BAT3
- Known as:
- BAT3
- Catalog number:
- Y214082
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- BAT3
Related genes to: BAT3
- Gene:
- BAG6 NIH gene
- Name:
- BCL2 associated athanogene 6
- Previous symbol:
- BAT3
- Synonyms:
- G3, D6S52E
- Chromosome:
- 6p21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-13
- Date modifiied:
- 2016-10-05
Related products to: BAT3
Related articles to: BAT3
- The small GTPase Rab9 plays a major role in the vesicular trafficking of cation-independent mannose-6-phosphate receptor (CI-M6PR). CI-M6PR trafficking has also been reported to be perturbed by the dysfunction of a ubiquitin ligase necessary for protein quality control (PQC). However, the mechanism underlying the participation of the PQC machinery in CI-M6PR trafficking is poorly understood. In this study, we found an extremely short half-life of GDP-bound Rab9, which is in clear contrast to its phylogenetically closest relative, Rab7. Comparison of the amino acid sequences of these relatives revealed that hydrophobic residues are specifically exposed in the switch I region of Rab9a and that these residues are recognized by the PQC machinery. We defined this exposed hydrophobicity as a conformation-dependent hydrophobic (CDH) degron because its existence determines the instability of Rab proteins in a nucleotide-dependent manner. CDH degron-mediated instability is essential for Rab9a function, given that forced accumulation of CDH degron-mutated Rab9a in cells resulted in the defective localization of CI-M6PR, a similar phenotype observed in PQC dysfunction. Thus, the CDH degron-driven PQC system is necessary for the proper vesicular trafficking of CI-M6PR. We also identified valosin-containing protein/p97 as a CDH degron-dependent PQC factor for GDP-bound Rab9a. - Source: PubMed
Publication date: 2026/01/31
Shirai JunTakahashi ToshikiKawahara Hiroyuki - Ubiquilin-2 (UBQLN2) is a ubiquitin (Ub)-binding shuttle protein that is mutated in X-linked forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS/FTD-linked mutations in UBQLN2 disrupt its conformation, increasing its tendency to form cytoplasmic aggregates that may disrupt cellular regulation through loss-of-function (LOF) and gain-of-function (GOF) effects. Here, we performed quantitative mass spectrometry (MS)-based interactome analysis of wild-type (UBQLN2) and ALS-mutant UBQLN2 (UBQLN2) proteins using inducible pluripotent stem cells (iPSCs) and induced motor neurons (iMNs). Proteins showing enhanced association with UBQLN2 proteins included PEG10, a known degradation target of UBQLN2, and BAG6, a chaperone involved in the triage of mislocalized proteins (MLPs). BAG6 knockdown inhibited the solubility recovery of both UBQLN2 and UBQLN2 proteins following heat stress (HS), suggesting it functions as a UBQLN2 holdase. In addition, knockdown of BAG6 or knockout of UBQLN2 led to PEG10 accumulation, implicating both in PEG10 turnover; however, neither BAG6 nor UBQLN2 was required for PEG10 degradation in response to HS. A highly aggregation-prone UBQLN2 mutant harboring four different ALS-associated mutations showed increased PEG10 binding and modestly delayed PEG10 turnover while PEG10 degradation was not significantly different between UBQLN2 and iPSCs expressing a UBQLN2 clinical mutant. The combined findings implicate BAG6 as a UBQLN2 holdase and identify a suite of proteins whose altered binding may contribute to pathologic changes in UBQLN2-associated ALS/FTD. - Source: PubMed
Publication date: 2026/01/05
Kim Sang HwaBoos Claire EScalf MarkWilkemeyer Akasha KSmith Lloyd MTibbetts Randal S - Bcl-2-associated Athanogene 6 (BAG6) plays critical roles in multiple tumors, but its biological functions and clinical significance in hepatocellular carcinoma (HCC) remain unclear. Multi-omics analyses showed that BAG6 mRNA and protein levels are significantly upregulated in HCC tissues, linked to genetic mutations and aberrant DNA methylation. In the TCGA cohort, BAG6 exhibits high diagnostic accuracy (AUC = 0.935) and is independently associated with poor overall survival (HR = 1.62) and adverse clinicopathological features, as well as correlates with tumor immune microenvironment, tumor mutation burden (TMB), and immunotherapy response. From a public health perspective, its diagnostic value supports integration into machine learning models for early HCC screening to optimize risk stratification, enhance efficiency, and reduce advanced HCC burden. Functional experiments revealed that BAG6 knockdown remarkably inhibits HCC cell growth in vitro and in vivo. BAG6 knockdown decreased PLK1 expression in HCC cells, an essential regulator of the aerobic glycolytic process. Mechanistically, BAG6 directly binds to PLK1 and suppresses its ubiquitination and degradation, and enhances PLK1-mediated Warburg effect, thereby promoting HCC growth. Overall, we identify BAG6 as an HCC progression driver via the PLK1-mediated Warburg effect, a potential therapeutic and early screening marker. - Source: PubMed
Publication date: 2025/12/11
Zhang WenmingDu DongnianLu HongchengZhang WenzhenLei Jun - Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with highly diverse survival time. However, genetic and epigenetic factors influencing ALS survival across diverse populations remain unclear. - Source: PubMed
Publication date: 2025/12/10
Gu YuqiChen YanTang XuelinGuo JingyanHu JialiYang WanliLi JiahaoChen XiFan DongshengChen Guo-BoHe JiRen YongfeiDong YiSato ChristineChen YelinZinman LorneRogaeva EkaterinaZhang Ming - Alzheimer's disease (AD) is characterized by widespread molecular dysregulation, with the APOEe4 allele recognized as its strongest genetic risk factor. However, the mechanisms by which APOEe4 drives distinct molecular changes - whether by exacerbating pathology or triggering compensatory responses - remain incompletely understood. We generated and analyzed proteomic, epigenetic, and genetic data from post-mortem dorsolateral prefrontal cortex samples of a uniquely APOEe4-enriched subset of the Religious Orders Study and Memory and Aging Project (ROSMAP). Specifically, we generated DIA LC-MS proteomic data (n = 302), analyzed previously generated DNA methylation profiles from our group (n = 310), and used published whole-genome sequencing data (n = 254) to compute polygenic risk scores (PRS). In this cohort, 69% (n = 214) were APOEe4 carriers, and 19.6% (n = 42) of them showed no pathological evidence of AD based on NIA-Reagan criteria, enabling identification of APOEe4-related risk and resilience mechanisms. In the absence of AD, APOEe4 carriers exhibited lower levels of 27 proteins, suggesting early synaptic (e.g., VAMP1, SYN3, CASKIN1) and metabolic (e.g., GLUD1, PI4KA) vulnerability. By contrast, APOEe4 carriers with AD displayed marked upregulation of inflammatory and proteostatic proteins (e.g., GNAO1, AHNAK, FGG, HEBP1, APEX1, RAB4A, SLC12A5, LRP1, BAG6) and hypermethylation of cg06329447 in ELAVL4. Network analyses highlighted convergent disruptions in synaptic transmission, metabolism, and proteostasis - key pathways altered in APOEe4-associated AD. Mediation analyses identified GRIPAP1 and GSTK1 as top protein mediators (accounting for ~26-33% of APOEe4's effect), with VAMP1, CASKIN1, DPP3, SYN3, and FGG each contributing ~9-15%. ELAVL4 hypermethylation also mediated ~12% of the APOEe4 effect, linking epigenetic dysregulation to disease risk. To assess whether the identified proteins reflected broader genetic risk for AD or were specific to APOEe4, we calculated PRS both excluding and including the APOE genomic region. While the non-APOE PRS showed no association with identified molecular markers, the APOE-inclusive PRS was significantly associated with eight AD-related proteins in carriers, indicating they are not explained by polygenic risk outside of APOE. Finally, predictive modeling stratified by APOEe4 status revealed that in non-carriers, PRS most effectively classified AD (AUC = 0.73), whereas in carriers, proteomic and epigenetic markers outperformed PRS (AUC up to 0.74). Together, these findings demonstrate that APOEe4 confers AD risk through early synaptic and metabolic disruptions and later-stage inflammatory and epigenetic changes, laying the groundwork for genotype-tailored biomarker development and therapeutic strategies. - Source: PubMed
Publication date: 2025/10/16
Markov YaroslavPriyanka AhanaXu LeqiWang WeiweiThrush-Evensen KyraGonzalez JohnBorrus DanielKasamoto JessicaSehgal RaghavZou GraceFraij JenelCarlyle Becky CHorvath SteveBennett David AZhao Hongyuvan Dyck Christopher HLam TuKiet TLevine Morgan EHiggins-Chen Albert T