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måndag 8 augusti 2022

Inflammasomi NLRP12 säätelee RIG-1 proteiinia TRIM25 ja RNF125 sinkkisormiproteiinien avulla.

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=NLRP12

Genecards tietoa tästä inflammasomista, joka järjestää  RIG-1 RNA-virussensoria  silppuroitumaan unikitiiniproteosomijärjestelmässä..

Aliases for NLRP12 Gene

  • GeneCards Symbol: NLRP12 2
  • NLR Family Pyrin Domain Containing 12 2 3 5
  • PYPAF7 2 3 4 5
  • CLR19.3 2 3 5
  • NALP12 3 4 5
  • RNO2 2 3 5
  • PAN6 2 3 5
  • Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat And Pyrin Domain Containing 12 2 3
  • NACHT, LRR And PYD Domains-Containing Protein 12 3 4
  • PYRIN-Containing APAF1-Like Protein 7 3 4
  • Regulated By Nitric Oxide 3 4
  • Monarch1 2 5
  • RNO 3 4
  • NACHT, Leucine Rich Repeat And PYD Containing 12 2
  • Monarch 1 3
  • Monarch-1 4
  • FCAS2 3

Protein details for NLRP12 Gene (UniProtKB/Swiss-Prot)

Protein Symbol:
P59046-NAL12_HUMAN
Recommended name:
NACHT, LRR and PYD domains-containing protein 12
Protein attributes for NLRP12 Gene
Size:1061 amino acidsMolecular mass: 120173 Da
Quaternary structure:Interacts (via pyrin domain) with ASC. Interacts (via pyrin domain) with FAF1 (via UBA domain) (PubMed:21978668). Interacts with MAP3K14; this interaction promotes proteasomal degradation of MAP3K14 (PubMed:17237370). Interacts with NOD2; this interaction promotes degradation of NOD2 through the ubiquitin-proteasome pathway (PubMed:30559449). Interacts with HSPA1A and HSPA8 (PubMed:17947705). Interacts with HSP90AA1 (PubMed:17947705, PubMed:30559449).
 
 Interacts with TRIM25 (alias RNF147, ZNF147, EFP) ; this interaction inhibits DDX58-mediated signaling pathway (  alias RIG-1 sensoritie)  (PubMed:30902577).
 
 Kommentti:  
TRIM 25 on sinkkisormiproteiini, jolla on RING- tyyppinen sinkkisormi (ZNF147, RNF147)  ja tämä suorittaa DDX5 (-proteiinin aktivaation ubikitinoimalla lysiinin K63, mutta tätä aktivaatiota estää  NLRP12. 
 
Lisäksi NLPR12 vaikuttaa, että toinen RING-tyyppinen sinkkisormiproteiini RNF125 (TRAC1)  ubikitinoi  DDX58-proteiinin toiseen lysiiniin K48, jolloin se suuntautuu proteosomaaliseen silppuriin.
Protein Domains for NLRP12 Gene
InterPro:
Blocks:
  • Leucine-rich repeat signature
  • Pyrin domain
  • Leucine-rich repeat, ribonuclease inhibitor subtype

 RNF125 proteiinista lisää tietoa. Se säätelee positiivisesti T-solureseptorin signalointiteitä.
  • This gene encodes a novel E3 ubiquitin ligase that contains a RING finger domain in the N-terminus and three zinc-binding and one ubiquitin-interacting motif in the C-terminus. As a result of myristoylation, this protein associates with membranes and is primarily localized to intracellular membrane systems. The encoded protein may function as a positive regulator in the T-cell receptor signaling pathway. [provided by RefSeq, Mar 2012]

GeneCards Summary for RNF125 Gene
RNF125 (Ring Finger Protein 125) is a Protein Coding gene. Diseases associated with RNF125 include Tenorio Syndrome and Overgrowth Syndrome. Among its related pathways are DDX58/IFIH1-mediated induction of interferon-alpha/beta and Innate Immune System. Gene Ontology (GO) annotations related to this gene include ligase activity and ubiquitin-protein transferase activity. An important paralog of this gene is RNF166.
UniProtKB/Swiss-Prot Summary for RNF125 Gene
  • E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as DDX58/RIG-I, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525, PubMed:17460044, PubMed:17643463, PubMed:26027934, PubMed:26471729, PubMed:25591766, PubMed:27411375). Acts as a negative regulator of type I interferon production by mediating ubiquitination of DDX58/RIG-I at 'Lys-181', leading to DDX58/RIG-I degradation (PubMed:17460044, PubMed:26471729). Mediates ubiquitination and subsequent degradation of p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of T-cell activation (PubMed:15843525).
Lisätietoa RNF125  ja sen  kaltaisista RING-sinkkisormiproteiineista (RNFs)  proteiineista:
. 2008 Feb 15;410(1):101-11.
doi: 10.1042/BJ20070995.
T-cell regulator RNF125/TRAC-1 belongs to a novel family of ubiquitin ligases with zinc fingers and a ubiquitin-binding domain


 

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