NTR: [signal peptidase activity]

[ValWood]

Please provide as much information as you can:

• Suggested term label:

signal peptidase activity

• Definition (free text)

Catalysis of the hydrolysis of a signal peptide of a polypeptide chain, in a reaction that requires a free N-terminal amino group, C-terminal carboxyl group or both.

• Comment

This reaction occurs during or after transport to a specific location in the cell

• Reference, in format PMID:#######

use a ref from https://en.wikipedia.org/wiki/Signal_peptidase

• Gene product name and ID to be annotated to this term

These https://www.pombase.org/term/GO:0006465

All are proteases (with one regulatory subunit), so this appears to be single step. Instead I would annotate the process to "protein maturation" or "mitochondrial protein maturation"

• Parent term(s)

GO:0008238 exopeptidase activity

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

• Cross-references

not sure about this:

• For enzymes, please provide RHEA and/or EC numbers.
• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

@pgaudet no hurry for this, but do you think this is OK? Otherwise we aren't really capturing the process often (or the function).

[sjm41]

@ValWood We used to have a bunch of signal peptidase terms, but they were all obsoleted because they 'referred to gene products". E.g.:

id: GO:0042499 name: obsolete signal peptide peptidase activity namespace: molecular_function def: "OBSOLETE. Catalysis of the intramembrane proteolysis of a signal peptide, following its removal from a preprotein." [PMID:12077416] comment: This term was made obsolete because it represents a gene product. synonym: "signal peptide peptidase activity" EXACT [] synonym: "SPP" EXACT [] xref: EC:3.4.23.- is_obsolete: true replaced_by: GO:0042500

id: GO:0009003 name: obsolete signal peptidase activity namespace: molecular_function def: "OBSOLETE. Catalysis of the cleavage of a signal peptide from a protein precursor." [GOC:mah] comment: This term was made obsolete because 'signal peptide' is difficult to define unambiguously, and because the term refers to gene products. synonym: "signal peptidase activity" EXACT [] is_obsolete: true replaced_by: GO:0008233

id: GO:0009004 name: obsolete signal peptidase I activity namespace: molecular_function def: "OBSOLETE. Catalysis of the cleavage of N-terminal leader sequences from secreted and periplasmic proteins precursor." [GOC:curators] comment: This term was made obsolete because it represents a gene product. synonym: "bacterial leader peptidase 1" RELATED [] synonym: "bacterial leader peptidase I activity" NARROW [] synonym: "Escherichia coli leader peptidase" NARROW [] synonym: "eukaryotic signal peptidase" NARROW [] synonym: "eukaryotic signal proteinase" NARROW [] synonym: "HOSP" RELATED [] synonym: "leader peptidase activity" RELATED [] synonym: "leader peptidase I" RELATED [] synonym: "leader peptide hydrolase activity" RELATED [] synonym: "leader proteinase activity" RELATED [] synonym: "phage-procoat-leader peptidase activity" NARROW [] synonym: "pilin leader peptidase" NARROW [] synonym: "prokaryotic leader peptidase" NARROW [] synonym: "prokaryotic signal peptidase" NARROW [] synonym: "prokaryotic signal proteinase" NARROW [] synonym: "propeptidase activity" RELATED [] synonym: "PuIO prepilin peptidase" NARROW [] synonym: "signal peptidase I activity" EXACT [] synonym: "signal peptide hydrolase activity" RELATED [] synonym: "signal proteinase activity" RELATED [] synonym: "signalase activity" RELATED [] synonym: "SPase I activity" RELATED [] synonym: "SPC" RELATED [] is_obsolete: true replaced_by: GO:0004252

Regarding EC xrefs, EC 3.4.21.89 (signal peptidase I = GO:0009004 above) may match what you require? In UniProt, EC 3.4.21.89 is annotated to "Signal peptidase complex catalytic subunit SEC11A/B/C" (in humans), which are orthologs of pombe sec11.

EC 3.4.21.89 Accepted Name: signal peptidase I Alternative Name(s): bacterial leader peptidase I, phage-procoat-leader peptidase, SPase I Reaction catalysed: Cleavage of hydrophobic, N-terminal signal or leader sequences from secreted and periplasmic proteins Comment(s):

• Unaffected by inhibitors of most serine peptidases, but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity.
• Cleaves a single bond -Ala-|-Ala- in M13 phage procoat protein, producing free signal peptide and coat protein.
• Eukaryote signal peptidases that may have somewhat different specificity are known from the endoplasmic reticulum membrane and mitochondrial inner membrane.
• Belongs to peptidase family S26.

Also, the parent term for 'signal peptide peptidase' would be endopeptidase, rather than exopeptidase.

[ValWood]

OK. I can't find the closure ticket, but this one isn't really a single gene product.

[ValWood]

@pgaudet do you have any thoughts on this? We have a process term GO:0006465 | signal peptide processing but shouldn't this really be an activity?

[pgaudet]

Right, there was a massive purge of peptidases in 2015, I am also not sure of the reason, but possibly to match MEROPs classification: https://www.ebi.ac.uk/merops/about/glossary.shtml#CATTYPE

Right now the peptidase classification is by mechanism; if we add substrates, we might need to create many descendant terms or do co-annotations to describe the substrate and the mechanism.

Right now based on other priorities, I would leave this as it is, since we can capture what we need using GO:0006465 | signal peptide processing. Protein maturation (as your proposed annotation in the original comment) seems too wide as a category, see children

I would first clean up that branch (including removing gene products like 'insulin processing), and then we can see what is needed in MF.

OK?

Thanks, Pascale

[ValWood]

OK.

[pgaudet]

Closing for now. We ca revisit later