SII-SWORD/CoKE huggingface dataset:
Lycopene cyclase, beta/epsilon (Lycopene_cyclase_b/e)
Type: Family

Lycopene cyclases generate provitamin A carotenoids which are essential building blocks for cyclic xanthophylls involved in photosynthesis and regulatory networks. The cyclization of lycopene is the final step in carotenoid biosynthesis and may proceed via one of two pathways: the formation of a β-ring by beta-cyclase, or an ε-ring by epsilon-cyclase. Epsilon-cyclase adds only one ring, forming the monocyclic δ-carotene, whereas beta-cyclase introduces a ring at both ends of lycopene to form the bicyclic β-carotene . Lycopene cyclases are widely distributed across taxonomic groups and have structural diversity. Four partly related families of lycopene cyclases are known: CrtY, CrtL (β-ionone end group producing), CrtL (η-ionone end group producing) and CrtL (capsanthin/capsorubin synthase).

This family includes lycopene beta-and epsilon-cyclases, which are involved in the biosynthesis of carotenoids in bacteria and plants, and the related capsanthin capsorubin synthase (Ccs) from plants, which converts antheraxanthin or violaxanthin into capsanthin or capsorubin by a mechanism similar to lycopene cyclization. This family also includes neoxanthin synthase, which is involved in the synthesis of neoxanthin, the last product of carotenoid synthesis and a precursor of abscisic acid .
Citrate synthase, eukaryotic-type (Citrate_synthase_euk)
Type: Family

This entry includes both mitochondrial and peroxisomal forms of citrate synthase. Peroxisomal forms of the enzyme, recognised by the C-terminal targeting motif SKL, act in the glyoxylate cycle.

Citrate synthase

is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).
Shikimate dehydrogenase, AroM-type (Shikimate_DH_AroM-type)
Type: Domain

This entry represents a clade of shikimate-5-dehydrogenases found in Corynebacterium, Mycobacteria and fungi. The fungal sequences are pentafunctional proteins known as AroM which contain the central five seven steps in the chorismate biosynthesis pathway. The Corynebacterium and Mycobacterial sequences represent the sole shikimate-5-dehydrogenases in species which otherwise have every enzyme of the chorismate biosynthesis pathway.
Kynureninase (Kynureninase)
Type: Family

This entry describes kynureninase, it is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the hydrolytic cleavage of L-kynurenine to anthranilic acid and L-alanine. Kynurinine is a Trp breakdown product and a precursor for NAD. This reaction is a key step in the catabolism of L-tryptophan by Pseudomonas fluorescens and some other bacteria (1). In fungi and vertebrates, kynurenine is first hydroxylated to 3-hydroxykynurenine, which is the preferred substrate of kynureninase in those organisms, resulting in 3-hydroxyanthranilate and L-alanine .

Sequence alignment with other PLP-dependent enzymes indicated that kynureninase is in subgroup IVa of the aminotransferases, along with nifS, CsdB, and serine-pyruvate aminotransferase, which suggests that kynureninase has an aminotransferase fold .
Anthranilate synthase, bacteria (TrpE-G_bact)
Type: Family

This entry represents a small group of anthranilate synthases mainly from alpha proteobacteria and Nostoc (a cyanobacterium). Anthranilate synthase catalyses the first step in the pathway for the biosynthesis of tryprophan from chorismate. The genes involved in this enzymatic reaction are trpE and trpG, which encode component I and II of the anthranilate synthase. This group of proteins consists of a TrpE(G) fused protein .
Nif-specific regulatory protein (Nif-specific_regulatory_prot)
Type: Family

This entry represents NifA, a DNA-binding regulatory protein for nitrogen fixation. Not included in this group are: the homologue in Aquifex aeolicus (which lacks nitrogenase), transcriptional activators of alternative nitrogenases (VFe or FeFe instead of MoFe), and truncated forms.

In diazotrophic proteobacteria, the sigma54-dependent activator NifA activates transcription of the nif (nitrogen fixation) genes by a conserved mechanism common to members of the enhancer binding protein family. Although NifA proteins have similar domain structures, both transcriptional regulation of nifA expression and posttranslational regulation of NifA activity by oxygen and fixed nitrogen vary significantly from one organism to another. In Klebsiella pneumoniae and Azotobacter vinelandii, nifA is co-ordinately transcribed with a second gene, nifL, whose product inhibits NifA activity in response to oxygen and fixed nitrogen .
DNA-binding transcriptional regulator NtrC (Transcript_reg_NtrC)
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 Nitrogen regulatory protein C (NtrC), which is a bacterial enhancer-binding protein that activates the transcription of genes encoding enzymes required for nitrogen metabolism. It is phosphorylated by NtrB and interacts with sigma-54. One of the best studied examples is its activation of the gene glnA, which encodes the enzyme glutamine synthetase .
NtrC is composed of three domains . The 124 residue N-terminal domain is homologous to receiver domains of other response regulator proteins in two-component signal transduction systems . The 240 residue central domain of NtrC is homologous to a domain found in all activators of the sigma-54 RNA polymerase holoenzyme . The C-terminal domain has been indicated to contain the determinants necessary for both DNA-binding and dimerization of full-length NtrC.
Phosphoenolpyruvate transferase/2-phospho-L-lactate transferase (FbiA/CofD)
Type: Family

This entry includes 2-phospho-L-lactate transferase (CofD), which catalyses the transfer of the 2-phospholactate moiety from (2S)-lactyl-2-diphospho-5'-guanosine to 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO), and phosphoenolpyruvate transferase (FbiA) which catalyses the transfer of the phosphoenolpyruvate moiety from enoylpyruvoyl-2-diphospho-5'-guanosine (EPPG) to 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) with the formation of dehydro coenzyme F420-0 and GMP . F420 is a hydride carrier, important for energy metabolism of methanogenic archaea, as well as for the biosynthesis of other natural products, like tetracycline in Streptomyces. F420 and some of its precursors are also utilized as cofactors for enzymes, like DNA photolyase in Mycobacterium tuberculosis . F420 is found in methanogens, Mycobacteria, and several other lineages. This enzyme is characterised so far in Methanocaldococcus jannaschii (Methanococcus jannaschii) but appears restricted to F420-containing species and is predicted to carry out the same function in these other species.
Anthranilate synthase component I, archaeal type (Anthranilate_synth_I_arc_typ)
Type: Family

This model represents an archaeal clade of anthranilate synthase component I
enzymes. This enzyme (

) is responsible for the first step of tryptophan biosynthesis from chorismate. The Sulfolobus enzyme has been reported to be part of a gene cluster for Trp biosynthesis .
Para-aminobenzoate synthase (PabB_fungal)
Type: Family

This entry represents the fungal clade of para-aminobenzoate synthase, which acts on chorismate to form para-aminobenzoic acid (PABA), a precursor of folate.
Para-aminobenzoate synthase/anthranilate synthase, component I (Para-NH2Bz/anthranilate_synth)
Type: Family

This clade of sequences is more closely related to TrpE (anthranilate synthase,

,

,

) than to the better characterised group of PabB enzymes (

,

). This clade includes one characterised enzyme from Lactococcus and the conserved function across the clade is supported by these pieces of evidence: 1) all genomes with a member in this clade also have a separate TrpE gene, 2) none of these genomes contain an apparent PabB from any of the other PabB clades, 3) none of these sequences are found in a region of the genome in association with other Trp biosynthesis genes, 4) all of these genomes apparently contain most if not all of the steps of the folate biosynthetic pathway (for which PABA is a precursor). Many of the sequences are annotated as TrpE enzymes, however, we believe that all members of this clade are, in fact, PabB. The sequences from Bacillus halodurans and Bacillus subtilis, are also likely to be PabB enzymes, but are too closely related to TrpE to be separated at this time.
Gluconeogenesis factor (Gluconeogen_factor)
Type: Family

In Bacillus subtilis the gluconeogenesis factor is required for morphogenesis under gluconeogenic growth conditions. It is required for the correct localisation of penicillin-binding protein PBP1, and hence for displaying a normal rod shape .
Probable glutamyl-tRNA(Gln) amidotransferase subunit C, archaea (Glu-ADT_subunit_C_archaea)
Type: Family

This entry represents a family related to GatC, the third subunit of an enzyme for completing the charging of tRNA(Gln) by amidating the Glu-tRNA(Gln). The few known archaea that contain a member of this family appear to produce Asn-tRNA(Asn) by an analogous amidotransferase reaction. This protein is proposed to substitute for GatC in the charging of both tRNAs.
Pyruvate, phosphate dikinase (Pyruvate_phosphate_dikinase)
Type: Family

Pyruvate phosphate dikinase (PPDK, or pyruvate orthophosphate dikinase) is found in plants, bacteria and archaea. The amino acid sequence identity between bacterial and plant enzymes is high, and they are similar in sequence to other PEP-utilizing enzymes. PPDK catalyses the reversible conversion of ATP and pyruvate to AMP and PEP (phosphoenolpyruvate). In bacteria such as Clostridium symbiosum (Bacteroides symbiosus), PPDK uses Mg2+ and NH4+ ions as cofactors . The enzyme has three domains: the N- and C-terminal domains each have an active site centre that catalyses a different step in the reaction, and the middle domain has a carrier histidine residue that moves between the two active centres.

In plants, PPDK is localised predominantly in chloroplast stroma where it catalyses the rate-limiting step in the C4 photosynthetic pathway, namely the synthesis of PEP, which acts as the primary CO2 acceptor in C4 photosynthesis . PPDK activity in C4 plants is strictly regulated by light, its activity decreasing in darkness. This response is regulated by phosphorylation and dephosphorylation of the enzyme using ADP; such regulation is not seen in the bacterial form of the enzyme. PPDK is also found in C3 plants, but it is not known to have a photosynthetic role .
Hydroxymethylglutaryl-CoA synthase, eukaryotic (HMG_CoA_synthase_euk)
Type: Family

Hydroxymethylglutaryl-CoA synthase (

) catalyses the condensation of acetyl-CoA with acetoacetyl-CoA to produce HMG-CoA and CoA, the second reaction in the mevalonate-dependent isoprenoid biosynthesis pathway. HMG-CoA synthase contains an important catalytic cysteine residue that acts as a nucleophile in the first step of the reaction: the acetylation of the enzyme by acetyl-CoA (its first substrate) to produce an acetyl-enzyme thioester, releasing the reduced coenzyme A. The subsequent nucleophilic attack on acetoacetyl-CoA (its second substrate) leads to the formation of HMG-CoA .

HMG-CoA synthase occurs in eukaryotes, archaea and certain bacteria . In vertebrates, there are two isozymes located in different subcellular compartments: a cytosolic form that is the starting point of the mevalonate pathway (leads to cholesterol and other sterolic and isoprenoid compounds), and a mitochondrial form responsible for ketone body biosynthesis. HMG-CoA is also found in other eukaryotes such as insects, plants and fungi . In bacteria, isoprenoid precursors are generally synthesised via an alternative, non-mevalonate pathway, however a number of Gram-positive pathogens utilise a mevalonate pathway involving HMG-CoA synthase that is parallel to that found in eukaryotes .

This entry is specific for eukaryotic HMG-CoA synthase enzymes.
Poly(R)-hydroxyalkanoic acid synthase, class III, PhaE subunit (PHA_synth_III_E)
Type: Family

Poly(R)-hydroxyalkanoic acids (PHAs) function as carbon and energy storage polymers in many bacteria. This entry represents the PhaE subunit of the heterodimeric class (class III) of PHA synthases. The most common PHA is polyhydroxybutyrate but about 150 different constituent hydroxyalkanoic acids (HAs) have been identified in various species.
Poly(R)-hydroxyalkanoic acid synthase, class III, PhaC subunit (PHA_synth_III_C)
Type: Family

This entry represents the PhaC subunit of a heterodimeric form of polyhydroxyalkanoic acid (PHA) synthase. Excepting the PhaC of Bacillus megaterium (which needs PhaR), all members require PhaE (

) for activity and are designated class III. This enzyme builds ester polymers for carbon and energy storage that accumulate in inclusions, and both this enzyme and the depolymerase associate with the inclusions. Class III enzymes polymerise short-chain-length hydroxyalkanoates.
Esterase, PHB depolymerase (Esterase_phb)
Type: Family

This entry describes a group of lipases, including bacterial depolymerases for poly(3-hydroxybutyrate) (PHB) and related polyhydroxyalkanoates (PHA), as well as acetyl xylan esterases , and feruloyl esterases from fungi .

Putative esterase NocK from Nocardia uniformis also belongs to this protein family. This protein is part of the biosynthetic gene cluster for the beta-lactam antibiotic nocardicin A but its specific role is unknown .
Phasin, subfamily 1 (Phasin_subfam-1)
Type: Family

Phasins (or granule-associate proteins) are surface proteins found covering Polyhydroxyalkanoate (PHA) storage granules in bacteria. Polyhydroxyalkanoates are linear polyesters produced by bacterial fermentation of sugar or lipids for the purpose of storing carbon and energy, and are accumulated as intracellular granules by many bacteria under unfavorable conditions, enhancing their fitness and stress resistance . The layer of phasins stabilises the granules and prevents coalescence of separated granules in the cytoplasm and nonspecific binding of other proteins to the hydrophobic surfaces of the granules. For example, in Ralstonia eutropha (strain ATCC 17699/H16/DSM 428/Stanier 337) (Cupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337)), the major surface protein of polyhydroxybutyrate (PHB) granules is phasin PhaP1(Reu), which occurs along with three homologues (PhaP2, PhaP3, and PhaP4) that have the capacity to bind to PHB granules but are present at minor levels . These four phasins lack a highly conserved domain but share homologous hydrophobic regions.

This entry describes a group of phasins associated with polyhydroxyalkanoate (PHA) inclusions, the most common of which consist of polyhydroxybutyrate (PHB). However, the member from Magnetospirillum sp. (strain AMB-1) is called a magnetic particle membrane-specific GTPase.
ATPase, type I secretion system, PrtD-like (ATPase_T1SS_PrtD-like)
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. PrtD, an ABC transporter, is one of three proteins of the type I secretion apparatus, which assemble with PrtE and PrtF to form the complex required for protein secretion . Targeted proteins are not cleaved at the N terminus, but rather carry signals located toward the extreme C terminus to direct type I secretion.
Type I secretion membrane fusion protein, HlyD family (T1SS_HlyD)
Type: Family

Type I secretion is an ABC transporter that exports proteins, without cleavage of any signal sequence, from the cytosol to extracellular medium across both inner and outer membranes. The secretion signal is found in the C terminus of the transported protein. This entry represents the adaptor protein between the ATP-binding cassette (ABC) protein of the inner membrane and the outer membrane protein, and is called the membrane fusion protein. This entry selects a group of sequences closely related to HlyD ; it is defined narrowly and excludes, for example, colicin V secretion protein CvaA and multidrug efflux proteins.
Type I secretion outer membrane protein, TolC (T1SS_OMP_TolC)
Type: Family

Members of group of are outer membrane proteins from the TolC family within the RND (Resistance-Nodulation-cell Division) efflux systems. These proteins, unlike the NodT family, appear not to be lipoproteins. All are believed to participate in type I protein secretion, an ABC transporter system for protein secretion without cleavage of a signal sequence, although they may, like TolC, participate also in the efflux of smaller molecules as well . This family includes the well-documented examples TolC (Escherichia coli), PrtF (Erwinia), and AprF (Pseudomonas aeruginosa) .
RND efflux system, outer membrane lipoprotein, NodT (RND_efflux_OM_lipoprot_NodT)
Type: Family

Members of group are outer membrane lipoproteins from the NodT family of the RND (Resistance-Nodulation-cell Division) type efflux systems. These proteins work with an inner membrane ABC transporter ATPase and an adapter called a membrane fusion protein. Most members of this family are likely to export primarily small molecules rather than proteins, but are related to the type I protein secretion outer membrane proteins TolC and PrtF.
ATPase, type I secretion system, HlyB (ATPase_T1SS_HlyB)
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 entry contains 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.
Bacteriocin-type signal sequence (Bacteriocin_signal_seq)
Type: Conserved_site

Bacteriocins are bacterial peptide products toxic to closely related bacteria. This entry represents a short N-terminal region up to the GG cleavage motif. Processing, to remove this bacteriocin leader peptide, occurs together with export by an ABC transporter.
Polyhydroxyalkanoate synthesis repressor PhaR (PHA_reg_PhaR)
Type: Family

This entry identifies the polyhydroxyalkanoate synthesis repressor, PhaR and related proteins. The gene for PhaR regulatory protein is found in general near other genes encoding proteins associated with polyhydroxyalkanoate (PHA) granule biosynthesis and utilization. It is found to be a DNA-binding homotetramer that is also capable of binding short chain hydroxyalkanoic acids and PHA granules. PhaR may regulate the expression of itself, of the phasins that coat granules, and of enzymes that direct carbon flux into polymers stored in granules . The C-terminal region is poorly conserved in this family of proteins.
N-acetyl-gamma-glutamyl-phosphate reductase, type 2 (AGPR_type-2)
Type: Family

N -Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymatic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by L-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined .

The pathway from glutamate to arginine is:

NAGS; N-acetylglutamate synthase (

) (glutamate to N-acetylglutamate)

NAGK; N-acetylglutamate kinase (

) (N-acetylglutamate to N-acetylglutamate-5P)

N-acetyl-gamma-glutamyl-phosphate reductase (

) (N-acetylglutamate-5P to N-acetylglumate semialdehyde)

Acetylornithine aminotransferase (

) (N-acetylglumate semialdehyde to N-acetylornithine)

Acetylornithine deacetylase (

) (N-acetylornithine to ornithine)

Arginase (

) (ornithine to arginine)

N-acetyl-gamma-glutamyl-phosphate reductase (

) (AGPR, NAGSA dehydrogenase) is the enzyme that catalyses the third step in the biosynthesis of arginine from glutamate, the NADP-dependent reduction of N-acetyl-5-glutamyl phosphate into N-acetylglutamate 5-semialdehyde. In bacteria it is a monofunctional protein of 35 to 38kDa (gene argC), while in fungi it is part of a bifunctional mitochondrial enzyme (gene ARG5,6, arg11 or arg-6) which contains a N-terminal acetylglutamate kinase (

) domain and a C-terminal AGPR domain. In the Escherichia coli enzyme, a cysteine has been shown to be implicated in the catalytic activity, and the region around this residue is well conserved.

This entry represents the less common of two related families of N-acetyl-gamma-glutamyl-phosphate reductase, an enzyme catalyzing the third step or Arg biosynthesis from Glu. The two families differ by phylogeny, similarity clustering, and gap architecture in a multiple sequence alignment.
Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase (Lipid_A_LpxA)
Type: Family

This entry describes LpxA, an enzyme for the biosynthesis of lipid A, a component of lipopolysaccharide (LPS) in the outer membrane outer leaflet of most Gram-negative bacteria. Some differences are found between lipid A of different species, but this protein represents the first step (from UDP-N-acetyl-D-glucosamine) and appears to be conserved in function . Proteins from this family contain many copies of the bacterial transferase hexapeptide repeat .