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atp6v1b2

Properties1
aliasesATP6V1B2, V-type proton ATPase subunit B2, vacuolar H+-ATPase B2 subunit, V1B2, csV1B2

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stub

⚠️ Auto-extracted by Claude on 2026-06-13. Stub seeded on basis of two inbound references from cellular-senescence and senolytics. Canonical IDs (UniProt P21281, NCBI Gene 526, HGNC 854) confirmed via UniProt REST API in this seeding run. Other fields require a full protein seeding pass. gap/needs-canonical-id (ensembl, genage-id, druggability-tier not yet looked up).

ATP6V1B2 (V-type proton ATPase subunit B2)

V-type proton ATPase subunit B, brain isoform (gene symbol ATP6V1B2; UniProt P21281; NCBI Gene 526). A catalytic subunit of the vacuolar-type H+-ATPase (v-ATPase) proton pump complex, which drives lysosomal acidification, endosomal trafficking, and intracellular pH homeostasis. Normally regarded as a lysosomal/endosomal membrane component.

Relevance to cellular senescence

A 2025 Weizmann Institute (Krizhanovsky lab) preprint identifies cell-surface ATP6V1B2 (csV1B2) as a marker of a functionally distinct subset of senescent cells 1. In response to DNA damage-induced senescence, a subset of senescent cells upregulates ATP6V1B2 on the cell surface — a localization that is atypical for this normally intracellular proton-pump subunit.

The csV1B2-positive subset is characterized by:

  • Altered lysosomal activity and intracellular pH (consistent with perturbed v-ATPase proton-pumping)
  • A transcriptional signature associated with DNA repair and resistance to apoptosis
  • Presence in aging lungs and fibrotic lungs in vivo (mouse and/or human — full-tissue composition not confirmed from abstract)
  • Correlation with resistance to ABT-737-induced apoptosis in culture — ABT-737 is the tool-compound analog of navitoclax (BCL-2/BCL-xL/BCL-w pan-inhibitor) used in the BH3-mimetic senolytic class

This makes csV1B2 a candidate biomarker of senolytic resistance within the navitoclax/ABT-263 drug class and a potential marker of a persistent, apoptosis-refractory senescent population. See senolytics for the BH3-mimetic class context and cellular-senescence § Senescent-cell heterogeneity and the senotype concept for the senotype framework.

Abstract-only: The mechanism by which csV1B2 confers apoptosis resistance is not established from the abstract. Causal evidence and mechanistic pathway details require full-text verification. gap/no-mechanism gap/preprint-not-peer-reviewed gap/needs-replication

Complex context

ATP6V1B2 is the B2 catalytic subunit of the V1 sector of the v-ATPase complex. The V1 sector (cytoplasmic) contains the ATP-hydrolysis machinery; it couples to the V0 sector (membrane) to drive proton translocation. A full protein seeding pass should enumerate the other V1 subunits and map the complex architecture. gap/needs-canonical-id

Cross-references

Footnotes

Footnotes

  1. freizus-2025-atp6v1b2-persistent-senescence · Freizus N et al. (Krizhanovsky lab, Weizmann Institute) · preprint (bioRxiv) · doi:10.1101/2025.11.30.691415 · 2025-12-01 · in-vitro (human + mouse senescent cells) + in-vivo (aging + fibrotic lungs) · abstract-only; not peer-reviewed · identifies csV1B2 as marker of apoptosis-resistant persistent senescent subset; ABT-737 resistance correlation gap/preprint-not-peer-reviewed ↩

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