Geeni POFUT1 vaikuttaa NOTCH, EGF- signalointialueella

"Six signal transduction system, notch, EGF, FGF, TGFbeta, Hedgehog, and Wnt, are utilized to provide spatial inputs in a myriad of diverse subcircuits in the development of any bilaterian, and in different contents  in different bilaterians. Though in their internal biochemical interactions these signal transduction cassetes are higly conserved across the bilateria, they are indeed "plugged in" at all levels of gene regulatory networks, in all sorts of regulatory spatial  specification processes.
Lähde:
Eric H. Davidson. 2006.
The Regulatory genome:Gene regulatory network in Development and Evolution.  p. 194."


Otan tänään  23.6. 2020  lisätietoja eräästä SARS-2 viruksen  interaktioproteiinista POFUT1.  se mainitaan listassa ORF8 interaktioproteiinina.  Olen tänään nimittäin ktomassa glycocalicasiaa ja veriryhmäepitooppeja. Niissä on FUT- entsyymeitä mainittu.  Tässä on eri joukon FUT, POFUT1 entsyymi siirtää fukoosia jonkin proteiinin seriini- tai threoniinin tähteeseen O-välitteisesti .  Vain seriinillä ja threoniinilla on - OH ryhmä ja siihen sivuhaaraan voi tapahtua  glycocalix epitooppien kertymää, niitä oligosakkarideja. 


POFUT1 (20q11.219

Aliases for POFUT1 Gene

Protein O-Fucosyltransferase 1 ^{2 3 5}
GDP-Fucose Protein O-Fucosyltransferase 1 ^{2 3 4}
Peptide-O-Fucosyltransferase 1 ^{3 4}
EC 2.4.1.221 ^{4 52}
O-FucT-1 ^{3 4}
FUT12 ^{3 4}

O-Fucosyltransferase Protein ³
Peptide-O-Fucosyltransferase ²
KIAA0180 ⁴
O-Fuc-T ³
OFUCT1 ³
O-FUT ³
DDD2 ³

 POFUT1 Gene. This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like (EGFL)  repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary for POFUT1 Gene

POFUT1 (Protein O-Fucosyltransferase 1) is a Protein Coding gene. Diseases associated with POFUT1 include Dowling-Degos Disease 2 and Dowling-Degos Disease. Among its related pathways are Notch Signaling Pathway (WikiPathways) and Pre-NOTCH Expression and Processing. Gene Ontology (GO) annotations related to this gene include fucosyltransferase activity and peptide-O-fucosyltransferase activity.

UniProtKB/Swiss-Prot Summary for POFUT1 Gene

Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs). OFUT1_HUMAN,Q9H488

Kerään  tään mainitut   vaikutuskohteet.

NOTCH,  EGEF repeats https://www.genecards.org/cgi-bin/carddisp.pl?gene=NOTCH1&keywords=NOTCH1

FRINGE/RFNG, acetylglucosaminyltransferase

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

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

DLL1, (Delta like canonical Notch ligand 1), https://www.genecards.org/cgi-bin/carddisp.pl?gene=DLL1&keywords=DLL1

JAGGED1,  ( Notch 1ligand) , https://www.genecards.org/cgi-bin/carddisp.pl?gene=JAG1&keywords=JAGGED1

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

AChR, https://www.genecards.org/cgi-bin/carddisp.pl?gene=CHRNE&keywords=ACHR

• Kuva NOTCH signalointikartasta. modulaattorien joukossa n-kyy tämä POFUT1.Fukosylaation merkitys on signaalitien tarkennuksessa ja viitoituksessa.
   KUVA netistä: https://www.researchgate.net/profile/Adriana_Heguy/publication/23687986/figure/fig1/AS:341171915247620@1458353131550/The-Notch-pathway-in-mammals-The-pathway-is-triggered-by-the-Delta-like-or-Jagged.png

The Notch pathway in mammals. The pathway is triggered by the Delta-like or Jagged ligands interacting with one or more of the Notch receptors. The pathway is activated by intracellular cleavage of a Notch receptor, releasing the Notch intracellular domain, which translocates to the nucleus where it activates CBF1 (gene symbol, RBPSUH), the primary transcription factor to activate downstream Notch effector pathways (Hes1, 2, 5; Hey1, 2 and L). A variety of transcriptional coactivators and cytoplasmic and nuclear modulators tune the pathway, providing multiple points of control. When Notch signaling is active, differentiation is suppressed . When Notch signaling is turned ''off,'' differentiation to specific cell fates is allowed to proceed.

•  Otan netistä toisenkin kuvan  Agrin proteiinin  ja asetylkoliinireseptorin  ryhmittyminen (AchR)  näkyy siinä. 

https://www.researchgate.net/figure/Agrin-Lrp4-MuSK-pathways-leading-to-AChR-clustering-See-text-for-details_fig2_279750836 
Arnab Barik

Muscle-specific kinase (MuSK) is a RTK that is specifically expressed in skeletal muscle fibers and critical for the formation and maintenance of the neuromuscular junction (NMJ), a peripheral synapse formed between motoneurons and muscle fibers (1, 2). The acetylcholine receptors (AChRs) are concentrated at the crest of junctional folds on muscle...

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Siisrsin tämän SARS-2 proteiini-proteiini-interaktioproteiinin asian  Solusykli blogiini, koska  tänmä interaktioalue  on   NOTCh signalointikartasta, joten vaikutus ulottuu transkriptiotasoon.