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Spanos"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics","Data-independent acquisition"],"software":[""],"submitter_keywords":["Human","Tblr1","Setd5","Ankrd11","Set3c","Neurological disorders"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD063846"],"tissue":["Cell Culture"],"sample_protocol":["Protein samples from all biological replicates were processed at the same time and with using the same digestion protocol without any deviations. They were subjected for MS analysis under the same conditions. Protein and peptide lists generated using the same software and the same parameters. Specifically, protein samples were either digested using the Filter Aided Sample Preparation (FASP) protocol or by in-gel digestion as described by Idin et al, 2025 and Borek et al, 2021 respectively.  LC-MS analyses were performed on Orbitrap Fusion™ Lumos™ Tribrid™ Mass Spectrometer (Thermo Fisher Scientific, UK) using the Data Dependent Acquisition (DDA) mode and on Orbitrap Exploris 480™ on a Data Independent Acquisition (DIA) mode, both coupled on-line, to an Ultimate 3000 HPLC (Dionex, Thermo Fisher Scientific, UK). Peptides were separated on a 50 cm (2 µm particle size) EASY-Spray column (Thermo Scientific, UK), which was assembled on an EASY-Spray source (Thermo Scientific, UK) and operated constantly at 50oC. Mobile phase A consisted of 0.1% formic acid in LC-MS grade water and mobile phase B consisted of 80% acetonitrile and 0.1% formic acid. Peptides were loaded onto the column at a flow rate of 0.3 μL min-1 and eluted at a flow rate of 0.25 μL min-1 according to the following gradient: 2 to 40% mobile phase B in 150 min and then to 95% in 11 min. Mobile phase B was retained at 95% for 5 min and returned back to 2% a minute after until the end of the run (190 min).  For DDA, survey scans were recorded at 120,000 resolution (scan range 350-1500 m/z) with an ion target of 4.0e5, and injection time of 50ms. MS2 was performed in the ion trap at a rapid scan mode, with ion target of 2.0E4 and HCD fragmentation (Olsen et al, 2007) with normalized collision energy of 27. The isolation window in the quadrupole was 1.4 Thomson. Only ions with charge between 2 and 7 were selected for MS2. Dynamic exclusion was set at 60 s.  For DIA, MS1 scans were recorded at 120,000 resolution (scan range 350-1650 m/z) with an ion target of 5.0e6, and injection time of 20ms. MS2 was performed in the orbitrap at 30,000 resolution with a scan range of 200-2000 m/z, maximum injection time of 55ms and AGC target of 3.0E6 ions. We used HCD fragmentation with stepped collision energy of 25.5, 27 and 30. We used variable isolation windows throughout the scan range ranging from 10.5 to 50.5 m/z. Narrow isolation windows (10.5-18.5 m/z) were applied from 400-800 m/z and then gradually increased to 50.5 m/z until the end of the scan range. The default charge state was set to 3. Data for both survey and MS/MS scans were acquired in profile mode."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["The MaxQuant software platform (Cox and Mann, 2008) version 1.6.1.0 was used to process the raw files and search was conducted against the Mus musculus protein database (released in July 2017), using the Andromeda search engine (Cox et al, 2011). For the first search, peptide tolerance was set to 20 ppm while for the main search peptide tolerance was set to 4.5 pm. Isotope mass tolerance was 2 ppm and maximum charge to 7. Digestion mode was set to specific with trypsin allowing maximum of two missed cleavages. Carbamidomethylation of cysteine was set as fixed modification and oxidation of methionine was set as variable modifications. Label-free quantitation analysis was performed by employing the MaxLFQ algorithm as described by Cox et al (2014). Absolute protein quantification was performed as described in Schwanhäusser et al, 2011. Peptide and protein identifications were filtered to 1% FDR.  The DIA-NN software platform (Demichev et al, 2020) version 1.8.1. was used to process the DIA raw files and search was conducted against the Mus musculus  complete/reference proteome (Uniprot, released in July, 2017). Precursor ion generation was based on the chosen protein database (automatically generated spectral library) with deep-learning based spectra, retention time and IMs prediction. Digestion mode was set to specific with trypsin allowing maximum of two missed cleavages. Carbamidomethylation of cysteine was set as fixed modification.  Oxidation of methionine, and acetylation of the N-terminus were set as variable modifications. The parameters for peptide length range, precursor charge range, precursor m/z range and fragment ion m/z range as well as other software parameters were used with their default values. The precursor FDR was set to 1%."],"omics_type":["Proteomics"],"labhead":["Matthew Lyst"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["University of Edinburgh"],"species":["Mus Musculus (mouse)"],"submitter_mail":["spanos.christos@gmail.com"],"publication":["Not available"],"submitter_affiliation":["University of Edinburgh"],"submitter_country":["United Kingdom"],"additional_accession":[]},"is_claimable":false,"name":"Dysfunction of a SET3C-like complex underlies a family of related neurological disorders","description":"TBLR1, a subunit of the NCoR corepressor complex, is mutated in a range of neurodevelopmental disorders that only partially align symptomatically with those caused by mutations in its binding partner, MeCP2. In a search for novel TBLR1-binding partners, we identified ANKRD11 and SETD5 – mutations in which are amongst the most frequent genetic causes of neurodevelopmental disorders. Here we report that TBLR1 provides a molecular bridge between ANKRD11, SETD5 and NCoR in a complex with a strikingly resembles the SET3C complex of yeast. Pathogenic missense mutations in TBLR1, ANKRD11 and SETD5 disrupt this mammalian SET3C-like assembly. Mutations of this kind in Ankrd11 and Setd5 genes cause highly correlated changes in gene expression and severe developmental impairments. We present evidence that this complex restrains the expression of highly transcribed genes. Our results demonstrate that failure of transcriptional regulation by SET3C provides a convergent molecular basis for a family of neurodevelopmental disorders.","dates":{"publication":"2026-05-01","submission":"2025-05-12"},"accession":"PXD063846","cross_references":{"TAXONOMY":["NEWT:6945","NEWT:184922","NEWT:6703","NEWT:3555","NEWT:2","NEWT:157546","NEWT:35554","NEWT:38942","NEWT:307972","NEWT:32046","NEWT:544496","NEWT:2102","NEWT:2042546","NEWT:45351","NEWT:43179","NEWT:4513","NEWT:5722","NEWT:1247","NEWT:1129","NEWT:55153","NCBITaxon:10407","NEWT:1736309","NEWT:309800","NEWT:281395","NEWT:10360","NEWT:1211601","NEWT:876138","NEWT:47664","NEWT:317548","NEWT:3654","NEWT:237561","NEWT:5833","NEWT:6928","NEWT:10036","NEWT:36745","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:272563","NEWT:224326","NCBITaxon:79857","NEWT:1096976","NEWT:82688","NEWT:95648","NEWT:3885","NEWT:3888","NEWT:5821","NEWT:1589","NEWT:135622","NCBITaxon:4896","NEWT:6915","NEWT:3649","NEWT:101510","NEWT:28903","NEWT:3880","NEWT:272559","NEWT:28909","NEWT:515849","NEWT:3641","NEWT:383379","NEWT:466585","NEWT:10029","NEWT:913645","NEWT:1000589","NEWT:85963","NEWT:85962","NEWT:143361","NEWT:317447","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:398580","NEWT:4442","NEWT:4565","NEWT:1264690","NEWT:515619","NEWT:192875","NEWT:34305","NEWT:59729","NCBITaxon:183674","NEWT:224308","NEWT:84645","NEWT:626528","NEWT:3347","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:5888","NEWT:211586","NEWT:747078","NEWT:1282","NEWT:1283","NEWT:931281","NEWT:4550","NEWT:1000561","NEWT:294381","NEWT:197","NEWT:1390363","NEWT:77133","NEWT:288705","NEWT:29176","NCBITaxon:79824","NEWT:4787","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:3218","NEWT:5759","NEWT:1736231","NEWT:556182","NEWT:1270","NEWT:374990","NEWT:498217","NEWT:156471","NEWT:2242","NEWT:4784","NEWT:11320","NEWT:360106","NEWT:156476","NEWT:286","NEWT:391619","NEWT:360104","NEWT:287","NEWT:246197","NEWT:10117","NEWT:10239","NEWT:10116","NEWT:1280","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:44685","NEWT:317513","NEWT:1148","NEWT:580240","NEWT:5508","NEWT:294128","NEWT:11676","NEWT:55571","NEWT:35500","NEWT:1140","NEWT:100226","NEWT:4530","NEWT:1143","NEWT:4896","NEWT:75058","NEWT:13616","NEWT:1390","NEWT:1094343","NEWT:1336795","NEWT:296543","NEWT:316435","NEWT:1773","NEWT:1895","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:105023","NEWT:866628","NEWT:935293","NEWT:64152","NEWT:4924","NEWT:749200","NEWT:375146","NEWT:990346","NEWT:145953","NEWT:257309","NEWT:100816","NEWT:263","NEWT:230741","NEWT:52283","NEWT:284812","NEWT:8175","NCBITaxon:1313","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44544","NEWT:47946","NEWT:4911","NEWT:645463","NEWT:3702","NEWT:129249","NEWT:243277","NEWT:990119","NEWT:2850","NEWT:408172","NEWT:227321","NEWT:408170","NEWT:493760","NEWT:106590","NEWT:260710","NEWT:257313","NEWT:400772","NEWT:3708","NEWT:128161","NEWT:332648","NEWT:106592","NEWT:536231","NEWT:46704","NEWT:1436733","NEWT:460519","NEWT:1187947","NEWT:1432138","NEWT:269796","NEWT:10312","NEWT:1424507","NCBITaxon:1773","NEWT:9598","NEWT:8030","NEWT:9483","NEWT:1639","NEWT:188229","NEWT:3818","NEWT:480","NEWT:4909","NEWT:67767","NEWT:759272","NEWT:432359","NEWT:46835","NEWT:1182263","NEWT:109757","NEWT:943146","NEWT:2711","NEWT:300852","NEWT:1502","NEWT:376686","NEWT:95486","NEWT:9103","NEWT:1883446","NEWT:29159","NEWT:253","NEWT:10306","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:8022","NEWT:145943","NCBITaxon:4932","NEWT:595536","NEWT:240906","NEWT:593117","NEWT:89920","NEWT:3635","NEWT:5811","NEWT:235443","NEWT:180923","NEWT:108458","NEWT:272623","NEWT:272624","NEWT:411483","NEWT:884019","NEWT:198215","NEWT:411490","NEWT:983964","NEWT:118499","NEWT:169963","NEWT:32644","NEWT:527796","NEWT:225117","NEWT:746128","NEWT:499175","NEWT:109779","NEWT:43665","NEWT:1266464","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:367830","NEWT:1255228","NEWT:178616","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:375451","NEWT:352472","NEWT:357","NEWT:1071661","NEWT:360094","NEWT:470","NEWT:41364","NEWT:1313","NEWT:411469","NEWT:84023","NEWT:559292","NEWT:39491","NCBITaxon:5811","NEWT:29491","NEWT:411464","NEWT:411460","NEWT:2014887","NEWT:2762","NEWT:1174673","NEWT:1328426","NEWT:562","NEWT:411470","NEWT:33952","NEWT:2094720","NCBITaxon:2697049","NEWT:571256","NEWT:40483","NEWT:28038","NEWT:1663","NEWT:1423","NEWT:4932","NEWT:3603","NEWT:2759","NEWT:3847","NEWT:38293","NEWT:1428","NEWT:327159","NEWT:178876","NEWT:1660","NEWT:327160","NEWT:573","NEWT:9031","NEWT:1872122","NEWT:7091","NEWT:108931","NEWT:241368","NEWT:1055524","NEWT:42528","NEWT:190802","NEWT:9778","NEWT:150475","NEWT:303","NEWT:9417","NEWT:7111","NEWT:347515","NEWT:1216979","NEWT:7237","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:115104","NEWT:1121114","NEWT:663","NEWT:1081927","NEWT:1238993","NEWT:67825","NEWT:187878","NEWT:185579","NEWT:941442","NEWT:220668","NEWT:13076","NEWT:1821314","NEWT:1249668","NEWT:7108","NEWT:317","NEWT:5286","NEWT:7227","NEWT:7469","NEWT:885318","NEWT:9402","NEWT:9644","NEWT:415540","NEWT:550","NEWT:675060","NEWT:4081","NEWT: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