This family consists of several animal specific latexin and proteins related to latexin that belong to MEROPS proteinase inhibitor family I47, clan I- []. Latexin, a protein possessing inhibitory activity against rat carboxypeptidase A1 (CPA1) and CPA2 (MEROPS peptidase family M14A), is expressed in a neuronal subset in the cerebral cortexand cells in other neural and non-neural tissues of rat [, ]. OCX-32, the 32kDa eggshell matrix protein, is present at high levels in the uterine fluid during the terminal phase of eggshell formation, and is localised predominantly in the outer eggshell. The timing of OCX-32 secretion into the uterine fluid suggests that it may play a role in the termination of mineral deposition []. OCX-32 protein possesses limited identity (32%) to two unrelated proteins: latexin and to a skin protein that is encoded by a retinoic acid receptor-responsive gene, TIG1. Tazarotene Induced Gene 1 (TIG1) is a putative 228 transmembrane protein with a small N-terminal intracellular region, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal. TIG1 is up-regulated by retinoic acid receptor but not by retinoid X receptor-specific synthetic retinoids []. TIG1 may be a tumour suppressor gene whose diminished expression is involved in the malignant progression of prostate cancer [].
The CPA2 family is a moderately large family (over 100 sequenced members) from bacteria, archaea and eukaryotes. Among the functionally well-characterised members of the family are (1) the KefB/KefC K+ efflux proteins of Escherichia coli which may be capable of catalysing both K+/H+ antiport and K+ uniport, depending on conditions [, ], (2) the Na+/H+ antiporter of Enterococcus hirae []and (3) the K+/H+ antiporter of Saccharomyces cerevisiae. It has been proposed that under normal physiological conditions, these proteins may function by essentially the same mechanism [].KefC and KefB of E. coli are responsible for glutathione-gated K+ efflux [, ]. Each of these proteins consists of a transmembrane hydrophobic N-terminal domain, and a less well-conserved C-terminal hydrophilic domain. Each protein interacts with a second protein encoded by genes that overlap the gene encoding the primary transporter. The KefB ancillary protein is YheR. The ancillary proteins stimulate transport activity about 10-fold []. They are important for cell survival during exposure to toxic metabolites, possibly because they can release K+, allowing H+ uptake. Activation of the KefB or KefC K+ efflux system only occurs in the presence of glutathione and a reactive electrophile such as methylglyoxal or N-ethylmaleimide. Formation of the methylglyoxal-glutathione conjugate, S-lactoylglutathione, is catalysed by glyoxalase I, and S-lactoylglutathione activates KefB and KefC []. H+ uptake (acidification of the cytoplasm) accompanying or following K+ efflux may serve as a further protective mechanism against electrophile toxicity [, ]. Inhibition of transport by glutathione is enhanced by NADH []. This entry represents the Glutathione-regulated potassium-efflux system protein KefB.
Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group []. The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified [, ]: class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). Class-I (or type 1) GATase domains have been found in the following enzymes:The second component of anthranilate synthase (AS) []. AS catalyzes the biosynthesis of anthranilate from chorismate and glutamine. AS is generally a dimeric enzyme: the first component can synthesize anthranilate using ammonia rather than glutamine, whereas component II provides the GATase activity []. In some bacteria and in fungi the GATase component of AS is part of a multifunctional protein that also catalyzes other steps of the biosynthesis of tryptophan.The second component of 4-amino-4-deoxychorismate (ADC) synthase, a dimeric prokaryotic enzyme that functions in the pathway that catalyzes the biosynthesis of para-aminobenzoate (PABA) from chorismate and glutamine. The second component (gene pabA) provides the GATase activity [].CTP synthase. CTP synthase catalyzes the final reaction in the biosynthesis of pyrimidine, the ATP-dependent formation of CTP from UTP and glutamine. CTP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the C-terminal section [].GMP synthase (glutamine-hydrolyzing). GMP synthase catalyzes the ATP-dependent formation of GMP from xanthosine 5'-phosphate and glutamine. GMP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the N-terminal section [, ].Glutamine-dependent carbamoyl-phosphate synthase (GD-CPSase); an enzyme involved in both arginine and pyrimidine biosynthesis and which catalyzes the ATP-dependent formation of carbamoyl phosphate from glutamine and carbon dioxide. In bacteria GD-CPSase is composed of two subunits: the large chain (gene carB) provides the CPSase activity, while the small chain (gene carA) provides the GATase activity. In yeast the enzyme involved in arginine biosynthesis is also composed of two subunits: CPA1 (GATase), and CPA2 (CPSase). In most eukaryotes, the first three steps of pyrimidine biosynthesis are catalyzed by a large multifunctional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals). The GATase domain is located at the N-terminal extremity of this polyprotein [].Phosphoribosylformylglycinamidine synthase, an enzyme that catalyzes the fourth step in the de novo biosynthesis of purines. In some species of bacteria and rchaea, FGAM synthase II is composed of two subunits: a small chain (gene purQ) which provides the GATase activity and a large chain (gene purL) which provides the aminator activity. In eukaryotes and Gram-negative bacteria a single polypeptide (large type of purL) contains a FGAM synthethase domain and the GATase as the C-terminal domain [].Imidazole glycerol phosphate synthase subunit hisH, an enzyme that catalyzes the fifth step in the biosynthesis of histidine.A triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity [, ]. Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.
