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fredag 15 maj 2020

SARS-2 CoV nsp10 interaktioproteiinit

(1) AP2A2, 11p15.5),  AP-2 complex subunit alpha-2.
 https://www.genecards.org/cgi-bin/carddisp.pl?gene=AP2A2&keywords=AP2A2.
 Clathrin-Associated/Assembly/Adaptor Protein, Large, Alpha 2 2 3
Alpha-Adaptin C; Huntingtin Interacting Protein J 2  The protein encoded by this gene is a subunit of the AP-2 adaptor protein complex, which is involved in linking lipid and protein membrane components with the clathrin lattice. This interaction supports the formation of clathrin-coated vesicles, and the encoded subunit aids in the process by binding polyphosphoinositide-containing lipids in the cell membrane. [provided by RefSeq, Nov 2016].
 Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components.

 Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway.
During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity) AP2A2_HUMAN,O94973.

(2)  GFER, (16p13.3), FAD-linked sulfhydryl oxidase ALR,
https://www.genecards.org/cgi-bin/carddisp.pl?gene=GFER&keywords=GFER 
The hepatotrophic factor designated augmenter of liver regeneration (ALR) is thought to be one of the factors responsible for the extraordinary regenerative capacity of mammalian liver. It has also been called hepatic regenerative stimulation substance (HSS). The gene resides on chromosome 16 in the interval containing the locus for polycystic kidney disease (PKD1). The putative gene product is 42% similar to the scERV1 protein of yeast. The yeast scERV1 gene had been found to be essential for oxidative phosphorylation, the maintenance of mitochondrial genomes, and the cell division cycle. The human gene is both the structural and functional homolog of the yeast scERV1 gene. [provided by RefSeq, Jul 2008 . [Isoform 1]: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen. ALR_HUMAN,P55789

(3) ERCIG1(5q35.1),  Endoplasmic reticulum-Golgi intermediate compartment protein 1
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ERGIC1&keywords=ERGIC1.
This gene encodes a cycling membrane protein which is an endoplasmic reticulum-golgi intermediate compartment (ERGIC) protein which interacts with other members of this protein family to increase their turnover. [provided by RefSeq, Jul 2008].

(4) AP2M1,(3q27.1), AP-2 complex subunit mu. 
https://www.genecards.org/cgi-bin/carddisp.pl?gene=AP2M1&keywords=AP2M1
Clathrin Assembly Protein Complex 2 Mu Medium Chain 3 4 
This gene encodes a subunit of the heterotetrameric coat assembly protein complex 2 (AP2), which belongs to the adaptor complexes medium subunits family. The encoded protein is required for the activity of a vacuolar ATPase, which is responsible for proton pumping occurring in the acidification of endosomes and lysosomes. The encoded protein may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]
Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components.
  The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity).  AP2M1_HUMAN,Q96CW1

(5) GRPEL1, (4p16.1)  GrpE protein homolog 1, mitochondrial.
https://www.genecards.org/cgi-bin/carddisp.pl?gene=GRPEL1&keywords=GRPEL1
 Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and chaperone binding. An important paralog of this gene is GRPEL2
.Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner (By similarity). Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins. 
  Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner (By similarity). Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins

  • Mitä  Swiss model antoi  SARS-2 nsp10:lle funktioiksi? 

 Non-structural protein 10 (nsp10):
Alternative name(s) Growth factor-like peptide Short name: GFL
Plays a pivotal role in viral transcription by stimulating both nsp14     3'-5' exoribonuclease
 and nsp16    2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.
High quality models are available which are predicted to be homo-dodecamers. Hetero-oligomeric complexes with both nsp14 and nsp16 are available in the hetero section. Experimental structures of hetero-oligomeric complexes (PDB: 6w4h, 6w61, 6w75, 6wjt, 6wkq, 6wks, 6wq3, 6wrz, 6wvn, 6yz1) exist and high quality models can be extracted from them but should be used with care.
P0DTD1 · R1AB_SARS2
 
Localisation: Non-structural protein 10
Host cytoplasm, host perinuclear region
nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.

 https://swissmodel.expasy.org/interactive/3xFkkB/models/01
12-mer, homo-dodecamer

 https://swissmodel.expasy.org/templates/6w75.1

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