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torsdag 28 maj 2020

Tuma-aukkokompleksi on SARS2- virustekijöiden interaktioproteiineja.

Interaktiotekijäitä SARS2- viruksesta mainitaan
Nsp1, nsp9 ja ORF6 näiden tuma-aukkoproteiinien kimpussa. Nsp9 tekee useimpia interaktioita  NUP proteiineihin.
kuten  tumakalvon  sytoplasmiseen  NUP214,  tumakalvon sentraaliseen  NUP joukkoon NUP62, NUP54 ja NUP 58.
Myös  linkkerikohdan NUP88- proteiiniin.
ORF6 interaktio kohdistuuNUP98 proteiiniin.

Swiss model lähteestä tieto nsp1- proteiinista:
Host translation Inhibitor nsp1 (nsp1):
Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.

Nuclear import and export: Filmi. https://www.youtube.com/watch?v=ZGPpKk-6-K0
Nuclear export: : All or n  Import:  One at a  time.
https://www.youtube.com/watch?v=RDUUngYhRiU

Tuma-aukkokompleksin, (Nuclear Pore Complex)  GEENEJÄ ja  havaituja  mainittuja virus  proteiini-proteiini-interaktioita (ppi) 
  •   Cytoplasmic face  NUPS  ( Tuma-aukkokompleksin sytoplasman puoleinen sivu)

( SARSr2CoV nsp9 tekee interaktion  NUP214 kanssa.)

NUP214 (9q34.13). Nuclear pore complex protein Nup214. 
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP214&keywords=NUP214utative oncogene  (CAIN, CAN, BAE9)
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. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015] Homodimer. Interacts with ZFP36; this interaction increases upon lipopolysaccharide (LPS) stimulation (PubMed:14766228). Interacts with DDX19 (PubMed:19219046, PubMed:19208808). Interacts with NUP88 (PubMed:9049309, PubMed:30543681). Interacts with XPO1 (PubMed:9049309). Interacts with XPO5 (PubMed:11777942).(Microbial infection) Interacts with human herpes virus 1 (HHV-1) protein UL25; this interaction might be essential to the capsid docking onto the host nuclear pore.

  • Transmembrane ring NUPS:  (Kalvon läpäisevän renkaan kohdalla sijaitsevia NUP-proiineja)
(SARS2 nsp4 virusproteiini tekee interaktion NUP214 kanssa)

NUP210 (GP210)
 Recommended name: Nuclear pore membrane glycoprotein 210
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP210&keywords=NUP210
Nucleoporin essential for nuclear pore assembly and fusion, nuclear pore spacing, as well as structural integrity. Transmembrane ring  NUPS- group. 
Knockdown of NUP210 causes nuclear membranes to accumulate aberrant structures termed twinned and fusion-arrested membranes and nuclear pore complex to cluster. Induces cell death and chromatin disruptions.
  •  Central FG NUPS   ( Tuma-aukkokompleksin sentraalinen rakenne)
( SARS2 2 CoV  nsp9 tekee interaktion NUP54, NUP58 ja  NUP62 kanssa).

NUP5, (4q21.1), Nucleoporin p54. Recommended name:Nucleoporin p54. ( 507 a.a.) 
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP54&keywords=NUP54

 The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the phe-gly (FG) repeat-containing nucleoporin subset. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013 Quaternary structure: Component of the p62 complex, a complex composed of NUP62, NUP54, and the isoform p58 and isoform p45 of NUP58. Interacts with NUTF2.


NUP58 (13q12.13). Nucleoporin p58/p45.
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP58&keywords=NUP58
The protein is localized to the nuclear rim and is a component of the nuclear pore complex (NPC). All molecules entering or leaving the nucleus either diffuse through or are actively transported by the NPC. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008] Quaternary structure:  Component of the p62 complex, a complex at least composed of NUP62, NUP54, and NUP58. Interacts with NUTF2. Interacts with SRP1-alpha and Importin p97 proteins when they are together, but not with SRP1-alpha protein alone (By similarity).

NUP6, (19q13.33). Nuclear Pore Glycoprotein p62. 
 The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals.
 Quaternary structure: Component of the p62 complex, a complex at least composed of NUP62, NUP54, and NUP58 (By similarity). Interacts with NUP88 (PubMed:30543681). Interacts with NUTF2 (By similarity). Interacts with HIKESHI (PubMed:22541429). Interacts with OSBPL8 (PubMed:21698267). Interacts with CAPG (PubMed:18266911). Interacts with SAS6 and TUBG1 at the centrosome (PubMed:24107630). Interacts with MCM3AP isoform GANP (PubMed:23652018).(Microbial infection) Interacts with Epstein-barr virus BGLF4; this interaction allows BGLF4 nuclear entry.

(SARS2 ORF6 tekee interaktion  NUP98 kanssa).

NUP98. (11p15.4), Nuclear pore complex protein NUP98-NUP96.
Alias: ADIR, ADAR2. GLFG-repeat containing complex protein Nup98.  Quaternary structure.Part of the nuclear pore complex (NPC) (PubMed:15229283, PubMed:18287282). Interacts directly with NUP96 (PubMed:12191480). Part of the Nup160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and NUP96; this complex plays a role in RNA export and in tethering NUP98 and NUP153 to the nucleus (PubMed:11684705). Interacts with RAE1 (PubMed:10209021, PubMed:20498086). Does not interact with TPR (PubMed:11684705). Interacts with NUP88 (PubMed:30543681). Interacts directly with NUP88 and NUP214, subunits of the cytoplasmic filaments of the NPC (By similarity). Interacts (via N-terminus) with DHX9 (via DRBM, OB-fold and RGG domains); this interaction occurs in a RNA-dependent manner and stimulates DHX9-mediated ATPase activity (PubMed:28221134) (Microbial infection) Interacts with vesicular stomatitis virus protein M (PubMed:11106761).


  •  Linker NUPS  ( linkkiävän väyläjakson ja korin  NUP -proteiineja)
SARS2 nsp1 tehnee interaktion NUP93 kanssa  (disrupt it!) ja nsp9 tekee interaktion NUP88 kanssa.  

NUP93,  (16q13), Nuclear pore complex protein NUP93.
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP93&keywords=NUP93.
 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 encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]
 Quaternary structure: Part of the nuclear pore complex (NPC) (PubMed:9348540, PubMed:15229283, PubMed:15703211). Component of the p62 complex, a complex composed of NUP62 and NUP54 (PubMed:9348540). Forms a complex with NUP35, NUP155, NUP205 and lamin B; the interaction with NUP35 is direct (PubMed:15703211). Does not interact with TPR (PubMed:12802065, PubMed:15229283). Interacts with SMAD4 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (PubMed:26878725).


NUP88, (17p13.2), Nuclear pore complex protein NUP  88. 
 https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP88&keywords=NUP88
 Karyoporin, FADS4.
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, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
Size: 741 amino acids.  Molecular mass:83542 Da. Quaternary structure: Interacts with NUP214/CAN (PubMed:9049309, PubMed:30543681). Interacts with NUP62 and NUP98 (PubMed:30543681).



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