Nucleoporin 62

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Nucleoporin 62kDa

Nuclear pore complex
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsNUP62 (; IBSN; SNDI; p62)
External IDsOMIM605815 MGI1351500 HomoloGene68773 GeneCards: NUP62 Gene
Orthologs
SpeciesHumanMouse
Entrez2363618226
EnsemblENSG00000213024ENSMUSG00000043858
UniProtP37198Q63850
RefSeq (mRNA)NM_001193357NM_053074
RefSeq (protein)NP_001180286NP_444304
Location (UCSC)Chr 19:
50.41 – 50.43 Mb
Chr 7:
44.82 – 44.83 Mb
PubMed search[1][2]
 
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Nucleoporin 62kDa

Nuclear pore complex
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsNUP62 (; IBSN; SNDI; p62)
External IDsOMIM605815 MGI1351500 HomoloGene68773 GeneCards: NUP62 Gene
Orthologs
SpeciesHumanMouse
Entrez2363618226
EnsemblENSG00000213024ENSMUSG00000043858
UniProtP37198Q63850
RefSeq (mRNA)NM_001193357NM_053074
RefSeq (protein)NP_001180286NP_444304
Location (UCSC)Chr 19:
50.41 – 50.43 Mb
Chr 7:
44.82 – 44.83 Mb
PubMed search[1][2]

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.

The nuclear 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 the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform.[3]

Structure[edit]

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.[4] P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45 [5][6] 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.[7] 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.[8]

Function[edit]

P62 appears to interact with mRNA during transport out of the nucleus.[9] P62 also interacts with a nuclear transport factor (NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus.[10] 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.[11] Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62.[12] P62 also interacts with nucleoporin-93kDa,[13] and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes.[14] Mutant pores could not dock/transport proteins with nuclear localization signals or M9 import signals.

Pathology[edit]

Antibodies to p62 complex are involved in 1 or more autoimmune diseases. P62 glycosylation is increased in diabetes.[15] 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.[16]

Interactions[edit]

Nucleoporin 62 has been shown to interact with XPO1,[17][18] KPNB1,[11][19] TRAF3,[20] HSF2[21] and NUTF2.[22][23]

Further reading[edit]


References[edit]

  1. ^ Davis LI, Blobel G (1986). "Identification and characterization of a nuclear pore complex protein". Cell 45 (5): 699–709. doi:10.1016/0092-8674(86)90784-1. 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. doi:10.1073/pnas.84.21.7552. PMC 299337. PMID 3313397. 
  3. ^ "Entrez Gene: NUP62 nucleoporin 62kDa". 
  4. ^ 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. doi:10.1083/jcb.110.6.1861. PMC 2116139. PMID 2190987. 
  5. ^ 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. 
  6. ^ 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. doi:10.1083/jcb.128.3.251. PMC 2120351. PMID 7531196. 
  7. ^ 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. PMID 7849028. 
  8. ^ 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. PMC 301313. PMID 8589458. 
  9. ^ 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 (1): 257–63. PMID 7738103. 
  10. ^ 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. PMID 8757804. 
  11. ^ a b 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. 
  12. ^ Yaseen NR, Blobel G (1997). "Cloning and characterization of human karyopherin β3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. doi:10.1073/pnas.94.9.4451. PMC 20743. PMID 9114010. 
  13. ^ 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. PMC 25664. PMID 9348540. 
  14. ^ 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. PMC 30629. PMID 11248054. 
  15. ^ 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 (Pt 1): 109–14. doi:10.1042/0264-6021:3500109. PMC 1221231. PMID 10926833. 
  16. ^ 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. doi:10.1016/S0896-8411(03)00033-7. PMID 12753810. 
  17. ^ Kehlenbach, R H; Dickmanns A, Kehlenbach A, Guan T, Gerace L (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. (UNITED STATES) 145 (4): 645–57. doi:10.1083/jcb.145.4.645. ISSN 0021-9525. PMC 2133185. PMID 10330396. 
  18. ^ Lindsay, M E; Holaska J M, Welch K, Paschal B M, Macara I G (Jun 2001). "Ran-Binding Protein 3 Is a Cofactor for Crm1-Mediated Nuclear Protein Export". J. Cell Biol. (United States) 153 (7): 1391–402. doi:10.1083/jcb.153.7.1391. ISSN 0021-9525. PMC 2150735. PMID 11425870. 
  19. ^ Ben-Efraim, I; Gerace L (Jan 2001). "Gradient of Increasing Affinity of Importin β for Nucleoporins along the Pathway of Nuclear Import". J. Cell Biol. (United States) 152 (2): 411–7. doi:10.1083/jcb.152.2.411. ISSN 0021-9525. PMC 2199621. PMID 11266456. 
  20. ^ Gamper, C; van Eyndhoven W G, 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. (ENGLAND) 37 (1–2): 73–84. doi:10.1016/S0161-5890(00)00015-8. ISSN 0161-5890. PMID 10781837. 
  21. ^ 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. (UNITED STATES) 240 (1): 228–33. doi:10.1006/bbrc.1997.7662. ISSN 0006-291X. PMID 9367915. 
  22. ^ Hu, T; Guan T, Gerace L (Aug 1996). "Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins". J. Cell Biol. (UNITED STATES) 134 (3): 589–601. doi:10.1083/jcb.134.3.589. ISSN 0021-9525. PMC 2120945. PMID 8707840. 
  23. ^ Paschal, B M; Gerace L (May 1995). "Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62". J. Cell Biol. (UNITED STATES) 129 (4): 925–37. doi:10.1083/jcb.129.4.925. ISSN 0021-9525. PMC 2120498. PMID 7744965.