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Overview

Uniprot IDA5D9M6
Protein NameLarge proline-rich protein BAG6
Gene NameBAG6
OrganismSus scrofa

Kla Sites from experimental identification

Position Flanking peptide
1068 EAVSRAAKAAGARPL
56 SVSIPSEKQRLIYQG

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

Protein Sequence

10 MEPNDSTSTT 20 MEEPESLEVL 30 VKTLDSQTRT 40 FIVGAQMNVK 50 EFKEHIAASV 60 SIPSEKQRLI 70 YQGRVLQDDK 80 KLQEYNVGGK 90 VIHLVERAPP 100 QTQLPSGASS 110 GTGSASATHG 120 GGPPPGTRGP 130 GASVHDRNAN 140 SYVMVGTFNL 150 PSDGSAVDVH 160 INMEQAPIQS 170 EPRVRLVMAQ 180 HMIRDIQTLL 190 SRMECRGGSQ 200 AQHSQPPSQM 210 PTVAPEPVAL 220 SSQTSESVES 230 EVPPREPMAA 240 EEVEERASAQ 250 SPGLSPSGPA 260 PAGPTPAPET 270 NAPNHPSPAE 280 YVEVLQELQR 290 LESRLQPFLQ 300 RYYEVLGAAA 310 TTDYNNNQEG 320 REEDQRLINL 330 VGESLRLLGN 340 TFVALSDLRC 350 NLACAPPRHL 360 HVVRPMSHYT 370 TPMVLQQAAI 380 PIQINVGTTV 390 TMTGNGTRPP 400 PTPNAEAPPP 410 GPGQASSLAP 420 SSTTVESSTE 430 GAPPPGPAPP 440 PAASHPRVIR 450 ISHQSVEPVV 460 MMHMNIQDSG 470 TQPGGVPSAP 480 TGPLGPTGHG 490 QTLGQQVPGF 500 PTAPTRVVIA 510 RPTPPQSRPS 520 HPGGPPVSGA 530 LPGAGLGTNA 540 SLAQMVSGLV 550 GQLLMQPVLV 560 AQGTPGMAPP 570 PAPATASASA 580 GTTNTATTAG 590 PAPGGPAQPP 600 PPQPSASDLQ 610 FSQLLGNLLG 620 PAGPGAGGPG 630 MTSPTITVAM 640 PGVPAFLQGM 650 TDFLQATQTA 660 APPAPPPPPP 670 PPPPAPEQQT 680 APPPGSPPGG 690 AGSPGGLGPE 700 SLPLEFFTSV 710 VQGVLSSLLG 720 SLGARAGSSE 730 SIAAFIQRLS 740 GSSNIFEPGA 750 DGALGFFGAL 760 LSLLCQNFSM 770 VDVVMLLHGH 780 FQPLQRLQPQ 790 LRSFFHQHYL 800 GGQEPTPGNI 810 RTATHTLITG 820 LEEYVRESFS 830 LVQVQPGVDI 840 IRTNLEFLQE 850 QFNSIAAHVM 860 HCTDSGFGAR 870 LLELCNQGLF 880 ECLALNLHCL 890 GGQQMELAAV 900 INGRIRRMSR 910 GVNPSLVSWL 920 TTMMGLRLQV 930 VLEHMPVGPD 940 AILRYVRRVG 950 DPPQPLPEEP 960 MEVQGSERTS 970 PEPQRENASP 980 APGTTAEEAM 990 SRGPPPAPEG 1000 GSRDEQDGAA 1010 AETEPWAAAV 1020 PPEWVPIIQQ 1030 DIQSQRKVKP 1040 QPPLSDAYLS 1050 GMPAKRRKTM 1060 QGEGPQLLLS 1070 EAVSRAAKAA 1080 GARPLTSPES 1090 LSRDLEAPEV 1100 QESYRQQLRA 1110 DIQKRLQEDP 1120 NYSPQRFPNA HRAFAEDP

Gene Ontology

Classification GO ID Description
Biological Process GO:0030324 lung development
Biological Process GO:0001822 kidney development
Cellular Component GO:0071818 BAT3 complex
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005576 extracellular region
Cellular Component GO:0005634 nucleus
Molecular Function GO:0051787 misfolded protein binding
Molecular Function GO:0031593 polyubiquitin modification-dependent protein binding
Molecular Function GO:0070628 proteasome binding
Molecular Function GO:0043022 ribosome 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:0002376 immune system process
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:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process GO:0045861 negative regulation of proteolysis
Biological Process GO:0010498 proteasomal 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: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

[1] Fan S, Zhou R, Wen H, Ye H, Ma S et al.. Global profiling of protein lactylome in porcine granulosa cells.. J Ovarian Res 18(1):177. 2025 Aug 8. PMID: 40781717.