I am reading the following paper and I have come across the following statement:

It has been demonstrated that the phosphorylation of histone H2AX-Ser139 to form γH2AX.

I am not sure what the γ before the gene name H2AX means. Is γ used to indicate that H2AX is phosphorylated? Any insights are appreciated.


Yes, in this context $\gamma$ indicates phosphorylation. See e.g. "The phosphorylated form of H2AX is called $\gamma$-H2AX [18, 19]." from here, and references therein.

I am unsure of the exact basis of this, but I believe that it is because the gamma phosphate group of a nucleotide triphosphate is the one that is generally used by kinases to phosphorylate other functional groups. SEE UPDATE for derivation.

Other notations such as the $p$ prefix are more readable to me, but the usage appears to be cultural and somewhat field-specific.


In response to @MattDMO comment, I read further and found that the terminology derives from this paper. They don't directly explain the terminology, but in context it's pretty clear:

At the maximum, approximately 1% of the H2AX becomes $\gamma$-phosphorylated per Gy of ionizing radiation.

In mammals, the serine in this motif is residue 139, the site of γ-phosphorylation.

When mammalian cell cultures are exposed to ionizing radiation and the acid-soluble nuclear proteins are analyzed on two-dimensional AUT-AUC gels, novel components that will be referred to as $\gamma$ (Fig. 1, A and B) are found in the H2A region of these gels.

It appears that the name probably derives from an observation that was just "whatever in this 2-D gel is $\gamma$-P32 labeled when we induce DSBs when $\gamma$-P32 ATP is present."

@MattDMO also points out that the irradiation that induces the gamma component in this context is gamma radiation. So it's all a bit of a muddle, it could also be that.

  • $\begingroup$ I've never heard of $\gamma$ being used to denote phosphorylation except in the case of H2AX. I suspect the nomenclature derives from its discovery, probably as multiple isoforms by some sort of chromatography or gel electrophoresis, and the phosphorylated form was the third one named ($\gamma$ is the third letter of the Greek alphabet) or the third band/signal observed. This is just a guess, but an educated one. I don't think it has anything to do with the $\gamma-PO_4$ group. $\endgroup$ – MattDMo Oct 29 '20 at 16:50
  • $\begingroup$ @MattDMo Turns out we're both right- it is because of the $\gamma$ phosphate, but it is also H2AX-specific, if I read the paper that first described this correctly. Editing answer. $\endgroup$ – Maximilian Press Oct 29 '20 at 18:02
  • $\begingroup$ Thanks for the link to the paper, it's been helpful. After reading parts of it, especially the 4th paragraph of the results section, I think they called the novel components $\gamma$ because they appeared after ionizing $\gamma$ irradiation, which is the primary form of radiation emitted by $^{137}Cs$, which was the rad source used in these experiments. So, $\gamma$-H2AX is a phosphorylated form of H2AX observed after exposure to $\gamma$-irradiation. Actually, it's probably both $\gamma$ irradiation and $\gamma$-ATP. $\endgroup$ – MattDMo Oct 29 '20 at 18:35
  • $\begingroup$ Hm. a lot of gammas here... $\endgroup$ – Maximilian Press Oct 29 '20 at 18:39
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    $\begingroup$ @MattDMo tNo i was wrong! P32 is a beta emitter. sigh of relief $\endgroup$ – Maximilian Press Oct 29 '20 at 18:50

You're correct: the gamma denotes phosphorylation, as explained and used in this paper's abstract

H2AX is a variant of the H2A protein family, which is a component of the histone octomer in nucleosomes. It is phosphorylated by kinases such as ataxia telangiectasia mutated (ATM) and ATM-Rad3-related (ATR) in the PI3K pathway. This newly phosphorylated protein, gamma-H2AX, is the first step in recruiting and localizing DNA repair proteins.


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