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Calpain 3 (CAPN3) is a cysteine protease that when mutated causes Limb Girdle Muscular Dystrophy 2A. It is thereby the only described Calpain family member that genetically causes a disease. Due to its inherent instability little is known of its substrates or its mechanism of activity and pathogenicity. In this investigation we define a primary sequence motif underlying CAPN3 substrate cleavage. This motif can transform non-related proteins into substrates, and identifies >300 new putative CAPN3 targets. Bioinformatic analyses of these targets demonstrate a critical role in muscle cytoskeletal remodeling and identify novel CAPN3 functions. Among the new CAPN3 substrates are three E3 SUMO ligases of the Protein Inhibitor of Activated Stats (PIAS) family. CAPN3 can cleave PIAS proteins and negatively regulates PIAS3 sumoylase activity. Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation, with strong implications for muscle remodeling.
Pubmed ID: 20694146
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A sister database to ProSite, is constituted of manually created rules that increase the discriminatory power of PROSITE motifs (generally profiles) by providing additional information about functionally and/or structurally critical amino acids and can automatically generate annotation based on PROSITE motifs in the UniProtKB/Swiss-Prot format. Each ProRule is defined in the UniRule format. In addition to these rules corresponding to a unique PROSITE motif, there are also rules triggered by a specific combination of PROSITE motifs called metamotifs. Metamotifs allow the definition of arrangements of domains separated by spacers of variable size, as well as the anchoring to the N- and/or C-termini and the exclusion of a PROSITE motif. ProRule uses the UniRule format that is common to all types of rules created to annotate UniProtKB/Swiss-Prot, including the HAMAP family rules. Each rule contains information used to provide template based annotation associated with the domain or family detected by the PROSITE motif. ProRule is used to create UniProtKB/Swiss-Prot lines with basic and complex annotation derived from the presence of the domain and of biologically critical amino acids: domain name and boundaries, EC number, function, keywords, associated PROSITE patterns, PTMs, active sites, disulfide bonds, etc.). ProRule contains notably the position of structurally and/or functionally critical amino acid(s), as well as the condition(s) they must fulfil to play their biological role(s). Part of these supplementary data are used by ScanProsite that not only provides the protein sequence matched by a profile, but also information about the relevance of biologically meaningful residues, like active sites, binding sites, post-translational modification sites or disulfide bonds, to help function determination
View all literature mentionsPortal which provides access to scientific databases and software tools (i.e., resources) in different areas of life sciences including proteomics, genomics, phylogeny, systems biology, population genetics, transcriptomics etc. It contains resources from many different SIB groups as well as external institutions.
View all literature mentionsA software package and server used to identify and characterize proteins from primary sequence databases using mass spectrometry data. Mascot integrates peptide mass fingerprinting, sequence querying, and MS/MS ion searching in order to search for proteins in databases like SwissProt, NCBInr, EMBL EST divisions, contaminants, and cRAP. If a license is purchased, users may: search data sets that exceed the 1200 spectrum limit of the free version; set up automated, high throughput work; add and edit proteins and quantification methods; and search a preferred collection of sequence databases. The software package works with instruments from AB Sciex, Agilent, Bruker, Jeol, Shimadzu, Thermo Scientific, and Waters.
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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