SII-SWORD/CoKE huggingface dataset:
Uncharacterised conserved protein UCP004897, ACT- type (UCP004897_ACT)
Type: Family

This group represents a predicted ligand-binding protein with ACT domain, AF1020 type.
Uncharacterised protein family UPF0282, hydrolase, metallo-beta-lactamase (UPF0282_hydrls)
Type: Family

This group represents a predicted hydrolase, metallo-beta-lactamase superfamily.
Crossover junction endodeoxyribonuclease Hjc, archaeal (Hjc_arc)
Type: Family

This group contains Holliday junction resolvases (HJRs) of the archaeal type, Hjc and Hje proteins . The Holliday junction is an essential intermediate of homologous recombination. Holliday junctions are four-stranded DNA complexes that are formed during recombination and related DNA repair events. In the presence of divalent cations, these junctions exist predominantly as the stacked-X form, in which the double-helical segments are coaxially stacked and twisted by 60 degrees in a right-handed direction across the junction crossover. In this structure, the stacked arms resemble two adjacent double helices, but are linked at the junction by two common strands that cross over between the duplexes . During homologous recombination, genetic information is physically exchanged between parental DNAs via crossing single strands of the same polarity within the four-way Holliday structure. This process is terminated by the endonucleolytic activity of resolvases, which convert the four-way DNA back to two double strands. There is some structural similarity between the archeal HJRs and type II restriction endonucleases. This similarity includes their active site configurations .
Sterol desaturase Scs7 (Scs7)
Type: Family

This entry represents a family of fatty acid hydroxylases, including Scs7 from budding yeasts and FA2H from animals and plants. They contain an N-terminal Cytochrome b5-like heme/steroid binding domain.

Scs7 is a sphingolipid alpha-hydroxylase involved in the alpha-hydroxylation of sphingolipid-associated very long chain fatty acids .
Tellurite resistance methyltransferase, TehB type-2 (Tellurite-R_TehB-2)
Type: Family

Tellurite resistance protein TehB is encoded by tellurite-reducing operon
tehAB
. Members of this entry are two-domain proteins with a C-terminal S-adenosyl-L-methionine (SAM)-dependent methyltransferase domain and an N-terminal domain of unknown function. In Escherichia coli, Salmonella and some other organisms, the two domains exist in stand-alone form: YeaR protein (

) and single-domain TehB methyltransferase (

).

When upregulated or present in high copy number, TehB is responsible for potassium tellurite resistance, which is probably caused by increasing the reduction rate of tellurite to metallic tellurium within the bacterium. TehB is a cytoplasmic protein that possesses three conserved motifs (I, II, and III) found in SAM-dependent non-nucleic acid methyltransferases . Conformational changes in TehB are observed upon binding of both tellurite and SAM, suggesting that TehB utilises a methyltransferase activity in the detoxification of tellurite .
Nickel insertion ATPase/GTPase (CO dehydrogenase maturation factor), CooC type (CooC)
Type: Family

Carbon monoxide dehydrogenase (CO dehydrogenase), as well as other nickel metalloenzymes, it is synthesized as a precursor that is devoid of the metalloenzyme active site. These precursors undergo a complex post-translational maturation process that requires a number of accessory proteins .

Members of this entry are accessory proteins involved in maturation of metalloenzymes. Specifically, CooC participates in the incorporation of nickel into the carbon monoxide dehydrogenase metallocentre . CooC also catalyses the hydrolysis of ATP and GTP . Members contain a P-loop nucleotide-binding motif at the N terminus that is essential for their function in both ATP hydrolysis and nickel insertion . AcsF is thought to play a similar role in the maturation of the bifunctional enzyme acetyl-coenzyme A synthase/carbon monoxide dehydrogenase in Moorella thermoacetica , and its counterparts are known in other organisms with this bifunctional enzyme, for example in Methanosarcina thermophila . AcsF from Carboxydothermus hydrogenoformans (AcsFCh) was shown to act as a maturation factor of Acetyl-CoA synthase (ACS) . It catalyses the nickel and MgATP-dependent activation of ACS by forming a complex with apoACS that binds two nickel ions with higher affinity .

Members of this group contain the CobQ/CobB/MinD/ParA nucleotide-binding domain, typical of ATP-dependent amidoligases .
Monothiol glutaredoxin (Monothiol_GRX)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

In Saccharomyces cerevisiae (Baker's yeast), monothiol glutaredoxin 5 (Grx5p) is essential for the mitochondrial machinery involved in the synthesis and assembly of iron/sulphur centres . Absence of Grx5p leads to constitutive oxidative damage, exacerbating that caused by external oxidants.

Proteins in this group contain a conserved structural domain, PICOT-HD (amino acids 46-132 in Grx5p) .
N(4)-bis(aminopropyl)spermidine synthase (BpsA)
Type: Family

BpsA synthesizes N(4)-bis(aminopropyl)spermidine from spermidine via N(4)-aminopropylspermidine. It is involved in the biosynthesis of branched-chain polyamines, which support the growth of thermophiles under high-temperature conditions .
Extradiol aromatic ring-opening dioxygenase, DODA-type (Extradiol_dOase_DODA)
Type: Family

4,5-DOPA dioxygenase catalyses the incorporation of both atoms of molecular oxygen into 4,5-dihydroxy-phenylalanine (4,5-DOPA). The reaction results in the opening of the cyclic ring between carbons 4 and 5 and producing an unstable seco-DOPA that rearranges to betalamic acid. 4,5-DOPA dioxygenase is a key enzyme in the biosynthetic pathway of the plant pigment betalain . Homologues of DODA are present not only in betalain-producing plants, but also in bacteria and archaea . This enzyme is a member of the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon.
Glucan biosynthesis protein MdoG/MdoD (Glucan_biosyn_MdoG/MdoD)
Type: Family

Membrane-derived oligosaccharides (MDO) are members of a family of glucans found in the periplasmic space of Gram-negative bacteria. MdoG has been shown to be necessary for the synthesis of MDO , but its exact function is not known yet. MdoD, an MdoG paralog, is a twin-arginine-dependent periplasmic protein that controls osmoregulated periplasmic glucan backbone structures ; see also .
HCCA isomerase/glutathione S-transferase kappa (HCCAis_GSTk)
Type: Family

This group represents a HCCA isomerase/glutathione S-transferase kappa . HCCA isomerase is unique to bacteria that degrade polycyclic aromatic compounds. It is closely related to the eukaryotic protein, GSH transferase kappa (GSTK) .
Uncharacterised conserved protein UCP006425, beta-propeller-type (UCP006425_b-propeller)
Type: Family

There is currently no experimental data characterising members of this group or their homologues. However, they contain a β-propeller domain distantly related to WD-40 repeats in their mid- to C-terminal part (SCOP superfamily WD40 as detected by SMART with marginal score). Members of this group are thought to be secreted proteins based on the predicted signal peptide. Members are from prokaryotes.
Damage-control phosphatase PH1575-like (PH1575-like)
Type: Family

This family represents metal-dependent phosphatases found in bacteria and archaea, with probable damage-control functions, including Damage-control phosphatase PH1575 from Pyrococcus horikoshii . It shows phosphatase activity against p-nitrophenyl phosphate (pNPP), but natural substrates have not been identified yet. It has low phosphatase activity against 8-oxo nucleotides, which suggests that it could hydrolyse oxidatively damaged purine nucleotides or their biosynthetic intermediates .
Glutamine-dependent NAD(+) synthetase (Gln-dep_NAD_synthase)
Type: Family

This group represents the glutamine-dependent NAD(+) synthetases with the GAT domain from archaea, bacteria to humans.

NAD+ is involved electron transport and redox reactions and in DNA ligation and protein ADP-ribosylation. In yeast and most other organisms, NAD is generated through the de novo pathway and the salvage pathway. In the de novo pathway, quinolinic acid is converted to nicotinic acid mononucleotide (NaMN). In the salvage pathway, NaMN is generated by recycling of nicotinamide. Both pathways converge on NaMN, which is then converted into deamido-NAD+. Subsequently, deamido-NAD+ is converted to NAD+ by NAD+ synthetase .

NAD+ synthetase has been extensively studied in bacteria. It is encoded by nadE gene in E. coli and by outB gene in B. subtilis . However, these enzymes are ammonia-dependent (containing an ammonia-utilising domain) and are not included in this entry . The pokaryotic proteins in this family, such as that from Mycobacterium tuberculosis, contain a nitrilase-related domain, are glutamine-dependent and are included in this entry .
Antitoxin VapB-like, probable (VapB-like_prob)
Type: Family

This protein family includes a group of uncharacterised short sequences from actinobacteria, including the probable Antitoxin VapB from Streptomyces cyaneogriseus (

). Members of this family are predicted to adopt an α-β structure.
Anti-adapter protein IraM (Anti-adapter_IraM)
Type: Family

The IraM protein was originally named enhancing lycopene biosynthesis protein 1 on the basis of its ability to restore lycopene production in mutants . It has subsequently been shown that this protein inhibits rpoS proteolysis by regulating rssB activity, thereby increasing the stability of the sigma stress factor rpoS during magnesium starvation .
Uncharacterised conserved protein UCP007050, HI0931 (UCP007050_HI0931)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Uncharacterised conserved protein UCP008210 (UCP008210)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Uncharacterised conserved protein UCP008455 (UCP008455)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Inhibitor of vertebrate lysozyme (Inhibitor_vertebrate_lysozyme)
Type: Family

C-type lysozyme enzymes, such as hen egg white lysozyme (HEWL), provide anti-bacterial activity by cleaving peptidoglycan in Gram-positive bacterial cell walls. In humans, C-type lysozyme is found in all secretions, including tears and saliva. Certain Gram-positive bacteria can produce proteins with anti-lysozyme activity known as Inhibitor of Vertebrate Lysozyme (IVY), which act as virulence factors . IVY proteins have a 3-layer α(2)/β(5)/α(2) topology, and contain a protruding 5-residue loop that is essential for their inhibitory effect .
DNA methylase, N-6 adenine-specific, MK1259 type (N6_adenine_Mtase_MK1259)
Type: Family

Proteins of this group contain the N6-adenine-specific DNA methylase signature (

) in the C-terminal half of the sequence. This motif is characteristic of N6-adenine-specific DNA methylases and is thought to be involved in substrate binding or catalytic activity . Members also contain one or two Zn-ribbon motifs, corresponding to the consensus sequence CxxCG, and a domain of unknown function (

) at the N terminus.

In Rhizobium meliloti (Sinorhizobium meliloti) (

), the

motif differs slightly, whereby the second position of the consensus pattern is substituted by a serine residue. In addition, the Zn-ribbon motif is not evident.
Uncharacterised conserved protein UCP010244, integral membrane protein (UCP010244_IM)
Type: Family

This group represents a predicted integral membrane protein.
Uncharacterised conserved protein UCP010260 (UCP010260)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this group encoded by Streptomyces coelicolor and Streptomyces avermitilis colocalize with glycogen metabolism cluster I proteins (such as glycogen phosphorylase). However, proteins from other organisms are found in different genomic contexts.
Uncharacterised protein family, phage P2-GpU-fusion (Unchr_Phage_P2-GpU-fusion)
Type: Family

This entry consists of bacterial aproteins, restricted to Pseudomonas and Burkholderia species, of around 250 to 290 residues in length. The proteins all have a C-terminal bacteriophage P2 GpU domain, which is thought to be involved in tail assembly . These proteins are probable fusion proteins of unknown function.
Transcriptional activator VP30, Filoviridae type (VP30_FiloV)
Type: Family

VP30 is a nucleocapsid-associated Ebola virus-specific transcription factor . It acts by stabilising nascent mRNA in Ebola virus replication. The C-terminal domain of VP30 folds into a dimeric helical assembly. VP30 assembles into hexamers in solution by an N-terminal oligomerization domain which activates the transcription function of the protein. The oligomerization is mediated by hydrophobic amino acids at 94-112 . VP30 binds RNA in the presence of zinc and clamps the RNA template and the complex VP35-polymerase L together, increasing the polymerase affinity for the RNA template to increase transcription initiation despite the presence of RNA secondary structures . It also assists the reinitiation of transcription at gene junctions .

This entry represents the transcriptional activator VP30, Filoviridae type.
Signal transduction response regulator, predicted, VieB (Sig_transdc_resp-reg_VieB)
Type: Family

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .

This entry represents VieB-type response regulators. In Vibrio, it is part of a signal transduction pathway involved in cholera toxin production .

Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator . Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecules have been demonstrated in direct structural studies .

The output domain found in this group is so far unique. In part, it contains a divergent version of TPR repeats.
Vacuolar protein sorting-associated protein 17, Vps17 (Retromer_complex_Vps17)
Type: Family

Vps17 belongs to the sorting nexin family, which contains a conserved PX domain . Vps17 is a component of the membrane-associated retromer complex (consists of Vps29, Vps26, Vps35, Vps5 and Vps17), which is essential in endosome-to-Golgi retrograde transport. It forms a retromer subcomplex with Vps5 that may assemble onto the membrane to promote vesicle formation .
Phage-associated protein Gp45 (Phage_Mu_Gp45)
Type: Family

This entry includes Gp45 from bacteriophage Mu. Gp45 is a component of the baseplate that forms a central needlelike spike used to puncture the host cell membrane for tube insertion during virus entry. It serves as the distal plug of tail tube channel and might regulate the process of the phage DNA and protein ejection into the host cell . The characteristics of the protein distribution suggest prophage matches.
Conserved virulence factor B (CvfB_fam)
Type: Family

Conserved virulence factor B proteins contribute to the expression of virulence factors and to pathogenicity via both agr-dependent and agr-independent pathways .
Uncharacterised conserved protein UCP012622 (UCP012622)
Type: Family

This group represents an uncharacterised conserved protein.
Predicted transcriptional regulator, AF1742 type (Txn_rg_UCP012876)
Type: Family

There is currently no experimental data for members of this group or their homologues. However, they contain a "Winged helix" DNA-binding domain (according to SMART and SCOP) so are predicted to be transcriptional regulators.
Uncharacterised conserved protein UCP014979 (UCP014979)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Protein of unknown function DUF2271 (DUF2271)
Type: Family

This family of bacterial proteins is functionally uncharacterised. Members in this family contain the conserved [S/T]GA[S/T] motif and are ApbE substrates which suggests that they may be involved in extra cytosolic redox activities .
Uncharacterised conserved protein UCP01500 (UCP01500)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Choline/ethanolamine phosphotransferase (CHOPT)
Type: Family

This group represents a choline/ethanolamine phosphotransferase .
AT-hook motif nuclear-localized protein 15-29 (AHL15-29)
Type: Family

This entry includes AT-hook motif nuclear-localized proteins 15-29 (AHL15-29) from Arabidopsis . They have two conserved structural units, the AT-hook motif and the Plant and Prokaryote Conserved (PPC) domain, the latter also known as DUF296. Members of the AHL family regulate diverse aspects of growth and development in plants . AHL20 has been shown to negatively regulate defenses in Arabidopsis .
Putative membrane protein, NMB1733 type (UCP016195)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they are predicted to be integral membrane proteins (with several transmembrane segments).
Mannan endo-1,6-alpha-mannosidase (Mannan-1_6-alpha_mannosidase)
Type: Family

Mannan endo-1,6-alpha-mannosidases such as DCW1 and DFG5 from Saccharomyces cerevisiae are GPI-anchored membrane proteins required for normal biosynthesis of the cell wall .
Uncharacterised conserved protein UCP016662, toprim-type (UCP016662_toprim)
Type: Family

Members of this group contain the Toprim domain (topoisomerase-primase)

common to DnaG primases, type IA and type II topoisomerases, OLD family nucleases, as well as small primase-like proteins from bacteria and archaea, and bacterial DNA repair proteins of the RecR/M family .

The domain consists of approximately 100 amino acids and have two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). Examination of the structure of Topo IA and Topo II and modelling of the Toprim domains of the primases reveal a compact β/α fold, with the conserved negatively charged residues juxtaposed, and inserts seen in Topo IA and Topo II . The conserved glutamate may act as a general base in nucleotide polymerisation by primases and in strand rejoining by topoisomerases and as a general acid in strand cleavage by topoisomerases and nucleases. The role of this glutamate in catalysis is supported by site-directed mutagenesis data on primases and Topo IA . The DxD motif may coordinate Mg
2+
that is required for the activity of all Toprim-containing enzymes. The common ancestor could encode a prototype Toprim enzyme that might have had both nucleotidyl transferase and polynucleotide cleaving activity .

There is currently no experimental data for members of this group. As they lack the additional domains that are involved in numerous interactions typical of the larger proteins of the Toprim superfamily (primases and topoisomerases), they may represent a novel class of nucleotidyl transferases or nucleases .