SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein uL3, archaeal (Ribosomal_uL3_arc)
Type: Family

This entry represents archaeal uL3 proteins.

Ribosomal protein L3 (also known as uL3) is one of the proteins from the large ribosomal subunit. In Escherichia coli, L3 is known to bind to the 23S rRNA and may participate in the formation of the peptidyltransferase centre of the ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities includes bacterial, red algal, cyanelle, mammalian, yeast and Arabidopsis thaliana L3 proteins; archaeal Haloarcula marismortui HmaL3 (HL1), and yeast mitochondrial YmL9 .

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 .
Iron-regulated surface determinant protein IsdB (Iron-reg_IsdB)
Type: Family

Isd proteins are iron-regulated surface proteins found in Bacillus, Staphylococcus and Listeria species and are responsible for haem scavenging from hemoproteins . The IsdB protein is only observed in Staphylococcus and consists of an N-terminal hydrophobic signal sequence, a pair of tandem NEAT (NEAr Transporter,

) domains which confers the ability to bind haem and a C-terminal sortase processing signal which targets the protein to the cell wall. IsdB is believed to make a direct contact with methaemoglobin facilitating transfer of haem to IsdB . The haem is then transferred to other cell wall-bound NEAT domain proteins such as IsdA and IsdC. It has been shown that IsdA and IsdB co-localise within the Staphylococcal cell wall to discrete sites corresponding to regions of hemoglobin capture .
Iron-regulated surface determinant protein H (IsdH)
Type: Family

HarA (also known as isdH) is a haem-binding NEAT-domain (NEAr Transporter,

) protein which has been shown to bind to the haptoglobin-hemoglobin complex in order to extract haem from it. HarA has also been reported to bind haemoglobin directly . HarA (also known as IsdH) contains three NEAT domains as well as a sortase A C-terminal signal for localisation to the cell wall. The haem bound at the third of these NEAT domains has been shown to be transferred to the IsdA protein also localised at the cell wall, presumably through an additional specific protein-protein interaction . Haptoglobin is a haemoglobin carrier protein involved in scavenging haemoglobin in the blood following red blood cell lysis and targetting it to the liver.
LPXTG cell wall anchor domain (LPXTG_anchor)
Type: Domain

Surface proteins from Gram-positive cocci are covalently linked to the bacterial cell wall by sortase, a membrane-anchored transpeptidase that
cleaves proteins between the threonine and the glycine of a conserved LPxTG motif, with the formation of a thioester between the conserved cysteine of sortase and the threonine carboxyl group. The newly liberated C terminus of the threonine is transferred via an amide bond exchange to the amino group of the pentaglycine wall crossbridge, thereby tethering the C terminus end of the surface protein to the bacterial peptidoglycan .

Surface proteins from Gram-positive cocci contain an N-terminal signal peptide and a C-terminal sorting signal. The 35-residue sorting signal is composed of a conserved LPxTG motif, a hydrophobic domain, and a tail of positively charged residues.

In the case of immunoglobulin A1 proteases, the typical Gram-positive cell wall anchor motif LPxTG is located in their N-terminal regions, in contrast
with other known streptococcal and staphylococcal proteins .

This entry represents a domain covering the LPxTG motif, the hydrophobic stretch and the positively charged region.
Conserved hypothetical protein CHP03543 (CHP03543)
Type: Family

Members of this protein family contain two full and two partial repeats of a domain found at the N terminus of Bacillus subtilis cell-division initiation protein DivIVA. The portion repeated four times in these proteins includes the motif GYxxxxVD.
DivIVA domain (DivIVA_domain)
Type: Domain

This entry describes a domain found in Bacillus subtilis cell division initiation protein DivIVA, and homologues, toward the N terminus. It is also found as a repeated domain in other proteins.

This domain forms a parallel coiled-coil which is capped with two unique crossed and intertwined loops, exposing hydrophobic and positively charged residues that are essential for membrane binding . In addition to lipid binding, this domain can participate in self-assembly to form filamentous structures .
Conserved hypothetical protein CHP03545 (CHP03545)
Type: Family

This entry represents a relatively rare but broadly distributed uncharacterised protein family, distributed in 1 to 2 percent of bacterial genomes, all of which have outer membranes. In many of these genomes, it is part of a two-gene pair.
Conserved hypothetical protein CHP03546 (CHP03546)
Type: Family

Members of this family are uncharacterised proteins, usually encoded by a gene adjacent to a member of family

, which is also uncharacterised.
N-acetylneuraminate epimerase, proteobacteria (NanM_proteobact)
Type: Family

This entry represents N-acetylneuraminate epimerase from Escherichia coli (NanM, also known as YjhT) and similar proteobacterial proteins. NanM converts alpha-N-acetylneuranimic acid (Neu5Ac) to the beta-anomer, accelerating the equilibrium between the alpha- and beta-anomers. This enzyme probably facilitates sialidase-negative bacteria to compete sucessfully for limited amounts of extracellular Neu5Ac, which is likely taken up in the beta-anomer. In addition, the rapid removal of sialic acid from solution might be advantageous to the bacterium to damp down host responses. Besides, it forms linear aceneuramate during interconversion of Neu5Ac anomers . Some species carry what appears to be a cyclically permuted homologue of this protein.
Cyclically-permuted mutarotase family (Cycl-permuted_mutarotase)
Type: Family

Members of this protein family show essentially full-length homology, cyclically permuted, to YjhT from Escherichia coli. YjhT was shown to act as a mutarotase for sialic acid, and by this ability to be able to act as a virulence factor. Members of the YjhT family (

) and this cyclically-permuted family have multiple copies of the β-propeller-forming Kelch repeat.
YcaO domain protein (YcaO_dom_prot)
Type: Family

This family consists of remarkably well-conserved proteins from gamma and beta Proteobacteria, heavily skewed towards organisms of marine environments. Its gene neighbourhood is not conserved. This family has an OsmC-like N-terminal domain. It shares a YcaO domain, frequently associated with ATP-dependent cyclodehydration for peptide modification . The function of the family is unknown. A number of members of this family are from selenouridine-positive genomes, but this correlation may not be meaningful.
CofG family (CofG_family)
Type: Family

This entry represents either a subunit (CofG/subunit 1) or the N-terminal domain of a bifunctional protein that completes the synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, or FO . FO is the chromophore of coenzyme F(420), involved in methanogenesis in methanogenic archaea but found in certain other lineages as well. The chromophore also occurs as a cofactor in DNA photolyases in Cyanobacteria.
CofH family (CofH_family)
Type: Family

This enzyme (CofH), together with CofG, complete the biosynthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase, the chromophore of coenzyme F420. The chromophore is also used in cyanobacteria DNA photolyases . CofH catalyzes the radical-mediated synthesis of 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil from 5-amino-6-(D-ribitylamino)uracil and L-tyrosine .
Transcription regulator LuxR, chaperone HchA-associated (Tscrpt_reg_LuxR_HchA-assoc)
Type: Family

Members of this protein family belong to the LuxR transcriptional regulator family, and contain both autoinducer binding (

) and transcriptional regulator (

) domains. Members of this family only occur adjacent to the gene hchA (Hsp31, ) and are found in only a few gammaproteobacteria.
LL-diaminopimelate aminotransferase/aminotransferase ALD1 (DapL/ALD1)
Type: Family

Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways .

There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different .

The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria.

The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified.

The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana.

The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum.

Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.

This entry includes LL-diaminopimelate aminotransferase DapL from bacteria and aminotransferase ALD1 from plants. DapL is involved in the synthesis of meso-diaminopimelate (m-DAP or DL-DAP), required for both lysine and peptidoglycan biosynthesis. This enzyme catalyzes the direct conversion of tetrahydrodipicolinate to LL-diaminopimelate, a reaction that requires three enzymes in E.coli. It is also able to use meso-diaminopimelate, cystathionine, lysine or ornithine as substrates . ALD1 is involved in the biosynthesis of pipecolate (Pip), a metabolite that orchestrates defense amplification, positive regulation of SA biosynthesis, and priming to guarantee effective local resistance induction and the establishment of SAR .
Coenzyme F420 biosynthesis protein FbiB, C-terminal (F420_FbiB_C)
Type: Domain

Coenzyme F420 differs between the Archaea and the Actinobacteria, where the numbers of glutamate residues attached are 2 (Archaea) or 5 to 6 (Mycobacterium). The enzyme in the Archaea is homologous to the N-terminal domain of FbiB from Mycobacterium bovis, and is responsible for glutamate ligation. Therefore it seems likely that the C-terminal domain of FbiB is involved in additional glutamate ligation.
F420-dependent glucose-6-phosphate dehydrogenase (F420-dep_G6P_DH)
Type: Family

This family consists of the F420-dependent glucose-6-phosphate dehydrogenase of Mycobacterium and Nocardia . It shows homology to several other F420-dependent enzymes rather than to the NAD or NADP-dependent glucose-6-phosphate dehydrogenases .
F420-dependent glucose-6-phosphate dehydrogenase-related (F420_G6P_DH-rel)
Type: Family

Members of this protein family include F420-dependent glucose-6-phosphate dehydrogenases (

) and related proteins. All members of this family come from species that synthesise coenzyme F420, with the exception of those that belong to

, a subgroup within this family in which cofactor binding may instead be directed to FMN .
5,10-methylenetetrahydromethanopterin reductase (MeH4methanopterin_reductase)
Type: Family

Members of this protein family are 5,10-methylenetetrahydromethanopterin reductase, an F420-dependent enzyme of methanogenesis . It is restricted to the Archaea.
DNA photolyase class 1, 8-HDF type (Photolyase_8HDF)
Type: Family

This entry describes a narrow clade of cyanobacterial deoxyribodipyrimidine photolyase (or DNA photolyase). This group, in contrast to several closely related proteins, uses a chromophore that, in other lineages is modified further to become coenzyme F420. This chromophore is called 8-HDF in most articles on the DNA photolyase and FO in most literature on coenzyme F420. This entry includes PhrA from Synechocystis sp. strain PCC 6803. PhrA is a DNA photolyase responsible for the majority of the observed UV resistance in Synechocystis 6803 .

The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals . On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes . The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.
N-acetyl-S-alkylcysteine monooxygenase-like (CmoO-like)
Type: Family

This entry represents a family of prokaryotic alkanal monooxygenase, including Luciferase-like monooxygenase from Escherichia coli (YhbW) and N-acetyl-S-alkylcysteine monooxygenase from Bacillus subtilis (CmoO). CmoO is involved in a cysteine salvage pathway from S-alkylcysteine, which is likely important in the catabolism of alkylated cysteine generated by proteolysis of alkylated glutathione formed in the detoxification of a wide range of electrophiles . This protein family represents a well-resolved clade within

and shows no restriction to coenzyme F420-positive species, unlike some other clades within this larger group of proteins .
M protein-type anchor domain (M_anchor)
Type: Domain

Viruses, parasites and bacteria are covered in protein and sugar molecules that help them gain entry into a host by counteracting the host's defences. One such molecule is the M protein produced by certain streptococcal bacteria . M proteins embody an anchor motif that is now known to be shared by many Gram-positive bacterial surface proteins. The motif includes a conserved hexapeptide, with the consensus sequence LPXTGE, which precedes a hydrophobic region, which itself precedes a cluster of basic residues .
F420-dependent oxidoreductase-predicted, Rv3520c (F420_OxRdatse_Rv3520c_pred)
Type: Family

Members of this protein family are predicted to be oxidoreductases dependent on coenzyme F420. The family includes a single member in Mycobacterium tuberculosis (Rv3520c/MT3621) but four in Mycobacterium smegmatis. Prediction that this family is F420-dependent is based primarily on Partial Phylogenetic Profiling vs. F420 biosynthesis .
F420-dependent oxidoreductase-predicted, Rv1855c (F420_OxRdatse_Rv1855c_pred)
Type: Family

Coenzyme F420 has a limited phylogenetic distribution, including methanogenic archaea, Mycobacterium tuberculosis and related species, Colwellia psychrerythraea (strain 34H / ATCC BAA-681), Rhodopseudomonas palustris (strain HaA2), amongst others. Partial phylogenetic profiling identifies protein subfamilies, within the larger family called luciferase-like monooxygenanases (

), that appear only in F420-positive genomes and are likely to be F420-dependent. This model describes one such subfamily, exemplified by Rv1855c from M. tuberculosis.
Organic hydroperoxide resistance protein famiy (OHR)
Type: Family

The OsmC-like proteins (

) contain several deeply split clades of homologous proteins. This clade includes the protein Ohr, or organic hydroperoxide resistance protein.
Ubiquitin conserved site (Ubiquitin_CS)
Type: Conserved_site

This entry represents the conserved central region of Ubiquitin and related proteins.

Ubiquitin is a protein of 76 amino acid residues, found in all eukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. Ubiquitin acts through its post-translational attachment (ubiquitinylation) to other proteins, where these modifications alter the function, location or trafficking of the protein, or targets it for destruction by the 26S proteasome . The terminal glycine in the C-terminal 4-residue tail of ubiquitin can form an isopeptide bond with a lysine residue in the target protein, or with a lysine in another ubiquitin molecule to form a ubiquitin chain that attaches itself to a target protein. Ubiquitin has seven lysine residues, any one of which can be used to link ubiquitin molecules together, resulting in different structures that alter the target protein in different ways. It appears that Lys(11)-, Lys(29) and Lys(48)-linked poly-ubiquitin chains target the protein to the proteasome for degradation, while mono-ubiquitinylated and Lys(6)- or Lys(63)-linked poly-ubiquitin chains signal reversible modifications in protein activity, location or trafficking . For example, Lys(63)-linked poly-ubiquitinylation is known to be involved in DNA damage tolerance, inflammatory response, protein trafficking and signal transduction through kinase activation . In addition, the length of the ubiquitin chain alters the fate of the target protein. Regulatory proteins such as transcription factors and histones are frequent targets of ubquitinylation .

Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1,

), a ubiquitin-conjugating enzyme (E2,

), and a ubiquitin ligase (E3,

,

), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process . Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (

), SUMO1 (

), NEDD8, Rad23 (

), Elongin B and Parkin (

), the latter being involved in Parkinson's disease .
Ubiquitin domain (Ubiquitin_dom)
Type: Domain

Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1,

), a ubiquitin-conjugating enzyme (E2,

), and a ubiquitin ligase (E3,

,

), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process . Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (

), SUMO1 (

), NEDD8, Rad23 (

), Elongin B and Parkin (

), the latter being involved in Parkinson's disease .

Ubiquitin is a protein of 76 amino acid residues, found in all eukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. Ubiquitin acts through its post-translational attachment (ubiquitinylation) to other proteins, where these modifications alter the function, location or trafficking of the protein, or targets it for destruction by the 26S proteasome . The terminal glycine in the C-terminal 4-residue tail of ubiquitin can form an isopeptide bond with a lysine residue in the target protein, or with a lysine in another ubiquitin molecule to form a ubiquitin chain that attaches itself to a target protein. Ubiquitin has seven lysine residues, any one of which can be used to link ubiquitin molecules together, resulting in different structures that alter the target protein in different ways. It appears that Lys(11)-, Lys(29) and Lys(48)-linked poly-ubiquitin chains target the protein to the proteasome for degradation, while mono-ubiquitinylated and Lys(6)- or Lys(63)-linked poly-ubiquitin chains signal reversible modifications in protein activity, location or trafficking . For example, Lys(63)-linked poly-ubiquitinylation is known to be involved in DNA damage tolerance, inflammatory response, protein trafficking and signal transduction through kinase activation . In addition, the length of the ubiquitin chain alters the fate of the target protein. Regulatory proteins such as transcription factors and histones are frequent targets of ubquitinylation .
ABC transporter, high-affinity heme uptake system protein IsdE (ABC_transptr_haem-bd_IsdE)
Type: Family

This family of ABC substrate-binding proteins is observed primarily in close proximity with proteins localised to the cell wall and bearing the NEAT (NEAr Transporter,

) haem-binding domain . IsdE has been shown to bind heme and is involved in the process of scavenging haem for the purpose of obtaining iron .