SII-SWORD/CoKE huggingface dataset:
Interleukin-1 receptor type II (IL-1_rcpt_II-typ)
Type: Family

Interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis . Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors . The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location . The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA).

The crystal structures of IL1A and IL1B have been solved, showing them to share the same 12-stranded β-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors . The β-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel β-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

The Vaccinia virus genes B15R and B18R each encode proteins with N-terminal hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain . These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors . A similar gene product from Cowpox virus (CPV) has also been shown to specifically bind murine IL-1 beta .

This entry represents Interleukin-1 receptor, type II, the mature type II IL-1 receptor consists of (i) a ligand binding portion comprising three Ig-like domains; (ii) a single TM domain; and (iii) a short cytoplasmic domain of 29 amino acids . This contrasts with the ~215 amino acid cytoplasmic domain of the type I receptor, suggesting that the two IL-1 receptors may interact with different signal transduction pathways. The type II receptor is expressed in a number of different tissues, including both B and T lymphocytes, and can be induced in several cell types by treatment with phorbol ester. Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location. Like the type I receptor, the human type II IL-1 receptor can bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA) .
Interleukin-1 binding protein (IL-1-bd)
Type: Family

Interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis . Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors . The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location . The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA).

The crystal structures of IL1A and IL1B have been solved, showing them to share the same 12-stranded β-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors . The β-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel β-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

The Vaccinia virus genes B15R and B18R each encode proteins with N-terminal hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain . These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors . A similar gene product from Cowpox virus (CPV) has also been shown to specifically bind murine IL-1 beta .
Gonadoliberin I precursor (Gonadoliberin_I_precursor)
Type: Family

Reproduction is controlled in humans by the hypothalamic-pituitary-gonadal axis . A key molecule in this control circuit is the decapeptide luteinising hormone releasing hormone (LHRH), also termed gonadotropin-releasing hormone (GnRH). GnRH is produced by hypothalamic neurones, secreted in a pulsatile manner into the capillary plexus of the median eminence and mediates the release of luteinising hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary. The peptide may have additional functions, as LHRH or LHRH-like immuno-reactivity has been found in gonadal tissue, placenta and the central nervous system, and exogenously administered LHRH affects behaviour .

The GnRH decapeptide is processed from a larger precursor protein termed progonadoliberin I, which also contains prolactin release-inhibiting factor I.
Foot-and-mouth disease virus VP1 coat (FMDV_VP1_coat)
Type: Domain

The complete nucleotide sequence of cDNA coding for the structural capsid polypeptides of Foot-and-mouth disease virus (FMDV) has been determined. The FMDV capsid is composed of 60 icosahedral units, each of which comprises one copy each of proteins VP1, VP2, VP3 and VP4 . Specific enzymatic cleavages
in vivo
yield mature proteins. The VP1 coat protein contains the main antigenic determinants of the virion, and hence changes in its sequence must be responsible for the high antigenic variability of the virus.

The structure of FMDV has been determined to 2.9A resolution by means of X-ray diffraction. The virus shares similarities with other picorna-viruses, but also reveals unique features. The canyon found in other picornaviruses is absent, which has important implications for cell attachment. The most immunogenic portion of the capsid, which acts as a potent peptide vaccine, forms a disordered protrusion on the virus surface .
Protein OBERON (OBERON)
Type: Family

This entry represents a plant specific protein family, OBERON (OBE), also known as ptyvirus VPg-interacting protein (PVIP). In Arabidopsis, there are four OBEs, OBE1-4. OBE1 together with OBE2 are required for the maintenance and/or establishment of both the shoot and root meristems, probably by controlling the expression of the meristem genes such as WUS, PLT1 and PLT2 and of genes required for auxin responses . All four OBE proteins are able to interact with OBE1 and 2. However, OBE3 and 4 do not self-interact or interact with each other . OBE1 and OBE2 also bind to virus genome-linked proteins (VPgs) of a diverse range of potyviruses and functions as an ancillary factor to support potyvirus movement in plants .
Regulatory associated protein of TOR (Raptor)
Type: Family

This family consists of Raptor (regulatory associated protein of TOR) and its orthologs which includes Kog1p of Saccharomyces cerevisiae (Baker's yeast), a highly conserved 150kDa TOR-binding protein . The target-of-rapamycin (TOR) proteins are protein kinases that were first identified in S. cerevisiae through mutants that conferred resistance to growth inhibition induced by the immunosuppressive macrolide rapamycin .

All Raptor orthologs contain a unique conserved region in their N-terminal half (raptor N-terminal conserved, also called the RNC domain) followed by three HEAT (huntingtin, elongation factor 3, A subunit of protein phosphatase 2A and TOR1) repeats and seven WD-40 repeats near the C terminus. Research on mammalian Raptor suggests that its association with mTOR promotes the phosphorylation of downstream effectors in nutrient-stimulated cells . In concordance with these observations, the binding of TOR to Raptor or to Kog1p is necessary for TOR signalling in vivo in Caenorhabditis elegans and S. cerevisiae .

The RNC domain consists of 3 blocks with at least 67 to 79% sequence similarity and is predicted to have a high propensity to form α helices. The RNC domain is characterised by the presence of invariant catalytic Cys-His dyad, which is structurally and evolutionarily related to known caspases, suggesting that the raptor proteins may have protease activity .
Meiosis-specific protein Spo11 (Meiosis_Spo11)
Type: Domain

Spo11 is a meiosis-specific protein that is responsible for the initiation of recombination during the early stages of meiosis through the formation of DNA double-strand breaks (DSBs) by a type II DNA topoisomerase-like activity . These DSBs initiate homologous recombination, which is required for chromosomal segregation and generation of genetic diversity during meiosis. Spo11 acts in conjunction with several other proteins, including Rec102 in yeast, to bring about meiotic recombination . Mouse and human homologues of Spo11 have been cloned and characterised. The proteins are 82% identical and share ~25% identity with other family members. Mouse Spo11 has been localised to chromosome 2H4, and human SPO11 to chromosome 20q13.2-q13.3, a region amplified in some breast and ovarian tumours .

Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialisation of a DNA-cleavage function for meiotic recombination . Note that the yeast SPO11 protein shares far less similarity to other SPO11 proteins than the human and mouse homologues do to each other.
DNA topoisomerase VI, subunit A (TopoVI_A)
Type: Family

This entry represents subunit A of topoisomerase VI, a type IIB topoisomerase found predominantly in archaea, but also in a few eukayotes, such as the plant Arabidopsis thaliana . This enzyme assembles as a heterotetramer, consisting of two A subunits required for DNA cleavage and two B subunits required for ATP hydrolysis. The B subunit is structurally similar to the ATPase domain of type IIA topoisomerases, but the A subunit is distinct, and instead shares homology with the Spo11 protein that mediates double-strand DNA breaks during meiotic recombination in eukaryotes . The core of subunit A is a dimer, with a deep groove in which the DNA molecule is thought to bind, with the monomers separating during DNA transport. Therefore, though related to type IIA topoisomerases, topoisomerase VI may have a distinctive mechanism of action.

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils .
P pili tip fibrillum PapE protein, Enterobacteriaceae (P_pili_tip_fibrillum_PapE)
Type: Family

The Gram-negative pathogen Escherichia coli causes several common bacterial illnesses in humans, including diarrhoea, neonatal meningitidis and urinary tract infections. Attachment to host tissues is essential for successful invasion, and requires interaction between a bacterial adhesive protein and its target receptor. This protein is usually supported on a larger structure made up of heteropolymeric fibres . Pyelonephritogenic E. coli specifically invade the uroepithelium by expressing between 100 and 300 pili on their cell surface. Pili are macromolecular structures that allow binding to a digalactoside receptor in the urinary tract.

P pili, or fimbriae, are ~68A in diameter and 1 micron in length, the bulk of which is a fibre composed of the main structural protein PapA . At its tip, the pilus is terminated by a fibrillum consisting of repeating units of the PapE protein. This, in turn, is topped by the adhesins, PapF and PapG, both of which are needed for receptor binding. The tip fibrillum is anchored to the main PapA fibre by the PapK pilus-adaptor protein. PapH, an outer membrane protein, then anchors the entire rod in the bacterial envelope . A cytoplasmic chaperone (PapD) assists in assembling the monomers of the macromolecule in the membrane.

PapE can vary its structure and antigenic properties according to the serotype strain of bacteria , and therefore has the ability to evade host immune responses. A recent study into the assembly of P pili showed that both PapA and PapE automatically self-assemble into pilus rods and tip fibrillae, respectively, once released from the PapD chaperone.
K Homology domain (KH_dom)
Type: Domain

The K homology (KH) domain was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K. An evolutionarily conserved sequence of around 70 amino acids, the KH domain is present in a wide variety of nucleic acid-binding proteins. The KH domain binds RNA, and can function in RNA recognition . It is found in multiple copies in several proteins, where they can function cooperatively or independently. For example, in the AU-rich element RNA-binding protein KSRP, which has 4 KH domains, KH domains 3 and 4 behave as independent binding modules to interact with different regions of the AU-rich RNA targets . The solution structure of the first KH domain of FMR1 and of the C-terminal KH domain of hnRNP K determined by nuclear magnetic resonance
(NMR) revealed a β-α-α-β-β-α structure. Proteins containing KH domains include:

Bacterial and organelle PNPases .

Archaeal and eukaryotic exosome subunits .

Eukaryotic and prokaryotic small ribosomal subunit proteins uS3 .

Vertebrate Fragile X messenger ribonucleoprotein 1 (FMR1) .

Vigilin, which has 14 KH domains .

AU-rich element RNA-binding protein KSRP.

hnRNP K, which contains 3 KH domains.

Human onconeural ventral antigen-1 (NOVA-1) .

According to structural analyses , the KH domain can be separated in two groups - type 1 and type 2.
K Homology domain, type 1 (KH_dom_type_1)
Type: Domain

The K homology (KH) domain was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K. It is a domain of around 70 amino acids that is present in a wide variety of quite diverse nucleic acid-binding proteins . It has been shown to bind RNA . Like many other RNA-binding motifs, KH motifs are found in one or multiple copies (14 copies in chicken vigilin) and, at least for hnRNP K (three copies) and FMR-1 (two copies), each motif is necessary for
in vitro
RNA binding activity, suggesting that they may function cooperatively or, in the case of single KH motif proteins (for example, Mer1p), independently .

According to structural analysis the KH domain can be separated in two groups. The first group or type-1 contain a β-α-α-β-β-α structure, whereas in the type-2 the two last β-sheet are located in the N-terminal part of the domain (α-β-β-α-α-β). Sequence similarity between these two folds are limited to a short region (VIGXXGXXI) in the RNA binding motif. This motif is located between helices 1 and 2 in type-1 and between helices 2 and 3 in type-2. Proteins known to contain a type-1 KH domain include bacterial polyribonucleotide nucleotidyltransferase (

); vertebrate Fragile X messenger ribonucleoprotein 1 (FMR1); eukaryotic heterogeneous nuclear ribonucleoprotein K (hnRNP K), one of at least 20 major proteins that are part of hnRNP particles in mammalian cells; mammalian poly(rC) binding proteins; Artemia salina glycine-rich protein GRP33; yeast PAB1-binding protein 2 (PBP2); vertebrate vigilin; and human high-density lipoprotein binding protein (HDL-binding protein).
Methyl-accepting chemotaxis protein (MCP) signalling domain (MCPsignal_dom)
Type: Domain

Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour . Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs . For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides).

This entry represents the signalling domain found in several methyl-accepting chemotaxis proteins. This domain is thought to transduce the signal to CheA since it is highly conserved in very diverse MCPs.
Chemotaxis methyl-accepting receptor (Chemotax_Me-accpt_rcpt)
Type: Family

Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour . Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs . For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides).

This entry contains several methyl-accepting chemotaxis proteins, as well as related prokaryotic signalling receptors. All these proteins are composed of the same structural domains as found in classical MCPs.
Chemotaxis methyl-accepting receptor, methyl-accepting site (Chemotax_Me-accpt_rcpt_Me-site)
Type: PTM

Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour . Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs . For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides).

The methyl-accepting sites are specific glutamate residues (some of these sites are translated as glutamine but are irreversibly deamidated by cheB). They are clustered in two regions of the cytoplasmic domain that interacts with downstream signalling components. This entry represents the first of these two methyl-accepting regions.
Mbt repeat (Mbt)
Type: Repeat

The function of the malignant brain tumor (MBT) repeat is unknown, but is found in a number of nuclear proteins involved in transcriptional repression. The repeat contains a completely conserved glutamate at its amino terminus that may be important for function.

The crystal structure of the two MBT repeats of human SCM-like 2 protein has been reported. Each repeat consists of an extended "arm" and a globular core. The arm of the first repeat packs against the core of the second repeat and vice versa. The structure of the core-interacting part of each arm consists of an N-terminal α-helix and a turn of 3
10
helix connected by a short β-strand. The core consists of an Src homology 3-like five-stranded β-barrel followed by a C-terminal α-helix and another short β-strand. Each arm interacts with its partner core in a similar way, with the orientation of the N-terminal helix relative to the barrel varying slightly. There are also extensive interactions between the two barrels .
Staphylokinase (SAK)
Type: Family

This entry represents staphylokinases.

Staphylokinase (also known as SAK) from Staphylococcus aureus is a virulence factor due to its interaction with plasminogen and alpha-defensins in the hosts. The binding of staphylokinase to plasminogen results in the formation of active plasmin, a proteolytic enzyme facilitating bacterial penetration into the surrounding tissues . However, once the host tissues are infected, the interaction between staphylokinase and plasminogen decreases disease severity . The three-dimensional structure of streptokinase is believed to contain two independently folded domains, each with a ubiquitin-like fold.
Antistasin-like domain (Antistasin-like)
Type: Domain

Antistatin is a small, disulphide cross-linked serine protease inhibitor isolated from the salivary glands of the Mexican leech. It is a potent anticoagulant by virtue of its ability to inhibit factor Xa in the coagulation cascade. Antistatin also exhibits a strong antimetastatic activity. It contains internal repeats of a 25-26 amino acid sequence with a highly conserved pattern of 6 cysteine (Cys) and 2 glycine residues . Many metazoan proteins share sequence homology with this antistasin-like domain. The unique physical properties of these related Cys-rich proteins (protease resistance; heat, chemical resilience) appear to stem from the common six Cys loop that is cross-linked by three disulfide bonds . Disulfide linkages are between Cys1-Cys4, Cys2-Cys5, and Cys3-Cys6 .

The antistasin-like domain consists of very short antiparallel β-sheets and interacts with proteinases .
TGS (TGS)
Type: Domain

The TGS domain (named for its presence ThrRS, GTPase, and SpoT) is present in a number of enzymes, for example, in threonyl-tRNA synthetase (ThrRS), a distinct family of GTPases (the OBG family), and guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase (SpoT) and synthetase (RelA) which are involved in stringent response in bacteria. The TGS domain is also present at the N-terminal of the uridine kinase from the spirochaete Treponema pallidum (but not any other organism, including the related spirochaete Borrelia burgdorferi).

TGS is a small domain that consists of ~50 amino acid residues and has nucleic acid binding affinity. It is arranged in a six-stranded half-barrel that curves around an α-helix and belongs to the β-grasp fold superfamily . The function of the TGS domain of SpoT is in transcription of survival and virulence genes in response to environmental stress .