2io2
From Proteopedia
Crystal structure of human Senp2 in complex with RanGAP1-SUMO-1
Structural highlights
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[SENP2_HUMAN] Protease that catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO1, SUMO2 and SUMO3 to their mature forms and deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins. May down-regulate CTNNB1 levels and thereby modulate the Wnt pathway (By similarity).[2] [3] [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.[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 PubMedSUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a catalytically inert SENP2 protease domain in complex with conjugated RanGAP1-SUMO-1 or RanGAP1-SUMO-2, or in complex with SUMO-2 or SUMO-3 precursors. Common features within the active site include a 90 degrees kink proximal to the scissile bond that forces C-terminal amino acid residues or the lysine side chain toward a protease surface that appears optimized for lysine deconjugation. Analysis of this surface reveals SENP2 residues, particularly Met497, that mediate, and in some instances reverse, in vitro substrate specificity. Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing. Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.,Reverter D, Lima CD Nat Struct Mol Biol. 2006 Dec;13(12):1060-8. Epub 2006 Nov 12. PMID:17099700[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Lima, C D | Reverter, D | Complex | Hydrolase | Protein binding | Senp | Sumo | Ubiquitin | Ulp
