Affinage

SUMO1

Small ubiquitin-related modifier 1 · UniProt P63165

Length
101 aa
Mass
11.6 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUMO1 is a ubiquitin-like post-translational modifier that regulates protein–protein interactions, subcellular localization, transcriptional activity, protein stability, DNA repair, and organelle dynamics across diverse nuclear and cytoplasmic processes. SUMO1 is activated by the SAE1/SAE2 (Aos1/Uba2) E1 heterodimer, transferred to the E2 conjugase Ubc9, and conjugated via an isopeptide bond through its C-terminal glycine to lysine residues in substrates bearing a ΨKxE consensus motif; E3 ligases including RanBP2/Nup358, PIAS proteins, and Topors confer substrate specificity (PMID:9920803, PMID:11792325, PMID:12077349, PMID:16122737). Conjugation directs RanGAP1 to the nuclear envelope and kinetochores, is required for PML nuclear body integrity and transcription factor regulation (repressing Sp3, c-Jun, STAT1, PPARγ; activating p53, HSF1/2, GATA4), protects substrates such as Smad4 and Mdm2 from ubiquitin-dependent degradation, releases TDG from abasic DNA sites via a structurally defined conformational switch, and stabilizes DRP1 at mitochondrial fission sites (PMID:9442102, PMID:10779416, PMID:12419227, PMID:15959518, PMID:14972687, PMID:10892746). SUMO1 haploinsufficiency in humans is linked to cleft lip and palate, and Sumo1-null mice are viable with compensation by SUMO2/3 but show impaired RanGAP1 localization and PML nuclear body formation (PMID:16990542, PMID:19033381).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 High

    Determining that SUMO1 adopts a ubiquitin-like fold yet possesses a unique flexible N-terminal extension and lacks Lys48 explained why SUMO1 does not form ubiquitin-like polymeric chains and established it as a structurally distinct modifier.

    Evidence NMR structure determination of free SUMO-1

    PMID:9654451

    Open questions at the time
    • Functional role of the N-terminal extension was not defined
    • Whether SUMO1 forms its own chains via other lysines was unresolved
  2. 1998 High

    Mapping the isopeptide bond between SUMO1 Gly97 and RanGAP1 Lys526 and showing this modification directs RanGAP1 to the nuclear envelope established the first substrate and the principle that sumoylation controls subcellular localization.

    Evidence Peptide mapping, mass spectrometry, site-directed mutagenesis, and cell fractionation

    PMID:9442102

    Open questions at the time
    • The enzymes catalyzing conjugation were not yet identified
    • How sumoylation mediates nuclear envelope targeting was unknown
  3. 1999 High

    Reconstituting SUMO1 conjugation with only the E1 heterodimer (Aos1/Uba2) and the E2 Ubc9 defined the minimal enzymatic cascade and distinguished it from ubiquitination's obligate three-enzyme requirement.

    Evidence In vitro reconstitution with recombinant E1 and E2 enzymes using RanGAP1 as substrate

    PMID:9920803

    Open questions at the time
    • Whether E3 ligases exist for SUMO1 was unknown
    • Regulation of the E1–E2 cascade was not addressed
  4. 1999 High

    Identification of a SUMO1-specific cysteine protease that cleaves both the precursor and conjugated forms established that sumoylation is reversible and introduced the deconjugation arm of the pathway.

    Evidence Biochemical purification from bovine brain with in vitro hydrolase assays and inhibitor profiling

    PMID:10531301

    Open questions at the time
    • Molecular identity (gene) of the protease was not determined
    • Substrate selectivity among SUMO proteases was unknown
  5. 1999 High

    Showing that p53 is sumoylated at Lys386 and that this enhances transactivation revealed SUMO1 as a direct regulator of transcription factor activity, extending the pathway beyond localization control.

    Evidence In vitro sumoylation, site-directed mutagenesis, and reporter gene assay

    PMID:10562558

    Open questions at the time
    • The E3 ligase mediating p53 sumoylation was unknown
    • Whether sumoylation affects p53 stability or DNA binding was not resolved
  6. 2000 High

    Demonstrating that SUMO1 modification of PML is essential for nuclear body formation, and that sumoylation of Sp3 and c-Jun represses transcription while sumoylation of Mdm2 stabilizes it and redirects its E3 ligase activity, established SUMO1 as a broad regulator of nuclear architecture, transcription, and protein stability.

    Evidence PML−/− cell rescue and mutagenesis (PML); SUMO fusion, protease removal, and reporter assays (Sp3); in vitro/in vivo sumoylation with ubiquitination assays (Mdm2, c-Jun)

    PMID:10779416 PMID:10788439 PMID:10892746 PMID:12419227

    Open questions at the time
    • How SUMO1 on PML nucleates NB assembly at the molecular level was unclear
    • Whether SUMO1-mediated Mdm2 stabilization operates under physiological stoichiometry was not confirmed
  7. 2000 High

    Defining the ΨKxE consensus motif and showing that nuclear targeting is required for efficient in vivo sumoylation clarified substrate recognition rules and spatially restricted the modification to the nucleus.

    Evidence Chimeric protein constructs with mutagenesis, comparing in vitro vs. in vivo sumoylation

    PMID:11124955

    Open questions at the time
    • Non-consensus sumoylation sites were not addressed
    • The spatial requirement did not explain cytoplasmic sumoylation events (e.g., RanGAP1 at the NPC)
  8. 2002 High

    Identification of RanBP2/Nup358 and PIAS proteins as SUMO1 E3 ligases with distinct structural mechanisms (RING-finger-independent for RanBP2, RING-like for PIAS) established that E3 ligases enhance and specify sumoylation, and placed SUMO1 conjugation at the nuclear pore complex.

    Evidence In vitro reconstitution with domain mapping (RanBP2); reconstitution with mutagenesis and reporter assays (PIAS family)

    PMID:11792325 PMID:12077349

    Open questions at the time
    • Full structural basis of E3-mediated transfer was not determined
    • Substrate specificity of individual E3s in vivo was unclear
  9. 2002 High

    Showing that SUMO1-conjugated RanGAP1 localizes to mitotic spindles and kinetochores, and that SENP2 is tethered to the nucleoplasmic face of NPCs via Nup153, revealed mitotic and spatially regulated functions of the SUMO1 pathway beyond interphase.

    Evidence Immunofluorescence with sumoylation-deficient RanGAP1 mutants; Co-IP and domain deletion for SENP2-Nup153

    PMID:11854305 PMID:11896061

    Open questions at the time
    • Direct mitotic substrates of the RanBP2/RanGAP1*SUMO1 E3 were not identified
    • How NPC tethering restricts SENP2 substrate access was not mechanistically resolved
  10. 2003 High

    Demonstrating that SUMO1 modification of NEMO enables nuclear-to-cytoplasmic NF-κB signaling upon genotoxic stress, and that sumoylation of Smad4 protects it from ubiquitin-dependent degradation, established SUMO1 as an integrator of stress signaling and a competitive antagonist of ubiquitin on shared substrates.

    Evidence Cell fractionation, mutagenesis, kinase assays (NEMO); pulse-chase, Ubc9 knockdown, and fractionation (Smad4)

    PMID:12813045 PMID:14651848

    Open questions at the time
    • The E3 ligase for NEMO sumoylation was not identified
    • Quantitative competition between SUMO1 and ubiquitin on overlapping lysines was not measured
  11. 2004 Medium

    Finding that SUMO1 localizes to mitochondrial fission sites and stabilizes DRP1 extended the SUMO1 pathway to organelle dynamics beyond the nucleus.

    Evidence Co-IP, YFP-SUMO1 live imaging, mitochondrial fractionation, overexpression phenotype

    PMID:14972687

    Open questions at the time
    • The E3 ligase for DRP1 sumoylation was not identified
    • Whether endogenous SUMO1 levels at mitochondria are sufficient to regulate fission was not established
    • Overexpression approach may not reflect physiological stoichiometry
  12. 2005 High

    The crystal structure of SUMO1-conjugated TDG revealed an allosteric mechanism whereby covalent SUMO1 attachment induces a helical element in TDG that sterically ejects it from abasic DNA, providing the first atomic-resolution view of how sumoylation changes substrate function.

    Evidence X-ray crystallography at 2.1 Å resolution with mutagenesis and DNA-binding assays

    PMID:15959518

    Open questions at the time
    • Whether this allosteric mechanism generalizes to other SUMO1 substrates was unknown
    • In vivo validation of the structural model in base excision repair was limited
  13. 2006 High

    Structural characterization of SUMO-interacting motifs (SIMs) binding SUMO1's β2-strand established non-covalent SUMO recognition as a second axis of SUMO1 signaling, with paralogue specificity tuned by flanking acidic/phosphoserine residues.

    Evidence NMR spectroscopy of SUMO-SIM complexes, yeast two-hybrid, bioinformatics

    PMID:16524884

    Open questions at the time
    • Quantitative contribution of SIM-dependent interactions versus covalent conjugation to downstream signaling was unclear
  14. 2006 Medium

    Linking SUMO1 haploinsufficiency to cleft lip and palate in humans and mice provided the first direct genetic evidence that SUMO1 dosage is critical for craniofacial development.

    Evidence Human translocation mapping, mouse hypomorphic allele, genetic interaction analysis

    PMID:16990542

    Open questions at the time
    • The specific SUMO1 substrates whose reduced modification causes clefting were not identified
    • The phenotype was not independently replicated in a second mouse model at the time
  15. 2008 High

    Demonstrating that Sumo1-null mice are viable with compensation by SUMO2/3 revealed functional redundancy among SUMO paralogues while confirming non-redundant roles in RanGAP1 localization and PML body formation.

    Evidence Sumo1 knockout mouse with immunofluorescence and Western blot

    PMID:19033381

    Open questions at the time
    • Which SUMO1-specific substrates are not compensated by SUMO2/3 was not systematically cataloged
    • Tissue-specific phenotypes under stress were not explored
  16. 2012 High

    Reconstituting the RanBP2/RanGAP1*SUMO1/Ubc9 complex as a composite multisubunit E3 ligase — where RanBP2 catalytic activity requires RanGAP1*SUMO1 — redefined the architecture of sumoylation at the NPC.

    Evidence Full biochemical reconstitution with in vitro sumoylation of Borealin and domain mapping

    PMID:22464730

    Open questions at the time
    • In vivo substrates of the composite E3 beyond Borealin were not identified
    • Structural basis of allosteric activation by RanGAP1*SUMO1 was not resolved
  17. 2016 High

    Showing that the RanBP2/RanGAP1*SUMO1/Ubc9 complex also functions as an autonomous disassembly machine for Crm1-dependent nuclear export complexes integrated SUMO1 conjugation with nucleocytoplasmic transport directly at the pore.

    Evidence In vitro reconstitution of export complex disassembly intermediates with biochemical characterization

    PMID:27160050

    Open questions at the time
    • Whether SUMO E3 ligase activity and export complex disassembly are coupled or independent was not resolved
    • In vivo validation of the disassembly intermediates was limited
  18. 2019 Medium

    SUMO1-mediated sumoylation of Vps34 at K840 facilitates assembly of the Beclin-1–Vps34–Atg14 autophagy initiation complex, connecting SUMO1 to autophagy regulation.

    Evidence In vivo sumoylation, mutagenesis, Co-IP, autophagy flux assay, mouse PAH model

    PMID:30703554

    Open questions at the time
    • The E3 ligase for Vps34 sumoylation was not identified
    • Whether the effect is SUMO1-specific or shared with SUMO2/3 was not tested
  19. 2021 Medium

    Identifying that free SUMO1 protein itself can be targeted for ubiquitin-dependent degradation via the CAPRIN1–FBXO42–CUL1 complex (induced by the small molecule HB007) revealed a mechanism for regulated depletion of the SUMO1 pool.

    Evidence CRISPR-Cas9 knockout screen, pull-down proteomics, biolayer interferometry

    PMID:34644148

    Open questions at the time
    • Whether this degradation pathway operates under physiological conditions without HB007 is unclear
    • Impact on global sumoylation landscape was not fully characterized
  20. 2022 Medium

    Deleting SUMO1 in Huntington's disease knock-in mice reduced mutant huntingtin levels, suppressed nuclear/extracellular inclusions, and enhanced autophagic clearance, establishing SUMO1 as a modifier of aggregate pathology.

    Evidence Sumo1 knockout in HD knock-in mice with proximity ligation assay, autophagy flux analysis, and behavioral testing

    PMID:35086928

    Open questions at the time
    • Whether the beneficial effect is via direct mHtt sumoylation, indirect autophagy enhancement, or both was not distinguished
    • Therapeutic window of SUMO1 reduction versus potential side-effects from loss of other SUMO1 functions was not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full in vivo substrate repertoire that is exclusively SUMO1-dependent (not compensated by SUMO2/3), the structural basis of composite E3 activation, and whether SUMO1 depletion strategies are therapeutically viable remain open questions.
  • Systematic proteomic comparison of SUMO1-only versus SUMO2/3-compensated substrates is lacking
  • Structural model of the complete RanBP2/RanGAP1*SUMO1/Ubc9 E3 complex is not available
  • Tissue-specific consequences of SUMO1 loss under physiological stress are not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0031386 protein tag activity 5 GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 4 GO:0005635 nuclear envelope 4 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2
Partners
PIAS1PMLRANBP2RANGAP1SAE1TDGUBA2UBE2I
Complex memberships
RanBP2/RanGAP1*SUMO1/Ubc9 composite E3 ligase

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SUMO-1 adopts a ubiquitin-like βββαββαβ fold determined by NMR, but has a unique long flexible N-terminal extension absent in ubiquitin, and lacks Lys48 (replaced by Gln69), explaining its inability to form ubiquitin-like polymeric chains. NMR structure determination Journal of molecular biology High 9654451
1998 SUMO-1 is covalently linked to RanGAP1 via an isopeptide bond at Lys526 of RanGAP1 and Gly97 of SUMO-1 (requiring proteolytic removal of the last four residues of SUMO-1); this modification directs RanGAP1 to the nuclear envelope and is required for its role in nuclear protein import. Peptide mapping, mass spectrometry, site-directed mutagenesis, in vitro modification assay, fractionation The Journal of cell biology High 9442102
1999 In vitro SUMO-1 modification of RanGAP1 requires only two enzymatic steps: the E1 heterodimer Sua1/Uba2 (human Aos1/Uba2) and the E2 enzyme Ubc9, distinguishing sumoylation from ubiquitination which typically requires three enzymes. In vitro reconstitution with recombinant E1 and E2 enzymes Biochemical and biophysical research communications High 9920803
1999 p53 is covalently modified by SUMO-1 at Lys386 in vitro and in vivo; this modification increases p53 transactivation activity. In vitro sumoylation assay, site-directed mutagenesis, reporter gene assay The EMBO journal High 10562558
1999 A SUMO-1-specific cysteine protease (30 kDa) was isolated from bovine brain that cleaves SUMO-1 from its precursor and from SUMO-1-RanGAP1 conjugate, but not ubiquitin or NEDD8, and is inhibited by N-ethylmaleimide, indicating it is a cysteine protease. Biochemical purification, in vitro hydrolase assay with radiolabeled substrates, inhibitor profiling The Journal of biological chemistry High 10531301
2000 SUMO-1 conjugation in vivo requires both a consensus PsiKXE modification motif and nuclear targeting of the substrate; the motif alone is sufficient for modification in vitro but not in vivo without a nuclear localization signal. In vitro sumoylation assay, transfection with chimeric proteins, mutagenesis The Journal of biological chemistry High 11124955
2000 SUMO-1-modified PML is required for the formation of PML nuclear bodies; a PML mutant that cannot be SUMO-1 modified fails to recruit NB proteins (Sp100, CBP, ISG20, Daxx, SUMO-1) and displays aberrant nuclear localization. PML-/- primary cell transfection, immunofluorescence, mutagenesis Blood High 10779416
2000 c-Jun is modified by SUMO-1 at Lys229; SUMO-1 modification negatively regulates c-Jun transcriptional activity, and JNK phosphorylation at Ser63/Ser73 decreases SUMO-1 modification of c-Jun. In vitro sumoylation, in vivo modification assay, mutagenesis, reporter gene assay The Journal of biological chemistry High 10788439
2000 SUMO-1 modification of Mdm2 at Lys446 (within the RING finger domain) prevents Mdm2 self-ubiquitination and increases Mdm2 E3 ubiquitin ligase activity toward p53; radiation reduces Mdm2 sumoylation inversely correlating with p53 levels. In vitro sumoylation, in vitro ubiquitination assay, mutagenesis, cell-based assays Cell High 10892746
2000 SUMO-1 conjugation to topoisomerase I (TOP1) is induced by camptothecin in a UBC9-dependent manner; TOP1 physically interacts with UBC9, and UBC9 mutation causes hypersensitivity to camptothecin, implicating SUMO-1 in repair of TOP1-mediated DNA damage. Immunoblot with SUMO-1 antibody, genetic epistasis with UBC9 mutant yeast, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America Medium 10759568
2000 SUMO-1 modification of Sp3 transcription factor represses its transcriptional activity and relocalizes it to the nuclear periphery and nuclear dots; removal of SUMO-1 by mutation or SUMO protease expression converts Sp3 to a strong activator with diffuse nuclear localization. Covalent SUMO-1 fusion to Sp3 is sufficient to repress transcription and relocalize Sp3. Mutagenesis, SUMO protease expression, gene fusion, reporter assay, immunofluorescence Molecular cell High 12419227
2000 SUMO-1 conjugation to Sp100 and PML is specifically abrogated by HSV ICP0 and CMV IE1 viral proteins, correlating with nuclear body disruption; this demonstrates that SUMO-1 conjugation is required for structural integrity of PML nuclear bodies. Immunoblot, immunofluorescence, transfection of viral immediate-early proteins Journal of virology Medium 10233977
2000 SUMO-1 modification of the bovine papillomavirus E1 protein at Lys514 is required for normal intranuclear accumulation and replication capacity; mutations impairing sumoylation prevent nuclear accumulation. Mutagenesis, immunofluorescence, in vitro sumoylation, replication assay The Journal of biological chemistry Medium 11005821
2001 HSF1 undergoes stress-induced SUMO-1 modification at Lys298; this modification promotes conversion of HSF1 to its DNA-binding form, is required for HSF1 localization to nuclear stress granules, and is needed for full stress-induced transcriptional activity. In vitro reconstituted sumoylation, supershift assay, mutagenesis, immunofluorescence, reporter assay The Journal of biological chemistry High 11514557
2001 HSF2 is modified by SUMO-1 at Lys82 (in the DNA-binding domain); SUMO-1 modification directly converts HSF2 to the active DNA-binding form and causes its colocalization with PML bodies. Mutagenesis, EMSA, immunofluorescence The Journal of biological chemistry Medium 11278381
2002 RanBP2/Nup358 nucleoporin acts as a SUMO1 E3 ligase: it directly binds the E2 enzyme Ubc9 and strongly enhances SUMO1 transfer to Sp100 in vitro; the E3 activity resides in a 33 kDa domain lacking RING finger motifs, distinct from PIAS family E3s, placing sumoylation at cytoplasmic NPC filaments. In vitro sumoylation reconstitution, domain mapping, Co-IP Cell High 11792325
2002 PIAS proteins (xalpha, xbeta, 1, 3) function as SUMO-1 E3 ligases: they interact with SUMO-1 and Ubc9, are themselves sumoylated, and enhance Ubc9-mediated sumoylation of androgen receptor and c-Jun in vitro; E3 activity depends on the conserved RING finger-like domain. In vitro sumoylation reconstitution, Co-IP, reporter gene assay, mutagenesis Molecular and cellular biology High 12077349
2002 SUMO-1 modification of HDAC1 at Lys444 and Lys476 is required for HDAC1-mediated transcriptional repression and its effects on cell cycle and apoptosis; mutation of these sites does not affect HDAC1 association with mSin3A. In vitro and in vivo sumoylation, mutagenesis, reporter assay, cell cycle analysis The Journal of biological chemistry Medium 11960997
2002 SUMO-1-conjugated RanGAP1 localizes to mitotic spindles and kinetochores; a sumoylation-deficient RanGAP1 mutant fails to associate with spindles, demonstrating that SUMO-1 conjugation is essential for RanGAP1 mitotic localization. RanBP2 colocalizes with RanGAP1 on spindles, suggesting a complex mediates mitotic targeting. Immunofluorescence, mutagenesis, live cell imaging, fractionation The Journal of cell biology High 11854305
2002 SENP2 (SUMO-1 protease) associates with the nucleoplasmic face of nuclear pores via binding to nucleoporin Nup153 through its N-terminal domain; removal of the Nup153-binding region significantly changes the spectrum of SUMO-1 conjugates, indicating pore association negatively regulates SENP2 activity on a subset of conjugates. Co-IP, localization by immunofluorescence, domain deletion, immunoblot of conjugate profiles The Journal of biological chemistry Medium 11896061
2002 SUMO-1 modification of ARNT at Lys245 (PAS domain) represses its transcriptional activity and modulates its protein-protein interactions; sumoylated ARNT binds AHR but not PML, whereas unmodified ARNT interacts with both. In vitro and in vivo sumoylation, mutagenesis, Co-IP, reporter assay The Journal of biological chemistry Medium 12354770
2003 Genotoxic stress causes nuclear localization of IKK-unbound NEMO via site-specific SUMO-1 attachment; this sumoylation step is ATM-independent but enables subsequent ATM-dependent ubiquitylation of NEMO to activate cytoplasmic IKK and NF-κB. Cell fractionation, immunoprecipitation, mutagenesis, kinase assays Cell High 14651848
2003 PIAS proteins promote SUMO-1 conjugation to STAT1 at Lys703; STAT1 sumoylation negatively regulates IFN-γ-induced transcription and sumoylation-defective STAT1-K703R shows increased transactivation. In vitro sumoylation, mutagenesis, reporter assay, Co-IP Blood Medium 12855578
2003 SUMO-1 overexpression enhances TGF-β-induced transcriptional responses of Smad4; the MH1 domain of Smad4 interacts with Ubc9 and Smad4 is sumoylated at Lys113 and Lys159. Co-IP, in vivo sumoylation, mutagenesis, reporter assay The Journal of biological chemistry Medium 12621041
2003 SUMO-1 modification of Smad4 protects it from ubiquitin-dependent degradation, increasing its stability and nuclear accumulation, thereby enhancing TGF-β-induced growth inhibitory and transcriptional responses. siRNA knockdown of Ubc9, SUMO-1 overexpression, pulse-chase, subcellular fractionation The Journal of biological chemistry Medium 12813045
2003 Phosphorylation at Ser307 of HSF1 stimulates its SUMO-1 modification at Lys298; a conserved C-terminal leucine zipper sequence inhibits SUMO-1 modification, suggesting a conformational regulation mechanism. In vitro phosphorylation and sumoylation assays, mutagenesis, transfection Biochemical and biophysical research communications Medium 12646186
2004 SUMO-1 modifies DRP1 (dynamin-related protein 1); SUMO-1 and Ubc9 are DRP1-interacting proteins, SUMO-1 is found at mitochondrial fission sites, overexpression of SUMO-1 promotes mitochondrial fragmentation by protecting DRP1 from degradation. Co-IP, video microscopy (YFP:Sumo1), immunofluorescence, mitochondrial fractionation Current biology Medium 14972687
2004 PPARγ is sumoylated primarily in the AF-1 domain; PIAS1 and PIASxβ act as E3 ligases for PPARγ sumoylation; SUMO-1 modification represses PPARγ transcriptional activity. In vitro sumoylation, Co-IP, mutagenesis, reporter assay The Journal of biological chemistry Medium 15123625
2004 RanGAP1*SUMO1 is phosphorylated by Cdk1/cyclin B at Thr409, Ser428, and Ser442 at the onset of mitosis; phosphorylated RanGAP1 remains associated with RanBP2/Nup358 and Ubc9, suggesting a link between mitotic phosphorylation and sumoylation activity. In vitro kinase assay, mass spectrometry, immunofluorescence, Co-IP The Journal of cell biology Medium 15037602
2004 GATA4 is sumoylated by SUMO-1 at Lys366; sumoylation enhances GATA4 transcriptional activity and promotes its nuclear localization; PIAS1 acts as E3 ligase via its RING finger domain. In vitro and in vivo sumoylation, mutagenesis, reporter assay, immunofluorescence The Journal of biological chemistry Medium 15337742
2005 Crystal structure of human TDG conjugated to SUMO-1 at 2.1 Å reveals that SUMO-1 attachment induces a helix on TDG that interferes with product DNA, promoting TDG dissociation from the abasic site; both covalent and non-covalent SUMO-1–TDG contacts are required for this release mechanism. X-ray crystallography, mutagenesis, DNA-binding assay Nature High 15959518
2005 Topors acts as a SUMO-1 E3 ligase for p53, enhancing p53 sumoylation in vitro and in vivo independently of its RING finger; Topors-induced p53 sumoylation increases endogenous p53 protein levels in HeLa cells. In vitro sumoylation reconstitution, in vivo sumoylation assay, mutagenesis FEBS letters Medium 16122737
2005 SUMO-1 modification of STAT1 at Lys703 negatively regulates IFN-γ–induced transcription of selective target genes (GBP1, TAP1 but not IRF1); sumoylation-defective STAT1 shows prolonged DNA-binding and nuclear localization. Mutagenesis, reporter assay, chromatin/DNA-binding assay, immunofluorescence Blood Medium 15761017
2006 SUMO-interacting motifs (SIMs) form a β-strand that binds in parallel or antiparallel orientation to the β2-strand of SUMO1 or SUMO2; specificity for distinct SUMO paralogues is determined by flanking acidic residues and/or phosphoserine residues. Yeast two-hybrid, NMR spectroscopy, bioinformatics The Journal of biological chemistry High 16524884
2006 DJ-1 is sumoylated at Lys130 by PIASxα or PIASy; K130 mutation abolishes all major DJ-1 functions (ras-dependent transformation, cell growth promotion, anti-UV apoptosis); PD-associated L166P mutant DJ-1 is improperly sumoylated and becomes insoluble, mislocalizes to mitochondria, and is degraded by the proteasome. In vivo sumoylation, mutagenesis, functional cell assays, immunofluorescence, proteasome inhibition Cell death and differentiation Medium 15976810
2006 SUMO-1 modification of SOD1 at Lys75 increases SOD1 steady-state levels and promotes SOD1 aggregation; SUMO-1 colocalizes with SOD1 aggregates. In vitro and in vivo sumoylation, mutagenesis, aggregation assay, immunofluorescence Biochemical and biophysical research communications Medium 16828461
2006 SUMO-1 poly-chain is assembled on human TOP1 at Lys117 in vitro; a poly-SUMO1 chain appears to form on Ubc9 first and is then transferred en bloc to the substrate. In vitro reconstitution with purified SAE1/2, Ubc9, SUMO1 and TOP1 peptides; mutational analysis The Journal of biological chemistry Medium 16428803
2006 SUMO1 haploinsufficiency in humans disrupts a chromosomal translocation causing cleft lip and palate; in mice, a Sumo1 hypomorphic allele manifests orofacial clefting, and Sumo1 interacts genetically with loci encoding sumoylated clefting-related proteins. Human translocation mapping, mouse hypomorphic allele, genetic interaction analysis Science Medium 16990542
2007 Increased SUMO-1 modification of nuclear PML in rheumatoid arthritis synovial fibroblasts promotes recruitment of DAXX to PML nuclear bodies, conferring resistance to Fas-induced apoptosis; SENP1 reverses this by releasing DAXX from PML NBs. Overexpression, knockdown, immunoprecipitation, immunofluorescence, apoptosis assay Proceedings of the National Academy of Sciences of the United States of America Medium 17360386
2008 SUMO-1 serine-2 (N-terminal arm) is phosphorylated in vivo in human, Drosophila, and yeast cells, representing an evolutionarily conserved modification of the modifier itself; SUMO-3 but not SUMO-2 shares this phosphorylatable residue. High mass accuracy MS/MS, complementary fragmentation techniques on endogenous SUMO-1 Journal of proteome research High 18707152
2008 Loss of SUMO1 in mice (complete knockout) is viable and compensated by SUMO2 and/or SUMO3 for sumoylation of SUMO1 targets; SUMO1 knockout results in altered RanGAP1 localization and impaired PML nuclear body formation. Knockout mouse, immunofluorescence, Western blot Journal of cell science High 19033381
2012 The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a composite multisubunit E3 ligase (not just an E2-E3 complex); complex formation activates a catalytic site in RanBP2 that shows no activity in free RanBP2; cellular RanBP2 is quantitatively associated with RanGAP1. Biochemical reconstitution of the complex, in vitro sumoylation of the substrate Borealin, domain mapping Molecular cell High 22464730
2015 PML IV specifically binds ARF, which stabilizes UBC9 at PML nuclear bodies, enhancing global SUMO-1 conjugation particularly of p53, leading to p53 stabilization, activation, and senescence induction. Co-immunoprecipitation, in vivo sumoylation assay, senescence assay, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America Medium 26578773
2015 Energy stress triggers SUMO1 modification of LKB1 at Lys178, which promotes LKB1 interaction with AMPK via a SUMO-interacting motif (SIM) on AMPK, enabling AMPK activation; LKB1 K178R mutant shows defective AMPK signaling and mitochondrial function. In vivo sumoylation, mutagenesis, Co-IP, AMPK kinase assay, cell viability under energy stress Cell reports Medium 26212320
2016 The RanBP2/RanGAP1*SUMO1/Ubc9 complex functions as an autonomous disassembly machine for Crm1-dependent nuclear export complexes by: (1) binding export complexes via FG-repeat patches, (2) releasing cargo via Ran-binding domains, and (3) retaining free Crm1 after GTP hydrolysis; all intermediates are compatible with SUMO E3 ligase activity. In vitro reconstitution of disassembly intermediates, biochemical characterization Nature communications High 27160050
2019 SUMO1 promotes Vps34 SUMOylation (at K840), which facilitates assembly of the Beclin-1–Vps34–Atg14 complex and induces autophagy; Vps34 K840R mutation reduces SUMOylation and inhibits VSMC dedifferentiation in pulmonary arterial hypertension. In vivo sumoylation, mutagenesis, Co-IP, autophagy flux assay, mouse PAH model Pulmonary pharmacology & therapeutics Medium 30703554
2021 SUMO1 is ubiquitinated and degraded via a CAPRIN1–FBXO42–CUL1 E3 ubiquitin ligase complex when bound by the small-molecule HB007; FBXO42 knockout abrogates HB007 activity, demonstrating this as the mechanism of SUMO1 degradation. CRISPR-Cas9 knockout screen, pull-down proteomics, biolayer interferometry, competitive immunoblot Science translational medicine Medium 34644148
2022 SUMO1 deletion in HD knock-in mice reduces soluble mutant huntingtin levels, suppresses nuclear and extracellular mHtt inclusions, and promotes autophagic flux (increased LC3B-LAMP1 and mHtt-LAMP1 interactions, decreased p62-LAMP1 interactions in MSNs), ameliorating HD-like behavioral and anatomical deficits. SUMO1 knockout mouse, immunofluorescence, proximity ligation assay, autophagy flux analysis, behavioral testing Proceedings of the National Academy of Sciences of the United States of America Medium 35086928

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell 687 11792325
2000 SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. The Journal of biological chemistry 633 11124955
2003 Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell 481 14651848
2000 Role of SUMO-1-modified PML in nuclear body formation. Blood 464 10779416
2006 Specification of SUMO1- and SUMO2-interacting motifs. The Journal of biological chemistry 439 16524884
1999 Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. The EMBO journal 432 10562558
2002 PIAS proteins modulate transcription factors by functioning as SUMO-1 ligases. Molecular and cellular biology 352 12077349
2000 c-Jun and p53 activity is modulated by SUMO-1 modification. The Journal of biological chemistry 344 10788439
1998 Structure determination of the small ubiquitin-related modifier SUMO-1. Journal of molecular biology 326 9654451
2002 SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization. Molecular cell 311 12419227
2004 Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Current biology : CB 306 14972687
1997 Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. The Journal of cell biology 284 9412458
1999 SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation. Journal of cell science 261 9885291
1999 Viral immediate-early proteins abrogate the modification by SUMO-1 of PML and Sp100 proteins, correlating with nuclear body disruption. Journal of virology 258 10233977
1998 Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. The Journal of cell biology 243 9442102
2002 SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles. The Journal of cell biology 238 11854305
2000 SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell 214 10892746
2002 Association of the human SUMO-1 protease SENP2 with the nuclear pore. The Journal of biological chemistry 203 11896061
2001 Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification. The Journal of biological chemistry 202 11514557
2002 SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological activities. The Journal of biological chemistry 197 11960997
2005 Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 187 15959518
1999 In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2. Biochemical and biophysical research communications 187 9920803
2000 SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage. Proceedings of the National Academy of Sciences of the United States of America 176 10759568
2004 Transcriptional activity of peroxisome proliferator-activated receptor gamma is modulated by SUMO-1 modification. The Journal of biological chemistry 161 15123625
2003 SUMO-1/Ubc9 promotes nuclear accumulation and metabolic stability of tumor suppressor Smad4. The Journal of biological chemistry 155 12813045
2002 Ubiquitin-related modifier SUMO1 and nucleocytoplasmic transport. Traffic (Copenhagen, Denmark) 155 12010456
2001 Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor. The Journal of biological chemistry 151 11278381
2006 Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. Cell death and differentiation 148 15976810
2006 SUMO1 haploinsufficiency leads to cleft lip and palate. Science (New York, N.Y.) 146 16990542
2012 The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Molecular cell 144 22464730
2005 Topors acts as a SUMO-1 E3 ligase for p53 in vitro and in vivo. FEBS letters 134 16122737
2003 PIAS proteins promote SUMO-1 conjugation to STAT1. Blood 128 12855578
2008 Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3. Journal of cell science 126 19033381
2000 A new SUMO-1-specific protease, SUSP1, that is highly expressed in reproductive organs. The Journal of biological chemistry 124 10799485
2000 SUMO-1 conjugation to human DNA topoisomerase II isozymes. The Journal of biological chemistry 124 10862613
2003 Activation of transforming growth factor-beta signaling by SUMO-1 modification of tumor suppressor Smad4/DPC4. The Journal of biological chemistry 113 12621041
2002 The nuclear receptor interaction domain of GRIP1 is modulated by covalent attachment of SUMO-1. The Journal of biological chemistry 112 12060666
2007 Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. Proceedings of the National Academy of Sciences of the United States of America 109 17360386
2001 A novel factor required for the SUMO1/Smt3 conjugation of yeast septins. Gene 106 11587849
2003 Sterol regulatory element-binding proteins are negatively regulated through SUMO-1 modification independent of the ubiquitin/26 S proteasome pathway. The Journal of biological chemistry 100 12615929
2001 Regulation of Pax3 transcriptional activity by SUMO-1-modified PML. Oncogene 95 11244500
2002 P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2. FEBS letters 86 12297306
2004 SUMO-1 modification activated GATA4-dependent cardiogenic gene activity. The Journal of biological chemistry 84 15337742
2016 The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes. Nature communications 83 27160050
2007 Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation. Proceedings of the National Academy of Sciences of the United States of America 83 17428914
2002 SUMO-1 and p53. Cell cycle (Georgetown, Tex.) 82 12429940
2018 miR-146a Suppresses SUMO1 Expression and Induces Cardiac Dysfunction in Maladaptive Hypertrophy. Circulation research 81 30355233
2009 Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition. Molecular & cellular proteomics : MCP 80 19596686
2004 Post-translational modification of Rta of Epstein-Barr virus by SUMO-1. The Journal of biological chemistry 80 15229220
2006 SUMO-1 modification increases human SOD1 stability and aggregation. Biochemical and biophysical research communications 79 16828461
2005 SUMO-1 conjugation selectively modulates STAT1-mediated gene responses. Blood 79 15761017
2006 Functional modulation of parkin through physical interaction with SUMO-1. Journal of neuroscience research 78 16955485
2010 Modification of nonstructural protein 1 of influenza A virus by SUMO1. Journal of virology 74 21047957
2011 The chloroplast permease PIC1 regulates plant growth and development by directing homeostasis and transport of iron. Plant physiology 68 21343424
2015 PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence. Proceedings of the National Academy of Sciences of the United States of America 67 26578773
2005 Covalent modification of human immunodeficiency virus type 1 p6 by SUMO-1. Journal of virology 67 15613319
2000 SUMO-1 modification of bovine papillomavirus E1 protein is required for intranuclear accumulation. The Journal of biological chemistry 67 11005821
2014 The role of SUMO-1 in cardiac oxidative stress and hypertrophy. Antioxidants & redox signaling 66 24893265
1999 A new 30-kDa ubiquitin-related SUMO-1 hydrolase from bovine brain. The Journal of biological chemistry 66 10531301
2006 Assembly of a polymeric chain of SUMO1 on human topoisomerase I in vitro. The Journal of biological chemistry 61 16428803
2002 The aryl hydrocarbon receptor nuclear transporter is modulated by the SUMO-1 conjugation system. The Journal of biological chemistry 60 12354770
2010 Small ubiquitin-related modifier (SUMO)-1 promotes glycolysis in hypoxia. The Journal of biological chemistry 58 21123177
2007 Post-translational modification of POU domain transcription factor Oct-4 by SUMO-1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 58 17496161
2012 Chromatin modification by SUMO-1 stimulates the promoters of translation machinery genes. Nucleic acids research 56 22941651
2004 Modification of the erythroid transcription factor GATA-1 by SUMO-1. Proceedings of the National Academy of Sciences of the United States of America 55 15173587
2004 RanGAP1*SUMO1 is phosphorylated at the onset of mitosis and remains associated with RanBP2 upon NPC disassembly. The Journal of cell biology 54 15037602
2002 SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin. Oncogene 47 12439742
2003 Modification of promyelocytic leukemia zinc finger protein (PLZF) by SUMO-1 conjugation regulates its transcriptional repressor activity. The Journal of biological chemistry 44 14527952
2015 A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress. Cell reports 43 26212320
2013 PIASxα ligase enhances SUMO1 modification of PTEN protein as a SUMO E3 ligase. The Journal of biological chemistry 42 24344134
2006 Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. Journal of virology 42 16352559
2020 Resveratrol Attenuates Inflammatory Bowel Disease in Mice by Regulating SUMO1. Biological & pharmaceutical bulletin 41 32115503
2014 Elevated salicylic acid levels conferred by increased expression of ISOCHORISMATE SYNTHASE 1 contribute to hyperaccumulation of SUMO1 conjugates in the Arabidopsis mutant early in short days 4. The Plant journal : for cell and molecular biology 39 24816345
2019 SUMOylation of Vps34 by SUMO1 promotes phenotypic switching of vascular smooth muscle cells by activating autophagy in pulmonary arterial hypertension. Pulmonary pharmacology & therapeutics 37 30703554
2012 SUMO-1 is associated with a subset of lysosomes in glial protein aggregate diseases. Neurotoxicity research 37 23229893
2010 Overexpression of SUMO-1 in hepatocellular carcinoma: a latent target for diagnosis and therapy of hepatoma. Journal of cancer research and clinical oncology 37 20502916
2008 Phosphorylation of SUMO-1 occurs in vivo and is conserved through evolution. Journal of proteome research 37 18707152
2003 Insights into the regulation of heat shock transcription factor 1 SUMO-1 modification. Biochemical and biophysical research communications 37 12646186
2018 Pharmacological inhibition of SUMO-1 with ginkgolic acid alleviates cardiac fibrosis induced by myocardial infarction in mice. Toxicology and applied pharmacology 36 29524504
2015 Increased SUMO-1 expression in response to hypoxia: Interaction with HIF-1α in hypoxic pulmonary hypertension. International journal of molecular medicine 36 25976847
2008 Analysis of SUMO-1 modification of neuronal proteins containing consensus SUMOylation motifs. Neuroscience letters 36 18400391
2017 Analysis of SUMO1-conjugation at synapses. eLife 35 28598330
2013 SUMO-1 modification on K166 of polyQ-expanded ataxin-3 strengthens its stability and increases its cytotoxicity. PloS one 34 23382880
2012 SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish. Development (Cambridge, England) 34 23132242
2011 Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5. PloS one 34 21931855
2019 Ginkgolic Acid, a SUMO-1 Inhibitor, Inhibits the Progression of Oral Squamous Cell Carcinoma by Alleviating SUMOylation of SMAD4. Molecular therapy oncolytics 32 31970286
2022 Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease. Proceedings of the National Academy of Sciences of the United States of America 30 35086928
2020 Protein sumoylation with SUMO1 promoted by Pin1 in glioma stem cells augments glioblastoma malignancy. Neuro-oncology 30 32592588
2014 Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories. Journal of psychiatry & neuroscience : JPN 30 24690371
2009 Adenosine signaling mediates SUMO-1 modification of IkappaBalpha during hypoxia and reoxygenation. The Journal of biological chemistry 30 19297320
2021 A SUMO1-Derived Peptide Targeting SUMO-Interacting Motif Inhibits α-Synuclein Aggregation. Cell chemical biology 29 33444530
2013 Increased SUMO-1 expression in the unilateral rotenone-lesioned mouse model of Parkinson's disease. Neuroscience letters 29 23583339
2010 Sumo1-ylation of human spermatozoa and its relationship with semen quality. International journal of andrology 29 21039605
2023 Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases. Cells 28 38201212
2015 Peptide Inhibitor of Complement C1 (PIC1) Rapidly Inhibits Complement Activation after Intravascular Injection in Rats. PloS one 28 26196285
2005 Comparison of the SUMO1 and ubiquitin conjugation pathways during the inhibition of proteasome activity with evidence of SUMO1 recycling. The Biochemical journal 28 16117725
2013 The chromatin modification by SUMO-2/3 but not SUMO-1 prevents the epigenetic activation of key immune-related genes during Kaposi's sarcoma associated herpesvirus reactivation. BMC genomics 27 24267727
2012 Lamin A/C mutants disturb sumo1 localization and sumoylation in vitro and in vivo. PloS one 27 23029315
2021 Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors. Science translational medicine 25 34644148
2008 Covalent conjugation of Groucho with SUMO-1 modulates its corepressor activity. Biochemical and biophysical research communications 25 19101520