| IED ID | IndEnz0002018821 |
| Enzyme Type ID | protease018821 |
| Protein Name |
Large proline-rich protein BAG6 BCL2-associated athanogene 6 HLA-B-associated transcript 3 |
| Gene Name | Bag6 Bat3 |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MEPSDSTSTAMEEPDSLEVLVKTLDSQTRTFIVGAQMNVKEFKEHIAASVSIPSEKQRLIYQGRVLQDDKKLQDYNVGGKVIHLVERAPPQTQLPSGASSGTGSASATHGGGPLPGTRGPGASGHDRNANSYVMVGTFNLPSDGSAVDVHINMEQAPIQSEPRVRLVMAQHMIRDIQTLLSRMECRGGTQAQASQPPPQTPTVASETVALNSQTSEPVESEAPPREPMESEEMEERPPTQTPELPPSGPAPAGPAPAPETNAPNHPSPAEHVEVLQELQRLQRRLQPFLQRYCEVLGAAATTDYNNNHEGREEDQRLINLVGESLRLLGNTFVALSDLRCNLACAPPRHLHVVRPMSHYTTPMVLQQAAIPIQINVGTTVTMTGNGARPPPAPGAEAASPGSGQASSLPPSSATVDSSTEGAPPPGPAPPPATSHPRVIRISHQSVEPVVMMHMNIQDSGAQPGGVPSAPTGPLGPPGHGQSLGQQVPGFPTAPTRVVIARPTPPQARPSHPGGPPVSGALQGAGLGTNTSLAQMVSGLVGQLLMQPVLVAQGTPGMAPASASAPATAQAQAPAPAPAPAPAPATASASAGTTNTATTAGPAPGGPAQPPPPQPSAADLQFSQLLGNLLGPAGPGAGGPSLASPTITVAVPGVPAFLQGMTEFLQASQAAPPPPPPPPPPPPAPEQQTTPPPGSPSGGTASPGGLGPESLPPEFFTSVVQGVLSSLLGSLGARAGSSESIAAFIQRLSGSSNIFEPGADGALGFFGALLSLLCQNFSMVDVVMLLHGHFQPLQRLQPQLRSFFHQHYLGGQEPTSSNIRMATHTLITGLEEYVRESFSLVQVQPGVDIIRTNLEFLQEQFNSIAAHVLHCTDSGFGARLLELCNQGLFECLALNLHCLGGQQMELAAVINGRIRRMSRGVNPSLVSWLTTMMGLRLQVVLEHMPVGPDAILRYVRRIGDPPQALPEEPMEVQGAERTSPEPQREDASPAPGTTAEEAMSRGPPPAPEGGSRDEQDGASADAEPWAAAVPPEWVPIIQQDIQSQRKVKPQPPLSDAYLSGMPAKRRKTMQGEGPQLLLSEAVSRAAKAAGARPLTSPESLSRDLEAPEVQESYRQQLRSDIQKRLQEDPNYSPQRFPNAHRAFADDP |
| Enzyme Length | 1146 |
| Uniprot Accession Number | Q6MG49 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins. Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome. SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome. BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response. BAG6 is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress. By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis. Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. {ECO:0000250|UniProtKB:P46379}.; FUNCTION: Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity. When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2). {ECO:0000250|UniProtKB:P46379}.; FUNCTION: Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC). {ECO:0000250|UniProtKB:P46379}.; FUNCTION: May mediate ricin-induced apoptosis. {ECO:0000250|UniProtKB:P46379}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Chain (1); Compositional bias (7); Domain (1); Modified residue (8); Motif (1); Region (11); Repeat (4); Sequence conflict (9); Site (1) |
| Keywords | Acetylation;Alternative splicing;Apoptosis;Chaperone;Chromatin regulator;Cytoplasm;Differentiation;Immunity;Nucleus;Phosphoprotein;Reference proteome;Repeat;Secreted;Spermatogenesis;Transport |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P46379}. Nucleus {ECO:0000250|UniProtKB:P46379}. Secreted, extracellular exosome {ECO:0000250|UniProtKB:P46379}. Note=Normally localized in cytosol and nucleus, it can also be released extracellularly, in exosomes, by tumor and myeloid dendritic cells. {ECO:0000250|UniProtKB:P46379}. |
| Modified Residue | MOD_RES 1; /note=N-acetylmethionine; /evidence=ECO:0000250|UniProtKB:P46379; MOD_RES 96; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P46379; MOD_RES 117; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:P46379; MOD_RES 978; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P46379; MOD_RES 987; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1067; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:P46379; MOD_RES 1095; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1131; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P46379 |
| Post Translational Modification | PTM: Ricin can induce a cleavage by the caspase CASP3. The released C-terminal peptide induces apoptosis. {ECO:0000250|UniProtKB:P46379}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 18487607; 19935650; 27191843; |
| Motif | MOTIF 1026..1068; /note=Nuclear localization site; /evidence=ECO:0000250|UniProtKB:P46379 |
| Gene Encoded By | |
| Mass | 120,012 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |