PXD014119

PXD014119 is an original dataset announced via ProteomeXchange.

Title	Sir4 H-BRCT domain interacts with multiple phospho-proteins to regulate heterochromatic repression
Description	In Saccharomyces cerevisiae, the Silent Information Regulator (SIR) proteins Sir2/3/4 form a complex suppressing transcription of genes at subtelomeric regions and the homothallic mating type (HM) loci. Here we identify a non-canonical BRCA1 C-terminal domain (H-BRCT) in Sir4 which is responsible for tethering telomeres to the nuclear periphery. We show that Sir4 H-BRCT and the closely related Dbf4 H-BRCT serve as selective phospho-epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established Sir4 interactors (Esc1, Ty5, Ubp10) and identify several novel interactors of Sir4 H-BRCT, including the E3 ubiquitin ligase Tom1. Based on these findings, we propose a phospho-peptide consensus motif for interaction with Sir4 H-BRCT and Dbf4 H-BRCT. Ablation of the Sir4 H-BRCT phospho-peptide interaction disrupts SIR-mediated repression and perinuclear localization. In conclusion, the Sir4 H-BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:55:25.806.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vytautas Iesmantavicius
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-04 06:12:12	ID requested
1	2019-09-13 02:09:02	announced
2	2019-10-25 05:20:57	announced	2019-10-25: Updated publication reference for PubMed record(s): 31515872.
⏵ 3	2024-10-22 04:55:30	announced	2024-10-22: Updated project metadata.

10.15252/embj.2019101744;

Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H, The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin. EMBO J, 38(20):e101744(2019) [pubmed]

submitter keyword: Tom1, SIR complex, heterochromatin,BRCT, Dbf4

Heinz Gut
contact affiliation	Head of Protein Structure facility, Friedrich Miescher Institute for Biomedical Research
contact email	heinz.m.gut@gmail.com
lab head
Vytautas Iesmantavicius
contact affiliation	Friedrich Miescher Institute for Biomedical Research
contact email	vytautas.iesmantavicius@fmi.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/09/PXD014119

PRIDE project URI

• PRIDE
  1. PXD014119
     1. Label: PRIDE project
     2. Name: Sir4 H-BRCT domain interacts with multiple phospho-proteins to regulate heterochromatic repression