Affinage

SUMO2

Small ubiquitin-related modifier 2 · UniProt P61956

Length
95 aa
Mass
10.9 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUMO2 is a ubiquitin-like post-translational modifier that forms polymeric chains on protein substrates through its internal ψKXE motif, catalyzed by SAE1/SAE2 (E1), Ubc9 (E2), and paralog-selective E3 ligases including PIASy, RanBP2, ZNF451-1, PIAS4, and PIAS1, with chain disassembly mediated by SUMO2/3-specific proteases SENP3, SENP6, and SENP7 whose isoform selectivity is structurally encoded by their Loop1 insertions (PMID:11451954, PMID:15933717, PMID:24424631, PMID:36334780). Poly-SUMO2 chains serve as signals recognized by the SUMO-targeted ubiquitin ligase RNF4 to couple sumoylation to ubiquitin-dependent proteasomal degradation of substrates such as BMAL1, KDM5B, and misfolded CFTR, while proteolysis-independent SUMO2 polymer signaling regulates centromere assembly (via CCAN subunits), replication origin firing (via cyclin E), transcription–replication conflict resolution (via PCNA-recruited histone chaperones CAF1 and FACT), and innate immune homeostasis by suppressing a noncanonical type I interferon response (PMID:25772364, PMID:26627832, PMID:31485003, PMID:23673635, PMID:30006506, PMID:29891701). SUMO2 chain architecture is further regulated by acetylation at K11, which redirects linkage specificity, and by crosstalk with phosphorylation on substrates (PMID:30201799, PMID:20797634). Sumo2 is essential for mouse embryonic development and, in the adult brain, is required at synapses for hippocampal long-term potentiation and memory formation (PMID:24891386, PMID:32910521).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Established that SUMO-2, unlike SUMO-1, contains an internal ψKXE motif enabling polymeric chain formation via SAE1/SAE2 and Ubc9, revealing a fundamentally different signaling capacity for this paralog.

    Evidence In vitro reconstitution with purified E1/E2 plus in vivo detection of endogenous SUMO-2 chains

    PMID:11451954

    Open questions at the time
    • Chain linkage specificity (which lysines are used) not determined
    • Biological function of poly-SUMO2 chains unknown
    • No E3 ligase involvement assessed
  2. 2004 High

    High-resolution crystal structure of SUMO-2 revealed the ubiquitin-like βbαββαβ fold and a distinct C-terminal surface charge distribution that distinguishes it from SUMO-1, providing a structural basis for paralog-specific interactions.

    Evidence X-ray crystallography at 1.2 Å resolution

    PMID:15479240

    Open questions at the time
    • No structure of SUMO-2 in complex with binding partners
    • Functional significance of surface charge differences not tested
  3. 2004 High

    Proteomic identification of endogenous SUMO-2 conjugates and demonstration of their predominantly nuclear localization established the first substrate landscape for SUMO-2 in human cells.

    Evidence His6-SUMO-2 affinity purification from HeLa nuclear fractions with MS identification and immunoblot validation

    PMID:15175327

    Open questions at the time
    • Modification sites on substrates not mapped
    • Functional consequences for individual substrates unknown
  4. 2005 High

    Discovery that PIASy functions as a SUMO-2-specific E3 ligase on mitotic chromosomes, required for Topoisomerase-II SUMOylation and sister chromatid segregation, established the first biological role for targeted SUMO-2 conjugation in cell division.

    Evidence Xenopus egg extract depletion/reconstitution with PIASy mutants and chromosome segregation assays

    PMID:15933717

    Open questions at the time
    • How PIASy achieves SUMO-2 specificity not structurally resolved
    • Whether other mitotic E3 ligases contribute unknown
  5. 2006 High

    NMR-based mapping of the SUMO-interacting motif (SIM) binding surface on SUMO-2 showed that SIMs dock as β-strands along β2, with paralog specificity conferred by flanking acidic or phosphorylated residues, providing the molecular basis for SUMO-2-selective protein recognition.

    Evidence NMR spectroscopy, yeast two-hybrid, and bioinformatic analysis

    PMID:16524884

    Open questions at the time
    • SIM-SUMO2 interactions not yet validated for most endogenous targets
    • Contribution of phosphorylation-dependent SIM switching in vivo unclear
  6. 2006 High

    Quantitative SILAC proteomics demonstrated that SUMO-1 and SUMO-2 modify substantially non-overlapping substrate sets, and identification of SUSP1/SENP8 as a SUMO-2/3-preferring protease established that both conjugation and deconjugation are paralog-selective.

    Evidence SILAC-labeled HeLa cells with His6-SUMO isoforms; vinyl sulfone inhibitor profiling and RNAi for SUSP1

    PMID:17000644 PMID:17000875

    Open questions at the time
    • Determinants of substrate selectivity between SUMO-1 and SUMO-2 not resolved
    • Full catalog of SUMO-2-specific proteases incomplete
  7. 2008 High

    Studies on BMAL1 and Borealin revealed that poly-SUMO2/3 modification serves as a signal for ubiquitin-dependent proteasomal degradation and that the conjugation–deconjugation cycle (RanBP2/SENP3) is dynamically regulated during the cell cycle, linking SUMO-2 to both circadian and mitotic regulatory circuits.

    Evidence Mutagenesis of BMAL1 K259, SUMO protease manipulation, proteasome inhibition; in vitro RanBP2-mediated Borealin SUMOylation with SENP3 Co-IP and cell synchronization

    PMID:18644859 PMID:18946085

    Open questions at the time
    • Identity of the ubiquitin ligase coupling SUMO2-BMAL1 to ubiquitination not determined at this point
    • Stoichiometry and kinetics of mitotic SUMO2/3 cycling not measured
  8. 2010 High

    Proteome-scale mapping of SUMO-2 acceptor lysines revealed canonical ψKXE, inverted, and hydrophobic-cluster motifs, and identified crosstalk with phosphorylation via a conserved spacer, establishing the modification site grammar at systems level.

    Evidence Site-specific mass spectrometry identifying 103 SUMO-2 sites across endogenous proteins

    PMID:20797634

    Open questions at the time
    • Functional consequences of non-canonical motif usage not tested
    • Kinase-SUMOylation crosstalk validated for only a few substrates
  9. 2013 High

    SUMO-2 modification of cyclin E on chromatin during early S phase was shown to limit replication origin firing independently of Cdk2, and PIAS1 was identified as an E3 for SUMO-2 conjugation of huntingtin promoting its insoluble accumulation, expanding the functional scope to DNA replication control and neurodegeneration-linked proteostasis.

    Evidence Xenopus cell-free system with cyclin E depletion/reconstitution; systematic E3 screen with HTT mutagenesis and Drosophila model

    PMID:23673635 PMID:23871671

    Open questions at the time
    • Mechanism by which SUMO2-cyclin E limits origin firing not defined
    • Whether SUMO2-HTT aggregation is protective or pathogenic in mammalian neurons unclear
  10. 2014 High

    Three advances converged: (1) proteome-wide site-level cataloging of >1000 SUMO-2 sites; (2) demonstration that SUMO2 is essential for mouse embryogenesis while SUMO3 is dispensable, attributable to expression level; (3) identification of the ATM/ATR→DBC1→SUMO2/3→SIRT1→p53 apoptotic axis under genotoxic stress.

    Evidence His6-SUMO2(T90K)/diGly proteomics; Sumo2/Sumo3 knockout mice; Co-IP with phospho-switch mutagenesis and apoptosis assays

    PMID:24782567 PMID:24891386 PMID:25406032

    Open questions at the time
    • Why SUMO2 expression level exceeds SUMO3 in embryonic tissues not explained
    • Full substrate landscape under DNA damage only partially characterized
  11. 2014 High

    Structural determination of the SENP6 Loop1 insertion in complex with SUMO2 provided the molecular basis for SUMO2/3-selective chain editing, explaining how poly-SUMO2 chain length is controlled by a dedicated protease architecture.

    Evidence Crystal structure at 2.15 Å of chimeric SENP2-Loop1 with SUMO2 plus in vitro activity assays

    PMID:24424631

    Open questions at the time
    • Full-length SENP6 structure with poly-SUMO2 substrate not available
    • In vivo validation of Loop1 specificity determinants not yet performed
  12. 2014 High

    Quantitative SUMO-2 proteomics during DNA damage revealed that RNF4 (STUbL) ubiquitylates SUMOylated chromatin modifiers including KDM5B for proteasomal degradation while recruiting the paralog KDM5C, establishing the SUMO2→RNF4→ubiquitin cascade as a remodeling mechanism for the chromatin damage response.

    Evidence SILAC-based SUMO-2 proteomics after MMS, RNF4 knockdown, ChIP for histone marks

    PMID:25772364

    Open questions at the time
    • Selectivity of RNF4 for specific SUMO2 chain types not resolved
    • How replacement chromatin modifier recruitment is coordinated unclear
  13. 2016 High

    ZNF451-1 was identified as a SUMO2/3-specific E3 ligase for PML, and SUMO2 was shown to activate calcineurin-NFAT signaling independently of its conjugation activity via direct binding to CnA, revealing a conjugation-independent mode of SUMO2 action.

    Evidence In vitro SUMOylation and RNAi for ZNF451-1; Co-IP of SUMO2-CnA with ΔGG mutant and AAV9 cardiac delivery

    PMID:27343429 PMID:27767176

    Open questions at the time
    • Structural basis of conjugation-independent CnA interaction unknown
    • Physiological contexts of conjugation-independent SUMO2 functions poorly cataloged
  14. 2018 High

    Multiple discoveries expanded SUMO2 function to transcription–replication conflict resolution (SUMO2-PCNA recruits CAF1/FACT at fragile sites), chain architecture regulation (K11 acetylation redirects chain linkages), innate immune homeostasis (SUMO2/3 suppress noncanonical type I IFN), and TLR4 inflammatory signaling (SENP3-mediated MKK7 deSUMOylation activates JNK).

    Evidence SUMO2-PCNA interactome with SIM mutants and ChIP; in vitro chain assays with acetyl-mimetic SUMO2; Sumo2/Sumo3 double KO IFN reporter; Senp3 conditional KO macrophages with LPS

    PMID:29352108 PMID:29891701 PMID:30006506 PMID:30201799

    Open questions at the time
    • Acetyltransferase responsible for K11 acetylation not identified
    • Mechanism of noncanonical IFN induction upon loss of SUMO2/3 undefined
    • Whether PCNA SUMO2 modification is Ubc9-only or E3-dependent unknown
  15. 2019 High

    SENP6 was shown to control centromere integrity by editing poly-SUMO2/3 chains on CCAN subunits in a degradation-independent manner, establishing proteolysis-independent SUMO2 polymer signaling as a distinct functional paradigm from the STUbL-dependent pathway.

    Evidence SENP6 knockdown with quantitative SUMO proteomics, centromere assembly assays, cell cycle analysis, and micronuclei scoring

    PMID:31485003

    Open questions at the time
    • How poly-SUMO2 on CCAN disrupts centromere architecture mechanistically not determined
    • Whether SENP6 acts co-translationally or post-assembly unknown
  16. 2020 High

    Conditional forebrain deletion of Sumo2 demonstrated that SUMO2 conjugation is essential for hippocampal LTP maintenance and episodic/fear memory, establishing a non-redundant role in adult neuronal physiology.

    Evidence Forebrain-specific Sumo2 conditional knockout mice with electrophysiology and behavioral testing

    PMID:32910521

    Open questions at the time
    • Key synaptic SUMO2 substrates mediating plasticity not identified
    • Whether SUMO3 compensates partially in these neurons unknown
  17. 2022 High

    Crystal structure of SENP7 with SUMO2 confirmed that Loop1 is the conserved structural determinant of SUMO2/3 selectivity across the SENP6/7 subfamily, and SUMO2 was shown to localize prominently to synapses (not only nuclei) in mouse brain.

    Evidence X-ray crystallography of SENP7-SUMO2 complex; His6-HA-Sumo2 knockin mice with subcellular fractionation and MS

    PMID:36334780 PMID:37009224

    Open questions at the time
    • Synaptic SUMO2 targets and their functional roles remain largely uncharacterized
    • No full-length SENP7 structure in complex with poly-SUMO2 chain

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: which acetyltransferase modifies SUMO2 at K11 in vivo; how poly-SUMO2 chains on CCAN mechanistically disrupt centromere assembly; the identity of synaptic SUMO2 substrates underlying LTP; the mechanism by which loss of SUMO2/3 triggers noncanonical type I interferon; and the full scope of conjugation-independent SUMO2 functions.
  • K11 acetyltransferase identity
  • Structural basis of poly-SUMO2 chain recognition at centromeres vs. STUbL pathway
  • Synaptic SUMO2 substrate identification
  • Mechanism of SUMO2/3-dependent IFN suppression

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0031386 protein tag activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-112316 Neuronal System 2 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2 R-HSA-5357801 Programmed Cell Death 1
Partners
PIASYRNF4SAE1SAE2SENP3SENP6SENP7UBC9

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 SUMO-2 and SUMO-3 contain the internal consensus SUMO modification site (ψKXE), enabling SAE1/SAE2 (E1) and Ubc9 (E2) to catalyze the formation of polymeric SUMO-2 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, in vivo detection of SUMO-2 chains The Journal of biological chemistry High 11451954
2004 Crystal structure of human SUMO-2 (residues 9–93) resolved at 1.2 Å reveals a ubiquitin-like β-barrel flanked by α-helices (βbαββαβ topology) and a surface region near the C-terminus with charge distribution distinct from SUMO-1, potentially explaining their different intracellular localizations. X-ray crystallography (molecular replacement, R/Rfree 0.119/0.185 at 1.2 Å) European journal of biochemistry High 15479240
2004 SUMO-2 conjugates localize predominantly to the nucleus in HeLa cells; proteomic purification of His6-SUMO-2 conjugates identified novel endogenous substrates including SART1 and hnRNP M, both confirmed as genuine SUMO targets. Stable cell line expressing His6-SUMO-2, affinity purification from nuclear fractions, mass spectrometry, immunoblot validation The Journal of biological chemistry High 15175327
2006 SUMO-2 interacts with SIM (SUMO-interacting motif)-containing proteins via a hydrophobic core; the SIM forms a β-strand that binds the β2-strand of SUMO-2 in parallel or antiparallel orientation. Specificity for SUMO-2 versus SUMO-1 is conferred by neighboring acidic residues or phosphorylated serines. Yeast two-hybrid, bioinformatics, NMR spectroscopy, binding surface mapping The Journal of biological chemistry High 16524884
2005 PIASy, acting as an E3-like SUMO ligase on mitotic chromosomes, is specifically required for SUMO-2 modification of Topoisomerase-II and other chromosomal substrates in Xenopus egg extracts. PIASy binds mitotic chromosomes and recruits Ubc9 onto chromatin; its depletion abolishes chromosomal SUMO-2 conjugates and blocks anaphase sister chromatid segregation. Xenopus egg extract depletion, EGFP-SUMO-2 imaging, functional rescue with PIASy mutants, chromosome segregation assay The EMBO journal High 15933717
2006 SUSP1 (SENP/Ulp family protease) preferentially deconjugates SUMO-2/3 over SUMO-1, acting specifically on substrates bearing three or more SUMO-2/3 moieties; SUSP1 depletion causes redistribution of EGFP-SUMO-2 and EGFP-SUMO-3 into enlarged PML bodies. Vinyl sulfone inhibitor profiling, model substrate assays, EGFP-SUMO imaging after RNAi depletion The Journal of cell biology High 17000875
2006 Quantitative proteomics using SILAC-labeled HeLa cells stably expressing His6-SUMO-1 or His6-SUMO-2 identified 53 sumoylated proteins; SUMO-1 and SUMO-2 have distinct and overlapping target sets (25 preferential SUMO-1 targets, 19 preferential SUMO-2 targets, 9 shared), indicating non-redundant functions. Quantitative SILAC proteomics, IMAC enrichment, mass spectrometry, immunoblot confirmation Molecular & cellular proteomics High 17000644
2008 BMAL1 is predominantly conjugated to poly-SUMO2/3 (not SUMO-1) in a circadian manner, peaking at maximum transcriptional activity. SUMO2/3 modification localizes BMAL1 to PML nuclear bodies and promotes both its transactivation and ubiquitin-dependent proteasomal degradation. Mutation of the sumoylation site (K259) inhibits ubiquitination and proteolysis; SUSP1 (SUMO2/3-specific protease) abolishes BMAL1 ubiquitination. Immunoprecipitation, site-directed mutagenesis, SUMO protease overexpression, proteasome inhibitor treatment, luciferase reporter Molecular and cellular biology High 18644859
2008 RanBP2 acts as a SUMO E3 ligase for Borealin (a CPC component), stimulating SUMO2/3 modification in vitro and in vivo. SENP3 directly interacts with Borealin and removes SUMO2/3 from it. This conjugation-deconjugation cycle peaks in early mitosis, defining a mitotic SUMO2/3 regulatory circuit. In vitro SUMOylation assay with RanBP2, Co-IP, RNAi knockdown, cell synchronization, immunoblot Molecular biology of the cell High 18946085
2010 SENP3 deconjugates SUMO2/3 from PML in response to mild oxidative stress (low-dose H2O2); deSUMOylation of PML reduces PML body number and promotes cell proliferation. Only SUMOylated PML (not a SUMOylation-deficient mutant) inhibits cell proliferation, establishing SUMOylation status as a functional determinant. SENP3 knockdown/overexpression, co-localization, immunoprecipitation, mutant reconstitution, proliferation assays The Journal of biological chemistry High 20181954
2010 Proteome-wide mass spectrometry identified 103 SUMO-2 acceptor lysines in endogenous proteins; 76 fit the canonical ψKXE motif, 8 fit an inverted [ED]xK[VILFP] motif, and 16 fit a hydrophobic cluster SUMOylation motif (HCSM). Crosstalk with phosphorylation was observed with a preferred 4-residue spacer between the SUMOylated lysine and the phosphorylated serine. Site-specific mass spectrometry-based proteomics, SUMO-2 acceptor lysine identification Molecular cell High 20797634
2013 SUMO-2 modification of huntingtin (HTT) is mediated by the E3 ligase PIAS1 and regulates accumulation of insoluble HTT; PIAS1 is an E3 ligase for both SUMO-1 and SUMO-2 modification of HTT. SUMO-2 modification promotes insoluble HTT accumulation in a manner mimicking proteasome inhibition. Site-directed mutagenesis defining primary SUMO sites, systematic E3 ligase screen, HeLa cell assays, Drosophila model reduction of dPIAS Cell reports High 23871671
2013 Cyclin E is dynamically SUMOylated by SUMO2/3 on chromatin in early S phase in Xenopus cell-free system; cyclin E is the predominant SUMO2/3 target on chromatin at this stage and its SUMOylation limits replication origin firing independently of Cdk2 activity. Xenopus cell-free system, chromatin fractionation, cyclin E depletion/readdition, quantitative immunoblot Nature communications High 23673635
2014 Proteome-wide identification of SUMO2 modification sites using His6-SUMO2(T90K) expressing cells, Lys-C digestion generating diGly remnants, and anti-diGly immunoprecipitation revealed >1000 sumoylated lysines in 539 proteins, including many involved in cell cycle, transcription, and DNA repair. His6-SUMO2(T90K) expression, Lys-C digestion, diGly immunoprecipitation, mass spectrometry Science signaling High 24782567
2014 SUMO-2 is essential for mouse embryonic development: Sumo2-null embryos exhibit severe developmental delay and die at ~E10.5, whereas Sumo3-null mice are viable, demonstrating that SUMO2 expression level (not functional differences between SUMO2 and SUMO3) is critical for embryogenesis. Sumo2 and Sumo3 knockout mice, embryonic phenotyping, genetic complementation EMBO reports High 24891386
2014 DBC1 modification by SUMO2/3 (not SUMO1) promotes p53-mediated apoptosis under genotoxic stress: ATM/ATR-mediated phosphorylation of DBC1 switches its binding from SENP1 to PIAS3, increasing DBC1 SUMOylation, which enhances DBC1-SIRT1 interaction and releases p53 for transcriptional activation. Co-IP, site-directed mutagenesis, ATM/ATR inhibitors, SENP1/PIAS3 knockdown, apoptosis assays Nature communications High 25406032
2014 Quantitative proteomics identified a dynamic set of SUMO-2 conjugates and 755 SUMO-2 sites in response to the DNA damaging agent MMS; SUMOylated chromatin modifiers including JARID1B/KDM5B are ubiquitylated by the SUMO-targeted ubiquitin ligase RNF4 and degraded by the proteasome, while JARID1C is recruited to chromatin to demethylate H3K4. Quantitative SUMO-2 proteomics (SILAC), MMS treatment, RNF4 knockdown, proteasome inhibition, ChIP Cell reports High 25772364
2015 SUMO-2 (not SUMO-1) selectively modifies the non-native conformation of F508del CFTR NBD1; Hsp27 binds the mutant protein and collaborates with Ubc9 to promote SUMO-2 conjugation at K447, targeting it for degradation via RNF4 and the ubiquitin-proteasome system. In vitro SUMOylation assay with purified components, mutagenesis of K447, Hsp27 co-IP, fluorescence assay of NBD1 conformation, proteasome inhibition The Journal of biological chemistry High 26627832
2016 ZNF451-1 functions as a SUMO2/3-specific E3 ligase for PML and selected PML body components; ZNF451-1 RNAi depletion leads to PML stabilization and increased PML body number; the biochemical mechanism of substrate SUMOylation is identical to that used for SUMO chain formation by ZNF451-1. In vitro SUMOylation assay, mutagenesis, RNAi knockdown, immunofluorescence, PML body quantification The international journal of biochemistry & cell biology High 27343429
2018 SUMO2 conjugation of PCNA (but not SUMO1 or SUMO3), induced on transcribed chromatin by RNAPII-bound helicase RECQ5, recruits histone chaperones CAF1 and FACT via their SUMO-interacting motifs, enhances histone H3.1 deposition at common fragile sites (CFSs), and dislodges RNAPII to resolve transcription-replication conflicts and reduce DSBs. Proteomic analysis of SUMO2-PCNA interactome, SIM-dependent interaction assays, ChIP, Seahorse/DSB assays, RECQ5-deficient cells Nature communications High 30006506
2018 Acetylation of SUMO2 at K11 by an acetyltransferase (reversed by deacetylase SIRT1) impairs SUMO chain formation in vitro and alters chain architecture in cells, favoring K5- and K35-linked chains while inhibiting K7 and K21 linkages; K11 acetyl-mimicking SUMO2 does not affect the STUbL pathway, indicating that non-canonical chains predominate under basal/stress conditions. In vitro SUMO chain formation assay, SIRT1 deacetylase assay, MS-based SUMO proteomics, acetyl-mimetic mutations EMBO reports High 30201799
2018 SUMO2 and SUMO3 (but not SUMO1) redundantly prevent a noncanonical type I interferon response that is independent of IRF3, IRF7, and all known IFN-inducing pathways; loss of sumoylation results in spontaneous IFN production. Sumo2/Sumo3 double knockout cells, IFN reporter assays, genetic epistasis with IRF3/IRF7 knockouts Proceedings of the National Academy of Sciences of the United States of America High 29891701
2019 SENP6 acts as a poly-SUMO2/3 protease that controls the SUMO modification state of the constitutive centromere-associated network (CCAN) proteins; SENP6 depletion causes SUMO chain accumulation on CCAN subunits (CENP-T, CENP-W, etc.) without proteasomal degradation, impairs centromere assembly, causes G2/M accumulation and micronuclei formation, demonstrating proteolysis-independent SUMO polymer signaling. SENP6 knockdown, quantitative SUMO proteomics, centromere assembly assays, cell cycle analysis, micronuclei scoring Nature communications High 31485003
2009 The p150 subunit of chromatin assembly factor 1 (CAF-1) directly and preferentially interacts with SUMO2/3 (via residues 98–105) and is required for delivery of SUMO2/3 to DNA replication foci during S phase; p150 mutants deficient in SUMO2/3 interaction cause major reduction of SUMO2/3 at replication foci. Direct interaction assays, mutant p150 constructs, BrdU/PCNA co-localization, RNAi knockdown, live-cell imaging Biochemical and biophysical research communications Medium 19919826
2014 SENP6 Loop1 insertion is structurally required for SUMO2/3 specificity: a chimeric SENP2 containing SENP6 Loop1 shows increased proteolytic activity toward diSUMO2 and polySUMO2 substrates compared to wild-type SENP2; the crystal structure of SENP2-Loop1 in complex with SUMO2 at 2.15 Å reveals unique contacts at the Loop1-SUMO2 interface. X-ray crystallography (2.15 Å), chimeric protease construction, in vitro activity assays with diSUMO2 and polySUMO2 Protein science High 24424631
2016 SUMO2 activates Calcineurin-NFAT signaling via a direct interaction with CnA (calcineurin A), promoting CnA nuclear localization; this effect does not require SUMO2's conjugation activity (ΔGG mutant replicates effects), revealing a sumoylation-independent mechanism of SUMO2 in cardiac hypertrophy. Cardiac cDNA library screen, NFAT-luciferase reporter, Co-IP (SUMO2-CnA), sumoylation-deficient mutant (ΔGG), AAV9 in vivo cardiac expression Scientific reports Medium 27767176
2018 ATF5 is modified by SUMO2/3 at a conserved consensus site; SUMOylation is elevated in G1 and reduced in G2/M, disrupts ATF5 interaction with centrosomal proteins, and dislodges ATF5 from the centrosome at end of M phase. Blocking ATF5 SUMOylation deregulates the centrosome cycle and causes genomic instability and G2/M arrest. SUMO site mutagenesis, cell cycle synchronization, Co-IP with centrosomal proteins, centrosome cycle assays, genomic instability scoring The Journal of biological chemistry Medium 29326161
2018 SENP3 deconjugates SUMO2/3 from MKK7 in macrophages, promoting MKK7 binding to JNK and subsequent JNK phosphorylation upon LPS stimulation; ROS-dependent SENP3 accumulation after LPS drives this deSUMOylation, potentiating TLR4-mediated inflammatory signaling. Senp3 conditional knockout in myeloid cells, LPS challenge, JNK phosphorylation assays, MKK7 Co-IP, in vivo sepsis model The Journal of biological chemistry High 29352108
2019 SENP3 expression is downregulated during osteoclast differentiation; loss of SENP3 in BMDMs increases SUMO3 modification of IRF8 at K310, upregulating NFATc1 expression and promoting osteoclastogenesis; SENP3-conditional knockout mice show enhanced bone loss after ovariectomy. SENP3 conditional knockout in BMDMs, osteoclast differentiation assays, IRF8 SUMOylation site mutagenesis (K310), Co-IP, in vivo OVX 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, demonstrating that SUMO2 conjugation is critically required for synaptic plasticity and cognitive function. Conditional Sumo2 knockout mice, behavioral testing (episodic, fear memory), LTP electrophysiology, gene expression analysis FASEB journal High 32910521
2021 SUMO2 is modified by PIAS4 (E3 ligase) during oxidative stress on TDP-43 at stress granules; SUMO2/3-ylation of TDP-43 by PIAS4 protects it against irreversible aggregation. RNA binding to TDP-43 antagonizes PIAS4-mediated SUMO2/3-ylation, while RNA dissociation promotes it. PIAS4 depletion, pharmacological inhibition of TDP-43 SUMOylation, stress granule assembly/disassembly assays, RNA binding mutants, Co-IP Science advances High 39982984
2022 Crystal structure of SENP7 catalytic domain in complex with SUMO2 identifies Loop1 of SENP7 as the structural element responsible for SUMO2/3 isoform specificity, making specific contacts with SUMO2 not seen with other SENP family members. X-ray crystallography of SENP7-SUMO2 complex, structural comparison, Loop1 mutagenesis Journal of molecular biology High 36334780
2008 SMT3IP1 (nucleolar SUMO-specific protease) preferentially removes SUMO-2 from nucleophosmin (NPM); NPM was identified as an SMT3IP1 binding partner by yeast two-hybrid, and a catalytically inactive SMT3IP1 mutant increased SUMO-2-modified NPM accumulation in a dominant-negative manner. Yeast two-hybrid, dominant-negative catalytic mutant, Co-IP, immunofluorescence Biochemical and biophysical research communications Medium 18639523
2012 ARHGAP21 (a RhoGAP protein) is specifically modified by SUMO2/3 at K1443, confirmed by in vitro SUMOylation assay and Co-IP; ARHGAP21 co-localizes with SUMO2/3 in cytoplasm and membrane compartments. Co-immunoprecipitation, in vitro SUMOylation assay, immunofluorescence, mass spectrometry identification of modified form FEBS letters Medium 22922005
2014 SUMO-2 promotes formation of the active eIF4F complex by enhancing interaction between eIF4E and eIF4G, stimulating cap-dependent translation of a subset of proteins including cyclin D1 and c-Myc; SUMO-2 overexpression partially rescues the inhibitory effect of the eIF4E/eIF4G interaction disruptor 4EGI-1. Co-IP of eIF4E-eIF4G, SUMO-2 overexpression and knockdown, 4EGI-1 rescue, translation reporter assays PloS one Medium 24971752
2019 Crystal structure of SENP1 in noncovalent complex with SUMO2 at 2.62 Å reveals that complex formation is driven by polar interactions; the SUMO2 C-terminal QQTGG motif protrudes into the SENP1 catalytic triad, providing the structural basis for SUMO maturation and deSUMOylation. X-ray crystallography (2.62 Å, R/Rfree 22.92%/27.66%) Acta crystallographica. Section F, Structural biology communications High 31045562
2011 Mouse SUMO-2 inhibits IL-12 secretion in mature dendritic cells by blocking translocation of the p65 subunit of NFκB into the nucleus; SUMO-2 directly modifies IκBα. Ectopic SUMO-2 expression in DCs, NFκB nuclear translocation assay, IL-12 ELISA, Co-IP of SUMO-2 with IκBα Molecular immunology Medium 21632113
2016 Depletion of SUMO2 by shRNA enhances and accelerates somatic cell reprogramming to iPSCs (both mouse and human), identifying SUMO2 as a barrier to pluripotency acquisition; the SUMO2 pathway acts independently of c-MYC and in parallel with small-molecule reprogramming enhancers. Serial shRNA screen, iPSC formation assays, chimera formation, human iPSC generation Stem cell reports Medium 26947976
2023 In mouse brain, Sumo2 is specifically detected at extranuclear compartments including synapses (distinct from nuclear-predominant Sumo1); immunoprecipitation coupled with MS identified shared and specific neuronal targets of Sumo1 versus Sumo2 in vivo. His6-HA-Sumo2 knockin mice, whole-brain imaging, subcellular fractionation, Co-IP/MS, proximity ligation assays iScience High 37009224

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. The Journal of biological chemistry 694 11451954
2006 Specification of SUMO1- and SUMO2-interacting motifs. The Journal of biological chemistry 439 16524884
2010 Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif. Molecular cell 269 20797634
2006 Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics. Molecular & cellular proteomics : MCP 254 17000644
2007 Genetic analysis of SUMOylation in Arabidopsis: conjugation of SUMO1 and SUMO2 to nuclear proteins is essential. Plant physiology 224 17644626
2004 A proteomic study of SUMO-2 target proteins. The Journal of biological chemistry 183 15175327
2014 Proteome-wide identification of SUMO2 modification sites. Science signaling 175 24782567
2014 SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development. EMBO reports 161 24891386
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