hsp-1 (HSC70 / HSP70A) curation notes

UniProt P09446 (Swiss-Prot), WormBase F26D10.3. Constitutive cytosolic Hsc70 of
C. elegans, orthologous to human HSPA8.

Identity and expression

• hsp-1 (hsp70A) is one of six C. elegans hsp70 genes and is the constitutively
  expressed, mildly heat-inducible cognate member
  PMID:2841196.
• Localisation is cytosolic with nuclear entry during stress
  PMID:19858203.

Chaperone cycle and co-chaperones (core function 1)

• HSP-1 is an ATP-dependent folding chaperone whose ATPase is regulated by BAG
  and J-domain co-chaperones; the C-terminal BAG fragment of UNC-23 regulates
  HSP-1 in muscle
  PMID:25053410
  PMID:25053410.
• STI-1/Hop bridges HSP-1 and Hsp90 (DAF-21)
  PMID:19467242
  PMID:19559711.
• HSP-1 binds the TPR domain of the myosin chaperone UNC-45
  PMID:23332754.
• UNC-23 (BAG2 orthologue) recruits HSP-1 to muscle attachment structures
  PMID:26435886.

Clathrin uncoating (core function 2; module synaptic_vesicle_endocytosis)

• Hsc70 is the ATPase that strips clathrin coats, and needs a J-domain
  co-chaperone (auxilin). C. elegans has a single auxilin, dnj-25, whose in
  vitro uncoating co-chaperone activity matches mammalian auxilin; RNAi of the
  worm auxilin blocks yolk endocytosis and freezes clathrin dynamics
  PMID:11175756
  PMID:11175756
  PMID:11175756.
• Direct worm evidence that HSP-1 controls clathrin dynamics comes from the
  endosomal retromer study: loss of HSP-1 (like loss of the J-domain protein
  RME-8) causes endosomal clathrin to over-accumulate and become static
  PMID:19763082.
• No study has yet scored synaptic coated-vesicle accumulation after hsp-1
  perturbation; the synaptic-vesicle uncoating role is inferred from the
  dnj-25 phenotype, the unc-26 (synaptojanin) coated-vesicle phenotype and
  mammalian HSC70 biochemistry. GOA carries no clathrin-coat-disassembly row
  for hsp-1, so this is recorded as a core function (GO:0072318) with the
  above support rather than as a NEW annotation.

Non-core, evidence-supported roles

• Longevity: chaperone targets of HSF-1, including hsp-1, are required for
  the extended lifespan of insulin-signalling mutants
  PMID:14668486.
• Retrograde endosome-to-Golgi transport of MIG-14/Wntless is an indirect
  consequence of the endosomal clathrin role [PMID:19763082, quoted above];
  kept as non-core.

Review decisions (summary)

All 26 GOA rows were reviewed in the earlier COMPLETE review (17 ACCEPT,
3 KEEP_AS_NON_CORE, 5 MODIFY of generic protein binding / chaperone terms).
This pass added: a propagation_review block for the IBA MODIFY row, the
auxilin reference (PMID:11175756), and a clathrin-coat-disassembly core
function grounded in PMID:11175756 and PMID:19763082.