SENP2

Summary

SENP2 (SUMO specific peptidase 2, HGNC:23116) is a protein-coding gene on chromosome 3q27.2, encoding Sentrin-specific protease 2 (Q9HC62). Protease that catalyzes two essential functions in the SUMO pathway.

SUMO1 (UBL1; MIM 601912) is a small ubiquitin-like protein that can be covalently conjugated to other proteins. SENP2 is one of a group of enzymes that process newly synthesized SUMO1 into the conjugatable form and catalyze the deconjugation of SUMO1-containing species.

Source: NCBI Gene 59343 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 91 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021627

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23116
Approved symbol	SENP2
Name	SUMO specific peptidase 2
Location	3q27.2
Locus type	gene with protein product
Status	Approved
Aliases	SMT3IP2, KIAA1331, DKFZp762A2316, AXAM2
Ensembl gene	ENSG00000163904
Ensembl biotype	protein_coding
OMIM	608261
Entrez	59343

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 23 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296257, ENST00000413407, ENST00000430355, ENST00000439684, ENST00000444509, ENST00000453532, ENST00000458551, ENST00000459883, ENST00000465201, ENST00000473760, ENST00000476011, ENST00000478001, ENST00000483005, ENST00000889612, ENST00000889613, ENST00000889614, ENST00000889615, ENST00000889616, ENST00000889617, ENST00000889618, ENST00000889619, ENST00000889620, ENST00000889621, ENST00000889622, ENST00000889623, ENST00000889624, ENST00000953470, ENST00000953471, ENST00000953472, ENST00000953473, ENST00000953474, ENST00000953475, ENST00000953476

RefSeq mRNA: 1 — MANE Select: NM_021627 NM_021627

CCDS: CCDS33902

Canonical transcript exons

ENST00000296257 — 17 exons

Exon	Start	End
ENSE00001887141	185629782	185633551
ENSE00003476118	185613345	185613408
ENSE00003483656	185598412	185598545
ENSE00003505233	185626298	185626393
ENSE00003508969	185586295	185586514
ENSE00003514124	185600765	185600855
ENSE00003520570	185617480	185617611
ENSE00003546289	185612607	185612658
ENSE00003563554	185611651	185611745
ENSE00003581127	185619299	185619502
ENSE00003608445	185606330	185606498
ENSE00003615498	185623998	185624082
ENSE00003619286	185598958	185599024
ENSE00003648951	185590114	185590169
ENSE00003660783	185621826	185621905
ENSE00003669994	185614564	185614740
ENSE00003673142	185609247	185609350

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 95.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6963 / max 330.1445, expressed in 1810 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40245	17.9034	1807
40246	1.2787	627
40244	1.0854	673
40240	0.5844	75
40242	0.2997	59
40239	0.2444	53
40241	0.2023	53
40243	0.0800	33
40248	0.0181	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.02	gold quality
colonic epithelium	UBERON:0000397	94.67	gold quality
adrenal tissue	UBERON:0018303	93.63	gold quality
sural nerve	UBERON:0015488	93.14	gold quality
left testis	UBERON:0004533	92.29	gold quality
tendon	UBERON:0000043	91.93	gold quality
right testis	UBERON:0004534	91.86	gold quality
testis	UBERON:0000473	91.52	gold quality
muscle of leg	UBERON:0001383	90.61	gold quality
gastrocnemius	UBERON:0001388	90.35	gold quality
corpus callosum	UBERON:0002336	90.27	gold quality
ventricular zone	UBERON:0003053	89.86	gold quality
islet of Langerhans	UBERON:0000006	89.39	gold quality
prefrontal cortex	UBERON:0000451	89.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.89	gold quality
ovary	UBERON:0000992	88.86	gold quality
left ovary	UBERON:0002119	88.82	gold quality
ganglionic eminence	UBERON:0004023	88.76	gold quality
medial globus pallidus	UBERON:0002477	88.68	gold quality
monocyte	CL:0000576	88.50	gold quality
skeletal muscle organ	UBERON:0014892	88.25	gold quality
muscle organ	UBERON:0001630	88.24	gold quality
mononuclear cell	CL:0000842	88.15	gold quality
leukocyte	CL:0000738	87.85	gold quality
stromal cell of endometrium	CL:0002255	87.73	gold quality
cerebellar vermis	UBERON:0004720	87.71	gold quality
right ovary	UBERON:0002118	87.69	gold quality
tibialis anterior	UBERON:0001385	87.56	silver quality
popliteal artery	UBERON:0002250	87.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	10.94
E-ANND-3	yes	7.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBX15, TP63

miRNA regulators (miRDB)

121 targeting SENP2, 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-188-3P	100.00	68.76	1240
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-10401-5P	99.99	65.79	948
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-552-5P	99.93	68.56	1583

Literature-anchored findings (GeneRIF, showing 38)

• association with the pore plays an important negative role in the regulation of SENP2 (PMID:11896061)
• Restricting SENP2 in the nucleus by mutations in the NES impairs its polyubiquitination, whereas a cytoplasm-localized SENP2 made by introducing mutations in the NLS can be efficiently polyubiquitinated. (PMID:16738331)
• Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing (PMID:17099700)
• Results demonstrate that SENP1 is the most efficient SUMO protease acting on Elk-1, and that SENP3 has little effect on Elk-1. SENP2 has an intermediate effect, but its ability to activate Elk-1 is independent from its SUMO-deconjugating activity. (PMID:20337593)
• a mechanism underlying the SENP2-mediated regulation of Mdm2 that is critical for genome integrity in p53-dependent stress responses. (PMID:21183956)
• SENP2 null cells display biphasic NEMO SUMOylation and activation of IKK and NF-kappaB (PMID:21777808)
• Data suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation, and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity. (PMID:22028379)
• The SUMO-specific isopeptidase SENP2 associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex. (PMID:22031293)
• cardiac overexpression of SENP2 in the mice with Nkx2.5 haploinsufficiency promoted embryonic lethality and severity of congenital heart diseases (CHDs). (PMID:22155005)
• The SENP1 levels are influenced by the presence of Nup153, whereas SENP2 is not sensitive to changes in Nup153 abundance. (PMID:22688647)
• SENP2 regulates hepatocellular carcinoma cell growth by modulating the stability of beta-catenin. (PMID:23098437)
• SENP2 plays an important role in determining the dynamics and functional outcome of MEF2A SUMOylation and transcriptional activation. (PMID:23224591)
• SENP2 represses glycolysis and shifts glucose metabolic strategy (PMID:23691130)
• SENP2 inhibited bladder cancer cells migration and invasion by regulating the expression of MMP13. (PMID:24008762)
• Chromosome segregation depends on precise spatial and temporal control of sumoylation in mitosis; SENP1 and SENP2 are important mediators of this control. (PMID:24048451)
• Many nucleoporins are mislocalized and, in some cases, reduced in level when SENP1 and SENP2 are codepleted. (PMID:24196834)
• ESR1 repression by SENP2 is independent of its SUMO protease activity. (PMID:24422630)
• we show that WWOX required for stabilization of beta-catenin regulated by SENP2 in hepatocellular carcinoma cells (PMID:24969559)
• SENP2 regulates the transcriptional function of MEF2A via direct de-SUMOylation. (PMID:25483061)
• miR-181b targets SENP2 and positively regulated NF-kappaB activity. NF-kappaB activation by DNA damage in GBM cells confers resistance to radiation-induced death. (PMID:25633526)
• p90RSK-mediated SENP2-T368 phosphorylation is a master switch in disturbed-flow-induced signaling. (PMID:25689261)
• data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle (PMID:25784542)
• SENP2 inhibits MMP13 expression in BC cells through de-SUMOylation of TBL1/TBLR1, which inhibits nuclear translocation of beta-catenin. (PMID:26369384)
• The variability of the SENP1 and SENP2 genes may play a role in breast cancer occurrence. (PMID:27178176)
• Data show that Sentrin/SUMO specific protease (SENP2) interacts with N-myc downstream regulated gene 2 (NDRG2) and mediates the de-SUMOylation process of NDRG2. (PMID:29060933)
• Quantitative high-throughput screening identifies cytoprotective molecules that enhance SUMO conjugation via the inhibition of SUMO-specific protease (SENP)2. (PMID:29146736)
• SENP2 binds to intracellular membranes where it interacts with membrane-associated proteins and has the potential to regulate their sumoylation and membrane-associated functions. (PMID:29874116)
• research achievements of SENP2 are reviewed in order to understand its related functions and the underlying molecular mechanisms and provide a clue for future research on SENP2 (PMID:29908207)
• SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-beta induced cancer cell migration. (PMID:29955155)
• he nuclear factor (NF)kappaB signaling pathway was also regulated by the overexpression of SENP2. On the whole, the findings of this study indicate tha SENP2 can act as a tumor suppressor in CLL cells, and may thus prove to be a novel target for CLL treatment in clinical practice. (PMID:30431078)
• SENP2 is amplified as part of the chromosome 3q amplification in many cancers and Increased SENP2 expression prolongs MDC1 focus retention and increases NHEJ and radioresistance (PMID:30796017)
• Overexpression of SENP2 was correlated with a better overall survival of the Gastric Cancer patients with a marginally significance, indicating that SENP2 expression could be used as a novel biomarker to predict patient prognosis. (PMID:30997579)
• Silencing of SENP2 in Multiple Myeloma Induces Bortezomib Resistance by Activating NF-kappaB Through the Modulation of IkappaBalpha Sumoylation. (PMID:31964975)
• Hepatic Small Ubiquitin-Related Modifier (SUMO)-Specific Protease 2 Controls Systemic Metabolism Through SUMOylation-Dependent Regulation of Liver-Adipose Tissue Crosstalk. (PMID:33934381)
• SENP2 regulates mitochondrial function and insulin secretion in pancreatic beta cells. (PMID:35064188)
• Mitochondrial SENP2 regulates the assembly of SDH complex under metabolic stress. (PMID:36708515)
• Extracellular vesicle-mediated regulation of imatinib resistance in chronic myeloid leukemia via the miR-629-5p/SENP2/PI3K/AKT/mTOR axis. (PMID:39056503)
• Sumo-regulatory SENP2 controls the homeostatic squamous mitosis-differentiation checkpoint. (PMID:39152119)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Senp2	ENSMUSG00000022855
mus_musculus	Semp2l2a	ENSMUSG00000057116
mus_musculus	Semp2l2b	ENSMUSG00000069712
mus_musculus	Semp2l1	ENSMUSG00000091318
rattus_norvegicus	Senp2	ENSRNOG00000001773
rattus_norvegicus	Senp18	ENSRNOG00000066068
rattus_norvegicus		ENSRNOG00000074661
rattus_norvegicus	Senp17	ENSRNOG00000076735
rattus_norvegicus		ENSRNOG00000087192
drosophila_melanogaster	Ulp1	FBGN0027603
drosophila_melanogaster	CG32110	FBGN0052110
caenorhabditis_elegans		WBGENE00006736

Paralogs (3): SENP1 (ENSG00000079387), SENP5 (ENSG00000119231), SENP3 (ENSG00000161956)

Protein

Protein identifiers

Sentrin-specific protease 2 — Q9HC62 (reviewed: Q9HC62)

Alternative names: Axam2, SMT3-specific isopeptidase 2, Sentrin/SUMO-specific protease SENP2

All UniProt accessions (7): Q9HC62, C9IYB7, F8WCX8, F8WED6, F8WED7, F8WET6, H7C1A0

UniProt curated annotations — full annotation on UniProt →

Function. Protease that catalyzes two essential functions in the SUMO pathway. The first is the hydrolysis of an alpha-linked peptide bond at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3 leading to the mature form of the proteins. The second is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins, by cleaving an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein. May down-regulate CTNNB1 levels and thereby modulate the Wnt pathway. Deconjugates SUMO2 from MTA1. Plays a dynamic role in adipogenesis by desumoylating and promoting the stabilization of CEBPB. Acts as a regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS and STING1 during the late phase of viral infection.

Subunit / interactions. Binds to SUMO2 and SUMO3. Interacts with the C-terminal domain of NUP153 via its N-terminus. Interacts with MTA1.

Subcellular location. Nucleus. Nuclear pore complex. Nucleus membrane. Cytoplasm.

Post-translational modifications. Polyubiquitinated; which leads to proteasomal degradation.

Domain organisation. The N-terminus is necessary and sufficient for nuclear envelope targeting.

Similarity. Belongs to the peptidase C48 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HC62-1	1	yes
Q9HC62-2	2

RefSeq proteins (1): NP_067640* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003653	Peptidase_C48_C	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF02902

Enzyme classification (BRENDA):

• EC 3.4.22.B71 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (42 total): helix 12, strand 9, modified residue 3, short sequence motif 3, turn 3, active site 3, region of interest 2, mutagenesis site 2, sequence conflict 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3ZO5	X-RAY DIFFRACTION	2.15
1TH0	X-RAY DIFFRACTION	2.2
2IO0	X-RAY DIFFRACTION	2.3
2IO1	X-RAY DIFFRACTION	2.6
1TGZ	X-RAY DIFFRACTION	2.8
2IO2	X-RAY DIFFRACTION	2.9
5AEK	X-RAY DIFFRACTION	3
2IO3	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC62-F1	63.00	0.38

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 (3): 478; 495; 548 (nucleophile)

Post-translational modifications (3): 333, 344, 32

Mutagenesis-validated functional residues (2):

Position	Phenotype
548	does not desumoylate cebpb.
576–577	does not desumoylate cebpb.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3065679	SUMO is proteolytically processed
R-HSA-2990846	SUMOylation
R-HSA-3215018	Processing and activation of SUMO
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 235 (showing top): GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_CELL_CYCLE_DNA_REPLICATION, ATACCTC_MIR202, GOBP_CELL_CYCLE_PHASE_TRANSITION, CREBP1_Q2, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, CREB_Q4, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_PROTEIN_DESTABILIZATION

GO Biological Process (19): proteolysis (GO:0006508), heart development (GO:0007507), protein transport (GO:0015031), Wnt signaling pathway (GO:0016055), protein sumoylation (GO:0016925), protein desumoylation (GO:0016926), regulation of Wnt signaling pathway (GO:0030111), negative regulation of protein ubiquitination (GO:0031397), positive regulation of protein ubiquitination (GO:0031398), protein destabilization (GO:0031648), regulation of DNA endoreduplication (GO:0032875), fat cell differentiation (GO:0045444), positive regulation of transcription by RNA polymerase II (GO:0045944), mRNA transport (GO:0051028), trophoblast giant cell differentiation (GO:0060707), labyrinthine layer development (GO:0060711), regulation of G1/S transition of mitotic cell cycle (GO:2000045), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (6): deSUMOylase activity (GO:0016929), SUMO-specific endopeptidase activity (GO:0070139), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleus (GO:0005634), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytosol (GO:0005829), PML body (GO:0016605), nuclear membrane (GO:0031965), cytoplasm (GO:0005737), membrane (GO:0016020), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Processing and activation of SUMO	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
peptidyl-lysine modification	2
protein ubiquitination	2
regulation of protein ubiquitination	2
regulation of metabolic process	2
nuclear envelope	2
protein metabolic process	1
animal organ development	1
circulatory system development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cell surface receptor signaling pathway	1
protein modification by small protein conjugation	1
protein modification by small protein removal	1
regulation of signal transduction	1
Wnt signaling pathway	1
negative regulation of protein modification by small protein conjugation or removal	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of protein stability	1
regulation of cell cycle process	1
DNA endoreduplication	1
regulation of DNA-templated DNA replication	1
cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
RNA transport	1
cell differentiation involved in embryonic placenta development	1
embryonic placenta development	1
anatomical structure development	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
macromolecule metabolic process	1
primary metabolic process	1
cysteine-type peptidase activity	1
ubiquitin-like protein peptidase activity	1
ubiquitin-like protein-specific endopeptidase activity	1
binding	1

Protein interactions and networks

STRING

1058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SENP2	LMNB2	Q03252	768
SENP2	LMNB1	P20700	760
SENP2	RANGAP1	P46060	735
SENP2	SUMO1	P55856	712
SENP2	RGPD1	P0C839	584
SENP2	SUMO2	P55855	556
SENP2	RANBP2	P49792	467
SENP2	SELENOT	P62341	446
SENP2	SUMO4	Q6EEV6	437
SENP2	NUP153	P49790	416
SENP2	NUP133	Q8WUM0	399
SENP2	RNF4	P78317	371
SENP2	UBE2I	P50550	369
SENP2	PIAS1	O75925	362
SENP2	PIAS2	O75928	358

IntAct

100 interactions, top by confidence:

A	B	Type	Score
RANGAP1	SUMO1	psi-mi:“MI:0915”(physical association)	0.960
SUMO3	SENP2	psi-mi:“MI:0915”(physical association)	0.800
SENP2	SUMO3	psi-mi:“MI:0915”(physical association)	0.800
SENP2	SUMO3	psi-mi:“MI:0407”(direct interaction)	0.800
RANGAP1	SUMO2	psi-mi:“MI:0915”(physical association)	0.750
SUMO2	SENP2	psi-mi:“MI:0915”(physical association)	0.720
SENP2	KASH5	psi-mi:“MI:0915”(physical association)	0.720
SENP2	SUMO2	psi-mi:“MI:0407”(direct interaction)	0.720
KASH5	SENP2	psi-mi:“MI:0915”(physical association)	0.720
SENP2	SUMO1	psi-mi:“MI:0407”(direct interaction)	0.620
SENP2	IKBKG	psi-mi:“MI:0915”(physical association)	0.580
IKBKG	SENP2	psi-mi:“MI:0915”(physical association)	0.580
SENP2	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
SENP2	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
SENP2	FUNDC1	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	SENP2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (226): RANGAP1 (Biochemical Activity), SENP2 (Two-hybrid), SENP2 (Two-hybrid), SENP2 (Two-hybrid), SENP2 (Two-hybrid), FUNDC1 (Two-hybrid), CCDC155 (Two-hybrid), SYNE4 (Two-hybrid), TMEM239 (Two-hybrid), SENP2 (Reconstituted Complex), SENP2 (Reconstituted Complex), SUMO3 (Biochemical Activity), FZR1 (Affinity Capture-Western), SENP2 (Affinity Capture-Western), FZR1 (Reconstituted Complex)

ESM2 similar proteins: A0A1P8ASY1, B9EUM5, B9FL70, B9G8P1, D1KF50, F4I2H2, F4I9Q5, F4IBQ9, F4J2M6, F4JUI9, O01836, O13769, O59751, O65278, O81635, O93530, O94536, P0CB22, Q04692, Q09275, Q0IMS9, Q0WVW7, Q14191, Q19546, Q1EHT7, Q2PS26, Q3SWY8, Q4R4A2, Q5R7K7, Q651Z7, Q6P158, Q7X7H4, Q84RR2, Q8GYL3, Q8RWN0, Q8S949, Q8W1Y3, Q91ZX6, Q94F30, Q96AP4

Diamond homologs: A7MBJ2, D3ZF42, O42957, O65278, P59110, Q02724, Q09353, Q5R7K7, Q5RBB1, Q6NXL6, Q6P7W0, Q8BUH8, Q8GYL3, Q8WP32, Q91ZX6, Q94F30, Q96HI0, Q9BQF6, Q9EP97, Q9EQE1, Q9GZR1, Q9H4L4, Q9HC62, Q9P0U3, Q0WKV8, Q8RWN0, O13612, O13769, Q09275, Q8L7S0, Q2PS26, Q23238

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS6KA1	“down-regulates activity”	SENP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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 replication proteins	7	48.3×	2e-08
SUMOylation of RNA binding proteins	7	46.3×	2e-08
SUMOylation of SUMOylation proteins	5	45.3×	5e-06
SUMOylation of chromatin organization proteins	7	30.8×	2e-07
SUMOylation of DNA damage response and repair proteins	7	28.5×	3e-07
SUMO E3 ligases SUMOylate target proteins	5	24.8×	6e-05
SUMOylation	5	22.7×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	5	36.0×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2973 predictions. Top by Δscore:

Variant	Effect	Δscore
3:185590112:A:AG	acceptor_gain	1.0000
3:185590113:G:GG	acceptor_gain	1.0000
3:185606320:T:A	acceptor_gain	1.0000
3:185606323:T:A	acceptor_gain	1.0000
3:185606328:A:AG	acceptor_gain	1.0000
3:185606329:G:GA	acceptor_gain	1.0000
3:185606329:GTT:G	acceptor_gain	1.0000
3:185606329:GTTTT:G	acceptor_gain	1.0000
3:185609245:AG:A	acceptor_gain	1.0000
3:185609246:GG:G	acceptor_gain	1.0000
3:185609246:GGGT:G	acceptor_gain	1.0000
3:185609302:A:T	donor_gain	1.0000
3:185609307:G:GA	donor_gain	1.0000
3:185609357:G:GG	donor_gain	1.0000
3:185609369:A:G	donor_gain	1.0000
3:185611648:A:AG	acceptor_gain	1.0000
3:185611649:A:G	acceptor_gain	1.0000
3:185611746:G:GG	donor_gain	1.0000
3:185612605:A:AG	acceptor_gain	1.0000
3:185612606:G:GA	acceptor_loss	1.0000
3:185612606:G:GG	acceptor_gain	1.0000
3:185612606:GATA:G	acceptor_gain	1.0000
3:185612656:GAG:G	donor_gain	1.0000
3:185612657:AGGTA:A	donor_loss	1.0000
3:185612659:G:GG	donor_gain	1.0000
3:185612660:T:G	donor_loss	1.0000
3:185613343:A:AG	acceptor_gain	1.0000
3:185613343:A:T	acceptor_loss	1.0000
3:185613344:G:A	acceptor_loss	1.0000
3:185613344:G:GG	acceptor_gain	1.0000

AlphaMissense

3879 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:185617597:T:A	W410R	1.000
3:185617597:T:C	W410R	1.000
3:185617606:G:C	D413H	1.000
3:185617607:A:T	D413V	1.000
3:185619321:T:C	L422P	1.000
3:185619377:T:C	F441L	1.000
3:185619379:C:A	F441L	1.000
3:185619379:C:G	F441L	1.000
3:185619425:T:A	W457R	1.000
3:185619425:T:C	W457R	1.000
3:185619427:G:C	W457C	1.000
3:185619427:G:T	W457C	1.000
3:185619491:T:A	W479R	1.000
3:185619491:T:C	W479R	1.000
3:185619493:G:C	W479C	1.000
3:185619493:G:T	W479C	1.000
3:185619498:T:C	L481P	1.000
3:185624056:T:A	W529R	1.000
3:185624056:T:C	W529R	1.000
3:185626326:A:T	D547V	1.000
3:185626328:T:C	C548R	1.000
3:185626329:G:A	C548Y	1.000
3:185626332:G:A	G549E	1.000
3:185626337:T:C	F551L	1.000
3:185626338:T:C	F551S	1.000
3:185626339:T:A	F551L	1.000
3:185626339:T:G	F551L	1.000
3:185617546:T:C	F393L	0.999
3:185617548:C:A	F393L	0.999
3:185617548:C:G	F393L	0.999

dbSNP variants (sampled 300 via entrez): RS1000036273 (3:185596986 T>C), RS1000039846 (3:185621719 T>G), RS1000156015 (3:185607763 C>G,T), RS1000223672 (3:185596959 T>C), RS1000296297 (3:185607410 C>T), RS1000323047 (3:185604943 T>G), RS1000330248 (3:185627551 T>C), RS1000339618 (3:185600337 G>A,T), RS1000359500 (3:185630414 T>C,G), RS1000364252 (3:185611713 G>A,C,T), RS1000368377 (3:185612154 CAAAA>C,CA,CAA,CAAA,CAAAAA,CAAAAAA,CAAAAAAA,CAAAAAAAA), RS1000576870 (3:185618913 A>G), RS1000591893 (3:185604533 A>C,G), RS1000755776 (3:185631934 C>A,T), RS1000757046 (3:185586143 C>A,G)

Disease associations

OMIM: gene MIM:608261 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST003670_16	Systolic blood pressure	7.000000e-06
GCST004280_46	Diastolic blood pressure	9.000000e-09
GCST005655_9	Seborrheic dermatitis	4.000000e-06
GCST007045_25	PR interval	2.000000e-08
GCST007094_216	Diastolic blood pressure	4.000000e-13
GCST007098_21	Diastolic blood pressure	8.000000e-06
GCST007099_111	Systolic blood pressure	3.000000e-06
GCST007103_9	QRS duration	5.000000e-11
GCST007104_10	QRS duration	1.000000e-11
GCST007876_83	Estimated glomerular filtration rate	2.000000e-12
GCST008058_75	Estimated glomerular filtration rate	9.000000e-24
GCST008059_78	Estimated glomerular filtration rate	7.000000e-21
GCST008162_67	Hip circumference	7.000000e-07
GCST008163_255	Height	9.000000e-07
GCST010321_130	PR interval	2.000000e-13
GCST010796_2688	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_2689	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_2690	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_2691	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010918_1	JT interval	2.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0007885	JT interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2176776 (SINGLE PROTEIN), CHEMBL6066556 (PROTEIN COMPLEX), CHEMBL6066557 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,337 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11417	STREPTONIGRIN	2	43,337

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

Binding affinities (BindingDB)

8 measured of 21 human assays (21 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
SPI-02	IC50	2100 nM	US-9791447: Methods of identifying SENP1 inhibitors
SPI-04	IC50	2400 nM	US-9791447: Methods of identifying SENP1 inhibitors
SPI-10	IC50	2400 nM	US-9791447: Methods of identifying SENP1 inhibitors
NSC8676	IC50	3800 nM	US-9791447: Methods of identifying SENP1 inhibitors
NSC70551	IC50	3900 nM	US-9791447: Methods of identifying SENP1 inhibitors
SPI-01	IC50	5900 nM	US-9791447: Methods of identifying SENP1 inhibitors
SPI-05	IC50	13300 nM	US-9791447: Methods of identifying SENP1 inhibitors
SPI-08	IC50	22200 nM	US-9791447: Methods of identifying SENP1 inhibitors

ChEMBL bioactivities

82 potent at pChembl≥5 of 114 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.25	IC50	560	nM	CHEMBL4791433
6.16	IC50	690	nM	CHEMBL4776158
5.96	IC50	1100	nM	CHEMBL4781794
5.96	IC50	1100	nM	CHEMBL5276705
5.92	IC50	1200	nM	CHEMBL4792569
5.85	IC50	1400	nM	CHEMBL4780770
5.85	IC50	1420	nM	CHEMBL5276705
5.80	IC50	1600	nM	CHEMBL4780586
5.80	IC50	1600	nM	CHEMBL2009952
5.70	IC50	2000	nM	CHEMBL5175111
5.67	IC50	2150	nM	CHEMBL2009952
5.66	IC50	2200	nM	CHEMBL4796113
5.64	IC50	2300	nM	CHEMBL4778045
5.64	IC50	2300	nM	CHEMBL5269877
5.64	IC50	2300	nM	CHEMBL2009952
5.62	IC50	2400	nM	CHEMBL4783695
5.62	IC50	2400	nM	CHEMBL5266367
5.62	IC50	2400	nM	CHEMBL5315679
5.60	IC50	2500	nM	CHEMBL4793952
5.60	IC50	2500	nM	CHEMBL5287963
5.60	IC50	2500	nM	CHEMBL5315304
5.57	IC50	2700	nM	CHEMBL5175111
5.55	IC50	2800	nM	CHEMBL3799152
5.54	IC50	2900	nM	CHEMBL5276705
5.52	IC50	3000	nM	CHEMBL5315679
5.47	IC50	3420	nM	CHEMBL5175111
5.46	IC50	3500	nM	CHEMBL4791044
5.46	IC50	3500	nM	CHEMBL4796293
5.44	IC50	3620	nM	CHEMBL5290662
5.43	IC50	3700	nM	CHEMBL5207368
5.43	IC50	3700	nM	CHEMBL5188918
5.43	IC50	3700	nM	CHEMBL5290662
5.41	IC50	3900	nM	CHEMBL4789655
5.39	IC50	4100	nM	CHEMBL6030623
5.34	IC50	4600	nM	CHEMBL5278967
5.33	IC50	4700	nM	CHEMBL4791142
5.33	IC50	4700	nM	CHEMBL5194248
5.32	IC50	4800	nM	CHEMBL4778402
5.31	IC50	4900	nM	CHEMBL4785749
5.30	IC50	5000	nM	CHEMBL4792795
5.30	IC50	5000	nM	CHEMBL5265789
5.29	IC50	5100	nM	CHEMBL4785280
5.29	IC50	5170	nM	CHEMBL5315679
5.27	IC50	5400	nM	CHEMBL4800446
5.23	IC50	5900	nM	CHEMBL4789677
5.23	IC50	5900	nM	CHEMBL4789800
5.23	IC50	5900	nM	CHEMBL4780660
5.21	IC50	6200	nM	CHEMBL4790106
5.20	IC50	6300	nM	CHEMBL5278030
5.19	IC50	6400	nM	CHEMBL4786762

PubChem BioAssay actives

71 with measured affinity, of 107 total; 50 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
[3-[[2-[[(3S)-2-[[(2S)-5-amino-2-[[2-(4-hydroxy-3-nitrophenyl)acetyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-2-oxopropyl] anthracene-9-carboxylate	1799555: Fluorogenic Assay from Article 10.1016/j.chembiol.2011.05.008: “Development of small molecule inhibitors and probes of human SUMO deconjugating proteases.”	ic50	0.2500	uM
5-(dimethylamino)-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	0.5600	uM
ethyl 2-[[3-phenylmethoxy-2-[[3-(thiophene-2-carbonylamino)phenyl]methylcarbamoyl]-1-benzothiophen-5-yl]amino]acetate	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	0.6900	uM
[3-[[2-[[(3S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[2-(4-hydroxy-3-nitrophenyl)acetyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-2-oxopropyl] anthracene-9-carboxylate	1799555: Fluorogenic Assay from Article 10.1016/j.chembiol.2011.05.008: “Development of small molecule inhibitors and probes of human SUMO deconjugating proteases.”	ic50	0.8600	uM
2-[(E)-2-[4-[(2-aminonaphthalen-1-yl)diazenyl]-2-sulfophenyl]ethenyl]-5-(naphthalen-1-yldiazenyl)benzenesulfonic acid	1741430: Inhibition of human His-tagged SENP2 (364 to 589 residues) expressed in Escherichia coli (DE3) cells using DUB-Glo as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by luciferase assay	ic50	1.1000	uM
5-[(2-aminonaphthalen-1-yl)diazenyl]-2-[(E)-2-[4-[(2-aminonaphthalen-1-yl)diazenyl]-2-sulfophenyl]ethenyl]benzenesulfonic acid	1800082: SUMO Cleavage Assay from Article 10.1021/cb400177q: “Identification and Characterization of a New Chemotype of Noncovalent SENP Inhibitors.”	ic50	1.1000	uM
5-(methylamino)-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	1.2000	uM
5-(ethylamino)-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	1.4000	uM
5-amino-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	1.6000	uM
5-amino-8-[[4-[(E)-2-[4-[(4-amino-7-sulfonaphthalen-1-yl)diazenyl]-2-sulfophenyl]ethenyl]-3-sulfophenyl]diazenyl]naphthalene-2-sulfonate	1800082: SUMO Cleavage Assay from Article 10.1021/cb400177q: “Identification and Characterization of a New Chemotype of Noncovalent SENP Inhibitors.”	ic50	1.6000	uM
3-amino-4-[[4-[4-[(2-amino-6-sulfonaphthalen-1-yl)diazenyl]-3-methylphenyl]-2-methylphenyl]diazenyl]naphthalene-2,7-disulfonic acid	1859346: Inhibition of His-tagged human SENP2 (364 to 589 residues) expressed in Escherichia coli (DE3) using YFP-SUMO-ECFP as substrate incubated for 15 mins by Coomassie staining based SDS-PAGE analysis	ic50	2.0000	uM
N-[(3-benzamidophenyl)methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	2.2000	uM
N-[[3-(1-benzothiophene-2-carbonylamino)phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	2.3000	uM
171343867	1926193: Inhibition of SENP2 (unknown origin)	ic50	2.3000	uM
5-[(2-chloroacetyl)amino]-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	2.4000	uM
171351460	1926193: Inhibition of SENP2 (unknown origin)	ic50	2.4000	uM
3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	2.5000	uM
24186038	1926193: Inhibition of SENP2 (unknown origin)	ic50	2.5000	uM
3-phenyl-N-[[3-[[(E)-3-phenylprop-2-enoyl]amino]phenyl]methyl]benzamide	1297529: Inhibition of human recombinant His-tagged SENP2 (363 to 589 residues) expressed in Escherichia coli BL21 (DE3) using RanGAP-SUMO as substrate incubated for 10 mins prior to substrate addition followed by further 25 mins incubation by coomassie blue staining based SDS-PAGE/Odyssey infrared scanning assay	ic50	2.8000	uM
4-amino-3-[[4-[4-[(1-amino-4-sulfonaphthalen-2-yl)diazenyl]-2-methylphenyl]-3-methylphenyl]diazenyl]naphthalene-1-sulfonic acid	1800082: SUMO Cleavage Assay from Article 10.1021/cb400177q: “Identification and Characterization of a New Chemotype of Noncovalent SENP Inhibitors.”	ic50	3.0000	uM
N-[(3-benzamidophenyl)methyl]-3-[(3-nitrophenyl)methoxy]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	3.5000	uM
3-phenylmethoxy-5-(prop-2-enoylamino)-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	3.5000	uM
4-amino-3-[(2-methylphenyl)diazenyl]naphthalene-1-sulfonic acid	1800082: SUMO Cleavage Assay from Article 10.1021/cb400177q: “Identification and Characterization of a New Chemotype of Noncovalent SENP Inhibitors.”	ic50	3.6200	uM
2-(4-chloro-3-methylphenoxy)-N-[4-[[2-(4-chloro-3-methylphenoxy)acetyl]amino]-1,2,5-oxadiazol-3-yl]acetamide	1859348: Inhibition of recombinant human SENP2 in presence of DTT by FRET assay	ic50	3.7000	uM
3-[[4-[[[(2S,3S)-3-[3-naphthalen-1-yl-2-(naphthalen-1-ylmethyl)propanoyl]oxirane-2-carbonyl]amino]carbamoyl]phenyl]methylcarbamoyl]benzoic acid	1859343: Inhibition of human SENP2 using QTGG-AFC as substrate by fluorescence based analysis	ic50	3.7000	uM
3-[[4-[[[(2S,3S)-3-[bis(naphthalen-1-ylmethyl)carbamoyl]oxirane-2-carbonyl]amino]carbamoyl]phenyl]methylcarbamoyl]benzoic acid	1799555: Fluorogenic Assay from Article 10.1016/j.chembiol.2011.05.008: “Development of small molecule inhibitors and probes of human SUMO deconjugating proteases.”	ic50	3.7000	uM
5-nitro-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	3.9000	uM
4-amino-3-phenyldiazenylnaphthalene-1-sulfonate	1800082: SUMO Cleavage Assay from Article 10.1021/cb400177q: “Identification and Characterization of a New Chemotype of Noncovalent SENP Inhibitors.”	ic50	4.1000	uM
5-[(4-aminonaphthalen-1-yl)diazenyl]-2-[(E)-2-[4-[(4-aminonaphthalen-1-yl)diazenyl]-2-sulfophenyl]ethenyl]benzenesulfonic acid	1800082: SUMO Cleavage Assay from Article 10.1021/cb400177q: “Identification and Characterization of a New Chemotype of Noncovalent SENP Inhibitors.”	ic50	4.6000	uM
6-methoxy-3-phenylmethoxy-N-[[3-(thiophene-2-carbonylamino)phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	4.7000	uM
3-[[4-[[carboxymethyl-[(2S,3S)-3-[3-naphthalen-1-yl-2-(naphthalen-1-ylmethyl)propanoyl]oxirane-2-carbonyl]amino]carbamoyl]phenyl]methylcarbamoyl]benzoic acid	1859343: Inhibition of human SENP2 using QTGG-AFC as substrate by fluorescence based analysis	ic50	4.7000	uM
N-[[3-[(2-methylbenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	4.8000	uM
N-[(3-benzamidophenyl)methyl]-3-[(2-nitrophenyl)methoxy]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	4.9000	uM
2-(4-chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]-1,2,5-oxadiazol-3-yl]acetamide	1926193: Inhibition of SENP2 (unknown origin)	ic50	5.0000	uM
N-[[3-[(3-nitrobenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	5.0000	uM
N-[[3-(naphthalene-2-carbonylamino)phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	5.1000	uM
N-[[3-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	5.4000	uM
[3-[[2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[2-(4-hydroxy-3-nitrophenyl)acetyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]acetyl]amino]-2-oxopropyl] anthracene-9-carboxylate	1799555: Fluorogenic Assay from Article 10.1016/j.chembiol.2011.05.008: “Development of small molecule inhibitors and probes of human SUMO deconjugating proteases.”	ic50	5.7000	uM
3-phenylmethoxy-N-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	5.9000	uM
N-[[3-[(4-nitrobenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	5.9000	uM
2-(4-chloro-3-methylphenoxy)-N-[4-(4-ethoxy-3-methylphenyl)-1,2,5-oxadiazol-3-yl]acetamide	1741432: Inhibition of SNEP2 (unknown origin) using CyPet-pre-SUMO-1-YPet as substrate incubated for 1 hr by FRET assay	ic50	5.9000	uM
N-[[3-[(4-bromobenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	6.2000	uM
2-(4-chloro-3-methylphenoxy)-N-[4-(3-methyl-4-propan-2-yloxyphenyl)-1,2,5-oxadiazol-3-yl]acetamide	1926193: Inhibition of SENP2 (unknown origin)	ic50	6.3000	uM
N-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	6.4000	uM
N-[[3-[(3-methoxybenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	6.7000	uM
2-(4-chloro-3-methylphenoxy)-N-[4-(3,4-dimethylphenyl)-1,2,5-oxadiazol-3-yl]acetamide	1926193: Inhibition of SENP2 (unknown origin)	ic50	6.8000	uM
N-[[3-(butanoylamino)phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	6.9000	uM
5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylic acid	1859339: Inhibition of human SENP2 using AMC-tagged SUMO1 as substrate incubated for 10 mins by fluorescence based analysis	ic50	6.9000	uM
3-[[4-[[[(2S,3S)-3-[bis(naphthalen-1-ylmethyl)carbamoyl]oxirane-2-carbonyl]-(carboxymethyl)amino]carbamoyl]phenyl]methylcarbamoyl]benzoic acid	1799555: Fluorogenic Assay from Article 10.1016/j.chembiol.2011.05.008: “Development of small molecule inhibitors and probes of human SUMO deconjugating proteases.”	ic50	7.0000	uM
N-[[3-[(2-methoxybenzoyl)amino]phenyl]methyl]-3-phenylmethoxy-1-benzothiophene-2-carboxamide	1741434: Inhibition of recombinant human SNEP2 (365 to 589 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis	ic50	7.4000	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1
Carbamazepine	affects expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2187434	Binding	Inhibition of recombinant human SENP2 catalytic domain assessed as release of fluorescent AMC from SUMO-1-AMC preincubated at 10 to 100 uM for 10 mins before substrate addition by fluorescence assay	Discovery of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives as non-peptidic selective SUMO-sentrin specific protease (SENP)1 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9RF	Ubigene HEK293 SENP2 KO	Transformed cell line	Female
CVCL_TK57	HAP1 SENP2 (-) 1	Cancer cell line	Male
CVCL_TK58	HAP1 SENP2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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