KIF28P

Model summary

A cytoplasmic, ATP-driven microtubule motor that uses an N-terminal kinesin engine and a central phospho-recognition module to couple cargo transport with signaling. By binding and hydrolyzing nucleotides to move along microtubules, it assembles and positions complexes that regulate small GTPase pathways and build actin-rich protrusions. Its soluble pool in the cytosol and transient presence at the intercellular bridge and nucleoplasm reflect roles in cytokinesis and signaling-dependent cargo selection, enabling assembly of lamellipodia and filopodia through coordinated transport and adaptor-mediated interactions.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The N-terminus is dominated by a canonical kinesin motor module: IPR001752 (Kinesin motor domain, residues 6–363) sits within two broader signatures, IPR036961 (Kinesin motor domain superfamily, residues 9–375) and IPR027417 (P-loop containing nucleoside triphosphate hydrolase superfamily, residues 11–364). This arrangement establishes an ATP-dependent microtubule motor core that binds and hydrolyzes NTP to generate directed movement along microtubules. Midway through the sequence, IPR008984 (SMAD/FHA domain superfamily, residues 383–479) encompasses a discrete IPR000253 (Forkhead-associated, FHA domain, residues 425–472). FHA domains are phosphothreonine-recognition modules that recruit phosphorylated partners and thereby couple motor activity to signaling pathways and cargo selection. The C-terminal region carries IPR022140 (Kinesin-like KIF1-type, residues 599–633), a hallmark of kinesin-3/KIF1 family members whose architecture supports high-processivity transport and cargo-specific regulation. The ordered layout—N-terminal ATPase motor, central FHA signaling adaptor, and C-terminal KIF1-type tail—creates a transport machine whose activity is gated by phosphorylation-dependent interactions.

2. 02

   From this architecture, the molecular function resolves as ATP-driven microtubule-based motility with multivalent protein binding.

   The kinesin motor core causes ATP-dependent translocation and cargo engagement, while the FHA domain confers selective protein binding to phospho-marked adaptors and regulators. This supports GO:0005515 protein binding and implies ATPase-coupled motor activity that organizes cytoskeletal transport.

3. 03

   The biological processes follow from how this motor-scaffold shapes cell-edge dynamics and small GTPase signaling.

   The FHA adaptor recruits phospho-regulated complexes that tune Rho-family and Rab GTPase pathways; this coupling provides a direct route to GO:0051056 regulation of small GTPase mediated signal transduction. By delivering and positioning actin-assembly factors at the cortex, the motor promotes protrusive structures—consistent with GO:0046847 filopodium assembly and GO:0030032 lamellipodium assembly. The KIF1-type tail further biases cargo selection toward endomembrane and cytoskeletal assemblies that seed these protrusions.

4. 04

   Cellular localization emerges from both the transport mechanism and the observed compartments.

   The soluble motor operates in the cytoplasm and cytosol, aligning with GO:0005829 cytosol. Its role in mitotic and cytokinetic structures explains presence at the GO:0045171 intercellular bridge, where microtubule and actin systems converge during abscission. Transient nucleoplasmic residency (GO:0005654 nucleoplasm) is consistent with shuttling and regulatory sequestration typical of signaling-coupled motors and FHA-containing scaffolds.

5. 05

   Mechanistically, the N-terminal kinesin motor domain binds microtubules and hydrolyzes ATP to drive anterograde transport.

   The central FHA domain captures phosphorylated adaptors and checkpoint factors, which tunes cargo selection and pathway coupling. The C-terminal KIF1-type region specifies interactions that bias trafficking toward endomembrane and cytoskeletal cargos. Through this tri-modular system, the protein assembles and positions complexes that regulate small GTPase signaling and build lamellipodia and filopodia.

6. 06

   I hypothesize interactions with phosphorylated adaptor proteins and checkpoint modules that recognize the FHA domain (e.g., pThr-containing scaffolds), with microtubule tracks and associated MAPs.

   At the cell edge, it likely engages actin-assembly hubs and small GTPase regulators to coordinate protrusion dynamics and cytokinetic bridge maturation.