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The NFAT Naming Vote

Results of Voting on the NFAT Family Nomenclature

Results of a vote on the NFAT/NFATC nomenclature

Introduction
Approved symbols
Results
Annonomous comments

Introduction

The proposal to change the  nomenclature scheme for the genes encoding members of the NFAT family of transcription factors has provoked a number of responses and comments. The history of identification and naming of the various genes is clearly open to different interpretations, and the nomenclature committee has decided that it is counterproductive to publish extensive accounts of the history as seen by the key participants. Whatever has happened previously what is now at issue, from our perspective, is the clear and unambiguous naming of the genes concerned. I have recently asked the NFAT research community to vote on the names to be used, to prevent further confusion in the literature and databases. The closing date for this vote was 1 December 2000 and a decision has now been reached, see below for results and comments that were made during the past month. With thanks to all of you who have contributed to this survey of opinion.
Ruth Lovering

Approved Symbols

Following this vote and the comments received, the gene descriptions have been modified to:

NFATC1
Description: nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent  1

NFATC2
Description: nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent  2

NFATC3
Description: nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent  3

NFATC4
Description: nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent  4

NFAT5
Description: nuclear factor of activated T-cells-like 5, tonicity-resonsive

Please note that the GENE symbol is in capitals and with no hyphens. By using this standard system it should be easier to retrieve all future publications electronically. All other aliases for these genes will be listed in both our database, Entrez Gene and on the NFAT page.

Results

About 70 people were invited to vote on this issue. I received 40 replies from these people along with a further 3 unrequested votes. Because of the sensitivity of this matter these extra votes were not included.  There were 19 votes for NFAT# and 21 votes for NFATC#. As NFATC# are currently the approved symbols in both the mouse and human databases I suggest that this nomenclature is used in all future publications.

The Votes for the NFAT5/TONEBP/NFATL1 gene were more complex. Many of the voters did not express an opinion on this matter, while some gave two preferences. If two preferences were expressed they were counted as two votes.

There were 18 votes for NFAT5, 17 votes for TONEBP, 6 votes for NFATL1.

NFAT5 (nuclear factor of activated T-cells 5) is currently the approved symbol in both the mouse and human databases. As a gene database editor from my experience I would suggest that the use of NFATL1 for the gene locus would be the most logical. However this was not the favoured option. NFAT5 is distinct from the NFATC# and therefore would distinguish between the functional differences, yet maintain the structural link. It would also enable the “TONE” root to be used for other gene symbols. As we are currently hoping to approve 40, 000 gene symbols this root may be of use to us.

This issue has been discussed with the rest of the HUGO nomenclature committeeand we have agreed to keep the NFAT5 symbol.

Comments

I have not previously taken a position on NFAT nomenclature, because I find that the literature of NFAT protein chemistry and cell biology has had no difficulty keeping track of four proteins, despite different usages on the Sunrise Coast and the Sunset Coast of this country.  However, I recognize the need, in the genome nomenclature, to settle on a single symbol to identify each gene.

I do have some serious misgivings about conducting a vote on this issue, even while I applaud your attempt to give a fair hearing to all views. First, because the outcome will depend on who is included in the vote, and a different set of equally plausible voters will give a different outcome. And more sadly, because settling on a unified NFAT nomenclature has been turned into a contest. I feel strongly that the best outcome is one not listed in your message, which recognizes the common contributions of several laboratories to delineating the NFAT gene family and therefore adopts the designation for each NFAT gene that is preferred by the laboratory that first reported identification of the gene or its cDNA. Thus, in order of publication, the symbols would be NFAT1, NFATC1, NFATX, and NFAT3.

I think that the simplification misses the critical scientific point. The NF-ATc proteins are all located in the cytoplasm till activation, they are all alcineurin-dependent in function and they are all cyclosporin-sensitive. These characterisitics are due to a unique translocation domain on these proteins that is the signature of the group.  In contrast, the TonEB protein does not have this domain, but rather responds to toncity signals by transcriptional induction and is not cyclosporin sensitive. The only thing that TonEBP has in common with the NF-ATc1-4 proteins is the rel domain. The remaining 600 amino acids are completely different.

The reason for disbanding NFATC is because this is a historical hang-over from a time when NFAT was yet to be characterised, and was known to associate with other components, termed NFATN. However, NFATN is not a specific component of NFAT and NFAT can act as a partner with many different factors such as members of the Fos, Jun, CREB, ATF and Oct families. Because NFATN is no longer in use, NFATC should like-wise no longer be used. In addition, the simplest nomenclature is usually the best one.

I am glad that there is an effort to unify the nomenclature as it is currently very confusing since NFAT1 = NFATc2 and NFAT2 = NFATc1, etc. I look forward to hearing about the results. I hope that tabulating the voting is not as difficult as our current Presidential election has become!

Please note Disclaimer.


Footnotes (from the Human Gene Nomenclature Committee)
1. The convention for naming genes by their similarity to others is to use "L" for like, ie in this case NFATL1. Molecular weights are usually avoided in gene symbols as estimates are often variable, and hence including it can be confusing. Simple arbitrary numbering is used instead. HGNC Guidelines .

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