• The final step in the generation of Abeta from the beta-amyloid precursor protein is an apparently intramembranous proteolysis by the elusive gamma-secretase(s). (scienceopen.com)
  • Here we report that mutation of either of two conserved transmembrane (TM) aspartate residues in presenilin-1, Asp 257 (in TM6) and Asp 385 (in TM7), substantially reduces Abeta production and increases the amounts of the carboxy-terminal fragments of beta-amyloid precursor protein that are the substrates of gamma-secretase. (scienceopen.com)
  • Amyloid-beta precursor protein ( APP ) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons . (handwiki.org)
  • Amyloid-beta precursor protein is an ancient and highly conserved protein . (handwiki.org)
  • ADAMs cleave a number of transmembrane proteins within their extracellular domains, resulting in the release (shedding) of their ectodomains. (bu.edu)
  • Human JAM-B cDNA predicts a 298 amino acid (aa) precursor protein with a putative 28 aa signal peptide, a 209 aa extracellular region containing two Ig domains, a 23 aa transmembrane domain and a 38 aa cytoplasmic domain containing a PDZ-binding motif and a PKC phosphorylation site. (rndsystems.com)
  • Human G-CSF R is 863 amino acids (aa) in length, with a 604 aa extracellular domain, a 26 aa transmembrane domain, and a 183 aa cytoplasmic domain that include a 23 amino acid signal sequence. (rndsystems.com)
  • The deduced 4660-aa sequence, expected to constitute a mature protein of M(r) 516,715, consists of a probable N-terminal signal peptide sequence (25 aa), an extracellular region (4400 aa), a single transmembrane domain (22 aa), and a C-terminal cytoplasmic tail (213 aa). (embl.de)
  • Like other membrane-anchored ADAMs, ADAM9 consists of a pro domain with a cysteine switch and furin cleavage sequence, a catalytic domain with the zinc-binding site and Metturn expected for reprolysins, a disintegrin like domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and the cytoplasmic domain. (reliatech.de)
  • In recent work, we have examined aspects of the regulation of mitogen-activated protein kinases (MAPK), mammalian target of rapamycin (mTOR), and integrin-dependent signaling by muscarinic receptor subtypes. (bu.edu)
  • Cell activation by G-CSF is mediated by a type I membrane protein belonging to the cytokine receptor superfamily. (rndsystems.com)
  • Binding of G-CSF to its receptor induces dimerization or oligomerization of the receptor activating cytoplasmic tyrosine kinases. (rndsystems.com)
  • Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. (embl.de)
  • The fifth domain is the cytoplasmic tail that directs the receptor to clathrin-coated pits. (embl.de)
  • The repeat is found in a variety of proteins that include, vitellogenin receptor from Drosophila melanogaster, low-density lipoprotein (LDL) receptor [ ( PUBMED:6091915 ) ], preproepidermal growth factor, and nidogen (entactin). (embl.de)
  • Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA. (bio-protocol.org)
  • ADAM9 is able to cleave peptides corresponding to cleavage sites of tumor necrosis factorα (TNFα), the p75 TNF receptor, the β-amyloid protein precursor, and the c-kit ligand1, implying that it may participate in shedding of these membrane proteins. (reliatech.de)
  • The non-receptor proteins tyrosine phosphatase type 14 (PTPN14) is situated in the adheren junctions (AJ) in both endothelial and epithelial cells and is important in rules of cell adhesion and cell development 32C35. (colinsbraincancer.com)
  • 19 normal healthy in- receptor protein (CD117) that is structurally dividuals were recruited as a control group. (who.int)
  • Slack, B.E. and Wurtman, R.J. (2007) Regulation of Synthesis and Metabolism of the Amyloid Precursor Protein by Extracellular Signals. (bu.edu)
  • TLR ligands include high-mobility group B1 (HMGB1), heat shock proteins (HSP60, HSP70), endotoxins, and extracellular matrix components [ 23 ]. (hindawi.com)
  • The extracellular E2 domain, a dimeric coiled coil and one of the most highly conserved regions of the protein from Drosophila to humans. (handwiki.org)
  • Proteolytic APP processing generates various cleavage products, including extracellular amyloid beta (Aß) and the cytoplasmic APP intracellular domain (AICD). (bvsalud.org)
  • The addition of an affinity tag allowed us to avoid the use of antibodies targeted toward the intracellular C-terminal tail of APP, a region to which a number of reported interacting proteins bind ( King and Turner, 2004 ). (jneurosci.org)
  • It is generated by proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor of head-to-tail monomers, or as a single N-terminal moiety to ribosomal proteins. (123dok.net)
  • Flotillin-1 (FLOT1) directly binds to the cytoplasmic tail of β-secretase and affects the sorting and recycling of the enzyme. (phcog.com)
  • Recent studies have identified the mitochondrial outer membrane proteins MOM19, MOM72, MOM38 (approximately ISP42) and p32 which have a role in initial steps of protein import. (nih.gov)
  • 10-formylTHF serves as a formyl donor for MET-tRNA in mitochondrial protein synthesis, and as a precursor of purines. (alzforum.org)
  • Mitochondrial and chloroplast proteins are therefore synthesized in the cytosol as preproteins with an NH 2 -terminal targeting sequence, which is both necessary and sufficient for directing the preproteins to the correct organelle. (silverchair.com)
  • Signal transduction from pathways that involve Janus tyrosine kinases/signal transducer and activator of transcription proteins (Jak1, Jak2, and Tyk2/STAT3, STAT3, and STATG), src-related protein tyrosine kinases (Lyn and Syk), Ras/MAP kinase, and phosphatidylinositol have been reported to be activated upon G-CSF stimulation (1). (rndsystems.com)
  • This image is one of a group of 4 images that supports the conclusion that hRio2 kinase activity is required for cytoplasmic 18S-E pre-rRNA processing. (ucsd.edu)
  • This image shows the distribution of all 18S rRNA precursors (white), via fluorescence in situ hybridization (FISH) with a 5' ITS1 probe, upon depletion of a protein important in rRNA processing, hRio2, and subsequent attempted rescue by transfection with an EGFP-tagged kinase-dead version of hRio2, in Hela cells. (ucsd.edu)
  • Depletion of hRio2 leads to the accumulation of 18S-E pre-rRNA in the cytoplasm (white), and this is rescued only by WT hRio2 (a companion image in this group), but not by hRio2 protein that lacks kinase activity, seen here in green. (ucsd.edu)
  • The cytoplasmic domain of ADAM9 interacts with Src homology 3 (SH3)containing proteins and protein kinase C, and may mediate different signaling pathways. (reliatech.de)
  • The protein kinase is found in the cytosol of pea mesophyll cells or in wheat germ extract. (silverchair.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • These mutations typically led to a truncation in the cytoplasmic domain of the G-CSF R leading to maturation arrest of neutrophil precursors in the bone marrow and neutropenia in peripheral blood (2). (rndsystems.com)
  • Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimer's disease. (handwiki.org)
  • While it is hypothesized that mutations in Nesprin and Lamin proteins lead to a mechanical instability of the nuclear envelope, these results indicate that signalling pathways through the nuclear envelope are disturbed as well. (fu-berlin.de)
  • All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (medscape.com)
  • Note that the 5' ITS1 probe shows the localization of all 18S rRNA precursors, but only 18S-E pre rRNA is detected in the cytoplasm. (ucsd.edu)
  • TDP-43 is a highly conserved, ubiquitously expressed, multifunctional nucleic acid-binding protein composed of two RNA recognition motifs (RRM), nuclear localization (NLS) and export signals (NES), and a carboxy-terminal glycine rich region. (nature.com)
  • Indeed, a dual localization of SecY protein in both cytoplasmic and thylakoid membranes from the cyanobacterium Synechococcus PCC7942 was reported [ 4 ]. (biomedcentral.com)
  • YAP activity could be also inhibited through the relationships with angiomotin (AMOT) family members proteins, which result in localization and sequestration from the YAP proteins to limited junction 29C31. (colinsbraincancer.com)
  • Several hundred different proteins are imported from the cytosol into the mitochondria. (nih.gov)
  • Thus, citric acid cycle intermedi- ates are not used for adenosine triphosphate (ATP) production and are shuttled out of the mitochondria, providing precursors for nucleotide, amino acid, and lipid synthesis path- ways for the dividing cell [13]. (who.int)
  • YAP, also called Yes-associated proteins 1, is usually an element of nuclear transcriptional complexes 9. (colinsbraincancer.com)
  • Nesprin proteins, together with SUN proteins, form a nuclear envelope-spanning protein complex, the LINC complex. (fu-berlin.de)
  • Most chloroplastic proteins are nuclear encoded, synthesized in the cytosol, and posttranslationally imported into the organelle. (silverchair.com)
  • The Gcn4p population within unstarved yeast consists of a small relatively stable cytoplasmic fraction and a larger less stable nuclear fraction. (uni-luebeck.de)
  • The expression of Wnt-5a protein was evaluated as membranous, cytoplasmatic and/or nuclear. (bvsalud.org)
  • The cytoplasmic / nuclear expression of Wnt-5a was the most frequent, with the strong intensity being the most prevalent. (bvsalud.org)
  • Short chains of RNA (100-300 nucleotides long) that are abundant in the nucleus and usually complexed with proteins in snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR). (bvsalud.org)
  • Our laboratory studies signal transduction pathways coupled to G protein-coupled receptors. (bu.edu)
  • Work from my laboratory and others has established roles for G protein-coupled (including muscarinic) receptors, growth factor receptors, protein kinases and calcium influx as activators of APP ectodomain shedding. (bu.edu)
  • The specific targeting of precursor proteins synthesized in the cytosol to various cell organelles is a central aspect of intracellular protein traffic. (nih.gov)
  • The precursor forms of prominent chloroplast proteins like the small subunit of stromal Rubisco (SSU), the thylakoid a/b binding protein (LHCP), or the thylakoid lumen localized subunits of the oxygen evolving complex of 23 kD and 33 kD (OE23, OE33) contain a phosphorylation site within the chloroplast targeting signal ( Waegemann and Soll 1996 ). (silverchair.com)
  • MTHFD1L encodes a protein, methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like, that may help convert homocysteine into methionine, so problems with this gene might lead to elevated homocysteine levels. (alzforum.org)
  • Older male patients with relapsing polychondritis who develop macrocytic anemia and thrombocytopenia may have VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, a rare disorder caused by a mutation in the UBA1 gene that encodes the enzyme-1-activating enzyme (E1) involved in intracellular destruction of defective proteins. (msdmanuals.com)
  • Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF- κ B p100, IRF8, and Def6. (frontiersin.org)
  • [6] APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. (handwiki.org)
  • Aβ peptide is generated by the proteolysis of amyloid precursor protein by two distinct proteases β and γ-secretase. (phcog.com)
  • The γ -secretase then liberates A β , as well as an APP cytoplasmic fragment, which may move to the nucleus and regulate gene expression. (csbsju.edu)
  • SREBP-2 is expressed in both the cytoplasm and nucleus on a subcellular level, depending on the state of the protein. (novusbio.com)
  • Control of protein stabilization which antagonizes Gcn4p function is restricted to the nucleus. (uni-luebeck.de)
  • The proximal events of TLR-mediated intracellular signaling are initiated by interactions with cytosolic adapters, mainly myeloid differentiation primary response protein 88 (MyD88) [ 25 ]. (hindawi.com)
  • Using lysate-based single-molecule motility assays and live-cell imaging in primary neurons, we show that JNK-interacting proteins 3 (JIP3) and 4 (JIP4) are activating adaptors for dynein that are regulated on autophagosomes and lysosomes by the small GTPases ARF6 and RAB10. (bvsalud.org)
  • Our results show that the rare late endosomal signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] directs the axonal cotransport of synaptic vesicle and active zone proteins in precursor vesicles in human neurons. (bvsalud.org)
  • G-CSF R is expressed in mature neutrophils, neutrophilic precursors, myeloid leukemia cells, and placenta. (rndsystems.com)
  • It shows strong granular cytoplasmic staining of chronic and acute myeloid leukemia and also reacts with rare cases of true histiocytic neoplasia. (enquirebio.com)
  • Endoplasmic reticulum and Golgi apparatus membranes,cytoplasmic vesicle. (novusbio.com)
  • Our findings identify a crucial mechanism that mediates the delivery of synaptic vesicle and active zone proteins to developing synapses. (bvsalud.org)
  • Here, we show that APP can coimmunoprecipitate NEEP21 from nontransgenic mouse brain and from mammalian cells stably coexpressing both proteins. (jneurosci.org)
  • Sterol regulatory element-binding proteins (SREBPs) compose a family of transcriptional factors that regulate the expression of various genes required for the synthesis of phospholipids, fatty acids, and cholesterol. (novusbio.com)
  • We conclude that ubiquitin might serve as a cis-acting molecular chaperone that assists in the folding and synthesis of the fused eL40 and eS31 ribosomal proteins. (123dok.net)
  • Therefore, there is a strict spatial separation of protein synthesis and degradation of Gcn4p in yeast. (uni-luebeck.de)
  • Purification of APP-AT protein complexes and identification of the constituents by mass spectrometry revealed several previously reported APP-interacting proteins as well as proteins involved in synaptic maintenance. (jneurosci.org)
  • Ubiquitin functions as a reversible post-translational modifier of proteins to regulate many different cellular processes such as DNA repair, chromatin dynamics, cell cycle regulation, membrane and protein trafficking, endocytosis, autophagy, but most notably proteasome-dependent protein degradation [2-4]. (123dok.net)
  • More than half of all human genes are alternatively spliced, so it is expected that alternative pre- mRNA splicing will be responsible for the identification of more than 90 percent of all human proteins. (genomicglossaries.com)
  • 20,000 Human Proteins ), and application (e.g. (enquirebio.com)
  • Understanding the role of the ubiquitin fused to ribosomal proteins becomes relevant, as these proteins are practically invariably eS31 and eL40 in the different eukaryotes. (123dok.net)
  • In most eukaryotes studied, ubiquitin is encoded by two classes of genes: (i) The first comprises genes coding for a single copy of ubiquitin fused to ribosomal proteins (r-proteins), most commonly eL40 and eS31. (123dok.net)
  • Ubiquitin fusion to other r-proteins, such as P1 or P2, and even to non-ribosomal proteins such as actin, has been reported in diverse genera of rare single-celled algae as, for example, Bigelowiella [6]. (123dok.net)
  • Others, the snoRNAs (RNA, SMALL NUCLEOLAR), are involved with the processing of ribosomal RNA precursors. (bvsalud.org)
  • The most common APP gene variant changes one of the protein building blocks (amino acids) in the amyloid precursor protein. (medlineplus.gov)
  • These variants change single amino acids in the amyloid precursor protein. (medlineplus.gov)
  • Human SREBP2 protein (amino acids 48-403). (novusbio.com)
  • Ubiquitin is a small eukaryotic protein of 76 amino acids whose name (i.e., it occurs ubiquitously) results from its remarkable evolutionary conservation [1]. (123dok.net)
  • This involves an initial cleavage of the amyloid precursor protein (APP) by an enzyme called BACE (or β -secretase). (csbsju.edu)
  • The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. (nih.gov)
  • In the cytoplasm formate enters the one-carbon pool through an ATP-dependent conversion to 10-formylTHF, catalyzed by the trifunctional enzyme MTHFD1-the cytoplasmic form of the enzyme (MacFarlane et al. (alzforum.org)
  • SHC-transforming protein 3 is a protein that in humans is encoded by the SHC3 gene. (wikipedia.org)
  • The APP gene provides instructions for making a protein called amyloid precursor protein. (medlineplus.gov)
  • Because alternative RNA splicing allows different types of mRNA molecules to be created from a single gene, it generates the diversity of protein function and structure that is essential to complex organisms. (genomicglossaries.com)
  • Highly specific and effective gene silencing of any disease can be achieved by an accurate knowledge of the target mRNA sequence and rational design of its complementary antisense agents for the downregulation of its protein message. (genomicglossaries.com)
  • A patient with congenital muscular dystrophy harboring a nonsense mutation in the gene coding for Nesprin-1 should express a truncated protein Nesprin1-ΔKASH lacking the SUN binding domain, probably disturbing the LINC complex. (fu-berlin.de)
  • This liberates the cytoplasmic domain, which, in the case of a number of proteins, has been shown to be signaling-competent. (bu.edu)
  • Following these repeats is a 350 residue domain that resembles part of the epidermal growth factor (EGF) precursor. (embl.de)
  • Taxonomic distribution of proteins containing LDLa domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with LDLa domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing LDLa domain in the selected taxonomic class. (embl.de)
  • Taxonomic distribution of proteins containing LY domain. (embl.de)
  • [12] The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's native-state biological functions. (handwiki.org)
  • Normally, the conjugation of ubiquitin to other proteins involves the formation of an isopeptide bond between the α-carboxyl group of the C-terminal glycine of a ubiquitin molecule with an ε-amino group of a specific lysine residue within the target protein [2,3]. (123dok.net)
  • It reacts with myeloid precursors and peripheral blood granulocytes. (enquirebio.com)
  • The amyloid precursor protein (APP) is an ADAM substrate that plays a central role in the pathology of Alzheimer's disease (AD). (bu.edu)
  • The transcriptional activity of YAP is usually subject to unfavorable rules by cytoplasmic sequestration or ubiquitin-mediated degradation. (colinsbraincancer.com)
  • The Sec tranlocation machinery is unable to translocate folded proteins (in contrast to the Tat machinery). (biomedcentral.com)
  • Thus, this study demonstrates that using proteomic methods on our transgenic model can uncover important in vivo APP-interacting proteins that will provide insights into the biology of APP. (jneurosci.org)
  • single-stranded RNA (ssRNA) segments that encode four structural proteins: the Gn and Gc glycoproteins, nucleocapsid protein (N), and RNA-dependent RNA polymerase. (hwupdate.org)
  • Ubiquitin is a highly conserved small eukaryotic protein. (123dok.net)
  • In addition, heterologous antisera directed against components of the Toc/Tic translocons and binding of a labeled precursor protein were used to discriminate between inner and outer envelope membranes. (biomedcentral.com)
  • A phosphorylated precursor protein can still bind to the chloroplast import machinery, but must become dephosphorylated before translocating through the membranes. (silverchair.com)
  • The γ -secretase protein quartet, and its roles in brain development and Alzheimer's disease. (csbsju.edu)
  • Many different proteins are cleaved by ADAM proteases, and although ADAMs are believed to exert a mitigating influence in Alzheimer's disease, they may exacerbate the pathologies of cancer, inflammation, and vascular disease. (bu.edu)
  • The amyloid precursor protein (APP) plays a central role in the pathophysiology of Alzheimer's disease in large part due to the sequential proteolytic cleavages that result in the generation of β-amyloid peptides (Aβ). (scienceopen.com)
  • Accumulation of the amyloid-beta protein (Abeta) in the cerebral cortex is an early and invariant event in the pathogenesis of Alzheimer's disease. (scienceopen.com)
  • The amyloid precursor protein (APP) is a key molecular component of Alzheimer's disease (AD) pathogenesis. (bvsalud.org)
  • To investigate the APP in vivo interactome in an unbiased manner, we generated mice that harbor a mouse prion protein promoter-driven cDNA encoding human APP-695 fused to a C-terminal affinity tag. (jneurosci.org)
  • When preSSU or preOE33 are synthesized in a wheat germ lysate, they form an oligomeric guidance complex with other proteins, two of which are hsp70 and 14-3-3 ( May and Soll 2000 ). (silverchair.com)
  • Finally, YAP buy AdipoRon mediates hedgehog-driven neural precursor proliferation and promotes radioresistance and genomic instability in medulloblastoma23C24. (colinsbraincancer.com)
  • It seems that not until the technologies for working with nucleic acids and proteins are better integrated will their researchers be more connected than they are now. (genomicglossaries.com)
  • Type I membrane protein. (lu.se)
  • It has been known to interact and form a complex with the SCAP protein at the ER, in turn inhibiting interaction between SCAP and SEC24B. (novusbio.com)
  • Protein-protein interaction study of FLOT1 deciphered the interactors playing key role in AD. (phcog.com)
  • Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. (bio-protocol.org)
  • Precursor vesicles are distinct from conventional secretory organelles, endosomes, and degradative lysosomes and are transported by coincident detection of PI(3,5)P2 and active ARL8 via kinesin KIF1A to the presynaptic compartment. (bvsalud.org)
  • In this thesis, I studied three proteins that are participating in two different pathways of mechanotransduction. (fu-berlin.de)