SII-SWORD/CoKE huggingface dataset:
Phosphoserine aminotransferase (Pser_aminoTfrase)
Type: Family

Phosphoserine aminotransferase (PSAT) is involved in serine biosynthesis . The enzyme catalyses the reversible conversion of 3-phosphohydroxypyruvate to L-phosphoserine. PSAT from Escherichia coli has been shown to be a homodimer of Mr79,000 with a conserved lysine that binds covalently to pyridoxal phosphate (PLP). PSAT is a vitamin B6-dependent enzyme and belongs to the alpha family of PLP enzymes. PSAT is also classified as a member of the aspartate aminotransferase family of PLP enzymes . According to the structural classification of PLP-dependent enzymes , PSAT belongs to the pyridoxal phosphate (PLP)-dependent aspartate aminotransferase superfamily (fold I), where it is allocated to a separated subclass. The mechanism of action in all these enzymes is similar: PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which, depending on the reaction, is the substrate in four kinds of reactions: transamination (movement of amino groups), racemization (redistribution of enantiomers), decarboxylation (removing COOH groups), and various side-chain reactions depending on the enzyme involved.
Pup--protein ligase (Pup_ligase)
Type: Family

Pupylation is a novel protein modification system found in some bacteria . This entry represents a family of proteins involved in this system. Pup ligases, such as PafA, conjugate the prokaryotic ubiquitin-like protein Pup to lysine residues in target proteins, marking them for degradation by the proteasome . It has been suggested that proteins in this entry are related to gamma-glutamyl-cysteine synthetases .
ParB-related, ThiF-related cassette, protein B (PRTRC_protein-B)
Type: Family

This entry contains a novel genetic system characterised by six major proteins, including a ParB homologue and a ThiF homologue. It is designated PRTRC, or ParB-Related, ThiF-Related Cassette. This protein family is designated protein B.
ATP-dependent protease subunit HslV (ATP-dep_Prtase_HsIV_su)
Type: Family

ATP-dependent protease complexes are present in all three kingdoms of life, where they rid the cell of misfolded or damaged proteins and control the level of certain regulatory proteins. They include the proteasome in Eukaryotes, Archaea, and Actinomycetales and the HslVU (ClpQY, clpXP) complex in other eubacteria. Genes homologues to eubacterial HslU (ClpY, clpX) have also been demonstrated in to be present in the genome of trypanosomatid protozoa .

The prokaryotic ATP-dependent proteasome is coded for by the heat-shock locus VU (HslVU). It consists of HslV, a peptidase, and HslU (

), the ATPase and chaperone belonging to the AAA/Clp/Hsp100 family. The crystal structure of Thermotoga maritima HslV has been determined to 2.1-A resolution. The structure of the dodecameric enzyme is well conserved compared to those from Escherichia coli and Haemophilus influenzae .

This entry represents the HslV peptidase subunit of the ATP-depdendent HSIVU protease complex found in bacteria and some lower eukaryotes.
ParB-related, ThiF-related cassette, protein F (PRTRC_protein-F)
Type: Family

This entry contains a novel genetic system characterised by seven (usually) major proteins including a ParB homologue and a ThiF homologue. It is commonly found on plasmids or in bacterial chromosomal regions near phage, plasmid or transposon markers. It is most common among the beta Proteobacteria. It has been named the system PRTRC, or ParB-Related, ThiF-Related Cassette. This family is designated protein F, and it is the most divergent of the families.
Glycerol-3-phosphate O-acyltransferase/Dihydroxyacetone phosphate acyltransferase (GPAT/DHAPAT)
Type: Family

This entry represents the Glycerol-3-phosphate O-acyltransferase/dihydroxyacetone phosphate acyltransferase (GPAT/DAPAT) family.

This entry includes PlsB, a GPAT from E. coli in which membrane synthesis depends on allosteric control of this enzyme. PlsB regulation plays an important role in the phospholipid synthesis pathway and is part of the response to certain stress signals . In many other bacteria, PlsB is not found, and appears to be replaced by a two enzyme system for 1-acyl-glycerol-3-phosphate biosynthesis, the PlsX/Y system

.

GPATs are classified into four isoforms in mammals; GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, whereas GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane . This entry includes the mitochondrial isoform, GPAT1 and GPAT2.

Dihydroxyacetonephosphate acyltransferase (DHAPAT) catalyses the first step in the biosynthesis of ether phospholipid plasmalogen, and may play also a significant role in nonether glycerolipid biosynthesis . In humans, mutations in DHAPAT results in the genetic disorder rhizomelic chondrodysplasia punctata type 2, characterised by rhizomelic shortening of femur and humerus, cataract,and severe mental retardation .
Conserved hypothetical protein CHP03879, regulatory domain, putative (CHP03879_regulat_dom_put)
Type: Domain

This entry represents a domain shared by two different protein families of unknown function. These proteins are regularly encoded next to their corresponding putative partner family, a probable regulatory protein with homology to KaiC. By implication, therefore, proteins in this entry may also be involved in sensory transduction and/or regulation.
VPDSG-CTERM protein sorting domain (VPDSG_CTERM)
Type: Domain

The PEP-CTERM/exosortase system has been previously identified through in silico analysis . This entry describes a PEP-CTERM-like variant C-terminal protein sorting signal, as found at the C terminus of twenty otherwise unrelated proteins in Verrucomicrobiae bacterium DG1235. The variant motif, VPDSG, seems an intermediate between the VPEP motif (

) of typical exosortase systems and the classical LPXTG of sortase in Gram-positive bacteria .
ParB-related, ThiF-related cassette, protein C (PRTRC_protein-C)
Type: Domain

This entry represents a novel genetic system which is characterised by six major proteins, one of which is a ParB and ThiF homologue designated PRTRC (ParB-Related,ThiF-Related Cassette). This PRTRC system c protein is often found on plasmids.
Luciferase-like monooxygenase Atu2307-like (LLM_Atu2307-like)
Type: Family

This entry represents a related group of prokaryotic proteins of unknown function within the luciferase-like monooxygenase (LLM) superfamily, including Atu2307 from Agrobacterium tumefaciens (

), whose crystal structure has been solved. As most proteins in this entry are from species incapable of synthesising coenzyme F420, they are likely to use FMN as a cofactor.
Bacteriocin biosynthesis, cyclodehydratase domain (Bacteriocin_synth_cyclodeHase)
Type: Domain

A subset of microcins has been recently described in which the amino acid side chains of cysteine, serine and threonine from a ribosomally produced precursor undergo heterocyclization to generate a product with thiazole or (methyl)oxazole moieties. This small bacteriocins are called TOMMs (thiazole/oxazole-modified microcins). A trimeric complex is reponsible for the formation of these heterocycle-containing metabolites, consisting of a zinc-tetrathiolate containing cyclodehydratase, a flavin mononucleotide-dependent dehydrogenase and a docking scaffold protein.

This entry represents a ThiF-like domain of a fusion protein found in clusters associated with the production of TOMMs . This domain is thought to act as a cyclodehydratase, as do members of the SagC family modelled by

.
Conserved hypothetical protein CHP03843 (CHP03843)
Type: Family

This HMM represents a protein family largely restricted to the Actinobacteria (high-GC Gram-positives), although it is also found in the Chloroflexi. Distant similarity to the phosphatidylinositol 3- and 4-kinase is suggested by the matching of some members to

.
Integrating conjugative element protein, PFL4693 (Integrating-conj_element)
Type: Family

Members of this protein, such as PFL_4693 from Pseudomonas fluorescens Pf-5 belong to extended genomic regions that appear to be spread by conjugative transfer. Most members have a predicted N-terminal signal sequence. The function is unknown.
Lantibiotic protection ABC transporter permease subunit, MutG family (ABC-transptr_permeasesu)
Type: Family

This entry includes lantibiotic ABC transporter permease subunit MutG which is a highly hydrophobic, integral membrane protein, and part of the bacitracin ABC transport system that confers resistance to the Gram-positive bacteria in which this system operates, specifically to lantibiotic mutacin. This protein transports mutacin to the surface and expels it from the membrane. Lantibiotics are small peptides, produced by Gram-positive bacteria, which are ribosomally-synthesized as pre-peptides and act by disrupting membrane integrity. Genes encoding the lantibiotic ABC transporter subunits are highly organized in operons containing all the genes required for maturation, transport, immunity, and synthesis . This protein family is largely restricted to gallidermin-family lantibiotic cassettes, but also include orphan transporter cassettes in species that lack candidate lantibiotic precursor and synthetase genes . Members of this group of proteins are predominantly found in Firmicutes and some species of Actinobacteria.
Large ribosomal subunit protein P1, archaea (Ribosomal_P1_arc)
Type: Family

This entry represents the large ribosomal subunit protein P1 found in the the archaeal ribosome.

Archaeal L12 is functionally equivalent to L7/L12 in bacteria and the P1 and P2 proteins in eukaryotes. L12 is homologous to P1 and P2 but is not homologous to bacterial L7/L12. It is located in the L12 stalk, with proteins L10, L11, and 23S rRNA. In several mesophilic and thermophilic archaeal species, the binding of 23S rRNA to protein L11 and to the L10/L12p pentameric complex was found to be temperature-dependent and cooperative .
Proteasome, alpha subunit, bacterial (Proteasome_asu_bac)
Type: Family

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of α/β/β/α subunits. There are seven different alpha subunits and seven different beta subunits . Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like" or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") . The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.

Members of this entry are the alpha subunit of the 20S proteasome as found in Actinobacteria such as Mycobacterium, Rhodococcus, and Streptomyces. In most Actinobacteria (an exception is Propionibacterium acnes), the proteasome is accompanied by a system of tagging proteins for degradation with Pup.
CRISPR-associated protein, CsaX (CRISPR-assoc_prot_CsaX)
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 comprises of a minor CRISPR-associated protein. So far, members are only found in the context of the (strictly archaeal) Apern subtype of CRISPR/Cas system, and is further restricted to the Sulfolobales, including Metallosphaera sedula DSM 5348 and multiple species of the genus Sulfolobus.
Conjugative transposon, TraN (Conjug_transposon_TraN)
Type: Family

This entry represents the TraN protein, which is encoded by transfer region genes of conjugative transposons of Bacteroides. This protein is related to conjugative transfer proteins VirB9 and TrbG of Agrobacterium Ti plasmids.
Transcription regulator, NtcA (Tscrpt_reg_NtcA)
Type: Family

Proteins of this entry, found in the cyanobacteria, are the global nitrogen regulator NtcA. This DNA-binding transcriptional regulator is required for expressing many different ammonia-repressible genes. The consensus NtcA-binding site is GTA(N8)TAC .
Polyphosphate:nucleotide phosphotransferase, PPK2 (PPK2-rel_1)
Type: Family

Proteins in this entry belong to the polyphosphate kinase 2 (PPK2) family, which is not related in sequence to PPK1. While PPK1 tends to act in the biosynthesis of polyphosphate, or poly(P), members of the PPK2 family tend to use the terminal phosphate of poly(P) to regenerate ATP or GTP from the corresponding nucleoside diphosphate, or ADP from AMP as is the case with polyphosphate:AMP phosphotransferase (PAP). Members of this protein family use poly(P) as a donor to convert both AMP to ADP and ADP to ATP . AMP/ADP-polyphosphate phosphotransferase from Meiothermus ruber can also use GMP, CMP, UMP, GDP, CDP and UDP .
Integral membrane protein YjbE (Integral_membrane_YjbE)
Type: Family

This entry represents highly hydrophobic proteins that are commonly preceded by a structured RNA element called the yybP-ykoY leader or SraF, which may serve as a riboswitch. From the larger group of TerC homologues (

), this entry contains protein YjbE from Bacillus subtilis. A transport function is proposed.
Phosphoesterase, putative (Phosphoesterase_putative)
Type: Family

Proteins in this entry contain

(calcineurin-like phosphoesterase), a domain largely defined by small motifs of metal-chelating residues.
Conjugative transfer ATPase (Conjug_Trfer_ATPase)
Type: Family

This entry represents predicted ATP-binding proteins apparently associated with DNA conjugal transfer. They are found both in plasmids and in bacterial chromosomal regions that appear to derive from integrative elements such as conjugative transposons. More distant homologues, outside the scope of this entry, include type IV secretion/conjugal transfer proteins such as TraC, VirB4 and TrsE.
Integrating conjugative element, PFGI-1, ParB (ICE_PFGI_1_ParB)
Type: Domain

Proteins in this entry carry the ParB-type nuclease domain and are found in integrating conjugative elements (ICE) in the same class as PFGI-1 of Pseudomonas fluorescens Pf-5.
Sortase system response regulator (Response_regulator)
Type: Family

This entry describes a group of DNA-binding response regulator proteins that associate with histidine kinase (

) to form a two-component system. This system co-occurs with a proteobacterial variant form of the protein sorting transpeptidase called sortase (

), and a single target protein for the sortase.
DEAD/DEAH-box helicase, putative, actinobacteria (Helicase_put_actinobac)
Type: Family

A conserved gene neighbourhood widely spread in the Actinobacteria contains this uncharacterised DEAH-box family helicase. The operons are similar to operons encoding type II secretion and pilus formation proteins. The context suggests that this helicase may play a role in conjugal transfer of DNA.
Synaptic vesicle protein SV2 (SV2)
Type: Family

SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A and SV2B) and one minor isoform (SV2C) that resemble transporter proteins. SV2B knockout mice are phenotypically normal while SV2A-and SV2A/SV2B double knockout mice exhibit severe seizures and die postnatally. Without SV2 proteins, presynaptic Ca
2+
accumulation during consecutive action potentials causes abnormal increases in neurotransmitter release that destabilise synaptic circuits and induce epilepsy .
Ribosomal protein eS8/ribosomal biogenesis NSA2 (Ribosomal_Se8/biogenesis_NSA2)
Type: Family

This entry represents the small ribosomal subunit protein eS8 from archaea and eukaryotes , which consists of a number of proteins with either about 220 amino acids (in eukaryotes) or about 125 amino acids (in archaea).

This entry also contains proteins annotated as NSA2, which are though to be involved in ribosomal biogenesis of the 60S ribosomal subunit, having a role in the quality control of pre-60S particles. They are a component of the pre-66S ribosomal particle.
NAD/GMP synthase (NAD/GMP_synthase)
Type: Domain

NAD+ synthase (

) catalyzes the last step in the biosynthesis of nicotinamide adenine dinucleotide and is induced by stress factors such as heat shock and glucose limitation. The three-dimensional structure of NH3-dependent NAD+ synthetase from Bacillus subtilis, in its free form and in complex with ATP shows that the enzyme consists of a tight homodimer with alpha/beta subunit topology .

This domain is also found in guanosine 5'-monophosphate (GMP) synthetase. GMP synthase catalyses the synthesis of GMP from XMP. The protein is a homodimer, but in some archaea it is a heterodimer composed of a glutamine amidotransferase subunit and a ATP pyrophosphatase subunit. In eucaryotes, bacteria, and some archaea the two catalytic units are encoded by a single gene, producing a two-domain-type GMP, with a GATase domain in the N-terminal half and a ATP-PPase domain in the C-terminal half. This entry represents the ATP pyrophosphatase domain.
DNA polymerase/3'-5' exonuclease PolX-like (PolX-like)
Type: Family

This entry represents DNA polymerase/3'-5' exonuclease PolX from Bacillus subtilis and similar proteins from bacteria and archaea. PolX is a strictly DNA-template-directed DNA polymerase, preferentially acting on DNA structures containing gaps from one to a few nucleotides and bearing a phosphate group at the 5' end of the downstream DNA. This enzyme has 3'-5' exonuclease activity, and edits unpaired 3'-termini in a gapped DNA substrate. It is also likely involved in resecting unannealed 3'-termini during DNA repair. The same PolX molecule could perform the subsequent gap-filling step . Members of this family have DNA polymerase X (POLIIIAc) and PHP hydrolase domains.
DNA polymerase family X (DNA_pol_X)
Type: Family

Family X DNA polymerases (PolX) are involved in DNA repair, being evolutionarily conserved in prokaryotes, eukaryotes and archaea. All DNA polymerases from this family are single-subunit enzymes, lacking the 3'-5' exonuclease activity and displaying very low processivity during primer extension reactions . Proteins in this family include in the well-characterised mammalian Pol beta; more recently discovered eukaryotic polymerases lambda, and mu; and a template-independent polymerase, terminal transferase (TdT) .

DNA carries the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the cell life cycle. This function is mediated by DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP) residues to the 3'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used. Three motifs, A, B and C , are seen to be conserved across all DNA-polymerases, with motifs A and C also seen in RNA- polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenow (Escherichia coli) structure: motif A contains a strictly-conserved aspartate at the junction of a β-strand and an α-helix; motif B contains an α-helix with positive charges; and motif C has a doublet of negative charges, located in a β-turn-β secondary structure .

DNA polymerases (

) can be classified, on the basis of sequence similarity , into at least four different groups: A, B, C and X. Members of family X are small (about 40kDa) compared with other polymerases and encompass two distinct polymerase enzymes that have similar functionality: vertebrate polymerase beta (same as yeast pol 4), and terminal deoxynucleotidyl-transferase (TdT) (

). The former functions in DNA repair, while the latter terminally adds single nucleotides to polydeoxynucleotide chains. Both enzymes catalyse addition of nucleotides in a distributive manner, i.e. they dissociate from the template-primer after addition of each nucleotide. DNA-polymerases show a degree of structural similarity with RNA-polymerases.
Phenylalanine/histidine ammonia-lyases, active site (Phe/His_NH3-lyase_AS)
Type: Active_site

This entry represents the active site of phenylalanine ammonia-lyase (PAL;

) and the mechanistically related protein histidine ammonia lyase (HAL;

). Both contain a catalytic Ala-Ser-Gly triad that is post-translationally cyclised . PAL is a key biosynthetic catalyst in phenylpropanoid assembly in plants and fungi, and is involved in the biosynthesis of a wide variety of secondary metabolites such as flavanoids, furanocoumarin phytoalexins and cell wall components. These compounds are important for normal growth and in responses to environmental stress. PAL catalyses the removal of an ammonia group from phenylalanine to form trans-cinnamate. HAL catalyses the first step in histidine degradation, the removal of an ammonia group from histidine to produce urocanic acid. The core domain in PAL and Hal share about 30% sequence identity, with PAL containing an additional approximately 160 residues extending from the common fold .

The two types of enzymes are functionally and structurally related . They are the only enzymes which are known to have the modified amino acid dehydro-alanine (DHA) in their active site. A serine residue has been shown to be the precursor of this essential electrophilic moiety. The region around the active site serine is well conserved and has been used as the signature pattern for this entry.
Tyrosine 2,3-aminomutase, putative (Tyr_aminomutase)
Type: Family

This entry includes tyrosine 2,3-aminomutase and histidine ammonia-lyase. It is variable from member to member as to whether the (R)-beta-Tyr or (S)-beta-Tyr is the preferred product from L-Tyr. This enzyme tends to occur in secondary metabolite biosynthesis systems, as in the production of chondramides in Chondromyces crocatus.
F420-dependent oxidoreductase-predicted, CPS4043 (F420_OxRdatse_CPS4043_pred)
Type: Family

This entry represents a group of putative F420-dependent oxidoreductases, fairly closely related to 5,10-methylenetetrahydromethanopterin reductase (mer,

). A fairly deep split (to about 40 % sequence identity) in the present family separates a strictly Actinobacterial clade from an alpha/beta/gamma-proteobacterial clade, in which the member is often the only apparent F420-dependent LLM family member. The specific function, and whether Actinobacterial and Proteobacterial clades differ in function, are unknown.