cd06173, MFS_MefA_like, Macrolide efflux protein A and similar proteins of the Major Facilitator Superfamily of transporters. This family is composed of Streptococcus pyogenes macrolide efflux protein A (MefA) and similar transporters, many of which remain uncharacterized. Some members may be multidrug resistance (MDR) transporters, which are drug/H+ antiporters (DHAs) that mediate the efflux of a variety of drugs and toxic compounds, conferring resistance to these compounds. MefA confers resistance to 14-membered macrolides including erythromycin and to 15-membered macrolides. It functions as an efflux pump to regulate intracellular macrolide levels. The MefA-like family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
TIGR02428, 3-oxoadipate_CoA-transferase_subunit_B, 3-oxoacid CoA-transferase, B subunit. Various members of this family are characterized as the B subunits of succinyl-CoA:3-ketoacid-CoA transferase (EC 2.8.3.5), beta-ketoadipate:succinyl-CoA transferase (EC 2.8.3.6), acetyl-CoA:acetoacetate CoA transferase (EC 2.8.3.8), and butyrate-acetoacetate CoA-transferase (EC 2.8.3.9). This represents a very distinct clade with strong sequence conservation within the larger family defined by pfam01144. The A subunit represents a different clade in pfam01144.
cd14014, STKc_PknB_like, Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
cd08563, GDPD_TtGDE_like, Glycerophosphodiester phosphodiesterase domain of Thermoanaerobacter tengcongensis and similar proteins. This subfamily corresponds to the glycerophosphodiester phosphodiesterase domain (GDPD) present in Thermoanaerobacter tengcongensis glycerophosphodiester phosphodiesterase (TtGDE, EC 3.1.4.46) and its uncharacterized homologs. Members in this family show high sequence similarity to Escherichia coli GP-GDE, which catalyzes the degradation of glycerophosphodiesters to produce sn-glycerol-3-phosphate (G3P) and the corresponding alcohols. Despite the fact that most of GDPD family members exist as the monomer, TtGDE can function as a dimeric unit. Its catalytic mechanism is based on the general base-acid catalysis, which is similar to that of phosphoinositide-specific phospholipases C (PI-PLCs, EC 3.1.4.11). A divalent metal cation is required for the enzyme activity of TtGDE.
cd05379, CAP_bacterial, Bacterial CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain proteins. Little is known about bacterial and archaeal members of the CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain family. The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1), cysteine-rich secretory proteins (CRISPs), and allergen 5 from vespid venom, among others. Studies of eukaryotic proteins show that CAP domains have several functions, including the binding of cholesterol, lipids and heparan sulfate. This group includes Borrelia burgdorferi outer surface protein BB0689, which does not bind to cholesterol, lipids, or heparan sulfate, and whose function is unknown.
cd00090, HTH_ARSR, Arsenical Resistance Operon Repressor and similar prokaryotic, metal regulated homodimeric repressors. ARSR subfamily of helix-turn-helix bacterial transcription regulatory proteins (winged helix topology). Includes several proteins that appear to dissociate from DNA in the presence of metal ions.
cd05245, SDR_a2, atypical (a) SDRs, subgroup 2. This subgroup contains atypical SDRs, one member is identified as Escherichia coli protein ybjT, function unknown. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif consensus that generally matches the extended SDRs, TGXXGXXG, but lacks the characteristic active site residues of the SDRs. This subgroup has basic residues (HXXXR) in place of the active site motif YXXXK, these may have a catalytic role. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.
cd06163, S2P-M50_PDZ_RseP-like, RseP-like Site-2 proteases (S2P), zinc metalloproteases (MEROPS family M50A), cleave transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. In Escherichia coli, the S2P homolog RseP is involved in the sigmaE pathway of extracytoplasmic stress responses. Also included in this group are such homologs as Bacillus subtilis YluC, Mycobacterium tuberculosis Rv2869c S2P, and Bordetella bronchiseptica HurP. Rv2869c S2P appears to have a role in the regulation of prokaryotic lipid biosynthesis and membrane composition and YluC of Bacillus has a role in transducing membrane stress. This group includes bacterial and eukaryotic S2P/M50s homologs with either one or two PDZ domains present. PDZ domains are believed to have a regulatory role. The RseP PDZ domain is required for the inhibitory reaction that prevents cleavage of its substrate, RseA.
COG1173, DppC, ABC-type dipeptide/oligopeptide/nickel transport systems, permease components [Amino acid transport and metabolism / Inorganic ion transport and metabolism].
pfam00665, rve, Integrase core domain. Integrase mediates integration of a DNA copy of the viral genome into the host chromosome. Integrase is composed of three domains. The amino-terminal domain is a zinc binding domain pfam02022. This domain is the central catalytic domain. The carboxyl terminal domain that is a non-specific DNA binding domain pfam00552. The catalytic domain acts as an endonuclease when two nucleotides are removed from the 3' ends of the blunt-ended viral DNA made by reverse transcription. This domain also catalyzes the DNA strand transfer reaction of the 3' ends of the viral DNA to the 5' ends of the integration site.
pfam10609, ParA, NUBPL iron-transfer P-loop NTPase. This family contains ATPases involved in plasmid partitioning. It also contains the cytosolic Fe-S cluster assembling factor NBP35 which is required for biogenesis and export of both ribosomal subunits.
COG0601, DppB, ABC-type dipeptide/oligopeptide/nickel transport systems, permease components [Amino acid transport and metabolism / Inorganic ion transport and metabolism].
cd03017, PRX_BCP, Peroxiredoxin (PRX) family, Bacterioferritin comigratory protein (BCP) subfamily; composed of thioredoxin-dependent thiol peroxidases, widely expressed in pathogenic bacteria, that protect cells against toxicity from reactive oxygen species by reducing and detoxifying hydroperoxides. The protein was named BCP based on its electrophoretic mobility before its function was known. BCP shows substrate selectivity toward fatty acid hydroperoxides rather than hydrogen peroxide or alkyl hydroperoxides. BCP contains the peroxidatic cysteine but appears not to possess a resolving cysteine (some sequences, not all, contain a second cysteine but its role is still unknown). Unlike other PRXs, BCP exists as a monomer. The plant homolog of BCP is PRX Q, which is expressed only in leaves and is cellularly localized in the chloroplasts and the guard cells of stomata. Also included in this subfamily is the fungal nuclear protein, Dot5p (for disrupter of telomere silencing protein 5), which functions as an alkyl-hydroperoxide reductase during post-diauxic growth.
cd08501, PBP2_Lpqw, The substrate-binding domain of mycobacterial lipoprotein Lpqw contains type 2 periplasmic binding fold. LpqW is one of key players in synthesis and transport of the unique components of the mycobacterial cell wall which is a complex structure rich in two related lipoglycans, the phosphatidylinositol mannosides (PIMs) and lipoarabinomannans (LAMs). Lpqw is a highly conserved lipoprotein that transport intermediates from a pathway for mature PIMs production into a pathway for LAMs biosynthesis, thus controlling the relative abundance of these two essential components of cell wall. LpqW is thought to have been adapted by the cell-wall biosynthesis machinery of mycobacteria and other closely related pathogens, evolving to play an important role in PIMs/LAMs biosynthesis. Most of periplasmic binding proteins are comprised of only two globular subdomains corresponding to domains I and III of the LpqW protein. The structural topology of these domains is most similar to that of the type 2 periplasmic binding proteins (PBP2), which are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the ligand-binding domains from ionotropic glutamate receptors, LysR-type transcriptional regulators, and unorthodox sensor proteins involved in signal transduction.
pfam10756, bPH_6, Bacterial PH domain. This domain has a bacterial type PH domain structure. This domain was previously known as DUF2581. This family is conserved in the Actinomycetales. Although several members are annotated as RbiX homologs, RbiX being a putative regulator of riboflavin biosynthesis, the function could not be confirmed.
pfam02517, Abi, CAAX protease self-immunity. Members of this family are probably proteases (after a isoprenyl group is attached to the Cys residue in the C-terminal CAAX motif of a protein to attach it to the membrane, the AAX tripeptide being removed by one of the CAAX prenyl proteases). The family contains the CAAX prenyl protease. The proteins contain a highly conserved Glu-Glu motif at the amino end of the alignment. The alignment also contains two histidine residues that may be involved in zinc binding. While they are involved in membrane anchoring of proteins in eukaryotes, little is known about their function in prokaryotes. In some known bacteriocin loci, Abi genes have been found downstream of bacteriocin structural genes where they are probably involved in self-immunity. Investigation of the bacteriocin-like loci in the Gram positive bacteria locus from Lactobacillus sakei 23K confirmed that the bacteriocin-like genes (sak23Kalphabeta) exhibited antimicrobial activity when expressed in a heterologous host and that the associated Abi gene (sak23Ki) conferred immunity against the cognate bacteriocin. Interestingly, the immunity genes from three similar systems conferred a high degree of cross-immunity against each other's bacteriocins, suggesting the recognition of a common receptor. Site-directed mutagenesis demonstrated that the conserved motifs constituting the putative proteolytic active site of the Abi proteins are essential for the immunity function of Sak23Ki - thus a new concept in self-immunity.
