Nuclear pore glycoprotein p62

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.

NUP62
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5IJN, 5IJO
Identifiers
Aliases	NUP62, IBSN, SNDI, p62, nucleoporin 62kDa, nucleoporin 62
External IDs	OMIM: 605815 MGI: 1351500 HomoloGene: 68773 GeneCards: NUP62
Gene location (Human) Chr. Chromosome 19 (human)^[1] Band 19q13.33 Start 49,906,825 bp^[1] End 49,929,763 bp^[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)^[2] Band 7 B3|7 28.93 cM Start 44,465,512 bp^[2] End 44,480,236 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in embryo ganglionic eminence monocyte oocyte appendix lymph node secondary oocyte right adrenal gland stromal cell of endometrium smooth muscle tissue Top expressed in condyle primitive streak fossa secondary oocyte hair follicle endocardial cushion renal corpuscle medullary collecting duct Paneth cell somite More reference expression data BioGPS n/a
Gene ontology Molecular function Hsp90 protein binding SH2 domain binding chromatin binding thyroid hormone receptor binding PTB domain binding Hsp70 protein binding protein binding ubiquitin binding signaling receptor complex adaptor activity structural constituent of nuclear pore phospholipid binding kinesin binding Cellular component nuclear membrane Flemming body nuclear pore lamellae anulatae cytoskeleton nuclear pore central transport channel spindle pole cytoplasm centrosome mitotic spindle nuclear envelope microtubule organizing center nucleus protein-containing complex ribonucleoprotein complex host cell Biological process mRNA transport negative regulation of epidermal growth factor receptor signaling pathway regulation of Ras protein signal transduction cell death negative regulation of apoptotic process transcription, DNA-templated negative regulation of Ras protein signal transduction positive regulation of transcription, DNA-templated cell surface receptor signaling pathway regulation of signal transduction negative regulation of MAP kinase activity spermatogenesis regulation of protein import into nucleus hormone-mediated signaling pathway positive regulation of I-kappaB kinase/NF-kappaB signaling protein transport negative regulation of programmed cell death nuclear transport viral process positive regulation of epidermal growth factor receptor signaling pathway negative regulation of cell population proliferation protein import into nucleus mRNA export from nucleus mitotic metaphase plate congression mitotic centrosome separation positive regulation of mitotic nuclear division positive regulation of centriole replication regulation of mitotic spindle organization centriole assembly positive regulation of mitotic cytokinetic process positive regulation of protein localization to centrosome centrosome cycle mitotic cell cycle protein heterotrimerization regulation of glycolytic process tRNA export from nucleus protein sumoylation viral transcription regulation of gene silencing by miRNA intracellular transport of virus regulation of cellular response to heat Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 7: 44.47 – 44.48 Mb PubMed search ^[3] ^[4]
Wikidata
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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

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

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

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

Nucleoporin 62 has been shown to interact with:

• HSF2,^[21]
• KPNB1,^[15][22]
• NUTF2,^[23][24]
• TRAF3,^[25] and
• XPO1,^[26][27]
• Nup93.^[17]

References

1. GRCh38: Ensembl release 89: ENSG00000213024 - Ensembl, May 2017
2. 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. 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. 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

• Stoffler D, Fahrenkrog B, Aebi U (1999). "The nuclear pore complex: from molecular architecture to functional dynamics". Curr. Opin. Cell Biol. 11 (3): 391–401. doi:10.1016/S0955-0674(99)80055-6. PMID 10395558.
• Geetha T, Wooten MW (2002). "Structure and functional properties of the ubiquitin binding protein p62". FEBS Lett. 512 (1–3): 19–24. doi:10.1016/S0014-5793(02)02286-X. PMID 11852044. S2CID 22029085.
• 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. PMID 1915414.
• Paschal BM, Gerace L (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.
• 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. PMID 8125298.
• 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. PMID 8537436.
• Guan T, Müller S, Klier G, Panté N, Blevitt JM, Haner M, Paschal B, Aebi U, Gerace L (1996). "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.
• Park I, Chung J, Walsh CT, Yun Y, Strominger JL, Shin J (1996). "Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12338–42. doi:10.1073/pnas.92.26.12338. PMC 40352. PMID 8618896.
• Joung I, Strominger JL, Shin J (1996). "Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain". Proc. Natl. Acad. Sci. U.S.A. 93 (12): 5991–5. Bibcode:1996PNAS...93.5991J. doi:10.1073/pnas.93.12.5991. PMC 39176. PMID 8650207.
• Vadlamudi RK, Joung I, Strominger JL, Shin J (1996). "p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins". J. Biol. Chem. 271 (34): 20235–7. doi:10.1074/jbc.271.34.20235. PMID 8702753.
• Hu T, Guan T, Gerace L (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.
• 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.
• 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.
• 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.
• 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. PMID 9367915.
• 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. PMID 9373149.
• Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, Gerace L (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.
• Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (1999). "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation". EMBO J. 18 (11): 3044–53. doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400.
• Rachubinski RA, Marcus SL, Capone JP (1999). "The p56(lck)-interacting protein p62 stimulates transcription via the SV40 enhancer". J. Biol. Chem. 274 (26): 18278–84. doi:10.1074/jbc.274.26.18278. PMID 10373430.