protein
V-type proton ATPase subunit B, brain isoform
aka V-ATPase subunit B 2
Gene
ATP6V1B2
Organism
Homo sapiens(9606)
Length
511 aa
Mass
56,501 Da
ATP6V1B2 encodes the V-type proton ATPase subunit B, brain isoform, a non-catalytic component of the V1 complex of vacuolar H+-ATPase (UniProt: P21281). This multisubunit enzyme hydrolyzes ATP to translocate protons across membranes, acidifying intracellular compartments and, in some cell types, the extracellular environment. The protein is particularly important in renal intercalated cells for proton secretion under baseline conditions.
UniProt documentation associates ATP6V1B2 mutations with Zimmermann-Laband syndrome 2 and congenital deafness with onychodystrophy, both rare developmental disorders (UniProt: P21281). The gene is expressed broadly in tissues requiring active proton pumping, including neural and epithelial cells.
In Alzheimer's disease, ATP6V1B2 is significantly downregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.34 across two subcellular fractions (Chaparral AD proteomics). The downregulation was detected in a TMT-labeled proteomics study analyzing four subcellular fractions, suggesting potential impairment of lysosomal and vacuolar acidification pathways relevant to amyloid and tau clearance in Alzheimer's pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.383
P2
-0.295
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3389 (2 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
Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In renal intercalated cells, can partially compensate the lack of ATP6V1B1 and mediate secretion of protons (H+) into the urine under base-line conditions but not in conditions of acid load (By similarity)
Disease associations
Zimmermann-Laband syndrome 2ZLS2
A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some patients manifest intellectual disability with or without epilepsy. ZLS2 inheritance is autosomal dominant.
Deafness, congenital, with onychodystrophy, autosomal dominantDDOD
An autosomal dominant syndrome characterized mainly by congenital sensorineural hearing loss accompanied by dystrophic or absent nails. Coniform teeth, selective tooth agenesis, and hands and feet abnormalities are present in some patients.
Sources
Last updated 5/8/2026, 6:26:39 AM