bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-Actin in
Authors: Celio Marco R 
Published: November 2023

Abstract
Alpha-actinin was first isolated from muscle cells (Ebashi and Ebashi 1965). It is present at the Z-discs where it is proposed to crosslink ends of both parallel and antiparallel arrays of actin filaments (Endo and Masaki 1982; Meyer and Aebi 1990). In non-muscle cells it is located in cell-cell and cell-extracellular matrix junctions, and along actin filaments in fibroblasts. It belongs to a family of F-actin binding proteins that includes spectrin, dystrophin, gelation factor, filamin and fimbrin and is defined by similar and functionally homologous actin binding domains (Hemmings etal. 1992). Alpha-actinin is an elongated molecule consisting of two identical subunits with a molecular mass of approximately 100 kDa. In the homodimer the subunits have an antiparallel arrangement (Wallraff et al. 1986; Imamura et al. 1988). Each subunit contains an N-terminal F-actin binding site which is followed by a central rod domain formed by four spectrin-like alpha-helical repeats. Two EF-hands at the C-terminus are responsible for the Ca2+ regulation of nonmuscle alpha-actinin. In an incomplete form they are also present in skeletal muscle alpha-actinins which exhibit a Ca2+-independent crosslinking activity. Mutational analyses of the two EF-hands of Dictyostelium alpha-actinin, a typical non-muscle alpha-actinin, indicate that they have a different impact on the activity of the molecule (Witke et al. 1993). The more N-terminal EF-hand is the low affinity Ca2+-binding site and regulates the crosslinking activity, the C-terminal EF-hand represents the high affinity binding site for Ca2+.
Calbindin D-28k
Authors: Celio Marco R 
Published: November 2023

Abstract
Calbindin D-28k from various species was found to consist of 261 (mammalian) or 262 (avian) amino acids as deduced from the corresponding cDNA sequences. The molecular weight and IEP of the human protein are 30,025 and 4.54, respectively. Calbindin D-28k (similar to most other EF-hand proteins) has a rather rigid structure and readily renatures after heat-or chemical denaturaton. Vitamin D-dependent Ca2+-binding protein (Wassermann and Taylor 1966), CaBP. Calbindin D-28k was first observed in the chicken duodenal mucosa as a protein which is induced by vitamin D (Wassermann and Taylor 1966). Since vitamin D was also found to induce the absorption of Ca2+ from the intestinal lumen, the possibility of a link was obvious. Indeed, Breddermann and Wasserman (1974) found that calbindin D-28k binds with high affinity 3-4 moles of Ca2+ per mole of protein. The original purification procedure included a heat denaturation step. More recent procedures take advantage of the differing properties of the protein in the presence or absence of Ca2+, e.g. a Ca2+-mediated elution from cation exchange chromatography (Friedlander and Norman 1980). Calbindin D-28k can easily be produced in an active conformation in E. coli (Gross etal. 1988).
Calcineurin
Authors: Celio Marco R 
Published: November 2023

Abstract
Calcineurin (Cn) is a Ca2+/calmodulin-dependent protein phosphatase, composed of a catalytic and a regulatory subunit. It has been found in the brain, where it is one of the most abundant calmodulin-binding proteins.
Recently it was demonstrated that calcineurin is the target of immunosuppressant drugs (cyc/osporin, FK-506). This observation indicated that calcineurin is a necessary component in the activation of T cells.
CaIcy phosine
Authors: Celio Marco R 
Published: November 2023

Abstract
Calcyphosine (p24) is a Ca2+-binding protein located in the cytosol and is present in numerous tissues. p24 was initially identified as being a major phosphorylated substrate for cyclic AMP-dependent protein kinase following stimulation of dog thyroid cells by thyrotropin (Lecocq et al. 1979). The role of p24 is as yet unknown. All cells where p24 has been found are epithelial and of the secretory type, which leads us to propose the hypothesis that calcyphosine may play a role in the regulation of ionic transport.
Calmodulin
Authors: Celio Marco R 
Published: November 2023

Abstract
Calmodulin (CaM) is a small (about 17 kDa), ubiquitously expressed, 4 EF-hand Ca2+-binding protein that appears to be the primary calcium sensor in eukaryotic cells. Calmodulin acts as a calcium signal-transmitting subunit for a multitude of different proteins in mammalian cells. CaM is highly conserved throughout eukaryotic species, and no naturally occurring mutations have as yet been identified in multicellular organisms. Calmodulin appears to act primarily by binding and sequestering self-interacting (e.g. autoinhibitory) domains in its target proteins, but other modes of action may also be found in the case of individual enzymes.
Calpains
Authors: Celio Marco R 
Published: November 2023

Abstract
Ca/pains (µ,- and m-) are non-Jysosoma/ cysteine proteinases present in most mammalian tissues in varying amounts and have been detected in all vertebrate species tested. Activation in vitro requires 1-100 µ,M, and 0.1-1 mM levels of Ca2• forµ,- and m-ca/pain, respectively. Suggested functions for the ca/pains include a role in modulating intracellular signal transduction, cell division, platelet activation, and memory formation.
Calmodulin-domain protein kinase
Authors: Celio Marco R 
Published: November 2023

Abstract
Calmodulin-domain protein kinases (CDPKs) are calcium-activated protein kinases that do not require exogenous calmodulin for activity since they contain a calmodulin-like domain as a part of their primary protein structure. CDPK activity has been found in plant genera from algae to higher plants, and also in protists, such as Plasmodium and Paramecium. In plants, CDPKs are encoded by a large gene family, and both cytoplasmic and membrane-bound activities have been reported. Information on the biological function of most CDPKs has not yet emerged.
Centrin
Authors: Celio Marco R 
Published: November 2023

Abstract
Centrin is a cytoskeletal Ca2•-binding EF-hand protein present in animal, plant, fungal, and protist cells. Mutational analyses, as well as its association with centrosomes, spindle pole bodies, and basal bodies, suggest that it plays a fundamental role in the cell cycle dependent duplication, functional assembly, and positioning of centrosomes.
ERC-55
Authors: Celio Marco R 
Published: November 2023

Abstract
ERC-55 is a human Ca2+-binding protein localized to the lumen of the endoplasmic reticulum. The protein sequence comprises six copies of the EF-hand Ca2+-binding motif. It is retained in the endoplasmic reticulum via a carboxyterminal HOEL (His-Asp-Glu-Leu) motif. The mRNA for ERC-55 is ubiquitously expressed in human tissue.
Invertebrate, plant, and lower organism calcium-binding proteins
Authors: Celio Marco R 
Published: November 2023

Abstract
Ca2+-binding proteins (CaBPs) are important relay elements in the Ca2+ signal-response coupling. Most of them possess a recurrent structural motif, i.e. the paired EF-hand Ca2+-binding domain (Kretsinger 1987). The interpreters of the Ca2+signal in invertebrate animals are to a large extent the same as in the vertebrates, and include calmodulin, troponin C, essential and regulatory myosin light chains, calcineurin B, o:-actinin, calpain, and neuronal CaBPs. Most of these proteins are already present in protista and fungi, and their presence extends up the evolutionary tree to plants and invertebrates. In contrast, no members of some well-known subfamilies, such as parvalbumin, 5100 protein, or calbindin, have been reported outside the vertebrate animal kingdom; hence they seem to be unique to vertebrates. Invertebrates, plants, fungi, protista, and even prokaryotes contain in turn some unique CaBPs, not yet found in vertebrates. The latter proteins, which are the subject of this chapter, are listed in Table 1. A caveat about uniqueness is warranted since classical detection strategies may fail for lack of immunoreactivity, ot low amount, or of transient expression. A good example is the caltractin and CDC31 subfamily which is present in the microtubule organizing centers of Chlamydomonas and of yeast, but whose homologs have recently been identified in vertebrates and cloned at the DNA level from human and mouse (Lee and Huang 1993; Errabolu et al. 1994). It is interesting to make the parallel here with the numerous actin-binding proteins which also are much more ubiquitous than initially thought (Pollard 1993).
Neuron specific calcium-sensors (the NCS subfamily)
Authors: Celio Marco R 
Published: November 2023

Abstract
Neurotransmitters, photons, hormones, odorants, or electrical activity can increase levels of Ca2+ within neuronal cells, either by the release of Ca2+ from internal stores or through influx from outside the cell across the plasma membrane. Ca2+, once released in the cytosol, functions as a second messenger that regulates cell cycle progression, transformation, proliferation, contraction, exocytosis, membrane potential, synaptic plasticity, enzyme activation, and proteins such as calmodulin, troponin C, or recoverin. In many cases, the function of Ca2+depends on the interaction with specific intracellular Ca2+-binding proteins (CaBPs) which may, for example, mediate the effects of Ca2+ on enzyme activities or control the effective concentration of the ion. In neurons, CaBPs can usually be divided into two distinct groups:
Sorcin
Authors: Celio Marco R 
Published: November 2023

Abstract
Sorcin is a Ca2+-binding protein initially identified as an abundant protein in cells selected for resistance to natural product cancer drugs, such as vincristine and adriamycin. Among normal tissues, it is abundant in heart, skeletal, and smooth muscle, as well as in other tissues, including brain and kidney. The major form of sorcin in resistant cells has a molecular weight of 22,000, whereas normal tissues may express a family of sorcin-related proteins. Transfection of sorcin into fibroblasts produces cells manifesting a muscle-like, caffeine-stimulated release of Ca2+from intracellular stores.
Calnexin
Authors: Celio Marco R 
Published: November 2023

Abstract
Calnexin is one of the major Ca2+-binding proteins of the endoplasmic reticulum (ER) membrane and has been demonstrated to interact transiently with nascent proteins. This membrane-bound chaperone is proposed to be directly involved in the quality-control mechanism of the ER. Canine calnexin is a type I membrane protein with no oligosaccharide chain (Wada et al. 1991). Although the primary transcript of calnexin cDNA encodes for a 56,403 Da polypeptide, this acidic phosphoprotein migrates abnormally on SDS-PAGE and gives an apparent molecular mass of ca. 90 kDa.
ER calcistorin/protein disulfide isomerase
Authors: Celio Marco R 
Published: November 2023

Abstract
ER calcistorin!Protein disulfide isomerase (ECaSt!POJ), identified in the endoplasmic reticulum (ER) of the sea urchin egg, is a high capacity, low affinity Ca2+-binding protein which also has POI activity. The molecule apparently has a dual function of Ca2+storage and POI activity in the ER of the sea urchin egg.
Introduction
Authors: Rappuoli R 
Published: November 2023

Abstract
The ability to sense extracellular signals is essential for all living organisms. In animals, the presence of specialized tissues with different functions, that need to coordinate and regulate their activities, makes signal transduction even more essential. Signals are most often delivered to surface receptors by hormones, growth factors, cell to cell contacts, etc. Once triggered by the ligand, the receptor is activated and the signal is transduced across the cell membrane by receptor clustering and/or conformational changes, that results in biochemical changes on the cytosolic side of the membrane. These occur mainly by two mechanisms:tyrosine kinase receptor phosphorylation of specific sites of its carboxyterminal cytoplasmic domain, that recruits SH2-transducers to start a cascade of phosphorylation of intracellular targets;modification of a receptor-coupled G protein that transduces the signal to enzymes, releasing second messengers such as cyclic-AMP (cAMP), inositoltriphosphate (ITP), diacyglycerol (DG), to a cytoplasmic kinase etc.
Pertussis toxin (Bordetella pertussis)
Authors: Rappuoli R , Pizza M G 
Published: November 2023

Abstract
PT (Sekura et al. 1985) is a protein of 105 000 daltons composed of five noncovalently linked subunits named 51 through 55, and organized into two functional domains called A and B (Tamura et al. 1982). The A domain, which is composed of the 51 subunit, is an enzyme that intoxicates eukaryotic cells by ADP-ribosylating their GTP¬ binding proteins (Rappuoli and Pizza 1991). The enzyme binds NAD and transfers the ADP-ribose group to a cysteine residue present in an ...XCGLX motif, located at the carboxy-terminal region of the alpha subunit of many G proteins such as G;, G0, G1, Ggust, and others. G, and G011, which in this position have a tyrosine instead of the cysteine, are not substrates for PT (Domenighini et al. 1995). The B domain is a nontoxic oligomer formed by subunits 52, 53, 54, and 55 which are present in a 1:1:2:1 ratio. This domain binds the toxin receptor on the surface of eukaryotic cells and facilitates the translocation of the 51 subunit across the cellular membrane, so that it can reach the target proteins.
Adenylate cyclase toxin (Bordetella sp.)
Authors: Sebo P , Ullmann A 
Published: November 2023

Abstract
Adenylate cyclase toxin (ACT or CyaA) is a key virulence factor produced by the human whooping cough agents, 8ordetella pertussis and parapertussis and by the related animal pathogens 8. bronchiseptica and 8. avium (Weiss and Hewlett 1986; Hanski and Coote 1991; Mock and Ullmann 1993). The toxin is essential in the early stages of bacterial colonization of the respiratory tract (Goodwin and Weiss 1990) and can induce apoptosis of lung alveolar macrophages (Khelef et al. 1993). ACT is produced as a single 177.7 kDa polypeptide chain protoxin of 1706 residues (Glaser et al. 198B) (EMBL accession number: Y00545), which is activated by a post-translational palmitoylation of the internal lysine residue 983 (Hackett et al. 1994), requiring an accessory protein, CyaC (Barry et al. 1991). As shown in Fig. 1, the toxin is a bifunctional protein consisting of a cell-invasive and calmodulin-dependent adenylate cyclase (AC) catalytic domain (400 amino-terminal residues), fused to a pore-forming hemolysin consisting of 1306 residues. The AC enzyme penetrates into target cells, where it binds calmodulin and catalyses high-level synthesis of the key signal molecule, cAMP, thereby disrupting cellular functions (Confer and Eaton 1982).
Pseudomonas aeruginosa exotoxin A
Authors: Olsnes S 
Published: November 2023

Abstract
Pseudomonas aeruginosa exotoxin A (PEA, MW 66 kDa, 613 amino acids, sequence accession number: PSEETA K01397) consists of three major domains (Allured et al. 1986), as indicated in Fig. 1. The N-terminal domain la (amino acids 1-252) binds to the ai-macroglobulin receptor at the cell surface (Kounnas et al. 1992), domain II (amino acids 253-364) mediates translocation of itself and domain Ill to the cytosol, and the (-terminal domain Ill (amino acids 405-613) catalyses the transfer of ADP-ribose from NAD to the diphthamide residue of elongation factor 2, which is thereby inactivated (lglewski and Kabat 1975; Carroll and Collier 1987; Wick et al. 1990a, b). Intoxication is initiated by binding of the toxin to its receptor and endocytotic uptake of the complex (Morris and Saelilnger 1986). Then follows proteolytic cleavage at a furin sensitive site between Arg279 and Gly280 and reduction of the disulfide between Cys265 and Cys287 (Ogata et al. 1990, 1992). The 37 kDa fragment thus generated is translocated to the cytosol. The translocation may occur from the lumen of the endoplasmic reticulum as the toxin contains a (-terminal REDLK sequence which, after removal of the (-terminal lysine residue, may function as an endoplasmic reticulum retention signal (Chaudhary et al. 1990). Removal of this signal strongly reduces the toxicity.
Introduction
Authors: Aktories K 
Published: November 2023

Abstract
Many cellular functions depend on the cytoskeleton. The cytoskeleton controls the shape and the spatial organization of the cell. It participates in all kinds of cellular movement and transport and is involved in processes like endo-and exocytosis, vesicle transport, cell-cell contact, and mitosis. The cytoskeleton consists of a fibre network that is formed of three major filament systems which are highly dynamic structures: the microfilaments, the micro-tubules, and the intermediate filaments. Rapid structural changes of these cytoskeletal proteins are based on their ability to polymerize and depolymerize. Much of what we know about functions of these proteins has been learned from the use of cytotoxins which have been applied as cell biological tools. The group of cytoskeleton-affecting toxins comprises agents which act directly on elements of the cytoskeleton but also toxins that affect regulatory components (e.g. low molecular mass GTP-binding proteins) which control the organization of the cytoskeleton. The toxins can be subdivided into protein toxins with enzymatic activity, protein toxins without apparent enzymic activity, and small non-proteinaceous compounds which bind to the cytoskeleton proteins. The bacterial protein toxins appear to act predominantly on the actin cytoskeleton.
C2 toxin (Clostridium botulinum type C and D)
Authors: Aktories K 
Published: November 2023

Abstract
C2 toxin is binary in structure and consists of a binding component (C211, 100 kDa) and an enzyme component (C2I, 50 kDa) (Aktories et al. 1992). Both components are separated proteins. The gene of the enzyme compo¬ nent has been cloned recently (Fujii et al. 1996; EMBL Data Library D63903). C2II has to be activated by trypsin treatment to release an 75 kDa active fragment. C2II binds to a membrane receptor (not identified), which is present on all cell types studied so far. Binding of C2II induces a binding site for C21. The toxin is taken-up by receptor-mediated endocytosis (Simpson 1989) (see Fig. 1). In artificial membranes, C2II induces cation selective and voltage-dependent channels (Schmid et al. 1994).
Zonula ocdudens toxin (Vibrio cholerae)
Authors: Fasano A 
Published: November 2023

Abstract
Zonula occludens toxin (ZOT) is a single peptide chain of 44. 8 kDa (399 amino acid residues, predicted pl of 8. 5, GenBank accession number M83563) (Baudry et al. 1992). It contains a modified version of the purine NTP-binding motif with a drastic substitution of tyrosine for a conserved glycine (Koonin 1992). ZOT seems to be distantly but reliably related to the product gene I of filamentous bacteriophages, which is a putative ATPase containing the classic NTP-binding motif (Koonin 1992). ZOT hydropathy plots revealed one membrane-spanning segment located downstream from the putative NTPase domain.
Introduction
Authors: Alouf J 
Published: November 2023

Abstract
Two different situations should be considered in this respect:Bacterial toxins whose main targets are exclusively or mainly IS cellular and molecular effectors per se, for which the generic name ‘immunocytotropic toxins’ could be designated, as proposed by the author.Bacterial toxins which may affect or modulate certain functions of IS cells but which mainly act on cellular and molecular targets unrelated to the IS network. They could be qualified as ‘lmmunoactive toxins’.The modification of IS cell functions and homeostatis by both groups of toxins may lead to various pathophysiological disorders and diseases including host death, resulting from the production by target cells of potent pharmacological and toxic effectors (cytokines, inflammatory cascade products, biogenic amines, etc.).
Botulinum neurotoxins type A and E (Clostridium botulinum)
Authors: Rossetto O , Pellizzari R 
Published: November 2023

Abstract
Botulinum neurotoxins are structurally related protein toxins (BoNTs) produced by Clostridia in seven different serotypes: A, B, C, D, E, F, and G. BoNTs penetrate motorneurons at the neuromuscular junction and block acetylcholine release, thus causing the flaccid paralysis of botulism. They impair neurotransmission via the selective cleavage of proteins of the synaptic vesicles docking and fusion complex. BoNT/A and E are involved in human botulism and cleave SNAP-25 (synaptosomal-associated protein of 25 kDa), a protein bound to the cytosolic face of the plasma membrane. Botulinum neurotoxins A and E are produced by bacteria of the genus Clostridium and are responsible for the flaccid paralysis of botulism (Hatheway 1995). They are synthesized as a single inactive polypeptide chain of 150 kDa complexed with non-neurotoxic components and released by bacterial lysis. Bacterial or tissue proteases cleave the neurotoxin within an exposed loop and generate the active di-chain form composed of a heavy-chain (H, 100 kDa) and a light chain (L, 50 kDa) bridged by a single interchain disulphide bond. BoNTs bind the presynaptic membrane via the heavy chain and enter the neuron cytosol, where the light chain exerts its proteolytic activity (Montecucco and Schiavo 1995). The gene encoding for BoNT/A is located on a plasmid of variable size (1295 amino acid residues, GeneBank accession number X52066), whereas the gene that codes for BoNT/E is on a bacteriophage (1250 amino acid residues, GeneBank accession number X62089) (Eklund et al. 1989; Minton 1995).
Kaliotoxin
Authors: Martin-Eauclaire M -F 
Published: November 2023

Abstract
KTX was originally described as an inhibitor of the intermediate conductance Ca2+-activated K+ channel (IKCa) of nerve cells from the mollusc Helix pomatia. Single channel experiments performed on IKCa excised from their Helix neurons showed that KTX acted exclusively at the outer face of the channel. KTX was first purified from the venom of the Moroccan scorpion Androctonus mauretanicus mauretanicus (Crest et al. 1992). It is a single 4-kDa polypeptide chain showing amino acid sequence homology with other scorpion-derived inhibitors of Ca2+-activated or voltage-gated K+ channels. Comparison of these sequences led to the identification of a short amino acid sequence (26-33) which may be implicated in the toxin channel interaction. Later, KTX and shorter peptides, (KTX (25-35) amide and KTX (26-32) amide), were successfully synthesized (Romi et al. 1993). These peptides expressed no KTX activity but were able to compete in binding experiments with the 125I-KTX bound to its receptor on rat brain synaptosomes. They were further shown to antagonize both the toxicity and blocking activity of the KTX. It was concluded that the highly conserved region may contain a low affinity binding site essential for potassium channel recognition.
Charybdotoxin and iberiotoxin (Leiurus quinquestriatus var. hebraeus and Buthus tamulus)
Authors: Garcia M L 
Published: November 2023

Abstract
Charybdotoxin (ChTX) and iberiotoxin (lbTX) are 37 amino acid peptides containing six Cys residues that form three disulfide bridges (Gimenez-Gallego et al. 1988; Galvez et al. 1990). Both peptides have their N-terminal residue blocked in the form of pyroglutamic acid and share 68 per cent homology in their amino acid sequences (Fig. 1). The three-dimensional structure of these peptides has been determined in solution by NMR techniques (Bontems et al. 1991; Johnson and Sugg 1992). The backbone of both peptides is identical. The surfaces of ChTX and lbTX are formed by three small antiparallel strands that are linked to a helix region by the three disulfide bonds. Most of the residues are exposed to the solvent, except for the Cys residues. It is interesting to note that all critical residues of ChTX necessary for its interaction with K channels are located on one face of the molecule, well separated from the unimportant amino acids (Stampe et al. 1994). The critical residues of ChTX are all conserved in lbTX and, therefore, it is expected that the corresponding face of lbTX is the one involved in close interaction with the high-conductance Ca2+-activated K+ (maxi-K) channel.