{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/2_FrIII_CD127.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/eTreg_110215_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/eTconv_040315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/eTconv_110215_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/eTreg_040315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/7_FrIII_CD127.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/13_FrIII_CD127-.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/3_FrIII_CD127-.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/nTreg_130315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/eTreg_130315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/6_mTconv_CD127.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/9_eTreg_CD127-.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/eTconv_130315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/8_FrIII_CD127-.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/14_eTreg_CD127-.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/nTconv_130315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/nTconv_040315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/nTreg_110215_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/1_mTconv_CD127.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/12_FrIII_CD127.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/11_mTconv_CD127.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/nTreg_040315_A.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/nTconv_110215_A.raw"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD007744/txt.rar"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":369,"searchCount":0},"additional":{"labhead_mail":["m.vandenbiggelaar@sanquin.nl"],"submitter":["Maartje van den Biggelaar"],"technology_type":["Mass Spectrometry","Shotgun proteomics"],"software":["Not available"],"submitter_keywords":["Human","Cd4+ t lymphocyte","Blood"],"full_dataset_link":["http://www.ebi.ac.uk/pride/archive/projects/PXD007744"],"tissue":["T Cell","Blood"],"sample_protocol":["Cell isolation and cell sorting Human peripheral blood mononuclear cells (PBMCs) were obtained from fresh buffy coats from healthy male donors using Ficoll-Paque Plus (GE Healthcare) gradient centrifugation. Total CD4+ T cells were isolated using magnetic sorting with CD4 microbeads (Miltenyi Biotec) and viable cells were separated using flow cytometric sorting for CD25, CD127 and CD45RA on a FACS Aria III (BD Biosciences). Blood samples were obtained from anonymized volunteers with written informed consent used in accordance to guidelines established by the Medical Ethical Committee. Antibodies The following antibodies were used: CD25 (43839) and CD45RA (560675) from BD Biosciences. CD127 (351309), NFB p50 (616704), IFN (502510), IL-17A (512325), and NFATc1 (649603) from Biolegend. FOXP3 (25-4777-42), Helios (48-9883), phospho-STAT4 Y693 (12-9044-42), GZMA (25-9177-41), GATA3 (12-9966-42), and RORt (17-6988-80) from eBioscience. SHMT2 (HPA020549), Actin (A3853), and NFB p52 (FCMAB346F) from Sigma. GZMK (21144054, Immunotools), FTL (ab69090, Abcam), ANXA1 (sc-12740, Santa Cruz), and NFATc2 (14324S, Cell Signaling). Sample preparation for mass spectrometry (MS) FACS-purified CD4+ subsets from 3-6 donors were washed in PBS and immediately lysed in lysis buffer (4% SDS, 100 mM DTT, 100 mM Tris HCl [pH 8.0]) in Protein LoBind tubes (Eppendorf). The samples were heated at 95 °C, sonicated (Bioruptor), and after centrifugation (16,000 g), the supernatants were kept frozen at -80 °C. Cell lysates were then processed using filter aided sample preparation (FASP) as described before (Wiśniewski et al., 2009). Briefly, lysates were subjected to alkylated and digested into peptides using sequencing-grade trypsin (Promega). After digestion, peptides were desalted using StageTips (Rappsilber et al, Anal. Chem., 2003, 75 (3), pp 663–670), reduced in a speedvac, and reconstituted in 2% acetonitrile in 0.1% TFA in water before analysis by MS. Mass spectrometry data acquisition Tryptic peptides were separated by nanoscale C18 reverse chromatography coupled on line to an Orbitrap Fusion Tribrid mass spectrometer (Thermo Scientific) via a nanoelectrospray ion source (Nanospray Flex Ion Source, Thermo Scientific). Peptides were loaded on a 20 cm 75–360 µm inner-outer diameter fused silica emitter (New Objective) packed in-house with ReproSil-Pur C18-AQ, 1.9 μm resin (Dr Maisch GmbH). The column was installed on a Dionex Ultimate3000 RSLC nanoSystem (Thermo Scientific) using a MicroTee union formatted for 360 μm outer diameter columns (IDEX) and a liquid junction. The spray voltage was set to 2.15 kV. Buffer A was composed of 0.5 % acetic acid and buffer B of 0.5 % acetic acid, 80% acetonitrile. Peptides were loaded for 17 min at 300 nl/min at 5% buffer B, equilibrated for 5 minutes at 5% buffer B (17-22 min) and eluted by increasing buffer B from 5-15% (22-87 min) and 15-38% (87-147 min), followed by a 10 minute wash to 90 % and a 5 min regeneration to 5%. Survey scans of peptide precursors from 400 to 1500 m/z were performed at 120K resolution (at 200 m/z) with a 1.5 × 105 ion count target. Tandem mass spectrometry was performed by isolation with the quadrupole with isolation window 1.6, HCD fragmentation with normalized collision energy of 30, and rapid scan mass spectrometry analysis in the ion trap. The MS2 ion count target was set to 104 and the max injection time was 35 ms. Only those precursors with charge state 2–7 were sampled for MS2. The dynamic exclusion duration was set to 60 s with a 10 ppm tolerance around the selected precursor and its isotopes. Monoisotopic precursor selection was turned on. The instrument was run in top speed mode with 3 s cycles. All data were acquired with Xcalibur software."],"repository":["Pride"],"quantification_method":["MS1 intensity based label-free quantification method"],"modification":["iodoacetamide derivatized residue","acetylated residue"],"data_protocol":["Data Processing and Analysis RAW mass spectrometry files were processed with the MaxQuant computational platform (Cox and Mann, 2008) version 1.5.2.8 using label-free quantitation (LFQ). Peptides were identified using the Andromeda search engine by querying the human Uniprot database (2015-02, 89796 entries) with a 1% false discovery rate (FDR) cut-off both at peptide and protein level. Potential contaminants, proteins only identified by site and reverse hits were eliminated using Perseus version 1.5.1.6. To compare proteomes of different cell populations, LFQ values were log2-transformed and the 3-6 biological replicates per experimental condition grouped. For further analysis, only proteins with 3 valid values in at least one of the groups were included. Missing values were imputed by normal distribution (width= 0.3, shift= 1.8). Intergroup differences in protein levels were calculated using ANOVA using Benjamini-Hochberg FDR of 0.05 and S0 0.4. General relatedness of samples was assessed through Principal Component Analysis (PCA) using Perseus’ built-in tool. Clusters of proteins with specific expression patterns were identified using unsupervised hierarchical clustering based on K-means and Euclidian distance after z-score normalization."],"omics_type":["Proteomics","Multiomics"],"labhead":["Maartje van den Biggelaar"],"instrument_platform":["Orbitrap Fusion ETD"],"labhead_affiliation":["Sanquin Research, department of Plasma Proteins, Plesmanlaan 125, 1066 CX, Amsterdam, the Netherlands"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["m.vandenbiggelaar@sanquin.nl"],"publication":["29752063 Cuadrado E, van den Biggelaar M, de Kivit S, Chen YY, Slot M, Doubal I, Meijer A, van Lier RAW, Borst J, Amsen D. Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity. Immunity. 2018 48(5):1046-1059.e6 10.1016/j.immuni.2018.04.008"],"curator_keywords":["Biological"],"submitter_affiliation":["Sanquin Research"],"submitter_country":["Netherlands"],"pubmed_abstract":["To obtain a molecular definition of regulatory T (Treg) cell identity, we performed proteomics and transcriptomics on various populations of human regulatory and conventional CD4+ T (Tconv) cells. A protein expression signature was identified that defines all Treg cells, and another signature that defines effector Treg cells. These signatures could not be extrapolated from transcriptome data. Unique cell-biological and metabolic features in Treg cells were defined, as well as specific adaptations in cytokine, TCR, and costimulatory receptor signaling pathways. One such adaptation-selective STAT4 deficiency-prevented destabilization of Treg cell identity and function by inflammatory cytokines, while these signals could still induce critical transcription factors and homing receptors via other pathways. Furthermore, our study revealed surface markers that identify FOXP3+CD4+ T cells with distinct functional properties. Our findings suggest that adaptation in signaling pathways protect Treg cell identity and present a resource for further research into Treg cell biology."],"pubmed_title":["Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity."],"pubmed_authors":["Cuadrado Eloy E, van den Biggelaar Maartje M, de Kivit Sander S, Chen Yi-Yen YY, Slot Manon M, Doubal Ihsane I, Meijer Alexander A, van Lier Rene A W RAW, Borst Jannie J, Amsen Derk D"],"sample_synonyms":["NF-ATp, DmelCG5178, dmMOF, CDw127, ion, BcDNA.GH12068, Nbla10317, Clox, Nbla10314, fat2, SDH, l(2)2647, SE1, dmTAF[[II]]230, SDS, M(3L)i, E260, Drug Tolerance, dMOF, B1, Ly-4, HCL-C, 2310042E05Rik, Analysis, hnRNP48, A, C, SET, D, SHMT2, E, AI662457, AW545633, NFATc2, NFATc1, Analyses, cel, Personnel, M, GATA-3, phosphatase 2A inhibitor I2PP2A, beta-Tub6D, T, ORF19, Acetic Acid Glacial, po1D2, DmelCG4299, isolation and purification, LACS1, KBF1, decreased, PIDX, NF-kappaB2, D1, NF-kappaB1, MeCO2H, Pros26S-RS6A, Acs, Act, D9, z, COY1, TRYP2, HRG, drug tolerance, COOL-1, dTAF[[II]]230, CTLA8, TSP1, Actin/BAP47, Volunteerism, Longterm Effect, act, Endogenous, CTLA3, breast sarcoma, Spectrum Analysis, not genetically inherited, Dm_Rpt5b, Glacial, Dm_Rpt5a, SLEB11, IMD3, rpS17, HRGalpha, XGATA3, DmelCG4027, NFAT transcription complex cytosolic component, DI-2, instrument, Ctla3, hrb27c, I-2Dm, FU, CG3401, beta3Tub, ASC1p50, Ctla8, Hrb48, inhibitor of granzyme A-activated DNase, C81413, act79B, I-2PP1, DMN, Applications, DmelCG7764, Taf250, hrb27C, Fu, bacteriolytic toxin activity, LPC1, Regeneration, P50BP, ANF1A2, Act5c, IL-2 receptor subunit alpha, Ctla-3, GOLIM6, anon-WO0153538.9, anon-WO0153538.8, 143391_i_at, ARIA, beta3 TU, Ctla-8, precursor, TNFRSF5, 154538_at, Hf, CG7826, mass-to-charge ratio, IFNA13, period, dyna, M(3)i, isolation, IT, FOXP3, DmelCG7749, GP39, Znfn1a2, CG7835, hrb27, foetal AEDS, Rpt5, Lpc-1, MAX, dTAF[[II]]250, FAM39E, Hydrogen chloride, Longterm, cell, Volunteer Worker, homopolymer, Open Source Software, 4733401P19Rik, 2pp2a, Act57, pk18, ions, MBR, CG10574, Computer Software Application, dTAF250, 2210017P03Rik, l(3)04210, hairy cell leukemia, CG18290, linha, dSet, PTBR, T10, peptidos, beta[[3]]-tubulin, T11, Kb, PTHB1, Ki, Acas1, 42A, AcOH, 1-(14)C-labeled, CG3025, nf-atc, HRP48, buffer, dTAF230, native protein, Immune Tolerance, T-cell differentiation antigen L3T4, C18, GGF2, chemical analysis, Long Term Effects, Act42, BcDNA:RE44119, BTF2 p52, p49|p100, Mass Spectrum Analyses, boundary, Taf[[II]]250, AU020952, CG10377, holin, Act88-F, Separations, M(3)q, NF-ATC, Magnetic, SWDS, ethanenitrile, P85COOL1, AI115586, CG10370, anon-EST:Posey48, COOL1, mus87E, Tub, Computer Programs, signalling process, ACETIC ACID, betatub60D, M(3L)i[55], NF-ATc, IL2RA, Bap47, Ethanoic acid, FKBP52, Rps17, FKBP59, Tfb2, T-cell surface antigen T4/Leu-3, NCMe, selection process, instrument configuration, classic hairy cell leukaemia, Untrained, jal, LACS 1, Hrb27c, protein, xgata-3, FKBP51, Helios, l(1)G0420, peptide, Facl2, peptido, ClvPrd, Hsp56, dRpt5, Alpha4 phosphoprotein, (2Z)-but-2-enedioate, protein aggregate, Injectables, TCGFR, rsd, peptides, TAF-I, p50Cdc37, dMax, Open, E430039A18Rik, hypoplasia, CG7764, mAPC, IBP, DmTBP-1, l(2)10280, Anx-A1, IGAAD, DmelCG10574, ppm, AI316800, CG4027, ethoic acid, tbp-1, DmelCG18290, Bladder pain syndrome, CD45RA, CD25, Long-Term Effects, Cytotoxic T-lymphocyte-associated antigen 8, PIXB, Il17, AI607462, Dmel_CG7826, AI836084, StF-IT-1, Th, pixb, TAFII-250, TAF250/230, SHMT, Source Softwares, Spectroscopy, ACTIN, TAFII250, NFKB-p105, nc16, IL17, dmax, Acetylcholine receptor-inducing activity, Computer Applications Softwares, Immunologic Tolerance, bacteriocin activity, CG5178, WASH, Tub60D, Acetic acid, Dmel_CG7835, MNB, beta-tub, CTLA-8, Painful Bladder Syndrome, p50|p105, MS/MS, T-cell surface glycoprotein CD4, IFL, 50kDa, IFN, Neuregulin-1, L-ferritin, p35, Actin, DmelCG10377, CG4299, AW124434, CG17603, merged with, TAF[[II]], PAK3, l(2)02647, NF-kappa-B, l(1)G0486, IL2R, l(1)G0245, MOF, lysin activity, fetal AEDS, l(1)G0009, Tolerance, P50, Computer Software Applications., P52, pak3, IGM, DmelCG10370, p44, p49, i2pp2a, time, PAIP, Bladder Pain Syndrome, IFN-ALPHA, criteria, l(1)G0010, p50, NF-kappaB, TRAP, Heregulin, p52, p49/p100, p53, p55, CH3-COOH, dTAFII250, Spectrum Analyses, Computer, anon-EST:CL2c12, PHAPII, Il2r, Volunteer Workers, l(1)G0025, CASP, Methanecarboxylic acid, M(3)S33, polypeptide chain, template-activating factor I, dmTAF1, subnumerary, Injection, Hgl, p63, p65, actin-12, Mass, tiny, IL-17, Pro-Mega, TAF250, TAC antigen, F7K24_80, AW208785, P85, D.m.BETA-60D, MS2, p75, ipp2a2, Minute, dDyn, GGF, Anx-1, DmelCG3922, 10^[-6], p85, Voluntary Workers, p200, HIGM1, ms(3)nc16, beta3-tubulin, Long-Term Effect, F7K24.80, TAF, AW494114, IL7R, small, Applications Software, beta-Tub60D, Ifm(3)7, Open Source, DYRK1, TAF[[II]]250, PSIP2, Computer Software, act 79B, protein complex, beta3-Tub, igaad, l(3)84Ab, Bp50, BEST:RE38067, rrm7, AI875693, anon-WO0153538.10, [HCl], Axin, HOAc, p230, I2PP2A, l(2)k16109, Dyrk1, ARM repeat protein interacting with ABF2, ACETONITRILE, tandem MS, l(1)G0079, Mass Spectrum, Volunteer, TAF[[II]]230, hsp56, MSTP131, act 57A, l(3)E35, CC1, Tripcellim, hnRNP27C, acide acetique, ANX1, CGI-97, EBP-1, dSET/TAF-Ibeta, IL-17A, 2610030F17Rik, DmelCG17603, Acas, velocity, RRM7, AA960152, CD4, INS No. 260, CG8269, HFSP, 1700112N14Rik, AV076380, Actin5C, TAF1, Zfpn1a2, DmelCG7478, MeCN, Tandem, Vinegar, NFKB-p50, CDP, PTPRC/iso:CD45RA, Consent, HDRS, Long Term, DmelCG12051, 5730420M11Rik, DmelCG9648, Pro-NRG1, Polypeptides, protein polypeptide chains, DCad76E, hydrogen chloride, IL-7RA, anon-WO0118547.648, CH3-C#N, Rbp7, Software Engineering, IPEX, Cad76E, MST131, Divorced, hrp48, LEDGF, cyt5C, TFIID TAF250, sarcoma of breast, C430014K04Rik, DmelCG13176, HELIOS, composition, Divorces, proteins, act88F, CDW127, CVID10, AI047805, set, Wasserstoffchlorid, Voluntary Worker, NFAT pre-existing subunit, column, NFATC2, NFATC1, fetal antiepileptic drug syndrome, CT23445, IDDM10, fused to, autolysin activity, TBP-1, SMDF, act87E, M(3)RpS17, p50/tubulin, single organism signaling, lyt, NFAT1-D, BZRP, IL7RA, immune system tolerance, Tnfrsf5, TAF200, antibodies, P85SPR, LYT10, act42A, Software Tools, PBS, bHLHd7, PBR, bHLHd6, bHLHd9, bHLHd8, Computer Applications, bHLHd5, bHLHd4, count, pp52, Dm1, M(3)i(55), AFFX-Dros-ACTIN_M_r_at, Computer Applications Software, Chlorwasserstoff, actin, 1110049F14Rik, leukemic reticuloendotheliosis, C130077D06Rik, GMP23-48K, Hydrogen Oxide, Act57A, Software Applications, HLA-DR-associated protein II, Ethylic acid, maleate, HEL-S-51e, Sensory and motor neuron-derived factor, Source Software, content, alpha-D-Glucopyranoside, AA986903, Spectrometry, beta3TUB, CD4mut, beta Trypsin, human, Act57b, CUTL1, DTB3, actin5C, Painful bladder syndrome, TAF-IBETA, Self Tolerance, Tbp1, CDP/Cut, BcDNA:GH12068, TAF-Ibeta, Lpc1, methyl cyanide, chlorane, fused, scurfin, TAF230, BPBS, beta[[3]]-Tub, FUSED, F10B6_15, knobbly, dmn, IL-7R-alpha, sarcoma of the breast, Effects, chlorure d'hydrogene, Fused, ACT5C, guidelines, protein-containing complex, thomson, F10B6.15, CG30294, DmelCG3025, NF-KB1, CG42273, Application, BETA-PIX, Ftl, portion of blood, RGD1562112, Open Source Softwares, LFTD, AA408223, NF-kB2, Software Application, NF-kB1, NDF, beta-Trypsin, mus79B, Long-Term, Worker, l(3)dtOA4, man, D230005F13Rik, CD156, ftl, Injectable, anon-EST:fe2D2, max, HEM45, 2PP2A, Tools, breakpoint, C87049, dSET, M(3)i[55], DFS70, Chromatographies, IL-7R subunit alpha, Act-5C, Pros26S, Dmbeta3, whole blood, Tap42, Breast cancer cell differentiation factor p45, ZNFN1A2, fkbp52, T-cell transcription factor NFAT1, beta3t, Protein phosphatase 2|4|6 regulatory subunit, IL2-RA, BG:DS00004.13, fkbp59, chloridohydrogen, compositionality, AI449492, acetonitrile, Cell, CG7749, B930045J24, Tool, polypeptide, Wash2, Wash1, Hrp48, anatomical junction, I-2PP2A, beta-actin, p53/tubulin, NFATP, Dm I-2, M32055, TAF[[II]]250/230, NFATc, NFkappaB, Nfatp, Regenerations, underdeveloped, CD79a-binding protein 1, NFAT2, NFAT1, foetal antiepileptic drug syndrome, NFATC, beta3, Mass Spectrometry-Mass Spectrometry, mDRC, CD156a, signalling, Longterm Effects, ME-IV, male human body, Hrp48/Hrb27C, Applications Softwares, MeCOOH, structure, DCTN-50, BAP47, CD127, IL-2-RA, hydrochloric acid, Immunological Tolerance, p50/Dmn, IPP2A2, TFB2, act 87E, determination, RPS17, Essigsaeure, Hydrogenchlorid, Lymphocyte signal transduction molecule alpha 4, RBP50, lysis, betaTub3, composed of, Mass Spectrometry Mass Spectrometry, Act5, CDP1, M(3)67, L3T4, act 88F, CUX, Glacial Acetic Acid, kinky, Min, Dmp52, XPID, present in fewer numbers in organism, Effect, Computer Program, DmelCG42273, male, Cux/CDP, T-BAM, Mass Spectrum Analysis, S6', FACS, l(3)67BDo, Acetic Acid, Untrained Personnel, sf, min, Computer Programs and Programming, purification, Mass Spectrometry, SCAN, IL-7Ralpha, B3t, DmelCG3401, A730095J18Rik, SOLO DANCERS, act 42A, signaling process, Ac5C, 6030402G23Rik, necrosis, Gata-3, Volunteer Personnel, junction, phapii, l(1)G0330, PPIase, T-cell surface antigen T4|Leu-3, GLYA, HBI, 2700043D08Rik, M(3)67C, CG9648, IFNA@, classic hairy cell leukemia, beta-D-fructofuranosyl, Thermo Scientific, Programs, 3t, Program, NF-ATc1, p50B, NF-ATc2, HCD, Ionen, Voluntary, ILRA, HCL, CG7478, Softwares, CG10067, Mnb, parent ion, CDW40, l(1)G0117, ZNF1A2, HCl, Rp S17, WP34, HDR, AI326936, H2TF1, FAC sorting, beta-actin/Bap47, 10280, nanospray, Mof, Endogenous Regeneration, precursor ion, p50/p105, SR3-5, Polypeptide, Ly-43, betaTub, act57b, RE-A, d230, biological signaling, E-260, human being, Act87e, IL-2R subunit alpha, GGFII, Ov5, CG12051, EfW1, act57B, Buffer, act57A, Act88f, reduced, Taf230, HGL, p50/dynamitin, Separated, cloruro de hidrogeno, CH3CO2H, Mass Spectroscopy, 143060_f_at, Taf200, HRGA, DmelCG8269, act5C, DmelCG10067, IFN-alphaD, iones, JM2, Nfatcb, Taf1p, decreased number, AIID, Act42a, Glial growth factor, Lsp-1, taf-ibeta, Informed, betaTub60C, Ftl-1, liquid, HRG1, mKIAA1278, l(1)G0177, data, DBI, 3H-labeled, Males, vertebrate blood, ASC1p100, NBIA3, BETA 60D, DIETER, p110, nfat2, Peptide, Isotope, Software Tool, Neu differentiation factor, PKBS, natural protein, IL-7 receptor subunit alpha, Protein, cool1, Hydrochloride, TFIID, p100, p105, TFIIH, beta[[3]] tubulin, Software, cyanomethane, kugel, CG13176, Separation, E 260, Engineering, beta60C, act 5C, TSP-1, l(2)k16218, Pc52, TAF[II]250, Anx1, CG3922, NRG1-IT2, Trypure, nfatc, Ion, Act(88F), joined with, Peptid, assay, Hrb27-C, acetic acid, LYT-10, AA407739, coalesced"],"pubmed_title_synonyms":["signalling., biological signaling, human being, signalling process, man, signaling process, human, Cell, single organism signaling"],"data_synonyms":["Bru, cox4, Aldehyde dehydrogenase family 1 member L1, Aldehyde dehydrogenase family 1 member L2, Raw, determination, protein, Principal Component Analyses, binding site, Normal Distributions, caudal communicating segment, peptide, dmTAF[[II]]230, Polypeptides, Cut, protein polypeptide chains, peptido, ClvPrd, diseases, l(1)7Ba, l(1)7Bb, diseases and disorders, Analysis, DmelCG10664, protein aggregate, Benson syndrome, Mass Spectrum Analysis, Svc, human disease, F, Pca-1, peptides, TFIID TAF250, Analyses, cel, COXIV, proteins, twy, COXA_DROME, free, CG11387, Mitochondrial 10-FTHFDH, Cox4, Normal, CT, Homo sapiens disease, 1.3.3.3, mtFDH, COX-VA, ratio, dTAF[[II]]230, atresia of nares, Pdnp1, Ct, TAF200, arteria cerebri communicans posterior, Search, TAFII-250, TAF250/230, Spectrum Analysis, Spectroscopy, TAFII250, 4833416E15Rik, C76301, VA, AL024441, Distributions, PCA, Pca, POSTERIOR, COX IV, BcDNA:GH10590, AXPC1, region, 10-FTHFDH, PCS, positional polypeptide feature, Va, Coprogen oxidase, COX IV-1, proportionality, Spectrometry, rate, CG17603, TAF[[II]], human, experimental procedures, data analysis, disease, Principal Component, Taf250, SR3-5, PC-1, DmelCG14724, Polypeptide, Gaussian, Proteomes, Ly-41, Cox4a, TAF230, protein levels, other disease, breadth, d230, CD203c, human being, l(1)VE614, NPP1, experimental, False, region or site annotation, 1.5.1.6, Gene, dTAFII250, Spectrum Analyses, protein-containing complex, EfW1, CG10664, Gaussian Distribution, polypeptide chain, dmTAF1, Taf230, IV, Mass, Gene Products, disease or disorder, Del(8)44H, Distribution, Mass Spectroscopy, TAF250, Npps, FLVCR, Search Engines, proportion, positional, Taf200, Coproporphyrinogenase, methods, dTAF[[II]]250, FDH, cell, experimental section, biparietal Alzheimer disease, Taf1p, man, kf, non-neoplastic, dTAF250, data processing, DmelCG11387, COX, site, disorder, peptidos, MFSD7B, posterior choanal atresia, TAF, TAF[[II]]250, protein complex, Proteins, disorders, l(3)84Ab, BG:DS00004.13, medical condition, Peptide, Cell, Engine, dTAF230, polypeptide, M6S1, native protein, imperforate nares, natural protein, p230, AI428932, chemical analysis, Protein, TAF[[II]]250/230, TFIID, condition, IV-1, Mass Spectrum Analyses, Data Base, Taf[[II]]250, Mass Spectrum, Col4a-1, TAF[[II]]230, Protein., INSDC_feature:misc_binding, tend, choanal atresia, TAF[II]250, posterior communicating segment of the basilar artery, incised, Protein Gene Products, Gene Proteins, CG14724, DmelCG17603, binding_or_interaction_site, PCARP, quotient, Peptid, assay, E-NPP1, ttw, TAF1"],"description_synonyms":["TC-NER, 2610315D21Rik, T-cell surface antigen T4/Leu-3, Feature, FKBP12-rapamycin complex-associated protein, Dstat92E, Receptors, Phases, l(2)k03905, type I programmed cell death, Divisions, DmTOR, dmTAF[[II]]230, L3T4, Extrinsic Pathway Apoptoses, Programmed, Nfat, Ly-4, Alleviating interaction, RAFT1, Mammalian target of rapamycin, IPEX, XPID, M Phases, TFIID TAF250, transcription-coupled NER, cel, FATE, DmSTAT, M, CG4257, sf, Stat, proteins, regulatory T-cell, Dstat 92E, dtor, Division Phase, allergic reaction, stat, Intrinsic Pathway Apoptosis, suppressor T-lymphocyte, PIDX, Classic, signaling process, Classical Apoptosis, STAT, associated, dTOR, dTor, l(3)06346, single organism signaling, FK506-binding protein 12-rapamycin complex-associated protein 1, Data Set., distinct from, Mechanistic target of rapamycin, cellular suicide, D-stat, dTAF[[II]]230, Caspase-Dependent Apoptosis, T-cell surface antigen T4|Leu-3, transcription-coupled repair, TAF200, pSTAT, D-STAT, TAFII-250, TAF250/230, Cell Divisions, alpha-beta regulatory T-lymphocyte, stat92, TAFII250, signaling (initiator) caspase activity, induction of apoptosis, Intrinsic Pathway, regulatory T-lymphocyte, Extrinsic Pathway Apoptosis, CT43, TNF Receptor, CD25-positive, Caspase-Dependent, RAPT1, Stat92, Factors, protein_coding_transcript, T-cell surface glycoprotein CD4, STAT92E, Rapamycin and FKBP12 target 1, common, CD4mut, Cell Death, CG17603, Features, TAF[[II]], human, SmokTcr, Intrinsic Pathway Apoptoses, TonEBP, DmelCG4257, induction of apoptosis by p53, Taf250, SR3-5, 5092, hypersensitivity reaction disease, Dominant negative form of Smok, Extrinsic Pathway, Tumor Necrosis Factor Receptor, T-cell receptor complex, D-Stat, Classical, Proteomes, Apoptoses, scurfin, TAF230, biological signaling, d230, human being, Peptidomics, TNF, CG5092, SD-stat, dstat, dSTAT, caspase-dependent programmed cell death, Gene, Caspase Dependent Apoptosis, dTAFII250, apoptotic programmed cell death, EfW1, Transcription Factor, l(2)k17004, activation of apoptosis, DSRC, Responder protein Smok-Tcr, dmTAF1, Taf230, sensitive, FOXP3, Gene Products, TOR, Type I, dSTAT92E, sensitivity, DmelCG8274, TAF250, RGD1562112, Taf200, Transcription, mrL, dTAF[[II]]250, Bx34, Cell Division Phase, alpha-beta regulatory T-cell, cell, JM2, CD4-positive, messenger RNA, Taf1p, flat, tor, Cell Division, Tpr, TPR, d-STAT, Division, apoptosis activator activity, man, suppressive genetic interaction (sensu inequality), suppressor T cell, AIID, dTAF250, template RNA, mrl, Dstat, Classic Apoptosis, execution phase of apoptotic process, stat92e, Cachectin Receptors, hypersensitivity reaction, Characteristics, TAF, Frap1, programmed cell death by apoptosis, CT24817, DSTAT, Apoptosis, l(3)j6C8, regulatory T lymphocyte, data, TAF[[II]]250, cell suicide, stat[92E], T-lymphocyte receptor complex, DIETER, Tumor Necrosis Factor Receptors, DRODSRC, Proteins, apoptotic cell death, total expressed protein, stat92E, l(3)84Ab, FRAP1, FRAP2, BG:DS00004.13, Factor, mTOR, FRAP/TOR, DmelCG5092, Cell, dTAF230, 2.7.11.1, STAT 92E, Characteristic, Cytokine, TCR complex, T-cell differentiation antigen L3T4, p230, Programmed Cell Death, Protein, INSDC_feature:mRNA, TAF[[II]]250/230, TFIID, M Phase, mrl stat92E, T lymphocyte receptor complex, dSTAT92E/marelle, Cachectin, Taf[[II]]250, apoptosis signaling, Tcr, TCR, Phase, hypersensitivity, NF-AT5, hypersensitive, TAF[[II]]230, suppressor T lymphocyte, apoptosis, mRNA, CT24745, Rapamycin target protein 1, AI327068, TAF[II]250, TNF Receptors, FRAP, Stat1alpha-like, signalling, D-stat/stat92E, Protein Gene Products, Classic Apoptoses, suppressor T-cell, Gene Proteins, DmelCG17603, Treg, CT16317, signalling process, CG8274, apoptotic program, MTOR, alpha-beta regulatory T lymphocyte, commitment to apoptosis, CD4, Receptor, TAF1"],"pubmed_abstract_synonyms":["TC-NER, d230, biological signaling, human being, T-cell surface antigen T4/Leu-3, Activity, Peptidomics, Transcriptome Profile, Laboratory, FON1, Feature, Gene Expression Profile, Gene, dTAFII250, SUPERMAN, protein, Profiles, FLORAL ORGAN NUMBER 1, protein-containing complex, EfW1, Transcription Factor, dmTAF[[II]]230, Responder protein Smok-Tcr, L3T4, protein polypeptide chains, surface, polypeptide chain, dmTAF1, Taf230, T suppressor cell., FOXP3, SUP, Ly-4, symptoms, Research Activity, protein aggregate, IPEX, XPID, Laboratory Research, integumentum commune, TAF250, RGD1562112, Priorities, study, Taf200, Transcription, dTAF[[II]]250, TFIID TAF250, alpha-beta regulatory T-cell, cel, transcription-coupled NER, Research, cell, Profile, JM2, CD4-positive, Bdr, sf, Taf1p, proteins, present in organism, regulatory T-cell, Super protein, man, Signatures, suppressor T cell, sp, AIID, SNAP-25, dTAF250, Mif1, suppressor T-lymphocyte, PIDX, Expression Signature, signaling process, Transcriptomes, Characteristics, Development and Research, Research Priority, TAF, single organism signaling, screening, regulatory T lymphocyte, data, dTAF[[II]]230, TAF[[II]]250, Treg cell, Transcriptome, findings, external covering of organism, T-cell surface antigen T4|Leu-3, protein complex, T-lymphocyte receptor complex, transcription-coupled repair, DIETER, Expression Profiles, TAF200, l(3)84Ab, Research Priorities, organism surface, BG:DS00004.13, Synaptosomal-associated 25 kDa protein, function, Factor, TAFII-250, TAF250/230, Cell, alpha-beta regulatory T-lymphocyte, dTAF230, Gene Expression, TAFII250, 2.7.11.1, Priority, Characteristic, Cytokine, SLEB11, native protein, TCR complex, natural protein, T-cell differentiation antigen L3T4, T suppressor cell, regulatory T-lymphocyte, p230, Expression Signatures, Protein, Gene Expression Signatures, Research Activities, TAF[[II]]250/230, TFIID, GENA70, Gene Expression Signature, CD25-positive, Expression Profile, T lymphocyte receptor complex, Transcriptome Profiles, Research and Development, Taf[[II]]250, Tcr, TCR, TAF[[II]]230, Factors, suppressor T lymphocyte, distinct, body surface, T-cell surface glycoprotein CD4, signs, CD4mut, TAF[II]250, FLO10, CG17603, HERP, Features, TAF[[II]], human, SmokTcr, signalling, Activities, suppressor T-cell, DmelCG17603, Treg, signalling process, Taf250, integumentary system, SR3-5, Gene Expression Profiles, alpha-beta regulatory T lymphocyte, Dominant negative form of Smok, CD4, T-cell receptor complex, Signature, Ts cell, dermal system, scurfin, TAF230, TAF1, FLORAL DEFECTIVE 10"],"name_synonyms":["suppressor T-cell, suppressor T cell., count in organism, regulatory T lymphocyte, biological signaling, suppressor T-lymphocyte, human being, Treg, signalling process, suppressor T lymphocyte, Peptidomics, signaling process, regulatory T-lymphocyte, number, quantitative, regulatory T-cell, man, presence, human, single organism signaling, signalling, presence or absence in organism"],"view_count":["369"],"additional_accession":[]},"is_claimable":true,"name":"Quantitative Proteomics Reveals Specialized Wiring of Signaling Pathways that Protects Human Regulatory T Cell Identity - 6 populations ex vivo","description":"Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Only 12% of 422 differentially expressed proteins was identified as such at the mRNA level, demonstrating the importance of direct proteome measurement. Fifty-one proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFB-, PI3 kinase/mTOR-, NFAT- and STAT pathways, and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, whereas transitional FOXP3+ cells can. Collectively, our data reveal that Treg identity is defined and protected by uniquely “wired” signaling pathways. Associated GEO dataset is available at GSE90600.","dates":{"publication":"2018-05-18","submission":"2017-09-15"},"accession":"PXD007744","cross_references":{"TAXONOMY":["2806551","646099","180498","511145","42249","2156843","544071","284218","327042","3633","3635","11983","430066","3636","2758385","696363","1217666","68888","1114301","55571","145263","145262","3649","34613","126957","366649","2","391619","3641","10665","68895","113636","476272","3661","1123294","42229","55583","2323","122586","3654","34607","92519","3659","1432059","712938","655819","1250232","1195774","81866","196821","586722","568076","1755437","35925","3668","408169","180454","2787751","201089","225058","3674","1479564","100392","3694","2049433","445974","1420012","935293","6715","67593","643867","71605","40483","1315282","69304","562716","391624","29204","277944","762376","1218100","329629","2211376","39488","40479","NCBITaxon:2157","1315273","1051067","2059687","2016516","368407","1736309","698936","104782","148364","32042","1061","32049","1381693","743277","32046","45351","11103","217459","216129","288671","288676","4100","694569","4101","6763","4102","1076","1277351","1316582","1358430","1417298","174633","6754","128735","6756","84030","135062","1813019","4111","929439","367110","4113","64459","1394984","32025","301270","1498751","104759","4120","478861","347495","153721","1097","1652998","2790513","9803","1758543","9801","2608663","9808","13757","55518","32019","64471","114155","421932","55521","1383439","1193181","9813","9818","1026970","10699","55529","NCBITaxon:4751","8502","9833","5476","4146","5477","9825","102169","157273","9823","89764","84074","13735","1862870","5482","4153","NCBITaxon:50557","9844","67525","1000364","334147","5480","35974","13708","115466","5478","9835","322159","9838","10677","103481","9852","348780","42253","1488414","222863","47946","1571871","59919","157295","29292","1175271","9860","1488406","334249","518691","234","235","152335","9858","9859","886559","74649","9870","392021","11072","36352","7215","9874","1908","28743","4182","35024","1451139","69293","1902","593907","1901","746360","12374","746361","7226","253","60013","197221","1915","85310","588596","9895","11051","9899","7237","9897","72000","263","419610","264","266","7227","588581","568996","287375","62690","7244","2023717","201999","8570","7240","747679","274","596153","335543","1931","335541","84005","13686","150596","86662","86661","347515","36329","NCBITaxon:1763","286","287","348837","670580","271848","186536","8595","986075","105135","294","296","11009","84023","210007","348824","12336","36307","1047005","187878","945556","449447","NCBITaxon:1335626","54195","913998","78168","11901","147828","1055524","NCBITaxon:9606","135858","469008","1979153","51930","72859","300852","641140","9005","118499","526225","412133","75913","9014","38111","39442","3704","1204414","3708","351581","990119","51953","2590841","3701","3702","39432","227748","62615","83558","3715","3716","333760","57267","998086","3711","3712","190650","3714","75917","2073127","262981","27457","57270","9030","9031","3728","1424337","142104","479249","11082","39412","NCBITaxon:9615","147802","69266","1006581","3735","2750454","1356638","1647520","3750","644223","669502","1293497","9054","632245","552536","51997","649908","1438992","3745","3747","264732","3760","264731","288705","595536","252740","327160","29385","1149786","479436","29382","479437","225117","75299","167387","1938441","3765","93934","327159","100226","3767","42344","42345","46700","1287689","591198","46704","146479","29365","28034","28038","28035","1080348","179392","295027","1131","6819","1126","526997","102862","10760","159736","1143","1140","981087","1355477","43658","1424507","229533","79698","204232","124223","321803","369822","34708","1645733","1654675","99287","77020","38293","1412529","5508","1148","1744888","643745","2649997","283035","718308","5507","176299","707678","92683","70415","1562887","651388","563924","56115","2086595","5516","5518","113549","1432137","159749","535026","1432138","58781","707683","194963","401614","28005","31646","104660","381518","45474","48500","97476","97477","1180","51240","1748418","55601","555479","204274","2014887","1105325","329726","1005941","28909","316435","9900","13894","382835","4232","4233","1082934","1220585","604162","9913","112273","170187","9915","429131","267818","1871049","316407","299467","303","337330","485264","638301","1306413","9925","306","4236","1211620","652616","103372","8612","9940","207340","115357","652611","1147161","338654","312017","253237","1255232","9935","316","317","NCBITaxon:11084","9938","41063","267872","8623","219334","8620","8621","160791","392227","681196","1255228","149539","321","322","323","34774","1218275","329","1757312","9948","8618","1408434","103351","9963","1392488","115338","115339","330","439375","56992","8626","339","1120948","8624","157183","9975","8644","42374","8643","533244","426066","533241","343","909768","212717","8637","8639","9983","9986","8655","352914","86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