SII-SWORD/CoKE huggingface dataset:
C chemokine (Chemokine_XCL1/XCL2)
Type: Family

Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role . They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system , and endothelial cells, where they may act as either angiogenic or angiostatic factors .

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors . Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells . Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).

The C chemokine subfamily is composed of two members, XC chemokine ligand 1 (XCL1), also known as lymphotactin or SCM-1 alpha, and XC chemokine ligand 2 (XCL2), also known as SCM-1 beta . The cognate receptor for these chemokines is XCR1 .

XCL1 is an inflammatory chemokine that produced by activated CD8+ T cells and natural killer cells. It is involved in the mediation of interactions between antigen-presenting dendritic cells and T-cells, and induction of CD8+ effector T-cell responses . It is also involved in the formation of self-tolerance mechanisms through the development of T regulatory cells within the thymus . Less is known about its closely related paralogue XCL2, although the in vitro functional profiles are virtually identical . Human XCL2 and XCL1 amino acid sequences differ at only two positions near the N terminus .

Viral XCL1 (vXCL1) exclusively binds to CD4(-) rat dendritic cells (DC), a subset of DC that express the corresponding chemokine receptor XCR1, a strategy to subvert cytotoxic immune responses .
Neisseria toxin MafB (Adhesin_MafB)
Type: Family

MafB constitutes a family of secreted toxins in pathogenic Neisseria species, probably involved in interbacterial competition . Genes immediately downstream of mafB encode a specific immunity protein (MafI). MafB proteins exhibit a signal peptide sequence, a N-terminal conserved domain and a C-terminal variable region. Toxic domains identified at the C terminus include

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,

, and

.

The genus Neisseria includes both commensal and pathogenic species. The pathogenic neisseriae are a small group of virulent bacteria that initiate infection at the human host mucosal membranes . Neisseria gonorrhoeae is passed through sexual transmission and can cause renal failure in extreme cases. The more extreme Neisseria meningitidis is a usually commensal nasopharynx microbe that causes meningococcemia and acute bacterial meningitis, especially in young children and teenagers .
Mycoplasma P48 major surface lipoprotein (Mycoplasma_p48)
Type: Family

Mycoplasma species are unique amongst bacteria in having very small genomes and lacking cell walls, and are wholly dependent on their host for survival, be it in a symbiotic or pathogenic lifestyle . Some virulent species can quickly adapt to new environments, and utilise a number of cell surface moieties to attach to target cells. Although the most common form of Mycoplasma pathogenesis is respiratory infection, some strains have also been implicated in bacterial vaginosis and rheumatoid arthritis .

An outer membrane lipoprotein, designated P48 on account of its 48kDa molecular weight, was purified from Mycoplasma agalactiae . It was found to be a potent differentiation/activation factor of human monocytes, and possesses both immunomodulatory and haematopoietic differentiation activities . This is believed to aid the bacterium by recruiting human blood cells to the point of infection, and altering them to allow intracellular invasion by Mycoplasma . Similar species also use the P48 lipoprotein to invade host cells of sheep and cattle, causing contagious agalactia .

Recently, recombinant studies on the Mycoplasma agalactiaeP48 major surface protein have shown that changing key elements at the genetic level decreases the immunomodulatory effects of the gene product . This may lead to a novel vaccine for Mycoplasma infections.
Phosphatase IpgD/SopB (IpgD/SopB)
Type: Family

Some Gram-negative animal enteropathogens express a specialised secretion system to directly "inject" exotoxins into the cytoplasm of host cells. Dubbed the type III secretion system, it is of specific interest to researchers, as the components of such a system are only expressed in pathogenic strains . The system is composed of structural proteins and exotoxin effectors; these are often encoded on large virulence plasmids or on the bacterial chromosome itself .

The IpgD and SopB virulence factor proteins, represented by this entry, are two such type III secretion system exotoxin effectors.

In Shigella flexneri, IpgD is translocated directly into eukaryotic cells and acts as a potent inositol 4-phosphatase that specifically dephosphorylates phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] into phosphatidylinositol 5-monophosphate [PtdIns(5)P], which then accumulates. Transformation of PtdIns(4,5)P(2) into PtdIns(5)P by IpgD is responsible for dramatic morphological changes of the host cell, leading to a decrease in membrane tether force associated with membrane blebbing and actin filament remodelling .
P2Y13 purinoceptor (P2Y13_rcpt)
Type: Family

There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides , known as P1, P2X and P2Y purinoceptors . These receptors induce a wide variety of biological effects and are involved in many different cellular functions . P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors . The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine , P2X via ATP , whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) .

The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 . P2Y3 has, as yet, only been found in birds , whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) .

This entry represents P2Y13 receptor (previously known as SP174 and GPR86), it is primarily coupled to Gi/o proteins . ADP is the naturally agonist of the P2Y13 receptor and upon activation and coupling inhibits adenylate cyclase formation . The P2Y12 receptor is expressed at highest levels in the brain and a number of immune tissues, particularly the spleen and is also found in the placenta, liver, bone marrow, lung . It is thought to play a role in hematopoiesis and the immune system .
Porphyromonas gingivalis fimbrillin protein (Fimbrillin)
Type: Family

Periodontal disease in humans is a major health problem in the developed world, and is caused by a number of specialised pathogens that inhabit the oral cavity. Amongst the bacterial species culturable from periodontal lesions are the streptococcal microbes Streptococcus mutans and Streptococcus sobrinus, and the Gram-negative anaerobe Porphyromonas gingivalis (Bacteroides gingivalis) . The latter bacterium has been implicated as the causative agent of peridontitis, pulpal infections and tonsillar abcesses .

Adherence by P. gingivalis to the periodontal surface is mediated by its major virulence factor fimbriae . This differs from other pathogenic Gram-negative bacterial polymeric Type I and IV fimbriae/pili in that it is much more simplified, consisting of only a monomeric fimbrillin repeating subunit, Fma1/FimA. Fma1/FimA has a molecular weight of 43kDa, and can exhibit antigenic diversity in different P. gingivalis strains . Unusually, this form of fimbrillin possesses a far longer leader peptide compared to the fimbrial subunits of other bacteria . It has been hypothesised that this allows for the maturation of the preprotein during secretion .

Recently, a study into the different antigenic types of P. gingivalis fimbrillin classified them into five distinct groups, depending on their gene sequences . Investigations into the functional differences of each type revealed that in the majority of peridontitis cases, bacterial strains possessing the type II Fma1/FimA were the most prevalent ; in healthy adults, type I strains were the most common. This has implications for particular strains that are associated with periodontal disease.
RNA-binding motif protein 8 (RNA-bd_8)
Type: Family

RNA-binding motif protein 8 (RBM8), also termed binder of OVCA1-1 (BOV-1) or RNA-binding protein Y14, is one of the components of the exon-exon junction complex (EJC) . It has two isoforms, RBM8A and RBM8B, both of which are identical except that RBM8B is 16 amino acids shorter at its N terminus . Three-dimensional modelling of the RBM8 RRM domain indicates that the sequences fold into an RNA-binding domain, forming a hydrophobic core between a β-sheet and two helices. The human RBM8A protein is ubiquitously expressed; the protein is localised predominantly in the cell nucleus and diffused throughout the cytoplasm . It preferentially associates with mRNAs produced by splicing, including both nuclear mRNAs and newly exported cytoplasmic mRNAs. Evidence suggests the protein remains associated with spliced mRNAs as a tag to indicate the position of spliced introns. Human RBM8A protein specifically binds to MAGOH, the human homologue of Drosophila mago nashi, a protein required for normal germ plasm development in the Drosophila embryo ; a similar association occurs with the Drosophila RBM8 protein, Tsunagi .
Relaxin receptor (Relaxin_rcpt)
Type: Family

Insulin is found in many animals, and is involved in the regulation of normal glucose homeostasis. It also has other specific physiological effects, such as increasing the permeability of cells to monosaccharides, amino acids and fatty acids, and accelerating glycolysis and glycogen synthesis in the liver . Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth .

Relaxin has diverse actions in the reproductive tract and in other tissues during pregnancy . Although binding sites for relaxin have been found in reproductive tissue, the nature of the receptor was previously unknown. Recently, two orphan GPCRs, LGR7 and LGR8, have been identified as receptors for the hormone. These two receptors contain large extracellular N-termini with leucine-rich repeat regions, and are structurally similar to the gonadotropin and thyrotropin receptors. LGR7 is expressed in the brain, kidney, testis, placenta, uterus, ovary, adrenal gland, prostate, skin and heart, while LGR8 is expressed mainly in the brain, kidney, muscle, testis, thyroid, uterus, peripheral blood cells and bone marrow. Upon binding to LGR7 or 8, relaxin stimulates a dose-dependent increase in cyclic AMP production, indicating coupling of the receptors to G proteins.
Septin 2 (Septin2)
Type: Family

Septin 2, also termed NEDD5, was originally cloned in mice. Orthologues from several other species have also been identified. Micro-injection of cells with an anti-septin 2 antibody blocks cytokinesis, giving rise to binucleated cells.

Septins were first discovered in budding yeast as a major component of bud neck filaments during cell septation . Later, its homologues were identified in nearly all eukaryotes, including humans. They are all GTP-binding proteins that are involved in diverse cellular functions, including cell cycle progression, vesicle trafficking, cytokinesis, cell migration, membrane dynamics, and chromosome segregation . Similar to cytoskeleton components such as actins and tubulins, they can assemble into filaments and bundles. However, unlike actin filaments and microtubules, septin filaments are not polar, similarly to intermediate filaments . The number of septin genes per organism is variable: S. cerevisiae has seven and humans have 13 (SEPT1-12 and SEPT14; SEPT13 is a pseudogene now called SEPT7P2) . All septins can form heteromeric complexes, which associate to form higher-order structures, including filaments, rings and cage-like formations .
Septin 3 (Septin3)
Type: Family

Septins constitute a eukaryotic family of guanine nucleotide-binding proteins, most of which polymerise to form filaments . Members of the family were first identified by genetic screening for Saccharomyces cerevisiae (Baker's yeast) mutants defective in cytokinesis . Temperature-sensitive mutations in four genes, CDC3, CDC10, CDC11 and CDC12, were found to cause cell-cycle arrest and defects in bud growth and cytokinesis. The protein products of these genes localise at the division plane between mother and daughter cells, indicating a role in mother-daughter separation during cytokinesis . Members of the family were therefore termed septins to reflect their role in septation and cell division. The identification of septin homologues in higher eukaryotes, which localise to the cleavage furrow in dividing cells, supports an orthologous function in cytokinesis. Septins have since been identified in most eukaryotes, except plants .

Septins are approximately 40-50kDa in molecular mass, and typically comprise a conserved central core domain (more than 35% sequence identity between mammalian and yeast homologues) flanked by more divergent N-and C-termini. Most septins possess a P-loop motif in their N-terminal domain (which is characteristic of GTP-binding proteins), and a predicted C-terminal coiled-coil domain .

A number of septin interaction partners have been identified in yeast, many of which are components of the budding site selection machinery, kinase cascades or of the ubiquitination pathway. It has been proposed that septins may act as a scaffold that provides an interaction matrix for other proteins . In mammals, septins have been shown to regulate vesicle dynamics . Mammalian septins have also been implicated in a variety of other cellular processes, including apoptosis, carcinogenesis and neurodegeneration .

Northern blotting studies indicate that septin 3 expression is high in the brain but undetectable in other tissues, suggesting that the protein is primarily neuronal.
Septin 7 (Septin7)
Type: Family

Septin 7 (SEPT7) belongs to the septin family. It forms complexes with SEPT4/SEPT8 or SEPT5/SEPT11, and appears to be a common element in most such septin complexes and it has both unusual genomic and structural features . There are two paralogous septin 7 genes in zebrafish, sept7a and sept7b, among which Sept7b is essential for pronephric function and development of left-right asymmetry in zebrafish embryogenesis in zebrafish . Rat SEPT7 is associated with the cytoplasmic channels of myelinating cells and is required for actin organisation in Schwann cells . It interacts with centromere-associated protein E (CENPE) and is required for its kinetochore localisation . C. albicans hyphae is involved in the endocytosis .

Septins were first discovered in budding yeast as a major component of bud neck filaments during cell septation . Later, its homologues were identified in nearly all eukaryotes, including humans. They are all GTP-binding proteins that are involved in diverse cellular functions, including cell cycle progression, vesicle trafficking, cytokinesis, cell migration, membrane dynamics, and chromosome segregation . Similar to cytoskeleton components such as actins and tubulins, they can assemble into filaments and bundles. However, unlike actin filaments and microtubules, septin filaments are not polar, similarly to intermediate filaments . The number of septin genes per organism is variable: S. cerevisiae has seven and humans have 13 (SEPT1-12 and SEPT14; SEPT13 is a pseudogene now called SEPT7P2) . All septins can form heteromeric complexes, which associate to form higher-order structures, including filaments, rings and cage-like formations .
Sequence-specific single-strand DNA-binding protein (SSDP_DNA-bd)
Type: Family

The sequence-specific single-strand DNA-binding protein (SSDP) family is thought to be involved in transciption regulation. SSDP specifically binds single-stranded pyrimidine-rich mirror repeat elements commonly found in promoter regions, and is believed to regulate alpha-2(I) collagen . It has been identified as a target for unbalanced translocations and deletions in acute myelogenous leukemia cells, implying a role as a tumour suppressor gene. It is expressed in spleen, lymph node, peripheral blood, bone marrow, thymus and foetal liver. Family members have been identified in chicken, human, rat, mouse and Drosophila. The highest sequence identity is observed in the first 100 N-terminal residues, which contains a tryptophan-rich region in its centre. The C terminus is more viariable, with glycine/ proline-rich low complexity regions.
Micronemal protein 1 (Microneme_MIC1)
Type: Family

Toxoplasma gondii is an obligate intracellular apicomplexan protozoan parasite, with a complex lifestyle involving varied hosts . It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host . Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage .

The protozoan utilises a variety of secretory and antigenic proteins to invade a host and gain access to the intracellular environment . These originate from distinct organelles in the T. gondii cell, termed micronemes, rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target destinations .
Dense granule Gra2 protein (Gra2_protein)
Type: Family

Toxoplasma gondii is an obligate intracellular apicomplexan protozoan parasite, with a complex lifestyle involving varied hosts . It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host . Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage .

The protozoan utilises a variety of secretory and antigenic proteins to invade a host and gain access to the intracellular environment . These originate from distinct organelles in the T. gondii cell termed micronemes, rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target destinations . Dense granule antigens (GRAs) are released from the T. gondii tachyzoite while still encapsulated in a host vacuole.

Gra2, one of these moieties, is rapidly targeted to a network of membranous tubules that connect with the vacuolar membrane . A recent study into the exact mechanism of Gra2 secretion has revealed that the secondary structure of the protein plays a major role in its targeting and release from the apical pole of the parasitic cell . Two amphipathic α-helical regions ensure not only that association of Gra2 with the host vacuole membrane takes place, but also that it is correctly targeted to the cell posterior, where stabilising networks of tubules form and hold the cell steady in the vacuole.
Dense granule Gra6 protein (Gra6_protein)
Type: Family

Toxoplasma gondii is an obligate intracellular apicomplexan protozoan parasite, with a complex lifestyle involving varied hosts . It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host . Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage .

The protozoan utilises a variety of secretory and antigenic proteins to invade a host and gain access to the intracellular environment . These originate from distinct organelles in the T. gondii cell termed micronemes, rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target destinations . Dense granule antigens (GRAs) are released from the T. gondii tachyzoite while still encapsulated in a host vacuole.

Gra6, one of these moieties, is associated with the parasitophorous vacuole . It possesses a hydrophobic central region flanked by two hydrophilic domains, and is present as a single copy gene in the Toxoplasma gondii genome . Gra6 shares a similar function with Gra2, in that it is rapidly targeted to a network of membranous tubules that connect with the vacuolar membrane . Indeed, these two proteins, together with Gra4, form a multimeric complex that stabilises the parasite within the vacuole.
Dense granule Gra7 protein (Dense_granule_Gra7_protein)
Type: Family

Toxoplasma gondii is an obligate intracellular apicomplexan protozoan parasite, with a complex lifestyle involving varied hosts . It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host . Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage .

The protozoan utilises a variety of secretory and antigenic proteins to invade a host and gain access to the intracellular environment . These originate from distinct organelles in the T. gondii cell termed micronemes, rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target destinations . Dense granule antigens (GRAs) are released from the T. gondii tachyzoite while still encapsulated in a host vacuole.

Gra7, one of these moieties, is believed to be secreted by the parasite during the late phase of intra-vacuolar habitation . Studies utilising immunogold labelling have localised Gra7 to the parasitophorous vacuolar membrane, and the network tubules formed by the Gra2/4/6 complex . It has been suggested that dense granule antigens stimulate humoral immunity in the host . A homologue of Gra7 is found in Neospora caninum.