PXD072123-1

PXD072123 is an original dataset announced via ProteomeXchange.

Title	Molecular Basis and Cellular Effects of Janus-Class–Driven Cytoplasmic PYK2 Coacervates
Description	Kinase activity is increasingly associated with biomolecular phase separation. Focal adhesion kinase (FAK) forms membrane-associated condensates with paxillin to promote adhesion. Here we show that its paralogue, proline-rich tyrosine kinase 2 (PYK2), undergoes phase separation via a distinct mechanism. PYK2 forms cytoplasmic condensates primarily driven by its kinase–FAT linker (KFL) region. Overexpression of PYK2 induces condensates enriched in its autophosphorylated form, which sequester paxillin from focal adhesions and impair cell adhesion. We uncover an autoregulatory mechanism involving the KFL, linking self-association, autophosphorylation, and condensation. Uncommon among known phase separation drivers, KFL condensation is phosphorylation-independent and its sequence belongs to the “Janus” class. Using a transformer-based protein language model, we identified non-homologous sequences with similar features, many from adhesion and cytoskeletal regulators. We validated the phase-separating potential of several of these sequences in cells. These findings reveal a mechanism linking phase separation with kinase activation, and demonstrate distinct condensation behavior in homologues. Our results also highlight how protein concentration modulates condensate function, with implications for disease, and expand the landscape of phase separation drivers.
HostingRepository	PRIDE
AnnounceDate	2026-01-11
AnnouncementXML	Submission_2026-01-11_00:27:51.770.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD072123
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Afaque Ahmad Momin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-17 17:06:58	ID requested
⏵ 1	2026-01-11 00:27:52	announced

Colombo G, Salem I, Szczepski K, Yu P, Alfaiyz S, Guzm, á, n-Vega FJ, Abogosh A, Kulmanov M, Al-Harthi S, Kadar, é G, Hoehndorf R, Girault JA, Jaremko Ł, Momin AA, Arold ST, Molecular basis and cellular effects of Janus-class-driven cytoplasmic PYK2 coacervates. Commun Biol, 9(1):186(2026) [pubmed]

10.6019/PXD072123;

10.1038/s42003-025-09463-0;

submitter keyword: focal adhesion, ESM2, cancer, kinase, phase separation, Janus class

Stefan T. Arold
contact affiliation	King Abdullah University of Science and Technology
contact email	stefan.arold@kaust.edu.sa
lab head
Afaque Ahmad Momin
contact affiliation	King Abdullah University of Science and Technology
contact email	afaqueahmad.momin@kaust.edu.sa
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/2026/01/PXD072123

PRIDE project URI

• PRIDE
  1. PXD072123
     1. Label: PRIDE project
     2. Name: Molecular Basis and Cellular Effects of Janus-Class–Driven Cytoplasmic PYK2 Coacervates