{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD072759/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD072759/XA02959GP_NR1H2.raw"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD072759/SEARCH.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["liushuolin007@163.com"],"submitter":["shuolin liu"],"technology_type":["Data-dependent acquisition","Mass Spectrometry"],"software":[""],"submitter_keywords":["heart failure","Anthracyclines; macrophage; march2; heart failure; mice","Anthracyclines","march2","macrophage","mice"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD072759"],"tissue":["Heart"],"sample_protocol":["Mouse hearts were harvested and dissociated into single-cell suspensions according to the method mentioned above. The digested tissues were passed through a 70 μm cell strainer. After lysing the red blood cells (RBCs), cell suspensions were enriched with Anti-F4/80-MicroBeads UltraPure (Miltenyi, #130-110-443). F4/80+ cells were isolated using a magnet following the manufacturer’s protocols. The cardiac macrophages were cultured in RPMI 1640 medium supplemented with 1% FBS. Cardiac macrophages were quickly homogenized in phenol extraction buffer and then treated with lysate solution containg 5mM DTT. Cut the gel bands into particles about 1 cubic millimeter in size, add 50% ethanol for decolorization overnight. Remove the decolorizing solution, the sample was washed with 50mM NH4HCO3 for twice. Add 200 μL 50mM NH4HCO3 containing a final concentration of 20 ng/μL trypsin to the sample and the digestion was performed at 37℃ overnight. Add 200μL 100% acetonitrile for dehydration and repeat this step twice. Finally, the supernatant was combined and evaporated to dryness at room temperature by using a vacuum concentrator. Add 80 μL of 50mM NH4HCO3 to the dried samples and vortex for 30 s. Add the final concentration of 10 mM DTT and reduce it for 60 min at 37℃. Add the final concentration of 50 mM IAM and incubate at room temperature in the dark for 45 min. For LC-MS/MS analysis, the resulting peptides were desalted with C18 ZipTips (Millipore) according to the manufacturer’s instructions."],"repository":["Pride"],"modification":[""],"quantification_method":["Not available"],"data_protocol":["1 Mass Spectrometer The tryptic peptides were dissolved in solvent A, directly loaded onto a home-made reversed-phase analytical column (15-cm length, 100 μm i.d.). The mobile phase consisted of solvent A (0.1% formic acid in water) and solvent B (0.1% formic acid, 80% acetonitrile/in water). Peptides were separated with the following gradient:0-0.5 min，2.0%B；0.5-0.6 min，2.0%-5.0%B；0.6-13.6 min,5%-20.5%B；13.6-20.5 min，20.5%-32%B；20.5-20.9 min，32.0-55.0%B;20.9-21.4 min,55.0-99.0%B;21.4-22.6 min,99.0%B, and all at a constant flow rate of 400 nl/min on a Vanquish Neo UPLC system (ThermoFisher Scientific). The separated peptides were analyzed in Orbitrap Astral with a nano-electrospray ion source. The electrospray voltage applied was 1900 V . Precursors were analyzed at the Orbitrap detector,and the fragments were analyzed at the Astral detector. The full MS scan resolution was set to 240000 for a scan range of 380-980 m/z.  The MS/MS scan was fixed first mass as 150.0 m/z at a resolution of 80000. The HCD fragmentation was performed at a normalized collision energy (NCE) of 25 %. Automatic gain control (AGC) target was set at 500%, with a maximum injection time of 3 ms.  2 Database Search The DIA data were processed using Spectronaut (v.18) software.Tandem mass spectra were searched against the Homo_sapiens_9606_SP_20241202.fasta (20422 entries) concatenated with reverse decoy database.Trypsin/P was specified as cleavage enzyme allowing up to 2 missing cleavages. Carbamidomethyl on Cys was specified as fixed modification. Acetylation on protein N-terminal, oxidation on Met and phosphorylation(S/T) were specified as variable modifications. False discovery rate (FDR) of protein, peptide and PSM was adjusted to < 1%."],"omics_type":["Proteomics"],"labhead":["Shuolin Liu"],"instrument_platform":[""],"labhead_affiliation":["1 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China. 2 Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"publication":["41963318 Liu S, Li YE, Zhu T, Zhang L, Yang C, Bi Y, Bao C, Hu R, Ge J, Zhang Y. MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes. Nat Commun. 2026 17(1):5114 10.1038/s41467-026-71580-z"],"submitter_mail":["liushuolin007@163.com"],"submitter_affiliation":["Department of Cardiology and Shanghai Institute of Cardiovascular Diseases\nZhongshan Hospital, Fudan University"],"submitter_country":["China"],"pubmed_abstract":["Doxorubicin-induced cardiomyopathy (DiCM) involves impaired clearance of apoptotic cardiomyocytes (efferocytosis) by cardiac macrophages. This study reveals a central role for the MARCH2-NR1H2 axis in this process. We find that MARCH2 expression is significantly reduced in cardiac macrophages from DiCM mice and human dilated cardiomyopathy patients. Genetic ablation of MARCH2, either globally (MARCH2<sup>-/-</sup>) or specifically in resident cardiac macrophages (MARCH2<sup>f/f</sup>; CX3CR1<sup>Cre</sup>), exacerbates DiCM, impairs efferocytosis, and increases inflammation. Mechanistically, MARCH2 enhances the protein stability of the nuclear receptor NR1H2 via K27-linked polyubiquitination, leading to upregulation of the efferocytosis receptor MERTK. Conversely, macrophage-specific NR1H2 deficiency (NR1H2<sup>f/f</sup>; CX3CR1<sup>Cre</sup>) suppresses efferocytosis and worsens cardiac dysfunction. Importantly, pharmacological activation of NR1H2 attenuates DiCM progression. These findings identify the MARCH2-NR1H2 axis as a key regulator of macrophage efferocytosis and a potential therapeutic target for DiCM."],"pubmed_title":["MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes."],"pubmed_authors":["Liu Shuolin S, Li Yiran E YE, Zhu TingFang T, Zhang LaiHai L, Yang Cong C, Bi YaGuang Y, Bao Chenglong C, Hu Ronggui R, Ge Junbo J, Zhang Yingmei Y"],"additional_accession":[]},"is_claimable":false,"name":"MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes","description":"Doxorubicin-induced cardiomyopathy (DiCM) is a leading cause of heart failure and mortality in cancer patients, with doxorubicin-induced cardiomyocyte apoptosis constituting a fundamental pathological mechanism. Cardiac resident macrophages are primarily responsible for the effective clearance of apoptotic cardiomyocytes (efferocytosis), a process pivotal for suppressing inflammatory response and adverse cardiac remodeling. To identify genes implicated in DiCM, RNA sequencing was performed using heart tissues from saline- and DOX-treated wild-type (WT) mice. Ubiquitin mass spectrometry was used to identify the ubiquitin site of nuclear receptor subfamily 1 group H member 2 (NR1H2).","dates":{"publication":"2026-06-15","submission":"2026-01-07"},"accession":"PXD072759","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:111205","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:2086595","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:3357","NEWT:111225","NEWT:7719","NEWT:29073","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:2020713","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:2502409","NEWT:212790","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:3715","NEWT:1538","NEWT:2065263","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:2714896","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1608994","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:1122981","NEWT:2853422","NEWT:1122984","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:1380096","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:30455","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:299467","NEWT:9541","NEWT:51350","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:542","NEWT:2903","NEWT:185579","NEWT:872227","NEWT:13076","NEWT:2587410","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:2126337","NEWT:550","NEWT:10804","NEWT:33941","NEWT:554","NEWT:4515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