This family of proteins includes leukemia NUP98 fusion partner 1, the gene encoding this protein is involved in a chromosomal translocation with the NUP98 locus in a form of T-cell acute lymphoblastic leukemia [].
The entry includes components of the nuclear pore complex (NPC), which is required for transport of macromolecules in and out of the nucleus. These components are all nucleoporins. Components Nup98 and Nup96 are products of autolytic processing of a precursor protein that is effectively a serine endopeptidase (MEROPS identifier S59.001). The precursor is known as Nup189 in Schizosaccharomyces pombe. This entry also includes nucleoporin Nup100 from Saccharomyces cerevisiae, which does not process itself but which is important for poly(A)+ RNA and protein transport. Nup100 has a tetrapeptide glycine-leucine-phenylalanine-glycine (GLFG) motif where it binds karyopherin transport factor Kap95p [].
This entry represents nucleoporins, of which the precursors of some undergo autolytic processing. Some nucleoporins are synthesized as precursors, and each of these processes itself to release two large fragments that are both nucleoporins. Cleavage is dependent upon a His/Ser catalytic dyad, and cleavage occurs at the N-terminal side of the catalytic Ser. This means that the nucleoporin precursors are N-terminal nucleophile (NTN) hydrolases, but are structurally unrelated to other NTN hydrolases which are also peptidases, such as proteosome components. Autoprocessing nucleoporin precursors are members of peptidase family S59. The precursor Nup98-Nup96 (also known as nucleoporin 145 in Saccharomyces cerevisiae and Nup189 in Schizosaccharomyces pombe) processes itself to release Nup98 and Nup96 [, , ]. Nucleoporins Nup98 and Nup96 are components of the nuclear pore complex (NPC), which is the only means by which macromolecules enter and exit the nucleus. Other nucleoporins in family S59 are not synthesized as precursors and do not undergo autoprocessing, such as Nup100 (from Saccharomyces cerevisiae). Nup100 is also a component of the NPC and binds the karyopherin transport factor Kap95 at its repetitive tetrapeptide glycine-leucine-phenylalanine-glycine (GLFG) motifs [].
This entry represents the Nuclear pore complex protein Nup96 from animals its homologues from yeast and plants.Nuclear pore complexes (NPCs) facilitate all nucleocytoplasmic transport in eukaryotic cells, playing essential roles in cellular homeostasis. The NPC is a modular structure composed of multiple copies of ~30 proteins (nucleoporins, Nups) arranged into distinct subcomplexes [, ]. A number of these peptides are synthesised as precursors and undergo self-catalyzed cleavage. The largest NPC sub-complex is the heptameric Y-shaped mammalian Nup107-Nup160 complex (called Nup84 complex in budding yeast), an essential scaffolding component of the NPC [, , ]. Nup98 and Nup96 are encoded by the same gene that produces a 190 kDa polyprotein with autoproteolytic activity which generates the N-terminal NUP98 and C-terminal NUP96 proteins, part of the Nup107-Nup160 subcomplex [, ]. The yeast homologue Nup145 undergoes the similar proteolytic event to produce Nup145N and Nup145C, which are part of the Nup84 complex. The function of the heptamer is to coat the curvature of the nuclear pore complex between the inner and outer nuclear membranes. Nup96, which is predicted to be an alpha helical solenoid, complexes with Sec13 in the middle of the heptamer. The interaction between Nup96 and Sec13 is the point of curvature in the heptameric complex [, ].
Nuclear pore complexes (NPCs) facilitate all nucleocytoplasmic transport in eukaryotic cells, playing essential roles in cellular homeostasis. The NPC is a modular structure composed of multiple copies of ~30 proteins (nucleoporins, Nups) arranged into distinct subcomplexes [, ]. A number of these peptides are synthesised as precursors and undergo self-catalyzed cleavage. The largest NPC sub-complex is the heptameric Y-shaped mammalian Nup107-Nup160 complex (called Nup84 complex in budding yeast), an essential scaffolding component of the NPC [, , ]. Nup98 and Nup96 are encoded by the same gene that produces a 190 kDa polyprotein with autoproteolytic activity which generates the N-terminal NUP98 and C-terminal NUP96 proteins, part of the Nup107-Nup160 subcomplex [, ]. The yeast homologue Nup145 undergoes the similar proteolytic event to produce Nup145N and Nup145C, which are part of the Nup84 complex. The function of the heptamer is to coat the curvature of the nuclear pore complex between the inner and outer nuclear membranes. Nup96, which is predicted to be an alpha helical solenoid, complexes with Sec13 in the middle of the heptamer. The interaction between Nup96 and Sec13 is the point of curvature in the heptameric complex [, ].The proteolytic cleavage site of yeast Nup145p has been mapped upstream of an evolutionary conserved serine residue. Then, Nup145C form the heptameric Y-complex together with six other proteins while Nup145N shuttle between the NPC and the nuclear interior. [, ].Nup98,a component of the nuclear pore that plays its primary role in the export of RNAs, is expressed in two forms, derived from alternate mRNA splicing. Both forms are processed into two peptides through autoproteolysis mediated by the C-terminal domain of hNup98. The three-dimensional structure of the C-terminal domain reveals a novel protein fold, and thus a new class of autocatalytic proteases. The structure further reveals that the suggested nucleoporin RNA binding motif is unlikely to bind to RNA [].The following nucleoporins share an ~150-residue C-terminal domain responsible for NPC targeting [, ]:Vertebrate Nup98, a component of the nuclear pore that plays its primary role in the export of RNAs.Yeast Nup100, plays an important role in several nuclear export and import pathways including poly(A)+ RNA and protein transport.Yeast Nup116, involved in mRNA export and protein transport.Yeast Nup145, involved in nuclear poly(A)+ RNA and tRNA export.The NUP C-terminal domains of Nup98 and Nup145 possess peptidase S59autoproteolytic activity. The autoproteolytic sites of Nup98 and Nup145each occur immediately C-terminal to the NUP C-terminal domain. Thus, althoughthis domain occurs in the middle of each precursor polypeptide, it winds up atthe C-terminal end of the N-terminal cleavage product. Cleavage of the peptidechains are necessary for the proper targeting to the nuclear pore [, ].The NUP C-terminal domain adopts a predominantly β-strand structure. The molecule consists of a six-stranded β-sheet sandwiched against a two-stranded β-sheet and flanked by α-helical regions. The N-terminalhelical region consists of two short helices, whereas the stretch on the opposite side of molecule consists of a single, longer helix [, ].
This entry represents the non-structural protein NS6 (also known as ORF6, accessory protein 6, or X3 protein), which is highly conserved among SARS-related coronaviruses [](this is distinct from NSP6 which is encoded on the replicase polyprotein). NS6 is located in the endoplasmic reticulum []. It has been reported that NS6 can increase the cellular gene synthesis and it can also induce apoptosis through Jun N-terminal kinase and Caspase-3 mediated stress. This protein can modulate host antiviral responses by inhibiting synthesis and signalling of interferon-beta (IFN-beta) via two complementary pathways. One involves NS6 interaction with host N-Myc (and STAT) interactor (Nmi) protein inducing its degradation via ubiquitin proteasome pathway, suppressing Nmi enhanced IFN signalling. The other pathway suppresses the translocation of signal transducer and activator of transcription 1 (STAT1) and downstream IFN signalling [].This protein interacts with Rae1 and Nup98 to prevent both nuclear import and export, which renders host cells incapable of responding to SARS-CoV-2 infection [].
Nuclear pore complexes (NPCs) facilitate all nucleocytoplasmic transport in eukaryotic cells, playing essential roles in cellular homeostasis. The NPC is a modular structure composed of multiple copies of ~30 proteins (nucleoporins, Nups) arranged into distinct subcomplexes [, ]. A number of these peptides are synthesised as precursors and undergo self-catalyzed cleavage. The largest NPC sub-complex is the heptameric Y-shaped mammalian Nup107-Nup160 complex (called Nup84 complex in budding yeast), an essential scaffolding component of the NPC [, , ]. Nup98 and Nup96 are encoded by the same gene that produces a 190 kDa polyprotein with autoproteolytic activity which generates the N-terminal NUP98 and C-terminal NUP96 proteins, part of the Nup107-Nup160 subcomplex [, ]. The yeast homologue Nup145 undergoes the similar proteolytic event to produce Nup145N and Nup145C, which are part of the Nup84 complex. The function of the heptamer is to coat the curvature of the nuclear pore complex between the inner and outer nuclear membranes. Nup96, which is predicted to be an alpha helical solenoid, complexes with Sec13 in the middle of the heptamer. The interaction between Nup96 and Sec13 is the point of curvature in the heptameric complex [, ].The proteolytic cleavage site of yeast Nup145p has been mapped upstream of an evolutionary conserved serine residue. Then, Nup145C form the heptameric Y-complex together with six other proteins while Nup145N shuttle between the NPC and the nuclear interior. [, ].Nup98, a component of the nuclear pore that plays its primary role in the export of RNAs, is expressed in two forms, derived from alternate mRNA splicing. Both forms are processed into two peptides through autoproteolysis mediated by the C-terminal domain of hNup98. The three-dimensional structure of the C-terminal domain reveals a novel protein fold, and thus a new class of autocatalytic proteases. The structure further reveals that the suggested nucleoporin RNA binding motif is unlikely to bind to RNA [].The following nucleoporins share an ~150-residue C-terminal domain responsible for NPC targeting [, ]:Vertebrate Nup98, a component of the nuclear pore that plays its primary role in the export of RNAs.Yeast Nup100, plays an important role in several nuclear export and import pathways including poly(A)+ RNA and protein transport.Yeast Nup116, involved in mRNA export and protein transport.Yeast Nup145, involved in nuclear poly(A)+ RNA and tRNA export.The NUP C-terminal domains of Nup98 and Nup145 possess peptidase S59autoproteolytic activity. The autoproteolytic sites of Nup98 and Nup145each occur immediately C-terminal to the NUP C-terminal domain. Thus, althoughthis domain occurs in the middle of each precursor polypeptide, it winds up atthe C-terminal end of the N-terminal cleavage product. Cleavage of the peptidechains are necessary for the proper targeting to the nuclear pore [, ].The NUP C-terminal domain adopts a predominantly β-strand structure. The molecule consists of a six-stranded β-sheet sandwiched against a two-stranded β-sheet and flanked by α-helical regions. The N-terminal helical region consists of two short helices, whereas the stretch on the opposite side of molecule consists of a single, longer helix [, ].
Nup120 is conserved from fungi to plants to humans, and is homologous with the Nup160 of vertebrates. The nuclear core complex, or NPC, mediates macromolecular transport across the nuclear envelope. Deletion of the NUP120 gene causes clustering of NPCs at one side of the nuclear envelope, moderate nucleolar fragmentation and slower cell growth []. The vertebrate NPC is estimated to contain between 30 and 60 different proteins. most of which are not known. Two important ones in creating the nucleoporin basket are Nup98 and Nup153, and Nup120, in conjunction with Nup 133, interacts with these two and itself plays a role in mRNA export []. Nup160, Nup133, Nup96, and Nup107 are all targets of phosphorylation. The phosphorylation sites are clustered mainly at the N-terminal regions of these proteins, which are predicted to be natively disordered. The entire Nup107-160 subcomplex is stable throughout the cell cycle, thus it seems unlikely that phosphorylation affects interactions within the Nup107-160 subcomplex, but rather that it regulates the association of the subcomplex with the NPC and other proteins [].
