Nsp4 muodostuu pitkän replikaasipeptidin aminohappojaksosta 2764-3263 vaivan varhaisimmissa pilkkoutumisissa ja on 500 aminohappoa pitkä transmembraanisti (TM) asettuva.
LÄHDE1 antaa tietoa oletetusta struktuurista ja pääasiallisesta funktiosta.
Swiss model antaa siitä seuraavaa tietoa:
https://swissmodel.expasy.org/repository/species/2697049
Non-structural protein 4 (nsp4): Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles (DMV) necessary for viral replication.
High quality models are available for the C-terminus which we predict to be a homo-dimer.
Non-structural protein 4
Host membrane
Multi-pass membrane protein
Host cytoplasm
Localizes in virally-induced cytoplasmic double-membrane vesiclesNon-structural protein 4
Interacts with PL-PRO and nsp6
Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.1 Publication1 Publication
LÄHDE2 antaa tietoa SARS-2 CoV nsp4 proteiinin interaktioista isäntäkehon proteiinien kanssa.
löydän listasta seuraavat interaktioproteiinit.
Toiseksi vahvimpia interaktiokandidaattien (12 kpl) joukossa on kaksi nsp4-proteiinin kanssa interaktionsa tekevää, joiden geenitiedot otan ensiksi ja asetin FB- sivulle 8.5. 2020.
Nämä ovat:
ALG11 (alfa-1,2 mannosyylitransferaasi ),
NUP210 (nukleoporiini210).
Vähemmän vahvoja interaktioita tekevien proteiinien suuressa joukossa (280) havaitsen seuraavat interaktioproteiinit: niitä katson 9.5. 2020):
TIMM29,
TIMM10,
TIMM9,
TIMM10B.
DNAJC11,
KUVA: https://link.springer.com/article/10.1007/s00441-016-2433-7/figures/1
Lisäksi mainitaan:
IDE .
- TIMM 29 (19p13.2),TIM29, C19orf52.
Names: uncharacterized protein C19orf52
uncharacterized conserved protein (DUF2366)
This is a family of proteins conserved from nematodes to humans. The function is not known.
- IDE, insuliinia hajoittava tekijä. INSULYSIINI.sinkkimetallopeptidaasi. Hajoittaa bradykiniiniä, kallidiinia, ANP peptidiä.
https://www.ncbi.nlm.nih.gov/gene/3416
IDE; insulin degrading Also known as INSULYSIN.
Summary. This gene encodes a zinc metallopeptidase that degrades intracellular insulin, and thereby terminates insulins activity, as well as participating in intercellular peptide signalling by degrading diverse peptides such as glucagon, amylin, bradykinin, and kallidin. The preferential affinity of this enzyme for insulin results in insulin-mediated inhibition of the degradation of other peptides such as beta-amyloid. Deficiencies in this protein's function are associated with Alzheimer's disease and type 2 diabetes mellitus but mutations in this gene have not been shown to be causitive for these diseases. This protein localizes primarily to the cytoplasm but in some cell types localizes to the extracellular space, cell membrane, peroxisome, and mitochondrion. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but have not been experimentally verified.[provided by RefSeq, Sep 2009 Expression Ubiquitous expression in skin (RPKM 17.4), testis (RPKM 9.9) and 25 other tissues See more Preferred Names: insulin-degrading enzyme
Names: Abeta-degrading protease,
insulin protease,
insulinase.
NP_001159418.1 insulin-degrading enzyme isoform 2.
Conserved Domains (1) summary
| Ptr super family | cl34066 |
Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification,
|
ORIGIN 1 msklwfkqdd kfflpkacln feffspfayv dplhcnmayl ylellkdsln eyayaaelag 61 lsydlqntiy gmylsvkgyn dkqpillkki iekmatfeid ekrfeiikea ymrslnnfra 121 eqphqhamyy lrllmtevaw tkdelkeald dvtlprlkaf ipqllsrlhi eallhgnitk 181 qaalgimqmv edtliehaht kpllpsqlvr yrevqlpdrg wfvyqqrnev hnncgieiyy 241 qtdmqstsen mflelfcqii sepcfntlrt keqlgyivfs gprrangiqg lrfiiqsekp 301 phylesrvea flitmeksie dmteeafqkh iqalairrld kpkklsaeca kywgeiisqq 361 ynfdrdntev aylktltked iikfykemla vdaprrhkvs vhvlaremds cpvvgefpcq 421 ndinlsqapa lpqpeviqnm tefkrglplf plvkphinfm aakl //
Anthony J. Turner, Natalia N. Nalivaeva, in Handbook of Biologically Active Peptides (Second Edition), 2013 Insulin-Degrading Enzyme (Insulysin, IDE) In addition to insulin, IDE can hydrolyze a number of biologically active peptides including insulin-like growth factor II, tumor growth factor-α, and atrial natriuretic peptide .IDE also degrades somatostatin,
IDE differs from ACE and NEP in possessing an inverted zinc-binding motif
(His-Xaa-Xaa-Glu-His) and shows unusual allosteric behavior with small peptides.
- TIMM 10, (11q12.1), Mitokondrian sisäkalvon translokaasi 10.
https://www.ncbi.nlm.nih.gov/gene/26519,
translocase of inner mitochondrial membrane 10. Also known as TIM10; TIM10A; TIMM10A
The mitochondrial protein encoded by this gene belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane, functioning as intermembrane space chaperones for the highly insoluble carrier proteins
NP_036588.1 mitochondrial import inner membrane translocase subunit Tim10.
Tim10/DDP family zinc finger: Putative
zinc binding domain with four conserved cysteine residues. This domain
is found in the human disease protein TIMM8A. Members of this family
such as Tim9 and Tim10 are involved in mitochondrial protein import.
Members of this family seem to be localized to the mitochondrial
intermembrane space.
(Obs: Positional proteomics analysis identifies the cleavage of human
translocase of inner mitochondrial membrane 10 homolog (yeast) (TIMM10)
at amino acid residues 72-73 by the HIV-1 protease) .
CHAPERONE hexamer TIM9.10 : DOI:https://doi.org/10.1016/j.molcel.2005.11.010). Import of proteins into mitochondria occurs by coordinated actions of
preprotein translocases in the outer and inner membranes (TOM). Tim9 and Tim10
are translocase components of the intermembrane space, related to
deafness-dystonia peptide 1 (DDP1). They coassemble into a hexamer,
TIM9•10, which captures and chaperones precursors of inner membrane
metabolite carriers as they exit the TOM channel in the outer membrane.
The crystal structure of TIM9•10 reveals a previously undescribed
α-propeller topology in which helical “blades” radiate from a narrow
central pore lined with polar residues. The propeller blades are
reminiscent of “tentacles” in chaperones Skp and prefoldin. In each
TIM9•10 subunit, a signature “twin CX3C” motif forms two
intramolecular disulfides. There is no obvious binding pocket for
precursors, which we suggest employ the chaperone-like tentacles of
TIM9•10 as surrogate lipid contacts. The first reported crystal
structure of a mitochondrial translocase assembly provides insights into
selectivity and regulation of precursor import.
- DNAJC11, (1p36.31), Hsp40-perheen jäsen.
https://www.ncbi.nlm.nih.gov/gene/55735. DNAJC11p.
DnaJ heat shock protein family (Hsp40) member C11.
Also known as dJ126A5.1. Expression Ubiquitous expression in kidney (RPKM 23.0), colon (RPKM 15.3) and 25 other tissues See more
FEATURES: https://www.ncbi.nlm.nih.gov/protein/NP_060668.2
Evolution and structural organization of the mitochondrial contact
site (MICOS) complex and the mitochondrial intermembrane space
bridging (MIB) complex
NP_060668.2 dnaJ homolog subfamily C member 11Conserved Domains (2) summary
pfam00226 Location:14 → 79 DnaJ; DnaJ domain. DnaJ domains (J-domains) are associated with hsp70 heat-shock system and it is thought that this domain mediates the interaction. DnaJ-domain is therefore part of a chaperone (protein folding) system. The T-antigens, although not in Prosite are confirmed as DnaJ containing domains from literature.
pfam11875 Location:417 → 549
Domain of unknown function (DUF3395)
This
domain is functionally uncharacterized. This domain is found in
eukaryotes. This presumed domain is typically between 147 to 176 amino
acids in length. This domain is found associated with pfam00226. https://febs.onlinelibrary.wiley.com/doi/full/10.1016/j.febslet.2007.06.052https://www.ncbi.nlm.nih.gov/pubmed/17624330/
- TIMM 10B , (11q15.4) Mitokondrian sisäkalvon translokaasi 10B.
translocase of inner mitochondrial membrane 10B. Also known as FXC1; Tim9b; TIM10B
Summary: FXC1, or TIMM10B, belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004] Expression Ubiquitous expression in thyroid (RPKM 18.0), prostate (RPKM 12.0) and 25 other tissues See more.
Preferred Names: mitochondrial import inner membrane translocase subunit Tim10 B.
Names:fracture callus 1 homolog, fracture callus protein 1,(FXC1),
mitochondrial import inner membrane translocase subunit Tim9 B,
translocase of inner mitochondrial membrane 10 homolog B.
12..67 /region_name="zf-Tim10_DDP
Region 28..52 /region_name="Twin CX3C motif".
- TIMM 9, (14q23.1) Mitokondrian sisäkalvon translokaasi 9.
Translocase of inner mitochondrial membrane 9. Also known as TIM9; TIM9A.
Summary: TIMM9 belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004]. Expression Ubiquitous expression in thyroid (RPKM 11.9), ovary (RPKM 11.7) and 25 other tissues See more.
Preferred Names: mitochondrial import inner membrane translocase subunit Tim9
Names: translocase of inner mitochondrial membrane 9 homolog.
https://www.ncbi.nlm.nih.gov/pubmed/30445040
Cell. 2018 Nov 15;175(5):1365-1379.e25. doi: 10.1016/j.cell.2018.10.039. Structural Basis of Membrane Protein Chaperoning through the Mitochondrial Intermembrane Space.
Weinhäupl K1, Lindau C2 The exchange of metabolites between the mitochondrial
matrix and the cytosol depends on β-barrel channels in the outer
membrane (TOM) and α-helical carrier proteins in the inner membrane (TIM). The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial "transfer-chaperone" system is able to guide α-helical and β-barrel membrane proteins in a "nascent chain-like" conformation through a ribosome-free compartment.
https://www.researchgate.net/profile/Richard_Wagner2/publication/5674953/figure/fig1/AS:267529880862721@1440795502022/Two-main-protein-import-pathways-of-mitochondria-Presequences-direct-proteins-through.png ---------------
N-glykaanin biosynteesikartta näyttää ALG11 entsyymin tärkeän sijaintikohdan näiden glykaani rakenteiden synteesiketjussa. Alempi linkki näyttää näitä synteesirrakenelmia kuin "hirvensarvien" muodostusta. Senkaltaisia sitten lähetetään proteiinien pintaan ja ne muodostavat soluja suojaavia telinerakenteita: solujen Glycocalix.
https://www.genome.jp/kegg-bin/show_pathway?hsa00510
https://www.researchgate.net/figure/Comparison-of-protein-N-glycosylation-pathways-in-eukaryotes-Biosynthesis-steps_fig1_326041354
- ALG11 (13q14.3) ( isäntäsolun glycocalyx-suojakerroksen synteesin alkuvaiheen entsyymeitä)
Official Full Name ALG11 alpha-1,2-mannosyltransferase
Also known as GT8; CDG1P
Summary: This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010] Expression Ubiquitous expression in thyroid (RPKM 12.1), kidney (RPKM 8.8) and 25 other tissues
- Preferred Names
- GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
- Names
- GDP-Man:Man(3)GlcNAc(2)-PP-dolichol alpha-1,2-mannosyltransferase
- asparagine-linked glycosylation 11, alpha-1,2-mannosyltransferase homolog
- asparagine-linked glycosylation protein 11 homolog
- glycolipid 2-alpha-mannosyltransferase.
- FEATURES:
-
NM_001004127.3 → NP_001004127.2 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
- Conserved Domains (1) summary
-
- cd03806
Location:63 → 480 - GT1_ALG11_like; This family is most closely related to the GT1 family of glycosyltransferases. ALG11 in yeast is involved in adding the final 1,2-linked Man to the Man5GlcNAc2-PP-Dol synthesized on the cytosolic face of the ER. The deletion analysis of ALG11 was shown to block the early steps of core biosynthesis that takes place on the cytoplasmic face of the ER and lead to a defect in the assembly of lipid-linked oligosaccharides.
- cd03806
https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2292-6
- NUP210 (3p25.1) , ( nukleoporiini 210).
https://www.ncbi.nlm.nih.gov/gene/23225
Official Full Name nucleoporin 210.
Also known as GP210; POM210.
Summary. 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. The protein encoded by this gene is a membrane-spanning glycoprotein (gp) that is a major component of the nuclear pore complex. Multiple pseudogenes related to this gene are located on chromosome 3. [provided by RefSeq, Jul 2013] Expression Broad expression in lymph node (RPKM 17.2), bone marrow (RPKM 15.9) and 22 other tissues .
Preferred Names nuclear pore membrane glycoprotein 210
Names:
nuclear envelope pore membrane protein POM 210,
nuclear pore protein gp210,
nucleoporin 210kDa,
nucleoporin Nup210,
pore membrane protein of 210 kDa.
FEATURES:
NP_079199.2 nuclear pore membrane glycoprotein 210 precursor
Conserved Domains (1) summary
Ig-like domain-containing protein (domain architecture ID 10492496)
bacterial Ig-like domain-containing protein similar to human nuclear pore membrane glycoprotein 210 and Escherichia virus T5 major tail tube protein pb6
bacterial Ig-like domain-containing protein similar to human nuclear pore membrane glycoprotein 210 and Escherichia virus T5 major tail tube protein pb6
- pfam02368
- Location:1079 → 1152
- Big_2; Bacterial Ig-like domain (group 2) This family consists of bacterial domains with an Ig-like fold. Members of this family are found in bacterial and phage surface proteins such as intimins.
Nukleoporiinin tehtävä on estää suurten proteiinien diffuusiota tuman ja soluliman välillä.
Nukleoporiineja on kymmenä geenituotteita Ne toimivat kymmenien proteiinien yhteistyöllä kompleksina muodostamassa sitä aukkoa, josta tapahtuu nukleosytoplasminen kuljetus.
SARS-2-CoV nsp 9 tekee interaktion NUP88 , NUP62. NUP58, NUP214, NUP54 ja
SARS.2-CoV ORF6 tekee interaktion NUP98 kanssa. Lueteltu interaktiovahvuuden mukaisessa järjestyksessä.
kovasti näyttää Sars-2- viruksella olevan kiinnosusta tähän sytosolin ja tuman väliseen porttiin ja materian kuljetukseen.
Tieto nukleoporiineista vuonna 2002:
https://www.ncbi.nlm.nih.gov/pubmed/12196509?dopt=Abstract
J Cell Biol. 2002 Sep 2;158(5):915-27. Epub 2002 Aug 26.
Proteomic analysis of the mammalian nuclear pore complex.
Cronshaw JM1, Krutchinsky AN et al.
As
the sole site of nucleocytoplasmic transport, the nuclear pore complex
(NPC) has a vital cellular role. Nonetheless, much remains to be learned
about many fundamental aspects of NPC function. To further understand
the structure and function of the mammalian NPC, we have completed a
proteomic analysis to identify and classify all of its protein
components. We used mass spectrometry to identify all proteins present
in a biochemically purified NPC fraction. Based on previous
characterization, sequence homology, and subcellular localization, 29 of
these proteins were classified as nucleoporins, and a further 18 were
classified as NPC-associated proteins. Among the 29 nucleoporins were
six previously undiscovered nucleoporins and a novel family of WD repeat
nucleoporins. One of these WD repeat nucleoporins is ALADIN, the gene
mutated in triple-A (or Allgrove) syndrome. Our analysis defines the
proteome of the mammalian NPC for the first time and paves the way for a
more detailed characterization of NPC structure and functionValaiseva kuva vuodelta 2012https://www.annualreviews.org/na101/home/literatum/publisher/ar/journals/content/biophys/2012/biophys.2012.41.issue-1/annurev-biophys-050511-102328/production/images/medium/bb410557.f2.gif
Muistiin aluksi tietoa kahdesta melko vahvasta interaktioproteiinista ALG11 ja NUP210.
Varsinaiset nukleaariseen kuljetukseen sekaantuvat virusproteiinit ovat nsp9, nsp15 ja ORF6, vaikka nsp 4 myös osallistuu. Varsinaisesti nsp4 vaikuttaa mitokondriassa. Niistä interaktioproteiineista myöhemmin. myöhemmin.
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