1y8r

From Proteopedia

(Difference between revisions)

Revision as of 16:50, 20 October 2021

SUMO E1 ACTIVATING ENZYME SAE1-SAE2-SUMO1-MG-ATP COMPLEX

Structural highlights

1y8r is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1y8q
Gene:	UBLE1A, SAE1 (HUMAN), UBLE1B, SAE2 (HUMAN), UBL1, SUMO-1, SMT3C, SMT3H3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SUMO1_HUMAN] Defects in SUMO1 are the cause of non-syndromic orofacial cleft type 10 (OFC10) [MIM:613705]; also called non-syndromic cleft lip with or without cleft palate 10. OFC10 is a birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Note=A chromosomal aberation involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.^[1]

Function

[SAE1_HUMAN] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] [SUMO1_HUMAN] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development.^[9] ^[10] ^[11] ^[12] [SAE2_HUMAN] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.^[13] ^[14] ^[15] ^[16] ^[17] ^[18]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

E1 enzymes facilitate conjugation of ubiquitin and ubiquitin-like proteins through adenylation, thioester transfer within E1, and thioester transfer from E1 to E2 conjugating proteins. Structures of human heterodimeric Sae1/Sae2-Mg.ATP and Sae1/Sae2-SUMO-1-Mg.ATP complexes were determined at 2.2 and 2.75 A resolution, respectively. Despite the presence of Mg.ATP, the Sae1/Sae2-SUMO-1-Mg.ATP structure reveals a substrate complex insomuch as the SUMO C-terminus remains unmodified within the adenylation site and 35 A from the catalytic cysteine, suggesting that additional changes within the adenylation site may be required to facilitate chemistry prior to adenylation and thioester transfer. A mechanism for E2 recruitment to E1 is suggested by biochemical and genetic data, each of which supports a direct role for the E1 C-terminal ubiquitin-like domain for E2 recruitment during conjugation.

Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1.,Lois LM, Lima CD EMBO J. 2005 Feb 9;24(3):439-51. Epub 2005 Jan 20. PMID:15660128^[19]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Alkuraya FS, Saadi I, Lund JJ, Turbe-Doan A, Morton CC, Maas RL. SUMO1 haploinsufficiency leads to cleft lip and palate. Science. 2006 Sep 22;313(5794):1751. PMID:16990542 doi:10.1126/science.1128406
↑ Okuma T, Honda R, Ichikawa G, Tsumagari N, Yasuda H. In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2. Biochem Biophys Res Commun. 1999 Jan 27;254(3):693-8. PMID:9920803 doi:10.1006/bbrc.1998.9995
↑ Gong L, Li B, Millas S, Yeh ET. Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex. FEBS Lett. 1999 Apr 1;448(1):185-9. PMID:10217437
↑ Desterro JM, Rodriguez MS, Kemp GD, Hay RT. Identification of the enzyme required for activation of the small ubiquitin-like protein SUMO-1. J Biol Chem. 1999 Apr 9;274(15):10618-24. PMID:10187858
↑ Azuma Y, Tan SH, Cavenagh MM, Ainsztein AM, Saitoh H, Dasso M. Expression and regulation of the mammalian SUMO-1 E1 enzyme. FASEB J. 2001 Aug;15(10):1825-7. PMID:11481243
↑ Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001 Sep 21;276(38):35368-74. Epub 2001 Jul 12. PMID:11451954 doi:10.1074/jbc.M104214200
↑ Lois LM, Lima CD. Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1. EMBO J. 2005 Feb 9;24(3):439-51. Epub 2005 Jan 20. PMID:15660128
↑ Olsen SK, Capili AD, Lu X, Tan DS, Lima CD. Active site remodelling accompanies thioester bond formation in the SUMO E1. Nature. 2010 Feb 18;463(7283):906-12. PMID:20164921 doi:10.1038/nature08765
↑ Mahajan R, Delphin C, Guan T, Gerace L, Melchior F. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell. 1997 Jan 10;88(1):97-107. PMID:9019411
↑ Kamitani T, Nguyen HP, Yeh ET. Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem. 1997 May 30;272(22):14001-4. PMID:9162015
↑ Meulmeester E, Kunze M, Hsiao HH, Urlaub H, Melchior F. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell. 2008 Jun 6;30(5):610-9. doi: 10.1016/j.molcel.2008.03.021. PMID:18538659 doi:10.1016/j.molcel.2008.03.021
↑ Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. PMID:18408734 doi:10.1038/ncb1716
↑ Azuma Y, Tan SH, Cavenagh MM, Ainsztein AM, Saitoh H, Dasso M. Expression and regulation of the mammalian SUMO-1 E1 enzyme. FASEB J. 2001 Aug;15(10):1825-7. PMID:11481243
↑ Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001 Sep 21;276(38):35368-74. Epub 2001 Jul 12. PMID:11451954 doi:10.1074/jbc.M104214200
↑ Wang J, Lee B, Cai S, Fukui L, Hu W, Chen Y. Conformational transition associated with E1-E2 interaction in small ubiquitin-like modifications. J Biol Chem. 2009 Jul 24;284(30):20340-8. doi: 10.1074/jbc.M109.000257. Epub 2009, May 14. PMID:19443651 doi:10.1074/jbc.M109.000257
↑ Lois LM, Lima CD. Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1. EMBO J. 2005 Feb 9;24(3):439-51. Epub 2005 Jan 20. PMID:15660128
↑ Wang J, Hu W, Cai S, Lee B, Song J, Chen Y. The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications. Mol Cell. 2007 Jul 20;27(2):228-37. PMID:17643372 doi:http://dx.doi.org/10.1016/j.molcel.2007.05.023
↑ Olsen SK, Capili AD, Lu X, Tan DS, Lima CD. Active site remodelling accompanies thioester bond formation in the SUMO E1. Nature. 2010 Feb 18;463(7283):906-12. PMID:20164921 doi:10.1038/nature08765
↑ Lois LM, Lima CD. Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1. EMBO J. 2005 Feb 9;24(3):439-51. Epub 2005 Jan 20. PMID:15660128

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1y8r"

@@ Line 3: / Line 3: @@
 <StructureSection load='1y8r' size='340' side='right'caption='[[1y8r]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1y8r]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y8R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Y8R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1y8r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y8R FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1y8q|1y8q]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBLE1A, SAE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBLE1B, SAE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBL1, SUMO-1, SMT3C, SMT3H3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBLE1A, SAE1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBLE1B, SAE2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBL1, SUMO-1, SMT3C, SMT3H3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1y8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y8r OCA], [http://pdbe.org/1y8r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y8r RCSB], [http://www.ebi.ac.uk/pdbsum/1y8r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1y8r ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y8r OCA], [https://pdbe.org/1y8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y8r RCSB], [https://www.ebi.ac.uk/pdbsum/1y8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y8r ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/SUMO1_HUMAN SUMO1_HUMAN]] Defects in SUMO1 are the cause of non-syndromic orofacial cleft type 10 (OFC10) [MIM:[http://omim.org/entry/613705 613705]]; also called non-syndromic cleft lip with or without cleft palate 10. OFC10 is a birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Note=A chromosomal aberation involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.<ref>PMID:16990542</ref>
+[[https://www.uniprot.org/uniprot/SUMO1_HUMAN SUMO1_HUMAN]] Defects in SUMO1 are the cause of non-syndromic orofacial cleft type 10 (OFC10) [MIM:[https://omim.org/entry/613705 613705]]; also called non-syndromic cleft lip with or without cleft palate 10. OFC10 is a birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Note=A chromosomal aberation involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.<ref>PMID:16990542</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/SAE1_HUMAN SAE1_HUMAN]] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.<ref>PMID:9920803</ref> <ref>PMID:10217437</ref> <ref>PMID:10187858</ref> <ref>PMID:11481243</ref> <ref>PMID:11451954</ref> <ref>PMID:15660128</ref> <ref>PMID:20164921</ref>  [[http://www.uniprot.org/uniprot/SUMO1_HUMAN SUMO1_HUMAN]] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development.<ref>PMID:9019411</ref> <ref>PMID:9162015</ref> <ref>PMID:18538659</ref> <ref>PMID:18408734</ref>  [[http://www.uniprot.org/uniprot/SAE2_HUMAN SAE2_HUMAN]] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.<ref>PMID:11481243</ref> <ref>PMID:11451954</ref> <ref>PMID:19443651</ref> <ref>PMID:15660128</ref> <ref>PMID:17643372</ref> <ref>PMID:20164921</ref>
+[[https://www.uniprot.org/uniprot/SAE1_HUMAN SAE1_HUMAN]] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.<ref>PMID:9920803</ref> <ref>PMID:10217437</ref> <ref>PMID:10187858</ref> <ref>PMID:11481243</ref> <ref>PMID:11451954</ref> <ref>PMID:15660128</ref> <ref>PMID:20164921</ref>  [[https://www.uniprot.org/uniprot/SUMO1_HUMAN SUMO1_HUMAN]] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development.<ref>PMID:9019411</ref> <ref>PMID:9162015</ref> <ref>PMID:18538659</ref> <ref>PMID:18408734</ref>  [[https://www.uniprot.org/uniprot/SAE2_HUMAN SAE2_HUMAN]] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.<ref>PMID:11481243</ref> <ref>PMID:11451954</ref> <ref>PMID:19443651</ref> <ref>PMID:15660128</ref> <ref>PMID:17643372</ref> <ref>PMID:20164921</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 34: @@
 ==See Also==
-*[[Ubiquitin activating enzyme|Ubiquitin activating enzyme]]
+*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
 == References ==
 <references/>

1y8r

From Proteopedia

Revision as of 16:50, 20 October 2021

SUMO E1 ACTIVATING ENZYME SAE1-SAE2-SUMO1-MG-ATP COMPLEX

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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