PAMGO ML modifications

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Biological Process

Proposed term modifications

(only items to be changed are shown)

type I protein secretion system ; GO:0030253

Synonyms

  • broader: ABC translocator
Marcus

It appears to me that the extant terms for protein secretion systems (GO:0030253, GO:0015628, GO:0030254, GO:0030255) are named inappropriately for the biological process ontology. As worded, a "type I protein secretion system" is a thing (a complex of gene products); it is not a process or activity, e.g. attribute of the thing. Many obsolete GO terms were made obsolete because they represent gene products. For example, consider the following:

  • GO:0008014 calcium-dependent cell adhesion molecule activity
  • Definition: OBSOLETE. A calcium-dependent cell adhesion protein (type I membrane protein) that interacts in a homophilic manner in cell-cell interactions.
  • Comment: This term was made obsolete because it represents a gene product. To update annotations, use the biological process term 'calcium-dependent cell-cell adhesion ; GO:0016339', the cellular component term 'integral to membrane ; GO:0016021' and the molecular function term 'protein binding ; GO:0005515'.

Appending the word “activity” did not rescue GO:0008014 from obsolescing, I assume, because the definition described the protein rather than the process. I see strong parallels in the case of the type I-V protein secretion systems, for example:

  • GO:0030253 type I protein secretion system
  • Definition: A bacterial secretion system in which a complex of three proteins spans the inner membrane, periplasmic space, and outer membrane; does not involve proteolytic processing of secreted proteins.

The definition above describes the thing that does the secreting, rather than the process of secretion. Therefore, I think these protein secretion system terms (GO:0030253, GO:0015628, GO:0030254, GO:0030255) should be made obsolete, and new terms created that reflect the process rather than the thing. As an example, I suggest one of the following as a replacement for type I protein secretion system:

  • type I protein secretion system-dependent secretion (no… kind of bulky)
  • secretion via type I protein secretion system (no… sounds like dual annotating with a process and a component)
  • type I protein secretion (yes… simplicity is my favorite)

As a definition for type I protein secretion (the replacement for GO:0030253) I might suggest some minor re-wording of the obsoleted definition:

  • Definition: Secretion of protein via a complex of three proteins spanning the inner membrane, periplasmic space, and outer membrane of a cell, which does not involve proteolytic processing of the proteins secreted.

(Note: I am under the assumption that we even need this term because we want to be able to annotate the protein being secreted, for example an “effector,” not just the protein components of the secretory complex. Otherwise why not just dual annotate to GO:0009306 protein secretion and one of the appropriate protein secretion system complex terms, e.g. GO:0030256?)

I cut “bacterial secretion system” from the definition because I believe (I could be wrong—anyone care to correct me?) that whenever possible we should not specify organisms in definitions. For type V protein secretion system, would it be necessary to say “Gram-negative bacteria” or could that be cut?

I also suggest adding a comment to enhance clarity, such as the one for GO:0005234 glutamate-gated ion channel activity, which is not obsolete:

  • GO:0005234 glutamate-gated ion channel activity
  • Comment: Note that this term represents an activity and not a gene product. Consider also annotating to the molecular function term 'glutamate receptor activity ; GO:0008066'.


type II protein secretion system ; GO:0015628

Synonyms

  • exact: type II protein (Sec) secretion system
  • exact: T2SS
  • exact: main terminal branch
  • exact: MTB
  • related: Sec-dependent secretion system [sensu bacteria]
  • related: general secretion pathway [sensu bacteria]
  • related: general secretory pathway [sensu bacteria]

Definition:

  • A bacterial system for secretion of proteins across the outer membrane using a dedicated secretion apparatus involving multiple proteins. Proteins using this pathway are first translocated across the inner membrane via the Sec (general secretory) or TAT pathways.
Marcus

See comments above regarding thing vs. process

type III protein secretion system ; GO:0030254

Synonyms

  • exact: TTSS
  • exact: T3SS


Marcus

See comments above regarding thing vs. process

type IV protein secretion system ; GO:0030255

Synonyms

  • exact: T4SS


Marcus

See comments above regarding thing vs. process

Type IV pilus dependent-motility ; GO:0043107

(primary term name was switched with that of a synonym, since I think its better to not use acronyms (aka TFA) as the primary term name)

Synonyms:

  • exact: TFP-dependent motility


pilus biogenesis ; GO:0009297

I have tweaked the definition of the following term so that individual pili types (such as Type IV pili) can be children. As the definition was previously written, it implied that all children had to be involved in conjugation, adherence and so on…

Synonyms:

  • exact: pilus biosynthesis

Definition:

  • The assembly of a pilus, a short filamentous structure on a bacterial cell, flagella-like in structure and generally present in many copies. Pili are variously involved in transfer of nucleic acids, adherence to surfaces, and formation of pellicles Is required for bacterial conjugation and plays a role in adherence to surfaces (when it is called a fimbrium), and in the formation of pellicles.

Proposed new terms

Sec protein translocation system

  • Child of “Intracellular protein transport” GO:0006886
  • Child of “Protein insertion into membrane” GO:0051205

Synonyms:

  • exact: Sec protein export system
  • exact: Sec-dependent protein translocation
  • related: general secretion pathway
  • related: general secretory pathway
  • related: general export pathway

Definition:

  • A system for translocation of unfolded proteins across membranes, composed of a conserved heterotrimeric complex together with various accessory proteins. As in, but not restricted to, the taxon Bacteria (Bacteria, ncbi_taxonomy_id:2). In bacteria, Sec-translocated proteins are subsequently secreted via the type II, IV, or V secretion systems.
Marcus

I think that the proposed term sec protein translocation system needs to be reworded to reflect the process of which it is a part (see 1.1.1.1 above). Currently it sounds like a “thing” or gene product, rather than a process.

Twin-arginine translocation system

  • Child of “Intracellular protein transport” GO:0006886

Synonyms

  • exact: "Tat protein translocation system"
  • exact: "twin-arginine-dependent translocation"

Definition:

  • A system for translocation of folded proteins across membranes, generally involving three integral membrane proteins. As in, but not restricted to, the taxon Bacteria (Bacteria, ncbi_taxonomy_id:2). In bacteria, proteins translocated by the Tat pathway may be subsequently secreted via the type II secretion systems.
Marcus

I think that the proposed term twin-arginine translocation system needs to be reworded to reflect the process of which it is a part (see 1.1.1.1 above). Currently it sounds like a “thing” or gene product, rather than a process.

Type IV pilus biogenesis

  • Child of “pilus biogenesis”: GO:0009297

Synonyms:

  • exact: Type IV fimbria assembly
  • exact: Type IV fimbria biogenesis
  • exact: Type IV fimbriae assembly
  • exact: Type IV fimbriae biogenesis
  • exact: Type IV fimbrial assembly
  • exact: Type IV fimbrial biogenesis
  • exact: Type IV fimbrium assembly
  • exact: Type IV fimbrium biogenesis
  • exact: Type IV pilus biosynthesis
  • exact: TFP biogenesis
  • exact: Type 4 pilus biogenesis

Definition:

  • The assembly of a Type IV pilus, composed of a pilus fiber and approximately ten proteins at its base; Type IV pili play a role in cell motility, adherence to substrates, and aggregation


Cellular Component

Proposed term modifications

(only items to be changed are shown)

type I protein secretion system complex ; GO:0030256

Synonyms:

  • broader: ABC translocator complex
  • Change from being child of GO:0044459 “plasma membrane part” to child of GO:0044464 “cell part” (The decision to move large secretion complexes directly to “cell part” GO:0044464 was made with Michelle prior to the July meeting)
Marcus

A question regarding type I protein secretion system complex:

  • GO:0030256 type I protein secretion system complex
  • Definition: A complex of three secretory proteins that carry out secretion in the type I secretion system: an inner membrane transport ATPase (termed ABC protein for ATP-binding cassette), which provides the energy for protein secretion; an outer membrane protein, which is exported via the sec pathway; and a membrane fusion protein, which is anchored in the inner membrane and spans the periplasmic space.

Is the ATPase considered a “secretory protein”? If not, I suggest tightening up the definition. Is the ATPase membrane-bound? Does it have to be, or just the complex of which it is a part? (I agree with moving its parent term from plasma membrane part to “cell part.”)

type II protein secretion system associated complexes ; GO:0015627

  • Change from being child of GO:0044459 “plasma membrane part” to child of GO:0044464 “cell part”

Synonyms:

  • exact: type II protein (Sec) secretion system associated complexes
  • exact: T2SS associated complexes
  • exact: main terminal branch
  • exact: MTB
  • related: Sec-dependent secretion system associated complexes [sensu bacteria]
  • related: general secretion pathway associated complexes [sensu bacteria]
  • related: general secretory pathway associated complexes [sensu bacteria]

Definition:

  • A set of complexes composed of two or more of the approximately 15 proteins that together carry out Type II protein secretion across the outer membrane, following transport across the inner membrane by the Sec or TAT pathways


Request to move mis-annotated genes out of GO:0015627

  • Several genes using the three letter designation Sec or Yaj are presently annotated to GO:0015627. These need to be moved to “Sec complex” GO:0031522


type III protein secretion system complex ; GO:0030257

  • Change from being child of GO:0044459 “plasma membrane part” to child of GO:0044464 “cell part”

Synonyms

  • exact: TTSS complex
  • exact: T3SS complex


Sec complex (sensu Bacteria) ; GO:0031522

  • Change from being child of GO:0044459 “plasma membrane part” to child of GO:0044464 “cell part”

Definition:

  • A transmembrane protein complex involved in the translocation of proteins across the cytoplasmic membrane. In Gram-negative bacteria, Sec-translocated proteins are subsequently secreted via the type II, IV, or V secretion systems. Sec complex components include SecA,D,E,F,G,Y and YajC. As in, but not restricted to, the taxon Bacteria (Bacteria, ncbi_taxonomy_id:2).


Request to move mis-annotated genes out of GO:0015628

  • Several genes using the three letter designation Sec or Yaj are presently annotated to GO:0015628. These need to be moved to “Sec protein translocation system (sensu Bacteria)” (see above) when a GO term has been established


Proposed new terms

TAT protein translocation system complex (sensu Bacteria)

  • Child of “plasma membrane part” GO:0044459

Definition:

  • A complex of three proteins integral to the bacterial cytoplasmic membrane involved in translocation of folded proteins across the bacterial cytoplasmic membrane. As in, but not restricted to, the taxon Bacteria (Bacteria, ncbi_taxonomy_id:2).


type IV protein secretion system complex

  • Child of “cell part” GO:0044464

Synonyms:

  • exact: T4SS complex

Definition:

  • A complex of proteins related to those involved in bacterial DNA conjugative transfer, that permits the transfer of nucleoprotein DNA conjugation intermediates or proteins into the extracellular milieu or directly into host cells. In general the type IV complex forms a multisubunit cell-envelope-spanning structure composed of a secretion channel and often a pilus or other surface filament or protein(s)


Pilus and fimbria terms in GO

Right now, GO has a number of fimbrial terms in the cellular component ontology.

There are two problems with this:

  1. It was decided that the term pilus should be primary to fimbria
  2. These terms are all children of intracellular organelle (GO:0043229) instead of cell projection part (GO:0044463) where they more logically belong (as a sibling of other projections like flagella)

I don’t know the proper protocol, but I favor:

  1. adding the two new terms below
  2. transferring annotation under fimbrium GO:0009289 to pilus part (below)
  3. obsoleting the following terms:
  • fimbrium GO:0009289
  • fimbrial shaft GO:0009418
  • fimbrial tip GO:0009419


Proposed new terms

pilus part

  • Child of “cell projection part” GO:0044463

Synonyms:

  • exact: fimbriae

Definition:

  • Any constituent part of a pilus, a short filamentous structure on the surface of bacterial cell variously involved in nucleic acid transfer, motility, and adherence to substrates


Type IV pilus part

  • Child of “pilus part” (see above)

Synonyms:

  • exact: type IV fimbriae
  • exact: TFP part
  • exact: type 4 pilus part

Definition:

  • Any constituent part of a Type IV pilus, a short filamentous structure on the surface of a bacterial cell distinguished from other pili by post-translational N-methylation of the pilin monomers


Other questions

Can adhesion to host (GO:0044406) be a child of cell-substrate adhesion (GO 0031589)?

Amelia

I don't think so, unless an organism is a kind of substrate. Perhaps we should have a 'cell-organism surface adhesion' term?

Marcus

Two other questions I came across while considering protein transport:

GO:0042953 lipoprotein transport is_a GO:0015031 protein transport. This is true because a lipoprotein is a type of protein. But… GO:0015869 DNA-protein complex transport is_a GO:0015031 protein transport, which begs the question, is a DNA-protein complex a protein?

Why is GO:0009306 protein secretion (“The regulated release of proteins from a cell or group of cells”) a sibling of GO:0015031 protein transport (“The directed movement of proteins into, out of, within or between cells”) Isn’t “regulated release” a type of “directed movement… into, out of or within or between”? Why is secretion not a child of transport?

Amelia

In answer to the second question, at some point in the near future we are going to be splitting up transport and secretion into cellular transport, cellular secretion, organismal transport and organismal secretion. Once those changes are made, secretion will be made a child of transport.



Trudy

The statements below are made in response to issues raised by Marcus and Magdalen on the PAMGO discussion forum.

Marcus 1. I am under the assumption that we even need this term [secretion terms under biological process] because we want to be able to annotate the protein being secreted, for example an “effector,” not just the protein components of the secretory complex. Otherwise why not just dual annotate to GO:0009306 protein secretion and one of the appropriate protein secretion system complex terms, e.g. GO:0030256?

Magdalen’s response: At present, one cannot annotate the proteins being secreted to the process term (something that some of us would really like to change!) However, even without annotating the secreted proteins to these process terms, I still favor creation of biological process terms for each secretion system. Afterall, they are distinct processes. On the other hand, maybe they don’t add much to the information represented by the corresponding cellular components terms. Anyone else have an opinion on this?


Trudy's response: I am beginning to think we are populating the ontology with so many terms that at some point users are going to be confused as to which terms to annotate their gene products to.

These are the various terms we have that one can likely annotate attributes of gene products associated with the secretory pathways to. ( egs. chaperones, translocators, effectors, structural proteins). I have listed them below for clarity.


(A) Terms associated with the secretory systems in the general ontology.

Type 1 protein secretor activity(0) F GO:0015428

Type 1 protein secretion system (2): being changed to “Protein secretion by the type I secretion system” [P] GO:0030253

Type 1 protein secretion complex (0) [C] GO:0030256


Type II protein secretor activity (0) [F] GO:0015447 Type 1I protein secretion system (59): being changed to “Protein secretion by the type II secretion system” [P] GO:0015628 Type II protein secretion system complex (38) [C] GO:0015627


Type III protein secretor activity (0) F GO:0015448 Type III protein secretion system (11) being changed to “Protein secretion by the type III secretion system” [P] GO:0030254 Type II protein secretion system complex (0) [C]GO:0030257


Type IV protein secretor activity (0) [F] GO:0015449 Type IV protein secretion system (0). Being changed to “Protein secretion by the type IV secretion system” [P] GO:0030255 No component term available


Type V protein secretor activity (2) [F] GO:0015323 Type V protein secretion system (2): GO:0030255 being changed to “Protein secretion by the type V secretion system “ No component term available.

Summary We have function, process and component terms for almost all the secretion terms from Type I to Type V.

All the function terms and also the Type II protein secretion system complex term have no definitions.

Among the function terms, the “Type I protein secretor activity’ is the only one that has one gene product annotated to it, all others have none Type II process term has the most annotations (59)


(B)Now under the IBO, the newly created terms relevant to this discussion are in bold

symbiosis, encompassing mutualism through parasitism

          interaction with other organism via secreted substance during symbiotic 
          interaction
                           interaction with host via secreted substance 
                                     interaction with host via protein secreted by type II secretion 
                                     system
                                     interaction with other organism via protein secreted by type 
                                     III secretion
                                     system during symbiotic interaction
                                     interaction with other organism via substance secreted by 
                                     type IV secretion
                                     system during symbiotic


The big question is do we need all these terms in the ontology. To answer this we would have to ask ourselves another question “what comprise the various secretion systems and under which terms can they be annotated. This is what I think from what I gather from the literature.

Quite easily, all the effectors (the gene products that are actually secreted to interact with the plant) can be captured under the new terms under the IBO. In eukaryotic microbes, at least with Phytophthora, I do not think the facilitators of the secretory process are considered secreted products interacting with the host. That may not be the case for bacteria.

All the structural gene products can be captured under the component terms .

What are the function terms capturing? Currently if you look at the numbers in parenthesis under (A) the most annotated to any function term is two. Can all the other gene products (besides the effectors directly interacting with the plant and the components of the systems) associated with the secretory systems be annotated to the function terms? If this is doable then we probably do not need the process terms in the general ontology.

Any further thoughts?????