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Subcompartments of the plasma membrane are believed to be critical for lymphocyte responses, but few genetic tools are available to test their function. Here we describe a previously unknown X-linked B cell-deficiency syndrome in mice caused by mutations in Atp11c, which encodes a member of the P4 ATPase family thought to serve as 'flippases' that concentrate aminophospholipids in the cytoplasmic leaflet of cell membranes. Defective ATP11C resulted in a lower rate of phosphatidylserine translocation in pro-B cells and much lower pre-B cell and B cell numbers despite expression of pre-rearranged immunoglobulin transgenes or enforced expression of the prosurvival protein Bcl-2 to prevent apoptosis and abolished pre-B cell population expansion in response to a transgene encoding interleukin 7. The only other abnormalities we noted were anemia, hyperbilirubinemia and hepatocellular carcinoma. Our results identify an intimate connection between phospholipid transport and B lymphocyte function.
Pubmed ID: 21423173
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A platform that integrates a great variety of tools for protein sequence analysis. Many tools are developed in-house, and serveral public tools are offered with extended functionality. Most frequently used tools HHpred Sensitive protein homology detection and structure prediction by HMM-HMM-comparison. Starting from a query sequence, HHpred builds a multiple sequence alignment using HHblits and turns it into a profile HMM. This is then compared it with a database of HMMs representing proteins with known structure (e.g. PDB, SCOP) or annotated protein families (e.g. PFAM, SMART, CDD, COGs, KOGs). The output is a list of closest homologs with alignments. HHpred can also build 3d homology models using the identified templates in the PDB database. It can optimize template picking and query-template alignments for homology modeling. The HHblits software is part of the open source package HHsuite. HHblits Remote homology detection method based on iterative HMM-HMM comparison. HHblits can build high-quality MSAs starting from single sequences or from MSAs. It transforms these into a query HMM and iteratively searches through uniprot20 or nr20 databases by adding significantly similar sequences from the previous search to the updated query HMM for the next search iteration. Compared to PSI-BLAST, HHblits is faster, up to twice as sensitive and produces more accurate alignments. The HHblits software is part of the open source package HHsuite. Quick2d Quick2D gives you an overview of secondary structure features like alpha-helices, extended beta-sheets, coiled coils, transmembrane helices and disorder regions. Predictions by PSIPRED, JNET, Prof(Rost), Prof(Ouali), Coils, MEMSAT2, HMMTOP, DISOPRED2 and VSL2. Modeller A Program for Comparative Protein Structure Modelling by Satisfaction of Spatial Restraints. Coils/PCoils This server compares a single sequence (COILS) or a sequence alignment (PCOILS) to a database of known coiled-coils and derives a similarity score. The program then calculates the probability that the sequence will adopt a coiled-coil conformation. PSI-Blast Search with an amino acid sequence against protein databases for locally similar sequences. Similar to ProteinBLAST but more sensitive. PSI-BLAST first performs a BLAST search and builds an alignment from the best local hits. This alignment is then used as a query for the next round of search. After each successive round the search alignment is updated.
View all literature mentionsSoftware tool as Program for Comparative Protein Structure Modelling by Satisfaction of Spatial Restraints. Used for homology or comparative modeling of protein three dimensional structures. User provides alignment of sequence to be modeled with known related structures and MODELLER automatically calculates model containing all non hydrogen atoms.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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