CSN1S1 (human alpha-S1-casein, P47710) - review notes

Identity

• 185 aa precursor, 15 aa signal peptide, mature chain 16-185; alpha-casein family
  (Pfam PF00363), part of the SCPP gene cluster.
• Minor casein in human milk
  PMID:38339021;
  human casein ratio PMID:36903269.

Core function

• Calcium-sensitive casein in the micelle interior
  PMID:36903269.
• Core MF: GO:0140314 calcium ion sequestering activity, as for all calcium-sensitive
  caseins in this batch. This is an approximation (the real cargo is amorphous calcium
  phosphate nanoclusters), recorded as a suggested question.
• Lactation (GO:0007595) as process; extracellular region as location. Casein micelle
  proposed as a new CC term (same proposal as human CSN2/CSN3).

Immunomodulatory activity of the recombinant / non-phosphorylated protein (non-core)

• Monocyte skewing PMID:24083466;
  DC inhibition PMID:24083466.
• TLR4 dependence and phosphorylation switch
  PMID:26909866;
  PMID:30553868;
  PMID:38339021.
• All in vitro with recombinant protein; milk alpha-S1-casein is phosphorylated, so the
  physiological relevance is unclear. Not proposed as GO annotations; noted in description
  with the references above, and raised as a suggested question.

Annotation decisions

• Steroid-response IBA rows: MARK_AS_OVER_ANNOTATED (family convention; casein is the
  expression readout, PANTHER PTN000028262 seeded by bovine PMID:3585228).
• GO:0005515 (HuRI, WITH UniProtKB:Q9UHD9 UBQLN2): REMOVE; UBQLN2 is a cytosolic ubiquilin
  two-hybrid partner with no relevance to a secreted casein (as in human CSN2/CSN3).

Batch-standard revision (2026-10-24)

• Rewrote the description: removed unsupported claims, backed the TLR4, monocyte and
  dendritic-cell statements with PMID:24083466, PMID:26909866, PMID:30553868 and
  PMID:38339021 (all fetched and read; abstracts or full text).
• Rewrote the UBQLN2 protein-binding row (summary, reason, supporting_entities) and
  dropped the citation-fragment supporting_text.
• Split the core function so it covers calcium sequestering only (immune effects and
  bioactive peptides removed from it).
• Added proposed_new_terms (casein micelle), suggested questions (including that
  GO:0140314 is an approximation) and a suggested experiment.
• No OpenScientist deep-research report exists for human CSN1S1.