A large family of ATPases has been described [1,2,3,4,5,E1] whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. This family is now called AAA, for 'A'TPases 'A'ssociated with diverse cellular 'A'ctivities. The proteins that belong to this family either contain one or two AAA domains.

Proteins containing two AAA domains:

• Mammalian and drosophila NSF (N-ethylmaleimide-sensitive fusion protein) and the fungal homolog, SEC18. These proteins are involved in intracellular transport between the endoplasmic reticulum and Golgi, as well as between different Golgi cisternae.
• Mammalian transitional endoplasmic reticulum ATPase (previously known as p97 or VCP) which is involved in the transfer of membranes from the endoplasmic reticulum to the golgi apparatus. This protein forms a ring- shaped homooligomer composed of six subunits. The yeast homolog is CDC48 and it may play a role in spindle pole proliferation.
• Yeast protein PAS1, essential for peroxisome assembly and the related protein PAS1 from Pichia pastoris.
• Yeast protein AFG2.
• Sulfolobus acidocaldarius protein SAV and Halobacterium salinarium cdcH which may be part of a transduction pathway connecting light to cell division.

Proteins containing a single AAA domain:

• Escherichia coli and other bacteria ftsH (or hflB) protein. FtsH is an ATP-dependent zinc metallopeptidase that seems to degrade the heat-shock sigma-32 factor. It is an integral membrane protein with a large cytoplasmic C-terminal domain that contain both the AAA and the protease domains.
• Yeast protein YME1, a protein important for maintaining the integrity of the mitochondrial compartment. YME1 is also a zinc-dependent protease.
• Yeast protein AFG3 (or YTA10). This protein also seems to contain a AAA domain followed by a zinc-dependent protease domain.
• Subunits from the regulatory complex of the 26S proteasome [6] which is involved in the ATP-dependent degradation of ubiquitinated proteins: a) Mammalian subunit 4 and homologs in other higher eukaryotes, in yeast (gene YTA5) and fission yeast (gene mts2). b) Mammalian subunit 6 (TBP7) and homologs in other higher eukaryotes and in yeast (gene YTA2). c) Mammalian subunit 7 (MSS1) and homologs in other higher eukaryotes and in yeast (gene CIM5 or YTA3). d) Mammalian subunit 8 (P45) and homologs in other higher eukaryotes and in yeast (SUG1 or CIM3 or TBY1) and fission yeast (gene let1). d) Other probable subunits such as human TBP1 which seems to influences HIV gene expression by interacting with the virus tat transactivator protein and yeast YTA1 and YTA6.
• Yeast protein BCS1, a mitochondrial protein essential for the expression of the Rieske iron-sulfur protein.
• Yeast protein MSP1, a protein involved in intramitochondrial sorting of proteins.
• Yeast protein PAS8, and the corresponding proteins PAS5 from Pichia pastoris and PAY4 from Yarrowia lipolytica.
• Mouse protein SKD1 and its fission yeast homolog (SpAC2G11.06).
• Caenorhabditis elegans meiotic spindle formation protein mei-1.
• Yeast protein SAP1.
• Yeast protein YTA7.
• Mycobacterium leprae hypothetical protein A2126A.

It is proposed that, in general, the AAA domains in these proteins act as ATP-dependent protein clamps [5].

In addition to the ATP-binding 'A' and 'B' motifs (see the relevant entry <PDOC00017>), which are located in the N-terminal half of this domain, there is a highly conserved region located in the central part of the domain which we have used to develop a signature pattern.