| Structural highlights
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Disease
[NUP98_HUMAN] Note=A chromosomal aberration involving NUP98 is found in a form of acute myeloid leukemia. Translocation t(7;11)(p15;p15) with HOXA9. Translocation t(11;17)(p15;p13) with PHF23. Note=A chromosomal aberration involving NUP98 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NSD1. Translocation t(8;11)(p11.2;p15) with WHSC1L1. Note=A chromosomal aberration involving NUP98 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with TOP1. Note=A chromosomal aberration involving NUP98 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(3;11)(q12.2;p15.4) with LNP1. Note=A chromosomal aberration involving NUP98 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with PSIP1/LEDGF. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4. [NU155_HUMAN] Familial atrial fibrillation. The disease is caused by mutations affecting the gene represented in this entry.
Function
[NUP98_HUMAN] Nup98 and Nup96 play a role in the bidirectional transport across the nucleoporin complex (NPC). The FG repeat domains in Nup98 have a direct role in the transport. [NUP37_HUMAN] Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation.[1] [SEC13_HUMAN] Functions as a component of the nuclear pore complex (NPC) and the COPII coat. At the endoplasmic reticulum, SEC13 is involved in the biogenesis of COPII-coated vesicles.[2] [NUP85_HUMAN] Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP98/Nup98 and NUP153 to the nucleus. The Nup107-160 complex seems to be required for spindle assembly during mitosis. NUP85 is required for membrane clustering of CCL2-activated CCR2. Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol 3-kinase-Rac-lammellipodium protrusion cascade.[3] [4] [5] [NU160_HUMAN] Involved in poly(A)+ RNA transport.[6] [SEH1_HUMAN] Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation. This subunit plays a role in recruitment of the Nup107-160 subcomplex to the kinetochore. As a component of the GATOR2 complex, inhibits GATOR1 complex, an inhibitor of the amino acid-sensing branch of the TORC1 pathway.[7] [8] [9] [NU133_HUMAN] Involved in poly(A)+ RNA transport.[10] [NUP43_HUMAN] Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation.[11] [NU155_HUMAN] Essential component of nuclear pore complex. Could be essessential for embryogenesis. Nucleoporins may be involved both in binding and translocating proteins during nucleocytoplasmic transport.[UniProtKB:Q99P88] [NU107_HUMAN] Essential component of nuclear pore complex. Required for the assembly of peripheral proteins into the nuclear pore complex.[12]
Publication Abstract from PubMed
Nuclear pore complexes are fundamental components of all eukaryotic cells that mediate nucleocytoplasmic exchange. Determining their 110-megadalton structure imposes a formidable challenge and requires in situ structural biology approaches. Of approximately 30 nucleoporins (Nups), 15 are structured and form the Y and inner-ring complexes. These two major scaffolding modules assemble in multiple copies into an eight-fold rotationally symmetric structure that fuses the inner and outer nuclear membranes to form a central channel of ~60 nm in diameter. The scaffold is decorated with transport-channel Nups that often contain phenylalanine-repeat sequences and mediate the interaction with cargo complexes. Although the architectural arrangement of parts of the Y complex has been elucidated, it is unclear how exactly it oligomerizes in situ. Here we combine cryo-electron tomography with mass spectrometry, biochemical analysis, perturbation experiments and structural modelling to generate, to our knowledge, the most comprehensive architectural model of the human nuclear pore complex to date. Our data suggest previously unknown protein interfaces across Y complexes and to inner-ring complex members. We show that the transport-channel Nup358 (also known as Ranbp2) has a previously unanticipated role in Y-complex oligomerization. Our findings blur the established boundaries between scaffold and transport-channel Nups. We conclude that, similar to coated vesicles, several copies of the same structural building block--although compositionally identical--engage in different local sets of interactions and conformations.
In situ structural analysis of the human nuclear pore complex.,von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio AL, Vollmer B, Mackmull MT, Banterle N, Parca L, Kastritis P, Buczak K, Mosalaganti S, Hagen W, Andres-Pons A, Lemke EA, Bork P, Antonin W, Glavy JS, Bui KH, Beck M Nature. 2015 Oct 1;526(7571):140-3. doi: 10.1038/nature15381. Epub 2015 Sep 23. PMID:26416747[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zuccolo M, Alves A, Galy V, Bolhy S, Formstecher E, Racine V, Sibarita JB, Fukagawa T, Shiekhattar R, Yen T, Doye V. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 2007 Apr 4;26(7):1853-64. Epub 2007 Mar 15. PMID:17363900 doi:http://dx.doi.org/10.1038/sj.emboj.7601642
- ↑ Tang BL, Peter F, Krijnse-Locker J, Low SH, Griffiths G, Hong W. The mammalian homolog of yeast Sec13p is enriched in the intermediate compartment and is essential for protein transport from the endoplasmic reticulum to the Golgi apparatus. Mol Cell Biol. 1997 Jan;17(1):256-66. PMID:8972206
- ↑ Harel A, Orjalo AV, Vincent T, Lachish-Zalait A, Vasu S, Shah S, Zimmerman E, Elbaum M, Forbes DJ. Removal of a single pore subcomplex results in vertebrate nuclei devoid of nuclear pores. Mol Cell. 2003 Apr;11(4):853-64. PMID:12718872
- ↑ Terashima Y, Onai N, Murai M, Enomoto M, Poonpiriya V, Hamada T, Motomura K, Suwa M, Ezaki T, Haga T, Kanegasaki S, Matsushima K. Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis. Nat Immunol. 2005 Aug;6(8):827-35. Epub 2005 Jul 3. PMID:15995708 doi:http://dx.doi.org/ni1222
- ↑ Orjalo AV, Arnaoutov A, Shen Z, Boyarchuk Y, Zeitlin SG, Fontoura B, Briggs S, Dasso M, Forbes DJ. The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly. Mol Biol Cell. 2006 Sep;17(9):3806-18. Epub 2006 Jun 28. PMID:16807356 doi:http://dx.doi.org/10.1091/mbc.E05-11-1061
- ↑ Vasu S, Shah S, Orjalo A, Park M, Fischer WH, Forbes DJ. Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. J Cell Biol. 2001 Oct 29;155(3):339-54. Epub 2001 Oct 29. PMID:11684705 doi:http://dx.doi.org/10.1083/jcb.200108007
- ↑ Loiodice I, Alves A, Rabut G, Van Overbeek M, Ellenberg J, Sibarita JB, Doye V. The entire Nup107-160 complex, including three new members, is targeted as one entity to kinetochores in mitosis. Mol Biol Cell. 2004 Jul;15(7):3333-44. Epub 2004 May 14. PMID:15146057 doi:http://dx.doi.org/10.1091/mbc.E03-12-0878
- ↑ Zuccolo M, Alves A, Galy V, Bolhy S, Formstecher E, Racine V, Sibarita JB, Fukagawa T, Shiekhattar R, Yen T, Doye V. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 2007 Apr 4;26(7):1853-64. Epub 2007 Mar 15. PMID:17363900 doi:http://dx.doi.org/10.1038/sj.emboj.7601642
- ↑ Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013 May 31;340(6136):1100-6. doi: 10.1126/science.1232044. PMID:23723238 doi:http://dx.doi.org/10.1126/science.1232044
- ↑ Vasu S, Shah S, Orjalo A, Park M, Fischer WH, Forbes DJ. Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. J Cell Biol. 2001 Oct 29;155(3):339-54. Epub 2001 Oct 29. PMID:11684705 doi:http://dx.doi.org/10.1083/jcb.200108007
- ↑ Zuccolo M, Alves A, Galy V, Bolhy S, Formstecher E, Racine V, Sibarita JB, Fukagawa T, Shiekhattar R, Yen T, Doye V. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 2007 Apr 4;26(7):1853-64. Epub 2007 Mar 15. PMID:17363900 doi:http://dx.doi.org/10.1038/sj.emboj.7601642
- ↑ Boehmer T, Enninga J, Dales S, Blobel G, Zhong H. Depletion of a single nucleoporin, Nup107, prevents the assembly of a subset of nucleoporins into the nuclear pore complex. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):981-5. Epub 2003 Jan 27. PMID:12552102 doi:http://dx.doi.org/10.1073/pnas.252749899
- ↑ von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio AL, Vollmer B, Mackmull MT, Banterle N, Parca L, Kastritis P, Buczak K, Mosalaganti S, Hagen W, Andres-Pons A, Lemke EA, Bork P, Antonin W, Glavy JS, Bui KH, Beck M. In situ structural analysis of the human nuclear pore complex. Nature. 2015 Oct 1;526(7571):140-3. doi: 10.1038/nature15381. Epub 2015 Sep 23. PMID:26416747 doi:http://dx.doi.org/10.1038/nature15381
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