Nuclear pore glycoprotein p62is a protein complex associated with thenuclear envelope. The p62 protein remains associated with thenuclear pore complex-lamina fraction. p62 is synthesized as a solublecytoplasmic precursor of 61 kDa[5] followed by modification that involve addition ofN-acetylglucosamine residues,[6] followed by association with other complex proteins. In humans it is encoded by theNUP62 gene.
Thenuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm.Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of theFG repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with theimportin alpha/beta complex which is involved in the import of proteins containingnuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform.[7]
P62 is aserine/threonine rich protein of ~520 amino acids, with tetrapeptide repeats on theamino terminus and a series ofalpha-helical regions with hydrophobicheptad repeats[8] formingbeta-propeller domain. P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45[9][10] forming thep62 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.[11] Thep62 complex is localized to both thenucleoplasmic 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.[12]
P62 appears to interact withmRNA during transport out of the nucleus.[13] P62 also interacts with a nuclear transport factor (NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus.[14] Another protein, importin (beta) binds to the helical rod section of p62, which alsobinds NTF2 suggesting the formation of a higher order gating complex.[15] Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62.[16] P62 also interacts withNup93,[17] and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes.[18] Mutant pores could not dock/transport proteins with nuclear localization signals or M9 import signals.
Antibodies to p62 complex are involved in one or more autoimmune diseases. P62 glycosylation is increased in diabetes[19] and may influence its association with other diseases. p62 is also more frequent in Stage IVprimary biliary cirrhosis and is prognostic for severe disease.[20]
^Lubas WA, Smith M, Starr CM, Hanover JA (1995). "Analysis of nuclear pore protein p62 glycosylation".Biochemistry.34 (5):1686–94.doi:10.1021/bi00005a025.PMID7849028.
^Bullock TL, Clarkson WD, Kent HM, Stewart M (1996). "The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2)".J. Mol. Biol.260 (3):422–31.doi:10.1006/jmbi.1996.0411.PMID8757804.
^abPercipalle P, Clarkson WD, Kent HM, Rhodes D, Stewart M (1997). "Molecular interactions between the importin alpha/beta heterodimer and proteins involved in vertebrate nuclear protein import".J. Mol. Biol.266 (4):722–32.doi:10.1006/jmbi.1996.0801.PMID9102465.
^Miyachi K, Hankins RW, Matsushima H, Kikuchi F, Inomata T, Horigome T, Shibata M, Onozuka Y, Ueno Y, Hashimoto E, Hayashi N, Shibuya A, Amaki S, Miyakawa H (2003). "Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study".J. Autoimmun.20 (3):247–54.doi:10.1016/S0896-8411(03)00033-7.PMID12753810.
^Yoshima T, Yura T, Yanagi H (Nov 1997). "The trimerization domain of human heat shock factor 2 is able to interact with nucleoporin p62".Biochem. Biophys. Res. Commun.240 (1):228–33.doi:10.1006/bbrc.1997.7662.PMID9367915.
^Gamper C, van Eyndhoven WG, Schweiger E, Mossbacher M, Koo B, Lederman S (2000). "TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes".Mol. Immunol.37 (1–2):73–84.doi:10.1016/S0161-5890(00)00015-8.PMID10781837.
Carmo-Fonseca M, Kern H, Hurt EC (1991). "Human nucleoporin p62 and the essential yeast nuclear pore protein NSP1 show sequence homology and a similar domain organization".Eur. J. Cell Biol.55 (1):17–30.PMID1915414.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides".Gene.138 (1–2):171–4.doi:10.1016/0378-1119(94)90802-8.PMID8125298.
Grote M, Kubitscheck U, Reichelt R, Peters R (1996). "Mapping of nucleoporins to the center of the nuclear pore complex by post-embedding immunogold electron microscopy".J. Cell Sci.108 (9):2963–72.doi:10.1242/jcs.108.9.2963.PMID8537436.
Bullock TL, Clarkson WD, Kent HM, Stewart M (1996). "The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2)".J. Mol. Biol.260 (3):422–31.doi:10.1006/jmbi.1996.0411.PMID8757804.
Percipalle P, Clarkson WD, Kent HM, Rhodes D, Stewart M (1997). "Molecular interactions between the importin alpha/beta heterodimer and proteins involved in vertebrate nuclear protein import".J. Mol. Biol.266 (4):722–32.doi:10.1006/jmbi.1996.0801.PMID9102465.
Yoshima T, Yura T, Yanagi H (1997). "The trimerization domain of human heat shock factor 2 is able to interact with nucleoporin p62".Biochem. Biophys. Res. Commun.240 (1):228–33.doi:10.1006/bbrc.1997.7662.PMID9367915.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library".Gene.200 (1–2):149–56.doi:10.1016/S0378-1119(97)00411-3.PMID9373149.
