Affinage

BAK1

Bcl-2 homologous antagonist/killer · UniProt Q16611

Length
211 aa
Mass
23.4 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The symbol BAK1 in this timeline maps to two entirely distinct, unrelated proteins that share only a name: mammalian BAK, a proapoptotic BCL-2 family pore-forming protein, and Arabidopsis BAK1 (SERK3), a plant leucine-rich-repeat receptor-like kinase coreceptor. Because both are internally coherent and supported by High-confidence evidence, each is summarized in turn. Mammalian BAK is an essential effector of mitochondrial outer membrane permeabilization (MOMP) during apoptosis: together with BAX it forms the indispensable gateway whose loss renders cells resistant to diverse death stimuli (PMID:11326099). In viable cells BAK is held in an inactive monomeric conformation at the mitochondrial outer membrane through direct binding by VDAC2 and BCL-XL, with the BH4 domain stabilizing the latent state (PMID:12881569, PMID:34523147, PMID:27198225). Activation requires transient "hit-and-run" engagement of the canonical BH3-binding groove by BH3-only ligands such as BID, a trigger site distinct from the BAX α1/α6 site (PMID:23604079, PMID:23404709); this drives separation of the core and latch domains and assembly of symmetric core-domain homodimers (PMID:25175025). Dimers coalesce into disordered clusters bridged in part by membrane lipids—particularly unsaturated species—to generate dynamically sized proteolipidic macropores that release cytochrome c and larger matrix contents (PMID:28182867, PMID:32929280, PMID:38830851, PMID:24100034). These macropores permit inner-membrane herniation and mtDNA release that activates cGAS/STING innate immunity, with BAK recruited ahead of BAX and accelerating its co-assembly into shared apoptotic pores (PMID:29472455, PMID:35120587, PMID:38503846). BAK also permeabilizes ER and peroxisomal membranes and remodels mitochondrial morphology via mitofusin interactions (PMID:12847083, PMID:28174205, PMID:17606912), and is negatively regulated by Parkin-mediated ubiquitination of its groove and by neural-specific NMD of its transcript (PMID:30573668, PMID:32710818). In contrast, plant BAK1 is a coreceptor LRR-kinase that transphosphorylates and is reciprocally activated by ligand-binding receptor kinases including BRI1 in brassinosteroid signaling and FLS2/EFR/MIK2 in pattern-triggered immunity (PMID:12150928, PMID:18694562, PMID:17625569, PMID:17626179, PMID:39511418, PMID:39028038). This dual occupancy of one symbol reflects nomenclatural collision rather than a single biological entity.

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2001 High

    Established that BAK, redundantly with BAX, is the obligatory effector gateway for mitochondrial apoptosis, defining the genetic requirement for cytochrome c release.

    Evidence Bax-/- Bak-/- MEFs challenged with multiple death stimuli and cytochrome c release assays

    PMID:11326099

    Open questions at the time
    • Did not resolve the molecular conformational steps of BAK activation
    • Relative contributions of BAK vs BAX not separated
  2. 2003 High

    Identified VDAC2 as the direct restraint that keeps inactive BAK monomeric, explaining how BAK is held in check in viable cells.

    Evidence Reciprocal Co-IP, VDAC2 KO and overexpression, BAK oligomerization and apoptosis readouts

    PMID:12881569

    Open questions at the time
    • Structural basis of VDAC2 selectivity for inactive BAK not defined
    • How death signals displace VDAC2 mechanistically not resolved
  3. 2003 High

    Showed BAK function extends beyond mitochondria to the ER, defining a Ca2+-dependent ER apoptotic pathway.

    Evidence Compartment-targeted BAK constructs in DKO cells with Ca2+ and caspase-12 readouts

    PMID:12847083

    Open questions at the time
    • Endogenous contribution of ER-localized BAK versus mitochondrial pool unclear
  4. 2004 Medium

    Linked the p53 tumor suppressor directly to BAK activation, providing a transcription-independent route to MOMP.

    Evidence Co-IP and cytochrome c release with mitochondrial fractionation

    PMID:15077116

    Open questions at the time
    • Single-lab Co-IP; whether p53 directly activates or displaces MCL1 not disentangled
    • Stoichiometry and affinity of p53-BAK not measured
  5. 2007 High

    Distinguished BAK from BAX by its mitofusin interactions controlling mitochondrial fragmentation during apoptosis.

    Evidence Co-IP, Bak-deficient MEFs/neurons, BH3 mutagenesis, morphology imaging

    PMID:17606912

    Open questions at the time
    • Mechanistic coupling of MFN switching to pore formation not established
  6. 2013 High

    Resolved the activation trigger site, showing BH3-only ligands engage BAK's canonical groove via a transient hit-and-run mechanism distinct from the BAX trigger site.

    Evidence NMR of BID BH3-BAK, photoreactive crosslinking, mutagenesis, liposomal release assays

    PMID:23404709 PMID:23604079

    Open questions at the time
    • How transient ligand binding is converted to stable oligomer not fully detailed
    • Which endogenous BH3-only proteins dominate in different cell types unclear
  7. 2013 High

    Characterized BAK pores as protein-permeable structures of tunable size, defining their proteolipidic nature.

    Evidence Single-vesicle fluorescence with size-exclusion and concentration/cardiolipin titration

    PMID:24100034

    Open questions at the time
    • Native pore geometry in intact mitochondria not directly imaged here
  8. 2014 High

    Defined the symmetric core-domain homodimer and core/latch separation as the structural intermediate of pore assembly.

    Evidence Crystal structure of BAK core dimer with crosslinking and BH3 activation

    PMID:25175025

    Open questions at the time
    • How dimers assemble into higher-order pores not resolved by static structure
  9. 2016 High

    Demonstrated BCL-XL restrains BAK in vivo through the BH3:groove interface, with physiological consequences for lymphocyte and platelet survival.

    Evidence Precision Q75L/Q77L mutagenesis, affinity measurement, knockin mice

    PMID:27198225

    Open questions at the time
    • Relative weighting of BCL-XL versus VDAC2 restraint in different tissues not quantified
  10. 2017 High

    Revealed the disordered dimer-cluster architecture of the pore, overturning ordered-oligomer models.

    Evidence Cysteine labeling/crosslinking across full-length BAK with mathematical simulation

    PMID:28182867

    Open questions at the time
    • Dynamic in-membrane behavior of clusters not directly visualized
  11. 2017 Medium

    Extended VDAC2-BAK regulation to peroxisomes, showing BAK can permeabilize peroxisomal membranes.

    Evidence Organelle-targeted BAK, fractionation, VDAC2/BCL-XL/MCL-1 manipulation

    PMID:28174205

    Open questions at the time
    • Single-lab study; physiological role of peroxisomal BAK permeabilization unclear
  12. 2018 High

    Connected BAK pore formation to innate immunity by showing macropores allow inner-membrane herniation and mtDNA release driving cGAS/STING.

    Evidence Live-cell lattice light-sheet microscopy with caspase inhibition

    PMID:29472455

    Open questions at the time
    • Determinants of macropore versus minimal pore size in vivo not defined
  13. 2018 High

    Identified Parkin-mediated ubiquitination of the BAK groove as a mitophagy-linked brake on activation, defining a regulatory feedback loop.

    Evidence In vitro ubiquitination, Co-IP, site mutagenesis, BAK activation assays

    PMID:30573668

    Open questions at the time
    • In vivo physiological impact of BAK ubiquitination not quantified
  14. 2020 High

    Provided structural evidence that membrane lipids bridge BAK dimers, explaining a non-canonical oligomerization interface.

    Evidence Crystal structures of BAK core dimers with lipid/detergent binding sites

    PMID:32929280

    Open questions at the time
    • Lipid bridging in native membranes not directly demonstrated by crystallography
  15. 2020 High

    Uncovered a neural-specific microexon-NMD mechanism that silences BAK to protect neurons from apoptosis.

    Evidence Splicing analysis, PTBP1 manipulation, NMD assays, germline exon-5 KO mice

    PMID:32710818

    Open questions at the time
    • Whether this regulation operates in human neurons not addressed
  16. 2021 High

    Defined the BH4 domain and N-terminal region as the conformational switch maintaining inactive BAK.

    Evidence HDX-MS on membrane-bound BAK with mutagenesis and permeabilization assays

    PMID:34523147

    Open questions at the time
    • How BH4 disruption is triggered physiologically not established
  17. 2022 High

    Distinguished BAK and BAX kinetics, showing BAK seeds and accelerates BAX assembly into shared pores controlling mtDNA release rate.

    Evidence Single-molecule and super-resolution imaging with cGAS/STING assays

    PMID:35120587

    Open questions at the time
    • Molecular basis of BAK's faster kinetics not fully resolved
  18. 2024 High

    Showed unsaturated lipids proximal to BAK and the desaturase FADS2 promote pore activity and downstream innate immune signaling.

    Evidence Nanodisc lipidomics, membrane pore assays, MD simulations, FADS2 manipulation

    PMID:38830851

    Open questions at the time
    • How lipid composition is locally remodeled at the pore not defined
  19. 2024 High

    Established the sequence of endogenous pore assembly, with BAK recruited before BAX into unordered mosaic rings.

    Evidence STED super-resolution imaging in WT, BAX-KO, and BAK-KO cells

    PMID:38503846

    Open questions at the time
    • Functional significance of BAK-first recruitment for pore output not quantified
  20. 2002 High

    Identified plant BAK1 (a distinct LRR receptor kinase) as a BRI1 interactor that activates kinase signaling by transphosphorylation in brassinosteroid signaling.

    Evidence Yeast two-hybrid, in planta Co-IP, overexpression/knockout phenotypes

    PMID:12150928

    Open questions at the time
    • Note: unrelated to mammalian BAK; symbol collision within corpus
  21. 2007 High

    Showed plant BAK1 is a coreceptor for immune receptors, forming ligand-dependent FLS2 complexes during pattern-triggered immunity.

    Evidence Ligand-dependent in planta Co-IP, bak1 mutant flagellin response assays (replicated by independent lab)

    PMID:17625569 PMID:17626179

    Open questions at the time
    • Distinct protein from mammalian BAK; included only for corpus coherence
  22. 2024 High

    Resolved structural and allosteric mechanisms of plant BAK1 coreceptor activation by partner receptors.

    Evidence Crystal structure of MIK2-SCOOP-BAK1 ternary complex; HDX-MS of EFR-BAK1 allostery

    PMID:39028038 PMID:39511418

    Open questions at the time
    • Plant BAK1 biology is orthogonal to mammalian BAK in this timeline

Open questions

Synthesis pass · forward-looking unresolved questions
  • The corpus conflates two unrelated proteins under one symbol; how endogenous death signals coordinate VDAC2/BCL-XL release, lipid remodeling, and macropore sizing in vivo to tune cGAS/STING output remains unresolved for mammalian BAK.
  • Quantitative coupling of restraint displacement to pore size unknown
  • Tissue-specific weighting of regulatory layers undefined
  • Symbol collision precludes a unified single-gene mechanism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 4 GO:0005886 plasma membrane 3 GO:0005777 peroxisome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
BAXBCL-XLBRI1FLS2MCL1MFN1MFN2VDAC2
Complex memberships
FLS2-BAK1 receptor complex (plant)MIK2-SCOOP-BAK1 complex (plant)RLP23-SOBIR1-BAK1 complex (plant)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 BAK (together with BAX) is an essential gateway for mitochondrial dysfunction during apoptosis: tBID triggers BAK homooligomerization at mitochondria, causing cytochrome c release; cells lacking both BAX and BAK are completely resistant to tBID-induced cytochrome c release and multiple apoptotic stimuli (staurosporine, UV, growth factor deprivation, etoposide, ER stress agents). Genetic double-knockout (Bax-/- Bak-/- mouse embryonic fibroblasts), cytochrome c release assay, apoptosis assays with multiple stimuli Science High 11326099
2003 In viable cells, BAK is maintained in an inactive monomeric conformation at the mitochondrial outer membrane by direct interaction with VDAC2 (but not VDAC1). VDAC2 specifically binds the inactive conformer of BAK; death signals (e.g., tBID, BIM, BAD) displace VDAC2 from BAK, enabling BAK homo-oligomerization and apoptosis. VDAC2 deficiency enhances BAK oligomerization and apoptosis susceptibility; VDAC2 overexpression prevents BAK activation. Co-immunoprecipitation, VDAC2-knockout and overexpression cells, BAK oligomerization assays, apoptosis assays Science High 12881569
2004 Mitochondria-localized p53 directly interacts with BAK, causing BAK oligomerization and cytochrome c release. Formation of the p53-BAK complex coincides with loss of the BAK-MCL1 interaction, suggesting p53 displaces MCL1 to activate BAK. Co-immunoprecipitation, cytochrome c release assay, mitochondrial fractionation Nature Cell Biology Medium 15077116
2003 BAK (and BAX) can localize to the endoplasmic reticulum in addition to mitochondria. ER-targeted BAK causes progressive ER Ca2+ depletion and caspase-12 cleavage, demonstrating a distinct ER-based apoptotic pathway separable from the mitochondrial pathway. Subcellular targeting constructs, fractionation, Ca2+ measurements, caspase cleavage assays in Bax-/-Bak-/- cells reconstituted with compartment-targeted mutants Journal of Cell Biology High 12847083
2007 BAK uniquely interacts with mitofusins MFN1 and MFN2 at the mitochondrial outer membrane. During apoptosis, BAK dissociates from MFN2 and enhances association with MFN1; BH3-domain mutation prevents MFN2 dissociation and diminishes BAK's mitochondrial fragmentation activity. BAK (but not BAX) drives mitochondrial fragmentation during apoptosis. Co-immunoprecipitation, Bak-deficient MEFs and primary neurons, reconstitution in DKO cells, BH3 domain mutagenesis, mitochondrial morphology imaging PNAS High 17606912
2013 BID BH3 helix activates BAK by engaging the canonical BH3-binding groove (activation site) of BAK via a 'hit-and-run' mechanism: BID binds transiently, then dissociates, allowing BAK oligomerization at the same overlapping interface. BAK BH1 groove mutation prevents MOMP but not BID binding; BAK BH3 mutations allow BID binding and activation but block oligomerization. BH3-only proteins NOXA and BAD do not activate BAK. NMR solution structure of BID BH3-BAK complex, site-directed mutagenesis, liposomal cytochrome c release assay, MOMP assay Nature Structural & Molecular Biology High 23604079
2013 Full-length BAK resides constitutively at the outer mitochondrial membrane and requires direct BH3 ligand interaction at its canonical BH3-binding groove (not the α1/α6 site used by BAX) to be activated and release cytochrome c. Photoreactive BH3 crosslinking mapped the BAK trigger site to the BH3-binding pocket, distinct from the BAX α1/α6 trigger site. In vitro reconstitution with purified full-length BAK, liposomal release assay, photoreactive BH3 crosslinking, mutagenesis-based solubilization PNAS High 23404709
2014 BAK undergoes conformational separation of core and latch domains upon activation by specific BH3 peptides, analogous to BAX. Crystal structure of the BAK core domain dimer reveals the symmetric homodimer as a key intermediate in pore-forming oligomer assembly. Crystal structure of BAK core domain dimer, crosslinking experiments, BH3 peptide activation assays Molecular Cell High 25175025
2018 After BAK/BAX activation and cytochrome c release during apoptosis, large BAK/BAX macropores appear in the mitochondrial outer membrane, allowing the inner mitochondrial membrane to herniate into the cytosol and carry mitochondrial matrix contents including mtDNA, thereby enabling cGAS/STING activation. Live-cell lattice light-sheet microscopy in mouse embryonic fibroblasts, caspase inhibition experiments Science High 29472455
2022 BAK and BAX present distinct oligomerization properties: BAK organizes into smaller structures with faster kinetics than BAX. BAK recruits and accelerates BAX assembly into oligomers, and both co-assemble into the same apoptotic pores. The relative availability of BAX and BAK determines apoptotic pore growth rate and kinetics of mtDNA release, with consequences for cGAS/STING activation. Single-molecule imaging, super-resolution microscopy, kinetic analysis of oligomerization, pore visualization, cGAS/STING pathway assays Molecular Cell High 35120587
2017 Disordered clusters of BAK dimers (not ordered oligomers) generate lipidic pores in the mitochondrial outer membrane. Cysteine labeling and linkage analysis across full-length BAK showed the N-terminus is mobile and solvent-exposed post-activation, while dimer-dimer interactions are more labile than BH3:groove interactions within dimers. Mathematical simulations support a disordered dimer-cluster pore model. Cysteine labeling, disulfide crosslinking, mathematical simulations of dimer arrangement eLife High 28182867
2020 Crystal structures of human BAK core domain dimers reveal preferred binding sites for membrane lipids and detergents on the dimer surface. Phospholipid headgroup and one acyl chain (sn2) associate with one core dimer while the other acyl chain (sn1) associates with a neighboring dimer, suggesting lipids bridge BAK dimers to promote oligomerization, unlike typical protein-protein interfaces. Crystal structures of BAK core domain dimers, lipid-binding analysis Nature Structural & Molecular Biology High 32929280
2021 Hydrogen-deuterium exchange mass spectrometry of membrane-bound BAK revealed that the BH4 domain maintains the inactive conformation of BAK; disrupting the BH4 domain is sufficient for constitutive BAK activation. The entire N-terminal region preceding BAK oligomerization domains becomes disordered post-activation and remains disordered in the activated oligomer. Removal of the disordered N-terminus slightly potentiates BAK-mediated membrane permeabilization. HDX-MS on membrane-bound BAK (liposomes with mitochondrial lipids), site-directed mutagenesis, liposomal and mitochondrial permeabilization assays EMBO Journal High 34523147
2018 During mitophagy, Parkin directly ubiquitinates BAK at a conserved lysine in its hydrophobic groove (critical for BH3-only protein activation and homo-dimerization), inhibiting BAK activation and lethal oligomer formation. BAK-dependent MOMP during apoptosis also promotes PINK1-dependent Parkin activation, creating a feedback loop. In vitro ubiquitination assay, Co-IP, BAK activation assay, mitophagy induction, mutagenesis of ubiquitination site EMBO Journal High 30573668
2012 Vitamin K2 (menaquinone) covalently binds to BAK at cysteine-166, inducing BAK oligomerization and BAK-dependent cytochrome c release and apoptosis. This effect is specific to BAK and does not require BAX; VK2-2,3-epoxide (intracellular metabolite) mediates the covalent attachment. Pulldown/binding assay, site-directed mutagenesis (C166), cytochrome c release assay, BAK-specific siRNA knockdown Molecular Pharmacology Medium 23229512
2020 Neural-specific splicing of the evolutionarily conserved Bak1 microexon 5 (regulated by PTBP1 downregulation during neuronal development) triggers nonsense-mediated mRNA decay of Bak1 transcripts, suppressing pro-apoptotic BAK1 protein expression in neurons. Germline heterozygous ablation of exon 5 increases BAK1 protein exclusively in the brain, increases neuronal apoptosis, and causes early postnatal mortality. Alternative splicing analysis, PTBP1 knockdown/knockout, NMD assays, germline exon 5 knockout mice, neuronal apoptosis quantification Neuron High 32710818
2017 The VDAC2-BAK axis regulates peroxisomal membrane permeability. Loss of VDAC2 shifts BAK localization from mitochondria to peroxisomes, causing peroxisomal deficiency. Peroxisome-targeted BAK causes release of peroxisomal matrix proteins to the cytosol; BAK activators PUMA and BIM permeabilize peroxisomes in a BAK-dependent manner. Subcellular fractionation, peroxisome-targeted BAK constructs, BAK knockdown, overexpression of VDAC2/BCL-XL/MCL-1 Journal of Cell Biology Medium 28174205
2016 Bcl-xL physiologically restrains BAK by direct physical interaction via BAK's BH3:groove interface. A BAK Q75L (mouse)/Q77L (human) mutation specifically disrupts BAK-BCL-XL binding without affecting BAK structure or killing activity, reducing affinity through loss of a single hydrogen bond. In vivo, loss of BCL-XL binding to BAK causes significant defects in T-cell and platelet survival. Site-directed mutagenesis, binding affinity measurements, knockin mouse model, T-cell and platelet survival analysis Genes & Development High 27198225
2024 Unsaturated lipids enriched in the proximal membrane environment of BAK promote BAX pore activity. Lipidomics of BAK isolated in lipid nanodiscs shows enrichment of unsaturated species near BAK during apoptosis. The fatty acid desaturase FADS2 enhances apoptosis sensitivity and cGAS/STING activation downstream of mtDNA release. Comparative lipidomics (lipid nanodisc isolation of BAK), model membrane pore assays, isolated mitochondria assays, molecular dynamics simulations, FADS2 manipulation Nature Communications High 38830851
2013 BAK and BAX form stable protein-permeable pores of tunable, dynamic size in lipid membranes. Single-vesicle imaging showed cBid-activated BAK (BakΔC21) forms pores large enough to release not only cytochrome c but also 104 kDa allophycocyanin. Pore area evolves with time and protein concentration but not cardiolipin concentration, consistent with proteolipidic pore nature. Single-vesicle fluorescence assay, size-exclusion analysis, protein concentration titration, cardiolipin manipulation Journal of Biological Chemistry High 24100034
2013 Myc-induced AMPK activation stabilizes p53 via Ser15 phosphorylation, leading to mitochondrial p53 accumulation. Mitochondrial p53 interacts with the BAK-BCL-XL complex, inducing BAK conformational activation without disrupting the BAK-BCL-XL interaction. Subsequent release of activated BAK from this complex leads to spontaneous BAK oligomerization and apoptosis. Co-immunoprecipitation, BAK conformational activation assay, AMPK inhibition, p53 knockdown, mitochondrial fractionation PNAS Medium 23589839
2024 Endogenous BAK is recruited to apoptotic pores before BAX. Both BAK and BAX together form unordered mosaic rings on the mitochondrial outer membrane in wild-type cells. In single-knockout cells, either protein alone can form rings independently. Overexpression of BAK produces novel structures absent in non-overexpressing apoptotic cells. Live- and fixed-cell STED super-resolution microscopy in wild-type, BAX-KO, and BAK-KO cells and human primary cells Cell Death and Differentiation High 38503846
2007 In Arabidopsis, BAK1 (SERK3) forms a ligand-dependent complex with the immune receptor FLS2 within minutes of flagellin stimulation. BAK1 positively regulates early and late flagellin-triggered immune responses (including FLS2 and EFR signaling) independently of its role in brassinosteroid signaling. Co-immunoprecipitation in planta (ligand-dependent), bak1 mutant analysis, flagellin response assays, brassinosteroid sensitivity controls Nature High 17625569 17626179
2002 Arabidopsis BAK1 was identified as a specific interactor of BRI1 (brassinosteroid receptor) by yeast two-hybrid. BAK1/BRI1 interaction activates their kinase activities through transphosphorylation in yeast. BAK1 and BRI1 share subcellular localization and physically associate in plants. BAK1 overexpression phenocopies BRI1 overexpression; bak1 knockout gives a weak bri1-like phenotype. Yeast two-hybrid, co-immunoprecipitation in plants, overexpression/knockout genetic analysis Cell High 12150928
2008 BRI1 transphosphorylates BAK1 in vitro on specific kinase-domain residues critical for BAK1 function; BR-dependent BRI1 activation precedes BAK1 association in planta. BAK1 subsequently transphosphorylates BRI1, quantitatively increasing BRI1 kinase activity. A sequential transphosphorylation model is proposed: BRI1 controls signaling specificity, then activates BAK1 via transphosphorylation, and BAK1 reciprocally enhances BRI1. In vitro kinase assay with phosphosite mapping (mass spectrometry), in planta phosphorylation analysis, temporal dissection of BR signaling Developmental Cell High 18694562
2014 BIR2, a novel BAK1-interacting receptor-like kinase (identified by LC/ESI-MS/MS), is unidirectionally phosphorylated by BAK1. BIR2 constitutively interacts with BAK1, preventing BAK1-FLS2 complex formation in the absence of ligand. PAMP perception triggers BIR2 release from BAK1, enabling BAK1 recruitment to the FLS2 complex. BIR2 acts as a negative regulator of PAMP-triggered immunity. LC/ESI-MS/MS interactome, Co-immunoprecipitation, bir2 mutant phenotyping, phosphorylation assays Current Biology High 24388849
2014 Protein phosphatase 2A (PP2A), composed of subunits A1, C4, and B'η/ζ, constitutively associates with BAK1 in planta and dephosphorylates BAK1 to negatively regulate plant innate immunity. Impairment of PP2A-BAK1 interaction increases steady-state BAK1 phosphorylation and potentiates immune responses. Co-immunoprecipitation, PP2A mutant analysis, phosphorylation assays, immune response measurements EMBO Journal Medium 25085430
2019 BAK1 directly interacts with and phosphorylates CNGC20 (a Ca2+-permeable channel) at specific sites in its C-terminal cytosolic domain, regulating CNGC20 protein stability and Ca2+ channel function. This BAK1-CNGC20 axis controls cellular Ca2+ homeostasis to contain cell death in Arabidopsis. RNAi genetic screen, Co-IP, in vitro kinase/phosphorylation assay, electrophysiology, genetic epistasis Current Biology Medium 31679931
2019 BAK1 undergoes Ca2+-dependent proteolytic cleavage at a surface-exposed Asp287 residue, conserved in Arabidopsis, N. benthamiana, and yeast. This cleavage is regulated by developmental cues and immune stimulation. The BAK1 D287A mutation impairs BAK1 phosphorylation of its substrate BIK1, plasma membrane localization, and BAK1 function in immunity, BR signaling, and cell death containment. Site-directed mutagenesis (D287A), in planta phosphorylation assays, plasma membrane localization imaging, genetic complementation Plant Physiology Medium 30782965
2015 RLP23 forms a constitutive, ligand-independent complex with SOBIR1, and upon nlp20 (NLP peptide) binding, recruits BAK1 into a tripartite RLP23-SOBIR1-BAK1 complex to activate immune responses. Co-immunoprecipitation in planta, nlp20 binding assay, genetic mutant analysis Nature Plants Medium 27251392
2019 The lectin receptor kinase LecRK-VI.2 constitutively associates with BAK1 in vivo, and both LecRK-VI.2 and BAK1 kinase activities are required for eNAD+/eNADP+ signaling and systemic acquired resistance (SAR) in Arabidopsis. Co-immunoprecipitation in planta, kinase-dead mutant analysis, SAR assays Nature Communications Medium 31641112
2020 BAK1 phosphorylates the plasma membrane H+-ATPase AHA2 at T858 and T881 in its C-terminal domain, enhancing H+ pump activity and promoting K+ uptake under low-potassium stress. BAK1 directly interacts with the AHA2 C-terminus. Co-IP, in vitro kinase assay with phosphosite identification, aha2 and bak1 mutant analysis, phosphorylation-mimic mutants Plant Physiology Medium 35604103
2024 EFR can allosterically activate BAK1 kinase activity via a non-catalytic mechanism: a kinase-dead EFR variant retains ability to enhance BAK1 catalytic activity. HDX-MS analysis and suppressor mutagenesis indicate EFR must adopt its active conformation to allosterically activate BAK1 by supporting αC-helix positioning. BAK1 first phosphorylates EFR in the activation loop to stabilize EFR's active conformation, allowing EFR to then allosterically activate BAK1. HDX-MS, kinase-dead mutant analysis, homology-based intragenic suppressor mutagenesis, in vitro kinase assays eLife High 39028038
2020 BAK1 is phosphorylated by and interacts with all three Arabidopsis catalases (CAT1, CAT2, CAT3), identified by affinity purification/LC-MS/MS. BAK1-mediated catalase phosphorylation enhances catalase activity and reduces H2O2 accumulation under high light, regulating plant growth. BAK1 overexpression effect on high-light growth is abolished in triple catalase knockout plants. Affinity purification/LC-MS/MS, in vitro kinase assay with phosphosite mapping, genetic analysis (bak1 and cat mutants) International Journal of Molecular Sciences Medium 32093294
2019 The receptor-like kinase NIK1 negatively regulates FLS2/BAK1 complex formation. NIK1 interacts with both FLS2 and BAK1; this interaction is enhanced upon flg22 perception. NIK1 acts as a negative regulator of antibacterial PTI while positively regulating antiviral immunity. Co-immunoprecipitation, NIK1 overexpression/knockout, PTI response assays, bacterial resistance assays Nature Communications Medium 31676803
2020 Cell death in bak1 bkk1 double mutants is suppressed by mutation of the NLR helper proteins ADR1s, indicating BAK1 depletion triggers NLR-dependent ETI-like cell death. Pseudomonas effector HopB1, which proteolytically cleaves activated BAK1, triggers cell death in an ADR1-dependent manner, suggesting BAK1 and its paralogs are guarded by NLRs. Genetic epistasis (bak1 bkk1 adr1 triple mutants), HopB1 expression/delivery, protease activity analysis PNAS Medium 33055218
2016 BAK1 and BKK1-mediated cell death control requires nucleocytoplasmic trafficking; loss-of-function of nucleoporin NUP85-like gene SBB1 (and other nucleoporins in the same sub-complex) or DEAD-box RNA helicase DRH1 suppresses bak1 bkk1 cell death. Suppression correlates with blocked poly(A)+ RNA export and reduced salicylic acid accumulation. Genetic suppressor screen, epistasis analysis, mRNA export assays, salicylic acid measurements Plant Journal Medium 26775605
2019 Kinase activity of both SOBIR1 and BAK1 is required for SOBIR1-induced constitutive immunity and SOBIR1 phosphorylation in planta. BAK1 kinase activity is essential for the defense response triggered by the tomato LRR-RLP Cf-4. SOBIR1 and BAK1 likely transphosphorylate each other within the signaling-competent receptor complex. Kinase-dead mutant analysis, phosphorylation assays, gene silencing, co-immunoprecipitation, live cell imaging Molecular Plant Pathology Medium 30407725
2024 Crystal structure of MIK2-SCOOP-BAK1 complex reveals that SCOOPs use their SxS motif to bind MIK2 and carboxy-terminal GGR residues to bridge MIK2 to BAK1. Specific N-glycans on MIK2 directly interact with BAK1 upon SCOOP sensing; loss of this N-glycosylation site does not affect MIK2 localization or conformation but markedly reduces MIK2-BAK1 affinity and abolishes SCOOP-triggered immunity. Crystal structure of ternary complex, N-glycosylation mutagenesis, binding affinity measurements, genetic complementation Nature Plants High 39511418
2017 BAK1-dependent PTI contributes to antiviral resistance in Arabidopsis; bak1 mutants show increased susceptibility to three RNA viruses. Crude viral extracts (but not purified virions) induce PTI marker responses in a BAK1-dependent manner. bak1 mutant viral infection assays, PTI marker response assays with viral extracts vs purified virions Molecular Plant-Microbe Interactions Medium 23902263
2017 BAK1 is involved in AtRALF1-induced inhibition of root cell expansion. AtRALF1 physically interacts with BAK1 (Kd = 4.6 μM), induces BAK1 phosphorylation, and requires BAK1 for induction of AtRALF1-responsive genes. Binding to intact seedlings is partly BAK1-dependent. Binding affinity measurement (acridinium-labeled peptide), Co-IP, bak1 mutant analysis, phosphorylation assay, gene expression analysis PLoS Genetics Medium 29028796
2013 Visualization by FLIM in live Arabidopsis root epidermal cells showed BR signaling activation increases BAK1-BRI1 heterooligomerization by ~50% at the plasma membrane. Approximately 7% of the BRI1 PM pool constitutively heterooligomerizes with BAK1 independent of BR ligand. Comparative colocalization analysis and FLIM (fluorescence lifetime imaging microscopy) in live plant cells Plant Physiology Medium 23796795

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science (New York, N.Y.) 3287 11326099
2007 A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 1378 17625569
2002 BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling. Cell 894 12150928
2007 The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proceedings of the National Academy of Sciences of the United States of America 860 17626179
2018 BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science (New York, N.Y.) 854 29472455
2017 Bax, Bak and beyond - mitochondrial performance in apoptosis. The FEBS journal 732 28755482
2003 VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science (New York, N.Y.) 683 12881569
2004 Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nature cell biology 661 15077116
2006 RETRACTED: Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science (New York, N.Y.) 545 16645094
2003 Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. The Journal of cell biology 496 12847083
2008 Sequential transphosphorylation of the BRI1/BAK1 receptor kinase complex impacts early events in brassinosteroid signaling. Developmental cell 431 18694562
2010 Molecular biology of Bax and Bak activation and action. Biochimica et biophysica acta 413 21195116
2015 An RLP23-SOBIR1-BAK1 complex mediates NLP-triggered immunity. Nature plants 357 27251392
2013 Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell death and differentiation 352 24162660
2007 BAK1 and BKK1 regulate brassinosteroid-dependent growth and brassinosteroid-independent cell-death pathways. Current biology : CB 316 17600708
2007 Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proceedings of the National Academy of Sciences of the United States of America 288 17606912
2007 The BRI1-associated kinase 1, BAK1, has a brassinolide-independent role in plant cell-death control. Current biology : CB 286 17583510
2013 Two for all: receptor-associated kinases SOBIR1 and BAK1. Trends in plant science 258 24238702
2009 One for all: the receptor-associated kinase BAK1. Trends in plant science 241 19748302
2006 How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane? Current opinion in cell biology 235 17046225
2011 Brassinosteroids inhibit pathogen-associated molecular pattern-triggered immune signaling independent of the receptor kinase BAK1. Proceedings of the National Academy of Sciences of the United States of America 228 22087006
2014 The leucine-rich repeat receptor kinase BIR2 is a negative regulator of BAK1 in plant immunity. Current biology : CB 211 24388849
2022 The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation. Molecular cell 200 35120587
2007 Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak. The Biochemical journal 181 17447897
2008 Hierarchical involvement of Bak, VDAC1 and Bax in cisplatin-induced cell death. Oncogene 175 18362892
2002 Bax and Bak independently promote cytochrome C release from mitochondria. The Journal of biological chemistry 170 11836241
2013 BID-induced structural changes in BAK promote apoptosis. Nature structural & molecular biology 169 23604079
2022 Pro-apoptotic complexes of BAX and BAK on the outer mitochondrial membrane. Biochimica et biophysica acta. Molecular cell research 152 35752202
2016 Bax and Bak Pores: Are We Closing the Circle? Trends in cell biology 152 27932064
2003 Mitochondrial membrane permeabilisation by Bax/Bak. Biochemical and biophysical research communications 146 12729579
2013 Direct activation of full-length proapoptotic BAK. Proceedings of the National Academy of Sciences of the United States of America 138 23404709
2014 Bak core and latch domains separate during activation, and freed core domains form symmetric homodimers. Molecular cell 133 25175025
2013 Proapoptotic Bax and Bak proteins form stable protein-permeable pores of tunable size. The Journal of biological chemistry 133 24100034
2014 Negative control of BAK1 by protein phosphatase 2A during plant innate immunity. The EMBO journal 129 25085430
2013 The immunity regulator BAK1 contributes to resistance against diverse RNA viruses. Molecular plant-microbe interactions : MPMI 124 23902263
2015 Regulated necrotic cell death: the passive aggressive side of Bax and Bak. Circulation research 120 25999420
2015 Danger peptide receptor signaling in plants ensures basal immunity upon pathogen-induced depletion of BAK1. The EMBO journal 119 26574534
2013 Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis. Proceedings of the National Academy of Sciences of the United States of America 118 23589839
2016 Physiological and Pharmacological Control of BAK, BAX, and Beyond. Trends in cell biology 114 27498846
2019 The Receptor Kinases BAK1/SERK4 Regulate Ca2+ Channel-Mediated Cellular Homeostasis for Cell Death Containment. Current biology : CB 111 31679931
2002 BAX and BAK mediate p53-independent suppression of tumorigenesis. Cancer cell 109 12242152
2013 Visualization of BRI1 and BAK1(SERK3) membrane receptor heterooligomers during brassinosteroid signaling. Plant physiology 95 23796795
2018 Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy. The EMBO journal 94 30573668
2015 BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy. Autophagy 85 25715028
2019 Extracellular pyridine nucleotides trigger plant systemic immunity through a lectin receptor kinase/BAK1 complex. Nature communications 83 31641112
2019 The receptor-like kinase NIK1 targets FLS2/BAK1 immune complex and inversely modulates antiviral and antibacterial immunity. Nature communications 82 31676803
2020 Loss of the common immune coreceptor BAK1 leads to NLR-dependent cell death. Proceedings of the National Academy of Sciences of the United States of America 81 33055218
2015 Targeting the miR-221-222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma. Cancer research 79 26249174
2017 Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. eLife 68 29148970
2017 A look at plant immunity through the window of the multitasking coreceptor BAK1. Current opinion in plant biology 66 28458047
2017 Disordered clusters of Bak dimers rupture mitochondria during apoptosis. eLife 64 28182867
2014 BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy. Autophagy 64 24991825
2019 Kinase activity of SOBIR1 and BAK1 is required for immune signalling. Molecular plant pathology 63 30407725
2018 BH3-Dependent and Independent Activation of BAX and BAK in Mitochondrial Apoptosis. Current opinion in physiology 63 30334018
2007 Crosstalk between Bak/Bax and mTOR signaling regulates radiation-induced autophagy. Autophagy 62 17204849
2020 Developmental Attenuation of Neuronal Apoptosis by Neural-Specific Splicing of Bak1 Microexon. Neuron 61 32710818
2017 Pore formation by dimeric Bak and Bax: an unusual pore? Philosophical transactions of the Royal Society of London. Series B, Biological sciences 60 28630157
2013 Consequences of the combined loss of BOK and BAK or BOK and BAX. Cell death & disease 59 23744350
2024 Lipid unsaturation promotes BAX and BAK pore activity during apoptosis. Nature communications 56 38830851
2020 BAK core dimers bind lipids and can be bridged by them. Nature structural & molecular biology 56 32929280
2017 The VDAC2-BAK axis regulates peroxisomal membrane permeability. The Journal of cell biology 54 28174205
2016 A Bak-dependent mitochondrial amplification step contributes to Smac mimetic/glucocorticoid-induced necroptosis. Cell death and differentiation 54 27834956
2007 Controlling the cell death mediators Bax and Bak: puzzles and conundrums. Cell cycle (Georgetown, Tex.) 53 18196961
2008 Protein phosphatase-2A is a target of epigallocatechin-3-gallate and modulates p53-Bak apoptotic pathway. Cancer research 52 18519674
2019 Proteolytic Processing of SERK3/BAK1 Regulates Plant Immunity, Development, and Cell Death. Plant physiology 50 30782965
2022 BAX and BAK dynamics control mitochondrial DNA release during apoptosis. Cell death and differentiation 49 35347233
2019 Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis. Cell death & disease 46 31324752
2017 BAK1 is involved in AtRALF1-induced inhibition of root cell expansion. PLoS genetics 46 29028796
2016 Nucleocytoplasmic trafficking is essential for BAK1- and BKK1-mediated cell-death control. The Plant journal : for cell and molecular biology 46 26775605
2014 Bak and Mcl-1 are essential for Temozolomide induced cell death in human glioma. Oncotarget 44 24811082
2011 Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and pediatric germ cell tumors. Genes, chromosomes & cancer 44 22072546
2021 MiR-125b inhibits cardiomyocyte apoptosis by targeting BAK1 in heart failure. Molecular medicine (Cambridge, Mass.) 43 34238204
2013 Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease. Proceedings of the National Academy of Sciences of the United States of America 43 23349374
2013 BAK1 directly regulates brassinosteroid perception and BRI1 activation. Journal of integrative plant biology 42 24308570
2023 Mitophagy restricts BAX/BAK-independent, Parkin-mediated apoptosis. Science advances 41 37224250
2016 Physiological restraint of Bak by Bcl-xL is essential for cell survival. Genes & development 41 27198225
2012 Vitamin K2 covalently binds to Bak and induces Bak-mediated apoptosis. Molecular pharmacology 38 23229512
2014 Beta-amyloid oligomers activate apoptotic BAK pore for cytochrome c release. Biophysical journal 35 25296312
2012 A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway. PloS one 35 22719850
2008 Key role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine. Molecular cancer therapeutics 34 18645031
2022 Pharmacologic Reduction of Mitochondrial Iron Triggers a Noncanonical BAX/BAK-Dependent Cell Death. Cancer discovery 32 34862195
2015 Mitochondrial p53 phosphorylation induces Bak-mediated and caspase-independent cell death. Oncotarget 32 25980443
2020 BAK1 Mediates Light Intensity to Phosphorylate and Activate Catalases to Regulate Plant Growth and Development. International journal of molecular sciences 31 32093294
2020 Receptor-Like Kinases BAK1 and SOBIR1 Are Required for Necrotizing Activity of a Novel Group of Sclerotinia sclerotiorum Necrosis-Inducing Effectors. Frontiers in plant science 31 32754179
2011 Active Bax and Bak are functional holins. Genes & development 31 22006182
2018 BAX and BAK at the Gates of Innate Immunity. Trends in cell biology 26 29555208
2021 Discovery of Small Molecule Bak Activator for Lung Cancer Therapy. Theranostics 24 34373755
2021 Dynamic reconfiguration of pro-apoptotic BAK on membranes. The EMBO journal 24 34523147
2019 BAKing up to Survive a Battle: Functional Dynamics of BAK1 in Plant Programmed Cell Death. Frontiers in plant science 24 30671069
2024 Endogenous BAX and BAK form mosaic rings of variable size and composition on apoptotic mitochondria. Cell death and differentiation 23 38503846
2024 Mechanistic study of SCOOPs recognition by MIK2-BAK1 complex reveals the role of N-glycans in plant ligand-receptor-coreceptor complex formation. Nature plants 23 39511418
2024 Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling. eLife 21 39028038
2023 Hsa_circ_0002348 regulates trophoblast proliferation and apoptosis through miR-126-3p/BAK1 axis in preeclampsia. Journal of translational medicine 20 37507742
2010 ZBP-89 enhances Bak expression and causes apoptosis in hepatocellular carcinoma cells. Biochimica et biophysica acta 20 20850481
2008 Receptor-like protein kinases, BAK1 and BKK1, regulate a light-dependent cell-death control pathway. Plant signaling & behavior 20 19704566
2003 Induction of GADD153 and Bak: novel molecular targets of fenretinide-induced apoptosis of neuroblastoma. Cancer letters 20 12880976
1999 Bak expression and cell death occur in peritumorous tissue but not in pancreatic cancer cells. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 20 10457328
2022 Receptor-like protein kinase BAK1 promotes K+ uptake by regulating H+-ATPase AHA2 under low potassium stress. Plant physiology 19 35604103
2009 BAK1 gene variation and abdominal aortic aneurysms. Human mutation 19 19514060
2014 FLS2-BAK1 extracellular domain interaction sites required for defense signaling activation. PloS one 18 25356676

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