kferq motif prediction

"Which autophagy pathway is trigered by the KFERQ motif of cytosolic proteins?" "Which are the clinical characteristics of TSC?" "How does dabigatran therapy affect aPTT in patients with atrial fibrillation?" "List fish anti-freeze proteins." "Which is the phosphorylated residue in the promoter paused form of RNA polymerase II?" Mutation of this motif prevents EGFR degradation by CMA and promotes the degradation of EGFR through the proteasomal pathway in oz-apraA-treated cells. 1 The pLVX-KFERQ-PA-mCherryN1 plasmid was a gift from Guoqiang Chen and Qian Zhao of Shanghai Jiao Tong University School of Medicine, Shanghai, China . Proteins containing the KFERQ-like motif are recognized by the Heat Shock Cognate 70 (Hsc70) protein and other co . An increasing body of evidence suggests that endo-lysosomal dysfunction is a pathogenic mechanism of Alzheimer's disease. The ELM datasets have been used by bioinformaticians to develop and benchmark novel prediction strategies such as hunting for motifs in interaction data and to provide likelihood estimates for motif candidates based on structural and sequence conservation contexts (37- 41). (1) Macroautophagy: initiation of autophagy through isolation membrane, extension of membrane, and closure forming the autophagosome. While LM discovery remains challenging, if progress continues apace . The pLVX-KFERQ-PA-mCherryN1 plasmid was a gift from Guoqiang Chen and Qian Zhao of Shanghai Jiao Tong University School of Medicine, Shanghai, China . Pfam 35.0 is released (posted 19 November 2021) Pfam 35.0 contains a total of 19,632 families and clans. Its relevance to ILV sorting during microautophagy, however, remains to be assessed. ARL5B, an ARF-like small GTPase localized to the trans-Golgi, is known for regulating endosome-Golgi trafficking and promoting the migration and invasion of breast cancer cells. Hence, KFERQ motif was added along the both termini of each epitope. During CMA, soluble cytosolic proteins containing the pentapeptide motif KFERQ are selectively recognized by the hsc70 chaperone complex. Motif Finder. 5'---PAmCherry-NheI-KFERQ-NE----3' Figure 2. Motif scanning means finding all known motifs that occur in a sequence. We have found that KFERQ-like motifs are more frequently located in solvent-exposed regions of proteins, and that the position of acidic and hydrophobic residues in the motif plays the most important role in motif construction. Arouser is a member of the EPS8 (EGF receptor pathway substrate 8) protein family; mammalian EPS8 has been shown to be subject to CMA (Welsch et al, 2010). You should consult the home pages of Prosite on ExPASy, Pfam and InterPro for additional information. Approximately 40% of proteins in the mammalian proteome contain a canonical KFERQ-like motif. A (2,3) means that A appears 2 to 3 times consecutively. Quantitative proteomic analysis of temporal lysosomal proteome and the impact of the KFERQ-like motif and LAMP2A in lysosomal targeting. Reformat the results and check 'CDS feature' to . Since the last release, we have built 460 new families, killed 7 families and created 12 new clans. Background Alzheimer's disease is the most common form of dementia. It is estimated that 30% of all cellular proteins can be directed to the lysosome for CMA degradation, but only a few substrates have been formally identified so far. RNase A is the first protein to be identi-fied as a CMA substrate [36,37]. This motif includes at least two positively charged residues (K, R), up to two hydrophobic residues (F), one negatively charged residue (E) and a glutamine (Q) that can be positioned at the beginning or at the end of the motif. Pathologies Associated With Autophagy Dysfunctions Previous reports showed that cargos could be recognized by heat-shock proteins through its KFERQ-like motif for protein secretion; 28 therefore, we analyzed the protein sequence of Rab22a-NeoF1 . When the KFERQ-motif is exposed from the proteins, the motif is recognized by the cytosolic chaperone Hsc70, and they can be conveyed to the lysosome by interaction of Hsc70 and LAMP2 . A tiny mutation of KFERQ-like motif in the TDP-43 coding gene is enough to disrupt its degradation in this pathway, causing the aggregation of TDP-43 and the blockage of CMA [ 59 ]. Parkinson's disease (PD) is the second most common neurodegenerative disorder. See the beauty of sequence profiles. Both CMA and endosomal-microautophagy rely on the chaperone protein Hsc70 that can bind to substrate proteins containing a KFERQ motif. To get the CDS annotation in the output, use only the NCBI accession or gi number for either the query or subject. Its neuropathological hallmarks include neuronal loss in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies containing aggregates of α -synuclein ( α -syn). The prediction for the presence of a KFERQ-like motif by SLiMSearch was also confirmed using the web-based resource KFERQ Finder ( Kirchner et al, 2019 ). Similarly, KFERQ-like motifs in mIL-1β responsible for binding the cytosolic HSP90 have been indicated in our previous study ( Zhang et al., 2015 ). . To compute the p- value of a motif score, MCAST assumes that the sequences in the file were generated by a 0-order Markov process. Testing of lysosomes from starved H9c2 cells showed that the three proteins, which are predicted to have KFERQ-like motifs, are present in the lysosome. Recent findings indicate that the abundance of RGS9-2 determines sensitivity of signaling in the locomotor and reward systems in the striatum. This form lets you paste a protein sequence, select the collections of motifs to scan for, and launch the search. Enter one or more queries in the top text box and one or more subject sequences in the lower text box. Alternatively, it is also possible that the B domain is a linker that stabilizes In addition, in some substrate proteins, the same targeting motif can be generated through. Despite the demonstration of CMA blockade by mutant ASYNs protein, which contains the 'KFERQ'-like pentapeptide (CMA recognition motif), was used as a parallel reference for monitor-ing CMA degradation. Endoplasmic reticulum retention of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) mutants and their rapid degradation is the major cause of cystic fibrosis (CF). UniProt Reference Proteomes has increased by 7% since Pfam 34.0, and now contains 61 million sequences. Recent results suggest that only those proteins that bind Hsc70 (via the KFERQ motif) and the LAMP2A cytosolic tail are selected for CMA, which implies that the Hsc70 and LAMP2A interaction sites on the substrate must . A Biblioteca Virtual em Saúde é uma colecao de fontes de informacao científica e técnica em saúde organizada e armazenada em formato eletrônico nos países da Região Latino-Americana e do Caribe, acessíveis de forma universal na Internet de modo compatível com as bases internacionais. To determine whether related peptides exist in cellular proteins . Sulfation: Chaperone-mediated autophagy (CMA) degrades proteins containing the KFERQ-like motif in their amino acid sequence, by transporting them from the cytosol across the lysosomal membrane into the lysosomal lumen. Deletion of this motif increases the generation and release of APP-CTFs, which indicates that this sequence is important for the regulation of APP processing . An important feature of CMA is a KFERQ motif in the cytosolic cargo that is recognized by Hsc70 (Dice, 1990, Kaushik and Cuervo, 2018). The KFERQ motif exists in 30% of proteins in the cytosol and is a targeting motif recognized by the heat shock cognate protein of 73 kDa (cyt-hsc70). KFERQ peptide motif to lysosomes. KFERQ-finder. Kacal M, Zhang B, Hao Y, Norberg E, Vakifahmetoglu-Norberg H Autophagy 2021 Jan;():1-10. (2) Chaperone-mediated autophagy: identification of KFERQ-motif by Hsc70. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. Europe PMC is an archive of life sciences journal literature. A protein fold is the scaffold that can be used as a template to model a query protein sequence. We found that both the total lysosomal activity and clearance of CMA-specific substrates were This repository contains the scripts used for the analysis of KFERQ-like CMA targeting in the human proteome. KFERQ motif is required for EGFR degradation through CMA upon oz-apraA treatment. mal membrane where KFERQ or chemically equivalent amino acid motif carrying proteins are recruited by the cytosolic chaperone protein Heat shock cognate 71 kDa protein (hsc70) to the single pass lysosomal transmem-brane protein, lysosome-associated membrane glyco-protein 2 (LAMP2). The KFERQ motif can be activated or deactivated through the addition or removal of post-translational modifications, such as phosphorylation or acetylation, which alter side-chain charges or . Using a novel prediction program, we have also found that a greater percentage of proteins (46.5%) in the human protein sequences possess KFERQ-like motifs than previously thought (30%). Recent results suggest that only those proteins that bind Hsc70 (via the KFERQ motif) and the LAMP2A cytosolic tail are selected for CMA, which implies that the Hsc70 and LAMP2A interaction sites on the substrate must . The chaperone complex then targets the protein cargo for binding to the lysosomal receptor LAMP-2A (lysosome-associated membrane protein type 2A), which is an essential component of the CMA pathway. Testing of lysosomes from starved H9c2 cells showed that the three proteins, which are predicted to have KFERQ-like motifs, are present in the lysosome. The KFERQ motif nonetheless does not appear to be involved directly in binding to the receptor at the lysosomal membrane . [DE] means either D or E. {FWY} means any amino acid except for F, W and Y. A document deals with the interpretation of the match scores. The KFERQ motif nonetheless does not appear to be involved directly in binding to the receptor at the lysosomal membrane . The KFERQ motif exists in 30% of proteins in the cytosol and is a targeting motif recognized by the heat shock cognate protein of 73 kDa (cyt-hsc70). The pattern string must be terminated with . SUMOgo - prediction of sumoylation sites (small ubiquitin-like modifier (SUMO) binding (referred to as SUMOylation)) on lysines by motif screening models and the effects of various post-translational modifications (Reference: Chang C-C et al. Search for a particular nucleotide sequence in the reference genome. Prediction of MHC class-I epitopes analysis MHC class-I molecules deliver peptides from the cytosol and are Epitopes were evaluated for homology with human sequences recognized by CD8þ T-cells. Abstract Chaperone-mediated autophagy (CMA) ensures the selective degradation of cellular proteins endowed with a KFERQ-like motif by lysosomes. Only if everythings fail, use ab initio methods . Deconvolution of WNT-induced Frizzled conformational dynamics with fluorescent biosensors. Search life-sciences literature (Over 39 million articles, preprints and more) In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. Arouser is a member of the EPS8 (EGF receptor pathway substrate 8) protein family; mammalian EPS8 has been shown to be subject to CMA ( Welsch et al, 2010 ). Because most glycolytic proteins have long half-lives, an increase in degradation could function to down-regulate their abundance. (period). Such protein segments are likely to form stabilizing interactions upon binding. . Since later figures build on the data of previous ones scripts should be run in order to ensure all necessary intermediate files are generated. HT-1080 cells were stably infected with pLVX-KFERQ-PA-mCherryN1 lentivirus. The three main autophagic pathways—macroautophagy, microautophagy and CMA—all contribute to lysosomal degradation, but differ in their regulation, the type of cargo preferentially degraded, and the mechanisms that contribute to targeting the cargo to the lysosomal compartment (1, 5-7).Macroautophagy is the best-characterized autophagic process, and probably the one that contributes to . A motif 'hit' is a sequence position that is sufficiently similar to a motif in the query, where the score for a motif at a particular sequence position is computed without gaps. This analysis revealed that there is a high prevalence of predicted KFERQ-like motifs in proteins significantly enriched in the lysosomes following glucose starvation, including the experimentally validated EIF4A1, EIF4H and DDX3X proteins, where the functionality of CMA motifs was investigated by mutational studies previously [ 6 ]. HT-1080 cells were stably infected with pLVX-KFERQ-PA-mCherryN1 lentivirus. Then use the BLAST button at the bottom of the page to align your sequences. KFERQ extensions were inserted along both termini of each epitope in the CD4 + T construct sequence. Thus, the KFERQ-like motifs can be divided into "noncanonical" or "canonical." The KFERQ-like motifs are recognized by the HSC70 chaperone, which allows the interaction of the CMA target protein with the LAMP2A protein at the lysosomal membrane. The ﬁnal array of The pBI-CMV1 vector was chosen as an expression system to . Using a novel prediction program, we have also found that a greater percentage of proteins (46.5%) in the human protein sequences possess KFERQ-like motifs than previously thought (30%). In kidney and liver, up to 30% of proteins contains the KFERQ motif, including many of the proteins involved in glycolysis. Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Although a few interacting partners have been identified, the mechanism of the shuttling of ARL5B between the Golgi membrane and the cytosol is still obscure. Annexin A2 contains KFERQ motif that can bind to endosomes and then enter lysosomes. Local file name for a profile in HMM format. These organelles had persisted even within highly proteolytic microenvironments to generate truncated forms ( 44). The recruitment is followed by Types of autophagy. La Biblioteca Virtual en Salud es una colección de fuentes de información científica y técnica en salud organizada y almacenada en formato electrónico en la Región de América Latina y el Caribe, accesible de forma universal en Internet de modo compatible con las bases internacionales. Similarly, KFERQ-like motifs in mIL-1β responsible for binding the cytosolic HSP90 have been indicated in our previous study ( Zhang et al., 2015 ). BAG3, its name derived from "athanatos," Greek for "against death," is the third member of a family of six proteins that bind to the ATPase motif of heat shock cognate 70 (heat shock protein 70; hsp70) through a sequence in the BAG domain (12, 13).That BAG3 plays a critical role in living organisms is supported by the fact that a homolog of BAG3 is expressed in all domains of life . We identify a KFERQ-like motif as a conserved pentapeptide sequence in the kinase domain of epidermal growth factor receptor (EGFR) necessary for recognition as a CMA substrate. CMA is a cellular mechanism that promotes selective proteolysis of molecules that contain specific peptide sequences related to Lys-Phe-Glu-Arg-Gln (KFERQ)-like motifs, which are recognized by a cytosolic chaperone, heat shock cognate 71 kDa protein (HSC70), culminating in the lysosomal degradation of substrate-chaperone complexes ().The role of macroautophagy, a bulk cell degradation and . 2020. in chloroplasts [1, 2]. 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kferq motif prediction 2022