INO1 entsyymi. Inositolin synteesi linkkiytynee galaktoosin metaboliaan.

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788023/

 

 

Ihmisellä  geeni tunnetaan nimellä ISYNA1, sijainti19p13.11. 

Tämä on inositolia sisältävien yhdisteiden  metaboliassa tahtia rajoittava  entsyymi. Sen tehtävät on konvertoida glukoosi-6-fosfaattia myoinositoli-1-fosfaatiksi  (MIP) , siitä taas impaasi-entsyymit voivat  saada aikaan   myoinositolia mI. Sanon tätäsokeria "haisokeriksi"!. Hai käyttää tätä sokeria energiansa  kehittämiseen. Myös ihmisaivojen   harmaissa soluissa on inositolilipidien   kehittämää energia järjestelmää .  Glukoosin aueella toimii  ATP ja GTP, galaktoosin alueella UTP ja tämä  inositoli  alkaa CTP alueella synteesejään.  mutta   metabolinen tie yhtyy lopulta  jälleen ATP ja GTP  teihin, joitten  toimintaa   tämä  vahvistaa. 

 

Esimerkki Israelin nykyisestä pandemisesta vaiheesta

 i24news kertoo tänään, että Israelissa on pandemian alusta lähtien  todettuja  Covid-19 infektioita 166794. Täysin toipuneiksi katsotaan  120 727 eli yli 72%. C

ovid-19 tautiin kuolleita on todettu 1169 tai toisen tiedon mukaan 1147.  Tästä luvusta laskettuna mortaliteetti Israelissa on 0,687 %. Tarkistan vielä tuosta toisesta luvusta: 0,7%.  Viime tiistaina tehtiin koronavirustestauksia siellä 57 165 kpl.  Torstaina uusia tautitapauksia oli 5238, toisen tiedon mukaan 5523. Vakavassa tilassa on 577 henkilöä. Intuboituina on 149. Armeijasta ilmoitettiin  833 sotilasta ja  IDF siviilivirkmiestä  tartunnan saaneiksi, heillä tauti on aktiivissa vaiheessa ja lieväasteista. Lisäksi  koti-karanteeniin on määrätty 11 845 sotilasta. Koska Israelissa on   vuoden  suurimpiin ja väkirikkaimpiin  juhlatilaisuuksiin perinteisesti kuuluva aika meneillään, valtion johdon taholta on määrätty täysi 3 viikon  lockdown tila valtioon ja virkavalta  valvoo käskyn noudatusta. Tämä juhla-aika perinteisesti sisältää myös  Lehtimajanjuhlan johon on aiemmin tulvinut  koko maailmasta turisteja viettämään suuria joukkotilaisuuksia väkirikkaissa  kaupungeissa. 

Tänään on Uudenvuoden alku. Siirrytään vuodesta 5780 vuoteen 5781. ROSH HASHANA.

Siunattua Uutta Vuotta!

5`UTR ja 3`UTR koronaviruksissa SARS Cov ja MERS CoV

https://pubmed.ncbi.nlm.nih.gov/25736566/

Epub 2015 Feb 28.

The structure and functions of coronavirus genomic 3' and 5' ends

Dong Yang  ¹ , Julian L Leibowitz  ²

Affiliations

• PMID: 25736566
• PMCID: PMC4476908
• DOI: 10.1016/j.virusres.2015.02.025

Free PMC article

Abstract

Coronaviruses (CoVs) are an important cause of illness in humans and animals. Most human coronaviruses commonly cause relatively mild respiratory illnesses; however two zoonotic coronaviruses, SARS-CoV and MERS-CoV, can cause severe illness and death. Investigations over the past 35 years have illuminated many aspects of coronavirus replication. The focus of this review is the functional analysis of conserved RNA secondary structures in the 5' and 3' of the betacoronavirus genomes. The 5' 350 nucleotides folds into a set of RNA secondary structures which are well conserved, and reverse genetic studies indicate that these structures play an important role in the discontinuous synthesis of subgenomic RNAs in the betacoronaviruses. These cis-acting elements extend 3' of the 5'UTR into ORF1a. The 3'UTR is similarly conserved and contains all of the cis-acting sequences necessary for viral replication. Two competing conformations near the 5' end of the 3'UTR have been shown to make up a potential molecular switch. There is some evidence that an association between the 3' and 5'UTRs is necessary for subgenomic RNA synthesis, but the basis for this association is not yet clear. A number of host RNA proteins have been shown to bind to the 5' and 3' cis-acting regions, but the significance of these in viral replication is not clear. Two viral proteins have been identified as binding to the 5' cis-acting region, nsp1 and N protein. A genetic interaction between nsp8 and nsp9 and the region of the 3'UTR that contains the putative molecular switch suggests that these two proteins bind to this region.

Keywords: Coronaviruses; RNA binding proteins; RNA secondary structure; Virus replication; cis-Acting sequences. 

 

 

 

 

 

 

Pub Med luetuimpia artikkeleita 10 listan ensimmäistä 17.7. 2020. rokoteuutiset päälimmäisinä

Trending articles

1,000 results


 1 Tämä artikkeli kertoo mRNA-1273-rokotteesta, joka  sai aikaan anti-SARS-CoV-2 immuunivastetta kaikissa kokeeseen osallistuneissa. Kandidaattirokote mRNA-1273 on eräs lipidinanopartikkelin  sisään kapseloitu  nukleosidilla modifioitu  lähetti-RNA-pohjainen  rokote , jossa   SARS-CoV-2 viruksen  piikkiproteiini S  on stabiloitu prefuusiomuotoonsa.  Viruksen pintapiikki (Spike) on se, millä se koettaa tarttua isäntäsoluun ja  se on  välttämätön viruksen pääsylle solun sisään ja  tämän viruksen vastaisen rokotteen kehittelyssä  se on  ensisijalla. Artikkeli kertoo suoritetusta  I kliinisen vaiheen  kokeesta terveillä aikuisilla, jotta selvitetään   mRNA-1273:n turvallisuus ja immunogenisyys  Kyse on väliaikatiedotuksesta. 
 

• Conclusions: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461). 

• DOI: 10.1056/NEJMoa2022483

An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

Jackson LA, Anderson EJ et a. .." The candidate vaccine mRNA-1273 is a lipid nanoparticle–encapsulated, nucleoside-modified messenger RNA (mRNA)–based vaccine that encodes the SARS-CoV-2 spike (S) glycoprotein stabilized in its prefusion conformation. The S glycoprotein mediates host cell attachment and is required for viral entry³; it is the primary vaccine target for many candidate SARS-CoV-2 vaccines.^4-7We conducted a first-in-human phase 1 clinical trial in healthy adults to evaluate the safety and immunogenicity of mRNA-1273. Here we report interim results of the trial"

2.

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls.

Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A, Chng MHY, Lin M, Tan N, Linster M, Chia WN, Chen MI, Wang LF, Ooi EE, Kalimuddin S, Tambyah PA, Low JG, Tan YJ, Bertoletti A. Nature. 2020 Jul 15. doi: 10.1038/s41586-020-2550-z. Online ahead of print. PMID: 32668444.

Abstract

Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections¹. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

3

Potently neutralizing and protective human antibodies against SARS-CoV-2.

Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr. Nature. 2020 Jul 15. doi: 10.1038/s41586-020-2548-6.
 Online ahead of print. PMID: 32668443The COVID-19 pandemic is a major threat to global health¹ for which there are limited medical countermeasures^2,3. Moreover, we currently lack a thorough understanding of mechanisms of humoral immunity⁴. From a larger panel of human monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein⁵, we identified several that exhibited potent neutralizing activity and fully blocked the receptor-binding domain of S (S_RBD) from interacting with human ACE2 (hACE2). Competition-binding, structural, and functional studies allowed clustering of the mAbs into classes recognizing distinct epitopes on the S_RBD as well as distinct conformational states of the S trimer. Potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two mouse models of SARS-CoV-2 infection, passive transfer of either COV2-2196 or COV2-2130 alone or a combination of both mAbs protected mice from weight loss and reduced viral burden and inflammation in the lung. In addition, passive transfer of each of two of the most potently ACE2 blocking mAbs (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on S_RBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutics.

4

A perspective on potential antibody-dependent enhancement of SARS-CoV-2.

Arvin AM, Fink K, Schmid MA, Cathcart A, Spreafico R, Havenar-Daughton C, Lanzavecchia A, Corti D, Virgin HW. Nature. 2020 Jul 13. doi: 10.1038/s41586-020-2538-8. Online ahead of print. PMID: 32659783    Review.The possibility of antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection have the theoretical potential to amplify viral infections or trigger immunopathology. Observations relevant to the risks of ADE of disease require careful review at this critical point in the SARS-CoV-2 pandemic. At present, no clinical findings, immunologic assays or biomarkers are known to differentiate any severe viral infection from immune-enhanced disease, whether by antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same, and designing animal models depends on understanding how antiviral host responses may become harmful in people. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, since we cannot predict ADE of disease reliably after either vaccination or treatment with antibodies, regardless of what virus is the causative agent, it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 disease move forward.

5

The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis.

Winkler ES, Shrihari S, Hykes BL Jr, Handley SA, Andhey PS, Huang YS, Swain A, Droit L, Chebrolu KK, Mack M, Vanlandingham DL, Thackray LB, Cella M, Colonna M, Artyomov MN, Stappenbeck TS, Diamond MS. Cell. 2020 Jul 8:S0092-8674(20)30806-0. doi: 10.1016/j.cell.2020.06.029. Online ahead of print. PMID: 32668198

6

The link between Vitamin D and Covid-19: distinguishing facts from fiction.

Bergman P. J Intern Med. 2020 Jul 11. doi: 10.1111/joim.13158. Online ahead of print. PMID: 32652766https://doi.org/10.1111/joim.13158

7

Extrapulmonary manifestations of COVID-19.

Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Nat Med. 2020 Jul;26(7):1017-1032. doi: 10.1038/s41591-020-0968-3. Epub 2020 Jul 10. PMID: 32651579
  Review. Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

8

Ageing hallmarks exhibit organ-specific temporal signatures.

Schaum N, Lehallier B, Hahn O, Pálovics R, Hosseinzadeh S, Lee SE, Sit R, Lee DP, Losada PM, Zardeneta ME, Fehlmann T, Webber JT, McGeever A, Calcuttawala K, Zhang H, Berdnik D, Mathur V, Tan W, Zee A, Tan M; Tabula Muris Consortium, Pisco AO, Karkanias J, Neff NF, Keller A, Darmanis S, Quake SR, Wyss-Coray T. Nature. 2020 Jul 15. doi: 10.1038/s41586-020-2499-y. Online ahead of print. PMID: 32669715

9

Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease.

Schultheiß C, Paschold L, Simnica D, Mohme M, Willscher E, von Wenserski L, Scholz R, Wieters I, Dahlke C, Tolosa E, Sedding DG, Ciesek S, Addo M, Binder M. Immunity. 2020 Jun 30:S1074-7613(20)30279-X. doi: 10.1016/j.immuni.2020.06.024. Online ahead of print. PMID: 32668194 Free PMC article.

10

Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA.

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y; THALES Investigators. N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870. PMID: 32668111

TRIM59 ja ECSIT ovat SARS2 interaktioproteiineja ( ORF3a ja vastaavasti ORF9C kanssa)

 Päivitys 24.6. 2021. Olen  kirjoittanut  TRIM59.stä vuosi takaperin, mutta vasta tänään 24.6. 2021  törmäsin ECSIT- proteiiniin ja asetan tähän  asiayhteyden:  Olen aamusta asti  lukenut  rauta-rikki-klustereista  Fe-S clusters, joita on useissa  proteiineissa ja jonkalaista rakennetta myös Sars-2 virusproteiineissa  esiintyy funktion tehostajana ja struktuurin stabiloijana.  Koska sars-2 proteiinit tekevät interaktioita mitokondriaaliseen hengitysketjuun, jossa ihmisellä on useita Fe-S- klusterin omaavia proteiineja, etsin myös artikkelin  hengitysketjun kompleksien rakenteesta  . Ehdin katsoa Complex I (CI):n  evoluutiosta  perustavaa tietoa. 

 

Tässä yhteydessä  ECSIT- proteiini mainitaan ja sen nimi tulee sanoista: Evolutionally Conserved Signaling Intermediate In TOLL pathways.  se on  sytosolinen proteiini, joka osallistuu tulehdsvasteesee ja alkion kehitykseen. Lisäksi se on mitokondriaalinen proteiini ja tekee interaktion CI- kompleksin jäsenten kanssa siinä vaiheessa kun kompleksi I koostuu. NDUFAF1:n  stabiliteetti  ja siihen liittyvien komponenttien stabiliteetti on riippuvainen ECSIT-proteiinista. 

 Sars-2 ORF9c tekee interaktioita useisiin CI kompleksin  komponentteihin: CIAO30 eli NDUFAF1, ECSIT, ACAD9, NDUFB9) . Sars 2 nsp7 tekee interaktiota NDUFAF2 komponenttiin  muun muassa. 

Sitaatti:

GeneCards Summary for ECSIT Gene

ECSIT (ECSIT Signaling Integrator) is a Protein Coding gene. Among its related pathways are Activated TLR4 signalling and MAPK signaling pathway. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and oxidoreductase activity, acting on NAD(P)H.

UniProtKB/Swiss-Prot Summary for ECSIT Gene

• Adapter protein of the Toll-like and IL-1 receptor signaling pathway that is involved in the activation of NF-kappa-B via MAP3K1. Promotes proteolytic activation of MAP3K1. Involved in the BMP signaling pathway. Required for normal embryonic development (By similarity).

  • ECSIT_HUMAN,Q9BQ95
• Required for efficient assembly of mitochondrial NADH:ubiquinone oxidoreductase.

  • ECSIT_HUMAN,Q9BQ95

TRIM59, TSBF1 

https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRIM59&keywords=TRIM59 

Aliases for TRIM59 Gene

Tripartite Motif Containing 59 ^{2 3 5}
Tripartite Motif-Containing Protein 59 ^{3 4}
Tripartite Motif-Containing 57 ^{2 3}
Tumor Suppressor TSBF-1 ^{3 4}
RING Finger Protein 104 ^{3 4}
TRIM57 ^{3 4}
RNF104 ^{3 4}
TSBF1 ^{3 4}
Tripartite Motif-Containing 59 ²
Tumor Suppressor TSBF1 ³
IFT80L ³
MRF1 ³

External Ids for TRIM59 Gene

Tämä TRIM sijaitsee 3. kromosomin q-haarassa. Sen koodaama proteiini on 403 aminohappoa.Se kuuluu HC- struktuurin omaaviin TRIMproteiineihin. Sen rakenne on kaavaa ”RING-HC-TRIM59-C-V”. Se kuuluu HC- alaryhmään. Sen HC-rakenne on tarkemmin (C3HC4)-
TRIM59 saattaa ubikitinoida p53.
 TRIM59 säätää negatiivisesti NF-kB- ja IRF3/IRF7-välitteistä tietä ja tekee interaktion ECSIT:iin (joka on mitokondriaalinen, evolutionaalisesti konservoitunut signalointivälituote Tollin reseptorien signaaliteissä, signaloinnin integroija) (ECSIT on  SARS2  oref9C interaktioproteiini)
 
.TRIM59 omaa onkogeenista luonnetta ja sitä on havaittu poikkeavasti ilmenevänä monessa eri syövässä. Siitä löytää hyvin paljon artikkeleita netistä. TRIM59 on todettu luonnollisen immuniteetin multifunktionaaliseksi signaaliteitten säätelijäksi. Kun kaikki artikkelit käy läpi, voi ehkä jollain tavalla hahmottaa sen moninaisen normaalin ja  runsaan epänormaalin funktion. Se on aikamoinen palapeli. Sen nimi IFT80L tarkoittaa Intraflagellaarinen kuljetus (transport) (IFT) proteiini. Se on kaikissa cilioita omaavissa organismeissa konservoitunut ja essentielli, tärkeä cilia-rakenteen koostumukselle ja ylläpidolle. Sitä ilmenee paljon nopeasti proliferoituvissa soluissa, mutta ei differentioituneissa soluissa, jotka ovat siirtyneet pois solusyklistä. Tällä tekijällä on tärkeä osa solun proliferaatiossa ja differentiaatiossa. Tästä herää kiinnostus mikä on TRIM59 geenin normaali funktio esim värekarvoja (cilia) omaavassa hengitystie-epiteelissä. Jos TRIM59 geeni sammutetaan keuhkosyöpäsolussa, solusykli pysähtyy G2-vaiheeseen ja  solutuotetta kertyy- p53 ei toimi. Paljon onkin tutkittu sen osuutta NSCLC keuhkosyövissä. Ras- ja RB- signalointitiessä TRIM59 on proto-onkogeeni. TRIMgeenin sammutus voi eräissä syövissä säätää TGFbeta/SMAD2- tien vaimeammaksi,  samoin EMT vaimenee ( epiteliaalinen-mesenkymaalinen transitio). TRIM59 pystyy moduloimaan onkogeenejä MTOR ja EIF4E .
BCG-rokotus aktivoi makrofageja ja ne kykenevät siten tappamaan tuumorisoluja. Näiden makrofagien yksi pääominaisuus on TRIM59:n runsas ilmentäminen. TRIM59 omaa transmembraanisen domaanin ja on solukalvoproteiini. TRIM59 pystyy myös säätelemään onkogeeni EGFR/STAT3- signaalitietä (Glioomassa tällä tiellä on merkitystä) . Maksasyöpäsolut ilmentävät runsaasti TRIM59, joka voi toimia täten biomerkitsijänä tälle syövälle TRIM59 pystyy tekemään interaktion aktiiniin ja myosiiniin assosioituviin proteiineihin. TRIM59 puutteessa F-aktiinin polymerisaatio häiriintyi solun sisämaterian differentiaation aikana. TRIM59 saattaa olla kriittisen tärkeä alkion varhaiskehityksen säätelijänä blastokysti vaiheesta gastrulaan (F-aktiinin koostuminen).
https://genecards.weizmann.ac.il/v3/cgi-bin/carddisp.pl?gene=TRIM59
https://www.nature.com/articles/s41419-018-0370-y
https://www.ncbi.nlm.nih.gov/protein/NP_775107.1

ORIGIN      
        1 mhnfeeeltc picysifedp rvlpcshtfc rnclenilqa sgnfyiwrpl riplkcpncr
       61 siteiaptgi eslpvnfalr aiiekyqqed hpdivtcpeh yrqplnvycl ldkklvcghc
      121 ltigqhhghp iddlqsaylk ekdtpqklle qltdthwtdl thlieklkeq kshsekmiqg
      181 dkeavlqyfk elndtleqkk ksfltalcdv gnlinqeytp qiermkeire qqlelmalti
      241 slqeesplkf lekvddvrqh vqilkqrplp evqpveiypr vskilkeews rteigqiknv
      301 lipkmkispk rmscswpgkd ekeveflkil nivvvtlisv ilmsilffnq hiitflseit
      361 liwfseasls vyqslsnslh kvknilchif yllkefvwki vsh
//

MRF1; TSBF1; IFT80L; RNF104; TRIM57

Expression

Broad expression in testis (RPKM 4.6), lymph node (RPKM 4.6) , brain and 20 other tissues See more

TLE1, TLE3, TLE5 proteiinit ovat nsp13 interaktioproteiineja . Transkription vaimentajia. WDR propellit, Wnt signalointialue

Nämä kolme geeniä löytyvät WDR40 perheen joukosta. Sinä on 277 proteiinia.   (WD toistot).

TLE1 ,(9q21.32),Transducin-Like Enhancer Protein 1
https://www.genecards.org/cgi-bin/carddisp.pl?gene=TLE1&keywords=TLE1

Aliases for TLE1 Gene

TLE Family Member 1, Transcriptional Corepressor ^{2 3 5}
Transducin-Like Enhancer Of Split 1 (E(Sp1) Homolog, Drosophila) ^{2 3}
Enhancer Of Split Groucho-Like Protein 1 ^{3 4}
Transducin Like Enhancer Of Split 1 ^{2 3}
Transducin-Like Enhancer Protein 1 ^{3 4}

ESG1 ^{3 4}
Enhancer Of Split Groucho 1 ²
E(Sp1) Homolog ⁴
GRG1 ³
ESG ³

TLE1 (TLE Family Member 1, Transcriptional Corepressor) is a Protein Coding gene. Diseases associated with TLE1 include Glomus Tumor and Tibial Adamantinoma. Among its related pathways are Signaling by Wnt and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. Gene Ontology (GO) annotations related to this gene include identical protein binding and transcription factor binding. An important paralog of this gene is TLE4.

UniProtKB/Swiss-Prot Summary for TLE1 Gene
Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG. TLE1_HUMAN,Q04724

Protein attributes for TLE1 GeneSize: 770 amino acids Molecular mass: 83201 Da

Quaternary structure: Homooligomer and heterooligomer with other family members. Binds LEF1, RUNX1, RUNX3, FOXA2, KDM6A, UTY, histone H3, HESX1, ESRRG and the NF-kappa-B subunit RELA. Interacts with HES1 (via WRPW motif). Interacts with SIX3. Interacts with EFNB1.

Post-translational modifications for TLE1 Gene
Phosphorylated, probably by CDK1. The degree of phosphorylation varies throughout the cell cycle, and is highest at the G2/M transition. Becomes hyperphosphorylated in response to cell differentiation and interaction with HES1 or RUNX1.

Ubiquitinated by XIAP/BIRC4.
Modification sites at PhosphoSitePlus Modification sites at neXtProt 

TLE3 (15q23)Transducin-Like Enhancer Protein 3

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=TLE3&keywords=TLE3

Aliases for TLE3 Gene

TLE Family Member 3, Transcriptional Corepressor ^{2 3 5}
Transducin-Like Enhancer Of Split 3 (E(Sp1) Homolog, Drosophila) ^{2 3}
Enhancer Of Split Groucho-Like Protein 3 ^{3 4}
Transducin Like Enhancer Of Split 3 ^{2 3}
Transducin-Like Enhancer Protein 3 ^{3 4}
ESG3 ^{3 4}
Transducin-Like Enhancer Of Split 3, Homolog Of Drosophila E(Sp1) ³
Transducin-Like Enhancer Of Split 3 Short Isoform ³

Enhancer Of Split Groucho 3 ³
HSALNG0106903 ¹⁶⁷
HSALNG0106901 ¹⁶⁷
Lnc-UACA-6 ¹⁶⁸
HsT18976 ³
KIAA1547 ⁴
GRG3 ³
ESG ³

This gene encodes a transcriptional co-repressor protein that belongs to the transducin-like enhancer family of proteins. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]

GeneCards Summary for TLE3 Gene TLE3 (TLE Family Member 3, Transcriptional Corepressor) is a Protein Coding gene. Diseases associated with TLE3 include Chromosome 1Q21.1 Duplication Syndrome. Among its related pathways are Signaling by Wnt and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. An important paralog of this gene is TLE4.

UniProtKB/Swiss-Prot Summary for TLE3 Gene

Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity).

Protein attributes for TLE3 Gene

Size:772 amino acids. Molecular mass: 83417 Da Quaternary structure:Homotetramer and heterooligomer with other family members. Binds LEF1, TCF7 and TCF7L1 (By similarity). Binds FOXA2. Interacts with XIAP/BIRC4 and TCF7L2/TCF4. Interacts with TBX18 (via engrailed homology 1 repressor motif), leading to decreased of TBX18 transcriptional activity.SequenceCaution: Sequence=BAB13373.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 

 TLE5

https://www.genecards.org/Search/Keyword?queryString=TLE5

Aliases for TLE5 Gene

TLE Family Member 5, Transcriptional Modulator ^{2 3 4 5}
Amino-Terminal Enhancer Of Split ^{2 3 4}
Gp130-Associated Protein GAM ^{3 4}
Groucho-Related Protein 5 ^{3 4}
TLE Family Member 5 ^{3 4}
Grg-5 ^{3 4}
GRG5 ^{3 4}

AES ^{3 4}
GRG ^{3 4}
Amino Enhancer Of Split ⁴
Protein ESP1 ⁴
Protein GRG ⁴
AES-1 ³
AES-2 ³
ESP1 ³

The protein encoded by this gene is similar in sequence to the amino terminus of Drosophila enhancer of split groucho, a protein involved in neurogenesis during embryonic development. The encoded protein, which belongs to the groucho/TLE family of proteins, can function as a homooligomer or as a heteroologimer with other family members to dominantly repress the expression of other family member genes. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for TLE5 Gene

TLE5 (TLE Family Member 5, Transcriptional Modulator) is a Protein Coding gene. Among its related pathways are Signaling by Wnt and Ectoderm Differentiation. An important paralog of this gene is TLE4.

UniProtKB/Swiss-Prot Summary for TLE5 Gene

Transcriptional corepressor. Acts as dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development.TLE5_HUMAN,Q08117

 

 https://www.sciencedirect.com/science/article/abs/pii/S037811190000161X

 https://www.sciencedirect.com/science/article/abs/pii/S037811190000161X?via%3Dihub

Review

Groucho/TLE family proteins and transcriptional repression

Author links open overlay panelGuoqingChen¹Albert JCourey

https://doi.org/10.1016/S0378-1119(00)00161-X

Säästin tämän  kirjoituksen WIF1 mappiin, jossa on WDR proteiinit , niitä on paljon yli 200. tämä on TLE .perhettä WDR- tyyppiä  transdusiineja.

COVID 19 taudin molekyyleistä

https://www.cell.com/cell/fulltext/S0092-8674(20)30627-9

Summary

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

 

Introduction

Coronavirus disease 2019 (COVID-19) is an unprecedented global threat caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently spreading around the world rapidly. The sudden outbreak and accelerated spreading of SARS-CoV-2 infection have caused substantial public concerns. Within about 3 months, over 2 million individuals worldwide have been infected, leading to over 150,000 deaths.

Most COVID-19 studies have focused on its epidemiological and clinical characteristics (

Ghinai et al., 2020

,

Guan et al., 2020

). About 80% of patients infected with SARS-CoV-2 displayed mild symptoms with good prognosis. They usually recover with, or even without, conventional medical treatment and therefore are classified as mild or moderate COVID-19 (

Thevarajan et al., 2020

). However, about 20% of patients suffer from respiratory distress and require immediate oxygen therapy or other inpatient interventions, including mechanical ventilation (

Murthy et al., 2020

,

Wu and McGoogan, 2020

). These patients, classified as clinically severe or critical life-threatening infections, are mainly diagnosed empirically based on a set of clinical characteristics, such as respiratory rate (≥30 times/min), mean oxygen saturation (≤93% in the resting state), or arterial blood oxygen partial pressure/oxygen concentration (≤300 mmHg). However, patients exhibiting these clinical manifestations have already progressed to a clinically severe phase and require immediate access to specialized intensive care; otherwise, they may die rapidly. Therefore, it is critical to develop new approaches to assess early which cases will likely become clinically severe. In addition, effective therapy for severe patients remains speculative, largely due to limited understanding of SARS-CoV-2 pathogenesis.

In this study, we hypothesized that SARS-CoV-2 induces characteristic molecular changes that can be detected in the sera of severe patients. These molecular changes may shed light on therapy development for COVID-19 patients. To test this hypothesis, we applied proteomic (

Aebersold and Mann, 2016

,

Li et al., 2020

) and metabolomic (

Hou et al., 2020

,

Lee et al., 2019

) technologies to analyze the proteome and metabolome of sera from COVID-19 patients and several control groups.

Results

 Proteomic and Metabolomic Profiling of COVID-19 Sera

We procured a cohort of patients (

Zheng et al., 2020

) containing 28 severe COVID-19 patients. The detailed patient descriptions including the sampling date for each patient are shown in Figure 1A, Table 1, and Table S1. Controls with matched epidemiological features were included to identify severity-related molecular alterations. These controls were 28 healthy subjects, 25 non-COVID-19 patients (negative for the SARS-CoV-2 nucleic acid test) with similar clinical characteristics as COVID-19 patients, and 25 non-severe COVID-19 patients. A serum sample was obtained from each patient within a few days after hospital admission, with a few exceptions when samplings were performed at later disease stages. We analyzed 12 clinical measurements of the COVID-19 and non-COVID-19 patients (Figure S1), including white blood cell count, lymphocyte count, monocyte count, platelet count, C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), creatinine, and glucose. Compared to non-severe patients, severe patients showed significant suppression of lymphocyte count and monocyte count, as well as increase of CRP and AST (Figure S1).

 

 

 https://www.cell.com/cell/fulltext/S0092-8674(20)30627-9#figs1

Kansanterveyslaitoksen antama tieto SARS2 viruksesta joka lmentyy Ruotsissa

Ruotsi Kansanterveyslaitos tutkii  tänne tulleiden viruksen kokogenomeistä  tänne  tulleet variantit ja niiden leviämiset:

 Ruotsissa on sekvensoitu täällä kertävä SARS2 virus ja siitä on päätelty, mistä virus on alkanut tänne levitä.  Kolme geneettistä ryhmää oli  viruksessa erotettavissa purkauksen alussa ja edelleen kaksi niistä jatkaa  leviämistään. Näissä geneettisissä ryhmissä on tiettyjä eroja niihin variantteihin, joita maahan tuli Italiasta ja Itävallasta, mikä vahvistaa oletuksen siitä, että virusta johtui  useasta sisäänntulosta    tänne Ruotsiin. Nyt vielä  voidaan  nähdä  kahden geneettisen ryhmän leviämistä  kausi-influenssaseurannan  yhteydessä tehdyistä sekvensoinneista. Kolmas ryhmä  tuli New - Yorkista päin.  Varhaisimman Aasiasta Eurooppaan tulleen  viruksen  varianttia  on löytynyt ruotsalaisesta materiaalista   vain  jokin yksittäinen  ja mahdollisesti  kaukoidän   variantti  on   katkaissut  täällä   leviämisensä.
   Raportti antaa  alustavaa tietoa Kansanterveyslaitoksen  jatkuvasti käynnissä olevasta ponnistelusta   karakterisoida  yhteiskunnassa kiertelevien SARS-2 koronavirusten  geneettisten   ryhmien kokogenomit.


Helgenomsekvensering av svenska SARS-CoV-2 som orsakar covid-19, del 2

Lyssna

Slutsatserna från rapport 1 stärks ytterligare. Tre genetiska grupper etablerade sig i Sverige vid utbrottets start, varav två fortsätter att spridas. Dessa genetiska grupper har vissa skillnader med de varianter av dem som importerades från Italien och Österrike, vilket stärker hypotesen vilket stärker hypotesen att ett flertal separata introduktioner skedde in i landet. Slutligen kan man fortsatt se spridning av två av de genetiska grupperna givet resultat från sekvensering av prover från sentinelövervakningen.
Rapporten är ett kunskapsunderlag som redovisar Folkhälsomyndighetens fortlöpande arbete att helgenomkarakterisera de olika genetiska grupperna av SARS-CoV-2 som cirkulerar i samhället. Detta för att stärka kunskapsläget kring viruset och dess möjliga utveckling samt för att bidra med en förmåga att upptäcka nyintroduktioner av viruset.

Detta är den första genetiska karakteriseringen av SARS-CoV-2 i Sverige. Den fokuserar på de genetiska grupper som identifierats i diagnostiken under den tidiga fasen av pandemins utbredning i Sverige och omfattar isolat från fall diagnosticerade under perioden 31 januari 2020 när landets första fall av covid-19 diagnosticerades, till och med den 15 mars 2020 då samhällssmitta av covid-19 hade konstaterats i Sverige.
Utifrån analysen av virus arvsmassa kan den smitta vi ser i landet så här långt, i huvudsak grupperas två eller tre genetiska grupper beroende på system. De genetiska grupper som identifieras i Sverige är samma som förekommer i den omfattande smittspridning som utvecklades under februari i Europa. En av de genetiska grupperna är även förekommande i den smittspridning som konstaterats i New York i slutet av februari och början av mars. Majoriteten av de genetiska grupper som finns rapporterade från de tidiga smittkedjorna, främst från Asien till Europa, kan endast påvisas med enstaka fall i det analyserade svenska materialet vilket indikerar att smitta från dessa genetiska grupper hittills inte fått någon omfattande spridning i Sverige och potentiellt brutits helt.

SARS2 ORF8 tekee interaktion ihmisen proteiiniin PUSL1

https://pubmed.ncbi.nlm.nih.gov/32353859/

. 2020 Apr 30.

doi: 10.1038/s41586-020-2286-9. Online ahead of print.

A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug Repurposing

Abstract

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption^1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds).
 Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.


Tästä luettelosta  29. proteiini listassa on PUSL1 , johon ORF8 tekee  interaktion.

Aliases for PUSL1 Gene

• Pseudouridine Synthase Like 1 ^{2 3 5}
• TRNA Pseudouridylate Synthase-Like 1 ^{3 4}
• TRNA Pseudouridine Synthase-Like 1 ^{3 4}
• Pseudouridylate Synthase Like 1 ^{2 3}
• TRNA-Uridine Isomerase-Like 1 ^{3 4}
• EC 5.4.99.- ⁴

GeneCards Summary for PUSL1 Gene

PUSL1 (Pseudouridine Synthase Like 1) is a Protein Coding gene. Diseases associated with PUSL1 include Myopathy, Lactic Acidosis, And Sideroblastic Anemia. Gene Ontology (GO) annotations related to this gene include RNA binding and pseudouridine synthase activity. An important paralog of this gene is PUS3.