Nucleoporin 62

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Nucleoporin 62kDa

Nuclear pore complex
Symbol(s): NUP62 p62
Genetic data
Locus: Chr. 19 q13.33
Gene code: NUP62
Protein Structure/Function
Protein length: 522 (Amino Acids)
Molecular Weight: 62 k (Da)
Functions: Protein/RNA traffic regulator Nuclear pore complex
Other
Taxa expressing: Homo sapiens
Cell types: All
Subcellular localization: Nuclear membrane
Pathway(s): Nuclear/Cytoplasmic trafficking
Enzymatic Data
Cofactor(s): NUPs
Database Links
OMIM: 605815
RefSeq: NM_153718
UniProt: P37198
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Nucleoporin p62 (p62) is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa[1] followed by modification that involve addition of N-acetylglucosamine residues.[2] followed by association with other complex proteins.

Contents

[edit] Structure

P62 is a serine/threonine rich polypeptide of ~520 amino acids, with tetrapeptide repeats on the amino terminus and a series of alpha-helical regions with hydrophobic heptad repeats.[3] P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45 [4][5] forming the p62 complex of ~235 kDa. Glycosylation 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.[6] 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.[7]

[edit] Function

P62 appears to interact with mRNA during transport out of the nucleus.[8] P62 also interacts with a nuclear transport factor (NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus.[9] 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.[10] Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62.[11] P62 also interacts with nucleoporin-93kDa[12], and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes.[13] Mutant pores could not dock/transport proteins with nuclear localization signals or M9 import signals.

[edit] Pathology

Antibodies to p62 complex are involved in 1 or more autoimmune diseases. P62 glycosylation is increased in diabetes.[14] 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.[15]

[edit] References

  1. ^ Davis LI, Blobel G (1986). "Identification and characterization of a nuclear pore complex protein". Cell 45 (5): 699–709. PMID 3518946. 
  2. ^ Davis LI, Blobel G (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. 84 (21): 7552–6. PMID 3313397. 
  3. ^ Starr CM, D'Onofrio M, Park MK, Hanover JA (1990). "Primary sequence and heterologous expression of nuclear pore glycoprotein p62". J. Cell Biol. 110 (6): 1861–71. PMID 2190987. 
  4. ^ Kita K, Omata S, Horigome T (1993). "Purification and characterization of a nuclear pore glycoprotein complex containing p62". J. Biochem. 113 (3): 377–82. PMID 8486610. 
  5. ^ Buss F, Stewart M (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. 128 (3): 251–61. PMID 7531196. 
  6. ^ Lubas WA, Smith M, Starr CM, Hanover JA (1995). "Analysis of nuclear pore protein p62 glycosylation". Biochemistry 34 (5): 1686–94. PMID 7849028. 
  7. ^ Guan T, Müller S, Klier G, et al (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 6 (11): 1591–603. PMID 8589458. 
  8. ^ Dargemont C, Schmidt-Zachmann MS, Kühn LC (1995). "Direct interaction of nucleoporin p62 with mRNA during its export from the nucleus". J. Cell. Sci. 108 ( Pt 1): 257–63. PMID 7738103. 
  9. ^ 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. PMID 8757804. 
  10. ^ 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. PMID 9102465. 
  11. ^ Yaseen NR, Blobel G (1997). "Cloning and characterization of human karyopherin beta3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. PMID 9114010. 
  12. ^ Grandi P, Dang T, Pané N, et al (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 8 (10): 2017–38. PMID 9348540. 
  13. ^ Wu X, Kasper LH, Mantcheva RT, Mantchev GT, Springett MJ, van Deursen JM (2001). "Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3191–6. doi:10.1073/pnas.051631598. PMID 11248054. 
  14. ^ Han I, Oh ES, Kudlow JE (2000). "Responsiveness of the state of O-linked N-acetylglucosamine modification of nuclear pore protein p62 to the extracellular glucose concentration". Biochem. J. 350 Pt 1: 109–14. PMID 10926833. 
  15. ^ Miyachi K, Hankins RW, Matsushima H, et al (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. PMID 12753810. 
v • d • e
Antigens: Autoantigens
Dehydrogenase
Transglutaminase
Nucleoporins
Nucleoporin-62 - Nucleoporin-210
Other