SII-SWORD/CoKE huggingface dataset:
Tumour necrosis factor receptor 19-like (TNFR_19-like)
Type: Family

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain -a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .
Insulin-like growth factor II (IGF2)
Type: Family

The IGFs, or somatomedins, play a key role in pre-adolescent mammalian growth. IGF2 appears to be induced by placental lactogen and is thought to play a role in foetal development .

The insulin/IGF/relaxin superfamily is an ancient family of functionally diverse proteins . The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of four cysteines in their A chain, the first of which is linked by a disulfide bond to the third, while the second and fourth are linked by interchain disulfide bonds to cysteines in the B chain.

This family includes:

Insulin and insulin-like proteins

Relaxin and prorelaxin

Insect prothoracicotropic hormone (bombyxin)

Insulin-like growth factors (IGF1 and IGF2)

Mammalian Leydig cell-specific insulin-like peptide (gene INSL3)

Invertebrates insulin-related peptides (IRPs)
G protein-coupled receptor 153 (GPR153)
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 . The term clan can be used 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 rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) 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 .

Computational methods, including percent identity plots, hydropathy profiles and BLAST, have been used to analyse a gene-rich cluster at human chromosome 12p13 and to compare it with its syntenic region in mouse chromosome 6 . Of 6 genes identified, a number were novel receptors, including GPR153 (also known as PGR1) and GPR162 (also known as GRCA) . GPR153 is a cerebellar target of the Gli1 transcription factor, which is involved in the maintenance and proliferation of grabule neuron precursor cells in the cerebellum, and like GPR162 has a noted role in food uptake and decision making processes .

This entry represents G-protein coupled receptor 153, identified by conserved sections along the length of the protein that characterise GP153 and distinguish it from closely related GP162 proteins.
Neurogenic locus notch homolog protein 2 (Notch_2)
Type: Family

Notch cell surface receptors are large, single-pass type-1 transmembrane proteins found in a diverse range of metazoan species, from human to Caenorhabditis species. The fruit fly, Drosophila melanogaster, possesses only one Notch protein, whereas in C.elegans, two receptors have been found; by contrast, four Notch paralogues (designated N1-4) have been identified in mammals, playing both unique and redundant roles.

The hetero-oligomer Notch comprises a large extracellular domain (ECD), containing 10-36 tandem Epidermal Growth Factor (EFG)-like repeats, which are involved in ligand interactions; a negative regulatory region, including three cysteine-rich Lin12-Notch Repeats (LNR); a single trans-membrane domain (TM); a small intracellular domain (ICD), which includes a RAM (RBPjk-association module) domain; six ankyrin repeats (ANK), which are involved in protein-protein interactions; and a PEST domain. Drosophila Notch also contains an OPA domain .

Notch signalling is an evolutionarily conserved pathway involved in a wide variety of developmental processes, including adult homeostasis and stem cell maintenance, cell proliferation and apoptosis . Notch is activated by a range of ligands -the so-called DSL ligands (Delta/Seratte/LAG-2). Activation is also mediated by a sequence of proteolytic events: ligand binding leads to cleavage of Notch by ADAM proteases at site 2 (S2) and presenilin-1/g-secretase at sites 3 (S3)and 4 (S4) .The last cleavage releases the Notch intracellular part of the protein (NICD) from the membrane and, upon release, the NICD translocates to the nucleus where it associates with a CBF1/RBJk/Su(H)/Lag1 (CSL) family of DNA-binding proteins. The subsequent recruitment of a co-activator mastermind like (MAML1) protein promotes transcriptional activation of Notch target genes: well established Notch targets are the Hes and Hey gene families.

This entry represents Neurogenic locus notch homologue protein 2 from humans and similar proteins found in chordates.

Notch 2 has a widespread expression pattern. It is expressed in a number of tissues, including brain, heart, kidney, lung, teeth, skeletal muscle and liver. This protein functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus . It affects the implementation of differentiation, proliferation and apoptotic programs and is involved in bone remodelling and homeostasis . It positively regulates self-renewal of liver cancer cells .
Inositol monophosphatase SuhB-like (Inositol_monophosphatase_SuhB)
Type: Family

This entry represents a group of inositol monophosphatases (IMPases) mainly from bacteria. E. coli SuhB is part of the rRNA transcription anti-termination complex (rrnTAC) that prevents rho-dependent termination. The rrnTAC consists of Nus factors A, B, E and G, ribosomal protein S4 and inositol mono-phosphatase SuhB. SuhB directly binds a C-terminal acidic repeat domain of NusA and contacts at least one other region in NusA as well as the nut-like RNA signal element. It thereby facilitates entry of the NusB/E dimer into an rrnTAC .

E. coli SuhB has D,L-inositol-1-monophosphatase and beta-glycerophosphatase activity . However, E.coli makes very low amounts of myo-inositol-containing phospholipids, so the catalytic necessity for this enzyme is low .

Inositol polyphosphate 1-phosphatase (1PTASE) and inositol monophosphatase (MPTASE) are enzymes of the inositol signalling pathway that share similar enzymatic activity . Both enzymes exhibit an absolute requirement for metal ions (Mg2+ is preferred), and both are uncompetitively inhibited by submillimolar concentrations of Li+. Their amino acid sequences contain a number of conserved motifs, which are also shared by several other proteins related to MPTASE (including products of fungal QaX and qutG, bacterial suhB and cysQ, and yeast hal2) .

Structural analysis of these proteins has revealed a common core of 155 residues: the core comprises 5 α-helices and 11 β-strands, and includes residues essential for metal binding and catalysis. While the core has been conserved, presumably to impart catalytic function, the loops and regions of structure outside the core have evolved unique regulatory domains .

An interesting property of the enzymes of this family is their sensitivity to Li+ at levels achieved in patients undergoing therapy for manic depression. The targets and mechanism of action of Li+ are unknown, but over-active inositol phosphate signalling may account for symptoms of the disease . It has been proposed that these Li+-sensitive proteins could represent targets for Li+ in manic depressive disease .
Tumour necrosis factor receptor 13C (TNFR_13C)
Type: Family

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain -a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .

TNFRs are widely distributed and play important roles in many crucial biological processes, such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis . Drugs that manipulate their signalling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease .
MHC class II-associated invariant chain (MHC_II-assoc_invar_chain)
Type: Family

The CD74 antigen (also known as H-2 class II histocompatibility antigen gamma chain, MHC class II-associated invariant chain, Ia antigen-associated invariant chain, or Ii) plays a key role in MHC class II antigen processing: it stabilises peptide-free class II alpha/beta heterodimers in a nonameric (α-β-gamma)3 complex after their synthesis, and directs transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place .
G protein-coupled receptor GCR1 putative (GPCR_GCR1_put)
Type: Family

Heterotrimeric G protein-mediated signalling via activated 7-transmembrane (7TM) serpentine receptors is well known in a range of organisms, but evidence for the existence of this pathway in plants has been elusive. Over the years, however, evidence that G proteins are involved in signal transduction in plants has been accumulating, leading several researchers to seek plant 7TM receptors.

The first tangible evidence for a plant 7TM receptor came through an analysis of the expresssed sequence tag database, dbEST. This revealed an Arabidopsis thaliana gene (GCR1) that encodes a protein with 7 predicted TM domains, and other features characteristic of known 7TM receptors . The amino acid sequence of GCR1, however, is unusual in that it shows similarity to receptors from three different 7TM families , sharing greatest levels of similarity with the Dictyostelium cAMP receptors.
Insulin-like growth factor I (IGF-I)
Type: Family

The IGFs, or somatomedins, play a key role in pre-adolescent mammalian growth. IGFI expression is regulated by growth hormone and mediates post-natal growth . Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency), an autosomal recessive disorder characterised by growth retardation, sensorineural deafness and mental retardation .

The insulin/IGF/relaxin superfamily is an ancient family of functionally diverse proteins . The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of four cysteines in their A chain, the first of which is linked by a disulfide bond to the third, while the second and fourth are linked by interchain disulfide bonds to cysteines in the B chain.

This family includes:

Insulin and insulin-like proteins

Relaxin and prorelaxin

Insect prothoracicotropic hormone (bombyxin)

Insulin-like growth factors (IGF1 and IGF2)

Mammalian Leydig cell-specific insulin-like peptide (gene INSL3)

Invertebrates insulin-related peptides (IRPs)
Tumour necrosis factor receptor 19 (TNFR_19)
Type: Family

TNF receptor 19, also known as toxicity and JNK inducer (TAJ) and TROY, is highly expressed during embryonic development, where it may act as a regulator of cell activation and cell death . In adult tissues, the receptor is expressed in the central nervous system, and may mediate the inhibitory effects of myelin upon axon regeneration .

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain - a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .
GCR1-cAMP receptor (GCR1-cAMP_receptor)
Type: Family

Heterotrimeric G protein-mediated signalling via activated 7-transmembrane (7TM) serpentine receptors is well known in a range of organisms, but evidence for the existence of this pathway in plants has been elusive. Over the years, however, evidence that G proteins are involved in signal transduction in plants has been accumulating, leading several researchers to seek plant 7TM receptors.

The first tangible evidence for a plant 7TM receptor came through an analysis of the expresssed sequence tag database, dbEST. This revealed an Arabidopsis thaliana gene (GCR1) that encodes a protein with 7 predicted TM domains, and other features characteristic of known 7TM receptors . The amino acid sequence of GCR1, however, is unusual in that it shows similarity to receptors from three different 7TM families , sharing greatest levels of similarity with the Dictyostelium cAMP receptors.

It has been suggested that the cAMP receptors coordinate aggregation of individual cells into a multicellular organism, and regulate the expression of a large number of developmentally-regulated genes .
Gene transfer agent, major tail protein (GTA_major-tail)
Type: Family

Gene transfer agents belong to a group of unusual genetic exchange elements . GTAs are unusual in the sense they have the structure of a small tailed phage, which do not possess typical phage traits such as host cell lysis and infectious transmission of the GTA genes. In the Rhodobacter capsulatus GTA the GTA particles contain random 4.5 kb DNA fragments of the R.capsulatus genome. These DNA fragments can be transmitted to other cells where allelic conversion may occur via homologous recombination.

This entry is represented by ORFg9 (RCAP_rcc01691) of the Gene Transfer Agent (GTA) of Rhodobacter capsulatus [see Fig.1, in

]. ORFg9 has sequence homology to the major tail protein of bacteriophage TP901-1 (lactococcus phage TP901-1).
Bacteriophage 69, Orf23, major tail protein (Phage_69_Orf23_MTP)
Type: Family

This entry is represented by Bacteriophage 69, Orf23, the major tail protein. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
General secretion pathway, GspH (T2SS_GspH)
Type: Domain

GspH is involved in bacterial type II export systems . Like all pilins, GspH has an N terminus α helix . This helix is followed by nine β strands forming two β sheets, one of five antiparallel strands and one of four antiparallel strands . GspH is a minor pseudopilin; it is expressed much less than other pseudopilins in the type II secretion pilus (major pilins) . The function and localisation of minor pseudo-pilins are still to be fully unraveled . It has been suggested that some minor pseudopilins may assemble either into the base or the tip of pili, or both. They function as initiators or regulators of pilus biogenesis and dynamics, and/or as adaptors between various pseudopilin component and other members of the T2SS .
G protein-coupled receptor 153/162 (GCR_153/162)
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 . The term clan can be used 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 rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) 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 .

Computational methods, including percent identity plots, hydropathy profiles and BLAST, have been used to analyse a gene-rich cluster at human chromosome 12p13 and to compare it with its syntenic region in mouse chromosome 6 . Of 6 genes identified, a number were novel receptors, including GPR153 (also known as PGR1) and GPR162 (also known as GRCA) . GPR153 is a cerebellar target of the Gli1 transcription factor, which is involved in the maintenance and proliferation of grabule neuron precursor cells in the cerebellum, and like GPR162 has a noted role in food uptake and decision making processes .

This entry represents G-protein coupled receptor 153 and G-protein coupled receptor 162.
G protein-coupled receptor 162 (GPR162)
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 . The term clan can be used 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 rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) 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 .

Computational methods, including percent identity plots, hydropathy profiles and BLAST, have been used to analyse a gene-rich cluster at human chromosome 12p13 and to compare it with its syntenic region in mouse chromosome 6 . Of 6 genes identified, a number were novel receptors, including GPR153 (also known as PGR1) and GPR162 (also known as GRCA) . GPR153 is a cerebellar target of the Gli1 transcription factor, which is involved in the maintenance and proliferation of grabule neuron precursor cells in the cerebellum, and like GPR162 has a noted role in food uptake and decision making processes .

This entry represents G-protein coupled receptor 162.
Insulin-like growth factor IGF-1/2 (IGF-1/2)
Type: Family

This entry represents insulin-like growth factors, IGF-1/2, found in animals. IGF-1 and IGF-2 are peptide hormones structurally similar to insulin and play essential roles in growth and development. Both IGFs bind to IGF receptors, primarily IGF-1R, activating intracellular signaling pathways that regulate cell survival, differentiation, and protein synthesis. IGF levels are influenced by age, nutrition, and hormonal regulation, contributing to tissue maintenance and metabolic processes throughout life .

The insulin/IGF/relaxin superfamily is an ancient family of functionally diverse proteins . The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of four cysteines in their A chain, the first of which is linked by a disulfide bond to the third, while the second and fourth are linked by interchain disulfide bonds to cysteines in the B chain.

This family includes:

Insulin and insulin-like proteins

Relaxin and prorelaxin

Insect prothoracicotropic hormone (bombyxin)

Insulin-like growth factors (IGF1 and IGF2)

Mammalian Leydig cell-specific insulin-like peptide (gene INSL3)

Invertebrates insulin-related peptides (IRPs)