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Nuclear pore glycoprotein p62

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NUP62
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNUP62, IBSN, SNDI, p62, nucleoporin 62kDa, nucleoporin 62
External IDsOMIM: 605815; MGI: 1351500; HomoloGene: 68773; GeneCards: NUP62; OMA:NUP62 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

23636

18226

Ensembl

ENSG00000213024

ENSMUSG00000109511

UniProt

P37198

Q63850

RefSeq (mRNA)

NM_153719
NM_001193357
NM_012346
NM_016553
NM_153718

NM_053074

RefSeq (protein)

NP_001180286
NP_036478
NP_057637
NP_714940
NP_714941

NP_444304

Location (UCSC)Chr 19: 49.91 – 49.93 MbChr 7: 44.47 – 44.48 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Nuclear pore glycoprotein 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[5] followed by modification that involve addition of N-acetylglucosamine residues,[6] followed by association with other complex proteins. In humans it is encoded by the NUP62 gene.

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.[7]

Structure

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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[8] forming beta-propeller domain. P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45 [9][10] 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.[11] 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.[12]

Function

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P62 appears to interact with mRNA 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 also binds 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 with Nup93,[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.

Pathology

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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 IV primary biliary cirrhosis and is prognostic for severe disease.[20]

Interactions

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Nucleoporin 62 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000213024 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000109511 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. S2CID 22170880.
  6. ^ 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. Bibcode:1987PNAS...84.7552D. doi:10.1073/pnas.84.21.7552. PMC 299337. PMID 3313397.
  7. ^ "Entrez Gene: NUP62 nucleoporin 62kDa".
  8. ^ 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.
  9. ^ Kita K, Omata S, Horigome T (1993). "Purification and characterization of a nuclear pore glycoprotein complex containing p62". J. Biochem. 113 (3): 377–82. doi:10.1093/oxfordjournals.jbchem.a124054. PMID 8486610.
  10. ^ 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.
  11. ^ 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.
  12. ^ Guan T, Müller S, Klier G, Panté N, Blevitt JM, Haner M, Paschal B, Aebi U, Gerace L (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. doi:10.1091/mbc.6.11.1591. PMC 301313. PMID 8589458.
  13. ^ 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. doi:10.1242/jcs.108.1.257. PMID 7738103.
  14. ^ 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.
  15. ^ 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.
  16. ^ Yaseen NR, Blobel G (1997). "Cloning and characterization of human karyopherin β3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. Bibcode:1997PNAS...94.4451Y. doi:10.1073/pnas.94.9.4451. PMC 20743. PMID 9114010.
  17. ^ a b Grandi P, Dang T, Pané N, Shevchenko A, Mann M, Forbes D, Hurt E (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. doi:10.1091/mbc.8.10.2017. PMC 25664. PMID 9348540.
  18. ^ 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. Bibcode:2001PNAS...98.3191W. doi:10.1073/pnas.051631598. PMC 30629. PMID 11248054.
  19. ^ 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.
  20. ^ 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. PMID 12753810.
  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. 240 (1): 228–33. doi:10.1006/bbrc.1997.7662. PMID 9367915.
  22. ^ Ben-Efraim I, Gerace L (Jan 2001). "Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import". J. Cell Biol. 152 (2): 411–7. doi:10.1083/jcb.152.2.411. PMC 2199621. PMID 11266456.
  23. ^ 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. 134 (3): 589–601. doi:10.1083/jcb.134.3.589. PMC 2120945. PMID 8707840.
  24. ^ Paschal BM, Gerace L (May 1995). "Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62". J. Cell Biol. 129 (4): 925–37. doi:10.1083/jcb.129.4.925. PMC 2120498. PMID 7744965.
  25. ^ 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. PMID 10781837.
  26. ^ Kehlenbach RH, 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. 145 (4): 645–57. doi:10.1083/jcb.145.4.645. PMC 2133185. PMID 10330396.
  27. ^ Lindsay ME, Holaska JM, Welch K, Paschal BM, Macara IG (Jun 2001). "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export". J. Cell Biol. 153 (7): 1391–402. doi:10.1083/jcb.153.7.1391. PMC 2150735. PMID 11425870.

Further reading

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