SII-SWORD/CoKE huggingface dataset:
Wnt-16 protein (Wnt16)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

Expression of Wnt-16 is activated by E2A-Pbx1, a fusion protein resulting from a t(1;19) translocation that occurs in a large proportion of pediatric pre-B acute lymphoblastoid leukaemias (pre-B ALL) . The Wnt-16 transcript, normally absent in bone marrow, was found to be highly expressed in the bone marrow of pre-B ALL patients.
ABC transporter Tap-like (ABC_Tap-like)
Type: Family

The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein .

This entry includes Tap1/2 (transporter associated with antigen processing 1/2) and its homologue, Mdl2, from budding yeasts. They are a group of eukaryotic proteins belonging to the ABC transporter family. Tap proteins play a crucial role in the processing and presentation of the MHC class I-restricted antigens. Mdl2 is a mitochondrial inner membrane half-type ABC transporter that is required for respiratory growth at high temperature .
Superantigen, staphylococcal/streptococcal toxin, bacterial (Superantigen_bac)
Type: Family

The prokaryote Staphylococcus aureus is a well-characterised and specialised human pathogen, expressing a variety of virulence factors to allow successful infection of the host . Symptoms usually manifest in cases of food poisoning, pyrogenic fever and toxic shock syndrome, and can prove lethal in immunocompromised patients . Of all the exotoxins secreted from the bacterial cell, superantigens and haemolysins are amongst the most studied . Of these, the former are well characterised, and several S. aureus superantigenic enterotoxins exist that trigger excessive and aberrant T-cell activation in the host. Homologues of these S. aureus proteins have been found in Streptococcus pyogenes, and cause similar effects . In conventional Major Histocompatibility Complex (MHC)-II-restricted antigen processing, a peptide epitope is presented to a specific T-cell receptor (TCR) by the antigen presenting cell, and up to 0.0001% of the host T-cell repertoire is activated . By contrast, a bacterial superantigen (SAg) can bypass this process, binding non-specifically to constant regions on both the MHC-II and TCR . This results in up to 25% of the total host T-cell population being activated, with a consequent massive release of inflammatory cytokines. A recent study into the origins and functions of the S. aureus and S. pyogenes superantigens has identified distinct protein domains that are responsible for the slightly different actions of each protein subgroup . Based on these criteria, the staphylococcal and streptococcal entero/exo toxins discovered so far can be placed into several groups/subfamilies . Apart from the S. aureus toxic shock syndrome toxins, which form their own unique group, all superantigens described so far share a common motif that may bind to an as yet unknown ligand. Each different subgroup also contains a combination of domains and motifs that sets it apart . However, all of these toxins share a similar 2-domain fold, a β-barrel towards the N terminus and a β-grasp domain towards the C terminus .
Wnt inhibitory factor (WIF)-1 (Wnt-inh)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

Wnt inhibitory factor-1 (WIF-1) is a secreted protein that binds to Wnt proteins and inhibits their activities. It was first identified as an EST from human retina; ortholgues have since been identified in mouse, rat, Xenopus and zebrafish. WIF-1 proteins comprise an N-terminal signal sequence, a family-specific WIF domain, five epidermal growth factor (EGF) repeats and a hydrophilic C terminus. The interaction of Wnt proteins with WIF-1 and other inhibitors, such as frizzled-related protein, is thought to fine tune their activity .
Cysteinyl leukotriene receptor 1 (CLT1_recept)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions (including various autocrine, para-crine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family.

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid metabolism. They can be divided into two classes based on the presence or absence of a cysteinyl group. Leukotriene B4 (LTB4) does not contain such a group, whereas LTC4, LTD4, LTE4 and LTF4 are cysteinyl leukotrienes.

Cysteinyl leukotrienes (CysLTs), previously known as the "slow reacting substance of anaphylaxis", are produced predominantly by myeloid cells associated with inflammatory responses . They are the most potent bronchoconstrictors known and also have pro-inflammatory effects, making them important mediators in the pathophysiology of human asthma . CysLTs have also been implicated in a variety of other diseases, such as allergic rhinitis, inflammatory bowel disease and psoriasis . Pharmacological studies of the effects of CysLTs have provided evidence for the existence of at least 2 distinct receptor subtypes, belonging to the G protein-coupled receptor family, designated CysLT1 and CysLT2 . CysLT1 is thought to mediate bronchospasm, plasma exudation, vasoconstriction, mucus secretion and eosinophil recruitment . CysLT2 is less well defined, owing to a lack of specific agonists and antagonists, but is thought to mediate some of the vascular effects attributed to CysLTs . Both receptor subtypes have now been cloned .

CysLT1 has a much higher affinity for LTD4 than for the other cysteinyl leukotrienes and, upon activation, stimulates phosphatidyl inositol hydrolysis and increases in intracellular calcium. The receptor is expressed at highest levels in the spleen and in peripheral blood leukocytes, with lower levels in the lung, placenta, small intestine, pancreas, colon and heart .
Cysteinyl leukotriene receptor 2 (CLT2_recept)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions (including various autocrine, para-crine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family.

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid metabolism. They can be divided into two classes based on the presence or absence of a cysteinyl group. Leukotriene B4 (LTB4) does not contain such a group, whereas LTC4, LTD4, LTE4 and LTF4 are cysteinyl leukotrienes.

Cysteinyl leukotrienes (CysLTs), previously known as the "slow reacting substance of anaphylaxis", are produced predominantly by myeloid cells associated with inflammatory responses . They are the most potent bronchoconstrictors known and also have pro-inflammatory effects, making them important mediators in the pathophysiology of human asthma . CysLTs have also been implicated in a variety of other diseases, such as allergic rhinitis, inflammatory bowel disease and psoriasis . Pharmacological studies of the effects of CysLTs have provided evidence for the existence of at least 2 distinct receptor subtypes, belonging to the G protein-coupled receptor family, designated CysLT1 and CysLT2 . CysLT1 is thought to mediate bronchospasm, plasma exudation, vasoconstriction, mucus secretion and eosinophil recruitment . CysLT2 is less well defined, due to a lack of specific agonists and antagonists, but is thought to mediate some of the vascular effects attributed to CysLTs . Both receptor subtypes have now been cloned .

CysLT2 has highest affinities for LTC4 and LTD4 and, upon activation, stimulates phosphatidyl inositol hydrolysis leading to increased intracellular calcium concentration. The receptor is expressed widely, with highest levels in the heart, placenta, spleen, peripheral blood leukocytes and adrenal gland .
G protein-coupled receptor 40-related receptor (GPR40-rel_orph)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions (including various autocrine, para-crine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices . A cluster of four intronless GPCR genes, sharing significant sequence similarity with one another, have been identified on human chromosome 19q13.1, downstream from the CD22 gene . The receptors have been named GPR40, GPR41, GPR42 and GPR43. The GPR42 protein sequence shares more than 98% amino acid identity with GPR41 and is located on a possible polymorphic insert .
GPR40 receptor fatty acid (GPR40_recept_FA)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices . A cluster of four intronless GPCR genes, sharing significant sequence similarity with one another, have been identified on human chromosome 19q13.1, downstream from the CD22 gene . The receptors have been named GPR40, GPR41, GPR42 and GPR43. The GPR42 protein sequence shares more than 98% amino acid identity with GPR41 and is located on a possible polymorphic insert . GPR40 has recently been shown to bind long-chain free fatty acids, molecules that have a role in various cellular processes, including regulation of insulin secretion . Expression of GPR40 is restricted to the pancreas, with high levels in the islets and pancreatic beta cell lines . Upon activation, GPR40 appears to couple predominantly to Gq and partially to Gi proteins, and has been shown to amplify glucose-stimulated insulin secretion from pancreatic beta cells. The receptor may therefore be a potential target for anti-diabetic drugs .
Chromosomal replication initiator protein DnaA, ATPAse domain (DnaA_dom)
Type: Domain

This entry represents the central domain of bacterial DnaA proteins which play an important role in initiating and regulating chromosomal replication. DnaA is an ATP- and DNA-binding protein. It binds specifically to 9 bp nucleotide repeats known as dnaA boxes which are found in the chromosome origin of replication (oriC).

DnaA is a protein of about 50kDa that contains two conserved regions: the first is located in the N-terminal half and corresponds to the ATP-binding domain, the second is located in the C-terminal half and could be involved in DNA-binding. The protein may also bind the RNA polymerase beta subunit, the dnaB and dnaZ proteins, and the groE gene products (chaperonins) .

This entry also includes DnaA regulatory inactivator Hda (Homologous to DnaA), a protein that helps facilitate the conversion of DnaA-ATP to DnaA-ADP, thus inhibiting the inititation of DNA replication .
Glycoside hydrolase family 11/12 (GH11/12)
Type: Homologous_superfamily

Glycoside hydrolase family 11

comprises enzymes with only one known activity, xylanase (

), while family 12

comprises enzymes with two known activities, endoglucanase (

) and xyloglucan hydrolase.

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
Concanavalin A-like lectin/glucanase domain superfamily (ConA-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents the concanavalin A-like domain, which has a sandwich structure of 12-14 β-strands in two sheets with a complex topology. Proteins containing this domain include:

Legume lectins

Glycosyl hydrolases family 16

Galectin (animal S-lectin)

Laminin G-like module

Pentraxin

Clostridium neurotoxins

Exotoxin A

Vibrio cholera sialidase

Leech intramolecular trans-sialidase

Glycosyl hydrolase family 7

Xylanase/endoglucanase

Calnexin/calreticulin

Lectin leg-like

vp4 sialic acid binding protein

Trypanosoma sialidase

Thrombospondin

Hypothetical protein YesU

Alginate lyase

Glycosyl hydrolases family 32

Peptidase A4

Alpha-L-arabinofuranosidase B

SPRY domain containing proteins

Beta-D-xylosidase

SO2946-like

MAM domain containing proteins
Arc-type ribbon-helix-helix (Arc_rbn_hlx_hlx)
Type: Homologous_superfamily

This superfamily represents a domain with a ribbon-helix-helix topology consisting of four helices in an open array of two hairpins. This domain is found in Mnt and Arc, two structurally homologous repressors encoded by bacteriophage P22 . This entry also includes nickel-responsive regulator and protein CopG .
RNA polymerase sigma factor, region 3/4-like (RNA_pol_sigma_r3/r4-like)
Type: Homologous_superfamily

This entry represents regions 3 and 4 (or sigma3 and sigma4 domains) found in several sigma factors, often in conjunction with the sigma2 domain (

). Both regions 3 and 4 are present in Sigma70 , Sigma28 (FliA), and SigA , while region4 is also found in SigmaF and RpoE. Regions 3 and 4 have a nucleotide-binding 3-helical core structure, consisting of a closed or partly open bundle with a right-handed twist. Some other nucleotide-binding proteins are thought to contain domains with a similar topology.

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .
RNA polymerase sigma factor, region 2 (RNA_pol_sigma_r2)
Type: Homologous_superfamily

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, Sigma70 (gene rpoD; major sigma factor) and Sigma54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

This entry represents region 2 (sigma2 domain) found in several sigma factors, often in conjunction with sigma3 and sigma4 domains (

). This region is present in Sigma70 , Sigma28 (FliA), SigA , SigR and RpoE. The sigma2 domain has a conserved 4-helical core, and often a variable insert subdomain.