) assessed as reduction in fluorescent peptide FL-AR sumoylation using ATP, SUMO E1 and His-tagged SUMO-1 after 90 mins by competitive sumoylation microfluidic electrophoretic mobility shift biochemical ass	Synthetic derivatives of the SUMO consensus sequence provide a basis for improved substrate recognition. — Bioorg Med Chem Lett
CHEMBL1737862	Functional	PUBCHEM_BIOASSAY: SAR analysis of SUMOylation using HTRF in an in-Vitro dose response assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2006, AID2011, AID2018, AID2069, AID2658]	PubChem BioAssay data set

Clinical trials (associated diseases)

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