SII-SWORD/CoKE huggingface dataset:
Sarcosine oxidase, delta subunit, heterotetrameric (SoxD)
Type: Family

These sequences represent the delta subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Rhizobium loti (Mesorhizobium loti) and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate .
Sarcosine oxidase, gamma subunit, heterotetrameric (SoxG_het)
Type: Family

These sequences represent the gamma subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Rhizobium loti (Mesorhizobium loti) and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. The gamma subunit is the most divergent between operons of the four subunits. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate .
Sarcosine oxidase, monomeric (SoxA_mon)
Type: Family

This set of sequences describe the alpha subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Rhizobium loti (Mesorhizobium loti) and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate .
Thiamin pyrophosphokinase (Thi_PPkinase)
Type: Family

This entry represents prokaryotic and eukaryotic thiamin pyrophosphokinase, which converts thiamin (vitamin B1) into the enzyme cofactor thiamin pyrophosphate (TPP, coenzyme B1).
Thiamine-monophosphate kinase-like (ThiL-like)
Type: Family

This family represents thiamine-monophosphate kinase (ThiL), an enzyme that converts thiamine monophosphate into thiamine pyrophosphate (TPP, coenzyme B1), an enzyme cofactor . Thiamine monophosphate may be derived from de novo synthesis or from unphosphorylated thiamine, known as vitamin B1. The N-terminal domain of ThiL binds ATP and is related to the ATP-binding domains of hydrogen expression/formation protein HypE, the AIR synthases, FGAM synthase and selenophosphate synthetase (SelD). Eukaryotes lack this enzyme, and add pyrophosphate from ATP to unphosphorylated thiamine in a single step.
Glutathione synthetase, prokaryotic (Glut_synth_pro)
Type: Family

These are the glutathione synthetases found in Gram-negative bacteria. This gene does not appear to be present in genomes of Gram-positive bacteria. Glutathione synthetase has an ATP-binding domain in the COOH terminus and catalyzes the second step in the glutathione biosynthesis pathway: ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione. Glutathione is a tripeptide that functions as a reductant in many cellular reactions.
Ubiquitin-like modifier-activating enzyme Atg7 (Atg7)
Type: Family

This is a family of eukaryotic proteins found in animals, plants, and yeasts that includes Atg7p (YHR171W) from Saccharomyces cerevisiae (Baker's yeast) and ATG7 from Pichia angusta. Members are about 650 to 700 residues in length and include a central domain of about 150 residues shared with the ThiF/MoeB/HesA family of proteins. A low level of similarity to ubiquitin-activating enzyme E1 is described in a paper on peroxisome autophagy mediated by ATG7 , and is the basis of the name ubiquitin activating enzyme E1-like protein. Members of the family are involved in protein lipidation events analogous to ubiquitination and required for membrane fusion events during autophagy.

This protein is important for several processes. It plays a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration , the maintenance of hematopoietic stem cells , the formation of Paneth cell granules [[cite22291845]], as well as in adipose differentiation . It is involved in circadian clock regulation in the liver and glucose metabolism through the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner .
Deglycase PfpI-like (C56_PfpI-like)
Type: Family

PfpI from Pyrococcus furiosus functions as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated proteins . Pfpi-like proteins have been found in bacteria, archaea, in some plants and in amoebae. The structure of P. horikoshii PfpI shows an α/β sandwich fold, which consists of a central β sheet flanked by two helices and two strands on one side, and by six helices and two strands on the other side. The fold resembles that of glutamine amidotransferases (GATase) of class I, which are characterised by a conserved Cys-His-Glu active site. The catalytically essential cysteine is located at a nucleophile elbow. PfpI forms a hexameric structure and the active sites are formed at the interfaces between three pairs of monomers. Cys and His form a triad with a glutamate residue from an adjacent monomer .

Other proteins in this group:

Bacillus subtilis general stress protein 18 (GSP18/yfkM) .

E. coli protein yhbO. It is involved in protection against environmental stresses. It has deglycase activity, and can repair glyoxal- and methylglyoxal-glycated proteins and nucleic acids .

This group of proteins form part of the MEROPS peptidase family C56 (Pfp1 endopeptidase, clan PC(C)).
Protein/nucleic acid deglycase DJ-1 (DJ-1)
Type: Family

Glycation is a nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was described in vitro as a protein deglycase that repaired methylglyoxal-and glyoxal-glycated proteins . Since then there have been reports against , and supporting this role for DJ-1 .
Furthermore, supporting its deglycase activity, DJ-1 and its bacterial homologues have been shown to be able to repair methylglyoxal-and glyoxal-glycated nucleotides and nucleic acids . This ability would make DJ-1 a target for diabetic and cancer research . DJ-1, also known as Park7, has been associated with human parkinsonism .

Included in this family is also YajL from Escherichia coli, the bacterial homologue of DJ-1 . This group of proteins are classified as either DJ-1 putative peptidases or non-peptidase homologues in MEROPS peptidase family C56 (clan PC(C)).
Transcription factor S (TFS)
Type: Family

This entry represents the transcription factor S, a protein related in size and sequence to DNA-directed RNA polymerase subunit M, and in sequence and function to the much larger eukaryotic transcription factor IIS (TFIIS). Although originally suggested to be a subunit of the archaeal RNA polymerase (known as archaeal DNA-directed RNA polymerase subunit M), it elutes separately from active polymerase in gel filtration experiments and acts, like TFIIs, as an induction factor for RNA cleavage by RNA polymerase .
Transcription elongation factor, TFIIS (TFSII)
Type: Family

Transcription elongation factor IIS (TFIIS) is a component of RNA polymerase II preinitiation complexes, and is required for preinitiation complex assembly and stability . The association of TFIIS with a promoter depends on functional preinitiation complex components including Mediator and the SAGA complex . TFIIS is composed of three domains: domain 1 forms a 4-helical bundle that appears to bind certain initiation factors; domain 2 forms a 3-helical bundle and is required for Pol II binding; domain 3 forms a zinc ribbon and is essential for stimulation of RNA cleavage .
Heavy metal sensor kinase (CztS_silS_copS)
Type: Family

Members of this family contain a sensor histidine kinase domain (

) and a domain found in bacterial signal proteins (

). This group is separated phylogenetically from related proteins with similar architecture and contains a number of proteins associated with heavy metal resistance efflux systems for copper, silver, cadmium, and/or zinc.
Transcriptional regulatory protein CusR-like, heavy metal response (CusR-like)
Type: Family

This family represents Transcriptional regulatory protein CusR from Escherichia coli () and similar sequences predominantly found in proteobacteria. Proteins in this entry contain a response regulator receiver domain (

) and an associated transcriptional regulatory region (

). This group is separated phylogenetically from related proteins with similar architecture and contains a number of proteins associated with heavy metal resistance efflux systems for copper, silver, cadmium, and/or zinc. Most members are encoded by genes adjacent to genes which code for a member of the heavy metal sensor histidine kinase family (

), its partner in the two-component response regulator system.
Ribonuclease D (RNase_D)
Type: Family

This entry represents ribonuclease D, a bacterial 3'-5' exonuclease that acts on tRNA. Ribonuclease D contributes to the 3' maturation of several stable RNAs .
DNA helicase, ATP-dependent, RecQ type, bacterial (DNA_helicase_ATP-dep_RecQ_bac)
Type: Family

The ATP-dependent DNA helicase RecQ (

) is involved in genome maintenance . All homologues tested to date unwind paired DNA, translocating in a 3' to 5' direction and several have a preference for forked or 4-way DNA structures (e.g. Holliday junctions) or for G-quartet DNA. The yeast protein, Sgs1, is present in numerous foci that coincide with sites of
de novo
synthesis DNA, such as the replication fork, and protein levels peak during S-phase.

A model has been proposed for Sgs1p action in the S-phase checkpoint response, both as a 'sensor' for damage during replication and a 'resolvase' for structures that arise at paused forks, such as the four-way 'chickenfoot' structure. The action of Sgs1p may serve to maintain the proper amount and integrity of ss DNA that is necessary for the binding of RPA (replication protein A, the eukaryotic ss DNA-binding protein)-DNA pol complexes. Sgs1p would thus function by detecting (or resolving) aberrant DNA structures, and would thus contribute to the full activation of the DNA-dependent protein kinase, Mec1p and the effector kinase, Rad53p. Its ability to bind both the large subunit of RPA and the RecA-like protein Rad51p, place it in a unique position to resolve inappropriate fork structures that can occur when either the leading or lagging strand synthesis is stalled. Thus, RecQ helicases integrate checkpoint activation and checkpoint response.
2',3'-cyclic-nucleotide 2'-phosphodiesterase/3'-nucleotidase (Cyc_nuc_PDE_nucleotidase)
Type: Family

These sequences represent 2',3'-cyclic-nucleotide 2'-phosphodiesterase/3'-nucleotidases; it is a bifunctional enzyme localized to the periplasm of Gram-negative bacteria. 2',3'-cyclic-nucleotide 2'-phosphodiesters are intermediates formed during the hydrolysis of RNA by the ribonuclease I, which is also found in the periplasm, and other enzymes of the RNAse T2 family. Bacteria are unable to transport 2',3'-cyclic-nucleotides into the cytoplasm. 2',3'-cyclic-nucleotide 2'-phosphodiesterase/3'-nucleotidases contains 2 active sites which catalyze the reactions that convert the 2',3'-cyclic-nucleotide into a 3'-nucleotide, which is then converted into nucleic acid and phosphate. Both final products can be transported into the cytoplasm. Thus, it has been suggested that 2',3'-cyclic-nucleotide 2'-phosphodiesterase/3'-nucleotidases have a scavenging function. Experimental evidence indicates that a 2',3'-cyclic-nucleotide 2'-phosphodiesterase/3'-nucleotidase enables Yersinia enterocolitica O:8 to grow on 23-cAMP as a sole source of carbon and energy .
DNA primase, DnaG (DNA_primase_DnaG)
Type: Domain

Proteins with this domain are DNA primases, a ubiquitous bacteria protein. Most DNA primases contain nearly two hundred additional residues C-terminal to the region represented here, but conservation between species is poor.

DNA primase synthesises the RNA primers for the Okazaki fragments in lagging strand DNA synthesis. Escherichia coli family member DnaG has been shown to interact with the replicative DnaB helicase, single-stranded DNA binding protein (SSB), and DNA polymerase III holoenzyme . Although DnaG is capable of synthesizing 60-nucleotide-long primers in vitro , this primer length is restrained to 11 (+/-1) nucleotides in the context of the replisome .

On the basis of sequence analysis, these proteins appear structurally distinct from primases known to act in archaeal and eukaryotic replication , or to either of the two subunits, p50 and p60, of the heterodimeric eukaryotic DNA primase.
Elongation factor 4 (EF-4)
Type: Family

Elongation factor 4, also known as ribosomal back-translocase LepA, is required for accurate and efficient protein synthesis under certain stress conditions. Its function is not clear. However, it may act as a fidelity factor of the translation reaction, by catalysing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Back-translocation proceeds from a post-translocation (POST) complex to a pre-translocation (PRE) complex, thus giving elongation factor G a second chance to translocate the tRNAs correctly . Elongation factor 4 binds to ribosomes in a GTP-dependent manner. The eukaryotic homologue is known as GUF1 and promotes protein synthesis in chloroplasts and mitochondria .
GTP-binding protein BipA (BipA)
Type: Family

This family includes the GTP-binding protein BipA or TypA (Tyrosine phosphorylated protein A (TypA), also known as 50S ribosomal subunit assembly factor BipA) from bacteria and its homologue from Arabidopsis (putative elongation factor TypA-like SVR3). BipA is a 50S ribosomal subunit assembly protein with GTPase activity, required for 50S subunit assembly at low temperatures, also functions as a translation factor that is required specifically for the expression of the transcriptional modulator Fis. BipA binds the 70S ribosome at a site that coincides with that of EF-G and has a GTPase activity that is sensitive to high GDP:GTP ratios and is stimulated by 70S ribosomes programmed with mRNA and aminoacylated tRNAs . The growth rate-dependent induction of BipA allows the efficient expression of Fis, thereby modulating a range of downstream processes, including DNA metabolism and type III secretion. This GTPase impacts interactions between enteropathogenic E.coli (EPEC) and epithelial cells and also has an effect on motility . It appears to be involved in the regulation of several processes important for infection, including rearrangements of the cytoskeleton of the host, bacterial resistance to host defence peptides, flagellum-mediated cell motility, and expression of K5 capsular genes .

TypA-like SVR3 is a putative chloroplastic elongation factor involved in response to chilling stress. It is required for proper chloroplast rRNA processing and/or translation at low temperature and it is also involved in plastid protein homeostasis .
Flagellar basal-body rod protein FlgC (FlgC)
Type: Family

FlgC is a 14kDa flagellar basal-body protein that along with FlgBFG composes the rod of bacterial flagellin . Deletion of flgC results in a significant decrease in Salmonella motility .
Flagellar basal-body rod protein FlgB (FlgB)
Type: Family

FlgB is a flagellar basal-body protein that along with FlgCFG composes the rod of bacterial flagellin .
Flagellar biosynthesis protein FlhA (FlhA)
Type: Family

These sequences describe the flagellar biosynthesis protein FlhA, one of a large number of genes associated with the biosynthesis of functional bacterial flagella. FlhA is an integral membrane protein of the export apparatus and is involved in an early stage of the export process along with three soluble proteins, FliH, FliI, and FliJ . FlhA functions in type III protein secretion systems.
Type III secretion protein HrcV (T3SS_HrcV)
Type: Family

Members of this family are closely homologous to the flagellar biosynthesis protein FlhA and should all participate in type III secretion systems. Examples include InvA (Salmonella enterica), LcrD (Yersinia enterocolitica), HrcV (Xanthomonas), etc. Type III secretion systems resemble flagellar biogenesis systems, and may share the property of translocating special classes of peptides through the membrane.
Flagellar biosynthesis protein FliR (FliR)
Type: Family

This entry represents the bacterial flagellar biosynthesis protein FliR .
Type III secretion protein SpaR/YscT (T3SS_SpaR/YscT)
Type: Family

These sequences represent members of bacterial type III secretion systems homologous to the flagellar biosynthetic protein FliR (

).
Flagellar biosynthesis protein FliQ (FliQ)
Type: Family

These sequences represent FliQ, a protein involved in biosynthesis of bacterial flagella .
Type III secretion protein HrpO (T3SS_HrpO)
Type: Family

This is one of several families of proteins related to bacterial flagellar biosynthesis proteins and involved in bacterial type III protein secretion systems, and is represented by HrpO . This family is homologous to, but separate from, the flagellar biosynthetic protein FliQ.
Type III exporter system, secretion apparatus protein BsaZ-like (BsaZ-like)
Type: Family

This entry represents a group of proteins related to bacterial flagellar biosynthesis proteins and involved in bacterial type III protein secretion systems, including Secretion apparatus protein BsaZ from Burkholderia pseudomallei. BsaZ is involved in the intracellular replication of invading bacteria inside the host cell. It is likely to be necessary for the lysis of the vacuole membrane and escape into the host cell cytoplasm . Surface presentation of antigens protein SpaS from Salmonella typhimurium, involved in a secretory pathway responsible for the surface presentation of determinants needed for the entry of Salmonella species into mammalian cells, also belongs to this group. This family is homologous to, but distinguished from, flagellar biosynthetic protein FlhB (

) . Members of this group are mostly found in proteobacteria.
DNA polymerase III, alpha subunit, PolC-type, Gram-positive bacteria (Pol_III_a_PolC-type_gram_pos)
Type: Family

These are the polypeptide chains of DNA polymerase III. Full-length homologues of this protein are found mainly in Gram-positive lineages, including the Mycoplasmas. This protein is designated alpha chain and given the gene symbol polC, but is not a full-length homologue of other polC genes. The N-terminal region of about 200 amino acids is rich in low-complexity sequence and poorly alignable.
DNA polymerase 3, epsilon subunit (DnaQ_proteo)
Type: Family

These represent DnaQ, the DNA polymerase III epsilon subunit, as found in most Proteobacteria. It consists largely of an exonuclease region as described in

. In Gram-positive bacteria, closely related regions are found both in the Gram-positive type DNA polymerase III alpha subunit and as an additional N-terminal domain of a DinG-family helicase. Both are not included in this set of sequences, as they are smaller proteins.
3'-5' exonuclease DinG (DinG)
Type: Family

Canonical DinG is a bacterial helicase with 5'->3' polarity. In the bacilli and clostridia, the DinG helicase has become fused with an N-terminal exonuclease domain and lacks the FeS-binding domain essential for the helicase activity. Instead of being an helicase, the enzyme is a 3'->5' exonuclease acting on single-stranded DNA and RNA substrates. The inactive helicase domain seems to have a role in the control of the nuclease activity. By degrading rather than displacing RNA or DNA strands, exonuclease DinG may accomplish the same function as the canonical DinG helicase .
Twin-arginine translocation pathway, signal sequence (TAT_signal)
Type: Conserved_site

This entry represents the Tat signal, from the methionine to the A-x-A short motif.

The twin-arginine translocation (Tat) pathway serves the role of transporting folded proteins across energy-transducing membranes . Homologues of the genes that encode the transport apparatus occur in archaea, bacteria, chloroplasts, and plant mitochondria . In bacteria, the Tat pathway catalyses the export of proteins from the cytoplasm across the inner/cytoplasmic membrane. In chloroplasts, the Tat components are found in the thylakoid membrane and direct the import of proteins from the stroma. The Tat pathway acts separately from the general secretory (Sec) pathway, which transports proteins in an unfolded state .

It is generally accepted that the primary role of the Tat system is to translocate fully folded proteins across membranes. An example of proteins that need to be exported in their 3D conformation are redox proteins that have acquired complex multi-atom cofactors in the bacterial cytoplasm (or the chloroplast stroma or mitochondrial matrix). They include hydrogenases, formate dehydrogenases, nitrate reductases, trimethylamine N-oxide (TMAO) reductases and dimethyl sulphoxide (DMSO) reductases . The Tat system can also export whole heteroligomeric complexes in which some proteins have no Tat signal. This is the case of the DMSO reductase or formate dehydrogenase complexes. But there are also other cases where the physiological rationale for targeting a protein to the Tat signal is less obvious. Indeed, there are examples of homologous proteins that are in some cases targeted to the Tat pathway and in other cases to the Sec apparatus. Some examples are: copper nitrite reductases, flavin domains of flavocytochrome c and N-acetylmuramoyl-L-alanine amidases .

In halophilic archaea such as Halobacterium almost all secreted proteins appear to be Tat targeted. It has been proposed to be a response to the difficulties these organisms would otherwise face in successfully folding proteins extracellularly at high ionic strength .

The Tat signal peptide consists of three motifs: the positively charged N-terminal motif, the hydrophobic region and the C-terminal region that generally ends with a consensus short motif (A-x-A) specifying cleavage by signal peptidase. Sequence analysis revealed that signal peptides capable of targeting the Tat protein contain the consensus sequence [ST]-R-R-x-F-L-K. The nearly invariant twin-arginine gave rise to the pathway's name. In addition the h-region of Tat signal peptides is typically less hydrophobic than that of Sec-specific signal peptides .
Sec-independent protein translocase protein TatA/E (TatA/E)
Type: Family

Translocation of proteins across the two membranes of Gram-negative bacteria can be carried out via a number of routes. Most proteins marked for export carry a secretion signal at their N terminus, and are secreted by the general secretory pathway. The signal peptide is cleaved as they pass through the outer membrane. Other secretion systems include the type III system found in a select group of Gram-negative plant and animal pathogens, and the CagA system of Helicobacter pylori .

In some bacterial species, however, there exists a system that operates independently of the Sec pathway . It selectively translocates periplasmic-bound molecules that are synthesised with, or are in close association with, "partner" proteins bearing an (S/T)RRXFLK twin arginine motif at the N terminus. The pathway is therefore termed the Twin-Arginine Translocation or TAT system. Surprisingly, the four components that make up the TAT system are structurally and mechanistically related to a pH-dependent import system in plant chloroplast thylakoid membranes . The gene products responsible for the Sec-independent pathway are called TatA, TatB, TatC and TatE.

TatA and TatE are highly related proteins and appear to overlap in functionality . Translocation occurred in single mutants of either TatA or TatE, though much less efficiently, but double mutants showed no detectable translocation.