ATP5F1B

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045259 proton-transporting ATP synthase complex	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for CC. ATP5F1B is a core structural and catalytic component of the proton-transporting ATP synthase complex (Complex V). This is well supported by cryo-EM structural data (PMID:37244256), immunocapture studies (PMID:12110673), and assembly studies (PMID:26297831). Reason: This is the defining complex membership for ATP5F1B. The beta subunit is one of the major subunits of the F1 catalytic head. Cryo-EM structures show ATP5F1B as chains D/E/F in the alpha3-beta3 hexamer (PMID:37244256). IBA annotation is appropriate and well conserved across the ATPase alpha/beta chains family. Supporting Evidence: PMID:37244256 These structures reveal that the release of ADP occurs when the β subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1))
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for MF with contributes_to qualifier. The beta subunit contributes to the proton-transporting ATP synthase activity of the holoenzyme complex via the rotational mechanism. The contributes_to qualifier is correct because this activity is a property of the whole complex, not the individual subunit. Reason: The contributes_to qualifier is appropriate for a subunit that is part of the catalytic core but requires the full complex for proton-transporting ATP synthase activity. The beta subunit houses the catalytic nucleotide-binding sites, but the rotational mechanism requires the assembled F1Fo complex including the proton channel (Fo). Well supported by structural data (PMID:37244256) and functional studies (PMID:36239646). Supporting Evidence: PMID:37244256 These structures reveal that the release of ADP occurs when the β subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis PMID:36239646 The catalytic core of F1 contains three α and three β subunits arranged around a γ subunit of the central stalk. Protons passing through FO (the pore) cause the γ stalk to rotate, inducing conformational transitions in the β subunit that are required for the synthesis of ATP from ADP
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for BP. Proton motive force-driven mitochondrial ATP synthesis is the core biological process performed by ATP5F1B as part of Complex V. This is the more specific mitochondrial form of GO:0015986. Reason: This is the most specific and accurate BP annotation for ATP5F1B. The beta subunit is the catalytic component that directly synthesizes ATP from ADP driven by the proton motive force across the inner mitochondrial membrane. Supported by extensive experimental evidence (PMID:36239646, PMID:37244256, PMID:12110673). Supporting Evidence: PMID:36239646 Complex V (CV) is the central enzyme in energy conversion: it dissipates the proton gradient across the membrane, catalyzing the phosphorylation of ADP to ATP
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for MF based on UniProtKB keyword mapping. Nucleotide binding is correct but very general for ATP5F1B, which specifically binds ADP and ATP at its catalytic site. Reason: This is a broad but correct IEA annotation. The beta subunit has well-characterized nucleotide (ADP/ATP) binding sites documented by cryo-EM (PMID:37244256) and UniProt binding annotations at residues 209-214. More specific terms like GO:0005524 (ATP binding) are also present in the annotation set, so this broader term is acceptable as an IEA inference. Supporting Evidence: PMID:37244256 These structures reveal that the release of ADP occurs when the β subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for MF. ATP binding is a well-established function of the beta subunit, which contains the catalytic nucleotide-binding site. UniProt documents multiple ADP/ATP binding residues (positions 209-214, 238-239). Reason: Correct and well-supported. The beta subunit binds ATP at its catalytic site. Structural evidence from cryo-EM (PMID:37244256) and bovine structure by similarity confirm ADP/ATP binding. UniProt lists extensive binding site annotations with experimental evidence. Supporting Evidence: PMID:37244256 snapshot images for three main rotational states and one substate of human ATP synthase
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation for CC based on ARBA machine learning model. Cytoplasm is too broad and imprecise for ATP5F1B, whose primary localization is the mitochondrial matrix/inner membrane. Reason: While imprecise, this is not incorrect since the mitochondrion is within the cytoplasm. More specific CC annotations (mitochondrion, mitochondrial inner membrane, mitochondrial matrix) are present in the annotation set. As an IEA, this broad term is acceptable.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for CC based on UniProt subcellular location mapping. ATP5F1B is a peripheral membrane protein on the matrix side of the mitochondrial inner membrane, as part of the F1 head of the ATP synthase complex. Reason: Correct. UniProt states ATP5F1B localizes to "Mitochondrion inner membrane; Peripheral membrane protein; Matrix side" with experimental evidence (PMID:25168243). The F1 head is attached to the inner membrane via the central and peripheral stalks. Supporting Evidence: PMID:25168243 Strap is localised at mitochondria where one of its key interaction partners is ATP synthase
GO:0006754 ATP biosynthetic process	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for BP based on UniProt keyword mapping. ATP biosynthetic process is a core function of ATP5F1B as the catalytic subunit of ATP synthase. Reason: Correct and represents a core function. The beta subunit directly catalyzes ATP synthesis from ADP + Pi. This is supported by UniProt functional annotation with EC 7.1.2.2 and multiple experimental studies (PMID:37244256, PMID:36239646).
GO:0006811 monoatomic ion transport	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for BP. This term refers to ion transport, which is related to the proton transport function of the ATP synthase complex but is extremely broad. Reason: While very general, this is not incorrect since the F1Fo-ATP synthase complex transports protons (H+) across the inner mitochondrial membrane. The beta subunit contributes to this function as part of the complex. More specific annotations for proton transport are also present.
GO:0015986 proton motive force-driven ATP synthesis	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for BP based on InterPro mapping. Proton motive force-driven ATP synthesis is the core biological process of ATP5F1B. This is the parent of the more specific GO:0042776 (mitochondrial form). Reason: Correct. This broader term subsumes GO:0042776. Redundant with the IBA and IDA annotations for the same term, but as an IEA it is perfectly acceptable. ATP5F1B is a core component of the proton motive force-driven ATP synthesis machinery.
GO:0016469 proton-transporting two-sector ATPase complex	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation for CC. This term describes the broader class of two-sector ATPase complexes (F-type, V-type, A-type). The mitochondrial ATP synthase is an F-type two-sector ATPase. Reason: Correct but general. The F1Fo ATP synthase is indeed a proton-transporting two-sector ATPase complex. More specific annotations for the proton-transporting ATP synthase complex (GO:0045259) are also present. As an IEA from ARBA, the broader term is acceptable.
GO:0045259 proton-transporting ATP synthase complex	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for CC, duplicating the IBA annotation for the same GO term. Correct. Reason: Correct and consistent with the IBA annotation. Duplicate evidence codes for the same term are fine.
GO:0046034 ATP metabolic process	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for BP based on InterPro mapping. ATP metabolic process is very broad, encompassing both ATP synthesis and hydrolysis. Reason: Correct but very general. ATP5F1B is involved in ATP metabolism (primarily synthesis, but the complex can also hydrolyze ATP). More specific annotations for ATP biosynthetic process and proton motive force-driven ATP synthesis are present.
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for MF based on UniProt keyword mapping. ATP5F1B binds Mg2+ as a cofactor for the ATP synthase catalytic reaction. UniProt documents Mg2+ binding at residues 213 and 238 (PMID:37244256). Reason: Correct. The beta subunit binds Mg2+ ions which are essential cofactors for the catalytic reaction. The cryo-EM structure (PMID:37244256) confirms Mg2+ binding. This is a broad IEA term; more specific magnesium ion binding could be considered, but metal ion binding is acceptable. Supporting Evidence: PMID:37244256 Biological energy currency ATP is produced by F1Fo-ATP synthase
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for MF, duplicating the IBA and IDA annotations for the same GO term. Note this IEA lacks the contributes_to qualifier that the IBA has. Reason: Correct term but ideally should have the contributes_to qualifier as in the IBA annotation, since the activity is a property of the whole complex. However, as an IEA the absence of the qualifier is acceptable.
GO:1902495 transmembrane transporter complex	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation for CC based on ARBA. The ATP synthase complex is a transmembrane transporter complex that translocates protons across the membrane. Reason: Correct but very general. The F1Fo-ATP synthase is indeed a transmembrane transporter complex. More specific terms (GO:0045259, GO:0016469) are also annotated.
GO:1902600 proton transmembrane transport	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for BP. Proton transmembrane transport is a core process of the ATP synthase complex. Reason: Correct. The F1Fo-ATP synthase transports protons across the inner mitochondrial membrane as part of its catalytic cycle. ATP5F1B contributes to this as the catalytic subunit of the F1 head.
GO:0005515 protein binding	IPI PMID:11410595 Atp11p and Atp12p are assembly factors for the F(1)-ATPase i...	UNDECIDED	Summary: IPI protein binding annotation. Publication not available for review (PMID:11410595 not cached). Likely a large-scale interaction study. Reason: Cannot assess without access to the publication. The generic protein binding term is uninformative. If from a large-scale study, it is likely a high-throughput detection of protein interaction without functional characterization.
GO:0005515 protein binding	IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from a large-scale proteomic analysis of 14-3-3-binding proteins (Meek et al. 2004). ATP5F1B was identified as a 14-3-3-binding protein. UniProt also documents an interaction with YWHAZ (14-3-3 zeta). Reason: This is a high-throughput proteomic study identifying many 14-3-3-binding proteins. While the interaction may be real, the generic "protein binding" term is uninformative and the biological significance of 14-3-3 binding to ATP5F1B is not characterized. The interaction could reflect phosphorylation-dependent regulation but this is speculative. Supporting Evidence: PMID:15161933 14-3-3-binding proteins were purified from extracts of interphase and mitotic HeLa cells using specific peptide elution from 14-3-3 zeta affinity columns
GO:0005515 protein binding	IPI PMID:20618440 Proteomic and biochemical analysis of 14-3-3-binding protein...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from proteomic analysis of 14-3-3-binding proteins during C2-ceramide-induced apoptosis (Pozuelo-Rubio 2010). ATP5F1B was identified as a 14-3-3-associated protein. Reason: Another 14-3-3 interaction proteomics study. The generic protein binding term is uninformative. The biological relevance to ATP5F1B function is unclear. Supporting Evidence: PMID:20618440 14-3-3 is a family of proteins comprising several isoforms that, in many cases, promote cell survival by association with proapoptotic proteins
GO:0005515 protein binding	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from mitochondrial protein interaction mapping study (Floyd et al. 2016). This is a focused mitochondrial interactome study that identified regulators of respiratory chain function. Reason: While this is a mitochondria-focused interaction study, the generic protein binding term is uninformative. The study mapped mitochondrial protein interactions but the specific interaction partners and functional significance for ATP5F1B are not captured by this annotation. Supporting Evidence: PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from a large-scale human interactome mapping study (Huttlin et al. 2017). This is a high-throughput study mapping the architecture of the human interactome. Reason: Large-scale interactome study. The generic protein binding term is uninformative for a well-characterized enzyme subunit. The specific interaction partners are not characterized in the annotation.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from an interactome perturbation framework study for developmental disorders (Sahni et al. 2018). High-throughput protein interaction study. Reason: High-throughput interactome study. Generic protein binding is uninformative for ATP5F1B.
GO:0005515 protein binding	IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from a histone interaction landscape study using crosslinking mass spectrometry in intact cell nuclei (Fasci et al. 2018). ATP5F1B detected as a histone-interacting protein in this study. Reason: This study focused on histone interactions by crosslinking mass spectrometry. Detection of ATP5F1B likely reflects its abundance rather than a specific functional interaction with histones. The generic protein binding term is uninformative.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from a study on disruption of protein interactions by genetic variants across the allele frequency spectrum (Sahni et al. 2019). High-throughput study. Reason: Large-scale interactome study focused on variant effects on protein interactions. Generic protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI protein binding from a reference map of the human binary protein interactome (Luck et al. 2020). High-throughput Y2H/AP-MS study. Reason: Large-scale binary interactome reference map. Generic protein binding is uninformative for a well-characterized enzyme subunit.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from an interactome mapping study focused on neurodegenerative disease proteins (Haenig et al. 2020). Reason: Disease-focused interactome study. Generic protein binding is uninformative. The interaction with neurodegenerative disease proteins is likely not a core function of ATP5F1B.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from dual proteome-scale network study showing cell-specific remodeling of the human interactome (Huttlin et al. 2021). Reason: Large-scale interactome study. Generic protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from multimodal cell maps study (2024). High-throughput study mapping structural and functional genomics. Reason: Large-scale high-throughput study. Generic protein binding is uninformative for ATP5F1B.
GO:0005515 protein binding	IPI PMID:40355756 The solute carrier superfamily interactome.	MARK AS OVER ANNOTATED	Summary: IPI protein binding from solute carrier superfamily interactome study (2024). Reason: Focused interactome study for SLC superfamily. Generic protein binding is uninformative for ATP5F1B, which is not a solute carrier.
GO:0005739 mitochondrion	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for CC based on Ensembl Compara ortholog transfer. Mitochondrial localization is well established for ATP5F1B. Reason: Correct. ATP5F1B is a mitochondrial protein with a mitochondrial transit peptide (residues 1-47, UniProt). Localization to mitochondria is confirmed by multiple experimental methods.
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: IDA annotation for CC based on curation of immunofluorescence data. Mitochondrial localization confirmed by immunofluorescence. Reason: Correct. Direct experimental evidence for mitochondrial localization via immunofluorescence.
GO:0005743 mitochondrial inner membrane	NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep...	ACCEPT	Summary: NAS annotation for CC citing the assembly study of human mitochondrial ATP synthase (Fujikawa et al. 2015). The study demonstrates that ATP5F1B assembles into the F1-c-ring intermediate at the inner mitochondrial membrane. Reason: Correct. The beta subunit is part of the F1 head which is attached to the inner mitochondrial membrane via the central stalk connected to the Fo sector. This is well-established from the assembly pathway described in this study. Supporting Evidence: PMID:26297831 When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring)
GO:0015986 proton motive force-driven ATP synthesis	NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep...	ACCEPT	Summary: NAS annotation for BP citing the assembly study. The study addresses assembly of the ATP synthase rather than directly demonstrating the proton motive force-driven ATP synthesis activity, but the function is well established. Reason: While the cited study focuses on assembly, proton motive force-driven ATP synthesis is the core function of the complex that ATP5F1B assembles into. Well supported by other references.
GO:0045259 proton-transporting ATP synthase complex	NAS PMID:2870059 Human F1-ATPase: molecular cloning of cDNA for the beta subu...	ACCEPT	Summary: NAS annotation for CC citing the original cDNA cloning of the human F1-ATPase beta subunit (Ohta & Kagawa 1986). This foundational paper established the identity of ATP5F1B. Reason: Correct. The original cloning paper established that this gene encodes the beta subunit of human F1-ATPase, which is part of the proton-transporting ATP synthase complex. Supporting Evidence: PMID:2870059 F1-ATPase is the major enzyme for ATP synthesis, and its beta subunit is the catalytic site
GO:0015986 proton motive force-driven ATP synthesis	IDA PMID:37244256 Structure of the human ATP synthase.	ACCEPT	Summary: IDA annotation for BP from the cryo-EM structure of human ATP synthase (Lai et al. 2023). The study resolved multiple rotational states demonstrating the proton motive force-driven ATP synthesis mechanism. Reason: Correct. The structural study directly visualizes the rotary mechanism of ATP synthesis in the human enzyme. Represents core function. Supporting Evidence: PMID:37244256 Biological energy currency ATP is produced by F1Fo-ATP synthase
GO:0015986 proton motive force-driven ATP synthesis	IDA PMID:25168243 Cofactor Strap regulates oxidative phosphorylation and mitoc...	ACCEPT	Summary: IDA annotation for BP from the Strap/TTC5 study (Maniam et al. 2015). The study showed that Strap interaction with ATP synthase downregulates mitochondrial ATP production, demonstrating that ATP5F1B is involved in ATP synthesis. Reason: Correct. The study demonstrated that interaction with Strap downregulated ATP synthase activity, confirming the role of ATP5F1B in ATP synthesis. The fact that inhibiting ATP synthase reduces ATP production directly demonstrates the BP. Supporting Evidence: PMID:25168243 the interaction between Strap and ATP synthase downregulates mitochondrial ATP production
GO:0015986 proton motive force-driven ATP synthesis	IDA PMID:36239646 Congenital Hypermetabolism and Uncoupled Oxidative Phosphory...	ACCEPT	Summary: IDA annotation for BP from the congenital hypermetabolism study (Ganetzky et al. 2022, NEJM). The L335P variant in ATP5F1B uncouples proton motive force from ATP synthesis, demonstrating the role of the beta subunit in coupling. Reason: Strong direct evidence. The study engineered the L335P variant and demonstrated uncoupling of the proton motive force from ATP synthesis, directly implicating ATP5F1B in this process. Supporting Evidence: PMID:36239646 Oxygen consumption and membrane potential studies in both patient fibroblasts and cells with genetic introduction of the Leu335 variant show loosened coupling between the proton motive force (generated by mitochondrial respiration) and ATP synthesis due to intrinsic dysfunction of Complex V
GO:0045259 proton-transporting ATP synthase complex	IDA PMID:37244256 Structure of the human ATP synthase.	ACCEPT	Summary: IDA annotation for CC from the cryo-EM structure of human ATP synthase. The study directly resolved ATP5F1B as part of the intact complex. Reason: Direct structural evidence. The cryo-EM structure (PDB: 8H9E and others) shows ATP5F1B as chains D/E/F in the intact human ATP synthase complex. Supporting Evidence: PMID:37244256 Structure of the human ATP synthase
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IDA PMID:25168243 Cofactor Strap regulates oxidative phosphorylation and mitoc...	ACCEPT	Summary: IDA annotation for MF from the Strap study. The study demonstrated that ATP5F1B has ATP synthase activity that is modulated by Strap binding. Reason: Supported. The study demonstrated functional ATP synthase activity involving the beta subunit. While the study focused on Strap regulation, it confirmed the catalytic activity of the complex containing ATP5F1B. Supporting Evidence: PMID:25168243 the interaction between Strap and ATP synthase downregulates mitochondrial ATP production
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IDA PMID:36239646 Congenital Hypermetabolism and Uncoupled Oxidative Phosphory...	ACCEPT	Summary: IDA annotation for MF from the NEJM uncoupling study. The study showed that the L335P variant disrupts coupling, demonstrating the role of the beta subunit in the rotational mechanism. Reason: Strong evidence. The uncoupling phenotype of L335P, which lies near the hydrophobic sleeve that contacts the rotating gamma subunit, directly demonstrates the beta subunit's role in the rotational ATP synthase mechanism. Supporting Evidence: PMID:36239646 Leu335 lies close to the hydrophobic sleeve in the α3β3 assembly that holds the tip of the γ subunit of the central stalk
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: HTP annotation for CC from the quantitative high-confidence human mitochondrial proteome study (Morgenstern et al. 2021, Cell Metabolism). ATP5F1B was identified with high confidence as part of the mitochondrial proteome. Reason: Correct. This high-quality mitochondrial proteomics study provides strong quantitative evidence for mitochondrial localization. ATP5F1B is one of the most abundant mitochondrial proteins.
GO:0005739 mitochondrion	IC PMID:12110673 A functionally active human F1F0 ATPase can be purified by i...	ACCEPT	Summary: IC (inferred by curator) annotation for CC based on the immunocapture study of human F1F0 ATPase from heart tissue and fibroblasts (Aggeler et al. 2002). The study purified functionally active F1Fo from mitochondria. Reason: Correct. The study isolated F1Fo-ATPase from mitochondria using immunocapture, confirming the mitochondrial localization of the complex and its subunits including beta. Supporting Evidence: PMID:12110673 Human mitochondrial F(1)F(0) ATP synthase was isolated with a one-step immunological approach, using a monoclonal antibody against F(1) in a 96-well microplate activity assay system
GO:0045259 proton-transporting ATP synthase complex	IDA PMID:12110673 A functionally active human F1F0 ATPase can be purified by i...	ACCEPT	Summary: IDA annotation for CC from the immunocapture study. ATP5F1B (beta subunit) was identified as part of the purified F1Fo complex. Reason: Direct experimental evidence. The beta subunit was identified by specific antibodies in the immunocaptured F1Fo complex. Supporting Evidence: PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1))
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IDA PMID:12110673 A functionally active human F1F0 ATPase can be purified by i...	ACCEPT	Summary: IDA annotation for MF with contributes_to qualifier from the immunocapture study. The purified complex displayed ATP hydrolysis activity that was oligomycin-sensitive, confirming functional ATP synthase activity. Reason: Direct functional evidence. The immunocaptured complex showed ATP hydrolysis activity that was sensitive to oligomycin (an ATP synthase inhibitor) and IF1, confirming that the complex containing the beta subunit has proton-transporting ATP synthase activity. The contributes_to qualifier is appropriate. Supporting Evidence: PMID:12110673 The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-1592247	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "Expression of ATP5B". The F1 head containing the beta subunit faces the mitochondrial matrix. Reason: Correct. UniProt confirms the beta subunit is on the matrix side of the inner mitochondrial membrane. The F1 catalytic head protrudes into the matrix.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-164832	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "ATPase synthesizes ATP". Correct localization for ATP synthesis at the matrix side. Reason: Correct. ATP synthesis occurs in the matrix, where the F1 head containing ATP5F1B catalyzes ADP + Pi to ATP.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-164834	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "Enzyme-bound ATP is released". Reason: Correct. ATP release from the beta subunit occurs in the matrix.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-164840	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "ADP and Pi bind to ATPase". Reason: Correct. ADP and Pi bind to the catalytic site of the beta subunit on the matrix side.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-8949580	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "F1Fo ATP synthase dimerizes". The beta subunit is part of the complex that dimerizes. Reason: Correct. ATP synthase dimerization involves the F1 head containing the beta subunit on the matrix side.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838035	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "CLPXP binds mitochondrial matrix proteins". ATP5F1B is a substrate for the CLPXP protease quality control system. Reason: Correct. The beta subunit resides in the matrix and is subject to mitochondrial quality control by CLPXP protease.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838081	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "LONP1 degrades mitochondrial matrix proteins". Reason: Correct. The beta subunit in the matrix is subject to LONP1 protease quality control.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838093	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "LONP1 binds mitochondrial matrix proteins". Reason: Correct. Same as above, localization to matrix confirmed.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838289	ACCEPT	Summary: TAS annotation for CC from Reactome pathway "CLPXP degrades mitochondrial matrix proteins". Reason: Correct. Redundant with other Reactome matrix annotations. Matrix localization is well established.
GO:0006754 ATP biosynthetic process	IMP PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	KEEP AS NON CORE	Summary: IMP annotation for BP from the thymosin beta-4/purinergic signaling study (Freeman et al. 2011). The study demonstrated that blocking cell surface ATP synthase with oligomycin or antibodies inhibited extracellular ATP generation, confirming the biosynthetic function. Reason: This annotation relates to ATP biosynthesis at the cell surface (ecto-ATP synthase), not the core mitochondrial function. The study showed extracellular ATP generation by cell surface ATP synthase, which is a real but non-core function. The mutant phenotype was measured for cell surface ATP production by endothelial cells. Supporting Evidence: PMID:21106936 Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM; piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP synthase inhibited the Tβ4-induced increase in cell surface ATP levels
GO:0043536 positive regulation of blood vessel endothelial cell migration	IGI PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	KEEP AS NON CORE	Summary: IGI annotation for BP from the thymosin beta-4 study. The study showed that ATP synthase on endothelial cell surfaces mediates thymosin beta-4-induced endothelial cell migration. Blocking ATP synthase with antibodies or antagonists inhibited this migration. Reason: This is a non-core function related to the ecto-ATP synthase role on endothelial cell surfaces. The study demonstrates that cell surface ATP synthase contributes to angiogenesis-related endothelial migration via purinergic signaling, but this is not the primary evolved function of ATP5F1B. Supporting Evidence: PMID:21106936 Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM; piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP synthase inhibited the Tβ4-induced increase in cell surface ATP levels, as measured by luciferase assay, and the Tβ4-induced increase in HUVEC migration
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IMP PMID:36239646 Congenital Hypermetabolism and Uncoupled Oxidative Phosphory...	ACCEPT	Summary: IMP annotation for MF from the NEJM uncoupling study. The L335P variant in ATP5F1B disrupted ATP synthase coupling, demonstrating the beta subunit's role in the rotational mechanism via mutant phenotype analysis. Reason: Strong direct evidence from mutant phenotype. The L335P variant near the hydrophobic sleeve that contacts the rotating gamma subunit caused uncoupled ATP synthase activity, demonstrating the beta subunit's essential role in the rotational mechanism. Supporting Evidence: PMID:36239646 we propose that Leu335Pro is a group 1 mutation, because it probably impairs engagement of the γ subunit by the α–β hexamer by disrupting contact between the β and γ subunits. It thereby disrupts ATP synthesis, even with normal translocation of protons through FO
GO:0005515 protein binding	IPI PMID:25168243 Cofactor Strap regulates oxidative phosphorylation and mitoc...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from the Strap/TTC5 study. The study demonstrated a specific interaction between TTC5/Strap and ATP synthase (beta subunit) that downregulates ATP production. Reason: While this is a well-characterized interaction with functional consequences (Strap binding downregulates ATP production), the generic "protein binding" term is uninformative. The interaction is better captured by other annotations in this set. UniProt documents this as "Interacts with TTC5/STRAP; the interaction results in decreased mitochondrial ATP production." Supporting Evidence: PMID:25168243 one of its key interaction partners is ATP synthase. Significantly, the interaction between Strap and ATP synthase downregulates mitochondrial ATP production
GO:0005739 mitochondrion	IDA PMID:25168243 Cofactor Strap regulates oxidative phosphorylation and mitoc...	ACCEPT	Summary: IDA annotation for CC from the Strap study. The study confirmed mitochondrial localization of ATP5F1B through co-localization studies. Reason: Correct. The study demonstrated mitochondrial localization through interaction studies and subcellular fractionation. Supporting Evidence: PMID:25168243 Strap is localised at mitochondria where one of its key interaction partners is ATP synthase
GO:0005515 protein binding	IPI PMID:32243843 Mitoregulin Controls β-Oxidation in Human and Mouse Adipocyt...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from the Mitoregulin study (Friesen et al. 2020). The study showed that Mitoregulin (MTLN) interacts with ATP5F1B. UniProt confirms "Interacts with MTLN". Reason: While the MTLN interaction is documented, the generic "protein binding" term is uninformative. The interaction with Mitoregulin may regulate beta-oxidation but this is not a core function of ATP5F1B.
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	IDA PMID:12110673 A functionally active human F1F0 ATPase can be purified by i...	ACCEPT	Summary: IDA annotation for BP from the immunocapture study. The purified human F1Fo displayed functional ATP hydrolysis activity (reverse of synthesis), confirming the complex's role in mitochondrial ATP synthesis. Reason: Direct functional evidence. The immunocaptured complex from human heart mitochondria showed oligomycin-sensitive ATP hydrolysis activity, confirming the functional involvement of ATP5F1B in the ATP synthesis/hydrolysis cycle. Supporting Evidence: PMID:12110673 The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive
GO:0001649 osteoblast differentiation	HDA PMID:16210410 Differential expression profiling of membrane proteins by qu...	MARK AS OVER ANNOTATED	Summary: HDA annotation for BP from a quantitative proteomics study of membrane proteins during osteoblast differentiation of human mesenchymal stem cells (Foster et al. 2005). ATP5F1B was identified as differentially expressed during this process. Reason: This annotation appears to be based on differential protein expression during osteoblast differentiation, not direct involvement in the differentiation process. ATP5F1B expression changes likely reflect altered metabolic demands during differentiation rather than a specific role in osteoblast biology. Supporting Evidence: PMID:16210410 We identified 463 unique proteins with extremely high confidence
GO:0016020 membrane	HDA PMID:16210410 Differential expression profiling of membrane proteins by qu...	ACCEPT	Summary: HDA annotation for CC from the same osteoblast differentiation proteomics study. ATP5F1B was detected in the membrane fraction. Reason: Correct but very broad. ATP5F1B is associated with the mitochondrial inner membrane. Detection in a membrane fraction is consistent with this.
GO:0045259 proton-transporting ATP synthase complex	IDA PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	ACCEPT	Summary: IDA annotation for CC from the thymosin beta-4 study. The study identified F1-F0 ATP synthase on the endothelial cell surface using pulldown and mass spectrometry. Reason: Correct. The study demonstrated the presence of ATP synthase complex on endothelial cell surfaces, consistent with the ecto-ATP synthase literature. Supporting Evidence: PMID:21106936 we identified F1-F0 ATP synthase, a known target of antiangiogenic angiostatin. By surface plasmon resonance, we determined for Tβ4 binding to the β subunit of ATP synthase a K(D) of 12 nM
GO:0046933 proton-transporting ATP synthase activity, rotational mechanism	IMP PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	KEEP AS NON CORE	Summary: IMP annotation for MF from the thymosin beta-4 study. The study showed that ATP synthase inhibitors (oligomycin, piceatannol, angiostatin) blocked cell surface ATP generation, demonstrating functional ATP synthase activity on the cell surface. Reason: This demonstrates functional ATP synthase activity on the cell surface (ecto-ATP synthase), which is a real but non-core function. The MF annotation is correct but relates to the non-canonical cell surface localization. Supporting Evidence: PMID:21106936 Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM; piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP synthase inhibited the Tβ4-induced increase in cell surface ATP levels
GO:0005515 protein binding	IPI PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	MARK AS OVER ANNOTATED	Summary: IPI protein binding from the thymosin beta-4 study. The study identified ATP5F1B as an interactor of thymosin beta-4 with high affinity (Kd = 12 nM). Reason: While the thymosin beta-4 interaction is well-characterized (Kd = 12 nM by SPR), the generic "protein binding" term is uninformative. The angiostatin binding annotation (GO:0043532) from the same study is more informative. Supporting Evidence: PMID:21106936 we determined for Tβ4 binding to the β subunit of ATP synthase a K(D) of 12 nM
GO:0016020 membrane	IDA PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	ACCEPT	Summary: IDA annotation for CC from the thymosin beta-4 study. ATP5F1B detected in membrane fraction of endothelial cells. Reason: Correct but very broad. ATP5F1B is associated with membranes both as part of the mitochondrial inner membrane complex and as ecto-ATP synthase on the cell surface.
GO:0043532 angiostatin binding	IPI PMID:21106936 Regenerative protein thymosin beta-4 is a novel regulator of...	KEEP AS NON CORE	Summary: IPI annotation for MF from the thymosin beta-4 study. The study showed that angiostatin binds to and inhibits cell surface ATP synthase, and used angiostatin as an antagonist (IC50 ~2.9 ug/ml). Reason: Angiostatin binding to the beta subunit of cell surface ATP synthase is well documented in the ecto-ATP synthase literature (PMID:17510399, PMID:21106936). This is a real binding activity but relates to the non-canonical cell surface function rather than the core mitochondrial role. Supporting Evidence: PMID:21106936 Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM; piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP synthase inhibited the Tβ4-induced increase in cell surface ATP levels
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: HDA annotation for CC from proteomic analysis of exosomes from expressed prostatic secretions in urine. Reason: Detection of ATP5F1B in extracellular exosomes is consistent with the known presence of mitochondrial proteins in exosomes. This is a non-core localization. ATP5F1B is one of the most abundant mitochondrial proteins, and abundant proteins are commonly detected in exosome proteomics.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: HDA annotation for CC from NK cell membrane proteome study. ATP5F1B detected in the membrane proteome of NK cells. Reason: Correct but broad. Detection in membrane fractions is consistent with the mitochondrial inner membrane association and/or cell surface ecto-ATP synthase presence. NK cells are known to have cell surface ATP synthase which is involved in immune cytotoxicity (PMID:8006588).
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: HDA annotation for CC from proteomic characterization of the human sperm nucleus. ATP5F1B detected in the sperm nuclear fraction. Reason: Detection of ATP5F1B in sperm nuclear fractions is likely a contamination artifact from the abundant mitochondrial sheath surrounding the sperm nucleus. Mitochondrial proteins are common contaminants in nuclear preparations, especially from sperm where mitochondria are densely packed around the flagellum adjacent to the nucleus. There is no evidence for a functional role of ATP5F1B in the nucleus.
GO:0005739 mitochondrion	HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated...	ACCEPT	Summary: HDA annotation for CC from phosphoproteome analysis of functional mitochondria from resting human muscle. ATP5F1B identified as a phosphorylated mitochondrial protein. Reason: Correct. Detection in isolated functional mitochondria from human muscle tissue provides strong evidence for mitochondrial localization. The phosphorylation data is consistent with UniProt PTM annotations (Ser-415, Ser-529 phosphorylation).
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	KEEP AS NON CORE	Summary: HDA annotation for CC from proteomic analysis of human parotid gland exosomes. Reason: Detection in parotid gland exosomes. Non-core localization, likely reflecting abundance of the protein.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: HDA annotation for CC from large-scale proteomics of urinary exosomes. Reason: Non-core localization. Detection in urinary exosomes likely reflects protein abundance.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: HDA annotation for CC from MHC class II-associated proteins in B-cell exosomes study. Reason: Non-core localization. Detection in B-cell exosomes.
GO:0042645 mitochondrial nucleoid	IDA PMID:18063578 The layered structure of human mitochondrial DNA nucleoids.	KEEP AS NON CORE	Summary: IDA annotation for CC from the study on layered structure of human mitochondrial DNA nucleoids (Bogenhagen et al. 2008). ATP5F1B was identified in native nucleoid preparations but was characterized as a peripheral rather than core nucleoid component. Reason: The study identified ATP5F1B in nucleoid preparations but noted that metabolic proteins and chaperones in native nucleoids may represent peripheral associations rather than core components. The authors describe a layered nucleoid structure where "translation and complex assembly may occur in the peripheral region." ATP5F1B association with nucleoids likely reflects proximity during complex assembly rather than a direct role in mtDNA maintenance. Supporting Evidence: PMID:18063578 Several other metabolic proteins and chaperones identified in native nucleoids
GO:0001525 angiogenesis	IMP PMID:17510399 Angiostatin-like activity of a monoclonal antibody to the ca...	KEEP AS NON CORE	Summary: IMP annotation for BP from the angiostatin-like activity study (Chi et al. 2007). The study showed that a monoclonal antibody against ATP5F1B inhibited tube formation and ATP generation by cell surface ATP synthase, demonstrating a role in angiogenesis. Reason: This relates to the ecto-ATP synthase function on endothelial cell surfaces. Blocking cell surface ATP synthase inhibits tube formation (a hallmark of angiogenesis). This is a real but non-core function of ATP5F1B. Supporting Evidence: PMID:17510399 MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial cells exposed to low extracellular pH
GO:0006754 ATP biosynthetic process	IMP PMID:17510399 Angiostatin-like activity of a monoclonal antibody to the ca...	KEEP AS NON CORE	Summary: IMP annotation for BP from the angiostatin-like activity study. The study demonstrated that blocking cell surface ATP synthase with antibodies inhibited ATP generation. Reason: This relates to extracellular ATP generation by cell surface ATP synthase rather than mitochondrial ATP synthesis. Real but non-core function. Supporting Evidence: PMID:17510399 Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on the endothelial cell surface in acidic conditions, the typical tumor microenvironment where cell surface ATP synthase exhibits greater activity
GO:0009986 cell surface	IDA PMID:17510399 Angiostatin-like activity of a monoclonal antibody to the ca...	KEEP AS NON CORE	Summary: IDA annotation for CC. The study demonstrated cell surface localization of ATP5F1B on endothelial cells using antibody binding and functional assays. Reason: Cell surface localization of ATP5F1B is well documented in the ecto-ATP synthase literature. This is a real but non-canonical localization, distinct from the primary mitochondrial localization. Supporting Evidence: PMID:17510399 The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial cell surface
GO:0042288 MHC class I protein binding	IDA PMID:17643490 Ecto-F1-ATPase and MHC-class I close association on cell mem...	KEEP AS NON CORE	Summary: IDA annotation for MF from the ecto-F1-ATPase and MHC-class I study (Vantourout et al. 2008). The study demonstrated close association and co-immunoprecipitation of ecto-F1-ATPase beta chain with MHC class I molecules on cell membranes. Reason: This is a well-documented interaction at the cell surface where ecto-F1-ATPase associates with MHC class I molecules. The interaction is relevant to gammadelta T cell recognition and immune function, but this is a non-core function of ATP5F1B. Supporting Evidence: PMID:17643490 biotinylated F1-ATPase cell surface components co-immunoprecipitate with MHC-I molecules confirming the association of both complexes on Raji cells. Confocal microscopy analysis of MHC-I and ecto-F1-ATPase beta chain expression on HepG2 cells shows a co-localization of both complexes in punctate membrane domains
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IMP PMID:17510399 Angiostatin-like activity of a monoclonal antibody to the ca...	KEEP AS NON CORE	Summary: IMP annotation for MF. Note this is the ATPase (hydrolysis) direction, not synthase. The study demonstrated that cell surface ATP synthase also has ATPase (hydrolytic) activity that was inhibited by the anti-beta antibody. Reason: This annotation for ATPase activity (hydrolysis direction) on the cell surface is supported by the study. The cell surface enzyme can work in both directions. Non-core as it relates to ecto-ATP synthase. Supporting Evidence: PMID:17510399 MAb3D5AB1 inhibits the hydrolytic activity of F(1) ATP synthase at lower concentrations than angiostatin
GO:0051453 regulation of intracellular pH	IMP PMID:17510399 Angiostatin-like activity of a monoclonal antibody to the ca...	KEEP AS NON CORE	Summary: IMP annotation for BP. The study showed that blocking cell surface ATP synthase with antibodies decreased intracellular pH in endothelial cells at low extracellular pH. Reason: This is a downstream consequence of ecto-ATP synthase activity on pH regulation. Non-core pleiotropic effect of the cell surface function. Supporting Evidence: PMID:17510399 MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial cells exposed to low extracellular pH
GO:1902600 proton transmembrane transport	IMP PMID:17510399 Angiostatin-like activity of a monoclonal antibody to the ca...	KEEP AS NON CORE	Summary: IMP annotation for BP from the cell surface ATP synthase study. Proton transport activity of the cell surface ATP synthase. Reason: This relates to proton transport by cell surface ATP synthase. While proton transport is a core function in the mitochondrial context, here it refers to the ecto-enzyme. The IEA annotation for the same term covers the general case.
GO:0005739 mitochondrion	IDA PMID:2870059 Human F1-ATPase: molecular cloning of cDNA for the beta subu...	ACCEPT	Summary: IDA annotation for CC from the original cDNA cloning study (Ohta & Kagawa 1986). The study established that the protein has a mitochondrial transit peptide and localizes to mitochondria. Reason: Correct. The founding study established that the beta subunit is a mitochondrial protein with a presequence (transit peptide) for mitochondrial import. Supporting Evidence: PMID:2870059 The open reading frame started from a putative signal presequence, which was rich in both serine and arginine
GO:0005759 mitochondrial matrix	NAS PMID:2687158 The human ATP synthase beta subunit gene: sequence analysis,...	ACCEPT	Summary: NAS annotation for CC from the gene sequence/expression study (Neckelmann et al. 1989). The study described the gene encoding the beta subunit which is imported to the mitochondrial matrix. Reason: Correct. The beta subunit resides on the matrix side of the inner mitochondrial membrane as part of the F1 head. Supporting Evidence: PMID:2687158 the functional F0F1-ATP synthase beta subunit gene is located on chromosome 12
GO:0005886 plasma membrane	IDA PMID:10077593 Angiostatin binds ATP synthase on the surface of human endot...	UNDECIDED	Summary: IDA annotation for CC. Publication not cached (PMID:10077593). Based on the title and context, this likely documents the ecto-ATP synthase on the plasma membrane. Reason: Cannot fully assess without the publication. However, plasma membrane localization of ATP5F1B is well supported by the ecto-ATP synthase literature (PMID:8006588, PMID:17510399). If confirmed, this would be a non-core localization.
GO:0006091 generation of precursor metabolites and energy	NAS PMID:2870059 Human F1-ATPase: molecular cloning of cDNA for the beta subu...	ACCEPT	Summary: NAS annotation for BP from the original cDNA cloning study. Generation of precursor metabolites and energy is the broad process encompassing oxidative phosphorylation. Reason: Correct but very broad. ATP synthesis by the F1Fo-ATP synthase is a central part of energy generation. More specific annotations are present (GO:0042776, GO:0015986). Supporting Evidence: PMID:2870059 F1-ATPase is the major enzyme for ATP synthesis
GO:0031966 mitochondrial membrane	IDA PMID:8006588 A novel ligand in lymphocyte-mediated cytotoxicity: expressi...	ACCEPT	Summary: IDA annotation for CC from the study demonstrating beta subunit expression on tumor cell surfaces (Das et al. 1994). While the study focused on cell surface expression, the protein was identified as having "structural and immunologic characteristics of the beta subunit of H+ transporting ATP synthase" from mitochondria. Reason: Correct. ATP5F1B is associated with the mitochondrial inner membrane as part of the ATP synthase complex. The study confirmed the identity of the cell surface protein as the mitochondrial beta subunit. Supporting Evidence: PMID:8006588 A 51.5-kD protein (p51.5) bearing structural and immunologic characteristics of the beta subunit of H+ transporting ATP synthase
GO:0005515 protein binding	IPI PMID:10077593 Angiostatin binds ATP synthase on the surface of human endot...	UNDECIDED	Summary: IPI protein binding annotation. Publication not cached (PMID:10077593). Reason: Cannot assess without access to the publication. Generic protein binding is uninformative.

Core Functions

ATP5F1B is the catalytic beta subunit of the F1 head of the mitochondrial ATP synthase (Complex V). It contains the active site where ADP + Pi is converted to ATP via the binding change mechanism driven by rotation of the gamma subunit. The beta subunit binds ATP/ADP at its catalytic nucleotide-binding site (residues 209-214, 238-239) with Mg2+ as a required cofactor. It contributes_to the complex-level proton-transporting ATP synthase activity (GO:0046933) of the rotational mechanism. Three beta subunits alternate with three alpha subunits to form the alpha3-beta3 hexameric F1 catalytic head on the matrix side of the inner mitochondrial membrane. Structural evidence from cryo-EM at 2.53 A resolution (PMID:37244256) and functional evidence from the L335P uncoupling variant (PMID:36239646) confirm the catalytic role.

Molecular Function:

ATP binding

Directly Involved In:

proton motive force-driven mitochondrial ATP synthesis

Cellular Locations:

mitochondrial matrix

In Complex:

proton-transporting ATP synthase complex

Supporting Evidence:

PMID:37244256
These structures reveal that the release of ADP occurs when the β subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis
PMID:36239646
The catalytic core of F1 contains three α and three β subunits arranged around a γ subunit of the central stalk. Protons passing through FO (the pore) cause the γ stalk to rotate, inducing conformational transitions in the β subunit that are required for the synthesis of ATP from ADP
PMID:12110673
The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10077593

Angiostatin binds ATP synthase on the surface of human endothelial cells.

PMID:11410595

Atp11p and Atp12p are assembly factors for the F(1)-ATPase in human mitochondria.

PMID:12110673

A functionally active human F1F0 ATPase can be purified by immunocapture from heart tissue and fibroblast cell lines. Subunit structure and activity studies.

Human F1Fo ATP synthase was purified from heart tissue and fibroblasts by immunocapture and shown to be functionally active with oligomycin-sensitive ATP hydrolysis activity.

"The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive"

PMID:15161933

Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.

PMID:16210410

Differential expression profiling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation.

PMID:17510399

Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.

Cell surface ATP synthase on endothelial cells generates ATP and is inhibited by angiostatin and anti-beta antibodies, with effects on angiogenesis and intracellular pH.

"Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on the endothelial cell surface in acidic conditions, the typical tumor microenvironment where cell surface ATP synthase exhibits greater activity"

PMID:17643490

Ecto-F1-ATPase and MHC-class I close association on cell membranes.

Ecto-F1-ATPase beta chain co-localizes and co-immunoprecipitates with MHC class I molecules on cell surfaces, with expression inversely correlated with MHC-I levels.

"biotinylated F1-ATPase cell surface components co-immunoprecipitate with MHC-I molecules confirming the association of both complexes on Raji cells"

PMID:18063578

The layered structure of human mitochondrial DNA nucleoids.

ATP5F1B was identified in native nucleoid preparations as a peripheral component, not a core nucleoid protein.

"Several other metabolic proteins and chaperones identified in native nucleoids"

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:19199708

Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:20458337

MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

PMID:20618440

Proteomic and biochemical analysis of 14-3-3-binding proteins during C2-ceramide-induced apoptosis.

PMID:20833797

Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes.

PMID:21106936

Regenerative protein thymosin beta-4 is a novel regulator of purinergic signaling.

Thymosin beta-4 binds to the beta subunit of cell surface ATP synthase (Kd = 12 nM) and stimulates extracellular ATP production and endothelial cell migration via purinergic signaling.

"we determined for Tβ4 binding to the β subunit of ATP synthase a K(D) of 12 nM"

PMID:21630459

Proteomic characterization of the human sperm nucleus.

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.

PMID:25168243

Cofactor Strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase.

Strap/TTC5 interacts with ATP synthase (beta subunit) at mitochondria and downregulates ATP production, sensitizing cells to apoptosis under glucose limitation.

"the interaction between Strap and ATP synthase downregulates mitochondrial ATP production"

PMID:26297831

Assembly of human mitochondrial ATP synthase through two separate intermediates, F1-c-ring and b-e-g complex.

Human mitochondrial ATP synthase assembles through two separate intermediates: the F1-c-ring (containing the beta subunit) and the b-e-g stator complex.

"human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring)"

PMID:2687158

The human ATP synthase beta subunit gene: sequence analysis, chromosome assignment, and differential expression.

The human ATP5F1B gene is on chromosome 12, has 10 exons encoding a 49-aa leader peptide and 480-aa mature protein, with tissue-specific expression highest in heart.

"the functional F0F1-ATP synthase beta subunit gene is located on chromosome 12"

PMID:27499296

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:2870059

Human F1-ATPase: molecular cloning of cDNA for the beta subunit.

First full-length cDNA cloning of the human F1-ATPase beta subunit, establishing it as the catalytic site of ATP synthesis with high homology to beef heart (97.5%) and E. coli (71.7%) beta subunits.

"F1-ATPase is the major enzyme for ATP synthesis, and its beta subunit is the catalytic site"

PMID:29892012

An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.

PMID:30021884

Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:32243843

Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes.

Mitoregulin (MTLN) interacts with ATP5F1B, linking mitochondrial beta-oxidation regulation to ATP synthase.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34800366

Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.

PMID:36239646

Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.

The L335P variant in ATP5F1B causes dominant mitochondrial uncoupling, loosening the coupling between proton motive force and ATP synthesis, resulting in hypermetabolism.

"a de novo heterozygous variant in ATP5F1B, which encodes the β subunit of mitochondrial ATP synthase"

PMID:37244256

Structure of the human ATP synthase.

Cryo-EM structures of human ATP synthase at 2.53 A resolution reveal three rotational states, showing ADP release from the beta subunit in the open conformation and water molecules in the proton half-channels.

"These structures reveal that the release of ADP occurs when the β subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis"

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:40355756

The solute carrier superfamily interactome.

PMID:8006588

A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines.

The beta subunit of ATP synthase is expressed on the plasma membrane of tumor cells and functions as a ligand in NK cell and LAK cell-mediated cytotoxicity.

"A 51.5-kD protein (p51.5) bearing structural and immunologic characteristics of the beta subunit of H+ transporting ATP synthase"

Reactome:R-HSA-1592247

Expression of ATP5B

Reactome:R-HSA-164832

ATPase synthesizes ATP

Reactome:R-HSA-164834

Enzyme-bound ATP is released

Reactome:R-HSA-164840

ADP and Pi bind to ATPase

Reactome:R-HSA-8949580

F1Fo ATP synthase dimerizes

Reactome:R-HSA-9838035

CLPXP binds mitochondrial matrix proteins

Reactome:R-HSA-9838081

LONP1 degrades mitochondrial matrix proteins

Reactome:R-HSA-9838093

LONP1 binds mitochondrial matrix proteins

Reactome:R-HSA-9838289

CLPXP degrades mitochondrial matrix proteins

Deep Research

Falcon

(ATP5F1B-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 15 citations 2026-02-11T07:57:57.791805

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and verification
We verified the target identity: ATP5F1B (HGNC:830; UniProt P06576) encodes the mitochondrial F1-ATP synthase beta subunit (also known as ATP5B), a nuclear-encoded component of Complex V in Homo sapiens. It forms part of the F1 catalytic head (α3β3) on the matrix side of the inner mitochondrial membrane; this aligns with the ATPase alpha/beta chains family and expected domains for catalytic nucleotide binding and hydrolysis/synthesis (EC 7.1.2.2) (https://doi.org/10.33549/physiolres.935407, 2024-08-01) (tauchmannova2024variabilityofclinical pages 1-3). No conflicting gene symbol usage was found in the collected 2023–2024 literature targeting different organisms.

Key concepts and definitions (current understanding)
- Molecular identity and complex architecture. F1Fo-ATP synthase (Complex V) produces the bulk of cellular ATP. Its soluble F1 head comprises an alternating α3β3 hexamer in which β (ATP5F1B) houses the catalytic nucleotide-binding sites; F1 is connected via the central stalk (γ, δ, ε) to the membrane-embedded Fo (including the c-ring and mtDNA-encoded subunits a/A6L) and braced by the peripheral stalk (b, d, F6, OSCP). The F1 head faces the mitochondrial matrix, performing ATP synthesis/hydrolysis coupled to proton motive force across the inner membrane (reviewed with structural references; https://doi.org/10.33549/physiolres.935407, 2024-08-01) (tauchmannova2024variabilityofclinical pages 1-3).
- Catalytic mechanism and states. Recent cryo-EM shows multiple rotary substates and elastic coupling between F1 and Fo, capturing conformational ensembles that underpin catalysis and chemomechanical coupling across pH conditions; these studies reaffirm β’s catalytic role in nucleotide binding/hydrolysis/synthesis (https://doi.org/10.1038/s41594-024-01219-4, 2024-02-12) (sharma2024conformationalensembleof pages 19-21).
- Dimerization/oligomerization and cristae. ATP synthase forms dimers and higher-order oligomeric rows that shape cristae membrane curvature; altered high–molecular weight bands consistent with dimer/oligomeric Complex V can be resolved by BN-PAGE in human cells (https://doi.org/10.33549/physiolres.935407, 2024-08-01; https://doi.org/10.1093/brain/awad068, 2023-03-20) (tauchmannova2024variabilityofclinical pages 1-3, nasca2023variantsinatp5f1b pages 3-5).

Recent developments and latest research (prioritizing 2023–2024)
- Conformational plasticity and coupling (2024). Yeast mitochondrial ATP synthase cryo-EM under low pH resolved unique intermediates that illuminate flexible F1–Fo coupling and rotary substate transitions, advancing mechanistic models applicable to mammalian enzymes (https://doi.org/10.1038/s41594-024-01219-4, 2024-02-12) (sharma2024conformationalensembleof pages 19-21).
- Clinical genetics of ATP5F1B (2023) and spectrum expansion (2024–2025). A Brain 2023 study identified heterozygous ATP5F1B missense variants (p.Thr334Pro; p.Val482Ala) segregating with early-onset isolated dystonia with incomplete penetrance; patient fibroblasts showed severe isolated Complex V deficiency without reductions of other respiratory complex activities, mitochondrial membrane potential defects, and BN-PAGE evidence for altered high-MW Complex V species, suggesting a dominant-negative mechanism (https://doi.org/10.1093/brain/awad068, 2023-03-20) (nasca2023variantsinatp5f1b pages 2-3, nasca2023variantsinatp5f1b pages 5-6, nasca2023variantsinatp5f1b pages 3-5). A 2024 Movement Disorders review synthesizes that ATP5F1B-related dystonia often exhibits normal oxygen consumption, whereas some alleles cause an “uncoupling” phenotype with increased oxygen consumption, reinforcing allele-dependent bioenergetic signatures (https://doi.org/10.1002/mds.29657, 2024-11-01) (indelicato2024dystoniainatp pages 4-4). A 2025 Movement Disorders cohort further reported a heterozygous ATP5F1B splice-donor variant (c.1074+1G>T) leading to exon skipping, reduced ATP5F1B mRNA, and impaired Complex V ATPase activity; the clinical spectrum broadened to include dystonia, hereditary spastic paraplegia, and cerebral palsy phenotypes (https://doi.org/10.1002/mds.30209, 2025-04-01) (harrer2025expandingtheallelic pages 1-2).
- Regulation via IF1 and targeting approaches (2024). Experimental peptide tools that displace the inhibitory factor IF1 from ATP synthase OSCP altered mitochondrial permeability transition behavior in HeLa cells, underscoring regulatory interfaces and offering proof-of-concept for therapeutic modulation of ATP synthase regulation (https://doi.org/10.3390/ijms25094655, 2024-04-30) (grandi2024peptidestargetingthe pages 16-17).

Current applications and real-world implementations
- Diagnostic and functional genomics. For suspected ATP5F1B-related movement disorders, integration of exome/genome sequencing with fibroblast functional assays (Complex V activity assays, BN-PAGE oligomer profiling, mitochondrial membrane potential, and oxygen consumption) has been deployed in clinical studies to assign pathogenicity and mechanism (dominant-negative vs. haploinsufficiency) (https://doi.org/10.1093/brain/awad068, 2023-03-20; https://doi.org/10.1002/mds.30209, 2025-04-01) (nasca2023variantsinatp5f1b pages 3-5, harrer2025expandingtheallelic pages 1-2).
- Structural informatics for inhibitor design. High-resolution conformational ensembles inform binding-site exposure and coupling strain that can guide allosteric or catalytic-site inhibitor design or peptide modulators (https://doi.org/10.1038/s41594-024-01219-4, 2024-02-12) (sharma2024conformationalensembleof pages 19-21).
- Experimental modulation of IF1–ATP synthase interface. Mitochondria-targeted peptides engaging the IF1–OSCP interaction modulate permeability transition and apoptosis resistance in tumor cells, a potential lead for anti-cancer strategies that indirectly affect Complex V regulation (https://doi.org/10.3390/ijms25094655, 2024-04-30) (grandi2024peptidestargetingthe pages 16-17).

Expert opinions and analysis from authoritative sources
- Comprehensive clinical-pathophysiology synthesis. A 2024 review emphasizes that ATP5F1A/ATP5F1B subunits occur in multiple copies within the holoenzyme; expression levels, subunit stoichiometry, and environmental stressors likely determine penetrance and phenotypic variability. Notably, in ATP5F1B dystonia, oxygen consumption may be preserved or paradoxically increased (allele-specific uncoupling), guiding expectations for functional tests (https://doi.org/10.1002/mds.29657, 2024-11-01) (indelicato2024dystoniainatp pages 4-4).
- Structural-functional consensus. Recent reviews concur that the α3β3 head (with β catalytic sites) and rotary coupling underlie ATP production, and that ATP synthase dimer/oligomer rows contribute to cristae morphology—linking molecular defects to organelle-scale architecture (https://doi.org/10.33549/physiolres.935407, 2024-08-01) (tauchmannova2024variabilityofclinical pages 1-3).

Relevant statistics and data from recent studies
- Genetics and clinical penetrance (2023). Two heterozygous ATP5F1B missense variants (c.1000A>C; c.1445T>C) segregated with early-onset isolated dystonia across two families, with incomplete penetrance noted. Variants were absent from gnomAD. Structural modeling placed substitutions near α/γ interfaces (Thr334) and at the periphery of the α3β3 hexamer (Val482), altering local contacts (https://doi.org/10.1093/brain/awad068, 2023-03-20) (nasca2023variantsinatp5f1b pages 3-5).
- Biochemical readouts (2023). In patient fibroblasts, an isolated Complex V ATPase deficiency was observed in affected individuals, with other respiratory chain complex activities within normal range; one affected father showed Complex V activity 88% of the lower control range (mild defect). BN-PAGE revealed high-MW Complex V bands consistent with dimer/supercomplex alterations; mitochondrial membrane potential imaging (JC‑1) showed localized depolarization despite preserved maximal respiratory capacity (https://doi.org/10.1093/brain/awad068, 2023-03-20) (nasca2023variantsinatp5f1b pages 5-6, nasca2023variantsinatp5f1b pages 3-5).
- Transcript/protein levels (2023). cDNA analyses showed biallelic expression of the mutant allele; immunoblots for ATP5F1B/ATP5F1A generally showed stable steady-state levels (one subject with a significant ATP5F1B change), supporting dominant-negative mechanisms over loss-of-protein scenarios in many cases (https://doi.org/10.1093/brain/awad068, 2023-03-20) (nasca2023variantsinatp5f1b pages 5-6).
- Splice variant mechanism (2025). An ATP5F1B c.1074+1G>T variant caused exon skipping with significantly reduced ATP5F1B mRNA and impaired ATPase activity in fibroblasts, indicating haploinsufficiency-like effects and expanding phenotypes to dystonia/HSP/CP (https://doi.org/10.1002/mds.30209, 2025-04-01) (harrer2025expandingtheallelic pages 1-2).

Functional roles, pathways, and localization of ATP5F1B
- Enzymatic function. ATP5F1B contributes the catalytic β subunit to the F1 head; its active sites bind ADP/ATP and participate in the rotary mechanism that couples proton translocation in Fo to ATP synthesis (or reverse hydrolysis). Conformational ensembles captured by cryo-EM support a model of elastic coupling and sequential site catalysis at β subunits (https://doi.org/10.1038/s41594-024-01219-4, 2024-02-12) (sharma2024conformationalensembleof pages 19-21).
- Pathway membership. ATP5F1B is a core subunit of OXPHOS Complex V in the mitochondrial electron transport chain, positioned at the terminal energy-converting step of oxidative phosphorylation (https://doi.org/10.33549/physiolres.935407, 2024-08-01) (tauchmannova2024variabilityofclinical pages 1-3).
- Subcellular localization. The β subunit resides in the mitochondrial matrix-facing catalytic head attached to the inner mitochondrial membrane’s Fo sector; assembly defects or altered oligomerization can impact cristae morphology and bioenergetics (https://doi.org/10.33549/physiolres.935407, 2024-08-01; https://doi.org/10.1093/brain/awad068, 2023-03-20) (tauchmannova2024variabilityofclinical pages 1-3, nasca2023variantsinatp5f1b pages 3-5).

Assembly/biogenesis and regulation
- Assembly and quality control. Biogenesis of the α3β3 head requires dedicated assembly factors (e.g., ATPAF1/2) and mitochondrial Hsp70 functions for both assembly and quality control, ensuring only properly folded subunits integrate into the holoenzyme (review) (https://doi.org/10.33549/physiolres.935407, 2024-08-01) (tauchmannova2024variabilityofclinical pages 1-3).
- Regulatory proteins. IF1 binds the F1 sector under low pH or specific conditions to inhibit ATP hydrolysis; disrupting IF1–OSCP interactions with designed peptides modulates mitochondrial permeability transition in cancer cells, indicating a druggable regulatory interface (https://doi.org/10.3390/ijms25094655, 2024-04-30) (grandi2024peptidestargetingthe pages 16-17).

Clinical implications and translational directions (2023–2024 emphasis)
- Diagnostic recommendations. Given the allele-dependent functional fingerprints, comprehensive evaluation should include: (i) molecular genetics of ATP5F1B; (ii) fibroblast Complex V enzymology; (iii) BN-PAGE for oligomerization; (iv) mitochondrial membrane potential imaging; and (v) oxygen consumption profiling to detect uncoupling vs. preserved respiration (https://doi.org/10.1093/brain/awad068, 2023-03-20; https://doi.org/10.1002/mds.29657, 2024-11-01) (nasca2023variantsinatp5f1b pages 3-5, indelicato2024dystoniainatp pages 4-4).
- Therapeutic exploration. While no ATP5F1B-specific therapy exists, regulatory targeting of IF1–ATP synthase and structure-guided modulation of catalytic/rotary interfaces are under experimental study as anti-cancer or mitochondrial modulatory approaches (https://doi.org/10.3390/ijms25094655, 2024-04-30; https://doi.org/10.1038/s41594-024-01219-4, 2024-02-12) (grandi2024peptidestargetingthe pages 16-17, sharma2024conformationalensembleof pages 19-21).

Embedded summary table of key facts and 2023–2024 highlights
| Topic | Key points (1–3 concise bullets) | Best recent sources (journal/year) | DOI/URL |
|---|---|---:|---|
| Identity / Complex membership | Nuclear-encoded beta subunit of mitochondrial ATP synthase (ATP5F1B/ATP5B); constituent of the F1 catalytic α3β3 hexamer. | Physiological Research, 2024 (Tauchmannová et al.) (tauchmannova2024variabilityofclinical pages 1-3) | https://doi.org/10.33549/physiolres.935407 |
| Catalytic role & EC number | Catalytic nucleotide-binding ADP/ATP site in F1; mediates ATP synthesis/hydrolysis coupled to proton translocation; EC 7.1.2.2. | Nature Structural & Molecular Biology, 2024 (Sharma et al.) (sharma2024conformationalensembleof pages 19-21) | https://doi.org/10.1038/s41594-024-01219-4 |
| Cellular / mitochondrial localization | Localized on the matrix-facing side of the inner mitochondrial membrane as part of Complex V (F1 head attached to Fo rotor). | Physiological Research, 2024 (Tauchmannová et al.) (tauchmannova2024variabilityofclinical pages 1-3) | https://doi.org/10.33549/physiolres.935407 |
| Structural organization & cryo-EM insights | α/β alternate in an α3β3 catalytic head linked to central (γ) and peripheral stalks; cryo-EM reveals multiple rotary substates and elastic F1–Fo coupling. | Nature Structural & Molecular Biology, 2024 (Sharma et al.) (sharma2024conformationalensembleof pages 19-21) | https://doi.org/10.1038/s41594-024-01219-4 |
| Dimerization & cristae shaping | ATP synthase forms dimers/oligomer rows that induce membrane curvature and shape cristae; oligomeric state visible as dimer/oligomer bands by BN-PAGE. | Physiological Research, 2024 (Tauchmannová et al.); Brain, 2023 (Nasca et al.) (tauchmannova2024variabilityofclinical pages 1-3, nasca2023variantsinatp5f1b pages 3-5) | https://doi.org/10.33549/physiolres.935407 |
| Assembly / biogenesis & quality control | Assembly requires chaperones/assembly factors (e.g., ATPAF1/2, TMEM70) and mtHsp70 functions; quality-control prevents defective subunit incorporation. | Physiological Research, 2024 (Tauchmannová et al.) (tauchmannova2024variabilityofclinical pages 1-3) | https://doi.org/10.33549/physiolres.935407 |
| Regulation (IF1, PTMs, signaling) | IF1 inhibits ATP hydrolysis under low-pH/stress and during assembly; PTMs and kinase signaling can modulate stability/activity; IF1-targeting peptides reported experimentally. | International Journal of Molecular Sciences, 2024 (Grandi et al.); structural refs (grandi2024peptidestargetingthe pages 16-17, sharma2024conformationalensembleof pages 19-21) | https://doi.org/10.3390/ijms25094655 |
| Ectopic / cell-surface ATP synthase | Ectopic ATP synthase (eATP synthase) reported on cancer cell surfaces and extracellular vesicles; implicated in extracellular ATP production and signaling. | International Journal of Molecular Sciences, 2024 (Grandi et al.) (grandi2024peptidestargetingthe pages 16-17) | https://doi.org/10.3390/ijms25094655 |
| Disease associations (2023–2024 highlights) | Heterozygous ATP5F1B variants linked to dominantly inherited early-onset isolated dystonia; splice and missense alleles produce dominant-negative or haploinsufficient effects; phenotypic spectrum expanding to HSP/CP. | Brain, 2023 (Nasca et al.); Movement Disorders reviews/expansions 2024–2025 (nasca2023variantsinatp5f1b pages 2-3, nasca2023variantsinatp5f1b pages 3-5, indelicato2024dystoniainatp pages 4-4, harrer2025expandingtheallelic pages 1-2) | https://doi.org/10.1093/brain/awad068 |
| Quantitative readouts (activity / O2 / BN-PAGE) | Patient fibroblasts show isolated Complex V (ATPase) activity reductions in some cases; BN-PAGE reveals altered high-MW complex V/dimer bands; O2 consumption changes are allele-dependent (normal, reduced, or uncoupled). | Brain, 2023 (Nasca et al.); Movement Disorders review 2024 (nasca2023variantsinatp5f1b pages 5-6, nasca2023variantsinatp5f1b pages 3-5, indelicato2024dystoniainatp pages 4-4) | https://doi.org/10.1093/brain/awad068 |
| Translational applications (modulators / inhibitors) | Experimental strategies include IF1-displacing peptides and small-molecule OXPHOS modulators/inhibitors; structural studies inform inhibitor binding and design. | Nature Structural & Molecular Biology, 2024 (Sharma et al.); Int J Mol Sci, 2024 (Grandi et al.) (sharma2024conformationalensembleof pages 19-21, grandi2024peptidestargetingthe pages 16-17) | https://doi.org/10.1038/s41594-024-01219-4 |

Table: A corrected, compact markdown table summarizing vetted evidence (identity, catalytic role, localization, structure, assembly, regulation, ectopic presence, 2023–2024 disease links, quantitative readouts, and translational leads) for human ATP5F1B with recent source citations (context IDs).

Conclusion
Human ATP5F1B encodes the catalytic β subunit of ATP synthase’s F1 head, executing nucleotide-binding and ATP synthesis/hydrolysis within Complex V at the mitochondrial inner membrane. Contemporary cryo-EM substantiates elastic F1–Fo coupling and multi-state rotary catalysis centered on β subunits. Clinically, 2023–2024 work establishes heterozygous ATP5F1B variants as causes of isolated dystonia (dominant-negative mechanisms) with expanding phenotypes (HSP/CP), and allele-dependent functional readouts ranging from isolated Complex V defects with preserved respiration to uncoupling-like profiles. Regulatory interfaces (IF1–OSCP) are experimentally druggable, suggesting avenues for modulating ATP synthase function in disease contexts (https://doi.org/10.1038/s41594-024-01219-4, 2024-02-12; https://doi.org/10.1093/brain/awad068, 2023-03-20; https://doi.org/10.1002/mds.29657, 2024-11-01; https://doi.org/10.3390/ijms25094655, 2024-04-30; https://doi.org/10.33549/physiolres.935407, 2024-08-01) (sharma2024conformationalensembleof pages 19-21, nasca2023variantsinatp5f1b pages 2-3, indelicato2024dystoniainatp pages 4-4, grandi2024peptidestargetingthe pages 16-17, tauchmannova2024variabilityofclinical pages 1-3).

References

(tauchmannova2024variabilityofclinical pages 1-3): K. Tauchmannová, A. Pecinová, J. Houštěk, and T. Mrázek. Variability of clinical phenotypes caused by isolated defects of mitochondrial atp synthase. Physiological Research, pages S243-S278, Aug 2024. URL: https://doi.org/10.33549/physiolres.935407, doi:10.33549/physiolres.935407. This article has 11 citations and is from a peer-reviewed journal.
(sharma2024conformationalensembleof pages 19-21): Stuti Sharma, Min Luo, Hiral Patel, David M. Mueller, and Maofu Liao. Conformational ensemble of yeast atp synthase at low ph reveals unique intermediates and plasticity in f1-fo coupling. Nature structural & molecular biology, 31:657-666, Feb 2024. URL: https://doi.org/10.1038/s41594-024-01219-4, doi:10.1038/s41594-024-01219-4. This article has 3 citations and is from a highest quality peer-reviewed journal.
(nasca2023variantsinatp5f1b pages 3-5): Alessia Nasca, Niccolò E Mencacci, Federica Invernizzi, Michael Zech, Ignacio J Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe I Bustos, Luigi M Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J Lubbe, Barbara Garavaglia, and Daniele Ghezzi. Variants in atp5f1b are associated with dominantly inherited dystonia. Brain, 146:2730-2738, Mar 2023. URL: https://doi.org/10.1093/brain/awad068, doi:10.1093/brain/awad068. This article has 18 citations and is from a highest quality peer-reviewed journal.
(nasca2023variantsinatp5f1b pages 2-3): Alessia Nasca, Niccolò E Mencacci, Federica Invernizzi, Michael Zech, Ignacio J Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe I Bustos, Luigi M Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J Lubbe, Barbara Garavaglia, and Daniele Ghezzi. Variants in atp5f1b are associated with dominantly inherited dystonia. Brain, 146:2730-2738, Mar 2023. URL: https://doi.org/10.1093/brain/awad068, doi:10.1093/brain/awad068. This article has 18 citations and is from a highest quality peer-reviewed journal.
(nasca2023variantsinatp5f1b pages 5-6): Alessia Nasca, Niccolò E Mencacci, Federica Invernizzi, Michael Zech, Ignacio J Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe I Bustos, Luigi M Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J Lubbe, Barbara Garavaglia, and Daniele Ghezzi. Variants in atp5f1b are associated with dominantly inherited dystonia. Brain, 146:2730-2738, Mar 2023. URL: https://doi.org/10.1093/brain/awad068, doi:10.1093/brain/awad068. This article has 18 citations and is from a highest quality peer-reviewed journal.
(indelicato2024dystoniainatp pages 4-4): Elisabetta Indelicato, Sylvia Boesch, Niccolo' E. Mencacci, Daniele Ghezzi, Holger Prokisch, Juliane Winkelmann, and Michael Zech. Dystonia in atp synthase defects: reconnecting mitochondria and dopamine. Movement Disorders, 39:29-35, Nov 2024. URL: https://doi.org/10.1002/mds.29657, doi:10.1002/mds.29657. This article has 6 citations and is from a highest quality peer-reviewed journal.
(harrer2025expandingtheallelic pages 1-2): Philip Harrer, Magdalena Krygier, Martin Krenn, Volker Kittke, Martin Danis, Georgi Krastev, Alice Saparov, Virginie Pichon, Marlène Malbos, Clarisse Scherer, Ivana Dzinovic, Matej Skorvanek, Robert Kopajtich, Holger Prokisch, Sara Silvaieh, Anna Grisold, Maria Mazurkiewicz‐Bełdzińska, Jean‐Madeleine de Sainte Agathe, Juliane Winkelmann, Jan Necpal, Robert Jech, and Michael Zech. Expanding the allelic and clinical heterogeneity of movement disorders linked to defects of mitochondrial adenosine triphosphate synthase. Movement Disorders, 40:1388-1400, Apr 2025. URL: https://doi.org/10.1002/mds.30209, doi:10.1002/mds.30209. This article has 3 citations and is from a highest quality peer-reviewed journal.
(grandi2024peptidestargetingthe pages 16-17): Martina Grandi, Simone Fabbian, Giancarlo Solaini, Alessandra Baracca, Massimo Bellanda, and Valentina Giorgio. Peptides targeting the if1–atp synthase complex modulate the permeability transition pore in cancer hela cells. International Journal of Molecular Sciences, 25:4655, Apr 2024. URL: https://doi.org/10.3390/ijms25094655, doi:10.3390/ijms25094655. This article has 2 citations and is from a poor quality or predatory journal.

Citations

tauchmannova2024variabilityofclinical pages 1-3
sharma2024conformationalensembleof pages 19-21
indelicato2024dystoniainatp pages 4-4
harrer2025expandingtheallelic pages 1-2
grandi2024peptidestargetingthe pages 16-17
https://doi.org/10.33549/physiolres.935407,
https://doi.org/10.1038/s41594-024-01219-4,
https://doi.org/10.1093/brain/awad068,
https://doi.org/10.1002/mds.29657,
https://doi.org/10.1002/mds.30209,
https://doi.org/10.3390/ijms25094655,
https://doi.org/10.33549/physiolres.935407
https://doi.org/10.1038/s41594-024-01219-4
https://doi.org/10.3390/ijms25094655
https://doi.org/10.1093/brain/awad068

📄 View Raw YAML

---
id: P06576
gene_symbol: ATP5F1B
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ATP5F1B encodes the catalytic beta subunit of the mitochondrial F1Fo-ATP synthase
  (Complex V).
  Three copies of the beta subunit alternate with three alpha subunits (ATP5F1A) to
  form the
  alpha3-beta3 hexameric F1 catalytic head, which faces the mitochondrial matrix.
  The beta subunit
  contains the catalytic nucleotide-binding site where ADP is phosphorylated to ATP
  via a rotary
  mechanism driven by the proton motive force across the inner mitochondrial membrane
  (PMID:37244256).
  As part of the F1Fo complex, ATP5F1B contributes to proton-transporting ATP synthase
  activity
  (EC 7.1.2.2). Pathogenic variants in ATP5F1B cause hypermetabolism due to uncoupled
  oxidative
  phosphorylation (HUMOP2, PMID:36239646) and dominantly inherited dystonia (PMID:Nasca
  et al. 2023,
  Brain). ATP5F1B is also found on the cell surface as ecto-F1-ATPase, where it functions
  in
  extracellular ATP generation, angiogenesis regulation, and immune recognition (PMID:8006588,
  PMID:17510399, PMID:17643490).
existing_annotations:
# ============================================================
# IBA ANNOTATIONS (Phylogenetic inference - generally reliable)
# ============================================================
  - term:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        IBA annotation for CC. ATP5F1B is a core structural and catalytic component
        of the
        proton-transporting ATP synthase complex (Complex V). This is well supported
        by cryo-EM
        structural data (PMID:37244256), immunocapture studies (PMID:12110673), and
        assembly studies
        (PMID:26297831).
      action: ACCEPT
      reason: >-
        This is the defining complex membership for ATP5F1B. The beta subunit is one
        of the major
        subunits of the F1 catalytic head. Cryo-EM structures show ATP5F1B as chains
        D/E/F in the
        alpha3-beta3 hexamer (PMID:37244256). IBA annotation is appropriate and well
        conserved across
        the ATPase alpha/beta chains family.
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            These structures reveal that the release of ADP occurs when the β subunit
            of F1Fo-ATP
            synthase is in the open conformation, showing how ADP binding is coordinated
            during
            synthesis
        - reference_id: PMID:12110673
          supporting_text: >-
            The immunoprecipitated F(1)F(0) contained a full complement of subunits
            that
            were
            identified with specific antibodies against five of the subunits (alpha,
            beta,
            OSCP,
            d, and IF(1))
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: contributes_to
    review:
      summary: >-
        IBA annotation for MF with contributes_to qualifier. The beta subunit contributes
        to the
        proton-transporting ATP synthase activity of the holoenzyme complex via the
        rotational
        mechanism. The contributes_to qualifier is correct because this activity is
        a property of
        the whole complex, not the individual subunit.
      action: ACCEPT
      reason: >-
        The contributes_to qualifier is appropriate for a subunit that is part of
        the
        catalytic
        core but requires the full complex for proton-transporting ATP synthase activity.
        The beta
        subunit houses the catalytic nucleotide-binding sites, but the rotational
        mechanism
        requires
        the assembled F1Fo complex including the proton channel (Fo). Well supported
        by structural
        data (PMID:37244256) and functional studies (PMID:36239646).
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            These structures reveal that the release of ADP occurs when the β subunit
            of
            F1Fo-ATP synthase is in the open conformation, showing how ADP binding
            is
            coordinated
            during synthesis
        - reference_id: PMID:36239646
          supporting_text: >-
            The catalytic core of F1 contains three α and three β subunits arranged
            around
            a γ subunit of the central stalk. Protons passing through FO (the pore)
            cause
            the
            γ stalk to rotate, inducing conformational transitions in the β subunit
            that
            are required for the synthesis of ATP from ADP
  - term:
      id: GO:0042776
      label: proton motive force-driven mitochondrial ATP synthesis
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        IBA annotation for BP. Proton motive force-driven mitochondrial ATP synthesis
        is the core
        biological process performed by ATP5F1B as part of Complex V. This is the
        more
        specific
        mitochondrial form of GO:0015986.
      action: ACCEPT
      reason: >-
        This is the most specific and accurate BP annotation for ATP5F1B. The beta
        subunit
        is the
        catalytic component that directly synthesizes ATP from ADP driven by the proton
        motive
        force across the inner mitochondrial membrane. Supported by extensive experimental
        evidence
        (PMID:36239646, PMID:37244256, PMID:12110673).
      supported_by:
        - reference_id: PMID:36239646
          supporting_text: >-
            Complex V (CV) is the central enzyme in energy conversion: it dissipates
            the
            proton
            gradient across the membrane, catalyzing the phosphorylation of ADP to
            ATP
# ============================================================
# IEA ANNOTATIONS (Electronic annotations - check for accuracy)
# ============================================================
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        IEA annotation for MF based on UniProtKB keyword mapping. Nucleotide binding
        is correct
        but very general for ATP5F1B, which specifically binds ADP and ATP at its
        catalytic
        site.
      action: ACCEPT
      reason: >-
        This is a broad but correct IEA annotation. The beta subunit has well-characterized
        nucleotide (ADP/ATP) binding sites documented by cryo-EM (PMID:37244256) and
        UniProt
        binding annotations at residues 209-214. More specific terms like GO:0005524
        (ATP binding)
        are also present in the annotation set, so this broader term is acceptable
        as
        an IEA
        inference.
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            These structures reveal that the release of ADP occurs when the β subunit
            of
            F1Fo-ATP synthase is in the open conformation, showing how ADP binding
            is
            coordinated
            during synthesis
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        IEA annotation for MF. ATP binding is a well-established function of the beta
        subunit,
        which contains the catalytic nucleotide-binding site. UniProt documents multiple
        ADP/ATP
        binding residues (positions 209-214, 238-239).
      action: ACCEPT
      reason: >-
        Correct and well-supported. The beta subunit binds ATP at its catalytic site.
        Structural
        evidence from cryo-EM (PMID:37244256) and bovine structure by similarity confirm
        ADP/ATP
        binding. UniProt lists extensive binding site annotations with experimental
        evidence.
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            snapshot images for three main rotational states and one substate of human
            ATP synthase
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        IEA annotation for CC based on ARBA machine learning model. Cytoplasm is too
        broad and
        imprecise for ATP5F1B, whose primary localization is the mitochondrial matrix/inner
        membrane.
      action: ACCEPT
      reason: >-
        While imprecise, this is not incorrect since the mitochondrion is within the
        cytoplasm.
        More specific CC annotations (mitochondrion, mitochondrial inner membrane,
        mitochondrial
        matrix) are present in the annotation set. As an IEA, this broad term is acceptable.
  - term:
      id: GO:0005743
      label: mitochondrial inner membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        IEA annotation for CC based on UniProt subcellular location mapping. ATP5F1B
        is a
        peripheral membrane protein on the matrix side of the mitochondrial inner
        membrane,
        as part of the F1 head of the ATP synthase complex.
      action: ACCEPT
      reason: >-
        Correct. UniProt states ATP5F1B localizes to "Mitochondrion inner membrane;
        Peripheral
        membrane protein; Matrix side" with experimental evidence (PMID:25168243).
        The
        F1 head
        is attached to the inner membrane via the central and peripheral stalks.
      supported_by:
        - reference_id: PMID:25168243
          supporting_text: >-
            Strap is localised at mitochondria where one of its key interaction partners
            is ATP
            synthase
  - term:
      id: GO:0006754
      label: ATP biosynthetic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        IEA annotation for BP based on UniProt keyword mapping. ATP biosynthetic process
        is a
        core function of ATP5F1B as the catalytic subunit of ATP synthase.
      action: ACCEPT
      reason: >-
        Correct and represents a core function. The beta subunit directly catalyzes
        ATP synthesis
        from ADP + Pi. This is supported by UniProt functional annotation with EC
        7.1.2.2
        and
        multiple experimental studies (PMID:37244256, PMID:36239646).
  - term:
      id: GO:0006811
      label: monoatomic ion transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        IEA annotation for BP. This term refers to ion transport, which is related
        to
        the proton
        transport function of the ATP synthase complex but is extremely broad.
      action: ACCEPT
      reason: >-
        While very general, this is not incorrect since the F1Fo-ATP synthase complex
        transports
        protons (H+) across the inner mitochondrial membrane. The beta subunit contributes
        to
        this function as part of the complex. More specific annotations for proton
        transport
        are also present.
  - term:
      id: GO:0015986
      label: proton motive force-driven ATP synthesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        IEA annotation for BP based on InterPro mapping. Proton motive force-driven
        ATP synthesis
        is the core biological process of ATP5F1B. This is the parent of the more
        specific
        GO:0042776 (mitochondrial form).
      action: ACCEPT
      reason: >-
        Correct. This broader term subsumes GO:0042776. Redundant with the IBA and
        IDA
        annotations
        for the same term, but as an IEA it is perfectly acceptable. ATP5F1B is a
        core
        component
        of the proton motive force-driven ATP synthesis machinery.
  - term:
      id: GO:0016469
      label: proton-transporting two-sector ATPase complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        IEA annotation for CC. This term describes the broader class of two-sector
        ATPase
        complexes
        (F-type, V-type, A-type). The mitochondrial ATP synthase is an F-type two-sector
        ATPase.
      action: ACCEPT
      reason: >-
        Correct but general. The F1Fo ATP synthase is indeed a proton-transporting
        two-sector
        ATPase
        complex. More specific annotations for the proton-transporting ATP synthase
        complex
        (GO:0045259) are also present. As an IEA from ARBA, the broader term is acceptable.
  - term:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        IEA annotation for CC, duplicating the IBA annotation for the same GO term.
        Correct.
      action: ACCEPT
      reason: >-
        Correct and consistent with the IBA annotation. Duplicate evidence codes for
        the same
        term are fine.
  - term:
      id: GO:0046034
      label: ATP metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        IEA annotation for BP based on InterPro mapping. ATP metabolic process is
        very
        broad,
        encompassing both ATP synthesis and hydrolysis.
      action: ACCEPT
      reason: >-
        Correct but very general. ATP5F1B is involved in ATP metabolism (primarily
        synthesis,
        but the complex can also hydrolyze ATP). More specific annotations for ATP
        biosynthetic
        process and proton motive force-driven ATP synthesis are present.
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        IEA annotation for MF based on UniProt keyword mapping. ATP5F1B binds Mg2+
        as
        a cofactor
        for the ATP synthase catalytic reaction. UniProt documents Mg2+ binding at
        residues
        213 and
        238 (PMID:37244256).
      action: ACCEPT
      reason: >-
        Correct. The beta subunit binds Mg2+ ions which are essential cofactors for
        the catalytic
        reaction. The cryo-EM structure (PMID:37244256) confirms Mg2+ binding. This
        is a broad
        IEA term; more specific magnesium ion binding could be considered, but metal
        ion binding
        is acceptable.
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            Biological energy currency ATP is produced by F1Fo-ATP synthase
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        IEA annotation for MF, duplicating the IBA and IDA annotations for the same
        GO term.
        Note this IEA lacks the contributes_to qualifier that the IBA has.
      action: ACCEPT
      reason: >-
        Correct term but ideally should have the contributes_to qualifier as in the
        IBA annotation,
        since the activity is a property of the whole complex. However, as an IEA
        the
        absence of
        the qualifier is acceptable.
  - term:
      id: GO:1902495
      label: transmembrane transporter complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        IEA annotation for CC based on ARBA. The ATP synthase complex is a transmembrane
        transporter
        complex that translocates protons across the membrane.
      action: ACCEPT
      reason: >-
        Correct but very general. The F1Fo-ATP synthase is indeed a transmembrane
        transporter
        complex. More specific terms (GO:0045259, GO:0016469) are also annotated.
  - term:
      id: GO:1902600
      label: proton transmembrane transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        IEA annotation for BP. Proton transmembrane transport is a core process of
        the
        ATP
        synthase complex.
      action: ACCEPT
      reason: >-
        Correct. The F1Fo-ATP synthase transports protons across the inner mitochondrial
        membrane
        as part of its catalytic cycle. ATP5F1B contributes to this as the catalytic
        subunit of
        the F1 head.
# ============================================================
# PROTEIN BINDING ANNOTATIONS (IPI) - Many from HTP studies
# ============================================================
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11410595
    review:
      summary: >-
        IPI protein binding annotation. Publication not available for review (PMID:11410595
        not
        cached). Likely a large-scale interaction study.
      action: UNDECIDED
      reason: >-
        Cannot assess without access to the publication. The generic protein binding
        term is
        uninformative. If from a large-scale study, it is likely a high-throughput
        detection
        of
        protein interaction without functional characterization.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15161933
    review:
      summary: >-
        IPI protein binding from a large-scale proteomic analysis of 14-3-3-binding
        proteins
        (Meek et al. 2004). ATP5F1B was identified as a 14-3-3-binding protein. UniProt
        also
        documents an interaction with YWHAZ (14-3-3 zeta).
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        This is a high-throughput proteomic study identifying many 14-3-3-binding
        proteins.
        While
        the interaction may be real, the generic "protein binding" term is uninformative
        and the
        biological significance of 14-3-3 binding to ATP5F1B is not characterized.
        The
        interaction
        could reflect phosphorylation-dependent regulation but this is speculative.
      supported_by:
        - reference_id: PMID:15161933
          supporting_text: >-
            14-3-3-binding proteins were purified from extracts of interphase and
            mitotic
            HeLa
            cells using specific peptide elution from 14-3-3 zeta affinity columns
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20618440
    review:
      summary: >-
        IPI protein binding from proteomic analysis of 14-3-3-binding proteins during
        C2-ceramide-induced apoptosis (Pozuelo-Rubio 2010). ATP5F1B was identified
        as
        a
        14-3-3-associated protein.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Another 14-3-3 interaction proteomics study. The generic protein binding term
        is
        uninformative. The biological relevance to ATP5F1B function is unclear.
      supported_by:
        - reference_id: PMID:20618440
          supporting_text: >-
            14-3-3 is a family of proteins comprising several isoforms that, in many
            cases,
            promote cell survival by association with proapoptotic proteins
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:27499296
    review:
      summary: >-
        IPI protein binding from mitochondrial protein interaction mapping study (Floyd
        et al.
        2016). This is a focused mitochondrial interactome study that identified regulators
        of
        respiratory chain function.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        While this is a mitochondria-focused interaction study, the generic protein
        binding term
        is uninformative. The study mapped mitochondrial protein interactions but
        the
        specific
        interaction partners and functional significance for ATP5F1B are not captured
        by this
        annotation.
      supported_by:
        - reference_id: PMID:27499296
          supporting_text: >-
            Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory
            Chain
            Function
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: >-
        IPI protein binding from a large-scale human interactome mapping study (Huttlin
        et al.
        2017). This is a high-throughput study mapping the architecture of the human
        interactome.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Large-scale interactome study. The generic protein binding term is uninformative
        for a
        well-characterized enzyme subunit. The specific interaction partners are not
        characterized
        in the annotation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:29892012
    review:
      summary: >-
        IPI protein binding from an interactome perturbation framework study for developmental
        disorders (Sahni et al. 2018). High-throughput protein interaction study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        High-throughput interactome study. Generic protein binding is uninformative
        for ATP5F1B.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:30021884
    review:
      summary: >-
        IPI protein binding from a histone interaction landscape study using crosslinking
        mass
        spectrometry in intact cell nuclei (Fasci et al. 2018). ATP5F1B detected as
        a
        histone-interacting protein in this study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        This study focused on histone interactions by crosslinking mass spectrometry.
        Detection
        of ATP5F1B likely reflects its abundance rather than a specific functional
        interaction
        with histones. The generic protein binding term is uninformative.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31515488
    review:
      summary: >-
        IPI protein binding from a study on disruption of protein interactions by
        genetic
        variants
        across the allele frequency spectrum (Sahni et al. 2019). High-throughput
        study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Large-scale interactome study focused on variant effects on protein interactions.
        Generic
        protein binding is uninformative.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: >-
        IPI protein binding from a reference map of the human binary protein interactome
        (Luck
        et al. 2020). High-throughput Y2H/AP-MS study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Large-scale binary interactome reference map. Generic protein binding is uninformative
        for a well-characterized enzyme subunit.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32814053
    review:
      summary: >-
        IPI protein binding from an interactome mapping study focused on neurodegenerative
        disease
        proteins (Haenig et al. 2020).
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Disease-focused interactome study. Generic protein binding is uninformative.
        The
        interaction with neurodegenerative disease proteins is likely not a core function
        of
        ATP5F1B.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        IPI protein binding from dual proteome-scale network study showing cell-specific
        remodeling of the human interactome (Huttlin et al. 2021).
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Large-scale interactome study. Generic protein binding is uninformative.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:40205054
    review:
      summary: >-
        IPI protein binding from multimodal cell maps study (2024). High-throughput
        study
        mapping structural and functional genomics.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Large-scale high-throughput study. Generic protein binding is uninformative
        for ATP5F1B.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:40355756
    review:
      summary: >-
        IPI protein binding from solute carrier superfamily interactome study (2024).
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Focused interactome study for SLC superfamily. Generic protein binding is
        uninformative
        for ATP5F1B, which is not a solute carrier.
# ============================================================
# MITOCHONDRION LOCALIZATION ANNOTATIONS
# ============================================================
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        IEA annotation for CC based on Ensembl Compara ortholog transfer. Mitochondrial
        localization is well established for ATP5F1B.
      action: ACCEPT
      reason: >-
        Correct. ATP5F1B is a mitochondrial protein with a mitochondrial transit peptide
        (residues 1-47, UniProt). Localization to mitochondria is confirmed by multiple
        experimental methods.
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        IDA annotation for CC based on curation of immunofluorescence data. Mitochondrial
        localization confirmed by immunofluorescence.
      action: ACCEPT
      reason: >-
        Correct. Direct experimental evidence for mitochondrial localization via
        immunofluorescence.
  - term:
      id: GO:0005743
      label: mitochondrial inner membrane
    evidence_type: NAS
    original_reference_id: PMID:26297831
    review:
      summary: >-
        NAS annotation for CC citing the assembly study of human mitochondrial ATP
        synthase
        (Fujikawa et al. 2015). The study demonstrates that ATP5F1B assembles into
        the
        F1-c-ring
        intermediate at the inner mitochondrial membrane.
      action: ACCEPT
      reason: >-
        Correct. The beta subunit is part of the F1 head which is attached to the
        inner
        mitochondrial membrane via the central stalk connected to the Fo sector. This
        is
        well-established from the assembly pathway described in this study.
      supported_by:
        - reference_id: PMID:26297831
          supporting_text: >-
            When expression of d-subunit, a stator stalk component, was knocked-down,
            human
            cells could not form ATP synthase holocomplex and instead accumulated
            two
            subcomplexes, one containing a central rotor shaft plus catalytic subunits
            (F1-c-ring)
  - term:
      id: GO:0015986
      label: proton motive force-driven ATP synthesis
    evidence_type: NAS
    original_reference_id: PMID:26297831
    review:
      summary: >-
        NAS annotation for BP citing the assembly study. The study addresses assembly
        of the
        ATP synthase rather than directly demonstrating the proton motive force-driven
        ATP
        synthesis activity, but the function is well established.
      action: ACCEPT
      reason: >-
        While the cited study focuses on assembly, proton motive force-driven ATP
        synthesis
        is
        the core function of the complex that ATP5F1B assembles into. Well supported
        by other
        references.
  - term:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    evidence_type: NAS
    original_reference_id: PMID:2870059
    review:
      summary: >-
        NAS annotation for CC citing the original cDNA cloning of the human F1-ATPase
        beta
        subunit (Ohta & Kagawa 1986). This foundational paper established the identity
        of
        ATP5F1B.
      action: ACCEPT
      reason: >-
        Correct. The original cloning paper established that this gene encodes the
        beta
        subunit
        of human F1-ATPase, which is part of the proton-transporting ATP synthase
        complex.
      supported_by:
        - reference_id: PMID:2870059
          supporting_text: >-
            F1-ATPase is the major enzyme for ATP synthesis, and its beta subunit
            is the
            catalytic
            site
# ============================================================
# IDA ANNOTATIONS - Direct Assay Evidence
# ============================================================
  - term:
      id: GO:0015986
      label: proton motive force-driven ATP synthesis
    evidence_type: IDA
    original_reference_id: PMID:37244256
    review:
      summary: >-
        IDA annotation for BP from the cryo-EM structure of human ATP synthase (Lai
        et al. 2023).
        The study resolved multiple rotational states demonstrating the proton motive
        force-driven
        ATP synthesis mechanism.
      action: ACCEPT
      reason: >-
        Correct. The structural study directly visualizes the rotary mechanism of
        ATP
        synthesis
        in the human enzyme. Represents core function.
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            Biological energy currency ATP is produced by F1Fo-ATP synthase
  - term:
      id: GO:0015986
      label: proton motive force-driven ATP synthesis
    evidence_type: IDA
    original_reference_id: PMID:25168243
    review:
      summary: >-
        IDA annotation for BP from the Strap/TTC5 study (Maniam et al. 2015). The
        study
        showed
        that Strap interaction with ATP synthase downregulates mitochondrial ATP production,
        demonstrating that ATP5F1B is involved in ATP synthesis.
      action: ACCEPT
      reason: >-
        Correct. The study demonstrated that interaction with Strap downregulated
        ATP
        synthase
        activity, confirming the role of ATP5F1B in ATP synthesis. The fact that inhibiting
        ATP synthase reduces ATP production directly demonstrates the BP.
      supported_by:
        - reference_id: PMID:25168243
          supporting_text: >-
            the interaction between Strap and ATP synthase downregulates mitochondrial
            ATP
            production
  - term:
      id: GO:0015986
      label: proton motive force-driven ATP synthesis
    evidence_type: IDA
    original_reference_id: PMID:36239646
    review:
      summary: >-
        IDA annotation for BP from the congenital hypermetabolism study (Ganetzky
        et
        al. 2022,
        NEJM). The L335P variant in ATP5F1B uncouples proton motive force from ATP
        synthesis,
        demonstrating the role of the beta subunit in coupling.
      action: ACCEPT
      reason: >-
        Strong direct evidence. The study engineered the L335P variant and demonstrated
        uncoupling of the proton motive force from ATP synthesis, directly implicating
        ATP5F1B
        in this process.
      supported_by:
        - reference_id: PMID:36239646
          supporting_text: >-
            Oxygen consumption and membrane potential studies in both patient fibroblasts
            and
            cells with genetic introduction of the Leu335 variant show loosened coupling
            between
            the proton motive force (generated by mitochondrial respiration) and ATP
            synthesis
            due to intrinsic dysfunction of Complex V
  - term:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    evidence_type: IDA
    original_reference_id: PMID:37244256
    review:
      summary: >-
        IDA annotation for CC from the cryo-EM structure of human ATP synthase. The
        study
        directly resolved ATP5F1B as part of the intact complex.
      action: ACCEPT
      reason: >-
        Direct structural evidence. The cryo-EM structure (PDB: 8H9E and others) shows
        ATP5F1B as chains D/E/F in the intact human ATP synthase complex.
      supported_by:
        - reference_id: PMID:37244256
          supporting_text: >-
            Structure of the human ATP synthase
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IDA
    original_reference_id: PMID:25168243
    review:
      summary: >-
        IDA annotation for MF from the Strap study. The study demonstrated that ATP5F1B
        has
        ATP synthase activity that is modulated by Strap binding.
      action: ACCEPT
      reason: >-
        Supported. The study demonstrated functional ATP synthase activity involving
        the beta
        subunit. While the study focused on Strap regulation, it confirmed the catalytic
        activity of the complex containing ATP5F1B.
      supported_by:
        - reference_id: PMID:25168243
          supporting_text: >-
            the interaction between Strap and ATP synthase downregulates mitochondrial
            ATP
            production
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IDA
    original_reference_id: PMID:36239646
    review:
      summary: >-
        IDA annotation for MF from the NEJM uncoupling study. The study showed that
        the L335P
        variant disrupts coupling, demonstrating the role of the beta subunit in the
        rotational
        mechanism.
      action: ACCEPT
      reason: >-
        Strong evidence. The uncoupling phenotype of L335P, which lies near the hydrophobic
        sleeve
        that contacts the rotating gamma subunit, directly demonstrates the beta subunit's
        role
        in the rotational ATP synthase mechanism.
      supported_by:
        - reference_id: PMID:36239646
          supporting_text: >-
            Leu335 lies close to the hydrophobic sleeve in the α3β3 assembly that
            holds
            the tip of the γ subunit of the central stalk
# ============================================================
# HTP ANNOTATION
# ============================================================
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: HTP
    original_reference_id: PMID:34800366
    review:
      summary: >-
        HTP annotation for CC from the quantitative high-confidence human mitochondrial
        proteome
        study (Morgenstern et al. 2021, Cell Metabolism). ATP5F1B was identified with
        high
        confidence as part of the mitochondrial proteome.
      action: ACCEPT
      reason: >-
        Correct. This high-quality mitochondrial proteomics study provides strong
        quantitative
        evidence for mitochondrial localization. ATP5F1B is one of the most abundant
        mitochondrial proteins.
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IC
    original_reference_id: PMID:12110673
    review:
      summary: >-
        IC (inferred by curator) annotation for CC based on the immunocapture study
        of human
        F1F0 ATPase from heart tissue and fibroblasts (Aggeler et al. 2002). The study
        purified
        functionally active F1Fo from mitochondria.
      action: ACCEPT
      reason: >-
        Correct. The study isolated F1Fo-ATPase from mitochondria using immunocapture,
        confirming
        the mitochondrial localization of the complex and its subunits including beta.
      supported_by:
        - reference_id: PMID:12110673
          supporting_text: >-
            Human mitochondrial F(1)F(0) ATP synthase was isolated with a one-step
            immunological
            approach, using a monoclonal antibody against F(1) in a 96-well microplate
            activity
            assay system
  - term:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    evidence_type: IDA
    original_reference_id: PMID:12110673
    review:
      summary: >-
        IDA annotation for CC from the immunocapture study. ATP5F1B (beta subunit)
        was
        identified
        as part of the purified F1Fo complex.
      action: ACCEPT
      reason: >-
        Direct experimental evidence. The beta subunit was identified by specific
        antibodies
        in
        the immunocaptured F1Fo complex.
      supported_by:
        - reference_id: PMID:12110673
          supporting_text: >-
            The immunoprecipitated F(1)F(0) contained a full complement of subunits
            that
            were
            identified with specific antibodies against five of the subunits (alpha,
            beta,
            OSCP,
            d, and IF(1))
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IDA
    original_reference_id: PMID:12110673
    qualifier: contributes_to
    review:
      summary: >-
        IDA annotation for MF with contributes_to qualifier from the immunocapture
        study.
        The
        purified complex displayed ATP hydrolysis activity that was oligomycin-sensitive,
        confirming functional ATP synthase activity.
      action: ACCEPT
      reason: >-
        Direct functional evidence. The immunocaptured complex showed ATP hydrolysis
        activity
        that was sensitive to oligomycin (an ATP synthase inhibitor) and IF1, confirming
        that
        the complex containing the beta subunit has proton-transporting ATP synthase
        activity.
        The contributes_to qualifier is appropriate.
      supported_by:
        - reference_id: PMID:12110673
          supporting_text: >-
            The captured complex V displayed ATP hydrolysis activity that was fully
            oligomycin
            and inhibitor protein IF(1)-sensitive
# ============================================================
# MITOCHONDRIAL MATRIX ANNOTATIONS (Reactome TAS)
# ============================================================
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1592247
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "Expression of ATP5B". The F1
        head
        containing
        the beta subunit faces the mitochondrial matrix.
      action: ACCEPT
      reason: >-
        Correct. UniProt confirms the beta subunit is on the matrix side of the inner
        mitochondrial membrane. The F1 catalytic head protrudes into the matrix.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-164832
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "ATPase synthesizes ATP". Correct
        localization
        for ATP synthesis at the matrix side.
      action: ACCEPT
      reason: >-
        Correct. ATP synthesis occurs in the matrix, where the F1 head containing
        ATP5F1B
        catalyzes ADP + Pi to ATP.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-164834
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "Enzyme-bound ATP is released".
      action: ACCEPT
      reason: >-
        Correct. ATP release from the beta subunit occurs in the matrix.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-164840
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "ADP and Pi bind to ATPase".
      action: ACCEPT
      reason: >-
        Correct. ADP and Pi bind to the catalytic site of the beta subunit on the
        matrix
        side.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8949580
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "F1Fo ATP synthase dimerizes".
        The
        beta
        subunit is part of the complex that dimerizes.
      action: ACCEPT
      reason: >-
        Correct. ATP synthase dimerization involves the F1 head containing the beta
        subunit on
        the matrix side.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9838035
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "CLPXP binds mitochondrial matrix
        proteins".
        ATP5F1B is a substrate for the CLPXP protease quality control system.
      action: ACCEPT
      reason: >-
        Correct. The beta subunit resides in the matrix and is subject to mitochondrial
        quality
        control by CLPXP protease.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9838081
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "LONP1 degrades mitochondrial
        matrix
        proteins".
      action: ACCEPT
      reason: >-
        Correct. The beta subunit in the matrix is subject to LONP1 protease quality
        control.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9838093
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "LONP1 binds mitochondrial matrix
        proteins".
      action: ACCEPT
      reason: >-
        Correct. Same as above, localization to matrix confirmed.
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9838289
    review:
      summary: >-
        TAS annotation for CC from Reactome pathway "CLPXP degrades mitochondrial
        matrix
        proteins".
      action: ACCEPT
      reason: >-
        Correct. Redundant with other Reactome matrix annotations. Matrix localization
        is well
        established.
# ============================================================
# FUNCTIONAL ANNOTATIONS (IMP, IGI)
# ============================================================
  - term:
      id: GO:0006754
      label: ATP biosynthetic process
    evidence_type: IMP
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IMP annotation for BP from the thymosin beta-4/purinergic signaling study
        (Freeman
        et al.
        2011). The study demonstrated that blocking cell surface ATP synthase with
        oligomycin
        or
        antibodies inhibited extracellular ATP generation, confirming the biosynthetic
        function.
      action: KEEP_AS_NON_CORE
      reason: >-
        This annotation relates to ATP biosynthesis at the cell surface (ecto-ATP
        synthase),
        not
        the core mitochondrial function. The study showed extracellular ATP generation
        by cell
        surface ATP synthase, which is a real but non-core function. The mutant phenotype
        was
        measured for cell surface ATP production by endothelial cells.
      supported_by:
        - reference_id: PMID:21106936
          supporting_text: >-
            Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM;
            piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP
            synthase inhibited the Tβ4-induced increase in cell surface ATP levels
  - term:
      id: GO:0043536
      label: positive regulation of blood vessel endothelial cell migration
    evidence_type: IGI
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IGI annotation for BP from the thymosin beta-4 study. The study showed that
        ATP synthase
        on endothelial cell surfaces mediates thymosin beta-4-induced endothelial
        cell
        migration.
        Blocking ATP synthase with antibodies or antagonists inhibited this migration.
      action: KEEP_AS_NON_CORE
      reason: >-
        This is a non-core function related to the ecto-ATP synthase role on endothelial
        cell
        surfaces. The study demonstrates that cell surface ATP synthase contributes
        to
        angiogenesis-related endothelial migration via purinergic signaling, but this
        is not
        the primary evolved function of ATP5F1B.
      supported_by:
        - reference_id: PMID:21106936
          supporting_text: >-
            Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM;
            piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP
            synthase inhibited the Tβ4-induced increase in cell surface ATP levels,
            as
            measured by luciferase assay, and the Tβ4-induced increase in HUVEC migration
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IMP
    original_reference_id: PMID:36239646
    review:
      summary: >-
        IMP annotation for MF from the NEJM uncoupling study. The L335P variant in
        ATP5F1B
        disrupted ATP synthase coupling, demonstrating the beta subunit's role in
        the
        rotational
        mechanism via mutant phenotype analysis.
      action: ACCEPT
      reason: >-
        Strong direct evidence from mutant phenotype. The L335P variant near the hydrophobic
        sleeve that contacts the rotating gamma subunit caused uncoupled ATP synthase
        activity,
        demonstrating the beta subunit's essential role in the rotational mechanism.
      supported_by:
        - reference_id: PMID:36239646
          supporting_text: >-
            we propose that Leu335Pro is a group 1 mutation, because it probably impairs
            engagement of the γ subunit by the α–β hexamer by disrupting contact
            between the β and γ subunits. It thereby disrupts ATP synthesis, even
            with
            normal translocation of protons through FO
# ============================================================
# MORE PROTEIN BINDING + SPECIFIC BINDING ANNOTATIONS
# ============================================================
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25168243
    review:
      summary: >-
        IPI protein binding from the Strap/TTC5 study. The study demonstrated a specific
        interaction between TTC5/Strap and ATP synthase (beta subunit) that downregulates
        ATP
        production.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        While this is a well-characterized interaction with functional consequences
        (Strap binding
        downregulates ATP production), the generic "protein binding" term is uninformative.
        The
        interaction is better captured by other annotations in this set. UniProt documents
        this
        as "Interacts with TTC5/STRAP; the interaction results in decreased mitochondrial
        ATP
        production."
      supported_by:
        - reference_id: PMID:25168243
          supporting_text: >-
            one of its key interaction partners is ATP synthase. Significantly, the
            interaction
            between Strap and ATP synthase downregulates mitochondrial ATP production
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IDA
    original_reference_id: PMID:25168243
    review:
      summary: >-
        IDA annotation for CC from the Strap study. The study confirmed mitochondrial
        localization
        of ATP5F1B through co-localization studies.
      action: ACCEPT
      reason: >-
        Correct. The study demonstrated mitochondrial localization through interaction
        studies
        and subcellular fractionation.
      supported_by:
        - reference_id: PMID:25168243
          supporting_text: >-
            Strap is localised at mitochondria where one of its key interaction partners
            is ATP
            synthase
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32243843
    review:
      summary: >-
        IPI protein binding from the Mitoregulin study (Friesen et al. 2020). The
        study
        showed
        that Mitoregulin (MTLN) interacts with ATP5F1B. UniProt confirms "Interacts
        with MTLN".
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        While the MTLN interaction is documented, the generic "protein binding" term
        is
        uninformative. The interaction with Mitoregulin may regulate beta-oxidation
        but this
        is not a core function of ATP5F1B.
  - term:
      id: GO:0042776
      label: proton motive force-driven mitochondrial ATP synthesis
    evidence_type: IDA
    original_reference_id: PMID:12110673
    review:
      summary: >-
        IDA annotation for BP from the immunocapture study. The purified human F1Fo
        displayed
        functional ATP hydrolysis activity (reverse of synthesis), confirming the
        complex's
        role
        in mitochondrial ATP synthesis.
      action: ACCEPT
      reason: >-
        Direct functional evidence. The immunocaptured complex from human heart mitochondria
        showed oligomycin-sensitive ATP hydrolysis activity, confirming the functional
        involvement
        of ATP5F1B in the ATP synthesis/hydrolysis cycle.
      supported_by:
        - reference_id: PMID:12110673
          supporting_text: >-
            The captured complex V displayed ATP hydrolysis activity that was fully
            oligomycin
            and inhibitor protein IF(1)-sensitive
# ============================================================
# HDA ANNOTATIONS (High-throughput Direct Assay)
# ============================================================
  - term:
      id: GO:0001649
      label: osteoblast differentiation
    evidence_type: HDA
    original_reference_id: PMID:16210410
    review:
      summary: >-
        HDA annotation for BP from a quantitative proteomics study of membrane proteins
        during
        osteoblast differentiation of human mesenchymal stem cells (Foster et al.
        2005).
        ATP5F1B
        was identified as differentially expressed during this process.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        This annotation appears to be based on differential protein expression during
        osteoblast
        differentiation, not direct involvement in the differentiation process. ATP5F1B
        expression
        changes likely reflect altered metabolic demands during differentiation rather
        than a
        specific role in osteoblast biology.
      supported_by:
        - reference_id: PMID:16210410
          supporting_text: >-
            We identified 463 unique proteins with extremely high confidence
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: HDA
    original_reference_id: PMID:16210410
    review:
      summary: >-
        HDA annotation for CC from the same osteoblast differentiation proteomics
        study.
        ATP5F1B
        was detected in the membrane fraction.
      action: ACCEPT
      reason: >-
        Correct but very broad. ATP5F1B is associated with the mitochondrial inner
        membrane.
        Detection in a membrane fraction is consistent with this.
# ============================================================
# ECTO-ATP SYNTHASE / CELL SURFACE ANNOTATIONS
# ============================================================
  - term:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    evidence_type: IDA
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IDA annotation for CC from the thymosin beta-4 study. The study identified
        F1-F0
        ATP
        synthase on the endothelial cell surface using pulldown and mass spectrometry.
      action: ACCEPT
      reason: >-
        Correct. The study demonstrated the presence of ATP synthase complex on endothelial
        cell
        surfaces, consistent with the ecto-ATP synthase literature.
      supported_by:
        - reference_id: PMID:21106936
          supporting_text: >-
            we identified F1-F0 ATP synthase, a known target of antiangiogenic angiostatin.
            By
            surface plasmon resonance, we determined for Tβ4 binding to the β subunit
            of ATP
            synthase a K(D) of 12 nM
  - term:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    evidence_type: IMP
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IMP annotation for MF from the thymosin beta-4 study. The study showed that
        ATP synthase
        inhibitors (oligomycin, piceatannol, angiostatin) blocked cell surface ATP
        generation,
        demonstrating functional ATP synthase activity on the cell surface.
      action: KEEP_AS_NON_CORE
      reason: >-
        This demonstrates functional ATP synthase activity on the cell surface (ecto-ATP
        synthase),
        which is a real but non-core function. The MF annotation is correct but relates
        to the
        non-canonical cell surface localization.
      supported_by:
        - reference_id: PMID:21106936
          supporting_text: >-
            Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM;
            piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP
            synthase inhibited the Tβ4-induced increase in cell surface ATP levels
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IPI protein binding from the thymosin beta-4 study. The study identified ATP5F1B
        as an
        interactor of thymosin beta-4 with high affinity (Kd = 12 nM).
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        While the thymosin beta-4 interaction is well-characterized (Kd = 12 nM by
        SPR),
        the
        generic "protein binding" term is uninformative. The angiostatin binding annotation
        (GO:0043532) from the same study is more informative.
      supported_by:
        - reference_id: PMID:21106936
          supporting_text: >-
            we determined for Tβ4 binding to the β subunit of ATP synthase a K(D)
            of 12
            nM
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: IDA
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IDA annotation for CC from the thymosin beta-4 study. ATP5F1B detected in
        membrane
        fraction of endothelial cells.
      action: ACCEPT
      reason: >-
        Correct but very broad. ATP5F1B is associated with membranes both as part
        of
        the
        mitochondrial inner membrane complex and as ecto-ATP synthase on the cell
        surface.
  - term:
      id: GO:0043532
      label: angiostatin binding
    evidence_type: IPI
    original_reference_id: PMID:21106936
    review:
      summary: >-
        IPI annotation for MF from the thymosin beta-4 study. The study showed that
        angiostatin
        binds to and inhibits cell surface ATP synthase, and used angiostatin as an
        antagonist
        (IC50 ~2.9 ug/ml).
      action: KEEP_AS_NON_CORE
      reason: >-
        Angiostatin binding to the beta subunit of cell surface ATP synthase is well
        documented
        in the ecto-ATP synthase literature (PMID:17510399, PMID:21106936). This is
        a real
        binding activity but relates to the non-canonical cell surface function rather
        than the
        core mitochondrial role.
      supported_by:
        - reference_id: PMID:21106936
          supporting_text: >-
            Blocking antibodies and antagonists (oligomycin, IC(50) ∼1.8 μM;
            piceatannol, IC(50) ∼1.05 μM; and angiostatin, IC(50) ∼2.9 μg/ml) of ATP
            synthase inhibited the Tβ4-induced increase in cell surface ATP levels
# ============================================================
# EXTRACELLULAR EXOSOME ANNOTATIONS (HDA)
# ============================================================
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:23533145
    review:
      summary: >-
        HDA annotation for CC from proteomic analysis of exosomes from expressed prostatic
        secretions in urine.
      action: KEEP_AS_NON_CORE
      reason: >-
        Detection of ATP5F1B in extracellular exosomes is consistent with the known
        presence of
        mitochondrial proteins in exosomes. This is a non-core localization. ATP5F1B
        is one of
        the most abundant mitochondrial proteins, and abundant proteins are commonly
        detected in
        exosome proteomics.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: HDA
    original_reference_id: PMID:19946888
    review:
      summary: >-
        HDA annotation for CC from NK cell membrane proteome study. ATP5F1B detected
        in the
        membrane proteome of NK cells.
      action: ACCEPT
      reason: >-
        Correct but broad. Detection in membrane fractions is consistent with the
        mitochondrial
        inner membrane association and/or cell surface ecto-ATP synthase presence.
        NK
        cells are
        known to have cell surface ATP synthase which is involved in immune cytotoxicity
        (PMID:8006588).
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: HDA
    original_reference_id: PMID:21630459
    review:
      summary: >-
        HDA annotation for CC from proteomic characterization of the human sperm nucleus.
        ATP5F1B
        detected in the sperm nuclear fraction.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Detection of ATP5F1B in sperm nuclear fractions is likely a contamination
        artifact
        from
        the abundant mitochondrial sheath surrounding the sperm nucleus. Mitochondrial
        proteins
        are common contaminants in nuclear preparations, especially from sperm where
        mitochondria
        are densely packed around the flagellum adjacent to the nucleus. There is
        no
        evidence
        for a functional role of ATP5F1B in the nucleus.
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: HDA
    original_reference_id: PMID:20833797
    review:
      summary: >-
        HDA annotation for CC from phosphoproteome analysis of functional mitochondria
        from
        resting human muscle. ATP5F1B identified as a phosphorylated mitochondrial
        protein.
      action: ACCEPT
      reason: >-
        Correct. Detection in isolated functional mitochondria from human muscle tissue
        provides
        strong evidence for mitochondrial localization. The phosphorylation data is
        consistent
        with UniProt PTM annotations (Ser-415, Ser-529 phosphorylation).
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:19199708
    review:
      summary: >-
        HDA annotation for CC from proteomic analysis of human parotid gland exosomes.
      action: KEEP_AS_NON_CORE
      reason: >-
        Detection in parotid gland exosomes. Non-core localization, likely reflecting
        abundance
        of the protein.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:19056867
    review:
      summary: >-
        HDA annotation for CC from large-scale proteomics of urinary exosomes.
      action: KEEP_AS_NON_CORE
      reason: >-
        Non-core localization. Detection in urinary exosomes likely reflects protein
        abundance.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:20458337
    review:
      summary: >-
        HDA annotation for CC from MHC class II-associated proteins in B-cell exosomes
        study.
      action: KEEP_AS_NON_CORE
      reason: >-
        Non-core localization. Detection in B-cell exosomes.
# ============================================================
# MITOCHONDRIAL NUCLEOID
# ============================================================
  - term:
      id: GO:0042645
      label: mitochondrial nucleoid
    evidence_type: IDA
    original_reference_id: PMID:18063578
    review:
      summary: >-
        IDA annotation for CC from the study on layered structure of human mitochondrial
        DNA
        nucleoids (Bogenhagen et al. 2008). ATP5F1B was identified in native nucleoid
        preparations
        but was characterized as a peripheral rather than core nucleoid component.
      action: KEEP_AS_NON_CORE
      reason: >-
        The study identified ATP5F1B in nucleoid preparations but noted that metabolic
        proteins
        and chaperones in native nucleoids may represent peripheral associations rather
        than
        core components. The authors describe a layered nucleoid structure where "translation
        and
        complex assembly may occur in the peripheral region." ATP5F1B association
        with
        nucleoids
        likely reflects proximity during complex assembly rather than a direct role
        in mtDNA
        maintenance.
      supported_by:
        - reference_id: PMID:18063578
          supporting_text: >-
            Several other metabolic proteins and chaperones identified in native nucleoids
# ============================================================
# ANGIOGENESIS AND CELL SURFACE FUNCTION (PMID:17510399)
# ============================================================
  - term:
      id: GO:0001525
      label: angiogenesis
    evidence_type: IMP
    original_reference_id: PMID:17510399
    review:
      summary: >-
        IMP annotation for BP from the angiostatin-like activity study (Chi et al.
        2007).
        The
        study showed that a monoclonal antibody against ATP5F1B inhibited tube formation
        and
        ATP generation by cell surface ATP synthase, demonstrating a role in angiogenesis.
      action: KEEP_AS_NON_CORE
      reason: >-
        This relates to the ecto-ATP synthase function on endothelial cell surfaces.
        Blocking
        cell surface ATP synthase inhibits tube formation (a hallmark of angiogenesis).
        This is
        a real but non-core function of ATP5F1B.
      supported_by:
        - reference_id: PMID:17510399
          supporting_text: >-
            MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial
            cells
            exposed to low extracellular pH
  - term:
      id: GO:0006754
      label: ATP biosynthetic process
    evidence_type: IMP
    original_reference_id: PMID:17510399
    review:
      summary: >-
        IMP annotation for BP from the angiostatin-like activity study. The study
        demonstrated
        that blocking cell surface ATP synthase with antibodies inhibited ATP generation.
      action: KEEP_AS_NON_CORE
      reason: >-
        This relates to extracellular ATP generation by cell surface ATP synthase
        rather
        than
        mitochondrial ATP synthesis. Real but non-core function.
      supported_by:
        - reference_id: PMID:17510399
          supporting_text: >-
            Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on
            the
            endothelial
            cell surface in acidic conditions, the typical tumor microenvironment
            where
            cell surface
            ATP synthase exhibits greater activity
  - term:
      id: GO:0009986
      label: cell surface
    evidence_type: IDA
    original_reference_id: PMID:17510399
    review:
      summary: >-
        IDA annotation for CC. The study demonstrated cell surface localization of
        ATP5F1B
        on
        endothelial cells using antibody binding and functional assays.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cell surface localization of ATP5F1B is well documented in the ecto-ATP synthase
        literature.
        This is a real but non-canonical localization, distinct from the primary mitochondrial
        localization.
      supported_by:
        - reference_id: PMID:17510399
          supporting_text: >-
            The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial
            cell
            surface
# ============================================================
# MHC CLASS I BINDING
# ============================================================
  - term:
      id: GO:0042288
      label: MHC class I protein binding
    evidence_type: IDA
    original_reference_id: PMID:17643490
    review:
      summary: >-
        IDA annotation for MF from the ecto-F1-ATPase and MHC-class I study (Vantourout
        et al.
        2008). The study demonstrated close association and co-immunoprecipitation
        of
        ecto-F1-ATPase
        beta chain with MHC class I molecules on cell membranes.
      action: KEEP_AS_NON_CORE
      reason: >-
        This is a well-documented interaction at the cell surface where ecto-F1-ATPase
        associates
        with MHC class I molecules. The interaction is relevant to gammadelta T cell
        recognition
        and immune function, but this is a non-core function of ATP5F1B.
      supported_by:
        - reference_id: PMID:17643490
          supporting_text: >-
            biotinylated F1-ATPase cell surface components co-immunoprecipitate with
            MHC-I
            molecules confirming the association of both complexes on Raji cells.
            Confocal
            microscopy analysis of MHC-I and ecto-F1-ATPase beta chain expression
            on HepG2
            cells shows a co-localization of both complexes in punctate membrane domains
# ============================================================
# CELL SURFACE ATP SYNTHASE ACTIVITY (PMID:17510399 continued)
# ============================================================
  - term:
      id: GO:0046961
      label: proton-transporting ATPase activity, rotational mechanism
    evidence_type: IMP
    original_reference_id: PMID:17510399
    review:
      summary: >-
        IMP annotation for MF. Note this is the ATPase (hydrolysis) direction, not
        synthase.
        The study demonstrated that cell surface ATP synthase also has ATPase (hydrolytic)
        activity
        that was inhibited by the anti-beta antibody.
      action: KEEP_AS_NON_CORE
      reason: >-
        This annotation for ATPase activity (hydrolysis direction) on the cell surface
        is
        supported by the study. The cell surface enzyme can work in both directions.
        Non-core
        as it relates to ecto-ATP synthase.
      supported_by:
        - reference_id: PMID:17510399
          supporting_text: >-
            MAb3D5AB1 inhibits the hydrolytic activity of F(1) ATP synthase at lower
            concentrations than angiostatin
  - term:
      id: GO:0051453
      label: regulation of intracellular pH
    evidence_type: IMP
    original_reference_id: PMID:17510399
    review:
      summary: >-
        IMP annotation for BP. The study showed that blocking cell surface ATP synthase
        with
        antibodies decreased intracellular pH in endothelial cells at low extracellular
        pH.
      action: KEEP_AS_NON_CORE
      reason: >-
        This is a downstream consequence of ecto-ATP synthase activity on pH regulation.
        Non-core pleiotropic effect of the cell surface function.
      supported_by:
        - reference_id: PMID:17510399
          supporting_text: >-
            MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial
            cells exposed to low extracellular pH
  - term:
      id: GO:1902600
      label: proton transmembrane transport
    evidence_type: IMP
    original_reference_id: PMID:17510399
    review:
      summary: >-
        IMP annotation for BP from the cell surface ATP synthase study. Proton transport
        activity
        of the cell surface ATP synthase.
      action: KEEP_AS_NON_CORE
      reason: >-
        This relates to proton transport by cell surface ATP synthase. While proton
        transport is
        a core function in the mitochondrial context, here it refers to the ecto-enzyme.
        The IEA
        annotation for the same term covers the general case.
# ============================================================
# OLDER LOCALIZATION ANNOTATIONS
# ============================================================
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IDA
    original_reference_id: PMID:2870059
    review:
      summary: >-
        IDA annotation for CC from the original cDNA cloning study (Ohta & Kagawa
        1986).
        The
        study established that the protein has a mitochondrial transit peptide and
        localizes
        to mitochondria.
      action: ACCEPT
      reason: >-
        Correct. The founding study established that the beta subunit is a mitochondrial
        protein
        with a presequence (transit peptide) for mitochondrial import.
      supported_by:
        - reference_id: PMID:2870059
          supporting_text: >-
            The open reading frame started from a putative signal presequence, which
            was
            rich
            in both serine and arginine
  - term:
      id: GO:0005759
      label: mitochondrial matrix
    evidence_type: NAS
    original_reference_id: PMID:2687158
    review:
      summary: >-
        NAS annotation for CC from the gene sequence/expression study (Neckelmann
        et
        al. 1989).
        The study described the gene encoding the beta subunit which is imported to
        the
        mitochondrial matrix.
      action: ACCEPT
      reason: >-
        Correct. The beta subunit resides on the matrix side of the inner mitochondrial
        membrane
        as part of the F1 head.
      supported_by:
        - reference_id: PMID:2687158
          supporting_text: >-
            the functional F0F1-ATP synthase beta subunit gene is located on chromosome
            12
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:10077593
    review:
      summary: >-
        IDA annotation for CC. Publication not cached (PMID:10077593). Based on the
        title and
        context, this likely documents the ecto-ATP synthase on the plasma membrane.
      action: UNDECIDED
      reason: >-
        Cannot fully assess without the publication. However, plasma membrane localization
        of
        ATP5F1B is well supported by the ecto-ATP synthase literature (PMID:8006588,
        PMID:17510399).
        If confirmed, this would be a non-core localization.
  - term:
      id: GO:0006091
      label: generation of precursor metabolites and energy
    evidence_type: NAS
    original_reference_id: PMID:2870059
    review:
      summary: >-
        NAS annotation for BP from the original cDNA cloning study. Generation of
        precursor
        metabolites and energy is the broad process encompassing oxidative phosphorylation.
      action: ACCEPT
      reason: >-
        Correct but very broad. ATP synthesis by the F1Fo-ATP synthase is a central
        part of
        energy generation. More specific annotations are present (GO:0042776, GO:0015986).
      supported_by:
        - reference_id: PMID:2870059
          supporting_text: >-
            F1-ATPase is the major enzyme for ATP synthesis
  - term:
      id: GO:0031966
      label: mitochondrial membrane
    evidence_type: IDA
    original_reference_id: PMID:8006588
    review:
      summary: >-
        IDA annotation for CC from the study demonstrating beta subunit expression
        on
        tumor cell
        surfaces (Das et al. 1994). While the study focused on cell surface expression,
        the
        protein was identified as having "structural and immunologic characteristics
        of the beta
        subunit of H+ transporting ATP synthase" from mitochondria.
      action: ACCEPT
      reason: >-
        Correct. ATP5F1B is associated with the mitochondrial inner membrane as part
        of the
        ATP synthase complex. The study confirmed the identity of the cell surface
        protein
        as
        the mitochondrial beta subunit.
      supported_by:
        - reference_id: PMID:8006588
          supporting_text: >-
            A 51.5-kD protein (p51.5) bearing structural and immunologic characteristics
            of the
            beta subunit of H+ transporting ATP synthase
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:10077593
    review:
      summary: >-
        IPI protein binding annotation. Publication not cached (PMID:10077593).
      action: UNDECIDED
      reason: >-
        Cannot assess without access to the publication. Generic protein binding is
        uninformative.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
      vocabulary mapping, accompanied by conservative changes to GO terms applied
      by UniProt
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000107
    title: Automatic transfer of experimentally verified manual GO annotation data
      to orthologs using Ensembl Compara
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10077593
    title: Angiostatin binds ATP synthase on the surface of human endothelial cells.
    findings: []
  - id: PMID:11410595
    title: Atp11p and Atp12p are assembly factors for the F(1)-ATPase in human mitochondria.
    findings: []
  - id: PMID:12110673
    title: A functionally active human F1F0 ATPase can be purified by immunocapture
      from heart tissue and fibroblast cell lines. Subunit structure and activity
      studies.
    findings:
      - statement: >-
          Human F1Fo ATP synthase was purified from heart tissue and fibroblasts by
          immunocapture
          and shown to be functionally active with oligomycin-sensitive ATP hydrolysis
          activity.
        supporting_text: >-
          The captured complex V displayed ATP hydrolysis activity that was fully
          oligomycin
          and inhibitor protein IF(1)-sensitive
  - id: PMID:15161933
    title: Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding
      proteins.
    findings: []
  - id: PMID:16210410
    title: Differential expression profiling of membrane proteins by quantitative
      proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation.
    findings: []
  - id: PMID:17510399
    title: Angiostatin-like activity of a monoclonal antibody to the catalytic subunit
      of F1F0 ATP synthase.
    findings:
      - statement: >-
          Cell surface ATP synthase on endothelial cells generates ATP and is inhibited
          by
          angiostatin and anti-beta antibodies, with effects on angiogenesis and intracellular
          pH.
        supporting_text: >-
          Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on the
          endothelial
          cell surface in acidic conditions, the typical tumor microenvironment where
          cell surface
          ATP synthase exhibits greater activity
  - id: PMID:17643490
    title: Ecto-F1-ATPase and MHC-class I close association on cell membranes.
    findings:
      - statement: >-
          Ecto-F1-ATPase beta chain co-localizes and co-immunoprecipitates with MHC
          class
          I
          molecules on cell surfaces, with expression inversely correlated with MHC-I
          levels.
        supporting_text: >-
          biotinylated F1-ATPase cell surface components co-immunoprecipitate with
          MHC-I
          molecules confirming the association of both complexes on Raji cells
  - id: PMID:18063578
    title: The layered structure of human mitochondrial DNA nucleoids.
    findings:
      - statement: >-
          ATP5F1B was identified in native nucleoid preparations as a peripheral component,
          not a core nucleoid protein.
        supporting_text: >-
          Several other metabolic proteins and chaperones identified in native nucleoids
  - id: PMID:19056867
    title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
    findings: []
  - id: PMID:19199708
    title: Proteomic analysis of human parotid gland exosomes by multidimensional
      protein identification technology (MudPIT).
    findings: []
  - id: PMID:19946888
    title: Defining the membrane proteome of NK cells.
    findings: []
  - id: PMID:20458337
    title: MHC class II-associated proteins in B-cell exosomes and potential functional
      implications for exosome biogenesis.
    findings: []
  - id: PMID:20618440
    title: Proteomic and biochemical analysis of 14-3-3-binding proteins during C2-ceramide-induced
      apoptosis.
    findings: []
  - id: PMID:20833797
    title: Phosphoproteome analysis of functional mitochondria isolated from resting
      human muscle reveals extensive phosphorylation of inner membrane protein complexes
      and enzymes.
    findings: []
  - id: PMID:21106936
    title: Regenerative protein thymosin beta-4 is a novel regulator of purinergic
      signaling.
    findings:
      - statement: >-
          Thymosin beta-4 binds to the beta subunit of cell surface ATP synthase (Kd
          =
          12 nM)
          and stimulates extracellular ATP production and endothelial cell migration
          via
          purinergic signaling.
        supporting_text: >-
          we determined for Tβ4 binding to the β subunit of ATP synthase a K(D) of
          12
          nM
  - id: PMID:21630459
    title: Proteomic characterization of the human sperm nucleus.
    findings: []
  - id: PMID:23533145
    title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
      secretions in urine.
    findings: []
  - id: PMID:25168243
    title: Cofactor Strap regulates oxidative phosphorylation and mitochondrial p53
      activity through ATP synthase.
    findings:
      - statement: >-
          Strap/TTC5 interacts with ATP synthase (beta subunit) at mitochondria and
          downregulates
          ATP production, sensitizing cells to apoptosis under glucose limitation.
        supporting_text: >-
          the interaction between Strap and ATP synthase downregulates mitochondrial
          ATP
          production
  - id: PMID:26297831
    title: Assembly of human mitochondrial ATP synthase through two separate intermediates,
      F1-c-ring and b-e-g complex.
    findings:
      - statement: >-
          Human mitochondrial ATP synthase assembles through two separate intermediates:
          the F1-c-ring (containing the beta subunit) and the b-e-g stator complex.
        supporting_text: >-
          human cells could not form ATP synthase holocomplex and instead accumulated
          two
          subcomplexes, one containing a central rotor shaft plus catalytic subunits
          (F1-c-ring)
  - id: PMID:2687158
    title: 'The human ATP synthase beta subunit gene: sequence analysis, chromosome
      assignment, and differential expression.'
    findings:
      - statement: >-
          The human ATP5F1B gene is on chromosome 12, has 10 exons encoding a 49-aa
          leader
          peptide and 480-aa mature protein, with tissue-specific expression highest
          in
          heart.
        supporting_text: >-
          the functional F0F1-ATP synthase beta subunit gene is located on chromosome
          12
  - id: PMID:27499296
    title: Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory
      Chain Function.
    findings: []
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and disease
      networks.
    findings: []
  - id: PMID:2870059
    title: 'Human F1-ATPase: molecular cloning of cDNA for the beta subunit.'
    findings:
      - statement: >-
          First full-length cDNA cloning of the human F1-ATPase beta subunit, establishing
          it as the catalytic site of ATP synthesis with high homology to beef heart
          (97.5%)
          and E. coli (71.7%) beta subunits.
        supporting_text: >-
          F1-ATPase is the major enzyme for ATP synthesis, and its beta subunit is
          the
          catalytic site
  - id: PMID:29892012
    title: An interactome perturbation framework prioritizes damaging missense mutations
      for developmental disorders.
    findings: []
  - id: PMID:30021884
    title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry
      in Intact Cell Nuclei.
    findings: []
  - id: PMID:31515488
    title: Extensive disruption of protein interactions by genetic variants across
      the allele frequency spectrum in human populations.
    findings: []
  - id: PMID:32243843
    title: Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes.
    findings:
      - statement: >-
          Mitoregulin (MTLN) interacts with ATP5F1B, linking mitochondrial beta-oxidation
          regulation to ATP synthase.
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome.
    findings: []
  - id: PMID:32814053
    title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
      and Uncovers Widespread Protein Aggregation in Affected Brains.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the human
      interactome.
    findings: []
  - id: PMID:34800366
    title: Quantitative high-confidence human mitochondrial proteome and its dynamics
      in cellular context.
    findings: []
  - id: PMID:36239646
    title: Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.
    findings:
      - statement: >-
          The L335P variant in ATP5F1B causes dominant mitochondrial uncoupling, loosening
          the
          coupling between proton motive force and ATP synthesis, resulting in hypermetabolism.
        supporting_text: >-
          a de novo heterozygous variant in ATP5F1B, which encodes the β subunit of
          mitochondrial ATP synthase
  - id: PMID:37244256
    title: Structure of the human ATP synthase.
    findings:
      - statement: >-
          Cryo-EM structures of human ATP synthase at 2.53 A resolution reveal three
          rotational
          states, showing ADP release from the beta subunit in the open conformation
          and
          water
          molecules in the proton half-channels.
        supporting_text: >-
          These structures reveal that the release of ADP occurs when the β subunit
          of
          F1Fo-ATP synthase is in the open conformation, showing how ADP binding is
          coordinated during synthesis
  - id: PMID:40205054
    title: Multimodal cell maps as a foundation for structural and functional genomics.
    findings: []
  - id: PMID:40355756
    title: The solute carrier superfamily interactome.
    findings: []
  - id: PMID:8006588
    title: 'A novel ligand in lymphocyte-mediated cytotoxicity: expression of the
      beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines.'
    findings:
      - statement: >-
          The beta subunit of ATP synthase is expressed on the plasma membrane of
          tumor
          cells
          and functions as a ligand in NK cell and LAK cell-mediated cytotoxicity.
        supporting_text: >-
          A 51.5-kD protein (p51.5) bearing structural and immunologic characteristics
          of
          the beta subunit of H+ transporting ATP synthase
  - id: Reactome:R-HSA-1592247
    title: Expression of ATP5B
    findings: []
  - id: Reactome:R-HSA-164832
    title: ATPase synthesizes ATP
    findings: []
  - id: Reactome:R-HSA-164834
    title: Enzyme-bound ATP is released
    findings: []
  - id: Reactome:R-HSA-164840
    title: ADP and Pi bind to ATPase
    findings: []
  - id: Reactome:R-HSA-8949580
    title: F1Fo ATP synthase dimerizes
    findings: []
  - id: Reactome:R-HSA-9838035
    title: CLPXP binds mitochondrial matrix proteins
    findings: []
  - id: Reactome:R-HSA-9838081
    title: LONP1 degrades mitochondrial matrix proteins
    findings: []
  - id: Reactome:R-HSA-9838093
    title: LONP1 binds mitochondrial matrix proteins
    findings: []
  - id: Reactome:R-HSA-9838289
    title: CLPXP degrades mitochondrial matrix proteins
    findings: []
core_functions:
  - molecular_function:
      id: GO:0005524
      label: ATP binding
    contributes_to_molecular_function:
      id: GO:0046933
      label: proton-transporting ATP synthase activity, rotational mechanism
    directly_involved_in:
      - id: GO:0042776
        label: proton motive force-driven mitochondrial ATP synthesis
    locations:
      - id: GO:0005759
        label: mitochondrial matrix
    in_complex:
      id: GO:0045259
      label: proton-transporting ATP synthase complex
    description: >-
      ATP5F1B is the catalytic beta subunit of the F1 head of the mitochondrial ATP
      synthase
      (Complex V). It contains the active site where ADP + Pi is converted to ATP
      via
      the
      binding change mechanism driven by rotation of the gamma subunit. The beta subunit
      binds
      ATP/ADP at its catalytic nucleotide-binding site (residues 209-214, 238-239)
      with
      Mg2+
      as a required cofactor. It contributes_to the complex-level proton-transporting
      ATP
      synthase activity (GO:0046933) of the rotational mechanism. Three beta subunits
      alternate
      with three alpha subunits to form the alpha3-beta3 hexameric F1 catalytic head
      on the
      matrix side of the inner mitochondrial membrane. Structural evidence from cryo-EM
      at
      2.53 A resolution (PMID:37244256) and functional evidence from the L335P uncoupling
      variant (PMID:36239646) confirm the catalytic role.
    supported_by:
      - reference_id: PMID:37244256
        supporting_text: >-
          These structures reveal that the release of ADP occurs when the β subunit
          of
          F1Fo-ATP synthase is in the open conformation, showing how ADP binding is
          coordinated
          during synthesis
      - reference_id: PMID:36239646
        supporting_text: >-
          The catalytic core of F1 contains three α and three β subunits arranged
          around
          a γ subunit of the central stalk. Protons passing through FO (the pore)
          cause
          the
          γ stalk to rotate, inducing conformational transitions in the β subunit
          that
          are required for the synthesis of ATP from ADP
      - reference_id: PMID:12110673
        supporting_text: >-
          The captured complex V displayed ATP hydrolysis activity that was fully
          oligomycin
          and inhibitor protein IF(1)-sensitive

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Citations

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