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
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 80.8% of screened cell lines
• 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: 8 — 8 protein_coding

ENST00000314523, ENST00000420826, ENST00000578238, ENST00000897760, ENST00000919116, ENST00000919117, ENST00000919118, ENST00000970835

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.

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

294 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

70 targeting SUMO2, 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-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

DepMap (CRISPR cell-line fitness): dependent in 80.8% of screened cell lines.

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

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sumo2	ENSMUSG00000020738
rattus_norvegicus	Sumo2	ENSRNOG00000071259
drosophila_melanogaster	Sumo	FBGN0264922

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

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)

25 structures.

PDB	Method	Resolution (Å)
1WM3	X-RAY DIFFRACTION	1.2
1WM2	X-RAY DIFFRACTION	1.6
4NPN	X-RAY DIFFRACTION	1.63
2D07	X-RAY DIFFRACTION	2.1
4BKG	X-RAY DIFFRACTION	2.11
3ZO5	X-RAY DIFFRACTION	2.15
2IO0	X-RAY DIFFRACTION	2.3
5ELU	X-RAY DIFFRACTION	2.35
5D2M	X-RAY DIFFRACTION	2.4
7ZJV	X-RAY DIFFRACTION	2.4
5EQL	X-RAY DIFFRACTION	2.49
3UIN	X-RAY DIFFRACTION	2.6
3UIO	X-RAY DIFFRACTION	2.6
2CKH	X-RAY DIFFRACTION	3.2
2IO3	X-RAY DIFFRACTION	3.2
2IYD	X-RAY DIFFRACTION	3.2
1WZ0	SOLUTION NMR
2AWT	SOLUTION NMR
2N1W	SOLUTION NMR
2N9E	SOLUTION NMR
2RPQ	SOLUTION NMR
5GHB	SOLUTION NMR
5GHC	SOLUTION NMR
6JXW	SOLUTION NMR
6JXX	SOLUTION NMR

Predicted structure (AlphaFold)

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

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): 11, 21, 93, 11, 1, 5, 7, 11, 11, 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

32 pathways

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

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 (3): protein sumoylation (GO:0016925), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of transcription by RNA polymerase II (GO:0045944)

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 (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), 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), presynapse (GO:0098793), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-9 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
synapse	4
cellular anatomical structure	3
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
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	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
nuclear body	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
presynapse	1
postsynapse	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

176 interactions, top by confidence:

A	B	Type	Score
ESR1	PGR	psi-mi:“MI:0915”(physical association)	0.770
RANGAP1	SUMO2	psi-mi:“MI:0915”(physical association)	0.750
SENP1	SUMO2	psi-mi:“MI:0407”(direct interaction)	0.740
SUMO2	SENP1	psi-mi:“MI:0915”(physical association)	0.740
USP25	SUMO2	psi-mi:“MI:0915”(physical association)	0.720
SUMO2	SENP2	psi-mi:“MI:0915”(physical association)	0.720
SUMO2	USP25	psi-mi:“MI:0915”(physical association)	0.720
SENP2	SUMO2	psi-mi:“MI:0407”(direct interaction)	0.720
RANGAP1	RANBP2	psi-mi:“MI:0407”(direct interaction)	0.710
UBE2I	SUMO2	psi-mi:“MI:0407”(direct interaction)	0.690
CHD3	SUMO2	psi-mi:“MI:0915”(physical association)	0.670
SUMO2	CHD3	psi-mi:“MI:0915”(physical association)	0.670
BRCA1	SUMO2	psi-mi:“MI:0915”(physical association)	0.590
SUMO2	PELP1	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (867): SUMO2 (Reconstituted Complex), SUMO2 (Biochemical Activity), SUMO2 (Biochemical Activity), SUMO2 (Biochemical Activity), SUMO2 (Biochemical Activity), SUMO2 (Biochemical Activity), USP25 (Two-hybrid), HOMEZ (Two-hybrid), SENP2 (Two-hybrid), SUMO2 (Reconstituted Complex), SUMO2 (Reconstituted Complex), UBE2I (Reconstituted Complex), SUMO2 (Biochemical Activity), SUMO2 (Reconstituted Complex), SUMO2 (Affinity Capture-Western)

ESM2 similar proteins: A7WLH8, A7WLI0, B3H5R8, G2XKQ0, O13351, O57686, P29504, P55852, P55853, P55854, P55857, P61955, P61956, P61957, P61958, P61959, P62982, P62983, P63165, P63166, Q12306, Q17QV3, Q28H04, Q2EF74, Q2PFW2, Q3E8A8, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5XIF4, Q5ZHQ1, Q5ZJM9, Q6DEP7, Q6DHL4, Q6DI05, Q6DK72, Q6EEV6, Q6GPW2, Q6LDZ8

Diamond homologs: A7WLH8, A7WLI0, B3H5R8, G2XKQ0, O13351, O57686, P55852, P55853, P55854, P55857, P61955, P61956, P61957, P61958, P61959, P63165, P63166, Q0P4K8, Q12306, Q17QV3, Q28H04, Q2EF74, Q2PFW2, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5XIF4, Q5ZHQ1, Q5ZJM9, Q6DEP7, Q6DHL4, Q6DI05, Q6DK72, Q6EEV6, Q6GPW2, Q6LDZ8, Q6NV25, Q7SZ22, Q7SZR5

SIGNOR signaling

2 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 143 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 transcription factors	6	31.4×	6e-06
Rev-mediated nuclear export of HIV RNA	7	20.4×	8e-06
SUMOylation of DNA damage response and repair proteins	13	17.5×	3e-10
Nuclear import of Rev protein	5	15.4×	1e-03
SUMOylation of intracellular receptors	5	15.4×	1e-03
SUMOylation	10	15.0×	4e-07
SUMOylation of DNA replication proteins	6	13.7×	4e-04
SUMOylation of transcription cofactors	6	13.4×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	10	26.6×	5e-09
nucleocytoplasmic transport	5	16.1×	2e-03
cellular response to UV	5	12.1×	6e-03
double-strand break repair	6	10.0×	4e-03
regulation of protein stability	7	7.2×	6e-03
DNA damage response	12	5.3×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

469 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75174822:CC:C	acceptor_gain	1.0000
17:75174823:CC:C	acceptor_gain	1.0000
17:75181051:CCTCA:C	donor_loss	1.0000
17:75181052:CTCAC:C	donor_loss	1.0000
17:75181054:CACCT:C	donor_loss	1.0000
17:75181055:A:AG	donor_loss	1.0000
17:75181056:C:A	donor_loss	1.0000
17:75181185:CTTC:C	acceptor_gain	1.0000
17:75181188:CCTG:C	acceptor_loss	1.0000
17:75181189:C:A	acceptor_loss	1.0000
17:75181189:C:CC	acceptor_gain	1.0000
17:75182809:CTCA:C	donor_loss	1.0000
17:75182810:TCACC:T	donor_loss	1.0000
17:75182811:CA:C	donor_loss	1.0000
17:75182812:A:AG	donor_loss	1.0000
17:75182813:C:CG	donor_loss	1.0000
17:75168398:CCAA:C	acceptor_gain	0.9900
17:75168399:CAAC:C	acceptor_gain	0.9900
17:75168402:C:CC	acceptor_gain	0.9900
17:75168406:C:CT	acceptor_gain	0.9900
17:75168407:A:C	acceptor_gain	0.9900
17:75174746:TTTTA:T	donor_loss	0.9900
17:75174747:TTTAC:T	donor_loss	0.9900
17:75174748:TTACC:T	donor_loss	0.9900
17:75174749:TACCT:T	donor_loss	0.9900
17:75174750:A:T	donor_loss	0.9900
17:75174751:C:CA	donor_loss	0.9900
17:75174820:ATCC:A	acceptor_gain	0.9900
17:75174821:TCC:T	acceptor_gain	0.9900
17:75174822:CCC:C	acceptor_gain	0.9900

AlphaMissense

634 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75168376:A:T	I84N	1.000
17:75174759:G:T	P73H	1.000
17:75174777:A:T	I67N	1.000
17:75174786:C:A	G64V	1.000
17:75174797:G:C	F60L	1.000
17:75174797:G:T	F60L	1.000
17:75174798:A:G	F60S	1.000
17:75174799:A:G	F60L	1.000
17:75181114:A:C	F32L	1.000
17:75181114:A:T	F32L	1.000
17:75181115:A:C	F32C	1.000
17:75181115:A:G	F32S	1.000
17:75181116:A:G	F32L	1.000
17:75181151:A:G	L20S	1.000
17:75168366:G:C	F87L	0.999
17:75168366:G:T	F87L	0.999
17:75168368:A:G	F87L	0.999
17:75168376:A:C	I84S	0.999
17:75168382:T:A	D82V	0.999
17:75168383:C:G	D82H	0.999
17:75168394:A:C	M78R	0.999
17:75168394:A:G	M78T	0.999
17:75168394:A:T	M78K	0.999
17:75174759:G:C	P73R	0.999
17:75174786:C:T	G64E	0.999
17:75174787:C:A	G64W	0.999
17:75174787:C:G	G64R	0.999
17:75174787:C:T	G64R	0.999
17:75174791:A:C	F62L	0.999
17:75174791:A:T	F62L	0.999

dbSNP variants (sampled 300 via entrez): RS1000020841 (17:75171011 G>A), RS1000021233 (17:75167960 G>T), RS1000188657 (17:75166336 A>C), RS1000339637 (17:75171400 G>C), RS1000621831 (17:75169653 G>C), RS1000727418 (17:75168445 C>T), RS1000855716 (17:75171629 T>C), RS1000992364 (17:75184188 C>A,T), RS1001045942 (17:75182942 C>G,T), RS1001054052 (17:75179782 C>T), RS1001157602 (17:75179538 A>AT), RS1001320041 (17:75180415 A>AC,ACAAAAAACAAAAAAC,ACAC), RS1001370436 (17:75172884 G>T), RS1001433842 (17:75178291 G>A), RS1001476766 (17:75178245 G>C)

Disease associations

OMIM: gene MIM:603042 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006019_39	Gamma glutamyl transferase levels	5.000000e-08
GCST010118_65	Type 2 diabetes	8.000000e-09
GCST010727_36	Deep white matter hyperintensities	4.000000e-07
GCST011349_26	Gamma glutamyl transferase levels	3.000000e-08
GCST012020_530	Serum metabolite levels	1.000000e-25

EFO canonical traits (2, from GWAS)

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 (VIP=true, CPIC=false)

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	affects expression, decreases expression, increases expression	4
Arsenic Trioxide	increases expression, decreases reaction, affects reaction, increases reaction, increases sumoylation (+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	decreases expression, affects cotreatment	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
arsenite	affects binding, increases reaction	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	affects cotreatment, affects localization, decreases expression	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)

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