PXD076503

PXD076503 is an original dataset announced via ProteomeXchange.

Title	Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations
Description	Transcriptional regulatory proteins, including transcription factors (TFs) and chromatin modifiers, must act inside cell nuclei, but membrane-bound transcription factors (MBTFs) are first anchored in membranes before nuclear translocation. Known MBTFs are vital for processes from myelin expression (MYRF) to cholesterol homeostasis (SREBP), yet their overall diversity remains uncharted. We hypothesized that additional membrane-bound transcriptional regulators (MBTRs) might exist, so we developed a bioinformatics screen to prioritize membrane proteins that are likely to regulate transcription. Our approach leverages domain composition by positing that surprising domain combinations suggest novel biological functions. We searched for rare but evolutionarily conserved pairings of transmembrane domains with domains likely involved in transcriptional regulation. Our method rediscovered known MBTFs and membrane-bound histone kinases, and identified novel MBTR candidates, including transmembrane histone N-acetyltransferases, a putative new subclass of MBTFs that share MYRF's DNA-binding domain, and the prolactin regulatory element-binding protein PREB (SEC12). Assays using recombinant PREB demonstrated that the transmembrane domain is the determinant of PREB subcellular localization, governing its distribution between the membrane and the nucleus in mouse embryonic stem cells. These findings underscore the utility of our method and provide a framework for investigating MBTRs that likely facilitate the integration of extracellular signals with transcriptional responses.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:27:11.504.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ujwal Punyamurtula
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-02 05:02:12	ID requested
⏵ 1	2026-06-28 16:27:12	announced

Lee M, Jang Y, Guo Q, Punyamurtula U, Choi J, Kim J, Marcotte EM, Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations. Nucleic Acids Res, 54(12):(2026) [pubmed]

10.1093/nar/gkag635;

submitter keyword: None

Edward Marcotte
contact affiliation	Edward M. Marcotte, PhD Center for Systems and Synthetic Biology Department of Molecular Biosciences University of Texas at Austin 2500 Speedway, MBB 3.148BA Austin, TX 78712-0159
contact email	marcotte@utexas.edu
lab head
Ujwal Punyamurtula
contact affiliation	The University of Texas at Austin
contact email	usnpunyam@utexas.edu
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/2026/06/PXD076503

PRIDE project URI

• PRIDE
  1. PXD076503
     1. Label: PRIDE project
     2. Name: Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations