Nucleoporin 214 Explained

Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the NUP214 gene.^{[1] [2] [3]}

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.^[3]

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.^[4] 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.^[5]

Interactions

NUP214 has been shown to interact with:

• DDX19,^[5]
• CRM1
• NXF1,^[6] and
• NXF2,^[7] and
• ZFP36.^[8]

Further reading

• Stoffler D, Fahrenkrog B, Aebi U . The nuclear pore complex: from molecular architecture to functional dynamics . Current Opinion in Cell Biology . 11 . 3 . 391–401 . Jun 1999 . 10395558 . 10.1016/S0955-0674(99)80055-6 .
• von Lindern M, Fornerod M, van Baal S, Jaegle M, de Wit T, Buijs A, Grosveld G . 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 . 1549122 . 369612 . 10.1128/mcb.12.4.1687.
• Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S . 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 . 7584026 . 10.1093/dnares/1.1.27 . free .
• Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S . 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 . 7584028 . 10.1093/dnares/1.1.47 . free .
• Pilz A, Woodward K, Povey S, Abbott C . Comparative mapping of 50 human chromosome 9 loci in the laboratory mouse . Genomics . 25 . 1 . 139–49 . Jan 1995 . 7774911 . 10.1016/0888-7543(95)80119-7 .
• Stutz F, Izaurralde E, Mattaj IW, Rosbash M . 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 . 8943370 . 231718 . 10.1128/mcb.16.12.7144.
• Fornerod M, van Deursen J, van Baal S, Reynolds A, Davis D, Murti KG, Fransen J, Grosveld G . 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 . 9049309 . 1169681 . 10.1093/emboj/16.4.807 .
• Yaseen NR, Blobel G . 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 . 9114010 . 20743 . 10.1073/pnas.94.9.4451 . 1997PNAS...94.4451Y . free .
• Bonifaci N, Moroianu J, Radu A, Blobel G . 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 . 9144189 . 24630 . 10.1073/pnas.94.10.5055 . 1997PNAS...94.5055B . free .
• Bastos R, Ribas de Pouplana L, Enarson M, Bodoor K, Burke B . 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 . 9166401 . 2136229 . 10.1083/jcb.137.5.989 .
• Boer J, Bonten-Surtel J, Grosveld G . Overexpression of the nucleoporin CAN/NUP214 induces growth arrest, nucleocytoplasmic transport defects, and apoptosis . Molecular and Cellular Biology . 18 . 3 . 1236–47 . Mar 1998 . 9488438 . 108836 . 10.1128/mcb.18.3.1236.
• Bogerd HP, Echarri A, Ross TM, Cullen BR . 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 . 9765402 . 110274 . 10.1128/JVI.72.11.8627-8635.1998.
• Zolotukhin AS, Felber BK . Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev . Journal of Virology . 73 . 1 . 120–7 . Jan 1999 . 9847314 . 103815 . 10.1128/JVI.73.1.120-127.1999.
• Schmitt C, von Kobbe C, Bachi A, Panté N, Rodrigues JP, Boscheron C, Rigaut G, Wilm M, Séraphin B, Carmo-Fonseca M, Izaurralde E . 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 . 10428971 . 1171509 . 10.1093/emboj/18.15.4332 .
• Bachi A, Braun IC, Rodrigues JP, Panté N, Ribbeck K, von Kobbe C, Kutay U, Wilm M, Görlich D, Carmo-Fonseca M, Izaurralde E . 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 . 10668806 . 1369901 . 10.1017/S1355838200991994 .
• Herold A, Suyama M, Rodrigues JP, Braun IC, Kutay U, Carmo-Fonseca M, Bork P, Izaurralde E . 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 . 11073998 . 86553 . 10.1128/MCB.20.23.8996-9008.2000 .
• Hofmann W, Reichart B, Ewald A, Müller E, Schmitt I, Stauber RH, Lottspeich F, Jockusch BM, Scheer U, Hauber J, Dabauvalle MC . 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 . 11238447 . 2198816 . 10.1083/jcb.152.5.895 .

Notes and References

1. Kraemer D, Wozniak RW, Blobel G, Radu A . The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm . Proceedings of the National Academy of Sciences of the United States of America . 91 . 4 . 1519–23 . Feb 1994 . 8108440 . 43191 . 10.1073/pnas.91.4.1519 . 1994PNAS...91.1519K . free .
2. von Lindern M, Poustka A, Lerach H, Grosveld G . The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34 . Molecular and Cellular Biology . 10 . 8 . 4016–26 . Aug 1990 . 2370860 . 360912 . 10.1128/mcb.10.8.4016.
3. Web site: Entrez Gene: NUP214 nucleoporin 214kDa.
4. Napetschnig J, Blobel G, Hoelz A . Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN . Proc. Natl. Acad. Sci. U.S.A. . 104 . 6 . 1783–8 . 2007 . 17264208 . 1794303 . 10.1073/pnas.0610828104 . 2007PNAS..104.1783N . free .
5. Napetschnig J, Kassube SA, Debler EW, Wong RW, Blobel G, Hoelz A . Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19 . Proc. Natl. Acad. Sci. U.S.A. . 106 . 9 . 3089–94 . 2009 . 19208808 . 2651337 . 10.1073/pnas.0813267106 . 2009PNAS..106.3089N . free .
6. Schmitt I, Gerace L . In vitro analysis of nuclear transport mediated by the C-terminal shuttle domain of Tap . The Journal of Biological Chemistry . 276 . 45 . 42355–63 . Nov 2001 . 11551912 . 10.1074/jbc.M103916200 . free .
7. Herold A, Suyama M, Rodrigues JP, Braun IC, Kutay U, Carmo-Fonseca M, Bork P, Izaurralde E . 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 . 11073998 . 86553 . 10.1128/mcb.20.23.8996-9008.2000.
8. Carman JA, Nadler SG . Direct association of tristetraprolin with the nucleoporin CAN/Nup214 . Biochemical and Biophysical Research Communications . 315 . 2 . 445–9 . Mar 2004 . 14766228 . 10.1016/j.bbrc.2004.01.080 .