sec11 notes

Deep research

No sec11-deep-research-*.md provider file was present in the sparse
genes/NEUCR/sec11/ checkout. I did not write a synthetic provider file; the
manual literature and PAINT synthesis for this review is recorded here instead.

Literature search

Searches for Neurospora crassa sec11, NCU04519, Q7RY44, and
Neurospora signal peptidase found the genome paper that supplied the OR74A
gene model PMID:12712197, but no paper directly assaying NCU04519/sec11
signal-peptidase activity, essentiality, or localization.

The functional evidence comes from conserved fungal and eukaryotic Sec11/SPC
work:

• Budding yeast SEC11 was cloned by complementation of the sec11-7
  temperature-sensitive secretion mutant; sec11 cells accumulated
  core-glycosylated invertase and acid phosphatase with intact signal peptides,
  and a null allele at the SEC11 locus was lethal PMID:3283143.
• Yeast signal peptidase purification recovered Sec11 as a component of the
  ER signal peptidase complex PMID:1846444.
• Yeast mutational analysis showed that conserved Ser, His, and Asp residues
  in Sec11 are important for ER signal peptidase activity PMID:10206957.
• Human cryo-EM structures resolved SPC-A and SPC-C complexes with SEC11A or
  SEC11C catalytic subunits and placed the active site at the ER
  membrane-proximal transmembrane window PMID:34388369.
• The 2024 yeast Spc2 work used a yeast SPC AlphaFold2-Multimer model and
  in vivo cleavage assays to show that accessory subunits tune the substrate
  and cleavage-site specificity of the Sec11-containing complex
  PMID:39565596.
• A 2026 substrate-bound human SPC-A structure directly visualized how Sec11A
  engages a signal peptide c-region in a hydrophobic binding groove while the
  h-region sits in the transmembrane window PMID:42173868.
• A 2026 yeast Sec11 study mapped the C-terminal short helix of Sec11 as a
  membrane-spanning segment that helps stabilize internal signal sequences
  during productive SPC engagement PMID:42586426.

PAINT and PANTHER

Q7RY44 is in PTHR10806:SF6, the fungal Sec11 subfamily that also contains
S. cerevisiae SEC11/P15367. That supports the ISS transfers from the budding
yeast protein and argues against any metazoan-paralog-specific interpretation.

The PTHR10806 PAINT export has three IBD rows:

• PTN000086749 at the PTHR10806 root: GO:0008233 peptidase activity.
  This deliberately shallow root assertion spans bacterial, archaeal, and
  eukaryotic type I signal peptidase relatives. For Q7RY44 the term is true
  but too general because GO:0009003 signal peptidase activity is already
  supported.
• PTN000086750 at Eukaryota: GO:0005787 signal peptidase complex.
  This is the correct depth for the ER SPC complex claim.
• PTN000086750 at Eukaryota: GO:0051604 protein maturation.
  This is the conservative process assertion for eukaryotic Sec11-mediated
  signal peptide removal. The historically tempting GO:0006465 signal peptide processing process term is obsolete; the live process-level
  replacement used here is GO:0016485 protein processing.

Annotation decisions

The core conserved annotations are accepted: signal peptidase activity,
signal peptidase complex, and endoplasmic reticulum membrane.

GO:0004252 serine-type endopeptidase activity and GO:0009003 signal peptidase activity are both retained because they capture different aspects of
the Sec11 reaction: the Ser/His/Asp mechanism and the signal-peptide substrate
class.

Both GO:0051604 protein maturation rows are modified to GO:0016485 protein processing, the live process-level term for SPC-catalyzed signal peptide
cleavage. Both GO:0008233 peptidase activity rows, the GO:0005783 endoplasmic reticulum row, and the GO:0016020 membrane row are true but too
general beside accepted specific process, activity, and ER membrane terms.

GO:0045047 protein targeting to ER is removed. The SPC catalytic subunit
cleaves signal peptides once nascent chains have engaged or crossed the ER
translocon; it is not one of the factors that direct proteins toward the ER.