SUMO2

Summary

SUMO2 (small ubiquitin like modifier 2, HGNC:11125) is a protein-coding gene on chromosome 17q25, encoding Small ubiquitin-related modifier 2 (P61956). Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. It is a selective cancer dependency (DepMap: 80.8% of cell lines).

This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last two amino acids of the carboxy-terminus have been cleaved off. Numerous pseudogenes have been reported for this gene. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 6613 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 9 total
• GTEx eGene: eQTL in 27 tissues, sQTL in 3 (q < 0.05)
• Cancer dependency (DepMap): dependent in 80.8% of screened cell lines
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.39 (moderately constrained)
• MANE Select transcript: NM_006937

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11125
Approved symbol	SUMO2
Name	small ubiquitin like modifier 2
Location	17q25
Locus type	gene with protein product
Status	Approved
Aliases	SMT3B
Ensembl gene	ENSG00000188612
Ensembl biotype	protein_coding
OMIM	603042
Entrez	6613

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000420826

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

ENST00000420826, ENST00000314523, ENST00000578238, ENST00000897760, ENST00000919116, ENST00000919117, ENST00000919118, ENST00000970835, ENST00001069754, ENST00001102280, ENST00001102281, ENST00001102282, ENST00001102283, ENST00001102284, ENST00001102285, ENST00001102286, ENST00001134817

RefSeq mRNA: 2 — MANE Select: NM_006937 NM_001005849, NM_006937

CCDS: CCDS45773, CCDS45774

Canonical transcript exons

ENST00000420826 — 4 exons

Exon	Start	End
ENSE00001214228	75182814	75182959
ENSE00002509829	75174752	75174823
ENSE00002731638	75165586	75168401
ENSE00003679474	75181057	75181188

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 194.7912 / max 2788.0290, expressed in 1825 samples.

Highest expression (Bgee): ganglionic eminence, cortical plate, ventricular zone, mucosa of paranasal sinus, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SUMO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	3.2e-08	-0.14	17:75132206:G:C
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-07	-0.14	17:75161260:C:T
Esophagus Mucosa	eqtl	1.0e-07	-0.16	17:75126986:C:T
Artery Aorta	eqtl	9.4e-07	-0.16	17:75119141:T:TGTACACTG
Lung	eqtl	1.0e-06	+0.17	17:75180740:T:G
Whole Blood	eqtl	2.6e-06	+0.13	17:75159973:G:T
Adipose Subcutaneous	eqtl	3.7e-06	+0.14	17:75159973:G:T
Cells EBV-transformed lymphocytes	eqtl	3.8e-06	+0.18	17:75131588:T:C
Thyroid	eqtl	3.9e-06	-0.13	17:75161260:C:T
Skin Sun Exposed Lower leg	eqtl	2.6e-05	-0.12	17:75132206:G:C
Colon Sigmoid	eqtl	1.9e-04	-0.15	17:75119141:T:TGTACACTG
Brain Cerebellar Hemisphere	eqtl	2.5e-04	-0.23	17:74267491:C:T
Cells Cultured fibroblasts	sqtl	5.2e-04	+0.29	17:75157964:G:A
Heart Atrial Appendage	eqtl	5.6e-04	-0.15	17:75124833:G:A
Breast Mammary Tissue	eqtl	5.6e-04	-0.12	17:75143272:A:T
Nerve Tibial	eqtl	1.8e-03	+0.10	17:75020526:C:T
Adipose Visceral Omentum	eqtl	2.9e-03	-0.12	17:75124833:G:A
Skin Sun Exposed Lower leg	sqtl	4.7e-03	-0.56	17:75580778:A:AGAG
Cells Cultured fibroblasts	eqtl	4.9e-03	-0.06	17:75124833:G:A
Brain Cortex	eqtl	6.9e-03	-0.14	17:74202700:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
168047	188.1453	1824
168046	6.5331	1749
168045	0.0873	8
168044	0.0256	6

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.68	gold quality
cortical plate	UBERON:0005343	99.65	gold quality
ventricular zone	UBERON:0003053	99.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.56	gold quality
endothelial cell	CL:0000115	99.50	gold quality
lower lobe of lung	UBERON:0008949	99.41	gold quality
superficial temporal artery	UBERON:0001614	99.40	gold quality
islet of Langerhans	UBERON:0000006	99.22	gold quality
cerebellar vermis	UBERON:0004720	99.21	gold quality
oocyte	CL:0000023	99.19	gold quality
monocyte	CL:0000576	99.19	gold quality
mononuclear cell	CL:0000842	99.19	gold quality
cerebellar cortex	UBERON:0002129	99.19	gold quality
leukocyte	CL:0000738	99.18	gold quality
pancreatic ductal cell	CL:0002079	99.18	gold quality
cerebellar hemisphere	UBERON:0002245	99.18	gold quality
blood vessel layer	UBERON:0004797	99.18	gold quality
mammary duct	UBERON:0001765	99.16	gold quality
endometrium	UBERON:0001295	99.14	gold quality
cerebellum	UBERON:0002037	99.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.12	gold quality
thymus	UBERON:0002370	99.11	gold quality
prefrontal cortex	UBERON:0000451	99.10	gold quality
cardia of stomach	UBERON:0001162	99.10	gold quality
cervix squamous epithelium	UBERON:0006922	99.10	gold quality
renal medulla	UBERON:0000362	99.09	gold quality
left ovary	UBERON:0002119	99.08	gold quality
endocervix	UBERON:0000458	99.06	gold quality
ovary	UBERON:0000992	99.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.04	gold quality
germinal epithelium of ovary	UBERON:0001304	99.03	gold quality
periodontal ligament	UBERON:0008266	99.03	gold quality
body of uterus	UBERON:0009853	99.03	gold quality
pylorus	UBERON:0001166	99.02	gold quality
right ovary	UBERON:0002118	99.00	gold quality
lymph node	UBERON:0000029	98.99	gold quality
embryo	UBERON:0000922	98.99	gold quality
nasal cavity mucosa	UBERON:0001826	98.98	gold quality
vagina	UBERON:0000996	98.97	gold quality
right lung	UBERON:0002167	98.97	gold quality
ectocervix	UBERON:0012249	98.97	gold quality
nucleus accumbens	UBERON:0001882	98.95	gold quality
epithelium of mammary gland	UBERON:0003244	98.95	gold quality
CA1 field of hippocampus	UBERON:0003881	98.95	gold quality
amygdala	UBERON:0001876	98.94	gold quality
tongue squamous epithelium	UBERON:0006919	98.94	gold quality
type B pancreatic cell	CL:0000169	98.92	gold quality
left uterine tube	UBERON:0001303	98.92	gold quality
descending thoracic aorta	UBERON:0002345	98.92	gold quality
uterus	UBERON:0000995	98.91	gold quality
epithelium of nasopharynx	UBERON:0001951	98.91	gold quality
olfactory bulb	UBERON:0002264	98.90	silver quality
right testis	UBERON:0004534	98.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.90	gold quality
stromal cell of endometrium	CL:0002255	98.89	gold quality
caecum	UBERON:0001153	98.89	gold quality
nasopharynx	UBERON:0001728	98.89	gold quality
left testis	UBERON:0004533	98.89	gold quality
amniotic fluid	UBERON:0000173	98.88	gold quality
penis	UBERON:0000989	98.88	gold quality
hair follicle	UBERON:0002073	98.88	gold quality
adult organism	UBERON:0007023	98.87	gold quality
colonic epithelium	UBERON:0000397	98.86	gold quality
nasal cavity epithelium	UBERON:0005384	98.86	gold quality
caudate nucleus	UBERON:0001873	98.85	gold quality
popliteal artery	UBERON:0002250	98.85	gold quality
cingulate cortex	UBERON:0003027	98.85	gold quality
tibial artery	UBERON:0007610	98.85	gold quality
anterior cingulate cortex	UBERON:0009835	98.85	gold quality
artery	UBERON:0001637	98.84	gold quality
smooth muscle tissue	UBERON:0001135	98.83	gold quality
vermiform appendix	UBERON:0001154	98.83	gold quality
aorta	UBERON:0000947	98.82	gold quality
putamen	UBERON:0001874	98.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.81	gold quality
granulocyte	CL:0000094	98.80	gold quality
female reproductive system	UBERON:0000474	98.80	gold quality
calcaneal tendon	UBERON:0003701	98.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.80	gold quality
superior surface of tongue	UBERON:0007371	98.80	gold quality
thoracic aorta	UBERON:0001515	98.79	gold quality
right coronary artery	UBERON:0001625	98.79	gold quality
left coronary artery	UBERON:0001626	98.79	gold quality
spinal cord	UBERON:0002240	98.79	gold quality
urethra	UBERON:0000057	98.78	gold quality
coronary artery	UBERON:0001621	98.78	gold quality
adrenal tissue	UBERON:0018303	98.78	gold quality
ascending aorta	UBERON:0001496	98.77	gold quality
skin of abdomen	UBERON:0001416	98.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.76	gold quality
gall bladder	UBERON:0002110	98.75	gold quality
fallopian tube	UBERON:0003889	98.75	gold quality
testis	UBERON:0000473	98.74	gold quality
esophagus mucosa	UBERON:0002469	98.74	gold quality
nipple	UBERON:0002030	98.73	gold quality
trachea	UBERON:0003126	98.73	gold quality
pharyngeal mucosa	UBERON:0000355	98.72	gold quality
esophagus	UBERON:0001043	98.72	gold quality
left adrenal gland	UBERON:0001234	98.72	gold quality
palpebral conjunctiva	UBERON:0001812	98.72	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	62.37
E-CURD-112	yes	45.61
E-CURD-46	yes	24.93
E-CURD-122	yes	17.54
E-MTAB-10042	yes	13.34
E-CURD-88	yes	5.47
E-MTAB-9154	no	1787.03
E-MTAB-9388	no	1116.51
E-CURD-120	no	46.93
E-HCAD-10	no	35.35
E-HCAD-5	no	26.20
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	389.6
Caudate putamen	tissue	358.4
Ovary	tissue	269.4	high
Spinal cord	tissue	266.5
Hippocampal formation	tissue	257.9
Thymus	tissue	253.0
Putamen	tissue	248.8
Thalamus	tissue	246.6
Midbrain	tissue	244.8
Cerebral cortex	tissue	241.9	medium
Motor cortex	tissue	241.9
Superior colliculi	tissue	241.2
Pons	tissue	240.6
Septum	tissue	236.6
Occipital cortex	tissue	229.4
Entorhinal cortex	tissue	228.4
Substantia nigra	tissue	227.6
Prefrontal cortex	tissue	227.4
Somatosensory cortex	tissue	224.9
Corpus callosum	tissue	221.2
Olfactory bulb	tissue	220.0
Bone marrow	tissue	216.6	high
Cerebellum	tissue	215.8	low
Medulla oblongata	tissue	215.6
Skeletal muscle	tissue	215.1	medium
Temporal cortex	tissue	215.1
Basal ganglia	tissue	214.9	low
Tonsil	tissue	213.8	medium
Retrosplenial and cingulate cortex	tissue	212.0
Ventral forebrain	tissue	210.5
Hypothalamus	tissue	209.3
Amygdala	tissue	208.8
Retrosplenial cortex	tissue	208.1
Periaqueductal gray	tissue	202.2
Lymph node	tissue	200.5	medium
Vagina	tissue	194.3	high
Stomach 1	tissue	193.2	medium
Insular cortex	tissue	193.1
Adrenal gland	tissue	193.0	high
Endometrium 1	tissue	192.3	high
Appendix	tissue	191.9	medium
Retina	tissue	190.7
Adipose tissue	tissue	185.9	medium
Urinary bladder	tissue	175.7	high
Liver	tissue	173.1	low
Esophagus	tissue	173.0	high
Testis	tissue	170.1	high
Kidney	tissue	166.6	medium
Spleen	tissue	164.5	low
Colon	tissue	162.1	medium
Fallopian tube	tissue	161.7	high
Small intestine	tissue	159.2	medium
Pancreas	tissue	151.7	medium
Duodenum	tissue	151.6	medium
Epididymis	tissue	150.0	high
Salivary gland	tissue	149.4	high
Prostate	tissue	148.2	high
Nucleus accumbens	tissue	147.7
Skin 1	tissue	146.9	high
Postcentral gyrus	tissue	146.5

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal spinal cord (266.5), Dorsal hippocampus (257.9), Ventral spinal cord (249.2), Subiculum (230.7), White matter (221.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MTA1, MYC, SP1

miRNA regulators (miRDB)

Targeting SUMO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 70 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-5093	99.67	69.26	2291

Functional genomics

gnomAD constraint: pLI 0.983, LOEUF 0.394, missense Z 2.95 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000420826 — one region, missense o/e 0.14. DepMap (CRISPR cell-line fitness): dependent in 80.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): RL95-2 (-3.492), OPM-2 (-2.462), A-375 (-2.454), KP-N-YN (-2.107), KMS-11 (-2.093), PL4 (-2.021), RERF-GC-1B (-2.013), KNS-42 (-1.984), HT-29 (-1.968), EW-7 (-1.955), LP-1 (-1.894), HSC-39 (-1.797), MC-IXC (-1.751), MFM-223 (-1.749), HT-55 (-1.694).

Literature-anchored findings (GeneRIF, showing 40)

• HSF1 is modified by SUMO-1 and SUMO-2 in a stress-inducible manner. (PMID:12665592)
• CENPC target sites that can be sumoylated by SUMO-2 were shown to be equally susceptible to SUMO-1 attachments which include specific sites on SUMO-2 itself, Ubc9, and the recombinant CENP-C fragments (PMID:15272016)
• SUMO-1 shows patterns of utilization that are clearly discrete from the patterns of SUMO-2 and -3 throughout the cell cycle (PMID:15456902)
• Through a comprehensive structure-function analysis, we have identified a single critical sector along the second beta sheet and the following alpha helix of SUMO2 (PMID:15870296)
• c-Fos/c-Jun AP-1 dimer activity is downregulated by SUMO-1, SUMO-2, and SUMO-3 (PMID:16055710)
• Using yeast two-hybrid system, bioinformatics, and NMR spectroscopy we define a common SUMO-interacting motif (SIM) and map its binding surfaces on SUMO1 and SUMO2 (PMID:16524884)
• x-ray crystallographic structure of SENP1-SUMO-2 complex demonstrates structural basis for discrimination between SUMO paralogues during processing (PMID:16553580)
• SUMO-2-associated proteins identified in this study may contribute to SUMO-dependent regulation of transcription or other processes (PMID:16567619)
• Myeloid elf-1-like factor (MEF) or Elf4 is modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier). (PMID:16904644)
• p53 and pRB can be sumoylated by SUMO-2/3 in vivo, and such modification of p53 and pRB may play roles in premature senescence and stress response (PMID:17012228)
• sumoylation has a role in keratinocyte differentiation (PMID:17164289)
• Results support the notion that SUMO-2 are evolutionarily designed for function both structurally and thermodynamically in their low-populated, high-energy conformers rather than in their basic folded conformers. (PMID:18081309)
• SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-2/3 modification of different proteins regulating distinct processes. (PMID:18374647)
• SUMO-2/3 conjugation and the ubiquitin-proteasome system are tightly integrated and act in a cooperative manner. (PMID:18565875)
• SUMO-2/3, though expressed similarly to SUMO-1, may function separately and independently during pachytene in men. (PMID:18694876)
• BLM, the RecQ DNA helicase mutated in Bloom syndrome, is preferentially modified by SUMO-2/3 both in vitro and in vivo (PMID:18708356)
• Data describe a mitotic SUMO2/3 conjugation-deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway. (PMID:18946085)
• CTCF protein can be posttranslationally modified by the small ubiquitin-like protein SUMO. (PMID:19029252)
• RORalpha is SUMOylated by both SUMO-1 and SUMO-2. (PMID:19041634)
• Nm23-H1 was modified with SUMO-2 after X-ray irradiation. (PMID:19332021)
• Direct interactions between CoREST1 and SUMO-2 mediate SUMO-dependent changes in chromatin structure and transcription that are important for cell-type-specific gene expression. (PMID:19394292)
• HSP27-induced HSF1 modification by SUMO-2/3 takes place downstream of the transcription factor phosphorylation on S303 and S307 and does not affect its DNA-binding ability (PMID:19597476)
• Results show that nuclear actin is modified by SUMO2 and SUMO3 and that computational modeling and site-directed mutagenesis identified K68 and K284 as critical sites for SUMOylating actin. (PMID:19635839)
• A massive redistribution of SUMO-2 was observed that affected many biological pathways that are important for the heat shock response. (PMID:19638612)
• these findings suggest an expanded role of p150 as a SUMO2/3-interacting factor, and raise the intriguing possibility that p150 plays a role in promoting delivery of SUMO2/3 or SUMO2/3-modified proteins (or both) on chromatin fibers during replication. (PMID:19919826)
• SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress. (PMID:20181954)
• Report a mass spectrometry method to indentify SUMO-2 acceptor lysines in endogenous proteins and reveal an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif. (PMID:20797634)
• The authors demonstrate that LANA2 is covalently conjugated to SUMO1 and SUMO2 both in vitro and in latently KSHV-infected B-cells. (PMID:20881090)
• The expression of SUMO2 and SUMO3 is regulated differently by reactive oxygen species. (PMID:21291420)
• Loop 1 insertion in SENP6 and SENP7 as a platform to discriminate between SUMO1 and SUMO2/3 isoforms in this subclass of the SUMO protease family. (PMID:21878624)
• Conjugation of SUMO-2/3 to p53 correlates with a reduction of both activation and repression of a subset of p53-target genes. (PMID:21900752)
• TRIM28 acts as a SUMO E3 ligase by increasing SUMOylation of IRF7 both in vivo and in vitro, with little effect on the closely related IRF3. (PMID:21940674)
• SUMO-2/3 conjugates accumulating under the heat shock or MG132 treatment result largely from new protein synthesis. (PMID:22306003)
• SUMO2 binding by the Epstein-Barr virus protein kinase BGLF4 is crucial for BGLF4 function. (PMID:22398289)
• Co-immunoprecipitations and in vitro SUMOylation confirmed ARHGAP21 specific modification by SUMO2/3 and mapped the SUMOylation site to ARHGAP21 lysine K1443. (PMID:22922005)
• IRF8 is conjugated to SUMO2/3 in resting macrophages. (PMID:22942423)
• Data suggest that SUMO1 and SUMO2/3 are highly enriched in neck area of sperm; SUMOs are also associated with redundant nuclear envelope, flagella, and some sperm head regions. (PMID:23077236)
• findings show levels of SUMO1- and SUMO2/3-conjugated proteins are elevated in astrocytic tumors; findings highlight the pivotal role of SUMO conjugation in DNA damage repair processes (PMID:23078246)
• lysine 91, the major target of Nurr1 SUMOylation is contained in a canonical synergy control motif, indicating that SUMO-2 posttranslational modification of Nurr1 regulates its transcriptional synergy in complex promoters (PMID:23358114)
• Sumoylation of AMPKbeta2 subunit enhances AMP-activated protein kinase activity. (PMID:23552691)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Sumo	FBGN0264922

Paralogs (3): NFATC2IP (ENSG00000176953), SUMO4 (ENSG00000177688), SUMO3 (ENSG00000184900)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2158813) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased cell proliferation	1
decreased embryo size	1
embryonic growth arrest	1
delayed somite formation	1
embryonic growth retardation	1
absent amnion	1
increased apoptosis	1
abnormal extraembryonic mesoderm development	1
delayed chorioallantoic fusion	1
embryonic lethality during organogenesis, complete penetrance	1
delayed heart development	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Sus scrofa	A7WLH8	100.0%	Diamond
Bos taurus	P61955	100.0%	Diamond
Mus musculus	P61957	100.0%	Diamond
Rattus norvegicus	P61959	100.0%	Diamond
Macaca fascicularis	Q2PFW2	100.0%	Diamond
Xenopus laevis	Q5EAX4	100.0%	Diamond
Pongo abelii	Q5R6J4	100.0%	Diamond
Gallus gallus	Q5ZJM9	100.0%	Diamond
Xenopus tropicalis	Q6DEP7	100.0%	Diamond
Cricetulus griseus	Q6LDZ8	100.0%	Diamond
Ictidomys tridecemlineatus	Q2EF74	99.0%	Diamond
Cervus nippon	Q9MZD5	99.0%	Diamond
Danio rerio	Q6DHL4	98.9%	Diamond
Arabidopsis thaliana	P55852	93.5%	Diamond
Oryza sativa Japonica Group	P55857	89.6%	Diamond
Oncorhynchus mykiss	Q9PT08	88.0%	Diamond
Caenorhabditis elegans	P55853	66.7%	Diamond
Schizosaccharomyces pombe 972h-	O13351	61.3%	Diamond
Saccharomyces cerevisiae S288C	Q12306	61.3%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
NT5C	protein-coding	30833
JPT1	protein-coding	51155
ARMC7	protein-coding	79637
NUP85	protein-coding	79902
SLC16A5	protein-coding	9121
MIF4GD-DT	ncRNA	100287042
GGA3	protein-coding	23163
MRPS7	protein-coding	51081
MIF4GD	protein-coding	57409
SLC25A19	protein-coding	60386
ATP5PD	protein-coding	10476
KCTD2	protein-coding	23510

Protein

Protein identifiers

Small ubiquitin-related modifier 2 — P61956 (reviewed: P61956)

Alternative names: HSMT3, SMT3 homolog 2, SUMO-3, Sentrin-2, Ubiquitin-like protein SMT3B

All UniProt accessions (2): J3KRH1, P61956

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2, CBX4 or ZNF451. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. Plays a role in the regulation of sumoylation status of SETX.

Subunit / interactions. Interacts with SAE2 and UBE2I. Interacts with ZNF451. Identified in a complex with ZNF451 and UBE2I/UBC9, where one ZNF451 interacts with one UBE2I/UBC9 and two SUMO2 chains, one bound to the UBE2I/UBC9 active site and the other to another region of the same UBE2I/UBC9 molecule. Covalently attached to a number of proteins. Interacts with PELP1. Interacts with USP25; the interaction sumoylates USP25. Interacts with SIMC1, CASP8AP2, RNF111 and SOBP (via SIM domains). Interacts with MTA1. Interacts with HINT1. Interacts with GCNA (via SIM domains); this interaction allows the GCNA recruitment to DPCs sites. Interacts with TINCR (via SUMO-interacting motif); the interaction increases TINCR protein stability. (Microbial infection) Interacts with Epstein-barr virus BGLF4.

Subcellular location. Nucleus. PML body.

Tissue specificity. Broadly expressed.

Post-translational modifications. Polymeric chains can be formed through Lys-11 cross-linking. Polymeric SUMO2 chains undergo ‘Lys-6’-, ‘Lys-11’-, ‘Lys-48’- and ‘Lys-63’-linked polyubiquitination by RNF4. Cleavage of precursor form by SENP1 or SENP2 is necessary for function. Monoubiquitinated N-terminally by UBE2W, which primes it for RNF4-dependent polyubiquitination by the UBE2V1-UBE2N heterodimer.

Similarity. Belongs to the ubiquitin family. SUMO subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P61956-1	1	yes
P61956-2	2

RefSeq proteins (2): NP_001005849, NP_008868* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR022617	Rad60/SUMO-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily

Pfam: PF11976

UniProt features (33 total): cross-link 9, strand 9, mutagenesis site 4, turn 4, chain 1, propeptide 1, splice variant 1, sequence variant 1, domain 1, helix 1, modified residue 1

Structure

Experimental structures (PDB)

26 structures by resolution:

PDB	Title	Method	Resolution (Å)
1WM3	Crystal structure of human SUMO-2 protein	X-RAY DIFFRACTION	1.2
1WM2	Crystal structure of human SUMO-2 protein	X-RAY DIFFRACTION	1.6
4NPN	Crystal structure of human tetra-SUMO-2	X-RAY DIFFRACTION	1.63
7P99	Structure of human USPL1 in complex with SUMO2	X-RAY DIFFRACTION	1.8
2D07	Crystal Structure of SUMO-3-modified Thymine-DNA Glycosylase	X-RAY DIFFRACTION	2.1
4BKG	crystal structure of human diSUMO-2	X-RAY DIFFRACTION	2.11
3ZO5	Structure of SENP2-Loop1 in complex with preSUMO-2	X-RAY DIFFRACTION	2.15
2IO0	Crystal structure of human Senp2 in complex with preSUMO-2	X-RAY DIFFRACTION	2.3
5ELU	Isoform-specific inhibition of SUMO-dependent protein-protein interactions	X-RAY DIFFRACTION	2.35
5D2M	Complex between human SUMO2-RANGAP1, UBC9 and ZNF451	X-RAY DIFFRACTION	2.4
7ZJV	Structure of human USPL1 in covalent complex with DeltaN-SUMO2/3-PA probe	X-RAY DIFFRACTION	2.4
5EQL	Isoform-specific inhibition of SUMO-dependent protein-protein interactions	X-RAY DIFFRACTION	2.49
3UIN	Complex between human RanGAP1-SUMO2, UBC9 and the IR1 domain from RanBP2	X-RAY DIFFRACTION	2.6
3UIO	Complex between human RanGAP1-SUMO2, UBC9 and the IR1 domain from RanBP2 containing IR2 …	X-RAY DIFFRACTION	2.6
2CKH	SENP1-SUMO2 complex	X-RAY DIFFRACTION	3.2
2IO3	Crystal structure of human Senp2 in complex with RanGAP1-SUMO-2	X-RAY DIFFRACTION	3.2
2IYD	SENP1 covalent complex with SUMO-2	X-RAY DIFFRACTION	3.2
1WZ0	Solution Structure of Human SUMO-2 (SMT3B), a Ubiquitin-like Protein	SOLUTION NMR
2AWT	Solution Structure of Human Small Ubiquitin-Like Modifier Protein Isoform 2 (SUMO-2)	SOLUTION NMR
2N1W	Solution structure of human SUMO2	SOLUTION NMR
2N9E	Structure of SUMO-2 bound to phosphorylated RAP80 SIM	SOLUTION NMR
2RPQ	Solution Structure of a SUMO-interacting motif of MBD1-containing chromatin-associated …	SOLUTION NMR
5GHB	SOLUTION STRUCTURE OF LYS42 ACETYLATED HUMAN SUMO2	SOLUTION NMR
5GHC	SOLUTION STRUCTURE OF LYS33 ACETYLATED HUMAN SUMO2	SOLUTION NMR
6JXW	Complex of SUMO2 bound SLS4 from ICP0.	SOLUTION NMR
6JXX	SUMO2 bound to phosphorylated SLS4-SIM peptide from ICP0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61956-F1	84.19	0.62

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies; nucleoplasm; calyx; connecting piece; flagellar centriole

Antibody reliability (HPA): IH supported · IF supported

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 (10)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	11
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	21, 5, 7, 11
Glycyl lysine isopeptide (gly-lys) (interchain with k-? in acceptor proteins)	93
N6-acetyllysine	11
Peptide (met-gly) (interchain with g-cter in ubiquitin)	1
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	11
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	11

Mutagenesis-validated functional residues (4)

Position	Phenotype
11	abolishes the formation of poly(sumo) chains.
33	significantly impairs sumoylation of mta1.
35	significantly impairs sumoylation of mta1.
42	significantly impairs sumoylation of mta1.

Function

Pathways and Gene Ontology

Reactome pathways

11 curated (TAS) of 32; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

32 pathways:

ID	Pathway	Evidence
R-HSA-5696395	Formation of Incision Complex in GG-NER	curated
R-HSA-5693607	Processing of DNA double-strand break ends	curated
R-HSA-3065679	SUMO is proteolytically processed	curated
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins	curated
R-HSA-4615885	SUMOylation of DNA replication proteins	curated
R-HSA-4570464	SUMOylation of RNA binding proteins	curated
R-HSA-4085377	SUMOylation of SUMOylation proteins	curated
R-HSA-4551638	SUMOylation of chromatin organization proteins	curated
R-HSA-3899300	SUMOylation of transcription cofactors	curated
R-HSA-3232118	SUMOylation of transcription factors	curated
R-HSA-196791	Vitamin D (calciferol) metabolism	curated
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-8957322	Metabolism of steroids	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-3215018	Processing and activation of SUMO	—
R-HSA-9842860	Regulation of endogenous retroelements	—
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins	electronic
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-3065676	SUMO is conjugated to E1 (UBA2:SAE1)	electronic
R-HSA-3065678	SUMO is transferred from E1 to E2 (UBE2I, UBC9)	electronic
R-HSA-2990846	SUMOylation	—
R-HSA-4090294	SUMOylation of intracellular receptors	electronic

MSigDB gene sets: 290 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MYOGENIN_Q6, GCM_NPM1, MORF_SNRP70, MORF_UBE2I, MORF_HDAC1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_RAD21, MORF_CDK2, PID_REG_GR_PATHWAY, CAGCTG_AP4_Q5, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP

GO Biological Process (2): protein sumoylation (GO:0016925), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436)

GO Molecular Function (6): RNA binding (GO:0003723), SUMO transferase activity (GO:0019789), protein tag activity (GO:0031386), ubiquitin protein ligase binding (GO:0031625), ubiquitin-like protein ligase binding (GO:0044389), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), PML body (GO:0016605), hippocampal mossy fiber to CA3 synapse (GO:0098686), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), presynaptic cytosol (GO:0099523), postsynaptic cytosol (GO:0099524)

Reactome top-level categories

9 top-level categories:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	8
Processing and activation of SUMO	3
SUMOylation	2
Metabolism of steroids	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Regulation of endogenous retroelements	1
Gene expression (Transcription)	1
Post-translational protein modification	1

GO top-level categories

25 GO namespaces:

Category	Terms
synapse	2
cytosol	2
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
nucleic acid binding	1
ubiquitin-like protein transferase activity	1
molecular tag activity	1
ubiquitin-like protein ligase binding	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear body	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
presynapse	1
postsynapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	BP	direct assay
protein sumoylation	BP	direct assay
PML body	CC	direct assay
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

IntAct

Human interaction partners of SUMO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 58 partners by confidence:

Partner	Interaction type	MIscore	Records
RANGAP1	physical association	0.750	4
SENP1	direct interaction	0.740	6
USP25	physical association	0.720	6
SENP2	physical association	0.720	5
UBE2I	direct interaction	0.690	3
CHD3	physical association	0.670	3
PELP1	direct interaction	0.590	4
BRCA1	physical association	0.590	2
USPL1	physical association	0.570	2
SP100	physical association	0.560	4
HOMEZ	physical association	0.560	3
ZBTB33	physical association	0.560	3
ZBTB39	physical association	0.560	3
ZNF496	physical association	0.560	3
TDG	direct interaction	0.560	2
SETDB1	physical association	0.550	2
VIM	physical association	0.550	2
MYB	physical association	0.540	3
PIAS4	physical association	0.510	3
TANK	association	0.500	3
ESRRA	sumoylation reaction	0.440	1
ESRRG	sumoylation reaction	0.440	1
RAD51	direct interaction	0.440	1
KCNA5	physical association	0.400	1
MEF2A	physical association	0.400	1
NPM1	physical association	0.400	1
PARP1	physical association	0.400	1
V-MYB	physical association	0.400	1
ALAS1	physical association	0.370	1
BAD	physical association	0.370	1

BioGRID (873 interactions; top human partners by supporting records in a sample of 600 records): UBE2I (Reconstituted Complex; 15 records), RNF4 (Reconstituted Complex; 12 records), DAXX (Affinity Capture-Western; 6 records), SLX4 (Reconstituted Complex; 6 records), PIAS2 (Reconstituted Complex; 4 records), RNF8 (Two-hybrid; 4 records), SENP1 (Reconstituted Complex; 4 records), ZMYM2 (Reconstituted Complex; 4 records), DNM1L (Affinity Capture-MS; 3 records), MRE11A (Reconstituted Complex; 3 records), MSH2 (Reconstituted Complex; 3 records), PIAS1 (Reconstituted Complex; 3 records), PIAS4 (Reconstituted Complex; 3 records), USP25 (Two-hybrid; 3 records), ZBTB33 (Reconstituted Complex; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
RNF111	“down-regulates quantity by destabilization”	SUMO2	polyubiquitination
RNF4	“down-regulates quantity by destabilization”	SUMO2	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
SUMOylation of DNA damage response and repair proteins	8	23.9×	5e-07
SUMOylation	6	20.0×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	6	35.4×	1e-05

Disease & clinical

Genetic variants

Variant evidence for SUMO2: 9 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

9 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	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 204):

Position(s)	Effect	Δscore	Sites
17:75181055–75181056	donor_loss	1.0000	5
17:75181189	acceptor_loss	1.0000
17:75182812–75182813	donor_loss	1.0000	5
17:75168407	acceptor_gain	0.9900
17:75174750–75174751	donor_loss	0.9900	5
17:75174824–75174825	acceptor_loss	0.9900	5
17:75174836	acceptor_gain	0.9900
17:75181189–75181190	acceptor_loss	0.9900	3
17:75181192	acceptor_gain	0.9900
17:75174824	acceptor_loss	0.9800

AlphaMissense

448 missense substitutions predicted likely pathogenic (of 634 scored), across 84 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M44	9	0.962	0.996
M78	9	0.926	0.999
D82	8	0.996	0.999
F32	8	0.995	1.000
F60	8	0.993	1.000
D63	8	0.966	0.997
D85	8	0.965	0.994
D26	8	0.946	0.993
F87	8	0.942	0.999
D71	8	0.917	0.986
H17	8	0.895	0.988
D80	8	0.825	0.988
F62	7	0.996	0.999
I34	7	0.962	0.999
Q90	7	0.960	0.996
C48	7	0.953	0.999
Q25	7	0.848	0.962
Q51	7	0.840	0.995
E79	7	0.787	0.955
Q31	7	0.784	0.909

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.18e-06
Lung Adenocarcinoma (validation)	unfavorable	7.56e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000491
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.00065
Lung Adenocarcinoma (TCGA)	unfavorable	0.000863

Disease associations

OMIM: gene MIM:603042 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST012020_140	Serum metabolite levels	1e-25
GCST010118_115	Type 2 diabetes	8e-9
GCST011349_44	Gamma glutamyl transferase levels	3e-8
GCST006019_39	Gamma glutamyl transferase levels	5e-8
GCST010727_11	Deep white matter hyperintensities	4e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2146301 (SINGLE PROTEIN), CHEMBL3885639 (PROTEIN FAMILY), CHEMBL6066557 (PROTEIN COMPLEX), CHEMBL6066558 (PROTEIN FAMILY)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

4 measured of 11 human assays (11 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5653589	KD	1440 nM
NSC70551	IC50	3900 nM	US-11041859: Methods of identifying SENP1 inhibitors
SPI-05	IC50	13300 nM	US-11041859: Methods of identifying SENP1 inhibitors
SPI-08	IC50	22200 nM	US-11041859: Methods of identifying SENP1 inhibitors

ChEMBL bioactivities

12 potent at pChembl≥5 of 23 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.96	IC50	1100	nM	CHEMBL5276705
5.73	IC50	1880	nM	CHEMBL5276705
5.73	IC50	1860	nM	CHEMBL5315679
5.72	Kd	1900	nM	CHEMBL3580707
5.68	IC50	2080	nM	CHEMBL5175111
5.67	IC50	2150	nM	CHEMBL2009952
5.63	IC50	2320	nM	CHEMBL2009952
5.57	IC50	2700	nM	CHEMBL5175111
5.52	IC50	3000	nM	CHEMBL5315679
5.37	IC50	4320	nM	CHEMBL5290662
5.34	IC50	4600	nM	CHEMBL5278967
5.12	IC50	7500	nM	CHEMBL5278967

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	4
Arsenic Trioxide	affects localization, affects reaction, increases reaction, decreases reaction, affects binding (+3 more)	4
sodium arsenite	affects cotreatment, decreases expression	3
Valproic Acid	decreases expression	2
CB-5083	affects binding, increases reaction, decreases reaction	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
arsenite	increases reaction, affects binding	1
perfluorooctanoic acid	increases expression	1
hinokiflavone	increases localization	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Arsenic	affects binding, increases reaction, decreases reaction	1
Benztropine	decreases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Disulfiram	affects binding, decreases expression	1
Ethylmaleimide	affects binding, decreases reaction	1
Furaldehyde	decreases expression, affects cotreatment, affects localization	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 5 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114721	Functional	PubChem BioAssay. Dose response confirmation of uHTS inhibitor hits of SUMO1-mediated protein-protein interactions using a SUMO2 fluorescence polarization selectivity assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4731559	Binding	Inhibition of SUMO2 in human PC3 cells assessed as reduction in SUMOylation level at 10 uM measured after 24 hrs by western blot analysis	Synthesis and Evaluation of Ginkgolic Acid Derivatives as SUMOylation Inhibitors. — *ACS 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_RJ62	HeLa His10-SUMO-2 K0-Q87R	Cancer cell line	Female
CVCL_RJ63	U2OS His10-SUMO-2-K0-Q87R	Cancer cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SUMO2 across ~30M SureChEMBL compounds — explore on Sugi Predict.