Gene & Protein nomenclature: N-Myc, c-Myc, et. al

Question

Can someone explain (or point me to an explanation of) exactly what is meant by all the different symbols I see used for writing genes and proteins?

I think I know that for genes, we use an italic font and for proteins, we use a regular font.

I think I've also learned that for human, all letters are in uppercase (eg. SHH) whereas for mouse, only the first letter is in uppercase and the remaining letters are in lowercase (Shh). (From http://en.wikipedia.org/wiki/Gene_nomenclature)

But I'm stumped with all the other "tags" (in quotes because that's how they seem to be used and I don't know how else to think of them) that I see floating around gene and protein symbols.

For example, Myc (MYC?).

I see these three articles in uniprot.org:

http://www.uniprot.org/uniprot/Q99417 for C-Myc

http://www.uniprot.org/uniprot/P04198 for N-myc

http://www.uniprot.org/uniprot/P12524 for L-Myc

These proteins are all in human, and yet their recommended names are not all caps; what's up with that? But even more confusing to me are the "C-", "N-", and "L-" letters prefixed to them. What in the world are those supposed to be indicating?

Are these all fundamentally different proteins (coded by different genes), but maybe related somehow to each other (thus the common three letters, 'myc' even if they are not all the same case and not all upper case as I thought was supposed to be the case in human), and they are just given these "C-", "N-", and "L-" tags to distinguish one from the other? Does one tag indicate an oncogene or a proto-oncogene? Why do I sometimes see "c-Myc" and other times, "C-Myc"? Does the case of the "C-" mean something? Is there some kind of key or legend I can look at to get answers to all these questions? I've found some explanations in Scott Gilbert's Developmental Biology textbook, but it still doesn't give me all the answers I seek here

I just want to understand how these tags and symbols are being used because it seems to me that when I read research papers (of which I've read many), they are used by different authors in different papers in ways that are not consistent with each other. Either that, or else I'm missing something very basic, which is why I'm asking here.

Thanks in advance for any help.

Answer 1

There is a useful set of links to nomenclature guidelines for all of the main genetic systems at this Wikipedia page. Personally, I think that the Saccharomyces cerevisiae system works best: it manages to cover dominant and recessive alleles of a gene, the name of the protein, how to refer to a related phenotype, and the use of a parallel convention for the designation of ORFs.

Unfortunately there is now no going back - there are many different systems and there is no hope of unifying them. When this plethora of naming conventions is combined with the reluctance of so many scientists to stick to the guidelines, we have a recipe for near anarchy.

Edit - On the specific topic of MYC nomenclature:

The v- and c- prefixes come from the early days of oncogene research. Viral oncogenes such as myc and src were found to be related to (derived from?) similar genes in normal cells. Thus v- means viral and c- means cellular.

This can be seen if you peruse the HUGO entries for the four MYC family members encoded in the human genome (extracts below). They all have an approved name which relates them back to a viral oncogene found in the genome of avian myelocyomatosis virus. This was the founder member of this gene family. Thus c-myc was the first myc-related gene found in the human genome, and is the one that is responsible for Burkitt's lymphoma. It is true, as @Leonardo says, that in tumours the expression of this this myc gene in lymphatic tissue changes due to chromosomal rearrangements, but this is not the origin of the designation c-myc.

MYC
Approved Symbol:      MYC
Approved Name:   v-myc myelocytomatosis viral oncogene homolog (avian)
Previous Symbols & Names:   "v-myc avian myelocytomatosis viral oncogene homolog"
Synonyms:   bHLHe39, c-Myc
Chromosomal Location: 8q24

MYCL1
Approved Symbol:      MYCL1
Approved Name:   v-myc myelocytomatosis viral oncogene homolog 1, lung carcinoma derived (avian)
Previous Symbols & Names:   MYCL, "v-myc avian myelocytomatosis viral oncogene homolog 1, lung carcinoma derived"
Synonyms:   bHLHe38, "l-myc protein", LMYC, "myc-related gene from lung cancer", "oncogene lmyc"
Chromosomal Location: 1p34.3  

MYCL2
Approved Symbol:      MYCL2
Approved Name:   v-myc myelocytomatosis viral oncogene homolog 2 (avian)
Previous Symbols & Names:   "v-myc avian myelocytomatosis viral oncogene homolog 2"
Synonyms:   bHLHe38
Chromosomal Location: Xq22-q28

MYCN
Approved Symbol:      MYCN
Approved Name:   v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)
Previous Symbols & Names:   NMYC, "v-myc avian myelocytomatosis viral related oncogene, neuroblastoma derived"
Synonyms:   bHLHe37, N-myc
Chromosomal Location: 2p24.3  

Answer 2

That's a good question, and honestly, the nomenclature for genes and their coded proteins is somewhat abused in scientific literature. For example, when referring to microbes (like E. coli), gene names are all lowercase (eg, lacZ). The problem of protein names is compounded when the protein name is (often) an abbreviation.

With respect to myc, it can refer to the family of MYC transcription factor proteins (of which, c-Myc, L-myc and N-myc are members). More commonly, myc refers to c-Myc, and is the name given to a 10-amino acid segment of human proto-oncogene myc (EQKLISEEDL) and is a common epitope added to recombinant DNA for making fusion proteins.

From what I recall, the initial that precedes myc (in this instance) refers to what form of cancer that myc protein is associated with. I know c-myc comes from a mutation in wild-type myc that becomes constitutively expressed. Wikipedia tells me that N-myc is a neuroblastoma-associated myc transcription factor.