SUMOylation of immune response proteins (Homo sapiens)

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1, 23, 865, 7, 9411, 12cytosolnucleoplasmK298-NFKB2-G97-SUMO1 K90-NFKB2-G97-SUMO1 SUMO1-K277,K309-IKBKG 4SUMO1:NFKB2NFKBIA-G97-SUMO1 SUMO1:C93-UBE2ISUMO1:p-S172-IKBKEIKBKGPIAS4UBE2I-G97-SUMO1 RELA SUMO1-K231-p-S172-IKBKE SUMO1-C93-UBE2I SUMO1-C93-UBE2I K689-NFKB2-G97-SUMO1 UBE2I-G97-SUMO1 SUMO1-K90,K298,K689,K863-NFKB2(1-900) UBE2I-G97-SUMO1 K309-IKBKG-G97-SUMO1 NFKBIASUMO1:C93-UBE2ISUMO3:UBE2ISUMO3-K37,K122,K123-RELA SUMO3-RELA:SUMO3-RELA:DNANFKB2(1-900)2SUMO1:IKBKGUBE2ISUMO1:C93-UBE2IUBE2ISUMO3-C93-UBE2I p-S172-IKBKEUBE2ISUMO1-K21-NFKBIA SUMO1:C93-UBE2IUBE2I-G92-SUMO3 SUMO1-C93-UBE2I SUMO1:NFKBIAp-S172-IKBKE-G97-SUMO1 K277-IKBKG-G97-SUMO1 RELA:RELA:DNAUBE2I-G97-SUMO1 UBE2IK863-NFKB2-G97-SUMO1 DNA UBE2ITOPORSDNA PIAS3SUMO1-C93-UBE2I 4115, 9103, 86


Description

NF-kappaB transcription factors are sequestered in the cytosol due to their association with IkappaB. During activation of NF-kappaB, IKK phosphorylates IkappaB, releasing NF-kappaB for importation into the nucleus. NF-kappaB transcription factors, the NFKBIA component of IkappaB, and subunits of the IKK complex can be SUMOylated (reviewed in Kracklauer and Schmidt 2003, Liu et al. 2013). SUMOylations of IkappaB, NFKBIA, and RELA inhibit NF-kappaB signaling; SUMOylation of NFKB2 is required for proteolytic processing. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 4755510
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

Quality Tags

Ontology Terms

 

Bibliography

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  1. Kracklauer MP, Schmidt C.; ''At the crossroads of SUMO and NF-kappaB.''; PubMed Europe PMC
  2. Liu X, Wang Q, Chen W, Wang C.; ''Dynamic regulation of innate immunity by ubiquitin and ubiquitin-like proteins.''; PubMed Europe PMC
  3. Mabb AM, Wuerzberger-Davis SM, Miyamoto S.; ''PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress.''; PubMed Europe PMC
  4. Renner F, Moreno R, Schmitz ML.; ''SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death.''; PubMed Europe PMC
  5. Rodriguez MS, Dargemont C, Hay RT.; ''SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting.''; PubMed Europe PMC
  6. Vatsyayan J, Qing G, Xiao G, Hu J.; ''SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing.''; PubMed Europe PMC
  7. Liu Q, Li J, Khoury J, Colgan SP, Ibla JC.; ''Adenosine signaling mediates SUMO-1 modification of IkappaBalpha during hypoxia and reoxygenation.''; PubMed Europe PMC
  8. Huang TT, Wuerzberger-Davis SM, Wu ZH, Miyamoto S.; ''Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress.''; PubMed Europe PMC
  9. Desterro JM, Rodriguez MS, Hay RT.; ''SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.''; PubMed Europe PMC
  10. Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMed Europe PMC
  11. Liu Y, Bridges R, Wortham A, Kulesz-Martin M.; ''NF-κB repression by PIAS3 mediated RelA SUMOylation.''; PubMed Europe PMC
  12. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC.; ''Uncovering global SUMOylation signaling networks in a site-specific manner.''; PubMed Europe PMC

History

CompareRevisionActionTimeUserComment
101679view13:56, 1 November 2018DeSlOntology Term : 'immune response pathway' added !
101678view13:56, 1 November 2018DeSlOntology Term : 'sumoylation pathway' added !
101482view11:34, 1 November 2018ReactomeTeamreactome version 66
101193view21:39, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2SUMO1:IKBKGComplexR-HSA-4755492 (Reactome)
4SUMO1:NFKB2ComplexR-HSA-4755455 (Reactome)
DNA R-ALL-29428 (Reactome)
IKBKGProteinQ9Y6K9 (Uniprot-TrEMBL)
K277-IKBKG-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
K298-NFKB2-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
K309-IKBKG-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
K689-NFKB2-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
K863-NFKB2-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
K90-NFKB2-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
NFKB2(1-900)ProteinQ00653 (Uniprot-TrEMBL)
NFKBIA-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
NFKBIAProteinP25963 (Uniprot-TrEMBL)
PIAS3ProteinQ9Y6X2 (Uniprot-TrEMBL)
PIAS4ProteinQ8N2W9 (Uniprot-TrEMBL)
RELA ProteinQ04206 (Uniprot-TrEMBL)
RELA:RELA:DNAComplexR-HSA-4755471 (Reactome)
SUMO1-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO1-K21-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
SUMO1-K231-p-S172-IKBKE ProteinQ14164 (Uniprot-TrEMBL)
SUMO1-K277,K309-IKBKG ProteinQ9Y6K9 (Uniprot-TrEMBL)
SUMO1-K90,K298,K689,K863-NFKB2(1-900) ProteinQ00653 (Uniprot-TrEMBL)
SUMO1:C93-UBE2IComplexR-HSA-2993783 (Reactome)
SUMO1:C93-UBE2IComplexR-HSA-4656922 (Reactome)
SUMO1:NFKBIAComplexR-HSA-4656989 (Reactome)
SUMO1:p-S172-IKBKEComplexR-HSA-4755528 (Reactome)
SUMO3-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO3-K37,K122,K123-RELA ProteinQ04206 (Uniprot-TrEMBL)
SUMO3-RELA:SUMO3-RELA:DNAComplexR-HSA-4755423 (Reactome)
SUMO3:UBE2IComplexR-HSA-2993782 (Reactome)
TOPORSProteinQ9NS56 (Uniprot-TrEMBL)
UBE2I-G92-SUMO3 ProteinP55854 (Uniprot-TrEMBL)
UBE2I-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
UBE2IProteinP63279 (Uniprot-TrEMBL)
p-S172-IKBKE-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
p-S172-IKBKEProteinQ14164 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2SUMO1:IKBKGArrowR-HSA-4755411 (Reactome)
4SUMO1:NFKB2ArrowR-HSA-4755479 (Reactome)
IKBKGR-HSA-4755411 (Reactome)
NFKB2(1-900)R-HSA-4755479 (Reactome)
NFKBIAR-HSA-4656914 (Reactome)
PIAS3mim-catalysisR-HSA-4755536 (Reactome)
PIAS4mim-catalysisR-HSA-4755411 (Reactome)
R-HSA-4656914 (Reactome) NFKBIA (IKBA, IkappaBalpha) is SUMOylated at lysine-21 with SUMO1 (Desterro et al. 1998, Rodriguez et al. 2001, Liu et al. 2009). SUMOylation blocks ubiquitin-mediated proteolysis of NFKBIA and thereby inhibits NF-kappaB dependent transcription and acts as an anti-inflammatory. Adenosine signaling increases SUMOylation of NFKBIA with SUMO1. Nuclear import of NFKBIA is required for SUMOylation.
R-HSA-4755411 (Reactome) PIAS4 SUMOylates IKBKG with SUMO1 at lysine-277 and lysine-309 (Huang et al. 2003, Mabb et al. 2006). SUMOylation occurs in the nucleus when IKBKG is unbound to IKK. The interaction between PIAS4 and IKBKG is increased by genotoxic stress. SUMOylation is independent of ATM.
R-HSA-4755478 (Reactome) TOPORS SUMOylates phosphorylated IKBKE (IKKI, IKKE) with SUMO1 at lysine-231 (Renner et al. 2010). SUMOylation causes IKBKE to localize with PML in the nucleus and is required for IKBKE to trigger phosphorylation of NF-kappaB p65.
R-HSA-4755479 (Reactome) Unprocessed NFKB2 p100 is SUMOylated with SUMO1 at lysine-90, lysine-298, lysine-689, and lysine-863 (Vatsyayan et al. 2008). SUMOylation of p100 is required for phosphorylation of p100 prior to processing to yield p52. Blockage of SUMOylation consequently interferes with import of NFKB2 p52 into the nucleus.
R-HSA-4755536 (Reactome) PIAS3 SUMOylates RELA with SUMO3 at lysine-37, lysine-121, and lysine-122 (Liu et al. 2012, Hendriks et al. 2014). SUMOylation occurs when RELA is bound to NF-kB binding sites on DNA in the nucleus. SUMOylation represses transcriptional activity of RELA and is enhanced by NF-kB activation by TNFalpha.
RELA:RELA:DNAR-HSA-4755536 (Reactome)
SUMO1:C93-UBE2IR-HSA-4656914 (Reactome)
SUMO1:C93-UBE2IR-HSA-4755411 (Reactome)
SUMO1:C93-UBE2IR-HSA-4755478 (Reactome)
SUMO1:C93-UBE2IR-HSA-4755479 (Reactome)
SUMO1:C93-UBE2Imim-catalysisR-HSA-4656914 (Reactome)
SUMO1:C93-UBE2Imim-catalysisR-HSA-4755479 (Reactome)
SUMO1:NFKBIAArrowR-HSA-4656914 (Reactome)
SUMO1:p-S172-IKBKEArrowR-HSA-4755478 (Reactome)
SUMO3-RELA:SUMO3-RELA:DNAArrowR-HSA-4755536 (Reactome)
SUMO3:UBE2IR-HSA-4755536 (Reactome)
TOPORSmim-catalysisR-HSA-4755478 (Reactome)
UBE2IArrowR-HSA-4656914 (Reactome)
UBE2IArrowR-HSA-4755411 (Reactome)
UBE2IArrowR-HSA-4755478 (Reactome)
UBE2IArrowR-HSA-4755479 (Reactome)
UBE2IArrowR-HSA-4755536 (Reactome)
p-S172-IKBKER-HSA-4755478 (Reactome)
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