S100A10 (p11, annexin A2 light chain) - curation notes

UniProt: P60903 (human). 97 aa S100 family protein. PANTHER PTHR11639:SF74.

Deep research status

• just deep-research-falcon human S100A10 was launched at the start of this review
  (run in parallel with just fetch-gene-pmids). See end of file for outcome.
• Literature was gathered directly from cached publications (publications/PMID_*.md)
  and PubMed searches; additional key papers cached: PMID:16400147, PMID:12050667,
  PMID:21768297, PMID:12660155.

Core biology

Calcium-insensitive S100 protein; obligate homodimer

• UniProt: "Does not appear to bind calcium. Contains 2 ancestral calcium site related to
  EF-hand domains that have lost their ability to bind calcium." [file:human/S100A10/S100A10-uniprot.txt]
• PMID:9886297; PMID:9886297
• Consequence: the IBA-propagated calcium ion binding and calcium-dependent protein binding
  are inherited from the family ancestor but are lost in the S100A10 lineage (target-specific
  divergence). Ca2+-independence of its target binding is the defining feature that lets
  S100A10 hold ANXA2 in a permanent complex.

AnxA2-S100A10 heterotetramer (AIIt, calpactin I)

• PMID:9886297
• PMID:23091277
• PMID:23091277
• Submembranous localisation coupled to AnxA2: PMID:3126079.

Adaptor: bridging AnxA2 to third-party proteins (AHNAK, SMARCA3)

• AHNAK: PMID:14699089
• Structures: PMID:22940583;
  PMID:23275167
• Membrane repair context (AHNAK/dysferlin): PMID:22940583.
• SMARCA3 (HLTF): PMID:23415230; PMID:23415230

Trafficking / surface presentation of channels and receptors (best-supported core role)

• TASK-1 (KCNK3): PMID:12198146; masks ER retention signal.
• NaV1.8 (SCN10A): PMID:12050667
• TRPV5/TRPV6: PMID:12660155
• 5-HT1B receptor: PMID:16400147 and depression-like phenotype in KO mice.
• CCR10: PMID:26941067
• TRPM4 peptide binding in an S100ome-wide FP screen (PMID:31837246; abstract only).

Cell-surface plasminogen receptor / plasmin generation

• PMID:9836589; PMID:9836589
• In vivo: PMID:21768297
• S100A10 acts as a cofactor/template (binds plasminogen through C-terminal lysines),
  so positive regulation of plasminogen activation is well founded.

Peripheral / indirect phenotypes

• Actin stress fibres/cell spreading via Rac1 (siRNA): PMID:23129259 Indirect.
• Lipid domain/budding in GUVs (PMID:23861394): the property is AnxA2's; S100A10 is
  dispensable ("This property is observed for the full-length monomeric protein").
• Proteomics: urinary exosomes (PMID:19056867), vein ECM (PMID:27068509), ECM protocol
  (PMID:28675934) - HTP detections.

Annotation decisions (summary)

• Core: AnxA2-p11 complex; transmembrane transporter (ion channel) binding; protein
  localization to plasma membrane; positive regulation of plasminogen activation;
  cytoplasmic face of plasma membrane; homodimerization.
• Remove: calcium ion binding (IBA), calcium-dependent protein binding (IBA) - lost in S100A10;
  mRNA transcription by RNA pol II (IEA) - not a transcription machinery component.
• Generic protein binding: MODIFY where the cited paper supports adaptor activity
  (AHNAK/SMARCA3 recruitment), transmembrane transporter binding (TRPM4), GPCR binding (CCR10);
  REMOVE otherwise (interactions captured by GO:1990665 complex membership).

Additional literature (from falcon deep research, verified against PubMed abstracts)

• WPB exocytosis: PMID:28450451 -> supports positive regulation of exocytosis (non-core).
• Lipid interaction: PMID:34339205 -> weak model-membrane binding; NOT lipid binding (PMID:23861394)
  accepted with caveat.

Deep research outcome

• just deep-research-falcon human S100A10 succeeded (S100A10-deep-research-falcon.md), although it ran
  past the wrapper's 600 s timeout before the file was written. The review was drafted from primary
  literature first and then cross-checked against the falcon report; no conflicts with the annotation
  decisions apart from the two additions above.