SII-SWORD/CoKE huggingface dataset:
Interleukin-11 (IL-11)
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 .

This entry represents interleukin-11.
Interleukin-15 (IL-15)
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-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses . It is required for division of CD8+ T cells of memory phenotype, a process that is increased by inhibition of IL-2 . The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2.

This entry represents interleukin-15.
Interleukin-17, chordata (IL-17_chr)
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-17 (IL-17) is a potent proinflammatory cytokine produced by activated memory T cells . The IL-17 family (of which there are 6 known members, termed IL-17A to IL-17F) is thought to represent a distinct signalling system that appears to have been highly conserved across vertebrate evolution . Family members play an active role in inflammatory diseases, autoimmune diseases and cancer .

This entry represents interleukin-17 found in chordata.
Interleukin-20 (IL-20)
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-20 (IL-20) belongs to the family of IL-10-related cytokines, which includes IL-10, -19, -20, -22, -24 and -26 . IL-20 induces STAT activation through two types of receptor complex, one of which it shares with IL-19, indicating that their biological activities may overlap . Both cytokines may play an important role in regulating the development and proper functioning of skin . IL-20 has also been shown to promote endothelial cell tube formation, suggesting that it may be involved in vascular vessel maturation and remodelling .

This entry represents interleukin-20.
Interleukin-10/19/20/24/26 (IL-10/19/20/24/26)
Type: Family

This entry represents the interleukin-10, interleukin-19, interleukin-20, interleukin-24 and interleukin-26 family.

Interleukin-10 (IL-10) is a protein that inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T cells. Structurally, IL-10 is a protein of about 160 amino acids that contains four conserved cysteines involved in disulphide bonds . IL-10 is highly similar to the Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) BCRF1 protein which inhibits the synthesis of gamma-interferon and to Equid herpesvirus 2 (Equine herpesvirus 2) protein E7. It is also similar, but to a lesser degree, with human protein mda-7 , a protein which has antiproliferative properties in human melanoma cells. Mda-7 only contains two of the four cysteines of IL-10.
Interleukin-24 (IL-24)
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-24 (IL-24, also known as melanoma differentiation-associated gene-7) belongs to the family of IL-10-related cytokines, which includes IL-10, -19, -20, -22, -24 and -26 . It has been proposed, based on the expression pattern of IL-24 and its receptors, that the cytokine may play a role in epidermal functions, such as wound healing . IL-24 has also been shown to possess cancer-specific apoptosis-inducing activity, and has therefore been suggested as a potential anti-cancer agent .

This entry represents interleukin-24.
Tumour necrosis factor receptor 4 (TNFR_4)
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 rodlike 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 .
NT-3 growth factor receptor NTRK3 (NTRK3)
Type: Family

Neurotrophins are a family of secreted proteins that regulate development, maintenance and function of vertebrate nervous systems. They act via two different classes of receptor: p75NTR (a member of the TNF receptor superfamily), and neurotrophic tyrosine kinase receptors (NTRKs) - also known as tropomyosin-related kinases (Trks) .

NTRK3 (also termed TrkC) is a high-affinity receptor for neurotrophin-3 (NT-3). The receptor is widely expressed in the developing nervous system, and is also found in many non-neuronal tissues . In addition to roles in peripheral nerve cell myelination, mediating the inhibitory effects of NT-3 on this process .
Interleukin-9 (IL-9)
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-9 (IL-9) is expressed primarily by activated T cells . The growth factor and anti apoptotic activities of IL-9 on multiple transformed cells suggest a potential role for the cytokine in tumourigenesis . IL-9 has also been proposed as a candidate gene for asthma .

This entry represents interleukin-9.
Maltose fermentation regulatory protein, DNA-binding domain (Maltose_ferment_reg_DNA-bd)
Type: Domain

This entry represents a subset of the Zn2Cys6 DNA-binding domains found in maltose fermentation regulatory proteins such MAL13, MAL33 and MAL63. These proteins regulate the transcription of structural maltase (MAL1S, MAL3S or MAL6S) and maltose permease (AGT1, MAL3T or MAL6T) genes . This entry also includes Respiratory transcription factor ZNF1 that regulates respiratory growth and plays a critical role in stress adaptation during non-fermentative growth .

The N-terminal region of a number of fungal transcriptional regulatory proteins contains a Cys-rich motif that is involved in zinc-dependent binding of DNA. The region forms a binuclear Zn cluster, in which two Zn atoms are bound by six Cys residues . A wide range of proteins are known to contain this domain. These include the proteins involved in arginine, proline, pyrimidine, quinate, maltose and galactose metabolism, amide and GABA catabolism, leucine biosynthesis, amongst others. The structure of Zn2Cys6 DNA-binding domain from different proteins has been determined in free and DNA bound state (

) revealing details of the molecular basis of DNA recognition .
Transcription regulator HTH, AraC- type, HTH domain (Tscrpt_reg_AraC-type_HTH)
Type: Domain

Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis of sequence similarity. One such family groups together a range of proteins, including AppY, EnvY, ExsA, FapR, MmsR, RhaR, RhaS, Rns, SoxS, and VirF . Although the sequences belonging to this family differ somewhat in length, in each case the HTH motif, represented by this entry, is situated towards the C terminus.
Interleukin-16 (IL-16)
Type: Family

This entry represents human interleukin-16 (IL-16) and similar sequences mainly found in mammals and aves.

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-16 (IL-16, also known as Pro-interleukin-16 or Lymphocyte chemoattractant factor) is a proinflammatory cytokine that signals via CD4, inducing chemotactic and immunomodulatory responses of CD4+ lymphocytes, monocytes and eosinophils . The cytokine has been implicated in the exacerbation of a number of infectious, immune-mediated and autoimmune inflammatory disorders, including atopic dermatitis, irritable bowel syndrome, systemic lupus erythematosus, neurodegenerative disorders, and viral infections .
Interleukin-15, avian (IL-15_avian)
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-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses . It is required for division of CD8+ T cells of memory phenotype, a process that is increased by inhibition of IL-2 . The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2.

IL-15 has been identified in mammals, birds and fish. Avian IL-15s are expressed in a wide variety of tissues and cell types, including liver, muscle, heart, and intraepithelial lymphocytes . They have been shown to stimulate the growth of spleen T-cells and to enhance the activity of natural killer (NK) cells . Thsi entry represents IL-15 found in birds.
Subtilin biosynthesis protein SpaC (Subtilin_biosynthesis_SpaC)
Type: Family

The LanC-like protein superfamily encompasses a highly divergent group of peptide-modifying enzymes, including the eukaryotic and bacterial lanthionine synthetase C-like proteins (LanC) ; subtilin biosynthesis protein SpaC from Bacillus subtilis ; epidermin biosynthesis protein EpiC from Staphylococcus epidermidis ; nisin biosynthesis protein NisC from Lactococcus lactis ; GCR2 from Arabidopsis thaliana ; and many others.

The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution . The globular structure is characterised by an all-α fold, in which an outer ring of helices envelops an inner toroid composed of 7 shorter, hydrophobic helices. This 7-fold hydrophobic periodicity has led several authors to claim various members of the family, including eukaryotic LanC-1 and GCR2, to be novel G protein-coupled receptors ; some of these claims have since been corrected .

The SpacC protein from B. subtilis is a cyclase enzyme involved in the biosynthesis of the lantibiotic subtilin .The protein exists as a monomer in solution and contains a stoichiometric zinc atom , two cysteines and two histidines possibly acting as ligands to the metal; these cysteine residues are highly conserved in LanC-like proteins.
Interleukin-22 (IL-22)
Type: Family

This entry represents interleukin-22.

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.
Diacylglycerol/phorbol-ester binding (DAG/PE-bd)
Type: Domain

This entry represents the N-terminal region of PKC, known as C1. It has been shown to bind PE and DAG in a phospholipid and zinc-dependent fashion . The C1 region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain, which is about 50 amino-acid residues long, and which is essential for DAG/PE-binding. The DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.
BDNF/NT-3 growth factors receptor NTRK2 (NTRK2)
Type: Family

Neurotrophins are a family of secreted proteins that regulate development, maintenance and function of vertebrate nervous systems. They act via two different classes of receptor: p75NTR (a member of the TNF receptor superfamily), and neurotrophic tyrosine kinase receptors (NTRKs) - also known as tropomyosin-related kinases (Trks) .

This entry represents NTRK2 (also termed TrkB) is a high-affinity receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin (NT-4). It is broadly expressed in the nervous system, and is also found in some non neural tissues . The receptor is involved in synaptogenesis and neuronal development . It plays a crucial role in learning and memory .
Acylphosphatase (Acylphosphatase)
Type: Family

Acylphosphatase (

) is an enzyme of approximately 98 amino acid residues that specifically catalyses the hydrolysis of the carboxyl-phosphate bond of acylphosphates , its substrates including 1,3-diphosphoglycerate and carbamyl phosphate . The enzyme has a mainly β-sheet structure with 2 short α-helical segments. It is distributed in a tissue-specific manner in a wide variety of species, although its physiological role is as yet unknown : it may, however, play a part in the regulation of the glycolytic pathway and pyrimidine biosynthesis . There are two known isozymes. One seems to be specific to muscular tissues, the other, called 'organ-common type', is found in many different tissues. A number of bacterial and archebacterial hypothetical proteins are highly similar to that enzyme and that probably possess the same activity.
Zinc finger, B-box, chordata (Znf_B-box_chordata)
Type: Domain

This entry represents B-box-type zinc finger domains, which are around 40 residues in length.

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Zinc finger, DksA/TraR C4-type conserved site (Znf_DskA_TraR_CS)
Type: Conserved_site

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents the zinc fingers identified in zinc finger-containing members of the DksA/TraR family. DksA is a critical component of the rRNA transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. In delta-dksA mutants, rRNA promoters are unresponsive to changes in amino acid availability, growth rate, or growth phase. In vitro, DksA binds to RNAP, reduces open complex lifetime, inhibits rRNA promoter activity, and amplifies effects of ppGpp and the initiating NTP on rRNA transcription . The dksA gene product suppresses the temperature-sensitive growth and filamentation of a dnaK deletion mutant of Escherichia coli. Gene knockout and deletion experiments have shown the gene to be non-essential, mutations causing a mild sensitivity to UV light, but not affecting DNA recombination . In
Pseudomonas aeruginosa, dksA is a novel regulator involved in the post-transcriptional control of extracellular virulence factor production .
AMP-binding (AMP-binding)
Type: Domain

A number of prokaryotic and eukaryotic enzymes, which appear to act via an ATP-dependent covalent binding of AMP to their substrate, share a region of sequence similarity . This region is a Ser/Thr/Gly-rich domain that is further characterised by a conserved Pro-Lys-Gly triplet. The family of enzymes includes Pyochelin synthase PchF and various other closely-related synthases .
Zinc finger, DksA/TraR C4-type, bacteria (Znf_C4-type_bac)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents the zinc fingers identified in zinc finger-containing members of the DksA/TraR family. DksA is a critical component of the rRNA transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. In delta-dksA mutants, rRNA promoters are unresponsive to changes in amino acid availability, growth rate, or growth phase. In vitro, DksA binds to RNAP, reduces open complex lifetime, inhibits rRNA promoter activity, and amplifies effects of ppGpp and the initiating NTP on rRNA transcription . The dksA gene product suppresses the temperature-sensitive growth and filamentation of a dnaK deletion mutant of Escherichia coli. Gene knockout and deletion experiments have shown the gene to be non-essential, mutations causing a mild sensitivity to UV light, but not affecting DNA recombination . In
Pseudomonas aeruginosa, dksA is a novel regulator involved in the post-transcriptional control of extracellular virulence factor production .
High affinity nerve growth factor receptor NTRK1 (NTRK1)
Type: Family

Neurotrophins are a family of secreted proteins that regulate development, maintenance and function of vertebrate nervous systems. They act via two different classes of receptor: p75NTR (a member of the TNF receptor superfamily), and neurotrophic tyrosine kinase receptors (NTRKs) - also known as tropomyosin-related kinases (Trks) .

NTRK1 (also termed TrkA) is a high-affinity receptor for nerve growth factor (NGF). The receptor is expressed in the dorsal root ganglia, trigeminal ganglia and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons . It is also expressed in peripheral sites, such as scalp skin . Whereas p75NTR activation by NGF induces apoptosis, NTRK1 mediates the growth factor's cell survival-promoting effects .
Interleukin-11B, fish (IL-11B_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 .