2grr is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[UBC9_HUMAN] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.[1][2][3][4][5][6][7]
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
E2 conjugating proteins that transfer ubiquitin and ubiquitin-like modifiers to substrate lysine residues must first activate the lysine nucleophile for conjugation. Genetic complementation revealed three side chains of the E2 Ubc9 that were crucial for normal growth. Kinetic analysis revealed modest binding defects but substantially lowered catalytic rates for these mutant alleles with respect to wild-type Ubc9. X-ray structures for wild-type and mutant human Ubc9-RanGAP1 complexes showed partial loss of contacts to the substrate lysine in mutant complexes. Computational analysis predicted pK perturbations for the substrate lysine, and Ubc9 mutations weakened pK suppression through improper side chain coordination. Biochemical studies with p53, RanGAP1 and the Nup358/RanBP2 E3 were used to determine rate constants and pK values, confirming both structural and computational predictions. It seems that Ubc9 uses an indirect mechanism to activate lysine for conjugation that may be conserved among E2 family members.
Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway.,Yunus AA, Lima CD Nat Struct Mol Biol. 2006 Jun;13(6):491-9. Epub 2006 May 28. PMID:16732283[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Yasugi T, Howley PM. Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9. Nucleic Acids Res. 1996 Jun 1;24(11):2005-10. PMID:8668529
↑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
↑Kim YE, Kim DY, Lee JM, Kim ST, Han TH, Ahn JH. Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation. Biochem Biophys Res Commun. 2005 May 13;330(3):746-54. PMID:15809060 doi:10.1016/j.bbrc.2005.03.052
↑Kuo FT, Bentsi-Barnes IK, Barlow GM, Bae J, Pisarska MD. Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene. Cell Signal. 2009 Dec;21(12):1935-44. doi: 10.1016/j.cellsig.2009.09.001. Epub, 2009 Sep 8. PMID:19744555 doi:10.1016/j.cellsig.2009.09.001
↑Figueroa-Romero C, Iniguez-Lluhi JA, Stadler J, Chang CR, Arnoult D, Keller PJ, Hong Y, Blackstone C, Feldman EL. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 2009 Nov;23(11):3917-27. doi: 10.1096/fj.09-136630. Epub 2009 Jul 28. PMID:19638400 doi:10.1096/fj.09-136630
↑Capili AD, Lima CD. Structure and analysis of a complex between SUMO and Ubc9 illustrates features of a conserved E2-Ubl interaction. J Mol Biol. 2007 Jun 8;369(3):608-18. Epub 2007 Apr 6. PMID:17466333 doi:10.1016/j.jmb.2007.04.006
↑Sekiyama N, Arita K, Ikeda Y, Hashiguchi K, Ariyoshi M, Tochio H, Saitoh H, Shirakawa M. Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45. Proteins. 2009 Dec 4. PMID:20077568 doi:10.1002/prot.22667
↑Yunus AA, Lima CD. Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway. Nat Struct Mol Biol. 2006 Jun;13(6):491-9. Epub 2006 May 28. PMID:16732283 doi:https://dx.doi.org/10.1038/nsmb1104
