SII-SWORD/CoKE huggingface dataset:
Amino acid adenylation domain (AA_adenyl_dom)
Type: Domain

This entry represents a domain responsible for the specific recognition of amino acids and activation as adenylyl amino acids. The reaction catalysed is aa + ATP to aa-AMP + PPi. These domains are usually found as components of multi-domain non-ribosomal peptide synthetases and are usually called 'A-domains' in that context (for a review, see ). A-domains are almost invariably followed by 'T-domains' (thiolation domains) to which the amino acid adenylate is transferred as a thiol-ester to a bound pantetheine cofactor with the release of AMP (these are also called peptide carrier proteins, or PCPs. When the A-domain does not represent the first module (corresponding to the first amino acid in the product molecule) it is usually preceded by a 'C-domain' (condensation domain,

) which catalyses the ligation of two amino acid thiol-esters from neighbouring modules.

This domain is a subset of the AMP-binding domain, which also hits substrate--CoA ligases.
D-alanine--D-alanyl carrier protein ligase (DltA)
Type: Family

DltA is part of the operon for incorporation of D-Ala residues into lipoteichoic acids (LTAs), which requires the activity of four gene products (DltA to DltD). DltA is a cytoplasmic D-alanine-D-alanyl carrier protein ligase that catalyses the D-alanylation of the D-alanyl carrier protein DltC (or Dcp); DltB is a transmembrane protein thought to be involved in the efflux of activated D-alanine to the site of acylation; and DltD is thought to be a membrane-associated protein that may have multifunctional activities (hydrolysis of mischarged DltC, facilitation of D-alanine ligation to DltC and D-alanylation of LTAs) .
Phosphoribosylformylglycinamidine synthase PurL (PurL_large)
Type: Family

This entry represents a single-molecule form of phosphoribosylformylglycinamidine synthase, also called FGAM synthase, an enzyme of purine de novo biosynthesis. This form is known as large PurL and is found mostly in eukaryotes and proteobacteria. In Bacillus subtilis PurL (FGAM synthase II), PurQ (FGAM synthase I) and PurS, of unknown function, perform the equivalent function .
Phosphoribosylformylglycinamidine subunit PurL (PRibForGlyAmidine_synth_PurL)
Type: Family

This entry represents the small PurL, also known as phosphoribosylformylglycinamidine synthase II, or FGAM synthase II.

Formylglycinamide ribonucleotide amidotransferase (FGAR-AT), also known as phosphoribosylformylglycinamidine synthase, PurL and formylglycinamidine ribonucleotide (FGAM) synthase, catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to formylglycinamidine ribonucleotide (FGAM), ADP, Pi, and glutamate in the fourth step of the purine biosynthetic pathway .

Two types of phosphoribosylformylglycinamidine synthases (PurLs) have been detected. The first consists of a single polypeptide chain of about 1300 amino acids and is found in eukaryotes and Gram-negative bacteria. This type is designated large PurL. The second type consists of about 800 amino acids and is found in Gram-positive bacteria and archaebacteria. This type is designated small PurL. In this case PurL is part of the the FGAM synthase complex that is composed of three subunits and requires two additional proteins, PurQ, a glutaminase, and PurS, of unknown function .
Phosphoribosylformylglycinamidine synthase subunit PurQ (PRibForGlyAmidine_synth_PurQ)
Type: Family

In Gram-negative bacteria and eukaryotes, formylglycinamideribonucleotide amidotransferase is a single protein. In archaea and Gram-positive bacteria it is formed from three proteins. This entry describes the PurQ protein of Bacillus subtilis (where PurL, PurQ, and PurS are required for phosphoribosylformylglycinamidine synthase activity) and functionally equivalent proteins from other bacteria and archaea .
Pimeloyl-[acyl-carrier protein] methyl ester esterase (BioH)
Type: Family

This CoA-binding enzyme is required for the production of pimeloyl-coenzyme A, the substrate of the BioF protein early in the biosynthesis of biotin . Its exact function is unknown, but it has been shown to possess carboxylesterase activity with a preference for short acyl chain substrates . This enzyme belongs to the alpha/beta hydrolase fold family. Members of this family are restricted to the Proteobacteria.
Herpes virus tegument protein (Herpes_virus_tegument)
Type: Family

This is a family of major tegument proteins from Herpesviruses. Herpesvirus tegument proteins counteract the intrinsic anti-viral defenses and support the early steps of infection. BNRF1 is the Epstein-Barr virus (EBV) major tegument protein and plays an important role in viral transport from the endosomes to the nucleus . Furthermore, it supports EBV early infection by interacting with host nuclear protein Daxx and disrupting the formation of the Daxx-ATRX chromatin remodeling complex .
Pur operon repressor (PurR_Bsub)
Type: Family

This entry represents the pur operon repressor PurR of low-GC Gram-positive bacteria. This homodimeric repressor contains a large region homologous to phosphoribosyltransferases and is inhibited by 5-phosphoribosyl 1-pyrophosphate .

PurR is a DNA-binding transcriptional repressor that controls the expression of a number of genes involved in the synthesis, metabolism and transport of purines . In response to a signal of excess adenine, represses the transcription of the pur operon, which encodes enzymes of the purine biosynthetic pathway . it also responds to amino acid starvation via (p)ppGpp, which strongly increases PurR activity and repression of purine nucleotide biosynthesis genes .
Xanthine phosphoribosyltransferase (Xanthine_PRibTrfase)
Type: Family

This entry represent a xanthine-specific phosphoribosyltransferase of Bacillus subtilis and closely related proteins from other species, mostly from other Gram-positive bacteria. The adjacent gene is a xanthine transporter; B. subtilis can import xanthine for the purine salvage pathway or for catabolism to obtain nitrogen.
Diaminopropionate ammonia-lyase (DiNH2opropionate_NH3_lyase)
Type: Family

This small family includes diaminopropionate ammonia-lyase from Salmonella typhimurium and a small number of close homologues, about 50 % identical in sequence. The enzyme is a pyridoxal phosphate-binding homodimer homologous to threonine dehydratase (threonine deaminase).
Beta-hydroxyacyl-(acyl-carrier-protein) dehydratase FabA (FabA)
Type: Family

This enzyme, FabA, shows overlapping substrate specificity with FabZ with regard to chain length in fatty acid biosynthesis. It is commonly designated 3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase as if it were specific for that chain length, but its specificity is broader; it is active even in the initiation of fatty acid biosynthesis. This enzyme can also isomerise trans-2-decenoyl-ACP to cis-3-decenoyl-ACP to bypass reduction by FabI and instead allow biosynthesis of unsaturated fatty acids. FabA cannot elongate unsaturated fatty acids.

The FabA structure is a homodimer with two independent active sites located at the dimer interface. Each active site is tunnel-shaped and completely inaccessible to solvent. No metal ions or cofactors are required for ligand binding or catalysis .
Beta-hydroxyacyl-(acyl-carrier-protein) dehydratase FabZ (FabZ)
Type: Family

Fatty acids biosynthesis occurs by two distinct pathways: in fungi, mammals and mycobacteria, type I or associative fatty-acid biosynthesis (type I FAS) is accomplished by multifunctional proteins in which distinct domains catalyse specific reactions; in plants and most bacteria, type II or dissociative fatty-acid biosynthesis (type II FAS) is accomplished by distinct enzymes .

FabZ is the primary dehydratase involved in fatty-acid elongation in type II FAS. Both FabZ and FabA catalyse the dehydration of beta-hydroxyacyl acyl carrier protein (ACP) to trans 2-enoyl ACP. However, FabZ and FabA display subtle differences in substrate specificities, whereby FabA is most effective on acyl ACPs of 9-11 carbon atoms in length, while FabZ is less specific. Unlike FabA, FabZ does not function as an isomerase and cannot initiate unsaturated fatty acid biosynthesis. However, only FabZ can act during the elongation of unsaturated fatty acid chains.
Crotonyl-CoA reductase (Crot_CoA_red)
Type: Family

Crotonyl-CoA reductase an convert crotonyl-CoA to butyryl-CoA (crotonyl-CoA reductase activity), but more importantly, in the presence of CO2, generates (2S)-ethylmalonyl-CoA. In serine cycle methylotrophic bacteria this enzyme is involved in the process of acetyl-CoA to glyoxylate . In other bacteria the enzyme is used to produce butyrate for incorporation into polyketides such as tylosin from Streptomyces fradiae and coronatine from Pseudomonas syringae .
Flavodoxin, long chain (Flavodoxin_lc)
Type: Family

Flavodoxins are small redox-active proteins with a flavin mononucleotide (FMN) prosthetic group. They function as electron transfer agents in a variety of microbial metabolic processes, including nitrogen fixation by nitrogenase , sulphite reduction , and light-dependent NADP+ reduction during photosynthesis . This entry describes the long chain type , typical for nitrogen fixation but associated with pyruvate formate-lyase activation and cobalamin-dependent methionine synthase activity in Escherichia coli .
Flavodoxin, short chain (Flav_short)
Type: Family

Flavodoxins are small redox-active proteins with a flavin mononucleotide (FMN) prosthetic group. They function as electron transfer agents in a variety of microbial metabolic processes, including nitrogen fixation by nitrogenase , sulphite reduction , and light-dependent NADP+ reduction during photosynthesis . This entry describes the short chain type . Many of these are involved in sulphite reduction.
Ribonucleotide reductase-associated flavodoxin, putative (RNR_flavodoxin)
Type: Family

This entry represents a family of proteins found immediately downstream of ribonucleotide reductase genes in Xyella fastidiosa and some Gram-positive bacteria. It appears to be a highly divergent flavodoxin of the short chain type, more like the flavodoxins of the sulphate-reducing genus Desulfovibrio than like the NifF flavodoxins associated with nitrogen fixation.
Flavoprotein WrbA-like (Flavoprotein_WrbA-like)
Type: Family

WrbA (tryptophan (W) repressor-binding protein) was discovered in Escherichia coli, where it was proposed to play a role in regulation of the tryptophan operon , which has been put in question since then . Instead, WrbA has been shown to have FMN-dependent NAD(P)H:quinone oxidoreductase activity . A role in quinone detoxification has been proposed, supported by evidence suggesting its involvement in oxidative defence and/or cell signalling .

This entry also includes QR2 from Triphysaria versicolor. QR2 acts as a NAD(P)H:quinone oxidoreductase reducing quinones by a two-electron transfer mechanism .
Phage tail tape measure protein (Phage_tape_meas)
Type: Domain

This entry represents a reasonably well conserved core region of a family of phage tail proteins. The member from phage TP901-1 was characterised as a tail length tape measure protein in that a shortened form of the protein leads to phage with proportionately shorter tails .
Thiazolinyl imide reductase (Thiazolinyl_imide_reductase)
Type: Family

This reductase is found associated with gene clusters for the biosynthesis of various non-ribosomal peptide derived natural products in which cysteine is cyclised to a thiazoline ring containing an imide double bond. Examples include yersiniabactin and pyochelin. Yersiniabactin is a virulence factor secreted by Yersinia pestis in iron-deficient microenvironments, in order to scavenge ferric ions .
Chlorinating enzyme (Chlorin_enz)
Type: Family

This entry represents a group of highly homologous enzymes related to dioxygenases which chlorinate amino acid methyl groups. L-threonyl-[L-threonyl-carrier protein] 4-chlorinase (SyrB2) chlorinates the methyl group of threonine in the biosynthesis of syringomycin in Pseudomonas syringae in a reaction that requires oxygen, chloride ions, ferrous iron and α-oxoglutarate . α-oxoglutarate seems to provide structural stability to the protein, which shows an eight-stranded anti-parallel β-sandwich 'jelly-roll' motif .
SinI-like, DNA-binding domain (SinI_DNA-bd)
Type: Domain

This putative DNA-binding domain is found N-terminal in the modification methylase SinI , transcriptional repressor DcmR and in other uncharacterised proteins.
Transposase (putative), N-terminal (Transposase_put_N)
Type: Domain

This entry represents the N-terminal region of a family of putative transposases found in the largest copy number in Thermoanaerobacter tengcongensis. The three homologues in Bacillus anthracis are each split into two ORFs and this entry represents the upstream ORF.
Cas12f1-like, TNB domain (Cas12f1-like_TNB)
Type: Domain

This entry represents a zinc ribbon domain known as the target nucleic acid-binding (TNB) domain of CRISPR-associated endodeoxyribonuclease Cas12f1 and similar sequences found in all domains in life. This domain is also found in bacterial transposases, including putative transposes described by

. Some proteins containing this domain, in particular, Cas12m orthologs albeit containing D-E-D, H-D-D and N-D-D motifs in the RuvC active site do not exhibit dsDNA nuclease activity, but efficiently bind to dsDNA targets in a PAM-dependent manner . The DNA-binding activity without cleavage seems is a common feature of the Cas12m effectors .
NAD(P)H-quinone oxidoreductase, subunit N/subunit 2 (NADH-Q_OxRdtase_suN/2)
Type: Family

This entry describes the 14th (based on Escherichia coli) structural gene, N, of bacterial and chloroplast energy-transducing NADH (or NADPH) dehydrogenases (

). This entry does not describe any subunit of the mitochondrial complex I (for which the subunit composition is very different), nor NADH dehydrogenases that are not coupled to ion transport. For chloroplast members, the name NADH-plastoquinone oxidoreductase is used for the complex and this protein is designated as subunit 2 or B. This entry also includes a subunit of a related complex in the archaeal methanogen, Methanosarcina mazei (Methanosarcina frisia), in which F420H2 replaces NADH and 2-hydroxyphenazine replaces the quinone.
Malate dehydrogenase, type 1 (Malate_DH_type1)
Type: Family

This entry represents the NAD-dependent malate dehydrogenase found in eukaryotes and certain gamma proteobacteria. The enzyme is involved in the citric acid cycle as well as the glyoxalate cycle. Several isoforms exist in eukaryotes. In Saccharomyces cereviseae, for example, there are cytoplasmic, mitochondrial and peroxisomal forms. Although malate dehydrogenases have in some cases been mistaken for lactate dehydrogenases due to the similarity of these two substrates and the apparent ease with which evolution can toggle these activities, critical residues have been identified which can discriminate between the two activities.
Glycyl radical enzyme, PFL2/glycerol dehydratase family (PFL2/GDeHydtase_fam)
Type: Family

This family previously was designated pyruvate formate-lyase, but it now appears that members include the B12-independent glycerol dehydratase. This family includes the YbiW and PflD proteins of E. coli, described as isoforms of pyruvate-formate lyase found in a limited number additional species. PFL catalyses the reaction pyruvate + CoA -> acetyl-CoA + formate, which is a step in the fermentation of glucose .

(2S)-3-sulfopropanediol dehydratase from Klebsiella oxytoca, which is involved in the degradation of the organosulfur compound 2(S)-dihydroxypropanesulfonate (DHPS) , also belongs to this group of proteins.
Epimerase family protein SDR39U1 (SDR39U1)
Type: Family

This entry represents Epimerase family protein SDR39U1, which is a family of conserved proteins with NAD(P)-binding Rossmann-fold domain.
TonB-dependent copper receptor (TonB-dep_Cu_rcpt)
Type: Family

This entry represents a family of proteobacterial TonB-dependent outer membrane receptor/transporters which bind and translocate copper ions. Two characterised members of this family exist, outer membrane protein C (OprC) from Pseudomonas aeruginosa and NosA from Pseudomonas stutzeri, which is responsible for providing copper for the copper-containing N2O reductase .
TonB-dependent vitamin B12 transporter BtuB (B12_transptr_BtuB)
Type: Family

The outer membrane is an essential component of Gram-negative bacteria, providing them with increased resistance to antibiotics, digestive enzymes, detergents and immune surveillance . The outer membrane is permeable to small hydrophilic molecules because of the presence of aqueous diffusion channels (e.g. porins). Small molecules present at high concentration diffuse down their concentration gradients into the periplasmic space. Porins are inadequate for the efficient acquisition of iron siderophores, cobalamins (Cbl), and other molecules that are present at very low concentrations and that are too bulky to pass through the lumen of the porin. Another class of outer membrane proteins binds these substrates with high specificity and carries out active transport across the outer membrane. This active transport process requires an energy source and a second protein, TonB. Outer membrane active-transport proteins interact with the transperiplasmic protein TonB through a conserved sequence, the "Ton-box". Interaction with TonB couples the energy of the proton motive force of the inner membrane to drive an outer membrane transport cycle .

To date, crystal structures of four TonB-dependent transporters have been solved. Three of these are iron-siderophore transporters: ferrichrome transporter FhuA ; ferric enterobactin transporter FepA ; and ferric dicitrate transporter FecA . The fourth structure is the cobalamin transporter BtuB . All of these structures are composed of two domains, a conserved N-terminal globular domain (hatch) and a 22-stranded β-barrel (barrel). The hatch domain resides within the barrel and occludes the large pore of the large barrel domain. The hatch domains are composed of a central core of four β-strands connected by loops. The conserved Ton-box is located near the periplasmic opening of the barrel and precedes the conserved hatch core. The barrels have large extracellular loops and short periplasmic turns connecting the β-strands. TonB-dependent transporters bind their cognate substrates using residues from hatch loops, from the interior surfaces of β-strands in the barrel wall, and from extracellular loops of the barrel .
Succinate semialdehyde dehydrogenase (Succ_semiAld_DH)
Type: Family

Succinate semialdehyde dehydrogenase (SSADH) is one of three enzymes constituting 4-aminobutyrate (GABA) degradation in both prokaryotes and eukaryotes, catalysing the (NAD(P)+)-dependent catabolism reaction of succinate semialdehyde to succinate for metabolism by the citric acid cycle. In Escherichia coli, SSADH is located in a unidirectionally transcribed gene cluster encoding enzymes for GABA degradation and is suggested to be co-transcribed with succinate semialdehyde transaminase from a common promoter upstream of SSADH . Similar gene arrangements can be found in characterised Ralstonia eutropha (Alcaligenes eutrophus) and the genome analysis of Bacillus subtilis.

Prokaryotic SSADH enzymes (

) share high sequence homology to characterised SSADH from rat and human (

), exhibiting conservation of proposed cofactor binding residues, and putative active sites (G-237 and G-242, C-293 and G-259 respectively of rat SSADH) .
Clustered lipoprotein, Treponema denticola (Clustered_lipoprot_TREDE)
Type: Family

This entry represents a family of six predicted lipoproteins from a region of about 20 tandemly arranged genes in the Treponema denticola genome. Two other neighbouring genes share the lipoprotein signal peptide region but do not show more extensive homology. The function of this locus is unknown.
Bacterial TonB-dependent receptor (TonB_rcpt_bac)
Type: Family

This entry represents a family of TonB-dependent outer-membrane receptors which are found mainly in Xanthomonas and Caulobacter. These appear to represent the expansion of a paralogous family in that the 22 Xanthomonas axonopodis (21 in Xanthomonas campestris) and 18 Caulobacter crescentus (Caulobacter vibrioides) sequences are more closely related to each other than any of the many TonB-dependent receptors found in other species. In fact, the C. crescentus and Xanthomonas sequences are inseparable on a phylogenetic tree using a PAM-weighted neighbour-joining method, indicating that one of the two genuses may have acquired this set of receptors from the other. The mechanism by which this family is shared between Xanthomonas, a gammaproteobacterial plant pathogen and Caulobacter, an alpha proteobacterial aquatic organism is unclear.
TonB-dependent siderophore receptor (TonB_sidphr_rcpt)
Type: Family

This entry represents a number of TonB-like receptors. They fold into an antiparallel β-barrel with enclosed in their interior an α/β plug domain.

The outer membrane is an essential component of Gram-negative bacteria, providing them with increased resistance to antibiotics, digestive enzymes, detergents and immune surveillance . The outer membrane is permeable to small hydrophilic molecules because of the presence of aqueous diffusion channels (e.g. porins). Small molecules present at high concentration diffuse down their concentration gradients into the periplasmic space. Porins are inadequate for the efficient acquisition of iron siderophores, cobalamins (Cbl), and other molecules that are present at very low concentrations and that are too bulky to pass through the lumen of the porin. Another class of outer membrane proteins binds these substrates with high specificity and carries out active transport across the outer membrane. This active transport process requires an energy source and a second protein, TonB. Outer membrane active-transport proteins interact with the transperiplasmic protein TonB through a conserved sequence, the "Ton-box". Interaction with TonB couples the energy of the proton motive force of the inner membrane to drive an outer membrane transport cycle .
Recombination-promoting nuclease RpnA (RpnA)
Type: Family

This entry includes recombination-promoting nuclease RpnA (also known as YhgA) from
Escherichia coli
, which is a low activity DNA endonuclease active on single- and double-stranded DNA, but not RNA, with little sequence specificity . This aids horizontal gene transfer because the cleavage products are capable of providing priming sites for DNA polymerase, which can enable DNA joining by primer-template switching. Thus, many members of this family possess the YhgA-like domain (

).

Members are found in small numbers of genomes, but in large copy numbers in many of those species, including over 30 full length and fragmentary members in the oral pathogenic spirochete Treponema denticola. The strongest similarities are usually within rather than between species. In T. denticola, full-length members are often found near transporters or other membrane proteins.
Glutamate decarboxylase (Glutamate_decarboxylase)
Type: Family

This entry represents glutamate decarboxylase (Gad;

) it is a pyridoxal 5'-phosphate (PLP)-dependent enzyme, which catalyses the irreversible α-decarboxylation of L-glutamate to gamma-aminobutyrate (GABA). This enzyme is widely distributed amongst eukaryotes and prokaryotes, but its function varies in different organisms .

GadD has a crucial role in the vertebrate central nervous system where it is responsible for the synthesis of GABA, the major inhibitory neurotransmitter. In the majority of vertebrates Gad occurs in two isoforms, Gad65 and Gad67, both active at neutral pH . Gad isoforms (GadA and GadB) have also been reported in some bacterial species, including the Gram-negative bacterium and Gram-positive bacterium .

A unique feature of plant and yeast Gad is the presence of a calmodulin (CaM)-binding domain in the C-terminal region. In Saccharomyces cerevisiae (Baker's yeast), Gad expression is required for normal oxidative stress tolerance . In plants, Gad is thought to be a stress-adapter chaperonin sensing Ca2+ signals.