Interferonijärjestelmän molekyylit : IFNAR1 ja IFNAR2 IFNAR resedptorin muodostuksessa.

 COVID-19 virus  aiheuttaa  IRF3 alalssäätymisen, IFN-beta välitteisen  suoran interferonisignaloinnin  tyrehtymisen ja IFNAR1-reseptorin hajoittumisen. mikä myöhästyttää nopean suoran immuunivasteen ja painottaa päinvastoin  myöhemmin alkavaa  vastetta, joka on  sytokiinimyrskyn tapaista ja tällöin nähdään  mm IFNgamma, TNFa ja runsaasti interleukiineja kohonneina. 

https://www.ncbi.nlm.nih.gov/gene/3454

IFNAR1   (21q22.11) 

Preferred Names

interferon alpha/beta receptor 1

Names

CRF2-1

IFN-R-1

IFN-alpha/beta receptor 1

alpha-type antiviral protein

beta-type antiviral protein

cytokine receptor class-II member 1

cytokine receptor family 2 member 1

interferon (alpha, beta and omega) receptor 1

interferon receptor 1

interferon-alpha/beta receptor alpha chain

interferon-beta receptor 1

type I interferon receptor 1

Also known as

AVP; IFRC; IFNAR; IFNBR; IFN-alpha-REC

Summary

The protein encoded by this gene is a type I membrane protein that forms one of the two chains of a receptor for interferons alpha and beta. Binding and activation of the receptor stimulates Janus protein kinases, which in turn phosphorylate several proteins, including STAT1 and STAT2. The encoded protein also functions as an antiviral factor. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in thyroid (RPKM 14.1), urinary bladder (RPKM 11.9) and 25 other tissues See more

Orthologs

mouse all

(peptidin rakenteesta: 1-557 aminohappoa , propeptidi.  peptidi on opteimpi ja siinä o nuseita  erityisrakenteita , runsaasti glykosylaatiota  solun ulkopuolella olevassa osassa ja fosforylaatiokohtia solunsisäpuolella olevassa osassa )

(25..114) " FN3" Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

(126..224) "interfer-bind"

Interferon-alpha/beta receptor, fibronectin type III

Members of this family adopt a secondary structure consisting of seven beta-strands arranged in an immunoglobulin-like beta-sandwich, in a Greek-key topology. They are required for binding to interferon-alpha.

(334..430) "interfer-bind"  FN3 type

(437..457)  transmebrane domain ( kalvon läpäisevä jakso)

(491-500 ) important for interaction with   TYK2
 466Y,481Y, 495S, 535S  phosphorylation  site

https://www.ncbi.nlm.nih.gov/protein/NP_000620.2

ORIGIN      
        1 mmvvllgatt lvlvavapwv lsaaaggknl kspqkvevdi iddnfilrwn rsdesvgnvt
       61 fsfdyqktgm dnwiklsgcq nitstkcnfs slklnvyeei klriraeken tsswyevdsf
      121 tpfrkaqigp pevhleaedk aivihispgt kdsvmwaldg lsftyslviw knssgveeri
      181 eniysrhkiy klspettycl kvkaalltsw kigvyspvhc ikttvenelp ppenievsvq
      241 nqnyvlkwdy tyanmtfqvq wlhaflkrnp gnhlykwkqi pdcenvkttq cvfpqnvfqk
      301 giyllrvqas dgnntsfwse eikfdteiqa fllppvfnir slsdsfhiyi gapkqsgntp
      361 viqdypliye iifwentsna erkiiekktd vtvpnlkplt vycvkaraht mdeklnkssv
      421 fsdavcektk pgntskiwli vgicialfal pfviyaakvf lrcinyvffp slkpssside
      481 yfseqplknl llstseeqie kcfiienist iatveetnqt dedhkkyssq tsqdsgnysn
      541 edesesktse elqqdfv
//

(Alla oleva kuva on netistä kun ligandi ilmenee, reseptori dimerisoituu. )
https://www-ssrl.slac.stanford.edu/content/science/highlight/2012-04-30/how-single-receptor-discriminates-between-variety-different-ligands


...

Reseptorikompelksin toinen osapuoli:
IFNAR2  (21q22.11)
https://www.ncbi.nlm.nih.gov/gene/3455
isoform b structure:
 https://www.ncbi.nlm.nih.gov/protein/NP_000865.2

ORIGIN      
        1 mllsqnafif rslnlvlmvy islvfgisyd spdytdesct fkislrnfrs ilswelknhs
       61 ivpthytlly timskpedlk vvkncanttr sfcdltdewr stheayvtvl egfsgnttlf
      121 scshnfwlai dmsfeppefe ivgftnhinv mvkfpsivee elqfdlslvi eeqsegivkk
      181 hkpeikgnms gnftyiidkl ipntnycvsv ylehsdeqav iksplkctll ppgqesesae
      241 sakiggiitv flialvltst ivtlkwigyi clrnslpkvl rqGlakgwna Vaihrcshna
      301 lqsetpelkQ ssclsfpssW dykraslcps d

Putative domain of unknown function
 

Region (24--120)  Tissue factor
This family is found in 
metazoa, and is very similar to the fibronectin type III domain. The 
family is found in cytokine receptors, interleukin and interferon 
receptors and coagulation factor III proteins. It occurs multiple times,
 as does fn3, family pfam00041.

The region (134..231) 

Interferon-alpha/beta receptor, fibronectin type III
Members  of this family adopt a secondary structure consisting of seven 
beta-strands arranged in an immunoglobulin-like beta-sandwich, in a 
Greek-key topology. They are required for binding to interferon-alpha.

This GVQW (293..239) 
 short domain is often found nested inside other longer domains. The 
function is not known, but the domain carries a highly conserved GVQW 
motif. It is possile that this is an AluS that has expanded in Human and
 Macaque genomes. 

Miten  sinkkikloridi antioksidanttina vaikuttaa tähän järjestelmään:  https://www.ncbi.nlm.nih.gov/pubmed/19362011/