The P-Type ATPase Superfamily

Abstract

P-type ATPases function to provide homeostasis in higher eukaryotes, but they are essentially ubiquitous, being found in all domains of life. Thever and Saier [J Memb Biol 2009;229:115–130] recently reported analyses of eukaryotic P-type ATPases, dividing them into nine functionally characterized and 13 functionally uncharacterized (FUPA) families. In this report, we analyze P-type ATPases in all major prokaryotic phyla for which complete genome sequence data are available, and we compare the results with those for eukaryotic P-type ATPases. Topological type I (heavy metal) P-type ATPases predominate in prokaryotes (approx. tenfold) while type II ATPases (specific for Na⁺,K⁺, H⁺ Ca²⁺, Mg²⁺ and phospholipids) predominate in eukaryotes (approx. twofold). Many P-type ATPase families are found exclusively in prokaryotes (e.g. Kdp-type K⁺ uptake ATPases (type III) and all ten prokaryotic FUPA familes), while others are restricted to eukaryotes (e.g. phospholipid flippases and all 13 eukaryotic FUPA families). Horizontal gene transfer has occurred frequently among bacteria and archaea, which have similar distributions of these enzymes, but rarely between most eukaryotic kingdoms, and even more rarely between eukaryotes and prokaryotes. In some bacterial phyla (e.g. Bacteroidetes, Flavobacteria and Fusobacteria), ATPase gene gain and loss as well as horizontal transfer occurred seldom in contrast to most other bacterial phyla. Some families (i.e. Kdp-type ATPases) underwent far less horizontal gene transfer than other prokaryotic families, possibly due to their multisubunit characteristics. Functional motifs are better conserved across family lines than across organismal lines, and these motifs can be family specific, facilitating functional predictions. In some cases, gene fusion events created P-type ATPases covalently linked to regulatory catalytic enzymes. In one family (FUPA Family 24), a type I ATPase gene (N-terminal) is fused to a type II ATPase gene (C-terminal) with retention of function only for the latter. Several pseudogene-encoded nonfunctional ATPases were identified. Genome minimalization led to preferential loss of P-type ATPase genes. We suggest that in prokaryotes and some unicellular eukaryotes, the primary function of P-type ATPases is protection from extreme environmental stress conditions. The classification of P-type ATPases of unknown function into phylogenetic families provides guides for future molecular biological studies.

Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts

“…Consistent with detection of M3 species in MLNs, overrepresented genes include genes important for survival in macrophages, including genes involved in resisting pore-forming antimicrobial peptides (pilB; K02652), resisting attack with peroxide (peroxyredoxin; ahpC; K03386), and acquisition of Mg 2+ (Mg 2+ transporter-C mgtC family; K07507; macrophages represent low Mg 2+ environments, and mgtC is required by Salmonella for macrophage survival [Supplemental Table S4; Blanc-Potard and Groisman 1997]). Consistent with reports that osmotic stress responses are important for some enteric pathogens (Sleator and Hill 2002), M3 genomes overrepresent an inducible P-type ATPase K+ importer with high K+ affinity (Epstein 1992), whose primary function in bacteria may be protection from environmental stress (Chan et al 2010;Supplemental Table S4). M3 genomes overrepresent other genes known to confer oxidative stress resistance, including class I ribonucleotide reductase (RNR) genes and proteins that repair oxidative DNA damage (Supplemental Table S4).…”

The Amino Acid-Polyamine-Organocation Superfamily

“…The amino acid-polyamine-organocation (APC) superfamily is a large superfamily which on the basis of recent 3D structural analyses [Chan et al, 2010;Fang et al, 2009;Gao et al, 2010;Jeckelmann et al, 2011;Kowalczyk et al, 2011] appears to be much larger than previously thought. Previously we had established superfamily status for the APC superfamily [Chang et al, 2004;Jack et al, 2000;Young et al, 1999], but the five families then recognized for this superfamily included only one of the four families that have been suggested to be related, based on the recent 3D structural data.…”

Functional Determinants of Metal Ion Transport and Selectivity in Paralogous Cation Diffusion Facilitator Transporters CzcD and MntE in Streptococcus pneumoniae

“…Regardless of the mechanism of metal toxicity, bacteria have evolved ways to minimize the deleterious impact of metal ion excess. One well-characterized strategy involves the use of metal efflux transporters, such as cation diffusion facilitator (CDFs) (18) and P-type ATPase proteins (19), to remove excess metal ions from the cytoplasm.…”