YPEL4

Model summary

A human adaptor protein that uses a single Yippee fold to dimerize and bind partners, assembling regulatory complexes that operate both in the nucleoplasm and at the midbody. By scaffolding cytokinetic and nuclear modules, it helps coordinate late-mitotic events and tunes pathways that drive entry into and maintenance of cellular senescence. Its mechanism centers on multivalent protein binding that stabilizes midbody machinery and integrates nuclear checkpoint signaling.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The core of the protein is a single compact module: IPR034751 (Yippee domain, residues 27–124) that overlaps with IPR004910 (Yippee/Mis18/Cereblon domain, residues 29–120) and is encompassed by IPR039058 (Yippee family, residues 16–123). This tightly coextensive layout defines a solitary Yippee fold that typically forms obligate dimers and serves as a versatile protein–protein interaction hub rather than a catalytic center. The Yippee/Mis18/Cereblon signature links this fold to cell-cycle and centrosome-associated pathways (Mis18 at centromeres and cereblon-family E3 adaptors), reinforcing a role in assembling higher-order complexes. The absence of enzymatic motifs and the dominance of a single oligomerization/adaptor domain causally point to GO:0005515 protein binding as the primary molecular function.

2. 02

   From this binding-centric architecture, I infer process-level roles by mapping where and when such scaffolds act.

   The Yippee fold is frequently deployed in mitotic and cytokinetic assemblies; this aligns with localization to the midbody and supports GO:2000772 regulation of cellular senescence. A non-enzymatic adaptor that accumulates at the midbody can modulate signaling pathways that feed into senescence checkpoints. The nucleoplasmic presence further suggests coupling between nuclear stress responses and cytoskeletal remodeling.

3. 03

   Cellular localization consolidates this model.

   The protein resides in the nucleoplasm (GO:0005654 nucleoplasm) and concentrates at the midbody (GO:0030496 midbody). Midbody enrichment during cytokinesis positions the scaffold at the final abscission site, where it can coordinate ESCRT and microtubule-associated assemblies. Nucleoplasmic residency provides a route to integrate transcriptional and chromatin-associated cues that precede or accompany senescence.

4. 04

   Mechanistically, the Yippee domain drives homodimerization and heterotypic binding, creating a platform that recruits midbody and nuclear partners.

   At the cytokinetic bridge, it likely binds ESCRT adaptors and centralspindlin components to stabilize abscission machinery; in the nucleus, it may engage chromatin- and checkpoint-associated factors to tune senescence entry. This adaptor-centric mechanism explains how a single Yippee module can influence both midbody dynamics and senescence pathways.

5. 05

   I therefore hypothesize that the protein functions as a dimeric adaptor that nucleates complexes at the midbody and in the nucleoplasm.

   Likely partners include ESCRT-associated ALIX/PDCD6IP and TSG101 for membrane-remodeling at abscission; centralspindlin constituents such as KIF23/MKLP1 and RACGAP1 for microtubule bundling; and nuclear regulators such as Mis18-associated centromere organizers or cereblon-family E3 modules that couple cell-cycle status to senescence control.