In the present study, we have explored the function of the C-terminal sequences of complexins, relatively large sequences that account for nearly half of the complexin protein but nevertheless have remained functionally incompletely characterized. Because complexin-1 and complexin-2, and complexin-3 and complexin-4 form homologous pairs, we tested the effect of deleting or mutating the C-terminal sequences of complexin-1 and complexin-3, asking among others whether complexin-1 and complexin-3 perform similar functions in synaptic exocytosis and whether the functional differences between these complexins localize to their C-terminal regions. We made the following principal observations.. (1) Deletion of the complexin-1 C-terminal sequence revealed that it is essential for both its priming and clamping function but not for its synaptotagmin-activating function, thereby dissociating the two "positive " functions (synaptotagmin-activating and priming) of complexin.. (2) Complexin-1 and complexin-3 ...
Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.
TLR signaling is mediated by the recruitment of distinct combinations of adaptor molecules to the cytoplasmic TIR domain of each TLR. Distribution and localization of the adaptor molecules are important factors controlling TLR-mediated signaling. TIRAP/Mal was found to be associated with the plasma membrane via a phosphatidylinositol 4,5-biphosphate-binding domain and facilitates MyD88 delivery to activated TLR4 (22). Also, myristoylation of TICAM-2/TRAM targets it to the plasma membrane and the Golgi apparatus, where it colocalizes with TLR4 (23). Thus, the role of these adaptor proteins other than TICAM-1 has been clearly demonstrated; TIRAP/Mal and TICAM-2/TRAM mainly function as bridges between TLR4 and the signaling adaptors, whereas MyD88 restricts its localization by TIRAP to assemble signal molecules around the TLR4 complex (9, 10, 24, 25). In this study we demonstrated that TICAM-1/TRIF delivers a signal in a unique fashion distinct from that of MyD88.. This is the first study to ...
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The ENTH domain is about half the size of an ANTH domain, but is also alpha-helical and in fact some of the helices superimpose very nicely (see below). The ENTH domain also binds to PtdInsPhosphates but using completely different residues. We have shown that the binding of PtdIns(4,5)P2 to epsin1 ENTH domain causes the folding of an additional N-terminal helix that can insert into the membrane and drive positive membrane curvature. ...
The following pictures illustrate how the lipids must move apart to accommodate the insertion of helix zero. The first picture shows 2 different views of the ENTH domain with a space filled PtdIns(4,5)P2 docked in the structure. In the bottom picture a membrane (to scale) is added such that the PtdIns(4,5)P2 is inserted and consequently helix zero is buried. One can image a space filled helix zero an d the number of lipids that would have to be displaced to accommodate epsin docking on the membrane ...
VHS domains are found at the N-termini of select proteins involved inintracellular membrane trafficking. We have determined the crystalstructure of the VHS domain of the human Tom1 (target of myb 1) protein to1.5 A resolution. The domain consists of eight helices arranged in asuperhelix. The surface of the domain has two main features: (1) a basicpatch on one side due to several conserved positively charged residues onhelix 3 and (2) a negatively charged ridge on the opposite side, formed byresidues on helix 2. We compare our structure to the recently obtainedstructure of tandem VHS-FYVE domains from Hrs [Mao, Y., Nickitenko, A.,Duan, X., Lloyd, T. E., Wu, M. N., Bellen, H., and Quiocho, F. A. (2000)Cell 100, 447-456]. Key features of the interaction surface between theFYVE and VHS domains of Hrs, involving helices 2 and 4 of the VHS domain,are conserved in the VHS domain of Tom1, even though Tom1 does not have aFYVE domain. We also compare the structures of the VHS domains of Tom1 andHrs to the ...
Interferon regulatory aspect (IRF)-3 may have a crucial function in viral and bacterial innate immune system replies by regulating the creation of type We interferon (IFN). cells. This inhibition was because of its suppression from the transcriptional activation TC-E 5001 of IRF-3, as proven by inhibition of IRF-3 PRD (III-I) luciferase activity along with the phosphorylation design of IRF-3 within the immunoblotting test. Furthermore, TQ targeted the autophosphorylation of TANK-binding kinase 1 (TBK1), an upstream essential enzyme in charge of IRF-3 activation. Used together, these results claim that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would eventually decrease the creation of type I IFN. TQ also governed IRF-3, among the inflammatory transcription elements, offering a novel understanding into its anti-inflammatory actions. (TRIF). Upon arousal by LPS, TLR-4 recruits the adaptor proteins TRIF, which in turn recruits tumor necrosis TC-E 5001 aspect ...
Build: Sat Nov 17 23:53:08 EST 2018 (commit: a759bb7). National Center for Advancing Translational Sciences (NCATS), 6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-435-0888. ...
VMware Tools for linux exists in 2 forms: the official VMware Tools and Open-VM-Tools. VMware Tools is based on a stable snapshot of Open-VM-Tools. Open-VM-Tools contains more experimental code and features. The official VMware Tools are not available for Archlinux. Originally, VMware Tools provided the best drivers for network and storage, combined with the functionality for other features such as time synchronization. However, for quite a while now the drivers for the network adapter en scsi adapter are part of the linux kernel, and VMware Tools is only needed for extra features and support for the "old" vmxnet adapter. ...
Epsin 1兔多克隆抗体(ab82688)可与人样本反应并经WB, ELISA实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
TRIF兔多克隆抗体(ab62583)可与人样本反应并经WB, IHC, ICC/IF实验严格验证,被1篇文献引用并得到1个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
TLR4 recruits TRIF-related adaptor molecule (TRAM, also known as TICAM2) as a sorting adaptor to facilitate the interaction between TLR4 and TRIF and then initiate TRIF-dependent IRF3 activation. However, the mechanisms by which TRAM links downstream molecules are not fully elucidated. In this study, we show that TRAM undergoes tyrosine phosphorylation upon TLR4 activation and that is required for TLR4-induced IRF3 activation. Protein tyrosine phosphatase nonreceptor type 4 (PTPN4), a protein tyrosine phosphatase, inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRAM, resulting in the disturbance of TRAM-TRIF interaction. Consequently, PTPN4 specifically inhibits TRIF-dependent IRF3 activation and IFN-β production in TLR4 pathway. Therefore, our results provide new insight into the TLR4 pathway and identify PTPN4 as a specific inhibitor of TRIF-dependent TLR4 pathway. Targeting PTPN4 would be beneficial for the development of new strategy to control TLR4-associated ...
The vesicle-mediated membrane transport is a multi-step process, consisting of vesicle formation (budding), targeting, tethering and membrane fusion (Bonifacino and Glick, 2004; Jahn and Scheller, 2006). Cargo proteins are concentrated at a specialized region on the donor membrane and packed into a nascent vesicle generated by the assembly of coat proteins such as clathrin into a cage-like lattice around the budding vesicle. Adaptor protein complexes (AP) are required to recruit cargo into coated vesicles thus playing an essential role in cargo selectivity of the transport vesicle in traffic between the trans-Golgi network (TGN) and endosomes (Owen et al., 2004). Gga proteins are monomeric clathrin adaptor proteins mediating TGN to the endosome transport (Nakayama and Wakatsuki, 2003). Apart from the AP complexes and the monomeric GGA adaptors, the list is expanding to new sets of adaptors, which are specific to only a particular type of cargo or to one family of cargo (Bonifacino and Rojas, ...
The liver responds to inflammation by down-regulating key hepatic genes involved in regulation of metabolic processes in the liver. This leads to disruption of drug metabolism and clearance and can cause drugs to become potentially ineffective or even toxic. To understand the mechanism of alteration of hepatic drug metabolism in inflammation, we are focusing on elucidating inflammation-induced signaling pathways in the liver. Cross-talk between the signaling components and DME gene regulators contribute to the down-regulation of these genes. We find that the LTA-mediated regulation of hepatic DME genes and serum cytokines involves the LTA receptor TLR2 as expected. However, the first adaptor protein, TIRAP, mediates the effects of LTA on DME genes in vivo and in isolated primary hepatocytes but not on cytokine expression in the liver.. In the liver, cytokines released from Kupffer cells bind to their respective receptors on hepatocytes to initiate signaling events, leading to down-regulation of ...
Background: Epsins are a family of ubiquitin-binding endocytic clathrin adaptors. We recently published that endothelial epsins function as critical regulators of tumor angiogenesis by controlling VEGF signaling (JCI, 2012; ATVB, 2013). Our goal is to define the novel role of epsins in macrophages in regulating atherogenesis.. Methods and Results: We engineered mice with specific deletion of epsins in myeloid cells (MΦ-DKO). Strikingly, MΦ-DKO mice on ApoE-/- background fed western diet significantly reduced atherosclerotic lesion formation and foam cell accumulation. In macrophages, epsin deficiency did not alter LDL scavenger receptors, CD36, Lox1 or SRB1, or reverse cholesterol transport proteins, ABCA1 or ABCG1, but did significantly reduce Lucifer Yellow pinocytosis, indicating a major defect in lipid uptake. Epsin deficiency did decrease total and surface protein levels of LRP-1, a protein with anti-inflammatory and anti-atherosclerotic properties. Oil Red O staining of isolated ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Enlarged early endosomes in the neurons of young Down syndrome (DS) and pre-Alzheimers disease (AD) brains suggest that a disturbance in endocytosis is one of the earliest hallmarks of AD pathogenesis in both conditions. We identified a chromosome 21 gene, Intersectin-1 (ITSN1) that is up-regulated in DS brains and has a putative function in endocytosis and vesicle trafficking. To elucidate the function of ITSN1 and assess its contribution to endocytic defects associated with DS and AD, we generated Itsn1 null mice. In knockout mice we found alterations in a number of parameters associated with endocyic and vesicle trafficking events. We found a reduced number of exocytosis events in chromaffin cells and a slowing of endocytosis in neurons. Endosome size was increased in neurons and NGF levels were reduced in the septal region of the brain. Our data is the first indication that Itsn1 has a role in endocytosis in an in vivo mammalian model, and that a disruption in Itsn1 expression causes a ...
Genetic variations in the vacuolar protein sorting 10 protein (Vps10p) family have been linked to Alzheimers disease (AD). Here we demonstrate deposition of fragments from the Vps10p protein sortilin at senile plaques (SPs) in aged and AD human cerebrum. Sortilin changes were characterized in postmortem brains with antibodies against the extracellular and intracellular C-terminal domains. The two antibodies exhibited identical labeling in normal human cerebrum, occurring in the somata and dendrites of cortical and hippocampal neurons. The C-terminal antibody also marked extracellular lesions in some aged and all AD cases, appearing as isolated fibrils, mini-plaques, dense-packing or circular mature-looking plaques. Sortilin and β-amyloid (Aβ) deposition were correlated overtly in a region/lamina- and case-dependent manner as analyzed in the temporal lobe structures, with co-localized immunofluorescence at individual SPs. However, sortilin deposition rarely occurred around the pia, vascular wall or
In collaboration with Dr. Kerstin Reim, MPI Göttingen, Germany) Complexin (Cplx) 1, 2, 3 and 4 are a family of small, soluble proteins that bind to the assembled exocytotic core complex, and are involved in the regulated release of neurotransmitter at chemical synapses in the central nervous system. In the mouse genome the four proteins are encoded by different genes: Cplx 1 and 2 are - like Cplx 3 and 4 - highly homologous to each other, whereas Cplx 1 and 2 show only a very limited homology to Cplx 3 and 4. In contrast to Cplx 1 and 2, Cplx 3 and 4 contain a CAAX box motif, which leads to farnesylation. It has been shown that this farnesylation motif causes membrane targeting of Cplx 3 and 4. Whereas Cplxs 1, 2 and 3 are distributed in the retina and brain, Cplx 4 is restricted to the retina. With immunocytochemistry and high resolution light microscopy, I examine the cellular, synaptic and developmental expression of all four Cplx isoforms in the mouse retina. Using a variety of different ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Complete information for CPLX3 gene (Protein Coding), Complexin 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CPLX2 gene (Protein Coding), Complexin 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
References for Abcams Recombinant Human CPLX1 protein (ab79148). Please let us know if you have used this product in your publication
A three-piece anastomotic coupling device for end-to-end anastomosis of tubular members consisting of two open bore cylindrical adaptors and an open bore cylindrical connector. Each end of a tubular member is passed through the axial bore of an adaptor and everted over the end thereof. The adaptors are then inserted into opposite ends of the connector until the everted ends of the vessel abut under light compression. Integral locking means are provided to secure the adaptors and tubular members of the connector piece.
With the release of OS X 10.8.2, Apple disabled USB 2.0 drivers over Thunderbolt. Because many SD-to-SxS adapters use the ExpressCard USB interface, and Qio and Qio E3 support USB-based adapters through the ExpressCard (SxS) slots USB interfaces, the adapters are not recognized under 10.8.2+. Sonnets USB 2.0 Over Thunderbolt Patch for Qio/Qio E3 removes the limitation and allows your adapter to be recognized ...
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Most difficulties in working with Micro-Manager arise from configuring the system and from problems/issues with specific devices. In both of these cases you are interacting mainly with device adapters. These device adapters have been written by several different authors, all behave slightly differently, and interact with specific hardware that has its own peculiarities. On these pages we will maintain as much information as possible about Micro-Manager device adapters. This will help you configure and understand your Micro-Manager system. We hope that the authors of the device adapters will maintain this information, but please feel free to update the information here with your own experiences. The information here will refer to the most recent Micro-Manager release. ...
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Please make sure the part number Please make sure the part number, series number and model number are all matching your original adapter.
Please make sure the part number Please make sure the part number, series number and model number are all matching your original adapter.
GoPro™-adapter for ski poles. For mounting the original GoPro™ support on the grip. Compatible with these models: 6366872, 6366870, 6362707, 636685...
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Das Paket enthält die folgenden Tests:Pyruvatkinase-Defizienz (PK), Glykogenspeicherkrankheit Typ IV (GSD4) und die Fellfarbe Amber.
Diese Fotogalerie enthält eine Umfangreiche Bildersammlung, wie Astroaufnahmen,Wetterbilder,Landschaftsaufnahmen, und weitere Bilder davon.
Diese Fotogalerie enthält eine Umfangreiche Bildersammlung, wie Astroaufnahmen,Wetterbilder,Landschaftsaufnahmen, und weitere Bilder davon.
The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010 ...
Analyses with the yeast two-hybrid system showed that the cytosolic tail of the human CI-MPR interacted with full-length GGA3 as well as with the ∼150-amino acid VHS domain, but not the GAT or GAE domains of GGA3 (Fig. 1C). Further analyses revealed that the CI-MPR tail interacted with the VHS domains of all three GGAs and that the CD-MPR tail interacted with the VHS domains of GGA1 and, more weakly, GGA3 (Fig. 1D). These interactions were highly specific, because neither MPR tail bound to the VHS domains of STAM1, HRS, TOM1, and TOM1L1 (Fig. 1D). Likewise, we did not detect interactions between the GGA VHS domains and the cytosolic tails of TGN38, TRP2, tyrosinase, TRP1, LAMP-2, LIMP II, low density lipoprotein (LDL) receptor, β-amyloid precursor, and transferrin receptor (Fig. 1D), which contain either tyrosine-based sorting signals or dileucine-based sorting signals devoid of acidic clusters.. Deletion of the acidic-cluster-dileucine signals from the CI-MPR and CD-MPR tails abolished ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Sortilin (SORT1) is a protein that in humans is encoded by the SORT1 gene on chromosome 1. This protein is a type I membrane glycoprotein in the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors. While it is ubiquitously expressed in many tissues, sortilin is most abundant in the central nervous system. At the cellular level, sortilin functions in protein transport between the Golgi apparatus, endosome, lysosome, and plasma membrane, leading to its involvement in multiple biological processes such as glucose and lipid metabolism as well as neural development and cell death. Moreover, the function and role of sortilin is now emerging in several major human diseases such as atherosclerosis and coronary artery disease, Alzheimers disease, and cancer. The SORT1 gene also contains one of 27 loci associated with increased risk of coronary artery disease. The SORT1 gene resides on chromosome 1 at the band 1p13.3 and includes 23 exons. This gene encodes 2 isoforms through ...