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This study describes the crystal structures of optineurin/TBK1 (zeige TBK1 Proteine) complex and the related NAP1 (zeige IL8 Proteine)/TBK1 (zeige TBK1 Proteine) complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 (zeige TBK1 Proteine) interaction, and revealing a general binding mode between TBK1 (zeige TBK1 Proteine) and its associated adaptor proteins.
Data suggest that OPTN mRNA and protein expression are significantly decreased in fetal membranes and myometrium during spontaneous term labor; there appears to be no effect of preterm labor on OPTN expression in fetal membranes. In cultured myometrial cells, RNA interference of OPTN up-regulates expression of inflammation mediators in response to IL1B (zeige IL1B Proteine) (inteleukin-1B).
When yeast genetic interaction partners held in common between human OPTN and ANG (zeige ANG Proteine) were validated in mammalian cells and zebrafish, MAP2K5 (zeige MAP2K5 Proteine) kinase emerged as a potential drug target for amyotrophic lateral sclerosis therapy
A new variant associated with Paget's Disease of Bone in OPTN, reinforcing the relevance of this gene for the development of this bone disease.
OPTN colocalizes with LC3 (autophagic vesicle marker) and alpha-synuclein positive puncta in rotenone-treated animals, potentially indicating an important role in autophagy and PD pathogenesis
Given the critical roles of TBK1 (zeige TBK1 Proteine), important regulatory mechanisms are required to regulate its activity. Among these, Optineurin (Optn) was shown to negatively regulate the interferon (zeige IFNA Proteine) response, in addition to its important role in membrane trafficking, protein secretion, autophagy and cell division.
E50K, M98K, Q398X and E478G mutations in OPTN affect neuronal viability under normal or oxidative stress conditions.
These results suggest that the IRAK1 (zeige IRAK1 Proteine)-binding protein OPTN negatively regulates IL-1beta (zeige IL1B Proteine)/LPS (zeige IRF6 Proteine)-induced NF-kappaB (zeige NFKB1 Proteine) activation by preventing polyubiquitination of TRAF6 (zeige TRAF6 Proteine).
This study therefore provides novel information regarding the role of Optn during T-cell activation, suggesting the possible importance of Optn during inflammation and/or autoimmune diseases.
Frontotemporal dementia -linked mutations in gene OPTN encoding autophagy adaptor proteins , indicate that impaired autophagy might cause Frontotemporal dementia.
These results suggest that the IRAK1 (zeige IRAK1 Proteine)-binding protein OPTN negatively regulates IL-1beta (zeige IL1B Proteine)/LPS (zeige TLR4 Proteine)-induced NF-kappaB (zeige NFKB1 Proteine) activation by preventing polyubiquitination of TRAF6 (zeige TRAF6 Proteine).
Report establishes optineurin as a positive regulator TBK1 (zeige TBK1 Proteine) via a bipartite interaction between these molecules.
OPTN-deficient mice were more susceptible to infection with Salmonella, confirming in vivo the importance of OPTN in bacterial clearance.
Optineurin knockdown enhances osteoclast differentiation. Optineurin inhibits osteoclast formation by modulating NF-kappaB (zeige NFKB1 Proteine) and IFN-beta (zeige IFNB1 Proteine) signaling.
Mutation in Optineurin gene is associated with Glaucoma.
Disruption in optineurin and myosin VI (zeige MYO6 Proteine)-mediated cellular trafficking is associated with amyotrophic lateral sclerosis.
OPTN plays a role in acute inflammation and neutrophil recruitment, potentially via defective macrophage proinflammatory cytokine secretion.
that ubiquitin (Ub)-binding domain mutants compromise the maturation of autophagosomes, which in turn interfered with optineurin-mediated autophagy and clearance of inclusion bodies
results indicated that optineurin trimers may be the basic unit of these oligomers. The oligomeric state can be affected by many factors that induce covalent bonds, such as H2O2 or E50K
Loss of optineurin in vivo results in elevated cell death and alters axonal trafficking dynamics
The optineurin gene and protein are evolutionary conserved between humans and the rhesus monkey. High similarity of ocular expression and tissue distribution between the two optineurin proteins.
This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein.
, E3-14.7K-interacting protein
, Huntingtin interacting protein L
, huntingtin yeast partner L
, huntingtin-interacting protein 7
, huntingtin-interacting protein L
, nemo-related protein
, optic neuropathy-inducing protein
, transcription factor IIIA-interacting protein
, transcrption factor IIIA-interacting protein
, tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains
, 14.7K-interacting protein 2
, FIP-2-like protein