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In terms of nomenclature/semantics, why are some proteins named proteins, and some named factors?

I've been revising on eukaryotic DNA, and I've come across some proteins that seem to serve roughly the same function, but are named differently. For example,

  • Replication activator protein
  • Replication licensing factors
  • Replication protein A
  • Replication factor C
  • Transcriptional factor
  • Eukaryotic translation initiation factor
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TLDR: As far as I know, there's no specific reason some proteins are called "factors"; it's just a matter of what name was chosen.


"Protein" is a specific term meaning a long chain of amino acids. They are typically at least 50 amino acids long.

Conversely, the word "factor" is quite a loose term and is as broad as even being "an element of something". So, essentially anything in biology from a chemical to temperature could be called a factor.

In the context of biochemistry, a factor is a "substance which takes part in a biochemical reaction… …or process". This could include everything from proteins and enzymes (e.g. EGF), to non-protein chemicals such as substrates, co-factors. Even Ca$^{2+}$ (coagulation factor IV) and nitric oxide/arachidonic acid/etc. (EDHF) fall under this umbrella - a single ion is about as far from a protein as it's possible to get! So many proteins are also given the label of "factor". In fact, Protein C has been named both "Protein C" and "blood coagulation factor XIV".

One reason various proteins have been called "factors" is that the word factor used to be used to refer to genes. I'd speculate that another reason may be that certain names and acronyms were already in place. For example, protein C vs. factor C or CREB-binding protein (CBP) vs. core binding factor (CBF).

But as long as the naming of the proteins is standardized, I see no reason why we shouldn't just use acronyms to describe proteins. After all, protein names can be misleading (e.g. Sonic Hedgehog), and there is a large amount of confusion in the literature between names of proteins.

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    $\begingroup$ Looks like our answers are nearly identical, even down to the SHH reference - I think this one reference has to come up every time someone talks about protein nomenclature. :) $\endgroup$ – Bryan Krause Apr 18 '18 at 19:12
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    $\begingroup$ @BryanKrause I thought the exact same thing! I was slightly worried you'd think I was copying your answer with the SHH point too! I wouldn't have posted if I'd seen yours since you were first and perfectly answered the question but it's quite tricky to delete something that you've just written :) $\endgroup$ – Jam Apr 18 '18 at 19:16
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    $\begingroup$ I think it's pretty obvious with the 4 minute gap and completely different verbiage that no copying was involved. :) Welcome to Bio.SE $\endgroup$ – Bryan Krause Apr 18 '18 at 19:19
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    $\begingroup$ To be pedantic, isn't protein reserved for longer amino acid chains? With short chains referred to by the more genetic "polypeptide"? $\endgroup$ – Jack Aidley Apr 19 '18 at 13:48
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    $\begingroup$ @JackAidley Thanks for the correction; I've added a note. I was never too fond of the protein vs. peptide distinction, but it's nice to be precise $\endgroup$ – Jam Apr 19 '18 at 13:55
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Short Answer

There is no agreed upon naming convention for proteins - there are some rough standards because in language people usually try to convey their ideas in a way others can understand, but that doesn't necessarily mean fixed rules.

Longer Answer

I think it's important to recognize the process for understanding what proteins do is not always straightforward. Most often, a protein's function is first understood by seeing what happens if that protein is absent (and sometimes overexpressed).

The terminology factor implies that a protein is either modulating a process or at least is not by itself sufficient for a process. That is, it is named because when it was omitted, some other measurable process changed. It maybe implies something that has its main function by binding, rather than catalyzing a chemical reaction, or at least that the actual mechanism of action is not yet known at the time of naming.

You would not expect, for example, an enzyme with a known target to be called a factor: it's most likely to be named according to its target and the type of reaction being catalyzed.

However, it's possible for a name to stick from when there is less complete understanding. Something might be called a factor initially because of how it influences some process, but the actual contribution is only understood later. Just for an example, take Complement factor I. Initially named because it had some role in the complement system, now it's known that it enzymatically cleaves another protein.

Importantly, there isn't any pure terminology here or consistent naming convention: in most cases, it just goes back to however the first person to describe the protein discussed it. Some proteins are named (controversially, I'll add) things like Sonic hedgehog - related to the similarly named Hedgehog signalling pathway which is all named because of one person/group's creative description of a related fruit fly phenotype.

Naming something "protein" just identifies that it's a protein, little more.

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Short Answer
All factors are proteins, not all proteins are factors

Background
A factor is typically a small protein that regulates a larger target protein directly by specifically associating with it, or indirectly by affecting its substrate. For example, protein factors play key roles in protein synthesis (Berg et al., 2002) and see Fig. 1.:

  • An initiation factor binds to the much larger and more complex multi-subunit ribosome during the initiation of translation, a part of protein biosynthesis (fig. 1);
  • A release factor terminates translation by the ribosome by recognizing the termination codon or stop codon in an mRNA sequence
  • A transcription factor is a protein that regulates the much more complex and bigger RNA polymerase. Transcription factors control the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence.

Reference
-Berg et al., Biochemistry, 5th ed. New York: Freeman (2002)
<


IF

Fig. 1. Inititation factors are relatively small proteins that interact with the large ribosomal multi-subunit complex. source: Concepts Of Genetics

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    $\begingroup$ Only problem I have with this answer is there are lots of proteins that are named "factor" that don't fit into the better-defined categories you mention like initiation/release/transcription factors. Also there are plenty of proteins in those categories that are also certainly not named factor. $\endgroup$ – Bryan Krause Apr 18 '18 at 20:38
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    $\begingroup$ Hi, @AliceD, nice answer! I'm not sure about the "all factors are proteins" statement though? While it's clearly true that almost all factors are proteins and that the naming paradigm is pretty nebulous, I think there are still at least a couple (coagulation factor IV, EGHF) which might not be, since they may have been named before their molecular identity was known $\endgroup$ – Jam Apr 18 '18 at 23:01
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    $\begingroup$ @AliceD Whoops, that was a typo, sorry! en.wikipedia.org/wiki/… My main point about Factor IV was that I think some things are called "factor" before we know whether they're proteins :) $\endgroup$ – Jam Apr 18 '18 at 23:12
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    $\begingroup$ I agree with @Jam, a factor need not be a protein and, AFAIAA that is why many were originally called 'factors' - because it was not known what they were. Since then, of course, the word has been more widely applied. $\endgroup$ – Jack Aidley Apr 19 '18 at 13:11
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    $\begingroup$ @AliceD My understanding is that this is only true where the non-protein is required for the action of the protein. $\endgroup$ – Jack Aidley Apr 19 '18 at 13:46
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There are at least two reasons why certain compounds were historically named in the manner ‘function–factor’.

  1. When you have some impure preparation that exerts a biological function but do not know the chemical nature of the component responsible is.

For example an unknown growth factor, could be a protein, but it could also be a steroid etc.

  1. As a deliberate contrast to enzyme to emphasize that the activity is not catalytic. The point here is not the opposition to a different type of protein.

For example, in DNA or RNA synthesis you have the actual enzymes (DNA and RNA polymerases) that work catalytically to form phosphodiester bonds, and then various accessory proteins that are required to bind to specific regions of DNA, but do not catalyse any chemical reaction. In this case the word ‘protein’ does not distinguish the molecule from an enzyme.

In cases where the need to make such distinctions is not evident to a scientist who has established the protein nature of an activity, he may have chosen to designate it protein for greater precision.

Coda

When a field has matured sufficiently there is often an initiative to rationalize nomenclature. This is frequently resisted by the originators of the nomenclature. In this respect Fritz Lipmann is reputed to have said that “changing names is rewriting history”.

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