| 2001 |
SUMO-2 and SUMO-3 contain an internal consensus SUMOylation motif (ψKXE), enabling SAE1/SAE2 (E1) and Ubc9 (E2) to catalyze the formation of polymeric SUMO-2 and SUMO-3 chains on protein substrates in vitro; SUMO-2 chains were also detected in vivo. This chain-forming capacity is not shared by SUMO-1. |
In vitro conjugation assay with purified SAE1/SAE2 and Ubc9; in vivo detection of SUMO-2 chains |
The Journal of biological chemistry |
High |
11451954
|
| 2006 |
A SUMO-interacting motif (SIM) was defined that forms a beta-strand binding to the beta2-strand of SUMO2 in parallel or antiparallel orientation; a stretch of acidic/phosphorylated residues flanking the SIM determines specificity for distinct SUMO paralogues including SUMO2 versus SUMO1. |
Yeast two-hybrid, bioinformatics, NMR spectroscopy mapping of binding surfaces |
The Journal of biological chemistry |
High |
16524884
|
| 2004 |
Crystal structure of truncated human SUMO-2 (residues 9–93) determined at 1.2 Å resolution; the fold (βββαββαβ) is identical to ubiquitin and SUMO-1, but a surface region near the C-terminus shows significantly different charge distribution compared to SUMO-1, which may explain distinct intracellular localizations. |
X-ray crystallography (molecular replacement, R3 space group, 1.2 Å resolution) |
European journal of biochemistry |
High |
15479240
|
| 2005 |
PIASy, a PIAS-family SUMO E3 ligase, binds mitotic chromosomes, recruits Ubc9, and is specifically required for SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes in Xenopus egg extracts; PIASy depletion eliminated essentially all chromosomal SUMO-2-conjugated species and blocked anaphase sister chromatid segregation. |
Immunodepletion from Xenopus egg extracts, chromatin binding assays, epistasis with PIASy chromatin-binding mutants |
The EMBO journal |
High |
15933717
|
| 2006 |
SUSP1 (SENP/Ulp family protease) localizes in the nucleoplasm and has strong paralogue bias toward SUMO2/3; it acts preferentially on substrates bearing three or more SUMO2/3 moieties, antagonizing formation of highly conjugated SUMO2/3 species. Depletion of SUSP1 causes redistribution of EGFP-SUMO2/3 into enlarged PML bodies. |
Vinyl sulfone inhibitors, model substrate assays, siRNA depletion with fluorescence microscopy of EGFP-SUMO fusions |
The Journal of cell biology |
High |
17000875
|
| 2008 |
Borealin (chromosomal passenger complex component) is preferentially modified by SUMO2/3 during early mitosis. The SUMO E3 ligase RanBP2 interacts with the CPC and stimulates SUMO2/3 modification of Borealin in vitro and in vivo; the SUMO isopeptidase SENP3 specifically binds Borealin and removes SUMO2/3, delineating a mitotic SUMO2/3 conjugation–deconjugation cycle. |
Co-immunoprecipitation, in vitro SUMOylation assay, siRNA knockdown, cell synchronization |
Molecular biology of the cell |
High |
18946085
|
| 2008 |
BMAL1 is predominantly conjugated to poly-SUMO2/3 (not SUMO1) under physiological circadian conditions; this modification localizes BMAL1 to PML nuclear bodies and promotes both its transactivation and ubiquitin-dependent proteasomal degradation. Mutation of the BMAL1 sumoylation site (K259) blocked ubiquitination and proteolysis; covalent SUMO3 attachment restored these effects. SUSP1 (SUMO2/3-specific protease) abolished both sumoylation and ubiquitination of BMAL1. |
Site-directed mutagenesis, co-immunoprecipitation, immunofluorescence, proteasome inhibitor treatment, SUSP1 overexpression/knockdown |
Molecular and cellular biology |
High |
18644859
|
| 2010 |
Mass spectrometry identified 103 SUMO-2 acceptor lysines in endogenous target proteins: 76 in canonical ψKxE motifs, 8 in an inverted consensus [ED]xK[VILFP], and 16 in a newly defined hydrophobic cluster SUMOylation motif (HCSM). Cross-talk between SUMOylation and phosphorylation was observed with a preferred spacer of four residues. |
Site-specific mass spectrometry proteomics using mutant SUMO-2 with engineered trypsin cleavage site |
Molecular cell |
High |
20797634
|
| 2010 |
SENP3, a SUMO2/3-specific protease, is stabilized by low-dose H2O2 (mild oxidative stress), co-localizes with PML bodies, and removes SUMO2/3 from PML; this de-conjugation is responsible for accelerated cell proliferation. Only SUMOylated PML (not a SUMOylation-deficient mutant) inhibits cell proliferation, demonstrating that SUMO2/3 conjugation of PML suppresses proliferation. |
siRNA knockdown of SENP3, reconstitution with wild-type vs. SUMOylation-mutant PML, cell proliferation assays, co-localization imaging |
The Journal of biological chemistry |
High |
20181954
|
| 2013 |
PIAS1 is an E3 SUMO ligase for both SUMO-1 and SUMO-2 modification of mutant huntingtin (HTT). SUMO-2 modification of HTT regulates accumulation of insoluble HTT in HeLa cells in a manner mimicking proteasome inhibition; this can be modulated by PIAS1 overexpression and acute knockdown. |
Systematic E3 ligase screen, in vitro SUMOylation assays, co-immunoprecipitation, insoluble fraction analysis, PIAS1 knockdown/overexpression |
Cell reports |
Medium |
23871671
|
| 2013 |
Cyclin E is dynamically SUMOylated by SUMO2/3 on chromatin during early S phase in a Xenopus cell-free system, independently of Cdk2 activity and origin activation. Cyclin E is the predominant SUMO2/3 target on chromatin in early S phase; SUMO pathway inhibition increased the density of activated replication origins, indicating SUMO2/3-cyclin E conjugation limits replication origin firing. |
Xenopus cell-free replication system, immunodepletion, chromatin fractionation, SUMO pathway inhibition |
Nature communications |
High |
23673635
|
| 2014 |
Proteome-wide identification using SUMO2(T90K) with engineered Lys-C cleavage site revealed >1000 sumoylated lysines in 539 proteins, enabling systematic study of SUMO2 modification sites involved in cell cycle, transcription, and DNA repair. |
His6-SUMO2(T90K) expression, Lys-C digestion, diGly remnant immunoprecipitation, mass spectrometry |
Science signaling |
High |
24782567
|
| 2014 |
DBC1 (SIRT1 inhibitor) is specifically modified by SUMO2/3, not SUMO1, in response to DNA damage. ATM/ATR-mediated phosphorylation of DBC1 switches its binding from SENP1 to PIAS3, increasing SUMO2/3 conjugation. SUMOylated DBC1 enhances DBC1-SIRT1 interaction, releasing p53 from SIRT1-mediated repression to enable p53-dependent apoptosis. |
Co-immunoprecipitation, siRNA knockdown of PIAS3/SENP1/SUMO2/3, SUMOylation-deficient DBC1 mutant, etoposide treatment, apoptosis assays |
Nature communications |
High |
25406032
|
| 2014 |
SUMO2 is the predominantly expressed SUMO isoform during embryogenesis; Sumo2-null mouse embryos exhibit severe developmental delay and die at ~E10.5, whereas Sumo3-null mice are viable, demonstrating that SUMO2 is essential while SUMO3 is dispensable for embryonic development. |
Gene knockout mouse models (Sumo2-/- and Sumo3-/- null mutants), genetic analysis of compound mutants |
EMBO reports |
High |
24891386
|
| 2015 |
SUMO-2 orchestrates chromatin modifiers in the mammalian DNA damage response (DDR): 20 SUMO-2 conjugates were upregulated and 33 downregulated upon MMS treatment. SUMOylated JARID1B (KDM5B) is ubiquitylated by RNF4 (SUMO-targeted ubiquitin ligase) and degraded by the proteasome; in contrast, JARID1C is recruited to chromatin to demethylate H3K4, demonstrating substrate-specific functional outcomes of SUMO-2 modification in the DDR. |
Quantitative SUMO-2 proteomics (SILAC), siRNA knockdown, chromatin fractionation, ubiquitylation assays |
Cell reports |
High |
25772364
|
| 2015 |
Non-native conformers of CFTR NBD1 are recognized by Hsp27, which collaborates with Ubc9 to selectively conjugate SUMO-2 (not other SUMO paralogs) to NBD1 at K447; this SUMO-2 modification leads to RNF4-dependent ubiquitylation and proteasomal degradation. SUMOylation was greater for F508del NBD1 than wild-type in vitro with purified components, and was reduced by stabilizing mutations. |
In vitro SUMOylation with purified components, site-directed mutagenesis (K447R), Hsp27 co-immunoprecipitation, intrinsic fluorescence, proteasome assays |
The Journal of biological chemistry |
High |
26627832
|
| 2016 |
ZNF451 isoform 1 (ZNF451-1) functions as a SUMO2/3-specific E3 ligase for PML and selected PML body components in vitro; in vivo, ZNF451-1 RNAi depletion stabilizes PML and increases PML body number, indicating it fine-tunes physiological PML levels cooperatively with RNF4. |
In vitro SUMOylation assays, mutational analysis of E3 ligase mechanism, RNAi depletion, PML body quantification by immunofluorescence |
The international journal of biochemistry & cell biology |
Medium |
27343429
|
| 2018 |
SUMO2/3 conjugation of PCNA (specifically SUMO2, not SUMO1 or SUMO3) is induced on transcribed chromatin by the RNAPII-bound helicase RECQ5; SUMO2-PCNA enriches histone chaperones CAF1 and FACT via their SUMO-interacting motifs, enhances CAF1-dependent histone deposition, increases repressive chromatin marks at common fragile sites, and dislodges RNAPII to resolve transcription-replication conflicts. |
Proteomic analysis of SUMO2-PCNA complexes, SIM-dependent interaction assays, histone deposition assays, ChIP, DSB quantification in RECQ5-deficient cells |
Nature communications |
High |
30006506
|
| 2018 |
Acetylation of SUMO2 at lysine K11 is reversible, with SIRT1 acting as the K11 deacetylase. In a purified in vitro system, K11 acetylation impairs SUMO2/3 chain formation and restricts chain length. Mimicking K11 acetylation in cells alters chain architecture by favoring K5- and K35-linked chains while inhibiting K7 and K21 linkages, demonstrating K11 acetylation as a modulator of SUMO2/3 chain topology. |
In vitro chain formation assay with acetyl-mimic SUMO2, MS-based SUMO proteomics, SIRT1 deacetylase identification, acetyl-mimic K11Q mutant analysis in cells |
EMBO reports |
High |
30201799
|
| 2018 |
Loss of SUMO2/3 (but not SUMO1) results in a spontaneous, potent type I interferon response that is independent of all known IFN-inducing pathways (IRF3 and IRF7 not required), demonstrating that SUMO2 and SUMO3 redundantly and specifically suppress a noncanonical IFN induction mechanism. |
Genetic knockout of SUMO2 and SUMO3, IRF3/IRF7 double-knockout epistasis, IFN response measurement |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29891701
|
| 2018 |
DeSUMOylation of MKK7 by the SUMO2/3-specific protease SENP3 promotes MKK7 binding to JNK, enhancing JNK phosphorylation and downstream TLR4 inflammatory signaling in macrophages. ROS-dependent SENP3 accumulation and MKK7 deSUMOylation occur rapidly after LPS stimulation. SENP3 conditional knockout in myeloid cells compromises TLR4 signaling and protects against septic shock. |
Conditional SENP3 knockout mice, LPS stimulation assays, JNK phosphorylation measurement, co-immunoprecipitation of MKK7-JNK, in vivo septic shock model |
The Journal of biological chemistry |
High |
29352108
|
| 2019 |
SENP6, a poly-SUMO2/3-specific protease, regulates the constitutive centromere-associated network (CCAN) through group de-SUMOylation of >180 interconnected proteins. SENP6 deficiency impairs CENP-T, CENP-W, and CENP-A accumulation at centromeres, causes G2/M accumulation and micronuclei formation. Increased SUMO chains do not lead to proteasomal degradation of CCAN subunits, demonstrating a proteolysis-independent function of SUMO2/3 polymers. |
SENP6 knockdown proteomics, cell cycle analysis, immunofluorescence of centromere proteins, proteasome inhibitor experiments |
Nature communications |
High |
31485003
|
| 2020 |
SENP3-mediated deSUMOylation of IRF8 at K310 (SUMO3 modification) in bone-marrow-derived monocytes promotes osteoclast differentiation by upregulating NFATc1; SENP3 deficiency in BMDMs increases IRF8 SUMO3 modification and suppresses osteoclastogenesis, protecting against ovariectomy-induced bone loss. |
Conditional SENP3 knockout mice (myeloid-specific), co-immunoprecipitation, site-specific mutagenesis (K310), ovariectomy bone loss model |
Cell reports |
High |
32049023
|
| 2020 |
Conditional deletion of SUMO2 predominantly in forebrain neurons causes marked impairments in episodic and fear memory and a significant deficit in hippocampal long-term potentiation maintenance, without constitutive changes in gene expression or neuronal morphology, implicating dynamic SUMO2 conjugation in synaptic plasticity. |
Conditional Sumo2 knockout mice (forebrain neuron-specific), behavioral cognitive tests, electrophysiology (LTP measurement) |
FASEB journal |
High |
32910521
|
| 2021 |
During oxidative stress, TDP-43 is SUMOylated by SUMO2/3 via the E3 ligase PIAS4 and enriches in cytoplasmic stress granules (SGs); pharmacological inhibition of SUMO2/3-ylation or PIAS4 depletion causes irreversible TDP-43 aggregation. RNA binding to TDP-43 antagonizes PIAS4-mediated SUMO2/3-ylation, while RNA dissociation promotes it, indicating SUMO2/3 conjugation stabilizes cytosolic RNA-free TDP-43 against aggregation. |
PIAS4 depletion, pharmacological inhibition, stress granule assembly/disassembly experiments, co-IP, RNA-binding mutant analysis |
Science advances |
High |
39982984
|
| 2016 |
SUMO2 activates Calcineurin-NFAT signaling and cardiomyocyte hypertrophy through a direct interaction between SUMO2 and calcineurin A (CnA) that promotes CnA nuclear localization; this effect is sumoylation-independent, as a sumoylation-deficient SUMO2-ΔGG mutant replicates the Cn-NFAT activation and hypertrophic phenotype both in vitro and in vivo. |
cDNA library screen, NFAT luciferase reporter assay, sumoylation-deficient mutant (ΔGG), AAV9-mediated in vivo cardiac SUMO2 expression, co-immunoprecipitation of SUMO2-CnA |
Scientific reports |
Medium |
27767176
|
| 2014 |
SUMO2 modification of PCNA (via p150 subunit of CAF-1 interaction): the p150 subunit of chromatin assembly factor 1 (CAF-1) interacts directly and preferentially with SUMO2/3 through residues 98-105; p150 depletion causes delocalization of SUMO2/3 from DNA replication foci, and p150 mutants deficient in SUMO2/3 interaction markedly reduce SUMO2/3 at replication foci. |
Co-immunoprecipitation, site-directed mutagenesis of p150 (residues 98-105), siRNA knockdown, immunofluorescence at BrdU/PCNA replication foci |
Biochemical and biophysical research communications |
Medium |
19919826
|
| 2022 |
Crystal structure of the SENP7 catalytic domain bound to SUMO2 reveals that a unique Loop1 insertion in SENP7 makes specific contacts with SUMO2 that are absent in other SENP family members, establishing the structural basis for SENP6/7's SUMO2/3 isoform preference and poly-SUMO2 chain dismantling activity. |
X-ray crystallography of SENP7-SUMO2 complex, structure-function comparison with SENP2-Loop1 chimera |
Journal of molecular biology |
High |
36334780
|
| 2014 |
Crystal structure of SENP2-Loop1 chimera (containing the SENP6/7 Loop1 insertion) in complex with SUMO2 at 2.15 Å shows unique interface contacts exclusive to SENP6/7; the Loop1 chimera displays enhanced proteolytic activity toward diSUMO2 and polySUMO2 substrates, confirming Loop1 as determinant for SUMO2/3 activity and specificity. |
X-ray crystallography of chimeric SENP2-Loop1/SUMO2 complex, in vitro protease activity assays with diSUMO2 and polySUMO2 substrates |
Protein science |
High |
24424631
|
| 2019 |
Crystal structure of SENP1 catalytic domain in noncovalent complex with SUMO2 at 2.62 Å resolution shows that complex formation is driven by polar interactions and limited hydrophobic contacts; the SUMO2 C-terminal QQTGG motif protrudes into the SENP1 catalytic triad, providing the structural basis for SUMO2 maturation and deSUMOylation. |
X-ray crystallography of SENP1-SUMO2 noncovalent complex |
Acta crystallographica. Section F, Structural biology communications |
Medium |
31045562
|
| 2008 |
SMT3IP1 (nucleolar SUMO-specific protease) preferentially removes SUMO-2 from nucleophosmin (NPM) in both nucleolar and cytoplasmic compartments; catalytically inactive SMT3IP1 mutant increases SUMO-2-modified NPM in a dominant-negative manner; SUMO-2 conjugation of cytoplasmic mutant NPM is markedly elevated in an ARF-dependent manner. |
Yeast two-hybrid identification of NPM as SMT3IP1 substrate, dominant-negative catalytic mutant, ARF-dependent SUMOylation analysis |
Biochemical and biophysical research communications |
Medium |
18639523
|
| 2018 |
ATF5 is modified by SUMO2/3 at a conserved consensus site; SUMOylation of ATF5 is elevated in G1 phase and diminished in G2/M phase. SUMO2/3 modification disrupts ATF5 interaction with centrosomal proteins, dislodging ATF5 from the centrosome at end of M phase. Blockade of ATF5 SUMOylation deregulates the centrosome cycle, impedes ATF5 translocation, and causes genomic instability and G2/M arrest. |
Cell cycle synchronization, co-immunoprecipitation with centrosomal proteins, SUMOylation-deficient mutant, genomic instability assays |
The Journal of biological chemistry |
Medium |
29326161
|
| 2019 |
SUMOylation of polyQ-ataxin-7 (polyQ-ATXN7) by SUMO2/3 recruits the SUMO-targeted ubiquitin ligase RNF4; overexpression of RNF4 and/or SUMO2 significantly decreases polyQ-ATXN7 levels and increases its polyubiquitination upon proteasome inhibition, demonstrating a SUMO2-dependent degradation pathway for misfolded ataxin-7. |
Co-immunoprecipitation, immunofluorescence, proximity ligation assay, RNF4/SUMO2 overexpression, SCA7 knockin mouse model analysis |
Disease models & mechanisms |
Medium |
30559154
|
| 2025 |
Ferroptosis induces lactylation of SUMO2 at K11 (SUMO2-K11la); this modification impairs the interaction between SUMO2 and ACSL4, facilitating ACSL4 degradation, disrupting lipid metabolism, and mitigating ferroptosis in lung adenocarcinoma. AARS1 is the lactyltransferase and HDAC1 is the delactylase for SUMO2-K11la. |
SUMOylation proteomics, co-IP assays, metabolomic profiling, identification of AARS1 as lactyltransferase and HDAC1 as delactylase, cell-penetrating peptide inhibitor, xenograft models |
Cell discovery |
Medium |
41057295
|
| 2014 |
SUMO2 interacts with and promotes cap-dependent mRNA translation by enhancing the interaction between eIF4E and eIF4G to form the active eIF4F complex; SUMO2 overexpression partially reverses the effect of 4EGI-1 (eIF4E/eIF4G interaction inhibitor), while SUMO2 knockdown impairs cap-dependent translation and promotes apoptosis. |
Co-immunoprecipitation of eIF4E-eIF4G, SUMO2 overexpression/shRNA knockdown, 4EGI-1 rescue assay, polysome profiling |
PloS one |
Low |
24971752
|
| 2001 |
SMRZ (striated muscle RING zinc finger protein) interacts with SMT3b (SUMO2) through its RING domain; this interaction is abolished by mutagenesis of conserved RING domain residues, and SMRZ localizes to the nucleus in muscle cells. |
Co-immunoprecipitation, RING domain mutagenesis, transient transfection with nuclear localization imaging |
The Journal of biological chemistry |
Low |
11283016
|
| 2012 |
ARHGAP21 (a RhoGAP modulating cell migration via Cdc42 and FAK) is specifically modified by SUMO2/3 at lysine K1443; SUMO2/3-modified ARHGAP21 co-localizes with SUMO2/3 in cytoplasm and membrane compartments, and its SUMOylation may be related to cell proliferation. |
Mass spectrometry identification of modified form, co-immunoprecipitation, in vitro SUMOylation, immunofluorescence |
FEBS letters |
Low |
22922005
|
| 2022 |
γ-actin is SUMOylated by SUMO2 at K68 and K284 in cardiomyocytes; SUMOylation promotes nuclear deposition of γ-actin and DNA damage repair. SUMO2 silencing decreased nuclear γ-actin and exacerbated DNA damage; K68R/K284R double mutant γ-actin failed to protect cardiomyocytes against hypoxia-reoxygenation challenge. |
Strep-SUMO2 affinity purification with MALDI-TOF-MS identification, site-directed mutagenesis (K68R/K284R), in vivo myocardial infarction model, H9c2 hypoxia-reoxygenation model |
International journal of biological sciences |
Medium |
35864967
|