SUMOylation (Homo sapiens)

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4, 6, 7, 12, 13, 173, 285, 14, 15, 19, 20, 22...3, 282, 3, 10, 16, 24...3, 285, 9, 11, 14, 15, 19...5, 9, 11, 14, 15, 19...2, 3, 8, 10, 183, 28UBA2:SAE1[nucleoplasm]SUMO3S-glycyl-cys173UBA2:SAE1[nucleoplasm]SUMO2S-glycyl-cys173UBA2:SAE1[nucleoplasm]UBA2:SAE1[nucleoplasm]SUMO1S-glycyl-cys173UBA2:SAE1[nucleoplasm]UBA2:SAE1[nucleoplasm]SUMO2-C173-UBA2[nucleoplasm]cytosolnucleoplasmSUMO1-C173-UBA2[nucleoplasm]SUMO3-C173-UBA2[nucleoplasm]SUMO2-C93-UBE2IUBA2:SAE1UBA2 [nucleoplasm]SUMO2S-glycyl-cys173UBA2:SAE1SENP1/2/5AMPSAE1 [nucleoplasm]SUMO1S-glycyl-cys173UBA2:SAE1ABCA8 [plasmamembrane]SUMO1(2-101)ATPSUMO2(1-95)ATPSUMO3AMPPPiSAE1 [nucleoplasm]SUMO3-C93-UBE2ISUMO3S-glycyl-cys173UBA2:SAE1PPiABCB5 [plasmamembrane]UniProt:F1SC09UBA2 [nucleoplasm]SAE1 [nucleoplasm]UBE2IABCB1 [plasmamembrane]UniProt:F1SBZ0UBE2IATPSUMO1SAE1 [nucleoplasm]SAE1 [nucleoplasm]SUMO1-C93-UBE2IAMPPPiUBA2 [nucleoplasm]UBA2:SAE1SUMO2UBE2ISAE1 [nucleoplasm]UBA2:SAE1UniProt:Q28963SUMO3(1-103)2727212727272727272727272727727271, 21


Description

Small Ubiquitin-like MOdifiers (SUMOs) are a family of 3 proteins (SUMO1,2,3) that are reversibly conjugated to lysine residues of target proteins via a glycine-lysine isopeptide bond (reviewed in Hay 2013, Hannoun et al. 2010, Gareau and Lima 2010, Wilkinson and Henley 2010, Wang and Dasso 2009). Proteomic methods have yielded estimates of hundreds of target proteins. Targets are mostly located in the nucleus and therefore SUMOylation disproportionately affects gene expression.
SUMOs are initially translated as proproteins possessing extra amino acid residues at the C-terminus which are removed by the SUMO processing endoproteases SENP1,2,5 (Hay 2007). Different SENPs have significantly different efficiencies with different SUMOs. The processing exposes a glycine residue at the C-terminus that is activated by ATP-dependent thiolation at cysteine-173 of UBA2 in a complex with SAE1, the E1 complex. The SUMO is transferred from E1 to cysteine-93 of a single E2 enzyme, UBC9 (UBE2I). UBC9 with or, in some cases, without an E3 ligase conjugates the glycine C-terminus of SUMO to an epsilon amino group of a lysine residue on the target protein. SUMO2 and SUMO3 may then be further polymerized, forming chains. SUMO1 is unable to form polymers.
Conjugated SUMO can act as a biinding site for proteins possessing SUMO interaction motifs (SIMs) and can also directly affect the formation of complexes between the target protein and other proteins.
Conjugated SUMOs are removed by cleavage of the isopeptide bond by processing enzymes SENP1,2,3,5. The processing enzymes SENP6 and SENP7 edit chains of SUMO2 and SUMO3.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2990846

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Bibliography

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  8. Wilkinson KA, Henley JM.; ''Mechanisms, regulation and consequences of protein SUMOylation.''; PubMed Europe PMC Scholia
  9. Desterro JM, Rodriguez MS, Kemp GD, Hay RT.; ''Identification of the enzyme required for activation of the small ubiquitin-like protein SUMO-1.''; PubMed Europe PMC Scholia
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  21. Tatham MH, Matic I, Mann M, Hay RT.; ''Comparative proteomic analysis identifies a role for SUMO in protein quality control.''; PubMed Europe PMC Scholia
  22. Gong L, Millas S, Maul GG, Yeh ET.; ''Differential regulation of sentrinized proteins by a novel sentrin-specific protease.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
114754view16:24, 25 January 2021ReactomeTeamReactome version 75
113198view11:26, 2 November 2020ReactomeTeamReactome version 74
112423view15:36, 9 October 2020ReactomeTeamReactome version 73
101327view11:21, 1 November 2018ReactomeTeamreactome version 66
100865view20:54, 31 October 2018ReactomeTeamreactome version 65
100406view19:28, 31 October 2018ReactomeTeamreactome version 64
99954view16:12, 31 October 2018ReactomeTeamreactome version 63
99510view14:45, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99154view12:41, 31 October 2018ReactomeTeamreactome version 62
94055view13:54, 16 August 2017ReactomeTeamreactome version 61
93683view11:31, 9 August 2017ReactomeTeamreactome version 61
88416view11:53, 5 August 2016FehrhartOntology Term : 'sumoylation pathway' added !
86807view09:26, 11 July 2016ReactomeTeamreactome version 56
83213view10:24, 18 November 2015ReactomeTeamVersion54
81603view13:08, 21 August 2015ReactomeTeamVersion53
77059view08:36, 17 July 2014ReactomeTeamFixed remaining interactions
76764view12:12, 16 July 2014ReactomeTeamFixed remaining interactions
76088view10:15, 11 June 2014ReactomeTeamRe-fixing comment source
75799view11:33, 10 June 2014ReactomeTeamReactome 48 Update
75150view14:09, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74797view08:53, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ABCA8 [plasma membrane]ProteinI3L9I3 (Uniprot-TrEMBL)
ABCB1 [plasma membrane]ProteinI3L6P9 (Uniprot-TrEMBL)
ABCB5 [plasma membrane]ProteinF1SC09 (Uniprot-TrEMBL)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
PPiMetaboliteCHEBI:29888 (ChEBI)
SAE1 [nucleoplasm]ProteinQ9UBE0 (Uniprot-TrEMBL)
SENP1/2/5ProteinREACT_164483 (Reactome)
SUMO1

S-glycyl-cys173

UBA2:SAE1		ComplexREACT_164060 (Reactome)
SUMO1(2-101)ProteinP63165 (Uniprot-TrEMBL)
SUMO1-C93-UBE2IProteinP63279 (Uniprot-TrEMBL)
SUMO1ProteinP63165 (Uniprot-TrEMBL)
SUMO2

S-glycyl-cys173

UBA2:SAE1		ComplexREACT_164814 (Reactome)
SUMO2(1-95)ProteinP61956 (Uniprot-TrEMBL)
SUMO2-C93-UBE2IProteinP63279 (Uniprot-TrEMBL)
SUMO2ProteinP61956 (Uniprot-TrEMBL)
SUMO3

S-glycyl-cys173

UBA2:SAE1		ComplexREACT_165336 (Reactome)
SUMO3(1-103)ProteinP55854 (Uniprot-TrEMBL)
SUMO3-C93-UBE2IProteinP63279 (Uniprot-TrEMBL)
SUMO3ProteinP55854 (Uniprot-TrEMBL)
UBA2 [nucleoplasm]ProteinQ9UBT2 (Uniprot-TrEMBL)
UBA2:SAE1ComplexREACT_165291 (Reactome)
UBE2IProteinP63279 (Uniprot-TrEMBL)
UniProt:F1SBZ0Protein3730618 (Reactome)
UniProt:F1SC09Protein3730627 (Reactome)
UniProt:Q28963Protein3730623 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AMPArrowREACT_163792 (Reactome)
AMPArrowREACT_163917 (Reactome)
AMPArrowREACT_163921 (Reactome)
ATPREACT_163792 (Reactome)
ATPREACT_163917 (Reactome)
ATPREACT_163921 (Reactome)
PPiArrowREACT_163792 (Reactome)
PPiArrowREACT_163917 (Reactome)
PPiArrowREACT_163921 (Reactome)
REACT_163643 (Reactome) SUMO3 is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (Tatham et al. 2001, Werner et al. 2009).
REACT_163750 (Reactome) The SUMO1 precursor has 4 extra residues at the C-terminus which can be removed endoproteolytically by either SENP1, SENP2, or SENP5 (Zheng and Au, 2005, Mikolajczyk et al. 2007). The order of processing activity is: SENP1 greater than SENP2 greater than SENP5 (Mikolajczyk et al. 2007). Both SENP1 and SENP2 shuttle between the nucleus and cytoplasmic and both are predominantly nucleoplasmic (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006).
REACT_163792 (Reactome) The UBA2:SAE1 complex catalyzes the formation of a thioester bond between SUMO2 and cysteine-173 of UBA2 (Tatham et al. 2001, Werner et al. 2009). ATP reacts with the C-terminal glycine residue of SUMO2 to yield pyrophosphate and a transient intermediate, SUMO2 adenylate, which then reacts with the thiol group of the cysteine residue on UBA2.
REACT_163816 (Reactome) SUMO2 is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (Tatham et al. 2001, Werner et al. 2009).
REACT_163917 (Reactome) The UBA2:SAE1 complex catalyzes the formation of a thioester bond between SUMO3 and cysteine-173 of UBA2 (Tatham et al. 2001, Werner et al. 2009). ATP reacts with the C-terminal glycine residue of SUMO3 to yield pyrophosphate and a transient intermediate, SUMO3 adenylate, which then reacts with the thiol group of the cysteine residue on UBA2.
REACT_163921 (Reactome) The UBA2:SAE1 complex catalyzes the formation of a thioester bond between SUMO1 and cysteine-173 of UBA2 (Desterro et al. 1999, Okuma et al. 1999, Werner et al. 2009, Olsen et al. 2010, Wang and Chen 2010). ATP reacts with the C-terminal glycine residue of SUMO1 to yield pyrophosphate and a transient intermediate, SUMO1 adenylate, which then reacts with the thiol group of the cysteine residue on UBA2.
REACT_163937 (Reactome) The SUMO2 precursor has 2 extra residues at the C-terminus which can be removed endoproteolytically by SENP1, SENP2, or SENP5 (Zheng and Au, 2005, Gong and Yeh 2006, Mikolajczyk et al. 2007). The order of processing activity is: SENP1 greater than SENP2 greater than SENP5 (Mikolajczyk et al. 2007). SENP2 and SENP5 have highest activity on SUMO2, however the processing activity of SENP1 is higher overall (Mikolajczyk et al. 2007). SENP1 and SENP2 shuttle between the nucleus and cytosol and are predominantly nuclear (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006). SENP5 is located in the nucleolus (Di Bacco et al. 2006, Gong and Yeh 2006).
REACT_163945 (Reactome) The SUMO3 precursor has 11 extra residues at the C-terminus which can be removed endoproteolytically by SENP1, SENP2, or SENP5 (Zheng and Au, 2005, Gong and Yeh 2006, Mikolajczyk et al. 2007). The order of processing activity is: SENP1 greater than SENP2 greater than SENP5 (Mikolajczyk et al. 2007). Overall, processing of SUMO3 is the lowest of any SUMO (Mikolajczyk et al. 2007). SENP1 and SENP2 shuttle between the nucleus and cytosol and are predominantly nuclear (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006). SENP5 is located in the nucleolus (Di Bacco et al. 2006, Gong and Yeh 2006).
REACT_163963 (Reactome) SUMO1 is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (Desterro et al. 1999, Okuma et al. 1999, Tatham et al. 2003, Lois and Lima 2005, Wang et al. 2007, Werner et al. 2009). The UbL domain of E1 recruits E2 into proximity for the transfer of SUMO (Lois and Lima 2005, Wang et al. 2009),
SENP1/2/5mim-catalysisREACT_163750 (Reactome)
SENP1/2/5mim-catalysisREACT_163937 (Reactome)
SENP1/2/5mim-catalysisREACT_163945 (Reactome)
SUMO1

S-glycyl-cys173

UBA2:SAE1		ArrowREACT_163921 (Reactome)
SUMO1

S-glycyl-cys173

UBA2:SAE1		REACT_163963 (Reactome)
SUMO1(2-101)REACT_163750 (Reactome)
SUMO1-C93-UBE2IArrowREACT_163963 (Reactome)
SUMO1ArrowREACT_163750 (Reactome)
SUMO1REACT_163921 (Reactome)
SUMO2

S-glycyl-cys173

UBA2:SAE1		ArrowREACT_163792 (Reactome)
SUMO2

S-glycyl-cys173

UBA2:SAE1		REACT_163816 (Reactome)
SUMO2(1-95)REACT_163937 (Reactome)
SUMO2-C93-UBE2IArrowREACT_163816 (Reactome)
SUMO2ArrowREACT_163937 (Reactome)
SUMO2REACT_163792 (Reactome)
SUMO3

S-glycyl-cys173

UBA2:SAE1		ArrowREACT_163917 (Reactome)
SUMO3

S-glycyl-cys173

UBA2:SAE1		REACT_163643 (Reactome)
SUMO3(1-103)REACT_163945 (Reactome)
SUMO3-C93-UBE2IArrowREACT_163643 (Reactome)
SUMO3ArrowREACT_163945 (Reactome)
SUMO3REACT_163917 (Reactome)
UBA2:SAE1ArrowREACT_163643 (Reactome)
UBA2:SAE1ArrowREACT_163816 (Reactome)
UBA2:SAE1ArrowREACT_163963 (Reactome)
UBA2:SAE1REACT_163792 (Reactome)
UBA2:SAE1REACT_163917 (Reactome)
UBA2:SAE1REACT_163921 (Reactome)
UBA2:SAE1mim-catalysisREACT_163643 (Reactome)
UBA2:SAE1mim-catalysisREACT_163792 (Reactome)
UBA2:SAE1mim-catalysisREACT_163816 (Reactome)
UBA2:SAE1mim-catalysisREACT_163917 (Reactome)
UBA2:SAE1mim-catalysisREACT_163921 (Reactome)
UBA2:SAE1mim-catalysisREACT_163963 (Reactome)
UBE2IREACT_163643 (Reactome)
UBE2IREACT_163816 (Reactome)
UBE2IREACT_163963 (Reactome)
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