SII-SWORD/CoKE huggingface dataset:
Neural cell adhesion (Neural_cell_adh)
Type: Family

Neural cell adhesion molecules (NCAM) are cell surface glycoproteins that share structural motifs related to immunoglobulin (Ig) and fibronectin type III (FNIII) domains. Expressed in neurons, glial cells and skeletal muscle, NCAM binds both homophilically and heterophilically, mediating processes such as neural cell growth and migration . Polysialic acid binds to N-glycosylation sites in the Ig domains, affecting the binding of NCAM. Decreasing levels of sialynation on NCAM promotes aggregation, and is thought to be important in regulation of tissue stability .

The full length transcript contains (from N terminus to C terminus) five Ig domains, two FNIII domains, a transmembrane (TM) region and a cytosolic domain. Alternative splicing is known to generate at least four products with (apparent desialylated) molecular weights of 180, 140, 120 and 105kDa. The longer TM products are expressed in neurons (180 and 140kDa) and glial cells (140kDa), whereas the 120kDa product is GPI-anchored on the surface of myotubes and the 105kDa product is secreted (for review see ). Further splice variation arises from a variable alternatively spliced exon (VASE) in the fourth Ig domain and a muscle-specific domain (MSD) between the two FNIII domains containing an O-glycosylation site.
Wnt-1 protein (Wnt1)
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.

The Wnt-1 gene was first identified in 1982 as a proto-oncogene activated by the integration of mouse mammary tumour virus (MMTV) in mammary tumours. With the identification of Drosophila wingless, however, it became clear that Wnt genes are important regulators of many developmental decisions. Mutation of the embryonic mouse Wnt-1 gene leads to loss of the midbrain and cerebellum; and a number of processes including segment polarity and limb development are interrupted in Drosophila wingless mutants .
Wnt-2 protein (Wnt2)
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.

The Wnt-2 gene was isolated from a human lung cDNA library in 1988 . The protein was initially named IRP for Int-1 Related Protein and later termed Wnt-2. Northern blot analysis from a range of embryonic and adult tissues revealed that the gene was expressed almost exclusively in placenta and lung. Mutation of the mouse Wnt-2 gene leads to placental defects.
Wnt-3 protein (Wnt3)
Type: Family

This entry represents the family of proto-oncogene Wnt-3 and related proteins. Wnt-3, also called proto-oncogene Int-4, functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family. The Wnt-3 gene was first identified in mouse in 1987, where it was found to be expressed during embryogenesis and in adult brain . It is required for normal embryonic development, and especially for limb development. Wnt-3a functions in the canonical Wnt signaling pathway and plays crucial roles in both proliferation and differentiation processes in several types of stem cells . Wnt3a stimulates the migration and invasion of trophoblasts and induce the survival, proliferation, and migration of human embryonic kidney (HEK) 293 cells. It also up-regulates genes implicated in melanocyte differentiation and increases the expression and nuclear localization of the transcriptional co-activator with PDZ-binding motif (TAZ), a transcriptional modulator involved in activating osteoblastic differentiation.

Wnt-3 structure consists of a N-terminal helical domain, a linker region and an elongated disulfide-rich C-terminal domain and very closely resembles the structure of Wnt-8

.

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-4 protein (Wnt4)
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-4 cDNA was isolated from mouse using a PCR-based strategy, where it was found to be expressed in adult tissues, particularly in brain and lung . Wnt-4 is believed to act downstream of progesterone signalling to play an important role in mammary gland development. Furthermore, mutations in the Wnt-4 gene have been linked to kidney defects .
Wnt-6 protein (Wnt6)
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-6 cDNA was isolated from mouse using a PCR-based strategy, where it was found to be expressed in adult tissues, particularly in brain and lung . Furthermore, Wnt-6 is expressed in the ureter bud, where it is believed to activate kidney tubule development .
U2 auxiliary factor small subunit (U2AF_small)
Type: Family

The U2 small nuclear ribonucleoprotein auxiliary factor (U2AF) is a heterodimeric splicing factor composed of a large and a small subunit . The large U2AF subunit recognises the intronic polypyrimidine tract, a sequence located adjacent to the 3' splice site that serves as an important signal for both constitutive and regulated pre-mRNA splicing. The small subunit interacts with the 3' splice site dinucleotide AG and is essential for regulated splicing. The subunits shuttle continuously between the nucleus and the cytoplasm via a mechanism that involves carrier receptors and is independent of binding to mRNA. Both subunits contain an arginine/serine-rich (RS) domain, which acts as a nuclear localisation signal.
Furthermore, the presence of an RS domain on either subunit is sufficient to trigger the nucleocytoplasmic import of the heterodimeric complex .

The human form of the U2 auxiliary factor small subunit, hU2AF35, contains a degenerate RNA recognition motif (RRM) and a C-terminal RS domain. Mutations in this protein alters U2AF1 function affects the alternative splicing of target genes associated with myelodysplastic syndrome (MDS) . The murine form has been shown to be genomically imprinted with monoallelic expression from the paternal allele. However, this is not the case in humans .
Groucho/transducin-like enhancer (Groucho_enhance)
Type: Family

The Groucho (Gro)/transducin-like enhancers (TLE) are a family of evolutionarily conserved corepressor proteins that play a critical role in diverse developmental and cellular pathways, including lateral inhibition, segmentation, sex determination, dorsal/ventral pattern formation, terminal pattern formation, and eye development .
Cystic fibrosis transmembrane conductance regulator (CFTR/ABCC7)
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 .

Cystic fibrosis transmembrane conductance regulator (CFTR, also known as ABCC7) is an eukaryotic protein belonging to the ABC-C subfamily of the ABC transporter family. CFTR protein is a chloride ion channel controlled by phosphorylation. It has a major role in electrolyte and fluid secretion. CFTR is important in the determination of fluid flow, ion concentration and transepithelial salt transport. Dysfunction of the CFTR channel causes the life-threatening disease, cystic fibrosis, in which trans-epithelial ion transport is disrupted . Defective phosphorylation has been seen to be a cause for this altered activity .
Peptidoglycan hydrolase PcsB-like (PcsB-like)
Type: Family

This entry represents a family of proteins from bacteria and some lower eukaryotes, including Peptidoglycan hydrolase PcsB from Streptococcus pneumoniae.

PcsB is required for the maintenance of normal growth and cellular morphology and is involved in the splitting of the septum during cell division . This protein is organised into three regions: an α-helical coiled coil (CC) domain, an alanine-rich linker region and a globular catalytic CHAP domain (

) with an α+β papain-like amidase fold .

At present, Streptococci are amongst the most medically important bacterial species, causing a variety of diseases across a wide range of age groups. They are non-motile, Gram-positive cocci that are facultative or obligate anaerobes, and occur in pairs or chains. These microbes can be separated into groups according to their serological specificity, group A Streptococci (GAS) being amongst the most virulent and showing the most antibiotic resistance.
Neuropeptide B/W receptor family (Neuropept_B/W_rcpt)
Type: Family

Two closely related neuropeptide precursors, which share no significant sequence similarity with other known neuropeptides, have recently been identified neuropeptide B and neuropeptide W . Neuropeptide B is expressed in both the central nervous system (CNS) and in the periphery. In the CNS, highest levels of the peptide are found in the substantia nigra and hypothalamus, suggesting a possible role in locomotor control and the release of pituitary hormones. In the periphery, the peptide is most abundant in testis, ovary, uterus, placenta, spleen, lymph nodes and peripheral blood leukocytes, indicating potential roles in the reproductive and immune systems . Neuropeptide W has a more limited distribution in the brain than neuropeptide B and is found at highest levels in the substantial nigra , also suggesting an involvement in locomotor control. In the periphery, neuropeptide W is more widespread than neuropeptide B. In addition to the reproductive and immune tissues in which neuropeptide B is expressed, neuropeptide W has been found at high levels in the liver, stomach and trachea. Administration of neuropeptide W in rats has been reported to produce an acute increase in food intake and to stimulate prolactin release .

Two rhodopsin-like G protein-coupled receptors, neuropeptide B/W receptor 1 (also known as GPR7) and neuropeptide B/W receptor 2 (also known as GPR8) have recently been identified as receptors for these neuropeptides . Neuropeptide B/W receptor 1 is expressed at highest levels in the hippocampus, amygdala, trachea and in lung carcinoma and at moderate levels in foetal brain, pituitary and prostate whereas Neuropeptide B/W receptor 2 is most highly expressed in the caudate nucleus, hippocampus and amygdala, and moderately expressed in the adult brain, thalamus, parietal cortex, pituitary, adrenal gland, lymph nodes and in lymphoblastic leukaemia . Upon activation by neuropeptide B or W, neuropeptide B/W receptor 1 and neuropeptide B/W receptor 2 couple to pertussis toxin-sensitive G proteins to inhibit adenylate cyclase .

This entry represents the neuropeptide B/W receptor family.
Cytochrome bc1 complex, cytochrome c subunit (bc1_cytC-su)
Type: Family

Quinol-cytochrome c reductases (also called the cytochrome bc1 complex) constitute a large family of enzymes which transfer electrons from quinols to cytochrome c, translocating protons across membranes in the process. They function in bacterial and mitochondrial repiratory chains, and also the photosythetic electron transfer chains of bacteria and plastids. These enzymes share a common functional core consisting of cytochrome b, a Reiske Fe-S protein, and cytochrome c.

Actinobacteria such as Mycobacteria or Corynebacteria possess a branched aerobic respiratory chain in which electrons flow from NADH dehydrogenase and succinate dehydrogenase complexes into the menaquinone-menaquinol pool, from where they are transferred either to an aa3-type cytochrome c oxidase via the cytochrome bc1 complex, or to the cytochrome bd-type menaquinol oxidase; the latter important for microaerobic respiration . In these bacteria the aa3-type cytochrome c oxidase and the cytochrome bc1 complex form a supercomplex . This entry represents the cytochrome c subunit QcrC of the bc1 complex .
Cytochrome cL (Cyt_cL)
Type: Family

In Gram-negative bacteria, growth on methanol is dependent on the soluble, periplasmic quinoprotein methanol dehydrogenase, which oxidises methanol to formaldehyde. The electrons generated by this reaction are transferred from the reduced enzyme to the unusual cytochrome cL, which is subsequently oxidised itself by cytochrome c2 (also known as cytochrome cH), which then transfers the electrons to a membrane-bound cytochrome oxidase .

This entry represents cytochrome cL (also known as cytochrome C551i in some species), whose amino acid sequence is distinct from that of other c-type cytochromes and does not fit into any established amino acid sequence class. Despite its lack of homology to other proteins, many of its properties, eg the low-spin haem prosthetic group, are similar to those of class 1 cytochrome c proteins. Other properties, such as its large size and acidic nature are distinct to cytochrome cL. The core of this protein has a structure typical of class I cytochrome c proteins, consisting of compact α helices enclosing the haem c prosthetic group with one edge of the haem exposed . Unusually, there is a tightly bound calcium close to the haem group which is thought to help stabilise redox potential and may be involved in the transfer of electrons from methanol dehydrogenase to the haem group.
Membrane-bound tetrahaem cytochrome TorC/YecK (Membr-bd_4haem_cyt_TorC)
Type: Family

This family includes TorC, a pentahemic c-type cytochrome subunit of periplasmic reductases for trimethylamine-N-oxide (TMAO). The N-terminal half is closely related to tetrahemic NapC (or NirT) subunits of periplasmic nitrate (or nitrite) reductases; some species have both TMAO and nitrate reductase complexes .
Cytochrome b562 (Cyt_b562)
Type: Family

Cytochrome b562 is a haem-containing protein that is expressed in the periplasm of Escherichia coli. In b-type cytochromes, the haem atom is not covalently attached to the polypeptide. Cytochrome b562 has a four-helical bundle structure that is structurally similar to that found in members of the cytochrome c family (

). Cytochrome b562 has a reduction potential of 167 mV, which sets the energy yield possible in metabolism and is also a key determinant of the rate at which redox reactions proceed .
Ferredoxin zinc-binding (Fd_Zn-bd)
Type: Family

This entry represents a group of zinc-binding ferredoxins found in thermophilic archaea . These proteins consist of two structural domains: a core region which binds a [3Fe-4S] cluster and a [4Fe-S] cluster, and an N-terminal extension . The core region forms the (β-α-β)2 fold typical of di-cluster ferrodoxins, while the N-terminal extension is composed of three β strands. The zinc-binding site is located at the interface between the two domains, with the zinc ion thought to enhance thermostability by connecting the N-terminal extension to the core region.