Nuclear pore glycoprotein p62

Structure

P62 is a serine/threonine rich protein of ~520 amino acids, with tetrapeptide repeats on the amino terminus and a series of alpha-helical regions with hydrophobic heptad repeats forming beta-propeller domain. P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45 forming the p62 complex of ~235 kDa. O-GlcNAcylation appears to be involved in the assembly and disassembly of p62 into higher order complexes, and a serine/threonine rich linker region between Ser270 to Thr294 appear to be regulatory. The p62 complex is localized to both the nucleoplasmic and cytoplasmic sides of the pore complex and the relative diameter of p62 complex relative to the nuclear pore complex suggests it interacts in pore gating.

Function

P62 appears to interact with mRNA during transport out of the nucleus. P62 also interacts with a nuclear transport factor (NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus. Another protein, importin (beta) binds to the helical rod section of p62, which also binds NTF2 suggesting the formation of a higher order gating complex. Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62. P62 also interacts with Nup93, and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes. Mutant pores could not dock/transport proteins with nuclear localization signals or M9 import signals.

Pathology

Antibodies to p62 complex are involved in one or more autoimmune diseases. P62 glycosylation is increased in diabetes and may influence its association with other diseases. p62 is also more frequent in Stage IV primary biliary cirrhosis and is prognostic for severe disease.

Interactions

Nucleoporin 62 has been shown to interact with:

• HSF2,
• KPNB1,
• NUTF2,
• TRAF3, and
• XPO1,
• Nup93.

References

References

1. (1986). "Identification and characterization of a nuclear pore complex protein". Cell.
2. (1987). "Nuclear pore complex contains a family of glycoproteins that includes p62: glycosylation through a previously unidentified cellular pathway". Proc. Natl. Acad. Sci. U.S.A..
3. "Entrez Gene: NUP62 nucleoporin 62kDa".
4. (1990). "Primary sequence and heterologous expression of nuclear pore glycoprotein p62". J. Cell Biol..
5. (1993). "Purification and characterization of a nuclear pore glycoprotein complex containing p62". J. Biochem..
6. (1995). "Macromolecular interactions in the nucleoporin p62 complex of rat nuclear pores: binding of nucleoporin p54 to the rod domain of p62". J. Cell Biol..
7. (1995). "Analysis of nuclear pore protein p62 glycosylation". Biochemistry.
8. (1995). "Structural analysis of the p62 complex, an assembly of O-linked glycoproteins that localizes near the central gated channel of the nuclear pore complex". Mol. Biol. Cell.
9. (1995). "Direct interaction of nucleoporin p62 with mRNA during its export from the nucleus". J. Cell Sci..
10. (1996). "The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2)". J. Mol. Biol..
11. (1997). "Molecular interactions between the importin alpha/beta heterodimer and proteins involved in vertebrate nuclear protein import". J. Mol. Biol..
12. (1997). "Cloning and characterization of human karyopherin β3". Proc. Natl. Acad. Sci. U.S.A..
13. (1997). "Nup93, a Vertebrate Homologue of Yeast Nic96p, Forms a Complex with a Novel 205-kDa Protein and Is Required for Correct Nuclear Pore Assembly". Mol. Biol. Cell.
14. (2001). "Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function". Proc. Natl. Acad. Sci. U.S.A..
15. (2000). "Responsiveness of the state of O-linked N-acetylglucosamine modification of nuclear pore protein p62 to the extracellular glucose concentration". Biochem. J..
16. (2003). "Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study". J. Autoimmun..
17. (Nov 1997). "The trimerization domain of human heat shock factor 2 is able to interact with nucleoporin p62". Biochem. Biophys. Res. Commun..
18. (Jan 2001). "Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import". J. Cell Biol..
19. (Aug 1996). "Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins". J. Cell Biol..
20. (May 1995). "Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62". J. Cell Biol..
21. (2000). "TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes". Mol. Immunol..
22. (May 1999). "A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export". J. Cell Biol..
23. (Jun 2001). "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export". J. Cell Biol..