SII-SWORD/CoKE huggingface dataset:
FAD-dependent oxidoreductase, HpnW (FAD-dependent_OxRdtase_HpnW)
Type: Family

This entry represents a clade of FAD-dependent oxidoreductases syntenically associated with a family of proposed phosphonatase-like enzymes (

) and is also found (less frequently) in association with phosphonate transporter components. A likely role for this enzyme involves the oxidative deamination of an aminophosphonate differing slightly from 2-aminoethylphosphonate, possibly 1-hydroxy-2-aminoethylphosphonate (see the comments for

). Many members of the larger FAD-dependent oxidoreductase family act as amino acid oxidative deaminases.
7-carboxy-7-deazaguanine synthase (Deazaguanine_synth)
Type: Family

7-deazapurines are compounds that contain pyrrolopyrimidine functional groups (similar to purines, but lacking one of the nitrogens in the pentameric ring). These compounds form a structurally diverse class of nucleoside analogues that often possess antibiotic, antineoplastic, or antiviral activities. Examples of 7-deazapurines that are important for cell function include the bacterial/eukaryotic modified tRNA base queuosine and the archaeal modified base archaeosine. 7-cyano-7-deazaguanosine (preQ0) is the precursor for all 7-deazapurines and is produced from GTP in a four-step pathway . 7-carboxy-7-deazaguanine synthase catalyses the third step in this pathway, the conversion of 6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-deazaguanine.
Alcohol dehydrogenase, phosphonate catabolism-associated, putative (ADH_phosphonate_catab-assoc)
Type: Family

This entry represents a clade of zinc-binding alcohol dehydrogenases that are repeatedly associated with genes proposed to be involved with the catabolism of phosphonate compounds.
Cellulose biosynthesis protein BcsG (BcsG)
Type: Family

Cellulose biosynthesis protein BcsG, also known as YhjU, is a component of bacterial cellulose synthase complex that plays a role in biofilm formation in bacteria . It is a Zn-dependent phosphoethanolamine transferase that catalyses transfer of phosphoethanolamine residues from membrane phosphatidylethanolamine to the glucosyl residues in the nascent cellulose chain .
Cellulose biosynthesis protein BcsE (BcsE)
Type: Family

BcsE (bacterial cellulose synthase E) or YhjS, is required for cellulose biosynthesis in Salmonella enteritidis. Its role is this process across multiple bacterial species is implied by the partial phylogenetic profiling algorithm. Members are found in the vicinity of other cellulose biosynthesis genes .

BcsE contains the C-terminal GIL domain. The GIL domain, for GGDEF I-site like domain, is a c-di-GMP binding domain on the BcsE proteins of enterobacteria. It is not essential for cellulose synthesis but is critical for maximal cellulose production. Cellulose production in enterobacteria is controlled by a two-tiered c-di-GMP-dependent system involving BcsE and the PilZ domain containing glycosyltransferase BcsA. The RxGD motif of the GIL domain is required for c-di-GMP binding .
Cellulose synthase operon protein BcsQ (Cellulose_synthase_operon_BcsQ)
Type: Family

The BcsQ (also known as YhjQ) protein is encoded immediately upstream of bacterial cellulose synthase (bcs) genes in a broad range of bacteria, including both copies of the bcs locus in Klebsiella pneumoniae, and in several species is clearly part of the bcs operon. It is identified as a probable component of the bacterial cellulose metabolic process not only by gene location, but also by partial phylogenetic profiling, or Haft-Selengut algorithm , based on a bacterial cellulose biosynthesis genome property profile.

Cellulose plays an important role in biofilm formation and structural integrity in some bacteria. E. coli csQ may play a role in subcellular localization of an active cellulose biosynthesis apparatus at the bacterial cell pole .
Putrescine aminotransferase (Putrescine_aminotransferase)
Type: Family

This entry represents putrescine aminotransferase (

) as found in Escherichia coli , Erwinia carotovora subsp. atroseptica (Pectobacterium atrosepticum), and closely related species. Putrescine aminotransferase catalyzes the aminotransferase reaction from putrescine to 2-oxoglutarate, leading to glutamate and 4-aminobutanal, which spontaneously cyclizes to form 1-pyrroline. This pyridoxal phosphate enzyme, as characterised in E. coli, can also act on cadaverine and, more weakly, spermidine.
T6S-associated protein TagF (TagF)
Type: Family

This entry includes the T6S-associated protein, TagF, a post-translational repressor of the hemolysin co-regulated secretion island I (HSI-I)-encoded type VI secretion system (H1-T6SS), found in Pseudomonas aeruginosa. The type VI secretion system (T6SS) is found broadly among the Proteobacteria and is implicated in diverse processes including host-cell interactions, biofilm formation and gene regulation. Furthermore, studies indicate that the T6SS plays a critical role in interbacterial interactions. TagF has been shown to regulate the activity of the H1-T6SS in a manner that does not require phosphorylated-Fha1, PpkA, or other Tag proteins. TagF forms a homodimer with nearly identical monomers composed of alpha and beta elements assembled as a three-layer sandwich (α-β-α) .
Gamma-aminobutyraldehyde dehydrogenase (PatD)
Type: Family

This entry represents gamma-aminobutyraldehyde dehydrogenase (PatD,

) involved in the second step in one of two pathways for putrescine degradation. It catalyzes the oxidation 4-aminobutanal (gamma-aminobutyraldehyde) to 4-aminobutanoate (gamma-aminobutyrate or GABA) . It also functions as a 5-aminopentanal dehydrogenase in a a L-lysine degradation pathway to succinate that proceeds via cadaverine, glutarate and L-2-hydroxyglutarate . It can also oxidize n-alkyl medium-chain aldehydes, but with a lower catalytic efficiency .
ATPase, type I secretion system (ATPase_T1SS)
Type: Family

Type I protein secretion is a system in some Gram-negative bacteria to export proteins (often proteases) across both inner and outer membranes to the extracellular medium. This is one of three proteins of the type I secretion apparatus. Targeted proteins are not cleaved at the N terminus, but rather carry signals located toward the extreme C terminus to direct type I secretion. This model is related to models

and

, and to bacteriocin ABC transporters that cleave their substrates during export.
Glycerol-3-phosphate dehydrogenase, NAD-dependent, eukaryotic (G3P_DH_NAD-dep_euk)
Type: Family

This entry represents eukaryotic glycerol-3-phosphate dehydrogenase (

). The reaction catalysed by this enzyme is:

sn-glycerol 3-phosphate + NAD(+) = glycerone phosphate + NADH

Note that similar, though distinct, reactions (

and

), occur in the bacterial proteins.
Glycerol-3-phosphate dehydrogenase, GlpA subunit (G3P_DH_GlpA_su)
Type: Family

This entry represents the GlpA subunit. An archaeal homologue has also recently been characterised , which appears to be used under aerobic conditions in halophilic archaea.

In bacteria, glycerol uptake is mediated by the glycerol diffusion facilitator, an integral membrane protein catalysing the rapid equilibration of concentration gradients of glycerol across the cytoplasmic membrane. Intracellular glycerol is converted to glycerol-3-phosphate that is further metabolised to dihydroxyacetone phosphate (DHAP) by either of two membrane-bound enzymes, depending on the growth conditions.

Under aerobic growth conditions, in the presence of glycerol, a glycerol-3-phopshate dehydrogenase (encoded by the glpD gene) is induced, which passes the reducing equivalents to an electron transport chain terminating with oxygen as the electron acceptor. Under anaerobic growth conditions, in the presence of glycerol and fumarate, a different dehydrogenase is induced . Electrons derived from this reaction are ultimately passed to fumarate as the terminal electron acceptor. The enzyme is composed of three subunits, encoded by the glpABC operon, which are all essential for anaerobic growth on glycerol-3-phosphate . GlpA and B form the soluble subunit which carries the catalytic site of glycerol-3-phosphate oxidation; while GlpC forms a membrane-bound iron-sulphur subunit, which may act as an anchor for the soluble subunit, and is thought to function in electron transfer from GlpAB to the terminal electron acceptor.
Glycerol-3-phosphate dehydrogenase, GlpC subunit (G3P_DH_GlpC_su)
Type: Family

This entry represents the non-catalytic membrane-bound GlpC subunit. This protein lacks classical hydrophobic transmembrane helices; interaction with the membrane may involve amphipathic helices . GlcC has conserved Cys-containing motifs suggestive of iron-sulphur binding. An archaeal homologue has also recently been characterised , which appears to be used under aerobic conditions in halophilic archaea.

In bacteria, glycerol uptake is mediated by the glycerol diffusion facilitator, an integral membrane protein catalysing the rapid equilibration of concentration gradients of glycerol across the cytoplasmic membrane. Intracellular glycerol is converted to glycerol-3-phosphate that is further metabolised to dihydroxyacetone phosphate (DHAP) by either of two membrane-bound enzymes, depending on the growth conditions.

Under aerobic growth conditions, in the presence of glycerol, a glycerol-3-phopshate dehydrogenase (encoded by the glpD gene) is induced, which passes the reducing equivalents to an electron transport chain terminating with oxygen as the electron acceptor. Under anaerobic growth conditions, in the presence of glycerol and fumarate, a different dehydrogenase is induced . Electrons derived from this reaction are ultimately passed to fumarate as the terminal electron acceptor. The enzyme is composed of three subunits, encoded by the glpABC operon, which are all essential for anaerobic growth on glycerol-3-phosphate . GlpA and B form the soluble subunit which carries the catalytic site of glycerol-3-phosphate oxidation; while GlpC forms a membrane-bound iron-sulphur subunit, which may act as an anchor for the soluble subunit, and is thought to function in electron transfer from GlpAB to the terminal electron acceptor.
Agmatine deiminase (Agmatine_deiminase)
Type: Family

Agmatine deiminase (

) catalyses the conversion of agmatine into N-carbamoylputrescine. This enzyme usually functions as part of polyamine biosynthesis, though in some bacterial species, such as Enterococcus faecalis, it can also function in the generation of ATP from agmatine . The E. faecalis enzyme is a homotetramer where each monomer adopts a similar fold to that of the arginine deiminase catalytic domain, a five-bladed fan-like structure where the repeating unit is formed from three β sheets and an α helix .

This entry represents known and putative agmatine deiminases from bacteria and plants. Related deiminases not in this entry include the peptidyl-arginine deiminase (

) as found in Porphyromonas gingivalis.
N-carbamoylputrescine amidase (N-carbamoylputrescine_amidase)
Type: Family

This entry includes bacterial and plant members of the carbon-nitrogen hydrolase family, namely N-carbamoylputrescine amidase (NILP1/CPA) from Arabidopsis and citrullinase from Francisella tularensis subsp. tularensis. NILP1/CPA catalyses (

) the hydrolysis of N-carbamoylputrescine to putrescine , the final step of the arginine decarboxylase pathway of putrescine biosynthesis that operates in some plant and bacterial species. This protein is designated AguB in bacteria. Citrullinase catalyses the degradation of citrulline into ornithine, carbon dioxide and ammonia , which contributes to intramacrophage survival, in vivo growth and pathogenesis.
Transmembrane Gly-Cys-Arg, conserved site (TM_Gly-Cys-Arg_CS)
Type: Conserved_site

This entry represents a small (about 30 amino acids), hydrophobic, moderately conserved transmembrane helix-containing region. It is found once per protein, but in many proteins per genome in several bacteria of the order Myxococcales. The region begins with a signature Gly-Cys motif; other features, including a hydrophobic transmembrane helix, Arg-rich cluster, and its location at the protein C terminus, resemble the PEP-CTERM proposed protein targeting domain.
Transcriptional repressor BetI (Tscrpt_rep_BetI)
Type: Family

BetI is a DNA-binding transcriptional repressor of the bet (betaine) regulon which is related to TetR . Choline, through BetI, induces the expression of the betaine biosynthesis genes betA and betB by de-repression. The choline porter gene betT is also part of this regulon in Escherichia coli . Note that a different transcriptional regulator, ArcA, controls the expression of bet regulon genes in response to oxygen, as BetA is an oxygen-dependent enzyme.
Coenzyme A disulphide reductase (CoA_disulphide_reductase)
Type: Family

Coenzyme A disulphide reductase (

) has been characterised in Staphylococcus aureus, Pyrococcus horikoshii, and Borrelia burgdorferi (Lyme disease spirochete), and inferred in several other species on the basis of high levels of CoA and an absence of glutathione as a protective thiol. Coenzyme A disulphide reductase specifically catalyses the NAD(P)H-dependent reduction of coenzyme A disulphide using FAD and NAD(P)H . In some species the enzymes show a distinct preference for NADH or NADPH, while others can use either substrate equally well. The reduction of disulphides occurs by a thiol-disulphide exchange reaction, but involves only a single catalytic cysteine residue that forms a stable mixed disulphide with CoA during catalysis. This enzyme contains 2 FAD binding domains and a single NAD(P)H binding domain .
L-ascorbate oxidase, plants (L-ascorbate_oxidase_pln)
Type: Family

This entry represents the copper-containing enzyme L-ascorbate oxidase (

), also called ascorbase. These enzymes are found in flowering plants, and show greater sequence similarity to a family of laccases (

) from plants than to other known ascorbate oxidases.
Laccase (Laccase)
Type: Family

This entry represents the copper-containing enzyme laccase (

), often present in mutiple copies in a single plant species, and additional, uncharacterised, closely related plant proteins termed laccase-like multicopper oxidases. These enzymes show considerable sequence similarity to the L-ascorbate oxidases (

). Laccases are enzymes of rather broad specificity, acting on both o- and p-quinols, and often acting also on aminophenols and phenylenediamine .
Multicopper oxidase, fungi (Multicopper_oxidase_fun)
Type: Family

This entry describes a family of fungal ascorbate oxidases, which form part of a larger family of multicopper oxidases that also includes plant ascorbate oxidases (

), plant laccases and laccase-like proteins (

). The protein from Acremonium sp. HI-25 has been characterised as an ascorbate oxidase, a multicopper oxidase that catalyses the oxidation of ascorbate to dehydroascorbate with the concomitant reduction of molecular oxygen to water . TerE from Aspergillus terreus has also been characterised and is thought to be a multicopper oxidase. It is a component required for the biosynthesis of the metabolite terrein, which has antimicrobial, antiproliferative, and antioxidative activities. TerE and the Kelch-like protein TerF convert the intermediate 6-hydroxymellein to terrein .
Cysteine desulfurase, sulphur acceptor subunit CsdE (Cysteine_desulfurase_CsdE)
Type: Family

This entry represents CsdE (formerly known as YgdK), the sulphur acceptor subunit of a cysteine desulfurase. This protein, found as a paralogue of SufE in Escherichia coli, Yersinia pestis, Photorhabdus luminescens and related species, works together and physically interacts with CsdA (a paralogue of SufS). CsdA has cysteine desulfurase activity that is enhanced by this protein, where Cys-61 (numbered as in E. coli) is a sulphur acceptor site. CsdA and CsdE, although involved in FeS cluster biosynthesis, are not encoded next to other like the paralogous Suf proteins.
Indole-3-pyruvate decarboxylase, Enterobacteriaceae (IPDC_Enterobacteriaceae)
Type: Family

This entry represents Enterobacteriaceae indole-3-pyruvate decarboxylase, part of a pathway for biosynthesis of the plant growth hormone indole-3-acetic acid (IAA). Typically, these species interact with plants, either as pathogens or as beneficial, root-associated bacteria . It was suggested that the release of IAA benefits these bacteria by enabling them to modify their microhabitat, such as by increasing the rate of nutrient leakage from plant cells in their vicinity .
Indole-3-pyruvate decarboxylase (IPDC)
Type: Family

This entry represents indole-3-pyruvate decarboxylase, part of a pathway for biosynthesis of the plant growth hormone indole-3-acetic acid (IAA) . Typically, these species interact with plants, either as pathogens or as beneficial, root-associated bacteria . It was suggested that the release of IAA benefits these bacteria by enabling them to modify their microhabitat, such as by increasing the rate of nutrient leakage from plant cells in their vicinity .
Sphingomyelinase C/phospholipase C (Sphingomyelinase/PLipase_C)
Type: Family

This entry represents the proteins sphingomyelinase C (

) and phospholipase C (

). Sphingomyelinase (also known as sphingomyelin phosphodiesterase) is a hydrolase enzyme involved in sphingolipid metabolism, breaking down sphingomyelin to phosphocholine and ceramide . However, some of these enzymes act as haemolysins, virulence factors that promotes intracellular proliferation by mediating the disruption of the phagocytic vacuole and the release of bacteria into the host cell cytosol. It may act in concert with the phospholipases PlcA and PlcB and the hemolysin Hly to mediate efficient escape from the vacuole . Phospholipase C is a bacterial haemolysin, which are exotoxins that attack blood cell membranes and cause cell rupture. Beta-haemolysin is a phospholipase C with specific activity toward sphingomyelins, and has a high specificity for sphingomyelin .
Phosphocholine-specific phospholipase C (PC-PLC)
Type: Family

Proteins in this entry are bacterial phosphatidylcholine-hydrolysing, phospholipase C enzymes, with the characteristic domain architecture found in the hemolytyic (PlcH) and nonhemolytic (PlcN) secreted enzymes from Pseudomonas aeruginosa . PlcH hydrolyzes phosphatidylcholine to diacylglycerol and phosphocholine, but unlike PlcN can also hydrolyse sphingomyelin to ceramide (N-acylsphingosine) and phosphocholine. These proteins possess the twin-arginine signal sequence for Sec-independent transport across the plasma membrane. PlcH is secreted as a heterodimer with a small chaperone, PlcR, encoded immediately downstream.
Acid phosphatase, AcpA (AcpA)
Type: Family

Acid phosphatase A catalyzes the hydrolysis reaction via a phosphoseryl intermediate to produce inorganic phosphate and the corresponding alcohol, optimally at low pH . AcpA hydrolyzes a variety of substrates, including p-nitrophenylphosphate (pNPP), p-nitrophenylphosphorylcholine (pNPPC), peptides containing phosphotyrosine, inositol phosphates, AMP, ATP, fructose 1,6-bisphosphate, glucose and fructose 6-phosphates, NADP, and ribose 5-phosphate . AcpA is distinct from histidine ACPs and purple ACPs, as well as class A, B, and C bacterial nonspecific ACPs . This protein shares regions of sequence similarity with the phosphocholine-preferring phospholipase C enzymes (

) from many of the same species.
Phospholipase C accessory protein PlcR (PLipase_C_acessory_PlcR)
Type: Family

The two phosphocholine-preferring phospholipase C enzymes (

) in Pseudomonas aeruginosa, include the hemolytic protein PlcH, which can hydrolyse sphingomyelin as well as phosphatidylcholine. This entry represents PlcR, an accessory protein for PlcH with which it forms a heterodimer. PlcR is required for the secretion of PlcH and affects both its enzymatic and hemolytic activities . The P. aeruginosa protein, is encoded immediately downstream of PlcH, but the equivalent proteins from various Burkholderia species are not.
RNA 3'-terminal phosphate cyclase type 1 (RNA3'_term_phos_cyc_type_1)
Type: Family

This entry represents the type 1 RNA 3'-terminal phosphate cyclases.

RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea. Type 1 RNA 3'-terminal phosphate cyclases (

) catalyse the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA:

ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate

The physiological function of the cyclase is not known, but the enzyme could be involved in the maintenance of cyclic ends in tRNA splicing intermediates or in the cyclisation of the 3' end of U6 snRNA .

A second subfamily of RNA 3'-terminal phosphate cyclases (type 2) that do not have cyclase activity have been identified in eukaryotes. They are localised to the nucleolus and are involved in ribosomal modification .
Cyanamide hydratase (Cyanamide_hydratase_HD)
Type: Family

These proteins are found mostly in the Ascomycota, a branch of fungi, and contain an HD domain typically found in metal-dependent phosphohydrolases. The only currently characterised protein in this entry, from the soil fungus Myrothecium verrucaria, is cyanamide hydratase (

), a zinc-containing homohexamer that adds water to the fertilizer cyanamide, a nitrile compound, to produce urea. Homologues are likely to be nitrile hydratases.
Cysteine desulfurase NifS, bacterial/archaeal (Cys_deSase_NifS_bac/arc)
Type: Family

This entry represents NifS, one of several related families of cysteine desulfurase involved in iron-sulphur (FeS) cluster biosynthesis. NifS is part of the NIF (nitrogen fixation) system, and is usually encoded with other nif genes involved in nitrogenase expression and nitrogen fixation. These proteins include a clade nearly always found in extended nitrogen fixation genomic regions, plus a second clade more closely related to the first than to IscS and also part of NifS-like/NifU-like systems. This entry does not cover a more distant clade found in the epsilonproteobacteria such as Helicobacter pylori, also named NifS in the literature. This clade is covered instead by

.
Cysteine desulfurase NifS, proteobacteria (Cys_deSase_NifS_proteobacteria)
Type: Family

This entry represents a NifS-like cysteine desulfurase, similar to the NifS protein of nitrogen-fixing bacteria, found almost exclusively within the epsilon division of the Proteobacteria. Like NifS, and unlike IscS, this protein is found as part of a system of just two proteins, a cysteine desulfurase and a scaffold, for iron-sulphur cluster biosynthesis. This protein is often annotated as NifS , so this designation was used.
Bicupin, oxalate decarboxylase/oxidase (Bicupin_oxalate_deCO2ase/Oxase)
Type: Family

Proteins in this entry are known as bicupins as they posses two copies of the cupin domain. Two different activities have so far been identified in this group of proteins; oxalate decarboxylase activity(

) and oxalate oxidase activity (

), although the latter has more often been found in distantly related monocupin (germin) proteins .
Alcohol dehydrogenase, iron-type, PsrA-like (ADH_Fe_PsrA-like)
Type: Family

This group of iron-containing alcohol dehydrogenases is found in genomic contexts indicating a role in the metabolism of phosphonates. Recurring neighboring proteins include phosphonopyruvate decarboxylase, phosphonoacetaldehyde hydrolase, and phosphonate ABC transporter subunits. Recently, it has been identified a member of this family, called PsrA (peroxidative stress-associated aldehyde reductase) which, together with BcnA and LcoA, is part of the peroxidation detoxification system that protects the bacterial cell envelope from lipid peroxyl radicals.