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PXD018013

PXD018013 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNAA15 haploinsufficiency can cause congenital heart disease and perturbs protein levels in induced pluripotent stem cells
DescriptionNAA15 is a component of the NatA complex that acetylates amino terminal (Nt) protein residues and influences protein synthesis. We identified multiple damaging NAA15 variants in congenital heart disease patients, including four loss-of-function (LoF) variants, one missense (R276W) de novo variant and 15 rare inherited missense variants. To understand the effects of these variants on NatA complex activity, we introduced heterozygous LoF, compound heterozygous and missense residues iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to alterations in the amount and composition of the NatA complex. Mass spectrometry (MS)-based N-terminomics analyses showed that nearly 80% of iPS cell proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells, 32 and 9 NatA-specific targeted proteins differed in their Nt-acetylation degree, respectively. In addition, the steady-state protein levels of more than 560 proteins were altered in mutant compared to wild type cells. While most NatA-specific Nt-acetylated proteins were fully acetylated, ~19 proteins were partially acetylated. NAA15-haploinsufficiency abrogated Nt-acetylation of 4 of these proteins but did not affect the acetylation of the other 15 proteins. Similar patterns of acetylation loss in few proteins were observed in both NAA15 haploinsufficient and NAA15 R276W iPS cells. These studies define human proteins that appear to require the full NAA15 complex for normal acetylation and imply that deficiencies in one or more of these NAA15 target proteins contribute to normal cardiac development. The current dataset contains all N-terminomics data related to this study.
HostingRepositoryPRIDE
AnnounceDate2024-10-07
AnnouncementXMLSubmission_2024-10-07_10:37:29.247.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD018013
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAn Staes
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListOxidation; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-03-12 03:18:02ID requested
12024-10-07 10:37:30announced
Publication List
10.1161/circresaha.120.316966;
Ward T, Tai W, Morton S, Impens F, Van Damme P, Van Haver D, Timmerman E, Venturini G, Zhang K, Jang MY, Willcox JAL, Haghighi A, Gelb BD, Chung WK, Goldmuntz E, Porter GA, Lifton RP, Brueckner M, Yost HJ, Bruneau BG, Gorham J, Kim Y, Pereira A, Homsy J, Benson CC, DePalma SR, Varland S, Chen CS, Arnesen T, Gevaert K, Seidman C, Seidman JG, Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency. Circ Res, 128(8):1156-1169(2021) [pubmed]
10.6019/PXD018013;
Keyword List
submitter keyword: iPSC,N-terminal acetylation, N-terminomics
Contact List
Jonathan Seidman
contact affiliation1 Department of Genetics, Harvard Medical School, Boston, MA 02115
contact emailseidman@genetics.med.harvard.edu
lab head
An Staes
contact affiliationMedical Protein Chemistry
contact emailan.staes@vib-ugent.be
dataset submitter
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Dataset FTP location
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