ACS Discussion Page

Nomenclature
Dr Rosalind Coleman
    Some of us discussed the growing nomenclature problem with ACS, FATP, FACL, etc at the Lipid Gordon Conference last summer and wanted make the names and numbering system for mammals consistent within the field.
    In order to fix these problems, the acyl-CoA synthetase community needs to decide what to do.   First, we need to identify the interested scientists. Then we can make naming and numbering decisions.  We should send copies of all emails to the human genome nomenclature committee to keep them informed about what we are doing. (hgnc@genenames.org).  When we achieve a consensus and they agree, they will resolve issues with the mouse, etc. nomenclature.
Action Items
    1. Please take a few minutes to think about people not on the email list but who should be involved and let me know.
    2. Should this effort include scientist working on short, medium and very long chain enzymes or should we focus on the long chain acyl-CoA synthetases only?
    3. We are thinking about having a meeting this spring to discuss these issues.  Or will email suffice?  What is your thought?

HGNC response:
    The currently approved stem name for the long-chain genes is "fatty-acid-Coenzyme A ligase, long-chain #".  However, we appreciate that the gene name does not conform to the IUBMB ideal, and so one option is to change the name to "fatty-acid-Coenzyme A synthetase, long-chain #" which allows us to keep the approved FACL# stem symbol.
Questions we need answered
    1. Does the community prefer to use synthase or synthetase?
    2. How does the community feel about the "fatty-acid-Coenzyme A synthetase" part of the name?  Is this accurate for all the ACS family, or would a change to an acyl-CoA synthetase type name and symbol be preferred?

Dr Rosalind Coleman
    Personally I prefer LACS because we can then use MACS for med chain and VLACS for very-long chain, etc.  Would there be any problem with that?-- though I suppose we could go for families like the ABC transporters- but then only the initiated would know which family was which.
    Another problem is that some VLACS-like proteins are called FATP for "fatty acid transport protein." 

HGNC response:
    We would strongly advise against LACS, MACS etc. as these symbols are not hierarchical.  In this case the main family is acyl-CoA synthetase, so for example the ACS stem followed by M (medium chain), L (long chain) etc. would be better from a nomenclature point of view as it would enable easy database searching using the stem symbol.

Dr Concetta DiRusso
    A complication with the yeast and bacterial nomenclature may be that gene names are often assigned on the basis of homologies and the protein names are derived from the gene names.  For example, we called the gene FAT2 because the protein shared sequence identities with FAT1, which was named based on identities with murine FATP.  In standard yeast nomenclature, the protein is named for the gene so the FAT2 gene encodes the Fat2p protein.  It will be very hard, if not  impossible, to change gene names.
    Most of the long chain acyl-CoA synthetases in bacteria, yeast and plants are named for the E. coli FadD gene encoding a med-long chain acyl-CoA synthetase.  Thus there are many fadD genes in mycobacterium, for example, which merely have the AMP, adenylate forming, signature in common.
    My basic question is, are we going to suggest a nomenclature for the proteins or for both the proteins and genes?

HGNC response:
    The HGNC only has authority to name human genes.  Whilst we do try to approve gene names and symbols that could be used for the proteins, this is not always possible.  On this issue our guidelines state:

Dr Rosalind Coleman
In thinking about the numbering system, since most of the published studies are from rat, can we not keep the rat numbers and let either FACL1 or FACL2 be designated "6".

Other ACS family nomenclature
Dr Paul Black
    Regarding other ACS gene families - and more specifically the fatty acid transport proteins (FATP), it seems appropriate that we begin with the ACS root; as pointed out previously we do not know the precise substrates for this family of enzymes although there is significant information that they play a role in fatty acid trafficking (including transport).  The Lodish group has proposed FATP1,2,3,4,5,6; this is based on properties related to fatty acid transport.  We along with others (Bernlohr, Watkins, Stremmel, Berger) have shown members of this sub group do indeed have acyl CoA synthetase enzymatic activity.  In the case of FATP1 from mouse, the Bernlohr group has shown a fairly broad range specificity for activating fatty acids of varying chain lengths; data from our lab is consistent with this as well.
    The question to be addressed is how members of this sub group of ACS enzymes is also involved in fatty acid trafficking.  Perhaps a better statement is that all ACS enzymes are involved in fatty acid trafficking, with some being more specific towards the movement of exogenous fatty acids into the cell.  Clearly there is more to be done before there is a resolution.  This being stated, however, if one looks at the FATP family of proteins and compares them to the ACS family, it is quite clear both have the ATP/AMP binding motif that is a hallmark of adenylate-forming enzymes. Further all of the ACS enzymes with a long-chain specificity have a FACS motif (which we defined using affinity labeling and mutagenesis); many of the features of this later motif are found in the FATP family (or as I prefer a sub group of the ACS enzymes).  Watkins and colleagues have published alignments in the context of bubblegum, which emphasize these similarities further.

Dr Rosalind Coleman
    I agree with Paul Black.  Based on the amino acid sequences shown by Paul Watkins (J Biol Chem. 2000 Nov 10;275(45):35162-9) there is no difference between the so called "FATP"s and the so called "very-long-chain ACS"s.  Functionally, ALL the ACSs probably increase the amount of FA that enters cells because they trap FA as acyl-CoAs.  This property may have led to the designation of some as FATPs.  At the very least, there should be cross referencing.  A better solution would be to label both FATP and very-long-chain ACS as ACSVL with the thought that some may have additional functions.

HGNC response:
    I would just like to make it clear that the FATP# symbols are NOT approved gene symbols.  The genes encoding these proteins have the SLC27A# approved stem symbol.   We do not intend to change the nomenclature of the SLC27A genes.  However, we would be willing to add ACS-type symbols as aliases to the SLC27A gene records.  Please view the SLC27A gene family, and let me know if you think there are any members of this family missing from the table.

Orthology

Dr Paul A. Watkins
    Regarding the human long-chain enzymes, I have looked extensively into the sequences of FACL1 (NP_001986) and FACL2 (NP_066945). By comparison to both EST sequences and genomic sequences, there seems to be no hard evidence to support the existence of FACL1 as a distinct entity. As you know, this is what helped screw up the nomenclature between human and rodent long-chain enzymes. I am working with a local bioinformatics guru (Jonathan Pevsner--check out his recently published book!) to verify before communicating this to NCBI.
    I think a reasonable approach is to first deal with the long-chain enzymes since this seems relatively straightforward (once the FACL1/FACL2 controversy is resolved). Perhaps then we can deal with rest more efficiently.

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