SII-SWORD/CoKE huggingface dataset:
Synapsin, ATP-binding domain (Synapsin_ATP-bd_dom)
Type: Domain

This entry represent the ATP-grasp fold found in synapsins, which is responsible for Ca dependent ATP binding.

The synapsins are a family of neuron-specific phosphoproteins that coat synaptic vesicles and are involved in the binding between these vesicles and the cytoskeleton (including actin filaments). The family comprises 5 homologous proteins Ia, Ib, IIa, IIb and III. Synapsins I, II, and III are encoded by 3 different genes. The a and b isoforms of synapsin I and II are splice variants of the primary transcripts .

Synapsin I is mainly associated with regulation of neurotransmitter release from presynaptic neuron terminals . Synapsin II, as well as being involved in neurotransmitter release, has a role in the synaptogenesis and synaptic plasticity responsible for long term potentiation . Recent studies implicate synapsin III with a developmental role in neurite elongation and synapse formation that is distinct from the functions of synapsins I and II .

Structurally, synapsins are multidomain proteins, of which 3 domains are common to all the mammalian forms. The N-terminal `A' domain is ~30 residues long and contains a serine residue that serves as an acceptor site for protein kinase-mediated phosphorylation. This is followed by the `B' linker domain, which is ~80 residues long and is relatively poorly conserved. Domain `C' is the longest, spanning approximately 300 residues. This domain is highly conserved across all the synapsins (including those from Drosophila) and is possessed by all splice variants. The remaining six domains, D-I, are not shared by all the synapsins and differ both between the primary transcripts and the splice variants.
Arginine repressor, C-terminal (Arg_repress_C)
Type: Domain

The arginine dihydrolase (AD) pathway is found in many prokaryotes and some primitive eukaryotes, an example of the latter being Giardia lamblia (Giardia intestinalis) . The three-enzyme anaerobic pathway breaks down L-arginine to form 1 mol of ATP, carbon dioxide and ammonia. In simpler bacteria, the first enzyme, arginine deiminase, can account for up to 10% of total cell protein .

Most prokaryotic arginine deiminase pathways are under the control of a repressor gene, termed ArgR . This is a negative regulator, and will only release the arginine deiminase operon for expression in the presence of arginine . The crystal structure of apo-ArgR from Bacillus stearothermophilus has been determined to 2.5A by means of X-ray crystallography . The protein exists as a hexamer of identical subunits, and is shown to have six DNA-binding domains, clustered around a central oligomeric core when bound to arginine. It predominantly interacts with A.T residues in ARG boxes. This hexameric protein binds DNA at its N terminus to repress arginine biosyntheis or activate arginine catabolism. Some species have several ArgR paralogs. In a neighbour-joining tree, some of these paralogous sequences show long branches and differ significantly from the well-conserved C-terminal region.

The C-terminal domain of the arginine repressor is responsible for arginine binding and multimerization . It can also bind ornithine, Pro and Tyr (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
Arginine repressor, DNA-binding domain (Arg_repress_DNA-bd)
Type: Domain

The arginine dihydrolase (AD) pathway is found in many prokaryotes and some primitive eukaryotes, an example of the latter being Giardia lamblia (Giardia intestinalis) . The three-enzyme anaerobic pathway breaks down L-arginine to form 1 mol of ATP, carbon dioxide and ammonia. In simpler bacteria, the first enzyme, arginine deiminase, can account for up to 10% of total cell protein .

Most prokaryotic arginine deiminase pathways are under the control of a repressor gene, termed ArgR . This is a negative regulator, and will only release the arginine deiminase operon for expression in the presence of arginine . The crystal structure of apo-ArgR from Bacillus stearothermophilus has been determined to 2.5A by means of X-ray crystallography . The protein exists as a hexamer of identical subunits, and is shown to have six DNA-binding domains, clustered around a central oligomeric core when bound to arginine. It predominantly interacts with A.T residues in ARG boxes. This hexameric protein binds DNA at its N terminus to repress arginine biosyntheis or activate arginine catabolism. Some species have several ArgR paralogs. In a neighbour-joining tree, some of these paralogous sequences show long branches and differ significantly from the well-conserved C-terminal region.
Proteinase inhibitor I2, Kunitz, conserved site (Prtase_inh_Kunz-CS)
Type: Conserved_site

This entry represents a conserved site spanning a region starting after the third cysteine and ending with the fifth one.

The majority of the sequences having this domain belong to the MEROPS inhibitor family I2, clan IB; the Kunitz/bovine pancreatic trypsin inhibitor family, they inhibit proteases of the S1 family and are restricted to the metazoa with a single exception: Amsacta moorei entomopoxvirus. They are short (~50 residue) alpha/beta proteins with few secondary structures. The fold is constrained by 3 disulphide bonds. The type example for this family is aprotinin (bovine pancreatic trypsin inhibitor) (or basic protease inhibitor), but the family includes numerous other members , such as snake venom basic protease; mammalian inter-alpha-trypsin inhibitors; trypstatin, a rodent mast cell inhibitor of trypsin; a domain found in an alternatively-spliced form of Alzheimer's amyloid beta-protein; domains at the C-termini of the alpha(1) and alpha(3) chains of type VII and type VI collagens; and tissue factor pathway inhibitor precursor.
Actin/actin-like conserved site (Actin/actin-like_CS)
Type: Conserved_site

Actin is a ubiquitous protein involved in the formation of filaments that are major components of the cytoskeleton. These filaments interact with myosin to produce a sliding effect, which is the basis of muscular contraction and many aspects of cell motility, including cytokinesis. Each actin protomer binds one molecule of ATP and has one high affinity site for either calcium or magnesium ions, as well as several low affinity sites. Actin exists as a monomer in low salt concentrations, but filaments form rapidly as salt concentration rises, with the consequent hydrolysis of ATP. Actin from many sources forms a tight complex with deoxyribonuclease (DNase I) although the significance of this is still unknown. The formation of this complex results in the inhibition of DNase I activity, and actin loses its ability to polymerise. It has been shown that an ATPase domain of actin shares similarity with ATPase domains of hexokinase and hsp70
proteins .

In vertebrates there are three groups of actin isoforms: alpha, beta and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exists in most cell types as components of the cytoskeleton and as mediators of internal cell motility. In plants there are many isoforms which are probably involved in a variety of functions such as cytoplasmic streaming, cell shape determination, tip growth, graviperception, cell wall deposition, etc.

Recently some divergent actin-like proteins have been identified in several species. These proteins include centractin (actin-RPV) from mammals, fungi yeast ACT5, Neurospora crassa ro-4 and Pneumocystis carinii, which seems to be a component of a multi-subunit centrosomal complex involved in microtubule based vesicle motility (this subfamily is known as ARP1); ARP2 subfamily, which includes chicken ACTL, Saccharomyces cerevisiae ACT2, Drosophila melanogaster 14D and Caenorhabditis elegans actC; ARP3 subfamily, which includes actin 2 from mammals, Drosophila 66B, yeast ACT4 and Schizosaccharomyces pombe act2; and ARP4 subfamily, which includes yeast ACT3 and Drosophila 13E.

This entry contains a signature that picks up both actins and the actin-like proteins and corresponds to positions 106 to 118 in actins.
Epithelial sodium channel, conserved site (ENaC_CS)
Type: Conserved_site

The apical membrane of many tight epithelia contains sodium channels that are primarily characterised by their high affinity to the diuretic blocker amiloride . These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis . In vertebrates, the channels control reabsorption of sodium in kidney, colon, lung and sweat glands; they also play a role in taste perception.

Members of the epithelial Na
+
channel (ENaC) family fall into four subfamilies, termed alpha, beta, gamma and delta . The proteins exhibit the same apparent topology, each with two transmembrane (TM) spanning segments, separated by a large extracellular loop. In most ENaC proteins studied to date, the extracellular domains are highly conserved and contain numerous cysteine residues, with flanking C-terminal amphipathic TM regions, postulated to contribute to the formation of the hydrophilic pores of the oligomeric channel protein complexes. It is thought that the well-conserved extracellular domains serve as receptors to control the activities of the channels.

Vertebrate ENaC proteins are similar to degenerins of Caenorhabditis elegans : deg-1, del-1, mec-4, mec-10 and unc-8. These proteins can be mutated to cause neuronal degradation, and are also thought to form sodium channels.

Structurally, the proteins that belong to this family consist of about 510 to 920 amino acid residues. They are made of an intracellular N terminus region followed by a transmembrane domain, a large extracellular loop, a second transmembrane segment and a C-terminal intracellular tail .

For this entry the signature corresponds to the beginning of a conserved cysteine-rich region (there are nine conserved cysteines in a domain of about 65 residues), located at the C-terminal part of the extracellular loop.
Short-chain dehydrogenase/reductase, conserved site (Sc_DH/Rdtase_CS)
Type: Conserved_site

This entry represents one of the best conserved regions in this family of proteins It includes two perfectly conserved residues, a tyrosine and a lysine. The tyrosine residue participates in the catalytic mechanism.

The short-chain dehydrogenases/reductases family (SDR) is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterised was Drosophila alcohol dehydrogenase, this family used to be called 'insect-type', or 'short-chain' alcohol dehydrogenases. Most members of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least 2 domains , the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains .
NAD(P)H-quinone oxidoreductase subunit O (NdhO)
Type: Family

NAD(P)H-quinone oxidoreductase (NDH-1) shuttles electrons from an unknown electron donor, via FMN and iron-sulphur (Fe-S) centres, to quinones in the respiratory and/or the photosynthetic chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. It couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient. Cyanobacterial NDH-1 also plays a role in inorganic carbon-concentration. NDH-1 can be composed of about 15 different subunits, although different subcomplexes with different compositions have been identified which probably have different functions.

This entry represents subunit O.
Double-stranded DNA-binding Cren7 (dsDNA-bd_Cren7)
Type: Family

Cren7 is a chromatin protein found in Crenarchaeota and has a higher affinity for double-stranded DNA than for single-stranded DNA. The protein contains negative DNA supercoils and is associated with genomic DNA in vivo. Cren7 interacts with duplex DNA through a β-sheet and a long flexible loop. It is binding to double-stranded DNA without sequence specificity . There is approximately 1 Cren7 molecule for 12 bp of DNA. The function of Cren7 has not been completely determined but it is thought that the protein may have a role similar to that of archaeal proteins in Euryarchaea .
PhoP/PhoQ regulator MgrB (MgrB)
Type: Family

This entry represents MgrB, a short lipoprotein that is induced by low extracellular levels of magnesium via the PhoQ/PhoP two-component regulatory system . Deletion of MgrB results in a potent increase in PhoP-regulated transcription .
Uncharacterised protein family UPF0738 (UPF0738)
Type: Family

This entry describes proteins of unknown function.
UPF0736 (UPF0736)
Type: Family

This entry describes proteins of unknown function.
Uncharacterised protein family UPF0370 (UPF0370)
Type: Family

This entry describes proteins of unknown function that are thought to be membrane proteins.
Uncharacterised protein family UPF0325 (UPF0325)
Type: Family

This entry describes proteins of unknown function.
Uncharacterised protein family UPF0295 (UPF0295)
Type: Family

This entry describes proteins of unknown function, which are thought to be membrane proteins.
Uncharacterised protein family UPF0323 (UPF0323)
Type: Family

This entry describes proteins of unknown function that are confined to epsilonproteobacteria.
Probable succinate transporter subunit YjjB (YjjB)
Type: Family

This entry includes probable succinate transporter subunit YjjB from gammaproteobacteria. YjjB is thought to play a role in the production of succinate .
Uncharacterised protein family UPF0311 (UPF0311)
Type: Family

This entry describes proteins of unknown function.
Protein-glutamine gamma-glutamyltransferase, bacteria (Gln_gamma-glutamylTfrase_bac)
Type: Family

This entry represents a protein-glutamine gamma-glutamyltransferase which may play a role in the assembly of the spore coat proteins by catalysing epsilon-(gamma-glutamyl)lysine cross-links.
Primosomal protein 1 (DnaT)
Type: Family

This entry represents Primosomal protein 1 (DnaT) and similar proteins from Proteobacteria. DnaT, a DnaB/C complex loader protein, is required for primosome-dependent normal DNA replication . It is part of the "PriA-PriB" pathway for primosome assembly and is involved in inducing stable DNA replication during SOS response. The N-terminal domain of DnaT is crucial for PriB binding and self-trimerization while the C-terminal domain of DnaT is the DNA-binding domain .
Peptide chain release factor aRF1 (Peptide_chain-rel_aRF1)
Type: Family

Terminating protein synthesis on the ribosome requires the presence of a class I polypeptide chain release factor (RF) to induce peptidyl-tRNA hydrolysis. Bacteria possess two class I RFs; RF1 which recognises UAG and UAA, and RF2 which recognises UGA and UAA. Mitochondrial RFs are related structurally and functionally to those of bacteria. Eukaryotes posses only a single class 1 factor, eRF1, which recognises all three termination codons. Similarly, in all archaeal species where the complete sequence of the genome is available, only a single class I factor, aRF1, has been identified so far. The aRF1 family is highly homologous to the eRF1 family, indicating a common origin and ancestor molecule. The bacterial and mitochondrial class I RFs show no significant sequence similarity with their eukaryotic and archaeal counterparts and are considered to form a separate family. For more information see .

This entry represents the archaeal release factor aRF1, which seems to have functional resemblance to eukaryotic RF1 .
Small ribosomal subunit protein eS8, archaeal (Ribosomal_protein_eS8_arc)
Type: Family

This entry represents the archaeal eS8 proteins, which are about 125 amino acids in length.

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 .
L-lactate dehydrogenase, bacterial (LldD)
Type: Family

This entry represents the bacterial L-lactate dehydrogenase, a member of the FMN-dependent alpha-hydroxy acid dehydrogenase family. It catalyses the oxidation of L-lactate to pyruvate . The lld operon was previously named lct .
Erythronate-4-phosphate dehydrogenase (Erythronate-4-P_DHase)
Type: Family

Pyridoxal-5'-phosphate is the active form of vitamin B6 and is an essential cofactor for many enzymes, particularly those involved in amino acid metabolism . There are three known pathways for pyridoxal-5'-phosphate biosynthesis: the de novo pathway, the salvage pathway, and the fungal type pathway. Bacteria, fungi, parasites and plants all possess at least one of these pathways, but higher organisms, such as insects and mammals, are incapable of synthesising this compound and need vitamin B6 in their diet to survive.

Erythronate-4-phosphate dehydrogenase catalyses the first step in the de novo biosynthetic pathway, the oxidation of erythrose-4-phosphate to 4-phosphoerythronate .
dITP/XTP pyrophosphatase (dITP/XTP_pyrophosphatase)
Type: Family

This entry represents a family of nucleoside-triphosphatases that hydrolyse non-standard nucleotides such as deoxyinosine triphosphate (dITP) and xanthosine triphosphate (XTP). It has been suggested that they may function as part of a preemptive DNA repair system by excluding non-standard purines from DNA precursor pool, thus preventing their incorporation into DNA and avoiding chromosomal lesions .
DNA ligase B (DNA_ligase_B)
Type: Family

DNA ligase B, a protein that is is highly conserved throughout the Enterobacteriaceae family, is an NAD(+)-dependent enzyme that catalyses the sealing of 5' phosphate and 3' hydroxyl termini at nicks in duplex DNA by means of three sequential nucleotidyl transfer reactions. Unlike DNA ligase A, it is not essential under normal laboratory growth conditions but is related to specific DNA damaging agents and antibiotics

, .
Small ribosomal subunit protein eS6, archaeal (Ribosomal_eS6_arc)
Type: Family

This entry represents the archaeal eS6 proteins.

A number of eukaryotic and archaeal ribosomal proteins have been grouped on the basis of sequence similarities. Small ribosomal subunit protein eS6, previously known as Ribosomal protein S6 is the major substrate of protein kinases in eukaryotic ribosomes and may play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.

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 .