SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein uL4 (Ribosomal_uL4)
Type: Family

This family includes large ribosomal subunit protein uL4 from eukaryotes, archaea and bacteria. This protein is well characterised .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Beta-lactamase, class-D active site (Beta-lactam_class-D_AS)
Type: Active_site

Beta-lactamases (

) are enzymes which catalyse the hydrolysis of an amide bond in the beta-lactam ring of antibiotics belonging to the penicillin/cephalosporin family. Four kinds of beta-lactamase have been identified . Class-B enzymes are zinc containing proteins whilst class -A, C and D enzymes are serine hydrolases. The three classes of serine beta-lactamases are evolutionary related and belong to a superfamily that also includes DD-peptidases and a variety of other penicillin-binding proteins (PBP's). All these proteins contain a Ser-x-x-Lys motif, where the serine is the active site residue. Although clearly homologous, the sequences of the three classes of serine beta-lactamases exhibit a large degree of variability and only a small number of residues are conserved in addition to the catalytic serine.

This entry represents an active site signature present in all class D Beta-lactamases.
Peptidase C14, caspase non-catalytic subunit p10 (Pept_C14_p10)
Type: Domain

This group of sequences represent the p10 subunit found in caspases. Caspases (Cysteine-dependent ASPartyl-specific proteASE) are cysteine peptidases that belong to the MEROPS peptidase family C14 (caspase family, clan CD) based on the architecture of their catalytic dyad or triad . Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. Activated caspases act as cysteine proteases, using the sulphydryl group of a cysteine side chain for catalysing peptide bond cleavage at aspartyl residues in their substrates. The catalytic cysteine and histidine residues are on the p20 subunit after cleavage of the p45 precursor.

Caspases are mainly involved in mediating cell death (apoptosis) . They have two main roles within the apoptosis cascade: as initiators that trigger the cell death process, and as effectors of the process itself. Caspase-mediated apoptosis follows two main pathways, one extrinsic and the other intrinsic or mitochondrial-mediated. The extrinsic pathway involves the stimulation of various TNF (tumour necrosis factor) cell surface receptors on cells targeted to die by various TNF cytokines that are produced by cells such as cytotoxic T cells. The activated receptor transmits the signal to the cytoplasm by recruiting FADD, which forms a death-inducing signalling complex (DISC) with caspase-8. The subsequent activation of caspase-8 initiates the apoptosis cascade involving caspases 3, 4, 6, 7, 9 and 10. The intrinsic pathway arises from signals that originate within the cell as a consequence of cellular stress or DNA damage. The stimulation or inhibition of different Bcl-2 family receptors results in the leakage of cytochrome c from the mitochondria, and the formation of an apoptosome composed of cytochrome c, Apaf1 and caspase-9. The subsequent activation of caspase-9 initiates the apoptosis cascade involving caspases 3 and 7, among others. At the end of the cascade, caspases act on a variety of signal transduction proteins, cytoskeletal and nuclear proteins, chromatin-modifying proteins, DNA repair proteins and endonucleases that destroy the cell by disintegrating its contents, including its DNA. The different caspases have different domain architectures depending upon where they fit into the apoptosis cascades, however they all carry the catalytic p10 and p20 subunits.

Caspases can have roles other than in apoptosis, such as caspase-1 (interleukin-1 beta convertase) (

), which is involved in the inflammatory process. The activation of apoptosis can sometimes lead to caspase-1 activation, providing a link between apoptosis and inflammation, such as during the targeting of infected cells. Caspases may also be involved in cell differentiation .
Ribokinase/fructokinase (Ribo/fructo_kinase)
Type: Family

Ribokinases participate in the first step of ribose metabolism, and are members of the superfamily of carbohydrate kinases. Ribokinases phosphorylate ribose to ribose-5-phosphate in the presence of ATP and magnesium :

ATP + D-Ribose = ADP + D-Ribose-5-Phosphate

The phosphorylated sugar may then enter the pentose phosphate pathway . There are indications that the phosphorylated sugar may also be used in the synthesis of amino acids (histidine and tryptophan). Further, links to mammalian adenosine kinase have been identified, through sequence similarity, suggesting possible homology .

This family also includes fructokinases . Fructokinase may be involved in a sugar-sensing pathway in plants .

Other proteins included in this entry are: cytidine kinase from Thermococcus kodakarensis , Sulfofructose kinase from Escherichia coli , Pseudouridine kinase from Arabidopsis thaliana , deoxyribokinase and MJ0406 (

) from Methanocaldococcus jannaschii. MJ0406 was previously annotated as a 6-phosphofructokinases (PFK), but has since been characterised as a functional nucleoside kinase .
Ribosome maturation protein Sdo1/SBDS (Sdo1/SBDS)
Type: Family

The proteins in this entry are highly conserved in species ranging from archaea to vertebrates and plants . The family contains several Shwachman-Bodian-Diamond syndrome (SBDS, OMIM 260400) proteins from both mouse and humans. Shwachman-Diamond syndrome is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. It is characterised by bone marrow failure and leukemia predisposition . SBDS is required for the assembly of mature ribosomes and ribosome biogenesis .

Homologue of SBDS from budding yeast is known as Sdo1, which is a guanine nucleotide exchange factor (GEF) involved in ribosome maturation. Together with the EF-2-like GTPase RIA1 (EfI1), it triggers the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, allowing the assembly of mature ribosomes .
Influenza virus nucleoprotein (NP) (Flu_NP)
Type: Family

Influenza virus nucleoprotein (NP) is a structural protein which encapsidates the negative strand viral RNA. NP is one of the main determinants of species specificity. The question of how far the NP gene can cross the species barrier by reassortment and become adapted by mutation to the new host has been discussed .
Peptidase S49 (Peptidase_S49)
Type: Domain

This group of serine peptidases belong to MEROPS peptidase family S49 (protease IV family, clan S-). The predicted active site serine for members of this family occurs in a transmembrane domain.

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .
Large ribosomal subunit protein uL1 (Ribosomal_uL1)
Type: Family

Ribosomal protein uL1 (also known as L1) is the largest protein from the large ribosomal subunit. The uL1 protein contains two domains: 2-layer α/β domain and a 3-layer α/β domain (interrupts the first domain). In
Escherichia coli
, uL1 is known to bind to the 23S rRNA .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Ribbon-helix-helix protein, CopG (CopG)
Type: Domain

The structure of this protein repressor, which is the shortest reported to date and the first isolated from a plasmid, has a homodimeric ribbon-helix-helix arrangement . The helix-turn-helix-like structure is involved in dimerisation and not DNA binding as might have been expected .
ATP synthase, F0 complex, subunit b/b', bacterial/chloroplast (ATP_synth_b/b'su_bac/chlpt)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

This entry represents subunits b and b' from the F0 complex in F-ATPases found in chloroplasts and in bacterial plasma membranes. The b subunits are part of the peripheral stalk that links the F1 and F0 complexes together, and which acts as a stator to prevent certain subunits from rotating with the central rotary element. The peripheral stalk differs in subunit composition between mitochondrial, chloroplast and bacterial F-ATPases. In bacterial and chloroplast F-ATPases, the peripheral stalk is composed of one copy of the delta subunit (homologous to OSCP in mitochondria), and two copies of subunit b in bacteria, or one copy each of subunits b and b' in chloroplasts and photosynthetic bacteria .
5-Hydroxytryptamine 1B receptor (5HT1B_rcpt)
Type: Family

5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics .

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel , all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family , and they activate an intracellular second messenger cascade to produce their responses.

The 5-HT1 receptors are a subfamily of 5-HT receptors that were originally classified according to their inhibition of adenylyl cyclase, degree of sequence similarity and their overlapping pharmacological specificities. The subfamily is comprised of five different receptors 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, and they can couple to Gi/Go and mediate inhibitory neurotransmission, although signalling via other transduction systems are known. One of the 5-HT1 receptors, the 5-HT1E receptor, is yet to achieve receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR), since a robust response mediated via the protein has not been reported in the literature.

The 5-HT1B receptor is almost pharmacologically identical to the 5-HT1D receptor, but has a much higher expression level . 5-HT1B receptors are expressed in the CNS. They induce presynaptic inhibition and influence behaviour . They also have vascular effects, such as pulmonary vasoconstriction . The receptors are therapeutic targets of the antimigraine 'triptans' (e.g. sumitriptan and zolmitriptan), which are non-selective 5-HT1D/1B receptor agonists . In addition to the antimigraine activity of such drugs, other therapeutic uses include effects on bipolar disorder, autism and as anti-aggression agents . 5-HT1B receptors may also have a role in the regulation of bone, since blocking 5-HT1B receptors decreases the number of osteoblasts, bone mass, and the bone formation rate .
Rotavirus non-structural protein 1 (Rotavirus_NSP1)
Type: Family

The proteins in this family are non-structural protein 1 (NSP1), also known as non-structural RNA-binding protein 53(NS53). They are RNA binding proteins that contain a characteristic cysteine rich region . They are made at low levels in infected cells and are a component of early replication and are known to accumulate on the cytoskeleton of the infected cell.
Large ribosomal subunit protein bL31 type A/B (Ribosomal_bL31)
Type: Family

This entry groups large ribosomal subunit proteins bL31 classified as type A and type B.

Ribosomal protein bL31 is one of the proteins from the large ribosomal subunit. bL31 is a protein of 66 to 97 amino-acid residues which has only been found so far in bacteria and in some plant and algal chloroplasts.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Kinesin light chain (Kinesin_light)
Type: Family

Kinesin is a microtubule-associated force-producing molecular motor protein that transports numerous organelles along mirotubules. Kinesin is an oligomeric complex composed of two heavy chains and two identical light chains. The light chain has been proposed to function in the coupling of cargo to the heavy chain or in the modulation of its ATPase activity. The specificity of kinesin-cargo binding is thought to depend on the type of light chain that a kinesin molecule contains, where different isoforms of kinesin light chains are associated with different types of cargo, mitochondria and membranes of the Golgi complex .

The structure of Drosophila kinesin light chain was shown to have a core composed of a coiled-coil domain followed by five imperfect tandem repeats and a sixth shorter motif . These repeats are highly conserved across species. The N and C termini are more variable and alternative splicing is responsible for the production of isoforms that differ in those two regions.
Glycoside hydrolase, family 23 (Glyco_hydro_23)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Anser sp. (goose)-type lysozyme (lysozyme G) hydrolyses 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan hetero-polymers of prokaryote cell walls. Lysozyme G shows preference for N-acetylmuramic acid residues that are substituted with a peptide moiety; it acts only as a glycanohydrolase.

The structure of goose egg-white lysozyme (GEWL) with a bound trisaccharide has been refined to 1.6A resolution . The trisaccharide occupies analogous sites to the B, C and D subsites of chicken (HEWL) and Bacteriophage T4 (T4L) lysozymes. All of these enzymes display the same characteristic hydrogen bonding pattern between protein and substrate . Glu73 of GEWL corresponds closely to Glu35 of HEWL (Glu11 of T4L), supporting the view that this group is critical to the catalytic mechanism. However, lysozyme G has no obvious counterpart to Asp52 of chicken lysozyme (Asp20 in T4L), suggesting that a second acidic residue is not essential for its catalytic activity, and may not be required for the activity of other lysozymes. The structure of GEWL belongs to the mainly alpha class, its sequence showing no discernible similarity to other lysozymes. The enzyme has been classified as belonging to family 23 of glycosyl hydrolases (

).