asna-1 (C. elegans, UniProt P30632) - manual literature research

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literature survey done with PubMed searches (asna-1 elegans, 11 hits) and the cached
publications in publications/. Full text was read where full_text_available: true.

Identity and family

• ASNA-1 (ZK637.5, synonym tag-205) is the single C. elegans member of the ArsA/GET3
  ATPase family, the ortholog of yeast Get3 and human ASNA1/TRC40/GET3
  [file:worm/asna-1/asna-1-uniprot.txt "Belongs to the arsA ATPase family."].
• Domains: P-loop ATPase (Pfam PF02374 ArsA_ATPase; NCBIfam TIGR00345 GET3_arsA_TRC40;
  HAMAP MF_03112 Asna1_Get3). A zinc site formed by Cys285/Cys288 bridges the homodimer
  (HAMAP-predicted).

Biochemistry

• Purified MBP-ASNA-1 is an ATPase whose activity is stimulated by As(III) and Sb(III)
  PMID:17419726.
  Abstract-only in cache.
• Kao et al. 2007 describe asna-1 as encoding an ATPase PMID:17289575. Abstract-only in cache.

Tail-anchored (TA) protein targeting

• Raj et al. 2021 (full text) show ASNA-1 is required for ER targeting of the TA protein
  SEC-61beta in the intestine, identify WRB-1 as its ER receptor, and show WRB-1 and
  SEC-61beta co-immunoprecipitate with ASNA-1::GFP
  PMID:33883621
  PMID:33883621
  PMID:33883621.
• ASNA-1 exists in reduced and oxidized states; the reduced form is needed for TA
  targeting and cisplatin resistance, while the oxidized (chaperone/holdase-like) form is
  compatible with insulin secretion
  PMID:33883621.
• wrb-1 mutants share the TA targeting and cisplatin-sensitivity defects but not the
  insulin secretion defect, separating these functions
  PMID:33883621.
• Point mutants dHis164 and A63V (preferentially oxidized) are cisplatin sensitive and
  TA-targeting defective but insulin-secretion normal (Raj et al. 2022, PMID:36480541).

Insulin secretion and growth

• asna-1 null mutants arrest reversibly at L1, have reduced DAF-28/insulin secretion;
  expression in sensory neurons and intestine
  PMID:17289575.
• ASNA-1 acts in neurons for DAF-28 secretion; it interacts with the ER chaperone
  ENPL-1/GRP94 (likely in its oxidized chaperone form), localizes to Golgi in neurons, and
  loss of asna-1 perturbs ER/Golgi trafficking pathways
  PMID:36939052
  PMID:36939052.
• How ASNA-1 promotes insulin secretion mechanistically is not known; it does not bind
  proinsulin PMID:36939052.

Drug/metal sensitivity

• asna-1 mutants are hypersensitive to arsenite and antimonite (PMID:17419726) and to
  cisplatin (PMID:20966125; human ASNA1 rescues). In eukaryotes ArsA-family proteins have
  been repurposed for TA protein targeting, so these sensitivities are plausibly indirect
  consequences of loss of TA protein biogenesis or of redox-sensor function.

Peripheral mentions

• PMID:23705068 (Zhu et al. 2013, sphingolipid-TORC1) uses asna-1(ok938) only as a control
  L1-arrest strain: neither mmBCFA nor d17iso-sphingolipid supplementation rescues it
  PMID:23705068.
  It provides no information on ASNA-1 molecular function.
• PMID:22511947 (Billing et al. 2012) RNAi screen for asna-1-like larval arrest
  modifiers; context only.
• PMID:24058864 asna-1 mutants have elevated UPR activity; context only.
• PMID:14704431 and PMID:19123269: large-scale yeast two-hybrid maps reporting an
  ASNA-1/CEE-1 interaction; no functional follow-up.