Biology:Nucleoporin 214

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

Generic protein structure example

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

Function

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. This gene is a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is localized to the cytoplasmic face of the nuclear pore complex where it is required for proper cell cycle progression and nucleocytoplasmic transport. The 3' portion of this gene forms a fusion gene with the DEK gene on chromosome 6 in a t(6,9) translocation associated with acute myeloid leukemia and myelodysplastic syndrome.

Structure

The structure of the N-terminal domain of Nup214 reveals a sevenbladed beta-propeller fold followed by a 30-residue C-terminal extended peptide segment (CTE). The CTE folds back onto the beta propeller and binds to its bottom face. The structure of the Nup214 NTD bound to the helicase Ddx19 in its ADP-bound state reveals the molecular basis for the interaction between the two proteins. A conserved residue of Ddx19 is shown to be crucial for complex formation in vitro and in vivo. Strikingly, the interaction surfaces exhibit strongly opposing surface potentials, with the helicase surface being positively and the Nup214 surface being negatively charged. Ddx19 is shown to bind RNA only in its ATP-bound state, and the binding of RNA and the Nup214 NTD is mutually exclusive.

Interactions

NUP214 has been shown to interact with:

• DDX19,
• CRM1
• NXF1, and
• NXF2, and
• ZFP36.

Further reading

• "The nuclear pore complex: from molecular architecture to functional dynamics". Current Opinion in Cell Biology 11 (3): 391–401. Jun 1999. doi:10.1016/S0955-0674(99)80055-6. PMID 10395558. 
• "The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA". Molecular and Cellular Biology 12 (4): 1687–97. Apr 1992. doi:10.1128/mcb.12.4.1687. PMID 1549122. 
• "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1". DNA Research 1 (1): 27–35. 1995. doi:10.1093/dnares/1.1.27. PMID 7584026. 
• "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement)". DNA Research 1 (1): 47–56. 1995. doi:10.1093/dnares/1.1.47. PMID 7584028. 
• "Comparative mapping of 50 human chromosome 9 loci in the laboratory mouse". Genomics 25 (1): 139–49. Jan 1995. doi:10.1016/0888-7543(95)80119-7. PMID 7774911. 
• "A role for nucleoporin FG repeat domains in export of human immunodeficiency virus type 1 Rev protein and RNA from the nucleus". Molecular and Cellular Biology 16 (12): 7144–50. Dec 1996. doi:10.1128/mcb.16.12.7144. PMID 8943370. 
• "The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88". The EMBO Journal 16 (4): 807–16. Feb 1997. doi:10.1093/emboj/16.4.807. PMID 9049309. 
• "Cloning and characterization of human karyopherin beta3". Proceedings of the National Academy of Sciences of the United States of America 94 (9): 4451–6. Apr 1997. doi:10.1073/pnas.94.9.4451. PMID 9114010. Bibcode: 1997PNAS...94.4451Y. 
• "Karyopherin beta2 mediates nuclear import of a mRNA binding protein". Proceedings of the National Academy of Sciences of the United States of America 94 (10): 5055–60. May 1997. doi:10.1073/pnas.94.10.5055. PMID 9144189. Bibcode: 1997PNAS...94.5055B. 
• "Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic face of the nuclear pore complex". The Journal of Cell Biology 137 (5): 989–1000. Jun 1997. doi:10.1083/jcb.137.5.989. PMID 9166401. 
• "Overexpression of the nucleoporin CAN/NUP214 induces growth arrest, nucleocytoplasmic transport defects, and apoptosis". Molecular and Cellular Biology 18 (3): 1236–47. Mar 1998. doi:10.1128/mcb.18.3.1236. PMID 9488438. 
• "Inhibition of human immunodeficiency virus Rev and human T-cell leukemia virus Rex function, but not Mason-Pfizer monkey virus constitutive transport element activity, by a mutant human nucleoporin targeted to Crm1". Journal of Virology 72 (11): 8627–35. Nov 1998. doi:10.1128/JVI.72.11.8627-8635.1998. PMID 9765402. 
• "Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev". Journal of Virology 73 (1): 120–7. Jan 1999. doi:10.1128/JVI.73.1.120-127.1999. PMID 9847314. 
• "Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p". The EMBO Journal 18 (15): 4332–47. Aug 1999. doi:10.1093/emboj/18.15.4332. PMID 10428971. 
• "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. Jan 2000. doi:10.1017/S1355838200991994. PMID 10668806. 
• "TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture". Molecular and Cellular Biology 20 (23): 8996–9008. Dec 2000. doi:10.1128/MCB.20.23.8996-9008.2000. PMID 11073998. 
• "Cofactor requirements for nuclear export of Rev response element (RRE)- and constitutive transport element (CTE)-containing retroviral RNAs. An unexpected role for actin". The Journal of Cell Biology 152 (5): 895–910. Mar 2001. doi:10.1083/jcb.152.5.895. PMID 11238447.