bluuebunny/crossref_metadata_2025 huggingface dataset:
Calmodulin
Authors: Celio Marco R
Published: November 2023

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

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

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

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

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

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

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

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

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.
Calsequestrin
Authors: Celio Marco R
Published: November 2023

Calsequestrin is the major Ca2•-binding protein in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. It is concentrated in the terminal cisternae of the SR and suggested to function as a Ca2•-storage protein and to be involved in Ca2• release by a mechanism not fully understood at present.
ER calcistorin/protein disulfide isomerase
Authors: Celio Marco R
Published: November 2023

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

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

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

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

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

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

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

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

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

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

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

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.
ω-Grammotoxin SIA (Grammostola spatulata Chilean pink tarantula)
Authors: Lampe R A , Keith R A
Published: November 2023

ω-Grammotoxin SIA (ω-GsTx SIA) is a 36 amino acid, single chain peptide containing three disulfide bonds and an amidated carboxy terminus (Lampe et al. 1993). The average molecular weight of ω-GsTx SIA, determined by electrospray mass spectrometry (ES-MS), is 4109.2 Da in good agreement with the average theoretical molecular mass of 4109.7 Da. (Lampe et al. 1993). Reduction of the peptide results in the anticipated 6 amu shift with a corresponding ES-MS value of 4115.2 Da. Direct confirmation of the cysteine oxidation pattern has not been determined but is presumed to be the alternating Cys 1-4, Cys 2-5, and Cys 3-6 motif characteristic of the Conus snail toxins. The toxin is aqueous soluble, relatively temperature insensitive (extended storage as aqueous solution at 4 °C is routine), not readily susceptible to protease digestion and doesn’t demonstrate a high propensity to stick to either glass or plastic.
Hololena toxin (Hololena curta)
Authors: Bowers C W
Published: November 2023

Hololena toxin was isolated because of its ability to produce a presynaptic block of neuromuscular transmission in Drosophila larvae (Bowers et al. 1987). The nature of the presynaptic block indicated that the toxin was blocking neuronal calcium channels; this hypothesis has been verified directly using intracellular electro-physiology in Drosophila neurons (Leung et al. 1989; Leung and Byerly 1991). Hololena toxin is not active on any of the major voltage-dependent currents in Drosophila muscle, nor is it active at frog neuromuscular junction (Bowers et al. 1987). The isolated activity is only one of several that have now been described from the venom of this funnel web spider (Stapleton et al. 1990; Quistad et al. 1991; Lundy and Frew 1993; Meinwald and Eisner 1995), making the simple designation, hololena toxin, unavoidably anachronistic.
Calciseptine (Dendroaspis polylepis)
Authors: Romey G , Schweitz H , Lazdunski M
Published: November 2023

Calciseptine has been purified from the venom of the black mamba Dendroaspis polylepis polylepis. It is a single polypeptide chain of 7 kDa (60 amino acid residues with eight cysteines forming four disulfide bridges, sequence accession number to the Swiss Prot databank: P22947 TXCA-DENPO). Its primary structure is indicated below.Its sequence and its structural organization have similarities with neurotoxins that block the nicotinic receptors and with snake cyto-cardiotoxins (Rees and Bilwes 1993). Calciseptine has been shown to selectively block L-type calcium channels in a variety of cells but with a clearly tissue-dependent sensitivity. Calciseptine blocks L-type calcium current in aortic smooth muscle cells, ventricular cardiac cells, dorsal root ganglion nervous cells, and insulinoma cells.
Calcidudine (Dendroaspis angusticeps)
Authors: Romey G , Schweitz H , Lazdunski M
Published: November 2023

Calcicludine has been purified from the venom of the green mamba Dendroaspis angusticeps. It is a polypeptide of 7 kDa (60 amino acid residues with six cysteines forming three disulfide bridges, sequence accession number to PIR databank: A36989). Calcicludine is structurally homologous to Kunitz-type protease inhibitors. Homologies are 40 per cent with dendrotoxins, 29 per cent with the basic pancreatic trypsin inhibitor, and 39 per cent with the protease inhibitor domain of the amyloid b protein (APPi). Its primary structure is shown below.
Snake toxins against muscarinic acetylcholine receptors
Authors: Karlsson E , Jolkkonen M , Adem A
Published: November 2023

Muscarinic acetylcholine receptors participate in many physiological functions, such as reduction of heart rate, contraction of smooth muscles, glandular secretion, transmitter release and cognitive functions like learning and memory. There are five subtypes of receptors (m1-m5) and one organ or even a cell can express several subtypes. One exception is heart muscle which has only m2. Muscarinic receptors belong to a group of G-protein coupled receptors that consist of a single peptide chain which forms four extracellular, seven transmembrane and four intracellular domains (reviews: Hulme et al. 1990; Caulfield 1993: Wess 1993).
Introduction
Authors: Montecucco C
Published: November 2023

The synapse is a privileged site of communication of messages within the animal body. Synapses show different anatomical specializations depending on the type of cells involved: the main difference is between nerve-nerve and nerve-muscle synapses. The majority of synapses of vertebrates are present within the central nervous system. They are well protected from the rest of the body by anatomical barriers and are not easily reachable by toxins. Animal movement and behaviour strictly depends on the correct and timely function of central synapses and peripheral. The latter type of synapses are rapidly and easily accessible to a variety of molecules that enter body fluids. On this basis, it is not surprising that hundreds of protein toxins have been elaborated by many different animal species to block the transmission of nerve impulses to muscles. This result can be obtained by acting on the nerve terminal, i.e. presynaptically, or on the muscle cells, i.e. post-synaptically. This section focuses on those toxins blocking synaptic functions by binding to the presynaptic membrane. Several toxins acting on channels of the presynaptic membrane have been considered in previous parts.
Actin
Authors: Ampe Christophe , Vandekerckhove Joël
Published: November 2023

Different families of homologous proteins, the so called Actin-related proteins (Arps, see pp. 45-52), have recently been discovered.
Actin-binding protein-120 (ABP-120)
Authors: Cox Dianne , Condeelis John
Published: November 2023

Actin-binding protein-120 (ABP-120) is an actin-binding protein from Dictyostelium discoideum which cross-links actin filaments into networks containing orthogonal filaments in vitro.1 These networks closely resemble those found in ABP-120-rich pseudopods in situ (Fig. 1). The activity of ABP-120 in forming these networks is essential for the formation of normal pseudopods which, in turn, are necessary for normal cell migration, chemotaxis, and phagocytosis. The archetypical actin-binding site, shared by a large number of actin cross-linking proteins, was first identified in ABP-120. Other structural features of ABP-120 indicate that it is a member of the non-muscle filamin family of actin-binding proteins.
Actin Deploymerizing Factor (Adf)/Cofilin
Authors: Bamburg James R , Drubin David G
Published: November 2023

ADF/cofilins are essential proteins that increase the turnover rates of actin filaments. Within cells, they are concentrated in regions containing dynamic actin pools, such as ruffling membrane, and they are essential for cytokinesis. In higher vertebrates ADF and cofilin are products of different genes, but they have about a 70 per cent sequence identity within the same species. Since ADF and cofilin are often found in the same cell, they may be considered isoforms. Proteins of similar mass (15–19 kDa) and activity appear to exist in all eukaryoties.
Angiogenin
Authors: Hu Guo-fu , Vallee Bert L
Published: November 2023

Angiogenin, a potent inducer of neovascularization, is the first tumour-derived angiogenic factor to have been isolated based solely on its ability to induce the formation of new blood vessels. It is a member of the pancreatic ribonuclease superfamily and its characteristic ribonucleolytic activity is necessary for its angiogenic activity. ft induces most of the individual events in the process of angiogenesis, including binding to endothelial cells through its cell surface receptors; stimulating second messengers; mediating cell adhesion; promoting endothelial cell invasion; stimulating cell proliferation; and organizing endothelial cells to form a tubular structure. Angiogenin antagonists have been demonstrated to inhibit significantly the establishment of human cell tumours in athymic mice.
Nestin
Authors: Josephson Richard , McKay Ronald D G
Published: November 2023

Nestin is an approximately 220–240 kDa intermediate filament protein transiently expressed by mammalian neural precursor cells and myoblasts. Nestin is the first member of a new class of intermediate filaments, which appears to have evolved from an ancestral gene shared with the neurofilaments. Outside of the coiled-coil ‘core’ domain, nestin has little homology to other intermediate filaments; it has a large, acidic C-terminal tail with a novel repeated motif and virtually no N-terminal head domain. Its assembly into filaments requires a partner such as vimentin.
Neurofilament triplet proteins
Authors: Herrmann Harald , Aebi Ueli
Published: November 2023

The neurofilament triplet proteins (i.e. the low, middle, and high molecular weight neurofilament proteins NF-L, NF-M, and NF-H) are the most abundant cytoskeletal components found in neurones and their precursor cells. In vivo they assemble into obligate heteropolymeric filaments that, different from the other intermediate filaments (IF), run in parallel bundles for long distances. The intron-exon pattern of their genes deviates completely from that of the other four classes of IF proteins. However, all three NF proteins follow the general structural principles of IF protein architecture. At the cellular level, neurofilaments appear to be important for the establishment of the neuronal cytoskeleton, and particularly in specifying the axonal calibre.
Nuclear lamins
Authors: Moir Robert D , Spann Timothy P , Goldman Robert D
Published: November 2023

The nuclear lamins are intermediate filament proteins that are found exclusively in the cell nucleus of most multicellular animals and probably plants. The lamins assemble to form the nuclear lamina at the nuclear periphery. There also appear to be lamin assemblies within the nucleus. The lamins have been implicated as the major structural determinants of nuclear size and shape. The lamina, and therefore most likely the lamins, forms an interface between the nuclear envelope and chromatin, influencing both chromatin organization and DNA replication. The expression of different Jamin isotypes during development seems to parallel changes in nuclear structure and processes.
Peripherin
Authors: Parysek Linda
Published: November 2023

Peripherin is a neurone-specific 57 kDa intermediate filament subunit protein that is expressed mainly in the peripheral nervous system. Peripherin is initially expressed during the post-mitotic differentiation of neurones and during neuronal growth after axon injury,4,5 implicating a biological role for peripherin in the attainment or maintenance of the differentiated neuronal phenotype.
Vimentin
Authors: Chou Ying-Hao , Goldman Robert D
Published: November 2023

The expression of vimentin is developmentally regulated. Analyses of the vimentin gene structure indicate the presence of both positively and negatively regulated elements. In adult tissues, vimentin is mainly expressed in cells of mesenchymal origin. During early embryogenesis, it is expressed in parietal endoderm during midgestation, in neural crest cells, and in stem cells of the neuroepithelium. In most of these cases, vimentin expression precedes and overlaps transiently with the expression of tissue-specific IF proteins— that is, glial fibrillary acidic protein (GFAP) in astroglial cells, neurofilament proteins in neurones, and desmin and nestin in skeletal muscle cells. Many cultured cell lines express vimentin irrespective of their developmental origin.
FtsZ
Authors: Erickson Harold P , Stricker Jesse
Published: November 2023

FtsZ is a universal cytoskeletal protein in prokaryotes. FtsZ assembles into a ring that encircles the bacterium at the site of septation and contracts as the septum is formed. It is found in eubacteria, archaebacteria, and chloroplasts. FtsZ assembles into protofilaments and protofilament sheets in vitro, with a lattice similar to that of the microtubule wall. Sequence alignment, three-dimensional structure, and polymer similarity show that FtsZ is a bacterial homologue of tubulin.
Major sperm protein
Authors: Roberts Thomas M , Stewart Murray
Published: November 2023

Major sperm protein (MSP) polymerizes into filaments that are found in the amoeboid sperm of nematodes. These unique cells lack an actin-based locomotory apparatus and their motility is driven by their dynamic MSP cytoskeleton.
Introduction
Authors: Vale Ronald D
Published: November 2023

Lamin-associated polypeptides are relatively minor nuclear envelope components, and are estimated to be present at less that a few per cent of the abundance of lamins. lmmunoprecipitation has been used to isolate LAP1 and LAP2 from rat liver nuclear envelopes and LBR from avian erythrocyte nuclear envelopes after the proteins are solubilized in buffers containing non-ionic detergent.
Kinesin, chromo
Authors: Vernos Isabelle
Published: November 2023

Chromokinesin defines a new class of kinesin-like proteins (KLP) in the Kin N family that are characteristically associated to chromosome arms during mitosis. This new class comprises chicken chromokinesin and Xenopus Xklp. Other KLPs are related to them either at the sequence level or at the functional level. Xenopus Xklp1 participates in the positioning of chromosomes on to the metaphase plate probably by contributing to the ‘polar ejection forces’ that push chromosomes away from the poles. In addition, it is essential to maintain spindle bipolarity, probably by mediating the interaction of spindle microtubules with chromosomes.
Kinesin, internal motor domain
Authors: Walczak Claire E
Published: November 2023

The internal motor kinesins (Kin I family for kinesin internal) have an N-terminal globular domain, a centrally located catalytic domain, and a C-terminal α-helical tail. All Kin I family members to date are homodimers. Each subunit of the homodimer is approximately 85 kDa, and no accessory polypeptides have been identified. They have been implicated to function in both vesicle transport and in mitosis with a specific role in regulating microtubule dynamics.
Kinesin, monomeric
Authors: Hirokawa Nobutaka
Published: November 2023

KIF1 (k.inesin superfamily protein 1) forms a subfamily of kinesin superfamily proteins that function as monomeric proteins associated with microtubule-based motor activity. 1 KIF1 A and KIF1B have been suggested to be involved in the intracellular transport of membranous organelles such as synaptic vesicle precursors and mitochondria, respectively.
Muscle myosin, scallop
Authors: Szent-Györgyi Andrew G
Published: November 2023

Scallop myosin is a Ca2+-regulated contractile muscle protein that initiates contraction by the direct binding of Ca2+. Its regulatory subunits are the essential and regulatory light chains (ELC and RLC) present in one to one stoichiometry with the myosin heavy chain. The RLC inhibits contractile functions in the absence of Ca2+; the ELC contains a unique triggering Ca2+-binding site.
Muscle myosin, smooth
Authors: Trybus Kathleen M
Published: November 2023

Cytoplasmic myosin II has also been referred to as non-muscle myosin, non-sarcomeric myosin, cellular myosin, or just myosin IL The term conventional myosin has sometimes been used to distinguish this enzyme from the unconventional types of cellular myosins, like the myosin Is.
Arp2/3 complex
Authors: Mullins R Dyche , Pollard Thomas D
Published: November 2023

Actin-related proteins Arp2 and Arp3 are major cellular proteins in Acanthamoeba castel/ani, present at micromolar levels and concentrated in the actin-rich cortex. Arp2 and Arp3 are closely related to actin, with 40–50 per cent and 30–40 per cent sequence identity respectively but they appear to be incapable of forming actin-like filaments. Both are components of a multiprotein particle, the Arp2/3 complex, initially purified from Acanthamoeba castellani by affinity chromatography on profilin.
Myosin II, cytoplasmic
Authors: Warrick Hans M , Spudich James A
Published: November 2023

The term cytoplasmic myosin 11 is used to describe a family of eukaryotic force-generating enzymes that hydrolyse ATP to ADP and P; and use the derived chemical energy to produce force when attached to actin filaments. The biological roles of these myosins include generating contractile forces in the furrow during cytokinesis and in maintaining cortical tension. They have also been implicated in developmental processes where cellular shape changes, internal reorganizations, and directed cell migrations appear to drive morphogenesis.
Myosin III (NINAC)
Authors: Wes Paul D , Montell Craig
Published: November 2023

Skeletal, cardiac, and smooth muscle myosins are very similar in structure to the cytoplasmic myosin 11s. Unconventional myosins like the myosin I family are quite different in structure, but retain the elements of the ATPase and force-producing domains.
Kathryn G. Miller
Authors: Cheney Richard E
Published: November 2023

Class VI myosins are unconventional myosins that share sequence similarity to other myosins in the motor domain. One myosin in this class, Drosophila 95F myosin, has been demonstrated to participate in ATP-dependent, actin-based movement in vivo. This and other evidence suggest that class VI myosins do have enzymatic properties characteristic of myosins and that one function of this class of myosin is in intracellular transport.
Myomesin and M-protein
Authors: Perriard Jean-Claude , Fürst Dieter
Published: November 2023

Myomesin and M-protein are structural proteins with a molecular weight in the range of 163𩀓182 000 which typically localize in the centre of the M-band region of sarcomeres of skeletal and heart myofibrils. Although derived from different genes, both share the same domain organization and are members of the immunoglobulin superfamily of muscle proteins. It was proposed that these protein are involved in the maintenance of the regular lattice of the sarcomeric thick filaments. The spatial organization might be brought about by specific interactions of M-protein and myomesin with myosin thick filaments and titin.
Paramyosin
Authors: Cohen Carolyn
Published: November 2023

Genetic experiments in C elegans indicate that paramyosin is probably essential for the functional organization of invertebrate thick filaments. There is a rough correlation between thick filament length and paramyosin content. Since tension development in a muscle is proportional to thick filament length, muscles with large amounts of paramyosin develop large tensions. These same muscles are specialized for catch contraction, and it has been suggested that paramyosin may have a role in this mechanism.
Titin
Authors: Wang Kuan
Published: November 2023

The name connectin was originally used in 1977 to designate a SOS-insoluble protein mixture from exhaustively extracted striated muscle. Subsequent isolation of titin from the ‘connectin’ fraction in 1981 led to the synonymous usage of titin and connectin in recent literature. An unrelated 70 kDa actin- and laminin-binding protein from fibrosarcoma cells is also called connectin.
Adaptor proteins (AP-1-AP-3)
Authors: Robinson Margaret S
Published: November 2023

The ADP-ribosylation factors (Arf) are a family of 21 kDa GTP binding proteins which have been implicated as regulators of a wide variety of vesicular transport steps, as structural components of non-clathrin (COP!) coated vesicles and as direct activators of phospholipase D (PLD1). Activation of Arfs, coincident with the binding of GTP, causes a translocation of the otherwise soluble protein to membranes and is proposed to result in the nucleation of coat protein assembly and vesicular budding. Apparently conflicting data currently lead to uncertainty regarding the role of (Arf sensitive) PLO in vesicular transport, the role of Arf proteins in transport in general, and the view of Arf as a structural component of vesicle or membrane coated structures.
ADP-ribosylation factors (Arfs)
Authors: Kahn Richard A
Published: November 2023

AP180 is an abundant neurone-specific clathrin-associated phosphoprotein, which supports in vitro the assembly of clathrin triskelia into a homogeneous population of cage-like structures. This function appears to be regulated by inositol polyphosphates. Proteins related to AP180 are also expressed in non-neuronal cells.
Amphiphysin
Authors: McMahon Harvey T , Wigge Patrick
Published: November 2023

AP180 is extracted from coated vesicles with 0.5 M Tris along with other major coat proteins. AP180 can be purified by a combination of chromatographic techniques which include gel filtration, ion exchange chromatography on MQ resin and hydroxyapatite adsorption chromatography. Alternatively, AP180 has been expressed successfully in bacteria as either a GST or polyhistidinetagged fusion protein. Both are readily purified from bacterial lysates by affinity chromatography.
Caveolins
Authors: Rietveld Anton G , Simons Kai
Published: November 2023

Caveolins are principal components of caveolae, non-clathrin coated flask-shaped invaginations of the plasma membrane which are present in many mammalian cell types but are particularly abundant in endothelial cells, smooth muscle cells, adipocytes, and fibroblasts.
Coatomer
Authors: Lowe Martin , Pepperkok Rainer , Kreis Thomas E
Published: November 2023

lmmunofluorescence labelling of coatomer in tissue culture cells gives a perinuclear Golgi pattern with numerous smaller punctate structures scattered throughout the cell (Fig. 1(a)). The perinuclear labelling appears to form an envelope around the periphery of the Golgi complex, a localization consistent with the original immunoelectron microscopy studies showing coatomer predominantly on buds and vesicles on the rims of the Golgi complex.
Copii
Authors: Barlowe C
Published: November 2023

Genes encoding COPII proteins were first identified inS. cerevisiae through a genetic screen for secretion defective cells and later found to be required for transport vesicle budding from the ER. Subsequent biochemical approaches allowed for the isolation of three protein fractions, Sec23p/Sec24p complex, Sec13p/Sec31p, and Sar1p, that reproduce vesicle budding from ER membranes in vitro. The proteins that drive vesicle budding assemble into a uniform coat structure on ER-derived vesicles (Fig. 1). /n vitro synthesized COPl!-coated vesicles are competent to fuse with the Golgi and their composition is distinct from the donor membrane fraction in that they are enriched for cargo protein over resident ER protein.
Eps15
Authors: Sorkin Alexander
Published: November 2023

Eps15 is a prototype of the growing family of proteins containing EH domains.5 EH domains are found in yeast, worm, fly, frog, and mammalian proteins. The closest known homologue of Eps15 in mammalian cells is Eps15R, an Eps15-related protein4 (Fig. 1).
Giantin
Authors: Linstedt Adam D , Hauri Hans-Peter
Published: November 2023

Giantin is expressed and specifically localized to the Golgi complex in all avian and mammalian cells examined to date.1,5 Figure 1 shows a typical giantin staining pattern in a mammalian tissue culture cell. Following gradient fractionation, giantin is primarily recovered with markers of the cis/medial Golgi subcompartments.
GRASP 65
Authors: Barr Francis A , Warren Graham
Published: November 2023

GRASP6S was identified as part of a screen for N-ethylmaleimide (NEM)-sensitive Golgi membrane proteins involved in the formation of stacks of Golgi cisternae in a cell-free system.
p115
Authors: Sapperstein Stephanie K , Waters M Gerard
Published: November 2023

The mammalian intra-Golgi transport factor p 115 and the Saccharomyces cerevisiae ER to Golgi transport factor Uso 1 p are members of a novel family of proteins required for intracellular protein transport. These proteins possess a distinctive globular head/coiled-coil tail structure, reminiscent of myosin II, with three regions of high homology in the primary sequence. The available biochemical and genetic data suggest that p 115 is required for efficient docking of intracellular transport vesicles at the target compartment. The precise mechanism by which p 115 carries out this function remains to be determined.
Synaptojanin
Authors: Camilli Pietro De , Nemoto Yasuo
Published: November 2023

Synaptojanin (now referred to as synaptojanin 1) was initially identified as a major Grb2-binding protein in the total homogenate1,5 and synaptic fractions1 from rat brain and initially desdribed as p1451,2 or p150.
Synapsins
Authors: Czernik Andrew J , Greengard Paul
Published: November 2023

In the adult brain, synapsins are relatively abundant proteins that are specifically localized to presynaptic terminals of virtually all conventional synapses, where they are associated with the cytoplasmic surface of small synaptic vesicles.
Coronin
Authors: Hostos Eugenio L de
Published: November 2023

p57 (mammals), Cm1p (Saccharomyces), coronin-like protein (Caenorhabditis, other organisms).

Coronin is an actin-associated protein isolated from Dictyoste/ium discoideum which belongs to the WD-repeat family of proteins, a group of proteins which includes the β subunits of the trimeric G proteins. lmmunolocalization using monoclonal antibodies and, more recently, direct localization using GFP-tagged coronin have shown that coronin is found in a variety of dynamic F-actin rich structures derived from the cell cortex (Fig. 1).
Gelsolin
Authors: Yin Helen L
Published: November 2023

Gelsolin and gelsolin-like proteins are found throughout phylogeny from lower eukaryotes such as Dictyostelium up to mammals. They have powerful effects on actin filament length through Ca2+- and polyphosphoinositide-regulated filament severing and/or capping. The family includes gelsolin, villin, adseverin/ scinderin, CapG (also known as MCP, gCap39, and mbh1), flit, severin/fragmin, and several other novel members.
Nebulin
Authors: Wang Kuan
Published: November 2023

Nebulette is a petite nebulin isoform at the Z line region of cardiac myofibril in cardiac muscle. This 107 kDa protein consists of 22 nebulin modules bracketed by a unique N-terminal domain and C-terminal Src homology (SH3) domain. It bears a striking resemblance to the C-terminal region of skeletal muscle nebulin. Nebulette incorporates and aligns with the nascent myofibril early during cardiac myofibrillogenesis.
Protein 4.1
Authors: Conboy John
Published: November 2023

Erythrocyte protein 4.1, expressed predominantly as a group of alternatively spliced ∼80 kDa polypeptides, is a structural component of the erythroid membrane skeleton. Historically, the name protein 4.1 derived from its relative mobility on SDS-PAGE gels of red cell membranes (migrating slightly faster than the anion exchanger band 3). Purified erythroid protein 4.1 has been well characterized by biochemical, biophysical, and molecular biological approaches, and therefore serves as a paradigm for an expanding but less well understood family of non-erythroid 4.1 proteins.
Smoothelin
Authors: Eys Guillaume J J M van , Loop Frank T L van der
Published: November 2023

In all vertebrate species tested so far, smoothelin is expressed in adult smooth muscle tissues but not in skeletal or heart muscle. Unlike other smooth muscle-specific proteins (calponin, smooth muscle actin, meta-vinculin) smoothelin is not found in all smooth muscle cell (SMC) phenotypes.
Tenuin
Authors: Tsukita Shoichiro
Published: November 2023

In non-muscle cells, motility and maintenance of cell shape are largely dependent on actin-based structures. These structures show a variety of morphologies: some are ordered arrays of actin filaments and others are random networks. Examples of the ordered arrays are stress fibres in cultured fibroblasts and circumferential bundles in epithelial cells.