The AAA Protein Superfamily
What is the AAA superfamily?
The AAA (for ATPases Associated with various cellular Activities; suggested by Kunau et al., Biochimie 75, 209-224 (1993)) protein superfamily is characterized by a highly conserved module of approximately 230 amino acid residues including an ATP binding consensus, present in one or two copies in the AAA proteins. AAA proteins are found in all organisms (Archaea, Eubacteria, Eukaryota: Protista, Fungi, Plants, Animals) and are essential for, e.g., cell cycle functions, vesicular transport, mitochondrial functions, peroxisome assembly, and proteolysis.
The first sequence of an AAA protein (porcine VCP; Koller and Brownstein, Nature 325, 542-545) has been published 1987, and Peters et al. first observed that members of different families (VCP/p97 and Sec18p/NSF) are related (EMBO J. 9, 1757-1767 (1990)). While many details about interacting proteins have been described for some AAA families, the common function of the AAA module is still a matter of speculation.
References/Reviews
- For an in-depth review about the AAA superfamily, and a hypothesis about the function of the AAA module, see
F. Confalonieri, M. Duguet
A 200-amino acid ATPase module in search of a basic function
BioEssays 17(7), 639-650 (1995)
- For an analysis of the phylogeny of the AAA members, sequence "fingerprints" for subfamilies, and a secondary structure prediction, have a look at Andreas Beyer's review
A. Beyer
Sequence analysis of the AAA protein family
Protein Science (1997), 6: 2043-2058
- Jon Swaffield and Michael Purugganan give an overview of the evolution of the conserved AAA region:
Jonathan C. Swaffield and Michael D. Purugganan
The evolution of the conserved ATPase domain (CAD): Reconstructing the history of an ancient protein module
Journal of Molecular Evolution 45, 549-563 (1997)
- This review about the AAA family contains - besides a lot of information about the function of the different AAA members - some beautiful pictures of p97 molecules and an illustration of the targets of AAA action within the cell. Check it out:
Sheetal Patel and Martin Latterich
The AAA team:related ATPases with diverse functions
Trends in Cell Biology 8, 65-71 (1998)
- And an AAA reference on the WWW: The MIPS database now has a specific section about AAA genes and proteins with very nice graphics. The pages mostly focus on yeast YTA proteins and their homologues.
The phylogenetic tree (calculated from the conserved modules) provides an overview of the AAA superfamily and gives access to information about AAA proteins and families by clicking them in the tree. (If you use a non-graphical browser, choose the list view). The AAA-Tree is available in an object oriented (PICT) format to allow for high quality printouts and easy modification (colors, names of genes, additions...). Use it freely, but please mention who constructed it.
Congress announcements and summaries, and the latest published results about AAA. Latest news:
The Ninth International Meeting on AAA Proteins
is organized by Teru Ogura, Kumamoto University, Japan, Yukio Fujiki and Tsutomo Katayama, both Kyushu University, Japan, and will take place in Kumamoto, Japan, November 6 - 10, 2011 at the Kumamoto City International Center. The conference will feature advances in the areas of structure and mechanism of AAA+ proteins, a variety of cellular functions and role of AAA+ proteins in diseases. For details and for registration, see the AAA conference web site.
A special issue of Journal of Structural Biology on AAA+ proteins will be published in conjunction with the conference. Submission of papers for this special issue will be from November, 2011. Deadline for original papers will be December 10, 2011, and for review articles, January 10, 2012. The estimated publication date for the issue is July 2012.
The AAA Protein Superfamily site
has been chosen as HMS Beagle's "Web Pick of the Day" (January 31, 1999). HMS Beagle is a webzine for biological and medical researchers.
Especially for scientists new to the subject of AAA proteins, this list is meant to provide a starting point to get into contact with fellow researchers.
Why do you list my favourite AAA member as a "far relative" only???
And how definite is your classification within the AAA superfamily?
OK, I´ll show you what I based the substructure and limits of the AAA family on, and will even reveal some unsolved problems.
File of AAA Sequences
Sequences of all AAA proteins (except those submitted as confidential, see below) and of some distant relatives of the superfamily as "Text only" and as a MS Word 5 file in NBRF/PIR-format.
File of sequences of the conserved AAA domaines
Sequences of the conserved modules of all AAA proteins (except those submitted as confidential, see below) and of some distant relatives of the superfamily as "Text only" and as a MS Word 5 file in NBRF/PIR-format suited for the calculation of phylogenetic trees.
Are the sequences up to date?
EMBL and GenBank use protein identifiers (PIDs) as an indicator for sequence changes. While the accession number is unaffected by sequence corrections, the PID changes with each sequence update (but not with other alterations of the database entry, e.g., an added reference). I have appended PIDs to all EMBL links (if they were listed in the database entries) to enable you to verify their actuality. If different versions of a sequence exist, an asterisk marks the database entry used for tree construction and included in the sequence files.
Allows to search for sequence names, host organisms, or any text (author of an AAA reference, protein functions...). Maybe an overkill for a database of little more than 100 entries, but a challenge (=fun) for me to realize it in Hypercard. If an AAA protein you know of seems to be missing in my database, search for its database accession number: it might be listed with a different name (even a typo is not impossible:-), or as a "far relative" only.
Links to Sequence databases and to other services of interest for AAA researchers:
[To our home page]
Kai-Uwe Fröhlich
Last edited: June 16, 2011
Phylogenetic Tree of the AAA Superfamily
What's 
about AAA?