CBL10 (SCaBP8, At4g33000, UniProt Q7FRS8) - curation notes

Session 1 (2026-10-19): new review

No deep-research provider is available in this environment, so these notes record
manual literature research (cached publications under publications/, PubMed
E-utilities, web search). Most CBL10 primary papers are abstract-only in the cache;
PMID:19448033 and PMID:31858132 have full text.

Identity and domain architecture

• 256 aa calcineurin B-like (CBL) calcium sensor with four EF-hands; UniProt:
  "Belongs to the calcineurin regulatory subunit family." Only EF-hand 4 has a
  full canonical PROSITE Ca2+-binding loop annotated (residues 207-218).
• Unlike CBL4/SOS3 it has no N-myristoylation motif; an N-terminal hydrophobic
  extension targets it to membranes PMID:19448033. UniProt (from PMID:19832944): "The N-terminal 40
  amino acids are necessary and sufficient for vacuolar and endosomal targeting."
• Two splice isoforms differing at the N terminus (isoform 2: MTTGRPNNILALKIST -> MEQVSS);
  both interact with CIPK24 per IntAct.

Calcium binding and kinase activation (shoot SOS branch)

• Quan et al. 2007 PMID:17449811. Shoot-preferential
  role PMID:17449811.
  Partial redundancy with SOS3/CBL4 PMID:17449811.
• Phosphorylation by SOS2 at the C terminus (Ser-237 in the isoform numbering used by the
  paper; UniProt maps it to Ser-247 of the canonical isoform 1) stabilizes the complex at the
  membrane PMID:19448033. scabp8 has reduced PM Na+/H+ exchange
  PMID:19448033.
• General CBL mechanism: CIPK phosphorylates a conserved CBL C-terminal Ser
  PMID:22253446.
• CIPK8 is a second CBL10 partner activating SOS1 PMID:31858132.

Vacuolar branch / localization

• Kim et al. 2007 PMID:17825054; cbl10 shoots have lower Na+ PMID:17825054.
• Batistic et al. 2010: N-terminal targeting signals determine CBL localization
  PMID:19832944. UniProt:
  "Exclusively targeted to the tonoplast when interacting with CIPK24 (PubMed:19832944)."
• Localization is therefore dual (PM per Quan 2007 / Lin 2009; tonoplast + endosomes per
  Kim 2007 / Batistic 2010). Lin 2009 (Pardo unpublished) found tonoplast Na+/H+ exchange
  unchanged in scabp8, so the vacuolar mechanism is not settled PMID:19448033.
• Soluble pool also exists PMID:19448033 - basis for cytoplasm IDA. No evidence for nuclear localization
  (nucleus row is an AtSubP prediction).

Kinase-independent regulation of AKT1

• Ren et al. 2013 [PMID:23331977 "CBL10 directly interacted with AKT1, as verified in
  yeast two-hybrid, BiFC and co-immunoprecipitation experiments"; "CBL10 impairs
  AKT1-mediated inward K+ currents"; "CBL10 may compete with CIPK23 for binding to AKT1 and
  negatively modulate AKT1 activity"]. Evidence is from overexpression lines plus
  oocyte/protoplast electrophysiology; supports GO:0019870 potassium channel inhibitor
  activity and negative regulation of K+ transport, but it is a single study.

Reproductive development

• Monihan et al. 2016 [PMID:26979332 "CBL10 functions early in reproductive development
  before fertilization"; "Neither SOS2 nor SOS3 function in reproductive development in
  response to salt"]. Not annotated in GOA; this is a salt-conditional phenotype and I did
  not add a NEW developmental term (necessity, not demonstrated participation).

Curation decisions (summary)

• Ca2+ binding (IBA/IDA/IEA): accept.
• Protein binding IPI x3: per policy, MODIFY to informative MFs (CIPK24 activation ->
  GO:0030295 protein kinase activator activity; Kim 2007 binding only -> GO:0019901 protein
  kinase binding; AKT1 -> GO:0019870 potassium channel inhibitor activity).
• kinase binding IEA: MODIFY to GO:0030295 (specific supported activity).
• vacuolar membrane IEA -> MODIFY to plant-type vacuole membrane (is_a descendant, already
  IDA/IBA on the gene).
• nucleus ISM: REMOVE (prediction; contradicted by membrane targeting data).
• regulation of potassium ion transport IMP -> MODIFY to GO:0043267 negative regulation.
• monoatomic ion homeostasis IMP -> MODIFY to GO:0055078 sodium ion homeostasis.

2026-10-20: ported fixes from the parallel review branch

• Tonoplast core function MF changed from GO:0043539 to GO:0043495 protein-membrane adaptor activity, with a NEW IDA row on PMID:19832944 PMID:19832944, the curated UniProt note "Exclusively targeted to the tonoplast when interacting with CIPK24", and S-acylation-dependent tonoplast targeting (PMID:31441225, added to publications/).
• AKT1 binding row and the AKT1 core function: GO:0019870 refined to GO:0070320 inward rectifier potassium channel inhibitor activity (AKT1 is an inward rectifier).

2026-10-24: OpenScientist run on AKT1 inhibition

Report: CBL10-hypotheses/cbl10-akt1-inhibition/openscientist.md (3 iterations, ~26 min).
Hypothesis: CBL10 directly inhibits AKT1, independently of CIPK kinase activity, and this
has been replicated.

• Verdict from the run: partially supported, single-source. No study citing Ren et al. 2013
  re-measured AKT1 currents or root K+ in cbl10 loss-of-function plants. [file:ARATH/CBL10/CBL10-hypotheses/cbl10-akt1-inhibition/openscientist.md "The in-planta support that does exist is overexpression-based, not derived from cbl10-null plants"]
• Checked here: the Ren 2013 abstract confirms the in-planta lines are overexpressors and
  that the inhibition was shown by electrophysiology in oocytes and root protoplasts
  PMID:23331977.
  The HAK5 claim was confirmed from the PMID:26474642 abstract (CBL1/8/9/10 with CIPK23
  activate HAK5). I did not re-check the citation counts (76 citing papers, 105 Europe PMC records).
• Where I disagree with the report: it recommends against GO:0019870 because the mechanism
  is competition with CIPK23 and because CBL10 activates HAK5. GO:0019870 and its child
  GO:0070320 (used here since #5245) mean binding a potassium channel and reducing its
  activity, which a competitive binder satisfies, and HAK5 is a different target reached
  through a kinase. So the GO:0005515 MODIFY to GO:0070320 stays, with a single-source
  caveat added to its reason.
• The report would also keep the BP row as GO:0043266 regulation of potassium ion transport.
  The review keeps its MODIFY to GO:0043267 negative regulation: whatever the mechanism, the
  measured effect of CBL10 on AKT1 currents is a decrease, so the sign is known.
• Change made: the AKT1-inhibition core function was removed. Single-lab, overexpression-only
  in planta, and peripheral to the Ca2+-sensor role with CIPK24.