protein
ATP synthase F(1) complex subunit beta, mitochondrial
Gene
ATP5F1B
Organism
Homo sapiens(9606)
Length
529 aa
Mass
56,560 Da
ATP synthase F(1) complex subunit beta (ATP5F1B) is the catalytic subunit of the mitochondrial F(1)F(0) ATP synthase complex (Complex V), which synthesizes ATP from ADP using the proton gradient generated by the electron transport chain (UniProt: P06576). It forms the catalytic core of the F(1) domain together with subunit alpha and couples ATP synthesis to proton translocation via a rotary mechanism involving the central stalk. Mutations in ATP5F1B are associated with hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2 (HUMOP2), characterized by failure to thrive and developmental delay.
ATP5F1B is relevant to Alzheimer's disease pathology, with Chaparral AD proteomics data showing consistent downregulation in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.29). This reduction was observed in human brain samples analyzed by TMT-labeled proteomics across multiple subcellular fractions. The downregulation of this ATP synthase subunit suggests impaired mitochondrial energy production capacity in AD brain, consistent with documented mitochondrial dysfunction in Alzheimer's pathogenesis.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.293
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.2934 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable) (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain (PubMed:37244256)
Disease associations
Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2HUMOP2
A disorder apparent in infancy and characterized by euthyroid hypermetabolism, failure to thrive despite excessive caloric intake, intermittent hyperthermia, and developmental delay.
Sources
Last updated 5/8/2026, 6:27:27 AM