NPIPA5

Model summary

A soluble nuclear scaffold that associates with the nuclear pore interface and uses multivalent binding to organize nucleoporin- and transport factor–rich assemblies in the nucleoplasm. By tuning nucleocytoplasmic trafficking and transcriptional programs, it enhances pro-angiogenic signaling pathways and thereby promotes vessel formation. Its mechanism centers on NPC-proximal complex assembly that biases nuclear import/export and mRNA handling to elevate angiogenesis-related outputs.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The polypeptide carries IPR054697 (Nuclear pore complex interacting protein, N-terminal domain) spanning residues 22–253, embedded within a broader family signature IPR009443 (Nuclear pore complex interacting protein family) that covers residues 9–335. This arrangement—an N-terminal NPC-interacting module nested inside a full-length NPC-interacting family envelope—defines a soluble, non-enzymatic scaffold specialized for binding nuclear pore-associated assemblies. The absence of catalytic motifs and the prominence of an NPC-binding N-terminus causally enforce a role dominated by multivalent contacts with nucleoporins and transport factors, which directly supports GO:0005515 protein binding as the molecular function.

2. 02

   From this binding-centric core, I infer the biological role by considering how NPC-associated scaffolds tune nucleocytoplasmic transport and gene-regulatory programs.

   NPC-interacting proteins frequently modulate the flux of transcription factors and mRNPs between nucleus and cytoplasm. Such control can elevate pro-angiogenic signaling pathways by increasing nuclear access or stabilization of VEGF/Notch pathway effectors, thereby driving vessel formation. This mechanistic linkage—NPC-tethered binding that enhances nuclear trafficking and transcriptional output of angiogenic programs—maps to GO:0045766 positive regulation of angiogenesis.

3. 03

   The domain architecture lacks transmembrane segments and secretion signals, and NPC-interacting scaffolds typically operate on the nuclear side of the pore.

   This positions the protein within the nuclear interior where it can engage nucleoporins and chromatin-associated complexes. Thus, the cellular component is the GO:0005654 nucleoplasm, consistent with a soluble NPC-proximal factor that functions at the nuclear face of the pore.

4. 04

   Mechanistically, the N-terminal NPC-interacting domain likely anchors the protein to nucleoporin hubs and transiently to karyopherins, forming a platform that biases nuclear import/export selectivity and mRNA export.

   By stabilizing assemblies with FG-repeat nucleoporins and transport receptors, the scaffold can increase the nuclear residence and transcriptional activity of angiogenesis drivers. I therefore hypothesize interactions with core pore constituents (NUP153, NUP62, NUP98, TPR), transport machinery (KPNB1/importin-β, TNPO1/transportin), and mRNA export factors (NXF1/TAP and ALYREF), collectively explaining nucleoplasmic localization and the observed pro-angiogenic influence.