Nup62

Nup62 Full Name

nucleoporin 62kDa

Nup62 Introduction

NUP62 (Nucleoporin 62) encodes a 62 kDa glycoprotein that serves as a central component of the nuclear pore complex (NPC), the massive macromolecular structure that spans the nuclear envelope and regulates all bidirectional transport between the nucleus and cytoplasm. As a member of the FG-repeat containing nucleoporins, NUP62 is localized to the central plug or transport channel of the NPC, where it forms a stable subcomplex with two other nucleoporins, NUP54 and NUP58. This NUP62·NUP54·NUP58 complex constitutes the core transport channel, with structural studies revealing that NUP62 and NUP54 form parallel triple helical bundles that project from a flexible midplane ring, creating the nucleoplasmic and cytoplasmic entries of the pore. The channel contains up to 224 copies of these three nucleoporins, collectively contributing 256 phenylalanine-glycine (FG) repeat regions that establish the selective permeability barrier.

Figure 1.Nup62-mediated nuclear import of p63 in squamous cell carcinoma.(Borlido J, 2016)

Molecular Mechanism of Nucleocytoplasmic Transport
The NUP62 protein functions as a critical docking site for soluble nuclear transport receptors during the import and export of macromolecules. Through its extensive FG repeat domains, NUP62 interacts directly with the importin alpha/beta complex, which recognizes and transports proteins containing classical nuclear localization signals. This interaction is mediated by reversible binding between transport receptors and the FG repeats, allowing cargo-loaded complexes to traverse the permeability barrier while excluding non-specific macromolecules. The NUP62-containing channel exhibits remarkable structural plasticity, with the NUP54·NUP58 ring capable of undergoing large-scale rearrangements that change the channel diameter from approximately 20 to 40 nm, potentially regulated by the occupancy of FG repeats with transport receptors. Beyond its transport functions, NUP62 also localizes to the mitotic spindle poles during cell division, suggesting additional roles in cell cycle progression and chromosome segregation.

Clinical Significance in Human Disease
NUP62 is implicated in both rare genetic disorders and autoimmune conditions. Autosomal recessive mutations in the NUP62 gene, particularly the Gln391Pro substitution, cause infantile striatonigral degeneration (SNDI), also known as infantile bilateral striatal necrosis (IBSN). This severe neurological disorder is characterized by symmetrical degeneration of the caudate nucleus and putamen, leading to developmental regression, dystonia, spasticity, and optic atrophy. Structural analysis reveals that the disease-causing mutation destabilizes the NUP62·NUP54 triple helical complex, likely compromising NPC integrity and nucleocytoplasmic transport in affected neurons. Additionally, NUP62 serves as a major autoantigen in primary biliary cholangitis (PBC), with anti-p62 antibodies detected in approximately 22-32% of patients. These autoantibodies recognize the FG-repeat regions and are highly specific for PBC, serving as diagnostic markers particularly in patients lacking conventional antimitochondrial antibodies.

Alternate Names for Nup62

NUP62; nucleoporin 62kDa; nucleoporin 62kD; nuclear pore glycoprotein p62; DKFZp547L134; FLJ20822; FLJ43869; IBSN; MGC841; p62; SNDI; nucleoporin Nup62; 62 kDa nucleoporin; nucleoporin