SII-SWORD/CoKE huggingface dataset:
UDP-2,3-diacylglucosamine hydrolase (UDP-diacylglucosamine_Hdrlase)
Type: Family

This entry represents LpxH, or UDP-2,3-diacylglucosamine hydrolase (or diphosphatase), which is an essential enzyme in Escherichia coli that catalyses the fourth step in lipid A biosynthesis. This reaction involves pyrophosphate bond hydrolysis of the precursor UDP-2,3-diacylglucosamine to yield 2,3-diacylglucosamine 1-phosphate and UMP . Several Gram-negative bacteria have homologues of LpxH and/or LpxH2, while others have only distant orthologues of LpxH or LpxH2, or lack these enzymes altogether .
Imidazole glycerol phosphate synthase, subunit H (Imidazole-glycPsynth_HisH)
Type: Family

Imidazole glycerol phosphate synthetase (IGPS) is a key metabolic enzyme, which links amino acid and nucleotide biosynthesis: it catalyses the closure of the imidazole ring within histidine biosynthesis (fifth step), and provides the substrate for de novo purine biosynthesis. IGPS consists of two different subunits: HisH, a glutamine amidotransferase (glutaminase), and HisF, a synthase (cyclase). HisH functions to provide a source of nitrogen, which is required for the synthesis of histidine and purines. In the HisH glutaminase reaction, the hydrolysis of glutamine yields ammonia, which is then used by HisF in the subsequent synthase reaction. The X-ray structure of the HisH/HisF heterodimer of IGPS reveals a putative tunnel for the transfer of ammonia from HisH to HisF via a (β-α)8 barrel fold within HisF that abuts HisH . Ammonia tunnels connect the glutaminase and synthase active sites.

HisH belongs to a large group of enzymes found in diverse and fundamental anabolic pathways. These enzymes share a common domain, referred to as the type-I glutamine amidotransferase (GATase) domain, which can occur either as single polypeptides (as with HisH) or as domains of large multifunctional proteins.
Histidinol phosphate phosphatase, HisJ (Histidinol_P_phosphatase_HisJ)
Type: Family

This entry represents the histidinol phosphate phosphatase, HisJ of Bacillus subtilis, and related proteins from a number of species within a larger family of phosphatases in the PHP hydrolase family. HisJ catalyses the penultimate step of histidine biosynthesis but shows no homology to the functionally equivalent sequence in Escherichia coli, a domain of the bifunctional HisB protein. Note, however, that many species have two members and that Clostridium perfringens, predicted not to make histidine, has five members of this family; not all members of this family may act on HisJ.
Phosphoribosylformylglycinamidine synthase, FGAM (FGAM_synthase)
Type: Family

This entry represents a single-molecule form of phosphoribosylformylglycinamidine synthase, also called FGAM synthase, an enzyme of purine de novo biosynthesis, which represent a second clade of the enzymes found in Clostridia, Bifidobacteria and Streptococcus species. This enzyme performs the fourth step in IMP biosynthesis (the precursor of all purines) from PRPP.
Nitrogenase vanadium-iron protein, alpha chain (Nase_V-Fe_asu)
Type: Family

This entry represents the alpha chain of the vanadium-containing component of the vanadium-iron nitrogenase compound I. The complex also includes a second alpha chain, two beta chains and two delta chains. Component I interacts with compound II also known as the iron-protein which transfers electrons to compound I where the catalysis occurs.
Nitrogenase component 1, alpha chain (Nase_comp1_asu)
Type: Family

This entry represents all three varieties (Fe-Fe, Mo-Fe and V-Fe) of the component I alpha chain of nitrogenase.

Nitrogenase (

) is the enzyme system responsible for biological nitrogen fixation. Nitrogenase is an oligomeric complex which consists of two components: component 2 is an homodimer of an iron-sulphur protein, while component 1 which contains the active site for the reduction of nitrogen to ammonia exists in three different forms: the molybdenum-iron containing protein (MoFe) is a hetero-tetramer consisting of two pairs of alpha (nifD) and beta (nifK) subunits; the vanadium-iron containing protein (VFe) is a hexamer of two pairs each of alpha (vnfD), beta (vnfK), and delta (vnfG) subunits; the third form seems to only contain iron and is a hexamer composed of alpha (anfD), beta (anfK), and delta (anfG) subunits. The alpha and beta chains of the three types of component 1 are evolutionary related and they are also related to proteins nifE and nifN, which are most probably involved in the iron-molybdenum cofactor biosynthesis .
CRISPR-associated protein, Csd1-type (CRISPR-assoc_prot_Csd1-typ)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the Csd1 (CRISPR/Cas Subtype DVULG protein 1) family of Cas proteins, which tend to be found near CRISPR repeats of the DVULG subtype of CRISPR/Cas locus. The species range for this subtype, so far, is exclusively bacterial and mesophilic, although CRISPR loci in general are particularly common among archaea and thermophilic bacteria.
CRISPR-associated protein, Csn2-type (CRISPR-assoc_prot_Csn2-typ)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the Csn2 family of Cas proteins, which are found only in CRISPR-containing species, near other CRISPR-associated proteins (cas), as part of the NMENI subtype of CRISPR/Cas loci. The species range so far for this subtype is animal pathogens and commensals only. This protein is present in some but not all NMENI CRISPR/Cas loci.
CRISPR-associated protein, CasD (CRISPR-assoc_prot_CasD)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents CasD proteins, which includes CT1976 from Chlorobium tepidum. It shares a small N-terminal homology region with members of several other CRISPR/Cas subtypes; the families that share this region are denoted Cas5. The family is designated Subtype I-E, for CRISPR-associated protein Cas5, Ecoli subtype. CasD is a component of Cascade, which participates in CRISPR interference, the third stage of CRISPR immunity. Cascade binds both crRNA and in a sequence-specific manner negatively supercoiled dsDNA target. This leads to the formation of an R-loop in which the crRNA binds the target DNA, displacing the noncomplementary strand. Cas3 is recruited to Cascade, nicks target DNA and then unwinds and cleaves the target, leading to DNA degradation and invader neutralization .
CRISPR-associated protein, CT1975 (CRISPR-assoc_prot_CT1975)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents a family of Cas proteins, which includes CT1975 of Chlorobium tepidum. This family is also known as Cse4/CasC and Cas7 Type I-E .
CRISPR-associated protein, Csm2 Type III-A (CRISPR-assoc_prot_Csm2_III-A)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents Csm2 Type III-A, a family of CRISPR-associated proteins. These proteins are found adjacent to a characteristic short, palindromic repeat cluster termed CRISPR, a probable mobile DNA element. This family is also known as TM1810/Csm2 .
CRISPR-associated protein Cas2 subtype (CRISPR-assoc_prot_Cas2_sub)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents a minor branch of the Cas2 family of CRISPR-associated proteins. Cas2 is one of four protein families (Cas1 to Cas4) that are associated with CRISPR elements and always occur near a repeat cluster, usually in the order cas3-cas4-cas1-cas2. The function of Cas2 (and Cas1) is unknown. Cas3 proteins appear to be helicases while Cas4 proteins resemble RecB-type exonucleases, suggesting that these genes are involved in DNA metabolism or gene expression .
CRISPR-associated protein, Cas5a type (CRISPR-assoc_prot_Cas5a-typ)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents a minor family of CRISPR-associated proteins, which includes MJ0382 from Methanocaldococcus jannaschii (Methanococcus jannaschii). These proteins are found adjacent to a characteristic short, palindromic repeat cluster termed CRISPR, a probable mobile DNA element. The family is designated Cas5a, for CRISPR-associated protein Cas5, Apern subtype.
CRISPR-associated protein Cas7/Cst2/DevR (CRISPR-assoc_Cas7/Cst2/DevR)
Type: Family

This entry represents a family of Cas proteins, including the Cas7 (also known as DevR) protein from Myxococcus xanthus. Cas7 is a key regulator of development, and mutants of DevR are incapable of fruiting body development . The expression of Cas7 appears to be regulated through a number of means, including both location and autorepression.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR pre-crRNA endoribonuclease Cas5d (CRISPR-assoc_prot_Cas5d)
Type: Family

This entry represents CRISPR pre-crRNA endoribonuclease Cas5d, which is a sequence-specific endonuclease that cleaves pre-crRNA at G21 into mature crRNA .

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR-associated endoribonuclease Cas6 (CRISPR-assoc_prot_Cas6)
Type: Family

This entry represents Cas6, a broadly distributed, highly divergent Cas family, including TM1814 from Thermotoga maritima. TM1814 contains a C-terminal motif GXGXXXXXGXG, where the each X between two Gly is hydrophobic and the spacer XXXXX contains (usually) one Arg or Lys. Members of this protein family are found associated with several different CRISPR/cas system subtypes. Cas6 proteins share the ability to recognise and cleave a single phosphodiester bond in a short repeated sequence of the pre-crRNA transcript .

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR type I-A/APERN-associated protein Csa5 (CRISPR-assoc_Cas5)
Type: Family

This entry represents a minor family of Cas protein found in the (all archaeal) APERN subtype of CRISPR/Cas locus, so the family is designated Csa5, for CRISPR/Cas Subtype Protein 5
.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Amidase, carbamoylase-type (Amidase_Cbmase)
Type: Family

L-carbamoylases (N-carbamoyl-L-amino-acid amidohydrolases) hydrolyze the amide bond of the carbamoyl group in L-N-carbamoyl-amino acids . They are important industrial enzymes widely used for the production of optically pure amino acids due to their stereospecificity. Furthermore, their substrate promiscuity allows their use in different multienzymatic processes .

Also included in this family is allantoate amidohydrolase (allantoate deiminase), which catalyzes the conversion of allantoate to (S)-ureidoglycolate, one of the crucial alternate steps in purine metabolism , and yeast N-carbamyl-beta-alanine amidohydrolase (betaAS, beta-alanine synthase) .

These enzymes are members of the broader family of amidases.
N-acyl-L-amino-acid amidohydrolase (N-acyl_aa_amidohydrolase)
Type: Family

This entry represents a family of eukaryotic N-acyl-L-amino-acid amidohydrolase (

) is a homodimeric zinc-binding mammalian enzyme that catalyzes the hydrolysis of N-alpha-acylated amino acids except L-aspartic acid . These enzymes are listed as non-peptidase homologues in MEROPS peptidase family M20A (clan MH). Porcine AcyI is also shown to deacetylate certain quorum-sensing N-acylhomoserine lactones, while the rat enzyme has been implicated in degradation of chemotactic peptides of commensal bacteria. Prokaryotic arginine synthesis usually involves the transfer of an acetyl group to glutamate by ornithine acetyltransferase in order to form ornithine. However, Escherichia coli acetylornithine deacetylase (acetylornithinase, ArgE) (EC 3.5.1.16) catalyzes the deacylation of N2-acetyl-L-ornithine to yield ornithine and acetate. Phylogenetic evidence suggests that the clustering of the arg genes in one continuous sequence pattern arose in an ancestor common to Enterobacteriaceae and Vibrionaceae, where ornithine acetyltransferase was lost and replaced by a deacylase .
CRISPR-associated protein, Cmr5 (CRISPR-assoc_prot_Cmr5)
Type: Family

This entry represents a family of Cas proteins as represented by TM1791.1 from Thermotoga maritima. This family of Cas proteins are found in both archaeal and bacterial species.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Peptidase M20B, tripeptide aminopeptidase (Peptidase_M20B)
Type: Family

This entry represents metallopeptidases belonging to MEROPS peptidase family M20 (clan MH), subfamily M20B. They are tripeptide aminopeptidases commonly known as Peptidase T. PepT acts only on tripeptide substrates. It catalyses the release of N-terminal amino acids with hydrophobic side chains from tripeptides with high specificity; dipeptides, tetrapeptides or tripeptides with the N terminus blocked are not cleaved .

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
Peptidase M20B, peptidase T-like (PepT-like)
Type: Family

This entry represents a clade of enzymes closely related to Peptidase T, an aminotripeptidase found in bacteria .
CRISPR-associated CARF protein Csa3 (Csa3)
Type: Family

This entry represents CRISPR locus-related putative DNA-binding protein Csa3 in archaea and bacteria. These proteins are associated with CRISPR loci. The C-terminal region of this protein family is homologous to DNA-binding helix-turn-helix domains with predicted transcriptional regulatory activity .

Csa3 proteins consist of two domains that intertwine to form a homodimer. The N-terminal domain (also known as CARF domain) is a unique variation on the nucleotide-binding domain, and it is essential for dimer formation. It is composed of a mixed β-sheet flanked on both sides with α-helices . This domain contains two conserved sequence motifs [(D/N)-X-(S/T)-X3-(R/K) and L-X(2)-G-h-R] that map to a 2-fold symmetric pocket on the dimer axis. It has been shown that this pocket binds cyclic tetra-adenylate (cA4). The C-terminal domain is structurally similar to MarR-like winged helix-turn-helix domains and is involved in DNA recognition.
Ornithine aminotransferase (Orn_aminotrans)
Type: Family

Ornithine aminotransferase catalyses the conversion of L-ornithine and a 2-oxo acid to L-glutamate 5-semialdehyde and an L-amino acid. This enzyme is found in low-GC bacteria, where it is responsible for the fourth step in arginine biosynthesis, and in the mitochondrial matrix of eukaryotes, where it controls L-ornithine levels in tissues. In human hereditary ornithine aminotransferase deficiency, the elevated levels of intraocular concentrations of ornithine are responsible for gyrate atrophy, which affects the CNS and peripheral nervous system .
Type III-B CRISPR module-associated protein Cmr3 (CRISPR-Cmr3_IIIB)
Type: Family

This entry represents a highly divergent family of Cas proteins found in at least ten different archaeal and bacterial species. This family includes TM1793 from Thermotoga maritima.

Cmr3 folds into two structural domains that both structurally resemble a ferredoxin-like fold, with a four-stranded antiparallel β-sheet buttressed by one or two α-helices . The structural studies of S. islandicus Cmr-β revealed that the 3' antitag of the target RNA activates different configurations in a unique loop of the Cmr3 subunit. This acts as an allosteric sensor signaling of the self- versus non-self-recognition .

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Transcriptional regulator SarA/Rot domain (SarA/Rot_dom)
Type: Domain

This entry represents a domain found in a family of transcriptional regulatory proteins in Staphylococcal species, including SarA and Rot. Some members contain two tandem copies of this region. This family is related to the MarR transcriptional regulator family,

.

SarA is a global regulator with both positive and negative effects that controls expression of several virulence factors and biofilm formation process in a cell density-dependent manner .
Amino-acid N-acetyltransferase (NH2A_AcTrfase)
Type: Family

This entry represents amino-acid N-acetyltransferase or N-acetylglutamate synthase, which is the product of the argA gene and the first enzyme in arginine biosynthesis. This enzyme displays more diversity between bacteria, fungi and mammals than other enzymes in arginine metabolism, and N-acetylglutamate itself can have different roles in different taxonomic groups: in prokaryotes, lower eukaryotes and plants it is the first intermediate in arginine biosynthesis, while in vertebrates it is an allosteric cofactor for the first enzyme in the urea cycle . In bacteria, arginine can regulate ornithine biosynthesis via a feedback inhibition mechanism . This enzyme may also act on aspartate.
Acetylornithine deacetylase ArgE (AcOrn-deacetyl)
Type: Family

Acetylornithine deacetylase (ArgE, also known as acetylornithinase, AO or N2-acetyl-L-ornithine amidohydrolase) catalyses the conversion of N-acetylornithine to ornithine, which can then be incorporated into the urea cycle for the final stage of arginine synthesis. The substrate specificity of ArgE is quite broad; several alpha-N-acyl-L-amino acids can be hydrolysed, including alpha-N-acetylmethionine and alpha-N-formylmethionine . ArgE shares significant sequence homology and biochemical features, and possibly a common origin, with glutamate carboxypeptidase (CPG2) and succinyl-diaminopimelate desuccinylase (DapE), and aminoacylase I (ACY1), having all metal ligand binding residues conserved .
CRISPR system endoribonuclease Csx1 (CRISPR_Csx1)
Type: Family

This entry represents a family of Cas proteins including CRISPR system endoribonuclease Csx1. This family was previously known as CRISPR-associated protein, MJ1666 family.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR-associated protein, TM1791 (CRISPR-assoc_prot_TM1791)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This family represents a family of Cas proteins that includes TM1791. This family is both closely related to and frequently encoded next to the TM1792 family of Cas proteins. The two proteins are fused in an example from Methanopyrus kandleri (

), where it is describes as a predicted component of a thermophile-specific DNA repair system containing contains two domains of the RAMP family .
CRISPR-associated protein Csm5 (CRISPR-assoc_Csm5)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

Type III complexes share the Cas10 subunit but are subclassifed as type IIIA
(CSM) and type IIIB (CMR), depending on their specificity for DNA or RNA targets, respectively . This family represents the CRISPR system CMS protein Csm5.
Succinyl-diaminopimelate desuccinylase, DapE (Succinyl-DAP_deSuclase_DapE)
Type: Family

Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways .

There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different .

The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria.

The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified.

The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana.

The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum.

Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.

This entry represents a clade of succinyl-diaminopimelate desuccinylases from actinobacteria (high-GC Gram-positives) and is based on the characterisation of the enzyme from Corynebacterium glutamicum (Brevibacterium flavum) . This enzyme is involved in the biosynthesis of lysine, and is related to the enzyme acetylornithine deacetylase and other amidases and peptidases. They are classified as non-peptidases homologues belonging to MEROPS peptidase family M20A