The bipartite CS domain, which was named after CHORD-containing proteins and SGT1 [], is a ~100-residue protein-protein interaction module. The CS domain can be found in stand-alone form, as well as fused with other domains, such as CHORD (), SGS (), TPR (), cytochrome b5 () or b5 reductase, in multidomain proteins []. The CS domain has a compact antiparallel β-sandwich fold consisting of seven β-strands [, ]. Some proteins known to contain a CS domain are listed below []: Eukaryotic proteins of the SGT1 family. Eukaryotic Rar1, related to pathogenic resistance in plants, and to development in animals. Eukaryotic nuclear movement protein nudC. Eukaryotic proteins of the p23/wos2 family, which act as co-chaperone. Animal b5+b5R flavo-hemo cytochrome NAD(P)H oxydoreductase type B. Mammalian integrin beta-1-binding protein 2 (melusin).
This entry represents the CS domain found in Pih1 from Ascomycota. Pih1 is part of the R2TP complex []. The CS domain of Pih1 binds to the unstructured region of Tah1 []. The C-terminal domain of Pih1 consists of a seven-stranded beta sandwich with the topology of a CS domain, a structural motif also found in Hsp90 cochaperones such as p23/Sba1 and Sgt1.
This CS p23-like domain is found in the CacyBP/SIP protein (S100A6 binding protein and Siah-1 interacting protein) []. CacyBP/SIP interacts with S100A6 (calcyclin), with some other members of the S100 family, with tubulin, and with Siah-1 and Skp-1 []. The latter two are components of the ubiquitin ligase that regulates beta-catenin degradation. The beta-catenin gene is an oncogene participating in tumorigenesis in many different cancers. Overexpression of CacyBP/SIP, in part through its effect on the expression of beta-catenin, inhibits the proliferation, tumorigenicity, and invasion of gastric cancer cells []. CacyBP/SIP is abundant in neurons and neuroblastoma NB2a cells. An extensive re-organization of microtubules accompanies the differentiation of NB2a cells. CacyBP/SIP may contribute to NB2a cell differentiation through binding to and increasing the oligomerization of tubulin. CacyBP/SIP is also implicated in differentiation of erythroid cells, rat neonatal cardiomyocytes, in mouse endometrial events, and in thymocyte development [].
This entry represents the CS p23-like domain found in dyslexia susceptibility 1 (DYX1) candidate 1 (C1) protein, DYX1C1, also known as dynein axonemal assembly factor 4 (DNAAF4). The human gene encoding this protein is a positional candidate gene for developmental dyslexia (DD), it is located on 15q21.3 by the DYX1 DD susceptibility locus (15q15-21) []. Independent association studies have reported conflicting results [, , ]. However, association of short-term memory, which plays a role in DD, with a variant within the DYX1C1 gene has been reported []. Mutations in DYX1C1 have been found in patients with primary ciliary dyskinesia []. Most proteins belonging to this group contain a C-terminal tetratricopeptide repeat (TPR) protein binding region [].
This domain is conserved in fungi and might be a zinc-finger domain as it contains three conserved Cs and an H in the C-x8-C-x5-C-x3-H conformation typical of a zinc-finger.
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000106) is described by MIBiG as an example of the polyketide biosynthetic class, in particular the naphthomycin A biosynthetic genecluster from Streptomyces sp. CS [].
Cysteine- and histidine-rich domains (CHORDs) are 60-amino acid modules that bind two zinc ions. They are usually arranged in tandem and are found in all tested eukaryotes, with the exception of yeast, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. Six cysteine and two histidine residues are invariant within the CHORD domain. Three other residues are also invariant and some positions are confined to positive, negative, or aromatic amino acids [, ]. Silencing of the Caenorhabditis elegans CHORD-containing gene results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development. The CHORD domain is sometimes found N-terminal to the CS domain, , in metazoan proteins, but occurs separately from the CS domain in plants. This association is thought to be indicative of an functional interaction between CS and CHORD domains [].
Cyanide is produced in higher plants during ethylene biosynthesis and needs to be removed from plant tissues to avoid toxicity. L-3-cyanoalanine synthase or beta-cyanoalanine synthase (CAS) catalyses the conversion of cyanide and cysteine to beta-cyanoalanine and sulfide [], and then beta-cyanoalanine is converted into asparagine by beta-cyanoalanine hydrolyase. Ethylene is an essential hormone for ripening and expression of CAS is induced during fruit ripening []. CAS shows homology with Cys synthase (CS) and exhibits detectable CS activity. Both CAS and CS belong to the same enzyme family, the beta-substituted Ala synthases []. CAS is localised in the mitochondria [].
CfaE, the tip adhesin of enterotoxigenic Escherichia coli colonisation factor antigen I fimbriae (CFA/I), initiates binding of this enteropathogen to the small intestine. It comprises a stacked N-terminal β-sandwich adhesin domain (AD) and a C-terminal pilin domain (PD), with the putative receptor-binding pocket at one pole and an equatorial interdomain interface [, ].This superfamily represents the adhesin domain of CfaE, homologous to the pilus biogenesis initiator protein CbID and the major pilin subunits of CS pili.
This entry contains proteins with a CHORD (cysteine- and histidine-rich) domain. CHORDs are 60-amino acid modules that bind two zinc ions. They are usually arranged in tandem and are found in all tested eukaryotes, with the exception of yeast, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. Six cysteine and two histidine residues are invariant within the CHORD domain. Three other residues are also invariant and some positions are confined to positive, negative, or aromatic amino acids [, ]. Silencing of the Caenorhabditis elegans CHORD-containing gene results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development. The CHORD domain is sometimes found N-terminal to the CS domain, , in metazoan proteins, but occurs separately from the CS domain in plants. This association is thought to be indicative of an functional interaction between CS and CHORD domains [].Proteins with a CHORD domain include:Cysteine and histidine-rich domain-containing protein 1 (CHORDC1) regulates centrosome duplication [].Integrin beta-1-binding protein 2 (melusin), which is muscle-specific and interacts with the integrin cytoplasmic domain [].
The circumsporozoite (CS) protein is the most prominant surface antigen onthe sporozoite of the malaria parasite, Plasmodium spp. The sporozoite isthe infectious stage of the Plasmodium life cycle, the form in which malariais passed from the mosquito vector to the mammalian host []. Antibodies tothis protein are used in the field to detect exposure to malaria []and it is a target for several vaccines [].The sequence of the CS protein consists of head and tail regions, which arelargely conserved, and a large set of low-complexity repeats, which are variant across strain and species []. The C-terminal region is probably used for anchoring the protein to the cell membrane, while the centralrepeat sequences would be the surface antigen of the organism. The repeats,which encode the immunodominant epitope of the CS protein (see ), diverge morerapidly than the remainder of the gene. It is thought that the maintenanceand evolution of the repeats is achieved via a mechanism that acts not atthe protein level, but rather directly on the DNA sequence [].
NAD(P)H cytochrome b5 oxidoreductase (NCB5OR) is widely expressed in human organs and tissues and is localized in the ER (endoplasmic reticulum) [, ]. It appears to play a critical role in maintaining viable pancreatic beta cells []. Mice homozygous for a targeted knockout (KO) of the gene encoding NCB5OR develop an early-onset nonautoimmune diabetes phenotype with a non-inflammatory beta-cell deficiency. The role of NCB5OR in beta cells may be in maintaining or regulating their redox status []. The gene encoding NCB5OR has been considered as a positional candidate for type II diabetes and other diabetes subtypes related to B-cell dysfunction; however, variation in its coding region does not appear not to be a major contributor to the pathogenesis of these diseases [].This entry represents the CS p23-like domain found in NCB5OR. In addition to a p23-like domain NCB5OR contains an N-terminal cytochrome b5 domain and a C-terminal cytochrome b5 oxidoreductase domain [].
This domain is found in animal PIH1 domain-containing protein 1/2/3 (PIH1D1/2/3) and its homologues []. PIH1D1 is part of the HSP90 co-chaperone R2TP complex involved in the assembly process of many molecular machines []. This domain consists of a seven-stranded beta sandwich with the topology of a CS domain, a structural motif also found in Hsp90 co-chaperones such as p23/Sba1 and Sgt1 []. Proteins containing this domain also includes Kintoun from animals and uncharacterised proteins from fungi and plants. Kintoun (also known as ktu or dynein assembly factor 2, axonemal) is a cytoplasmic protein conserved from ciliated unicellular organisms to mammals. It is required for cytoplasmic pre-assembly of axonemal dynein arm complexes before intraflagellar transport loads them for the ciliary compartment. Its homologue in single-celled alga Chlamydomonas is known as PF13. A mutation in Ktu/PF13 has been identified in some patients with primary ciliary dyskinesia (PCD). In the absence of Ktu/PF13, both dynein arms (inner and outer) are missing or defective in the axoneme, leading to a loss of motility [].
Chorismate synthase (CS; 5-enolpyruvylshikimate-3-phosphate phospholyase; 1-carboxyvinyl-3-phosphoshikimate phosphate-lyase; E.C. 4.2.3.5) catalyzes the seventh and final step in the shikimate pathway which is used in prokaryotes, fungi and plants for the biosynthesis of aromatic amino acids. It catalyzes the 1,4-trans elimination of the phosphate group from 5-enolpyruvylshikimate-3-phosphate (EPSP) to form chorismate which can then be used in phenylalanine, tyrosine or tryptophan biosynthesis. Chorismate synthase requires the presence of a reduced flavin mononucleotide (FMNH2 or FADH2) for its activity. Chorismate synthase from various sources shows a high degree of sequence conservation [, ]. It is a protein of about 360 to 400 amino-acid residues.Depending on the capacity of these enzymes to regenerate the reduced form of FMN, chorismate synthases are divided into two groups: enzymes, mostly from plants and eubacteria, that sequester CS from the cellular environment, are monofunctional, while those that can generate reduced FMN at the expense of NADPH, such as found in fungi and the ciliated protozoan Euglena gracilis, are bifunctional, having an additional NADPH:FMN oxidoreductase activity. Recently, bifunctionality of the Mycobacterium tuberculosis enzyme (MtCS) was determined by measurements of both chorismate synthase and NADH:FMN oxidoreductase activities. Since shikimate pathway enzymes are present in bacteria, fungi and apicomplexan parasites (such as Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum) but absent in mammals, they are potentially attractive targets for the development of new therapy against infectious diseases such as tuberculosis (TB) [, , , , , , , , , ].
Chorismate synthase (CS; 5-enolpyruvylshikimate-3-phosphate phospholyase; 1-carboxyvinyl-3-phosphoshikimate phosphate-lyase; E.C. 4.2.3.5) catalyzes the seventh and final step in the shikimate pathway which is used in prokaryotes, fungi and plants for the biosynthesis of aromatic amino acids. It catalyzes the 1,4-trans elimination of the phosphate group from 5-enolpyruvylshikimate-3-phosphate (EPSP) to form chorismate which can then be used in phenylalanine, tyrosine or tryptophan biosynthesis. Chorismate synthase requires the presence of a reduced flavin mononucleotide (FMNH2 or FADH2) for its activity.Chorismate synthase from various sources shows a high degree of sequence conservation [, ]. It is a protein of about 360 to 400 amino-acid residues.Depending on the capacity of these enzymes to regenerate the reduced form of FMN, chorismate synthases are divided into two groups: enzymes, mostly from plants and eubacteria, that sequester CS from the cellular environment, are monofunctional, while those that can generate reduced FMN at the expense of NADPH, such as found in fungi and the ciliated protozoan Euglena gracilis, are bifunctional, having an additional NADPH:FMN oxidoreductase activity. Recently, bifunctionality of the Mycobacterium tuberculosis enzyme (MtCS) was determined by measurements of both chorismate synthase and NADH:FMN oxidoreductase activities. Since shikimate pathway enzymes are present in bacteria, fungi and apicomplexan parasites (such as Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum) but absent in mammals, they are potentially attractive targets for the development of new therapy against infectious diseases such as tuberculosis (TB) [, , , , , , , , , ].This entry represents conserved regions from chorismate synthase that are rich in basic residues.
The chorismate synthase AroC consists of two DCoH-like beta(2)-α-β(2)-alpha structural repeats.Chorismate synthase (CS; 5-enolpyruvylshikimate-3-phosphate phospholyase; 1-carboxyvinyl-3-phosphoshikimate phosphate-lyase; E.C. 4.2.3.5) catalyzes the seventh and final step in the shikimate pathway which is used in prokaryotes, fungi and plants for the biosynthesis of aromatic amino acids. It catalyzes the 1,4-trans elimination of the phosphate group from 5-enolpyruvylshikimate-3-phosphate (EPSP) to form chorismate which can then be used in phenylalanine, tyrosine or tryptophan biosynthesis. Chorismate synthase requires the presence of a reduced flavin mononucleotide (FMNH2 or FADH2) for its activity. Chorismate synthase from various sources shows a high degree of sequence conservation [, ]. It is a protein of about 360 to 400 amino-acid residues.Depending on the capacity of these enzymes to regenerate the reduced form of FMN, chorismate synthases are divided into two groups: enzymes, mostly from plants and eubacteria, that sequester CS from the cellular environment, are monofunctional, while those that can generate reduced FMN at the expense of NADPH, such as found in fungi and the ciliated protozoan Euglena gracilis, are bifunctional, having an additional NADPH:FMN oxidoreductase activity. Recently, bifunctionality of the Mycobacterium tuberculosis enzyme (MtCS) was determined by measurements of both chorismate synthase and NADH:FMN oxidoreductase activities. Since shikimate pathway enzymes are present in bacteria, fungi and apicomplexan parasites (such as Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum) but absent in mammals, they are potentially attractive targets for the development of new therapy against infectious diseases such as tuberculosis (TB) [, , , , , , , , , ].
