Biology:NUP98

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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

Function

Signal-mediated nuclear import and export proceed through the nuclear pore complex (NPC), which is composed of approximately 30 unique proteins collectively known as nucleoporins. The 98 kD nucleoporin is generated through a biogenesis pathway that involves synthesis and proteolytic cleavage of a 186 kD precursor protein. This cleavage results in the 98 kD nucleoporin as well as a 96 kD nucleoporin, both of which are localized to the nucleoplasmic side of the NPC. Rat studies show that the 98 kD nucleoporin functions as one of several docking site nucleoporins of transport substrates. The human gene has been shown to fuse to several genes following chromosome translocations in acute myelogenous leukemia (AML) and T-cell acute lymphocytic leukemia (T-ALL). This gene is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described.

Interactions

NUP98 has been shown to interact with:

• CREB-binding protein,
• KPNB1,
• NUP88,
• RAE1, and
• TNPO2.

Further reading

• "The role of NUP98 gene fusions in hematologic malignancy". Leuk. Lymphoma 45 (7): 1341–50. 2004. doi:10.1080/10428190310001659325. PMID 15359631. 
• "NUP98 dysregulation in myeloid leukemogenesis". Ann. N. Y. Acad. Sci. 1106 (1): 114–42. 2007. doi:10.1196/annals.1392.019. PMID 17442773. Bibcode: 2007NYASA1106..114M. 
• "The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex". Cell 81 (2): 215–22. 1995. doi:10.1016/0092-8674(95)90331-3. PMID 7736573. 
• "Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia". Nat. Genet. 12 (2): 154–8. 1996. doi:10.1038/ng0296-154. PMID 8563753. 
• "The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9". Nat. Genet. 12 (2): 159–67. 1996. doi:10.1038/ng0296-159. PMID 8563754. 
• "Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins". J. Cell Biol. 134 (3): 589–601. 1996. doi:10.1083/jcb.134.3.589. PMID 8707840. 
• "A role for nucleoporin FG repeat domains in export of human immunodeficiency virus type 1 Rev protein and RNA from the nucleus". Mol. Cell. Biol. 16 (12): 7144–50. 1996. doi:10.1128/mcb.16.12.7144. PMID 8943370. 
• "Cloning and characterization of human karyopherin beta3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. 1997. doi:10.1073/pnas.94.9.4451. PMID 9114010. Bibcode: 1997PNAS...94.4451Y. 
• "Karyopherin beta2 mediates nuclear import of a mRNA binding protein". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5055–60. 1997. doi:10.1073/pnas.94.10.5055. PMID 9144189. Bibcode: 1997PNAS...94.5055B. 
• "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. 1997. doi:10.1091/mbc.8.10.2017. PMID 9348540. 
• "Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev". J. Virol. 73 (1): 120–7. 1999. doi:10.1128/JVI.73.1.120-127.1999. PMID 9847314. 
• "CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity". Mol. Cell. Biol. 19 (1): 764–76. 1999. doi:10.1128/mcb.19.1.764. PMID 9858599. 
• "A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96". J. Cell Biol. 144 (6): 1097–112. 1999. doi:10.1083/jcb.144.6.1097. PMID 10087256. 
• "RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at the nuclear pore complex through multiple domains". J. Cell Biol. 145 (2): 237–54. 1999. doi:10.1083/jcb.145.2.237. PMID 10209021. 
• "The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion". Blood 94 (9): 3258–61. 1999. doi:10.1182/blood.V94.9.3258. PMID 10556215. 
• "The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates". RNA 6 (1): 136–58. 2000. doi:10.1017/S1355838200991994. PMID 10668806. 
• "The nucleoporin Nup98 is a site for GDP/GTP exchange on ran and termination of karyopherin beta 2-mediated nuclear import". J. Biol. Chem. 275 (40): 31289–96. 2000. doi:10.1074/jbc.M004651200. PMID 10875935. 
• "Vesicular stomatitis virus matrix protein inhibits host cell gene expression by targeting the nucleoporin Nup98". Mol. Cell 6 (5): 1243–52. 2000. doi:10.1016/S1097-2765(00)00120-9. PMID 11106761. 
• "Cofactor requirements for nuclear export of Rev response element (RRE)- and constitutive transport element (CTE)-containing retroviral RNAs. An unexpected role for actin". J. Cell Biol. 152 (5): 895–910. 2001. doi:10.1083/jcb.152.5.895. PMID 11238447.