Etymology of PAX proteins

Question

What is the reasoning behind naming proteins first found in Drosophila as paired box? All I could find on internet is that it was first found in Drosophila as a protein with paired domain, but I couldn't find anything about the term box along with it. Could anyone please signify the terms paired and box in the name of that protein?

Answer 1

According to InterPro, a paired domain is a DNA-binding element consisting of paired N-terminal and C-terminal subdomains, separated by a linker. PAX proteins follow this motif, and as such typically represent a class of helix-turn-helix transcription factors.

Box is the more interesting term here. In genetics, a box can be used to describe any regulatory element of a gene, including its promoter, UTRs and any enhancer or silencer elements. More loosely they also use box to describe coding segments of a gene, but in older publications.

Going back to Drosophila, however, studies in embryogenesis initially identified a protein called paired, a.k.a. prd. Homology studies into mammalian transcription factors found the presence of a prd-like domain in human HUP transcription factors, and these were renamed to PAX (ref). Thus, the naming of PAX family proteins classicaly denotes the presence not of a PRD regulatory element, but of a coding region for a prd-like domain in the gene product.

Answer 2

In addition to the other answer, the following is some historical context on the naming of these genes.

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1980 October: Discovery of pair-rule genes in Drosophila.

Nusslein-Volhard C, Wieschaus E. 1980. Mutations affecting segment number and polarity in Drosophila. Nature 287:795-801.

We have undertaken a systematic search for mutations that affect the segmental pattern depending on the zygotic genome... In [pair-rule mutants,] homologous parts of the pattern are deleted in every other segment

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1986 May: Isolation of the paired gene in Drosophila.

Kilchherr F, Baumgartner S, Bopp D, Frei E, Noll M. 1986. Isolation of the paired gene of Drosophila and its spatial expression during early embryogenesis.

Here we report the isolation of the pair-rule gene paired (prd)... Transcripts of prd exhibit a pattern of seven evenly spaced bands during late syncytial blastoderm, reflecting a double-segment periodicity...

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1986 December: Characterization of the paired box domain in paired.

Bopp D, Burri M, Baumgartner S, Frigerio G, Noll M. 1986. Conservation of a Large Protein Domain in the Segmentation Gene paired and in Functionally Related Genes of Drosophila. Cell 47:1033-1040.

...we show here that the prd gene contains a third domain about twice the size of the homeo domain, the paired box...

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1988 May: First use of the abbreviation Pax to describe paired box containing murine homologs to paired.

Deutsch U, Dressler GR, Griss P. 1988. Pax 1, A Member of a Paired Box Homologous Murine Gene Family, Is Expressed in Segmented Structures during Development. Cell 53:617-625.

With the objective of isolating murine paired box homologs, a mouse paired box sequence (Pax 1) was identified that shows extensive nucleotide and amino acid sequence homology to all three known Drosophila paired box genes.

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In response to a comment on the other answer:

Paired box refers to a DNA sequence/motif. The actual paired domain is a DNA binding motif present in some transcription factors. The crystal structure of the paired domain from prd has been solved. PDB: 1PDN. Expectedly, it doesn't really look like as box.

Xu W, Rould MA, Jun S, Desplan C, Pabo CO. 1995. Crystal structure of a paired domain-DNA complex at 2.5 Å resolution reveals structural basis for Pax developmental mutations. Cell 80:639-650.