SII-SWORD/CoKE huggingface dataset:
Tumour necrosis factor receptor 1B (TNFR_1B)
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 .
Interleukin-11, mammalian (IL-11_mml)
Type: Family

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine that stimulates megakaryocytopoiesis, resulting in increased production of platelets, as well as activating osteoclasts, inhibiting epithelial cell proliferation and apoptosis, and inhibiting macrophage mediator production. These functions may be particularly important in mediating the hematopoietic, osseous and mucosal protective effects of IL-11 . The cytokine also possesses anti-inflammatory activity, and has been proposed as a therapeutic agent in the treatment of chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis .

Although IL-11 was initially believed to be restricted to mammals, subsequent studies demonstrated it to be expressed in ray-finned fish . Two fish paralogues have now been identified, designated IL-11A and IL-11B .

This entry represents interleukin-11 found in mammals.
Tumour necrosis factor receptor 9 (TNFR_9)
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 .

TNF receptor 9 (also known as ILA and CD137 antigen) is expressed by activated T and B lymphocytes and monocytes. Stimulation of the receptor inhibits proliferation of activated T lymphocytes and induces programmed cell death .
Interleukin-34 (IL-34)
Type: Family

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

This entry represents interleukin-34 (IL-34), it was identified via functional screening of a library of secreted proteins . This cytokine promotes the differentiation and viability of monocytes and macrophages through the colony-stimulating factor-1 receptor (CSF1R) .
Tumour necrosis factor receptor 8 (TNFR_8)
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 .
Tumour necrosis factor receptor 1A (TNFR_1A)
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 signaling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease .
Atypical dual specificity phosphatase, subfamily B (Atypical_DUSP_subfamB)
Type: Family

Dual specificity phosphatases (DUSPs) are members of the superfamily of protein tyrosine phosphatases . They remove the phosphate group from both phospho-tyrosine and phospho-serine/threonine residues. They are structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR . They are characterised as VHR- or Cdc25-like .

In general, DUSPs are classified into the following subgroups :

Slingshot phosphatases

Phosphatase of regenerating liver (PRL)

Cdc14 phosphatases

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-like and myotubularin phosphatases

Mitogen-activated protein kinase phosphatases (MKPs)

Atypical DUSPs

The atypical DUSPs share a high degree of similarity with the MKP subgroup, but lack the N-terminal regulatory domain, which provides the substrate specificity towards the MAP kinases. These atypical-DUSPs form a heterogeneous group and have in common the presence of a single catalytic PTP domain. VHR was the first characterised member of this subfamily; its crystal structure is known .

The function of many atypical DUSPs remains unknown, although some have been related to regulation of MAP kinase pathways . VHR has also been related to the control of cell-senescence .

This entry also includes DUSP1 which does not belong to the atypical DUSP family.
Interleukin-19 (IL-19)
Type: Family

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

This entry represents interleukin-19.
Dual specificity protein phosphatase domain (TYR_PHOSPHATASE_DUAL_dom)
Type: Domain

Tyrosine specific protein phosphatases (PTPases) (

) contain two conserved cysteines, the second one has been shown to be absolutely required for activity. This entry represents the PTPase domain that centre on the active site cysteine. A number of conserved residues in its immediate vicinity have also been shown to be important. This domain can be found in dual specificity phosphatases.

Dual specificity phosphatases (DUSPs) are members of the superfamily of protein tyrosine phosphatases . They remove the phosphate group from both phospho-tyrosine and phospho-serine/threonine residues. They are structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR . They are characterised as VHR- or Cdc25-like .

In general, DUSPs are classified into the following subgroups :

Slingshot phosphatases

Phosphatase of regenerating liver (PRL)

Cdc14 phosphatases

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-like and myotubularin phosphatases

Mitogen-activated protein kinase phosphatases (MKPs)

Atypical DUSPs
Interleukin-10, conserved site (IL-10_CS)
Type: Conserved_site

Interleukin 10 (IL-10) is a secreted 17-21kDa protein that is non- glycosylated in humans but exists as a non-covalent homodimer. IL-10 is secreted by some types of T-lymphocyte, B-lymphocytes and macrophages late after antigen activation. Generally, IL-10 inhibits T-cell and natural killer cell synthesis of other cytokines at the transcriptional level, indirectly, by affecting macrophages. These cytokines include interferon-gamma, IL-2, IL-3, tumour necrosis factor and granulocyte-macrophage colony-stimulating factor (GM-CSF). The mechanism of IL-10 induced inhibition appears to involve a reduction in the abundance of the macrophage surface molecules that directly stimulate T-cells and natural killer cells. Proteins encoded by viruses such as Epstein-Barr virus and equine herpes virus show a high degree of sequence identity to IL-10. These proteins are thought to be involved in evasion of host immune responses. The IL-10 molecule is a tight dimer of 2 interpenetrating subunits that form a V-shaped structure. Each half of the structure consists of 6 α-helices (4 from 1 subunit and 2 from the other). Four of the helices form an up-up-down-down bundle, which is observed in all other helical cytokines. The overall topology resembles interferon-gamma.

This entry represents a Interleukin-10 conserved site found at the second of three conserved cysteines.
Nerve growth factor, beta subunit (Nerve_growth_factor_bsu)
Type: Family

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms . Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities.

Although NGF was originally identified in snake venom, its most abundant and best studied source is the submaxillary gland of adult male mice . Mouse NGF is a high molecular weight hexamer, composed of 2 subunits each of alpha, beta and gamma polypeptides. The beta subunit (NGF-beta) is responsible for the physiological activity of the complex .
Interleukin-11A, fish (IL-11A_fish)
Type: Family

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine that stimulates megakaryocytopoiesis, resulting in increased production of platelets, as well as activating osteoclasts, inhibiting epithelial cell proliferation and apoptosis, and inhibiting macrophage mediator production. These functions may be particularly important in mediating the hematopoietic, osseous and mucosal protective effects of IL-11 . The cytokine also possesses anti-inflammatory activity, and has been proposed as a therapeutic agent in the treatment of chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis .

Although IL-11 was initially believed to be restricted to mammals, subsequent studies demonstrated it to be expressed in ray-finned fish . Two fish paralogues have now been identified, designated IL-11A and IL-11B .
Atypical dual-specificity phosphatase Siw14-like, plant and fungi (PFA-DSPs)
Type: Family

This entry represent a group of atypical dual-specificity phosphatases from plant and fungi. Proteins in this entry include Siw14 and related proteins . Siw14 is a inositol pyrophosphate phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7isoform 5PP-IP5to IP6 . This entry also includes DSP1/2/3/4/5 from Arabidopsis. All DSPs tested (AtPFA-DSP1, -2, -3, and -5) displayed phosphatase activity toward PI(3,5)P2, with AtPFA-DSP2 showing a higher activity .
Brain-derived neurotrophic factor (Brain-der_neurotrophic_factor)
Type: Family

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms . Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities.

Originally purified from pig brain , the neurotrophin BDNF is expressed in a range of tissues and cell types in the CNS and periphery. It exerts its effects by binding to neurotrophic tyrosine kinase receptor type 2 (NTRK2; also called TrkB) and the low affinity nerve growth factor receptor, p75NTR. While the former receptor mediates the neurotrophin's prosurvival functions, activation of p75NTR by BDNF has been shown to promote apoptosis and to inhibit axonal growth .
Neurotrophin-6 (Neurotrophin-6)
Type: Family

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms . Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities.
Neurotrophin-4 (Neurotrophin-4)
Type: Family

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms . Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities.

Neurotrophin-4 (NT-4) exerts its effects by binding to neurotrophic tyrosine kinase receptor type 2 (NTRK2; also called TrkB). NT-4 has been shown to play a crucial role in the development of long-term memory . It has also been implicated in the regulation of appetite and in body weight control .
Venom nerve growth factor (Venom_nerve_growth_factor)
Type: Family

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms . Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities.
Tumour necrosis factor receptor 5 (TNFR_5)
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 .

TNF receptor 5 (also known as CD40 antigen) is expressed by a wide variety of cell types, including B lymphocytes, macrophages, dendritic cells, endothelial cells and epithelial cells. The receptor plays an important role in T cell-mediated B lymphocyte activation .
Somatomedin B domain, chordata (SMB_chordata)
Type: Domain

This entry includes chordates proteins.

Somatomedin B (SMB), a serum factor of unknown function, is a small cysteine-rich peptide, derived proteolytically from the N terminus of the cell-substrate adhesion protein vitronectin . Cys-rich somatomedin B-like domains are found in a number of proteins , including ectonucleotide pyrophosphatase/phosphodiesterase family member proteins (previously known as plasma-cell membrane glycoprotein) and placental protein 11 (also known as Poly(U)-specific endoribonuclease), which appears to possess amidolytic activity.

The SMB domain of vitronectin has been demonstrated to interact with both the urokinase receptor and the plasminogen activator inhibitor-1 (PAI-1) and the conserved cysteines of the NPP1 somatomedin B-like domain have been shown to mediate homodimerisation .

The SMB domain contains eight Cys residues, arranged into four disulphide bonds. It has been suggested that the active SMB domain may be permitted considerable disulphide bond heterogeneity or variability, provided that the Cys25-Cys31 disulphide bond is preserved. The three dimensional structure of the SMB domain is extremely compact and the disulphide bonds are packed in the centre of the domain forming a covalently bonded core . The structure of the SMB domain presents a new protein fold, with the only ordered secondary structure being a single-turn α-helix and a single-turn 3(10)-helix .
Nerve growth factor, beta subunit, mammalian (Nerve_growth_factor_bsu_mml)
Type: Family

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms . Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities.

Although NGF was originally identified in snake venom, its most abundant and best studied source is the submaxillary gland of adult male mice . Mouse NGF is a high molecular weight hexamer, composed of 2 subunits each of alpha, beta and gamma polypeptides. The beta subunit (NGF-beta) is responsible for the physiological activity of the complex .

NGF-beta induces its cell survival effects through activation of neurotrophic tyrosine kinase receptor type 1 (NTRK1; also called TrkA), and can induce cell death by binding to the low affinity nerve growth factor receptor, p75NTR . The neurotophin has been shown to be involved in sympathetic axon growth and innervation of target fields .