Nucleoporin 62

Last updated
NUP62
NuclearPore crop.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NUP62 , IBSN, SNDI, p62, nucleoporin 62kDa, nucleoporin 62
External IDs OMIM: 605815 MGI: 1351500 HomoloGene: 68773 GeneCards: NUP62
Orthologs
SpeciesHumanMouse
Entrez

23636

18226

Ensembl

ENSG00000213024

ENSMUSG00000109511

UniProt

P37198

Q63850

RefSeq (mRNA)

NM_153719
NM_001193357
NM_012346
NM_016553
NM_153718

Contents

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 n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

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 [4] followed by modification that involve addition of N-acetylglucosamine residues, [5] 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. [6]

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

Function

P62 appears to interact with mRNA during transport out of the nucleus. [12] P62 also interacts with a nuclear transport factor (NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus. [13] 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. [14] Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62. [15] P62 also interacts with Nup93, [16] and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes. [17] 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 [18] 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. [19]

Interactions

Nucleoporin 62 has been shown to interact with:

Related Research Articles

Nuclear pore

A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes (NPCs) in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in the life cycle. The human nuclear pore complex (hNPC) is a 110 megadalton (MDa) structure. The proteins that make up the nuclear pore complex are known as nucleoporins; each NPC contains at least 456 individual protein molecules and is composed of 34 distinct nucleoporin proteins. About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. The other half show structural characteristics typical of "natively unfolded" or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ordered tertiary structure. These disordered proteins are the FG nucleoporins, so called because their amino-acid sequence contains many phenylalanine—glycine repeats.

Ran (protein) GTPase functioning in nuclear transport

Ran also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily.

Nucleoporin 210kDa

Nuclear pore glycoprotein-210 (gp210) is an essential trafficking regulator in the eukaryotic nuclear pore complex. Gp-210 anchors the pore complex to the nuclear membrane. and protein tagging reveals its primarily located on the luminal side of double layer membrane at the pore. A single polypeptide motif of gp210 is responsible for sorting to nuclear membrane, and indicate the carboxyl tail of the protein is oriented toward the cytoplasmic side of the membrane.

Nucleoporin Family of proteins that form the nuclear pore complex

Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC). The nuclear pore complex is a massive structure embedded in the nuclear envelope at sites where the inner and outer nuclear membranes fuse, forming a gateway that regulates the flow of macromolecules between the cell nucleus and the cytoplasm. Nuclear pores enable the passive and facilitated transport of molecules across the nuclear envelope. Nucleoporins, a family of around 30 proteins, are the main components of the nuclear pore complex in eukaryotic cells. Nucleoporin 62 is the most abundant member of this family. Nucleoporins are able to transport molecules across the nuclear envelope at a very high rate. A single NPC is able to transport 60,000 protein molecules across the nuclear envelope every minute.

KPNB1 Protein-coding gene in the species Homo sapiens

Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.

NUP98

Nuclear pore complex protein Nup98-Nup96 is a protein that in humans is encoded by the NUP98 gene.

RANBP2

RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the RANBP2 gene. It is also known as nucleoporin 358 (Nup358) since it is a member nucleoporin family that makes up the nuclear pore complex. RanBP2 has a mass of 358 kDa.

Nucleoporin 153

Nucleoporin 153 (Nup153) is a protein which in humans is encoded by the NUP153 gene. It is an essential component of the basket of nuclear pore complexes (NPCs) in vertebrates, and required for the anchoring of NPCs. It also acts as the docking site of an importing karyopherin. On the cytoplasmic side of the NPC, Nup358 fulfills an analogous role.

Nucleoporin 214

Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the NUP214 gene.

Nucleoporin 88

Nucleoporin 88 (Nup88) is a protein that in humans is encoded by the NUP88 gene.

Nucleoporin 50

Nucleoporin 50 (Nup50) is a protein that in humans is encoded by the NUP50 gene.

Nucleoporin 107

Nucleoporin 107 (Nup107) is a protein that in humans is encoded by the NUP107 gene.

NUTF2

Nuclear transport factor 2 is a protein that in humans is encoded by the NUTF2 gene.

Nucleoporin 54

Nucleoporin 54 (Nup54) is a protein that in humans is encoded by the NUP54 gene.

Nucleoporin 133

Nucleoporin 133 (Nup133) is a protein that in humans is encoded by the NUP133 gene.

Nucleoporin 160

Nucleoporin 160 (Nup160) is a protein that in humans is encoded by the NUP160 gene.

Nucleoporin 93

Nucleoporin 93 (Nup93) is a protein that in humans is encoded by the NUP93 gene.

NUPL1

Nucleoporin p58/p45 is a protein that in humans is encoded by the NUPL1 gene.

Nucleoporin 35

Nucleoporin 35 (Nup35) is a protein that in humans is encoded by the NUP35 gene.

Nucleoporin 37 (Nup37) is a protein that in humans is encoded by the NUP37 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000213024 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ "Entrez Gene: NUP62 nucleoporin 62kDa".
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. 1 2 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.
  15. ↑ 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.
  16. 1 2 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  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. 134 (3): 589–601. doi:10.1083/jcb.134.3.589. PMC   2120945 . PMID   8707840.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.

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