MAP1A/BLC3? Now I am really confused

ABSTRACT

I routinely see people use incorrect names for MAP1LC3/LC3 isoforms in scientific papers. In fact, it happens often enough that I decided to investigate the reason for the apparent confusion. It turns out that the sources of misinformation are abundant, including UniProt and antibody supplier web sites.

I realize that I take uniformity in nomenclature more seriously than most people [1–3]. This concern with gene and protein nomenclature started several years ago when I found it difficult to ascertain the specific protein that researchers were referring to in a paper on mammalian autophagy. My lab works primarily with yeast, so I am in general less familiar with the names of mammalian proteins. Thus, even though the paper I was reading may have been using an alias that many people in the field are familiar with, I was not certain as to which protein was actually the subject of the paper. This is an important point, because we are not supposed to be writing papers in an unclear manner, or in a way that can only be deciphered by those working on particular model systems (which was one reason for unifying the nomenclature of the yeast autophagy-related genes [2]).

So, I have been somewhat surprised when I see papers that refer incorrectly to MAP1LC3. For example, a common error is to write ‘MAP1A/BLC3’ instead of MAP1LC3A/B to refer to both the A and B isoforms. There are several isoforms of MAP1LC3 including MAP1LC3A, MAP1LC3B, MAP1LC3B2 and MAP1LC3C. The official HGNC definition of these names is microtubule associated protein 1 light chain 3 alpha/beta/beta 2/gamma, respectively. These are distinct proteins, with MAP1LC3B being the most commonly analyzed. The point is that MAP1LC3A/LC3A is not the same as MAP1LC3B/LC3B. It is not clear which isoform ‘MAP1A/BLC3’ even refers to. So where did this confusion come from?

If you search for MAP1LC3B on UniProt you find the following: ‘Microtubule-associated proteins 1A/1B light chain 3B’ is the indicated protein name, and alternative names listed include ‘Autophagy-related protein LC3 B, Autophagy-related ubiquitin-like modifier LC3 B, MAP1 light chain 3-like protein 2, MAP1A/MAP1B light chain 3 B, and MAP1A/MAP1B LC3 B’, with ‘Microtubule-associated protein 1 light chain 3 beta’ (the correct name according to HGNC) being listed last. There are some obvious problems with this series of names, starting with ‘Microtubule-associated proteins’ in the plural. That is, we are referring to a single protein here, aren’t we?

Going to various antibody suppliers shows that this problem continues (in this case the names of the suppliers have been omitted for obvious reasons):

1. LC3B (Autophagy Marker Light Chain 3B, MAP1A/MAP1B LC3 B) in humans, is encoded by the gene MAP1LC3B (Microtubule-associated proteins 1A/1B light chain 3B).

2. Rabbit anti Human MAP1LC3A/B (N-Terminal) antibody specifically recognizes an epitope within the N-Terminal (NT) region of both MAP1LC3A (Microtubule-associated proteins 1A/1B light chain 3A/LC3A) and MAP1LC3B (Microtubule-associated proteins 1A/1B light chain 3B/LC3B)…

3. Autophagy-related protein LC3 B, Autophagy-related ubiquitin-like modifier LC3 B, MAP1ALC3, MAP1LC3B, Microtubule-associated proteins 1A/1B light chain 3B

4. Microtubule-associated proteins 1A/1B light chain 3B, Autophagy-related protein LC3 B, Autophagy-related ubiquitin-like modifier LC3 B, MAP1 light chain 3-like protein 2, MAP1A/MAP1B light chain 3 B, MAP1A/MAP1B LC3 B, Microtubule-associated protein 1 light chain 3 beta, Map1lc3b, Map1alc3, Map1lc3

And my current favorite:

1. Anti-Map1alc3, Anti-Map1lc3b, Anti-MAP1A/MAP1B LC3 B, Anti-MAP1A/MAP1B light chain 3 B, Anti-Autophagy-related protein LC3 B, Anti-MAP1 light chain 3-like protein 2, Anti-Autophagy-related ubiquitin-like modifier LC3 B

Really? Map1alc3 is the same as Map1lc3b and these are both the same as MAP1A/MAP1B light chain 3 B? No wonder researchers are confused.

Certainly some of these antibodies recognize more than one isoform, but that is still not an excuse for using the incorrect names. That is, if an antibody recognizes both MAP1LC3A and MAP1LC3B, just say so. Do not make up names such as MAP1A/BLC3, or as one company did when describing the specificity of their antibody that recognizes all MAP1LC3 isoforms as binding to ‘microtubule-associated protein 1 light chain 3 alpha, MAP1BLC3, MAP1ALC3, LC3, LC3A, ATG8E’.

Now, don’t even get me started on the GABARAP subfamily…