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Overview

Uniprot ID	P46379
Protein Name	Large proline-rich protein BAG6
Gene Name	BAG6
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
1049	YLSGMPAKRRKTMQG
1052	GMPAKRRKTMQGEGP

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:25535373, PubMed:28104892). 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:27193484, PubMed:28104892). 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)

Protein Sequence

10 MEPNDSTSTA 20 VEEPDSLEVL 30 VKTLDSQTRT 40 FIVGAQMNVK 50 EFKEHIAASV 60 SIPSEKQRLI 70 YQGRVLQDDK 80 KLQEYNVGGK 90 VIHLVERAPP 100 QTHLPSGASS 110 GTGSASATHG 120 GGSPPGTRGP 130 GASVHDRNAN 140 SYVMVGTFNL 150 PSDGSAVDVH 160 INMEQAPIQS 170 EPRVRLVMAQ 180 HMIRDIQTLL 190 SRMETLPYLQ 200 CRGGPQPQHS 210 QPPPQPPAVT 220 PEPVALSSQT 230 SEPVESEAPP 240 REPMEAEEVE 250 ERAPAQNPEL 260 TPGPAPAGPT 270 PAPETNAPNH 280 PSPAEYVEVL 290 QELQRLESRL 300 QPFLQRYYEV 310 LGAAATTDYN 320 NNHEGREEDQ 330 RLINLVGESL 340 RLLGNTFVAL 350 SDLRCNLACT 360 PPRHLHVVRP 370 MSHYTTPMVL 380 QQAAIPIQIN 390 VGTTVTMTGN 400 GTRPPPTPNA 410 EAPPPGPGQA 420 SSVAPSSTNV 430 ESSAEGAPPP 440 GPAPPPATSH 450 PRVIRISHQS 460 VEPVVMMHMN 470 IQDSGTQPGG 480 VPSAPTGPLG 490 PPGHGQTLGQ 500 QVPGFPTAPT 510 RVVIARPTPP 520 QARPSHPGGP 530 PVSGTLQGAG 540 LGTNASLAQM 550 VSGLVGQLLM 560 QPVLVAQGTP 570 GMAPPPAPAT 580 ASASAGTTNT 590 ATTAGPAPGG 600 PAQPPPTPQP 610 SMADLQFSQL 620 LGNLLGPAGP 630 GAGGSGVASP 640 TITVAMPGVP 650 AFLQGMTDFL 660 QATQTAPPPP 670 PPPPPPPPAP 680 EQQTMPPPGS 690 PSGGAGSPGG 700 LGLESLSPEF 710 FTSVVQGVLS 720 SLLGSLGARA 730 GSSESIAAFI 740 QRLSGSSNIF 750 EPGADGALGF 760 FGALLSLLCQ 770 NFSMVDVVML 780 LHGHFQPLQR 790 LQPQLRSFFH 800 QHYLGGQEPT 810 PSNIRMATHT 820 LITGLEEYVR 830 ESFSLVQVQP 840 GVDIIRTNLE 850 FLQEQFNSIA 860 AHVLHCTDSG 870 FGARLLELCN 880 QGLFECLALN 890 LHCLGGQQME 900 LAAVINGRIR 910 RMSRGVNPSL 920 VSWLTTMMGL 930 RLQVVLEHMP 940 VGPDAILRYV 950 RRVGDPPQPL 960 PEEPMEVQGA 970 ERASPEPQRE 980 NASPAPGTTA 990 EEAMSRGPPP 1000 APEGGSRDEQ 1010 DGASAETEPW 1020 AAAVPPEWVP 1030 IIQQDIQSQR 1040 KVKPQPPLSD 1050 AYLSGMPAKR 1060 RKTMQGEGPQ 1070 LLLSEAVSRA 1080 AKAAGARPLT 1090 SPESLSRDLE 1100 APEVQESYRQ 1110 QLRSDIQKRL 1120 QEDPNYSPQR 1130 FPNAQRAFAD DP

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0071818	BAT3 complex
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0030544	Hsp70 protein binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0051787	misfolded protein binding
Molecular Function	GO:0060090	molecular adaptor activity
Molecular Function	GO:0140677	molecular function activator activity
Molecular Function	GO:0031593	polyubiquitin modification-dependent protein binding
Molecular Function	GO:0070628	proteasome binding
Molecular Function	GO:0140597	protein carrier chaperone
Molecular Function	GO:0048018	receptor ligand activity
Molecular Function	GO:0043022	ribosome binding
Molecular Function	GO:0005102	signaling receptor binding
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Molecular Function	GO:1990381	ubiquitin-specific protease binding
Biological Process	GO:0006915	apoptotic process
Biological Process	GO:0007420	brain development
Biological Process	GO:0030154	cell differentiation
Biological Process	GO:0006325	chromatin organization
Biological Process	GO:0061857	endoplasmic reticulum stress-induced pre-emptive quality control
Biological Process	GO:0036503	ERAD pathway
Biological Process	GO:0002429	immune response-activating cell surface receptor signaling pathway
Biological Process	GO:0018393	internal peptidyl-lysine acetylation
Biological Process	GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Biological Process	GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Biological Process	GO:0001822	kidney development
Biological Process	GO:0030324	lung development
Biological Process	GO:0036506	maintenance of unfolded protein
Biological Process	GO:0030101	natural killer cell activation
Biological Process	GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process	GO:0045861	negative regulation of proteolysis
Biological Process	GO:0051132	NK T cell activation
Biological Process	GO:1904294	positive regulation of ERAD pathway
Biological Process	GO:0006620	post-translational protein targeting to endoplasmic reticulum membrane
Biological Process	GO:0010498	proteasomal protein catabolic process
Biological Process	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process	GO:0050821	protein stabilization
Biological Process	GO:0042981	regulation of apoptotic process
Biological Process	GO:0045995	regulation of embryonic development
Biological Process	GO:0031647	regulation of protein stability
Biological Process	GO:0007283	spermatogenesis
Biological Process	GO:0007130	synaptonemal complex assembly
Biological Process	GO:0071816	tail-anchored membrane protein insertion into ER membrane
Biological Process	GO:0006511	ubiquitin-dependent protein catabolic process

Reference

PMID: N/A