DegronMD - P46379(BAG6)

FUNCTION: ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). 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 (PubMed:20516149, PubMed:21636303, PubMed:21743475, PubMed:28104892). 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 (PubMed:20516149, PubMed:20676083, PubMed:28104892, PubMed:25535373). 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 (PubMed:24981174, PubMed:28104892, PubMed:27193484). SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins (PubMed:23129660, PubMed:25179605, PubMed:27193484). 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 (PubMed:21743475). 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 (PubMed:21636303). 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 (By similarity). 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 (PubMed:26565908). 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 (By similarity). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:Q9Z1R2, ECO:0000269|PubMed:20516149, ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; 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 (PubMed:17403783). When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2) (PubMed:18765639). {ECO:0000269|PubMed:17403783, ECO:0000269|PubMed:18765639}.; 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:0000269|PubMed:18055229, ECO:0000269|PubMed:18852879}.; FUNCTION: Mediates ricin-induced apoptosis. {ECO:0000269|PubMed:14960581}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S412C	TCGA-38-4628	LUAD	TCGA	APSST	DEG_SPOP_SBC_1	414:418	Mutation rewiring degron network	0.2778
p.S601C	TCGA-A2-A04Q	BRCA	TCGA	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation altering degron motif	0.7541
p.A603T	TCGA-AP-A1DV	UCEC	TCGA	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation rewiring degron network	0.2778
p.A257T	TCGA-B0-5098	KIRC	TCGA	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.2778
p.P273H	TCGA-B5-A1MX	UCEC	TCGA	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.0833
p.P273H	TCGA-DF-A2KN	UCEC	TCGA	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.0833
p.N419K	TCGA-FG-7637	LGG	TCGA	APSST	DEG_SPOP_SBC_1	414:418	Mutation rewiring degron network	0.3056
p.E421K	TCGA-G4-6293	COAD	TCGA	APSST	DEG_SPOP_SBC_1	414:418	Mutation rewiring degron network	0.25
p.P398S	TCGA-LH-A9QB	SKCM	TCGA	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.6752
p.H270N	TCGA-X9-A973	SARC	TCGA	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.1667
p.P271H	TCGA-XK-AAIW	PRAD	TCGA	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.1389
p.S595C	DO1678	BRCA	ICGC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation altering degron motif	0.7541
p.E415K	DO10405	COAD	ICGC	APSST	DEG_SPOP_SBC_1	414:418	Mutation altering degron motif	0.7022
p.E415K	DO233765	GACA	ICGC	APSST	DEG_SPOP_SBC_1	414:418	Mutation altering degron motif	0.7022
p.E272K	DO8264	COAD	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.1111
p.A251T	DO18938	KIRC	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation blocking phosphorylation signal	0.5556
p.N413K	DO22623	LGG	ICGC	APSST	DEG_SPOP_SBC_1	414:418	Mutation rewiring degron network	0.3056
p.A427T	DO22295	LGG	ICGC	APSST	DEG_SPOP_SBC_1	414:418	Mutation rewiring degron network	0.0833
p.F601L	DO45109	LIRI	ICGC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation altering degron motif	0.6981
p.S406C	DO26354	LUAD	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.1944
p.S406C	DO26354	LUAD	ICGC	APSST	DEG_SPOP_SBC_1	414:418	Mutation rewiring degron network	0.1111
p.P392S	DO220851	MELA	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.2778
p.P392S	DO51266	SKCM	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.2778
p.P398T	DO220872	MELA	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7031
p.P401L	DO220884	MELA	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7582
p.P389S	DO222550	MELA	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.1944
p.S417L	DO32831	PACA	ICGC	APSST	DEG_SPOP_SBC_1	414:418	Mutation altering degron motif	0.7667
p.A256S	DO51079	PRAD	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.25
p.P265H	DO51407	PRAD	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.3056
p.H264N	DO220329	SARC	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation altering degron motif	0.7423
p.L274P	DO38819	STAD	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.0556
p.A396V	DO229103	THCA	ICGC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.6936
p.P267H	DO223282	UCEC	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.25
p.P267H	DO41999	UCEC	ICGC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.25
p.A597T	DO43186	UCEC	ICGC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation altering degron motif	0.7139
p.A274V	SIDM01117	Small Cell Lung Carcinoma	GDSC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.0556
p.P398L	SIDM01060	Melanoma	GDSC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7582
p.P398L	IGR-1	skin	COSMIC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7582
p.T386I	SIDM00596	Endometrial Carcinoma	GDSC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.1111
p.T386I	HEC-1	endometrium	COSMIC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.1111
p.L250F	SIDM00596	Endometrial Carcinoma	GDSC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.0833
p.L250F	HEC-1	endometrium	COSMIC	PTPAPE	DEG_SCF_FBW7_2	259:264	Mutation rewiring degron network	0.0833
p.A402S	SIDM00606	Squamous Cell Lung Carcinoma	GDSC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.3056
p.A402S	KNS-62	lung	COSMIC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.3056
p.M602T	SIDM01101	Neuroblastoma	GDSC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation rewiring degron network	0.3056
p.M602T	ACH-000260	Neuroblastoma	CCLE	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation rewiring degron network	0.3056
p.M602T	SK-N-AS	autonomic ganglia	COSMIC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation rewiring degron network	0.3056
p.P394H	SIDM01682	Gastric Carcinoma	GDSC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7694
p.P388H	ACH-000110	Gastric Cancer	CCLE	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.1667
p.A396S	ACH-000858	Lung Cancer	CCLE	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7588
p.A396S	KNS-62	lung	COSMIC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7588
p.P392L	ACH-000882	Skin Cancer	CCLE	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.2778
p.P392L	IGR-1	skin	COSMIC	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation rewiring degron network	0.2778
p.P399R	ACH-001622	Brain Cancer	CCLE	PPPTPNAE	DEG_SCF_FBW7_2	394:401	Mutation altering degron motif	0.7512
p.M596T	SK-N-AS	autonomic ganglia	COSMIC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation altering degron motif	0.7423
p.E592K	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	PPPTPQPS	DEG_SCF_FBW7_1	594:601	Mutation rewiring degron network	0.2778

Kaplan plot for BAG6 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

BAG6

UniProt ID: P46379

Entrez ID: 7917

Protein name: Large proline-rich protein BAG6 (BAG family molecular chaperone regulator 6) (BCL2-associated athanogene 6) (BAG-6) (HLA-B-associated transcript 3) (Protein G3) (Protein Scythe)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for BAG6 in