SII-SWORD/CoKE huggingface dataset:
SO_2930-like, beta-helix domain (SO_2930-like_dom)
Type: Domain

This entry represents a domain found in a group of uncharacterised diheme c-type cytochrome proteins that contain repeats associated with the formation of a right-handed helical stack of parallel β-strands, homologous to those found in a number of carbohydrate-binding proteins and sugar hydrolases. Each repeat is expected to consist of three β-strands that form a single turn as they form a right-handed helix of stacked β-structure. Member proteins occur regularly in two-gene pairs along with members of

. In some cases, as in SO_2930 from Shewanella putrefaciens (

,

), both this entry and

are fused. Both groups of proteins exhibit either lipoprotein or regular signal peptides, suggesting transit through the plasma membrane. Its specific function is unknown.
KaiC-related (KaiC-rel)
Type: Family

Members of this entry are archaeal single-domain KaiC_related proteins, homologous to the Cyanobacterial circadian clock cycle protein KaiC, an autokinase/autophosphorylase that has two copies of the domain.
Cofactor-binding repeat, putative (Cofactor-bd_rpt)
Type: Repeat

This entry describes a small repeat found in a family of proteins that crosses the plasma membrane by twin-arginine translation, which usually signifies the presence of a bound cofactor. This repeat shows similarity to the β-helical repeat, in which three β-strands per repeat wind once per repeat around in a right-handed helical stack of parallel β structure.
Sortase, proteobacterial type (Sortase_proteobact_type)
Type: Family

This entry represents the GN class sortase, which includes sortase enzymes, cysteine transpeptidases involved in protein sorting activities, from Gram-negative bacteria, mainly proteobacteria, in a dedicated system with apparently only one target protein, a member of

. Many of these sortases appear to contain a signal target sequence, a protein with a Vault protein inter-alpha-trypsin domain and a von Willebrand factor type A domain, encoded by an adjacent gene .
N5-glutamine methyltransferase, putative (MeTrfrase_put)
Type: Family

This protein family is closely related to two different families of protein-(glutamine-N5) methyltransferase. The first is PrmB, which modifies ribosomal protein L3 in some bacteria. The second is PrmC (HemK), which modifies peptide chain release factors 1 and 2 in most bacteria and also in eukaryotes. The glutamine side chain-binding motif NPPY shared by PrmB and PrmC is N[VAT]PY in this family. The protein substrate is unknown.
Lysine-2,3-aminomutase-related (Lys_aminomutase-rel)
Type: Family

Members of this protein form a distinctive clade, homologous to lysine-2,3-aminomutase (of Bacillus, Clostridium, and methanogenic archaea) and likely similar in function. Members of this family are found in Rhodopseudomonas, Caulobacter vibrioides, Bradyrhizobium, etc.
Quinoprotein dehydrogenase-associated (Quinoprotein_dehydrogenase)
Type: Family

Proteins in this entry are found in known methanotrophs and a range of PQQ-biosynthesising species. Interpretation of evidence by homology and by direct experimental work suggest two different roles. By homology, these proteins appear to be the periplasmic substrate-binding protein of an ABC transport family. However, mutational studies and direct characterisation for some sequences related to these proteins suggests they may act as a maturation chaperone or additional subunit of a methanol dehydrogenase-like enzyme .
tRNA N6-adenosine threonylcarbamoyltransferase, TsaD (TsaD)
Type: Family

This entry represents the TsaD protein family that is widely distributed. TsaD and its archaeal homologue Kae1 belong to the Kae1/TsaD family (

), a conserved protein family with unknown function.

This entry includes bacterial TsaD and its homologues, such as Qri7 (localize to the mitochondria) from budding yeast .

TsaD (also known as Gcp or YgjD) was originally described as a glycoprotease essential for cell viability and a critical mediator involved in the modification of cell wall peptidoglycan synthesis and/or cell division . Gcp is a member of the Kae1/TsaD family, required for the formation of a threonylcarbamoyl group on adenosine at position 37 in tRNAs that read codons beginning with adenine . YgjD has been renamed as TsaD, and it has been shown that YgjD and proteins YrdC (TsaC), YjeE (TsaE), and YeaZ (TsaB), are necessary and sufficient for t6A biosynthesis in vitro, and may constitute a complex .

The first characterised member of the Kae1/TsaD family was annotated as Gcp for O-sialoglycoprotein endopeptidase , but this activity could not be confirmed . Later, its homologue, Kae1 from Pyrococcus abyssi, has been shown to have DNA-binding properties and apurinic-endonuclease activity . Members of this family have since been studied in yeast, archaea and bacteria resulting in sometimes conflicting data, several proposed functions and annotations but no definitive characterisation. For instance, some members have been linked to DNA maintenance in bacteria and mitochondria and transcription regulation and telomere homeostasis in eukaryotes , but their function remained unclear. Recent research indicates that this family is involved in the biosynthesis of N6-threonylcarbamoyl adenosine, a universal modification found at position 37 of tRNAs that read codons beginning with adenine .
Conserved hypothetical protein CHP03829, YokU (CHP03829_YokU)
Type: Family

Members of this protein family occur in various species of the genus Bacillus, always next to the gene (kamA or ablA) for lysine 2,3-aminomutase. Members have a pair of CXXC motifs, and share homology to the amino-terminal region of a family of putative transcription factors for which the C-terminal is modeled by

, a helix-turn-helix domain model. This family, however, is shorter and lacks the helix-turn-helix region. The function of this protein family is unknown, but a regulatory role in compatible solute biosynthesis is suggested by local genome context.
Antitoxin MqsA (MqsA)
Type: Family

This entry represents MqsA, the antitoxin of the MqsR/MqsA toxin/antitoxin (TA) system . It has a zinc-binding at the very N terminus indicating its DNA-binding capacity. The N-terminal region contains a novel domain, featuring two CXXC motifs. The C-terminal region consists of a helix-turn-helix domain.
Zinc finger, MqsA-type (Znf_MqsA-type)
Type: Domain

This entry describes a small domain with two copies of a putative zinc-binding motif CXXC (usually CXXCG). Most member proteins consist largely of this domain or else carry an additional C-terminal helix-turn-helix domain, resembling that of the phage protein Cro.
Conserved hypothetical protein CHP03883, F420 biosynthesis associated (CHP03883_F420-assoc)
Type: Family

This entry represents proteins found in coenzyme F420 biosynthesizing species of the Actinobacterial, Chloroflexi and Archaeal lineages. The few organisms having genes within this family and lacking F420 biosynthesis may either have an undiscovered F420 transporter, or may represent F420-to-FMN revertants. This family includes a Chloroflexus Aurantiacus protein whose crystal structure has been determined. This has been annotated as a putative hydrolase, but there is currently no supporting evidence for this. There is no cofactor present in the structure.
Methanol oxidation system protein MoxJ (Methanol_oxidation_MoxJ)
Type: Family

This entry represents a predicted periplasmic protein, called MoxJ or MxaJ and is required for methanol oxidation in Methylobacterium extorquens .

There are two differing opionions suggesting the role of this protein. The first is based on the homology of MoxJ, and suggests that it is the substrate-binding protein of an ABC transporter associated with methanol oxidation. The gene is also found in genomes with and only two or three genes away from a corresponding permease and ATP-binding cassette gene pair.

The other opinion, is that MoxJ is an accessory factor or additional subunit of methanol dehydrogenase itself . Mutational studies show a dependence of MoxJ for the expression of the PQQ-dependent two-subunit methanol dehydrogenase (MxaF and MxaI) in Methylobacterium extorquens, possibly acting as a chaperone for enzyme assembly or a third subunit. A homologous N-terminal sequence was found in Acetobacter methanolicus as a 32Kd third subunit .

It is thought that MoxJ may in fact be both, a component of a periplasmic enzyme that converts methanol to formaldehyde and a component of an ABC transporter that delivers the resulting formaldehyde to the cells interior.
PQQ-dependent catabolism-associated beta-propeller protein (PQQ_b_propeller)
Type: Family

Members of this protein family contain a variable number of repeats each of the YVTN family β-propeller repeat. Members occur invariably as part of a transport operon that is associated with PQQ-dependent catabolism of alcohols such as phenylethanol.
Aspartate-alanine antiporter (Asp_Ala_antiprt)
Type: Family

This entry represents the aspartate/alanine antiporter and some other uncharacterised transporters. Asparate-alanine anti-transporter (AspT) is encoded next to the gene for aspartate 4-decarboxylase (AspD), which converts asparate to alanine, releasing CO2. The exchange of Asp for Ala is electrogenic, so the AspD/AspT system confers a proton-motive force . AspT may forms homo-oligomers as a functional unit. Its transmembrane domain 3 (TM3) can undergoes l-aspartate-induced conformational alterations . The topology of AspT has been studied .
Conjugative coupling factor TraG/TraD (Conjugative_coupling_TraG/TraD)
Type: Family

Members of this protein family are the putative conjugative coupling factor, TraD (or TraG), rather distantly related to the well-characterised TraD of the F plasmid. Members are associated with conjugative-transposon-like mobile genetic elements of the class that includes SXT, an antibiotic resistance transfer element in some Vibrio cholerae strains.
Lysine-2,3-aminomutase (Lysine_aminomutase)
Type: Family

This entry describes lysine-2,3-aminomutase as found along with beta-lysine acetyltransferase in a two-enzyme pathway for making the compatible solute N-epsilon-acetyl-beta-lysine. This compatible solute, or osmolyte, is known to protect a number of methanogenic archaea against salt stress.

The proteins matched by this entry represent a tight clade with essentially full-length homology, and are distinct from additional homologues that are shorter or highly diverged in the C-terminal region. All members of this family have the radical SAM motif CXXXCXXC, while some but not all have a second copy of the motif in the C-terminal region.
Conserved hyptotheical flavoprotein, PP4765 (Flavoprotein_PP4765)
Type: Family

This entry describes a sharply distinctive clade of proteins within the larger family of flavoproteins. Their function is unknown.
Arginine/ornithine antiporter (Arg/Orn_antiprt_ArcD)
Type: Family

This entry represents Arginine/ornithine antiporter from Pseudomonas aeruginosa and similar bacterial proteins. ArcD catalyses an electroneutral exchange between arginine and ornithine to allow high-efficiency energy conversion in the arginine deiminase pathway . This exchanger occurs with the generation of ATP and release of CO2.
Lysine-2,3-aminomutase-like (EpmB)
Type: Family

Members of this radical SAM protein subfamily, including yjeK in E. coli, form a distinctive clade, homologous to lysine-2,3-aminomutase of Bacillus, Clostridium, and methanogenic archaea. Members of this family are found in E. coli, Buchnera, Yersinia, etc. The gene symbol is now reassigned as EpmB (Elongation factor P Modification B) .
Fructose 1-phosphate kinase (1-PFruKinase)
Type: Family

Fructose 1-phosphate kinase (also known as 1-phosphofructokinase) acts in concert with the fructose-specific phosphotransferase system (PTS), which phosphorylates fructose during transport to fructose-1-phosphate. The action of 1-phosphofructokinase results in beta-D-fructose-1,6-bisphosphate and is an entry point into glycolysis (

).
Streptococcal pilin isopeptide linkage domain (Strep_pil_isopept_link)
Type: Domain

This entry describes a domain that occurs once in the major pilin of Streptococcus pyogenes, Spy0128, but in higher copy numbers in other streptococcal and related bacteria proteins. The domain occurs nine times in a surface-anchored protein of Bifidobacterium longum. All members of this family have LPXTG-type sortase target sequences. The Streptococcus pyogenes major pilin has been shown to undergo isopeptide bond cross-linking, mediated by sortases, that are critical to maintaining pilus structural integrity. One such Lys-to-Asn isopeptide bond is to a near-invariant Asn near the C-terminal end of this domain. A Glu in the S. pyogenes major pilin, invariant as Glu or Gln, is described as catalytic for isopeptide bond formation .
Terminal organelle assembly protein TopJ (Termin_org_TopJ)
Type: Family

This entry describes TopJ (MG_200, CbpA), a DnaJ homologue and probable assembly protein of the Mycoplasma terminal organelle. The terminal organelle is involved in both cytadherence and gliding motility .
Enriched in aromatic and glycine residues box (EAGR_box)
Type: Domain

The EAGR box, Enriched in Aromatic and Glycine Residues, is found in three different proteins of the Mycoplasma genitalium terminal organelle, which acts in both cytadherence and gliding motility. The presence of this domain in a genome predicts the Mycoplasma-type terminal organelle structure, gliding motility, and cytadherence . The EAGR box may occur from one to nine times in a protein.
ABC transporter, ATP-binding subunit, PQQ-dependent alcohol dehydrogenase system (ABC_transprt_ATP-bd_su_PQQ)
Type: Family

Members of this protein family are the ATP-binding subunit of an ABC transporter system that is associated with PQQ biosynthesis and PQQ-dependent alcohol dehydrogenases. While this family shows homology to several efflux ABC transporter subunits, the presence of a periplasmic substrate-binding protein and association with systems for catabolism of alcohols suggests a role in import rather than detoxification.
Phosphonatase-like hydrolase (PhnX-like)
Type: Family

This clade of sequences are the closest homologues to the PhnX enzyme, phosphonoacetaldehyde (Pald) hydrolase (phosphonatase,

). This phosphonatase-like enzyme and PhnX itself are members of the haloacid dehalogenase (HAD) superfamily having a a number of distinctive features that set them apart from typical HAD enzymes. The typical HAD N-terminal motif DxDx(T/V) here is DxAGT and the usual conserved lysine prior to the C-terminal motif is instead an arginine. Also distinctive of phosphonatase, and particular to its bi-catalytic mechanism is a conserved lysine in the variable "cap" domain . This lysine forms a Schiff base with the aldehyde of phosphonoacetaldehyde, providing, through the resulting positive charge, a polarization of the C-P bond necesary for cleavage as well as a route to the initial product of cleavage, an ene-amine. The conservation of these elements in this phosphonatase-like enzyme suggests that the substrate is also, like Pald, a 2-oxo-ethylphosphonate. Despite this, the genomic context of members of this family are quite distinct from PhnX, which is almost invariably associated with the 2-aminoethylphosphonate transaminase PhnW (

), the source of the substrate Pald. Members of this clade are never associated with PhnW, but rather associate with families of FAD-dependent oxidoreductases related to deaminating amino acid oxidases (

) as well as zinc-dependent dehydrogenases (

). Notably, family members from Arthrobacter aurescens TC1 and Nocardia farcinica IFM 10152 are adjacent to the PhnCDE ABC cassette phosphonates transporter (

) typically found in association with the phosphonates C-P lyase system (

). These observations suggest two possibilities. First, the substrate for this enzyme family is also Pald, the non-association with PhnW not withstanding. Alternatively, the substrate is something very closely related such as hydroxyphosphonoacetaldehyde (Hpald). Hpald could come from oxidative deamination of 1-hydroxy-2-aminoethylphosphonate (HAEP) by the associated oxidase. HAEP would not be a substrate for PhnW due to its high specificity for AEP. HAEP has been shown to be a constituent of the sphingophosphonolipid of Bacteriovorax stolpii , and presumably has other natural sources. If Hpald is the substrate, the product would be glycoaldehyde (hydroxyacetaldehyde), and the associated alcohol dehydrogenase may serve to convert this to glycol.
6-pyruvoyl tetrahydropterin synthase, histidine active site (PTPS_His_AS)
Type: Active_site

6-pyruvoyl tetrahydropterin synthase (

) (PTPS) catalyzes the second step in the biosynthesis of tetrahydrobiopterin (BH4); a complex rearrangement of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin. PTPS is a small protein of about 145 residues and forms a homooligomeric complex of two trimers assembled in a head-to-head fashion. It binds a magnesium atom which is ligated by three histidine residues. Three residues are implicated in the catalytic mechanism: a cysteine, a histidine and a glutamate.

This entry contains the active site histidine.
6-pyruvoyl tetrahydropterin synthase, cysteine active site (PTPS_Cys_AS)
Type: Active_site

6-pyruvoyl tetrahydropterin synthase (

) (PTPS) catalyzes the second step in the biosynthesis of tetrahydrobiopterin (BH4); a complex rearrangement of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin. PTPS is a small protein of about 145 residues and forms a homooligomeric complex of two trimers assembled in a head-to-head fashion. It binds a magnesium atom which is ligated by three histidine residues. Three residues are implicated in the catalytic mechanism: a cysteine, a histidine and a glutamate.

This entry contains the active site cysteine and two of the three magnesium ligands.
Cysteine desulphurase, catalytic subunit, CsdA (Cys_desulphurase_CdsA)
Type: Family

In Escherichia coli, three cysteine desulfurases (IscS, SufS, and CsdA) initiate the delivery of sulfur for various biological processes such as the biogenesis of Fe-S clusters. CsdA is part of the Csd system. This protein, found in Escherichia coli, Yersinia pestis, Photorhabdus luminescens, and related species, is related to SufS. It works together with and physically interacts with CsdE (a paralogue of SufE) . CsdA has cysteine desulphurase activity that is enhanced by CsdE, a sulphur acceptor protein . This gene pair, although involved in FeS cluster biosynthesis, is not found next to other such genes as are its paralogs from the Suf or Isc systems.
VPLPA-CTERM sorting domain (VPLPA-CTERM)
Type: Domain

A probable protein export sorting signal, PEP-CTERM, has been described previously . It is predicted to interact with a putative transpeptidase we designate exosortase. This entry describes a variant with conserved motif VPLPA, rather than VPEP. It appears to be the recognition sequences for exosortase D. This variant is found prominently in two members of the Rhodobacterales, namely Jannaschia sp. CCS1 and Roseobacter denitrificans OCh 114 . One interesting member protein has a full-length duplication and therefore two copies of this putative sorting domain.
ABC transporter, Choline, ATP-binding subunit (ABC_trnsptr_Choline_ATP-bd)
Type: Family

Members of this protein family are the ATP-binding subunit of a three-protein transporter. This family belongs, more broadly, to the family of proline and glycine-betaine transporters, but members have been identified by direct characterisation and by bioinformatic means as choline transporters. Many species have several closely-related members of this family, probably with variable abilities to act additionally on related quaternary amines.
Thiopurine S-methyltransferase, Se/Te detoxification (Thiopur_S-MeTfrase_Se/Te_detox)
Type: Family

Members of this family are thiopurine S-methyltransferase from a branch in which at least some member proteins can perform selenium methylation as a means to detoxify selenium, or perform a related detoxification of tellurium . Note that the EC number definition does not specify a particular thiopurine, but rather represents a class of activity.
Uncharacterised protein family UPF0273, KaiC-like (UPF0273_KaiC-like)
Type: Family

Members of this family contain a single copy of the KaiC domain that occurs in two copies of the circadian clock protein kinase KaiC itself. Members occur primarily in archaea and in Thermotogales.
Spore protein YabP/YqfC (Spore_YabP/YqfC)
Type: Family

Members of this protein family are the YabP and YqfC proteins of the bacterial sporulation program, as found in Bacillus subtilis, Clostridium tetani, and other spore-forming members of the Firmicutes.

The structure of a fragment of the Spore protein YabP from Desulfitobacterium hafniense has been resolved using NMR spectroscopy, showing a homodimer with two monomeric subunits, each consisting of five anti-parallel β-strands .
Sporulation protein YqfC (Spore_YqfC)
Type: Family

This small protein, designated YqfC in Bacillus subtilis, is both restricted to and universal in sporulating species of the Firmcutes, such as Bacillus subtilis and Clostridium perfringens. It is part of the sigma(E)-controlled regulon, and its mutation leads to a sporulation defect . This protein is uncharacterised.
ABC transporter, substrate-binding protein, PQQ-dependent alcohol dehydrogenase system (ABC_transptr_sub-bd_PQQ)
Type: Family

Members of this protein family are putative substrate-binding proteins of an ABC transporter family that associates, in gene neighbourhood and phylogenomic profile, with pyrroloquinoline-quinone (PQQ)-dependent degradation of certain alcohols, such as 2-phenylethanol in Pseudomonas putida U.
Coenzyme PQQ synthesis D, bacteria (PqqD_bac)
Type: Family

This entry identifies PqqD, a protein involved in the final steps of the biosynthesis of pyrroloquinoline quinone, coenzyme PQQ .
F420-dependent oxidoreductase, MSMEG2906 (F420_MSMEG2906)
Type: Family

This entry describes a small family of enzymes in the bacterial luciferase-like monooxygenase family, which includes F420-dependent enzymes such as N5,N10-methylenetetrahydromethanopterin reductase as well as FMN-dependent enzymes. All members of this family are from species that produce coenzyme F420; SIMBAL analysis suggests that members of this family bind F420 rather than FMN.