SII-SWORD/CoKE huggingface dataset:
NlpC/P60 family, putative phage cell wall peptidase (Phage_pept_NlpC/P60)
Type: Family

Members of this family show sequence similarity to members of the NlpC/P60 family described by Anantharaman and Aravind . The NlpC/P60 family includes a number of characterised bacterial cell wall hydrolases. Members of this related family are all found in prophage regions of bacterial genomes.
Cell division protein FtsN (FtsN)
Type: Family

FtsN is a poorly conserved protein active in cell division in a number of Proteobacteria. The N-terminal 30 residue region tends to by Lys/Arg-rich, and is followed by a membrane-spanning region. This is followed by an acidic low-complexity region of variable length and a well-conserved C-terminal domain of two tandem regions (Sporulation related repeat), found in several cell division and sporulation proteins. The role of FtsN as a suppressor for other cell division mutations is poorly understood; it may involve cell wall hydrolysis .
Tyrosine recombinase XerC (Recomb_XerC)
Type: Family

The phage integrase family describes a number of recombinases with tyrosine active sites that transiently bind covalently to DNA. Many are associated with mobile DNA elements, including phage, transposons, and phase variation loci. This entry represents XerC, which is closely related to the other chromosomal protein XerD (

). XerC and XerD are site-specific recombinases which help resolve chromosome dimers to monomers for cell division after DNA replication. XerC and XerD interact with cell division protein FtsK .
Tyrosine recombinase XerD (Recomb_XerD)
Type: Family

Proteins in this entry are part of the wider so-called "phage" integrase fmaily which describes a number of recombinases with tyrosine active sites that transiently bind covalently to DNA. Many are associated with mobile DNA elements, including phage, transposons, and phase variation loci.

This entry represents the chromosomally-encoded polypeptide XerD, which is closely related to, and interacts with, another chromosomally-encoded polypeptide, XerC (

). These proteins are site-specific tyrosine recombinases, which act by catalyzing the cutting and rejoining of the recombining DNA molecules . They form a cyclic heterotetrameric complex composed of two molecules of XerC and two molecules of XerD. The XerC-XerD complex is essential to convert dimers of the bacterial chromosome into monomers to permit their segregation at cell division. It also contributes to the segregational stability of plasmids.

XerD is composed of two domains, an N-terminal α-helical domain, and a C-terminal domain composed mostly of α helices, with a three-stranded antiprallel β sheet along one edge . The active site is found at the extreme C-terminal end of the polypeptide. Most of the C-terminal domain is structurally homologous to that of other "phage" integrases, but the active site regions of these enzymes are stucturally distinct.
Double transmembrane domain (Double_TM_dom)
Type: Domain

This entry represents a prokaryotic N-terminal region of about 80 amino acids. The predicted membrane topology by TMHMM puts the N terminus outside and spans the membrane twice, with a cytosolic region of about 25 amino acids between the two transmembrane regions. Member proteins tend to be between 600 and 1000 amino acids in length.
Conserved hypothetical protein CHP02231 (CHP02231)
Type: Family

This family consists of proteins over 500 amino acids long in Caenorhabditis elegans and several bacteria (Pseudomonas aeruginosa, Anabaena sp. (strain PCC 7120), Leptospira interrogans, etc.). The function is unknown.
Myxococcus cysteine-rich repeat (Myxo_disulph_rpt)
Type: Repeat

This entry represents a sequence region shared between several proteins of Myxococcus xanthus (strain DK 1622) and some eukaryotic proteins that include human pappalysin-1. The region of about 40 amino acids contains several conserved Cys residues presumed to form disulphide bonds. The region appears in up to 13 repeats in Myxococcus.
2-carboxy-1,4-naphthoquinone phytyltransferase (DHNA_phytyltransferase_MenA)
Type: Family

This entry represents 2-carboxy-1,4-naphthoquinone phytyltransferase from plants and cyanobacteria. It catalyses the conversion of 1,4-dihydroxy-2-naphthoate (DHNA) to demethylphylloquinone .
DNA recombination/repair protein RadA (DNA_recomb/repair_RadA)
Type: Family

This family consists exclusively of archaeal RadA protein, a homologue of bacterial RecA, eukaryotic RAD51 (

), and archaeal RadB (

). This protein is involved in DNA repair and in homologous recombination, it binds and assembles on single-stranded DNA to form a nucleoprotein filament. RadA hydrolyzes ATP in a ssDNA-dependent manner and promotes DNA strand exchange between homologous DNA molecules involved in DNA repair and recombination. The member from Pyrococcus horikoshii contains an intein .
DNA repair and recombination protein RadB (DNA_repair_and_recomb_RadB)
Type: Family

The RadB family of archaeal proteins is involved in DNA repair and in homologous recombination . The proteins contain a conserved triplet of residues (Lys-His-Arg) at their C terminus that is crucial for DNA binding . RadB does not catalyse strand exchange and does not turn over ATP efficiently. It has been shown to inhibit Holliday junction resolution by Hjc in the absence of ATP, but has little effect when ATP is present .
Meiotic recombination protein Dmc1 (Dmc1)
Type: Family

Dmc1 is a meiosis-specific RecA homologue . It is a recombinase required for interhomologue recombination and double-strand break repair during meiosis .
DNA recombination/repair protein Rad51 (DNA_recomb/repair_Rad51)
Type: Family

Homologous recombination is an evolutionarily conserved mechanism for the repair of double-strand breaks in DNA and the generation of genetic diversity. The primary function of homologous recombination in mitotic cells is to repair double-strand breaks or single-strand gaps that form as a result of replication fork collapse, from processing of spontaneous damage, and from exposure to DNA-damaging agents. During meiosis, homologous recombination is essential to establish a physical connection between homologous chromosomes to ensure their correct disjunction at the first meiotic division. In addition, the high frequency of meiotic recombination contributes to diversity by creating new linkage arrangements between genes, or parts of genes .

The central step of homologous recombination is synapsis, the process of bringing together the two homologous strands. Rad51, a eukaryotic homologue of the prokaryotic recombinase RecA, mediates this process in eukaryotes . Firstly a single-stranded DNA tail is coated by ATP-bound Rad51 to yield a nucleoprotein filament. This filament then searches for a homologous sequence within double-stranded DNA, and catalyses the exchange of strands between the single-stranded and double-stranded DNA substrates. The original broken end of the resulting branched DNA is now aligned with an appropriate matching sequence in an intact duplex, and is further processed by other enzymes .

Rad51 contains an N-terminal α-helical DNA binding domain not found in RecA, and a RecA-like C-terminal ATPase domain . The active form of this protein is a long helical filament where the catalytically active unit is a homodimer .
Poly(3-hydroxyalkanoate) depolymerase (PHA_depoly_arom)
Type: Family

This family consists of the polyhydroxyalkanoic acid (PHA) depolymerase of Pseudomonas oleovorans and related species. This enzyme is part of polyester storage and mobilisation system as in many bacteria. However, species containing this enzyme are unusual in their capacity to produce aromatic polyesters when grown on carbon sources such as benzoic acid or phenylacetic acid .
HAD-superfamily hydrolase, subfamily IIID (HAD-SF_hydro_IIID)
Type: Domain

This family of sequences appears to belong to the Haloacid Dehalogenase (HAD) superfamily of enzymes by virtue of the presence of three catalytic domains , in this case: LLVLD(ILV)D(YH)T, I(VMG)IWS, and (DN)(VC)K(PA)Lx{15-17}T(IL)(MH)(FV)DD(IL)(GRS)(RK)N. Since this family has no large "cap" domain between motifs 1 and 2 or between 2 and 3, it is formally a "class III" HAD .
Steroid delta5-4-isomerase (Steroid_delta5-4_isomerase)
Type: Family

This entry consists mostly of uncharacterised proteins found in a number of bacterial species, including Streptomyces, Xanthomonas, Oceanobacillus iheyensis, Caulobacter crescentus CB15, and Xylella fastidiosa. One protein in this entry (

from Comamonas testosteroni) has been shown to be a steroid delta-isomerase enzyme (

). C. testosteroni is capable of growth on steroids as its sole source of carbon and this enzyme catalyses the isomerisation of a delta-5 steroid to a delta-4 form as shown below:

3-oxo-delta(5)-steroid == 3-oxo-delta(4)-steroid

This enzyme is one of the most efficient known, with a reaction rate equivalent to the diffusion-controlled limit . It is a 28kDa homodimer whose crystal structure has been examined in detail . Each monomer consists of three α-helices, a mixed β sheet, four turns, and two β-bulges. The β sheet forms a deep hydrophobic cavity with the active site residues near the base.
Predicted HAD-superfamily phosphatase, subfamily IA/Epoxide hydrolase, N-terminal (HAD-SF_ppase_IA/epoxid_hydro_N)
Type: Domain

This entry represents a small clade of sequences from the metazoa and bacteria. In eukaryotes, this domain exists as an N-terminal fusion to the soluble epoxide hydrolase enzyme and has recently been shown to be an active phosphatase, although the nature of the biological substrate is unclear . These appear to be members of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases by general homology and the conservation of all of the recognised catalytic motifs (although the first motif is unusual in the replacement of the more common aspartate with glycine). The variable domain is found in between motifs 1 and 2, indicating membership in subfamily I and phylogeny and prediction of the α helical nature of the variable domain indicate membership in subfamily IA.
Integrase, integron-type (Integrase_integron-type)
Type: Family

Members of this family are integrases associated with integrons (and super-integrons), which are systems for incorporating and expressing cassettes of laterally transferred DNA. Incorporation occurs at an attI site. A super-integron, as in Vibrio species, may include over 100 cassettes. This family belongs to the phage integrase family that also includes recombinases XerC (

) and XerD (

), which are bacterial housekeeping proteins. Within this family of integron integrases, some are designated by class, e.g. IntI4, a class 4 integron integrase from Vibrio cholerae O1 biovar eltor str. N16961.
FCP1-like phosphatase, phosphatase domain (FCP1_euk)
Type: Domain

This entry represents the phosphatase domain of the human RNA polymerase II subunit A C-terminal domain phosphatase (FCP1, ) and closely related phosphatases from eukaryotes including plants, fungi and slime mold. This domain is a member of the haloacid dehalogenase (HAD) superfamily by virtue of a conserved set of three catalytic motifs and a conserved fold as predicted by PSIPRED. The third motif in this family is distinctive (hhhhDDppphW). This domain is classified as a "Class III" HAD, since there is no large "cap" domain found between motifs 1 and 2 or motifs 2 and 3 . This domain is related to domains found in the human NLI interacting factor-like phosphatases.
Dullard phosphatase domain, eukaryotic (Dullard_phosphatase)
Type: Domain

This entry represents the putative phosphatase domain of a family of eukaryotic proteins including "Dullard" , and the NLI interacting factor (NIF)-like phosphatases .
HAD-superfamily hydrolase, subfamily IA, REG-2-like (HAD-SF_hydro_IA_REG-2-like)
Type: Family

This family of proteins includes uncharacterised sequences from eukaryotes, cyanobacteria and Leptospira as well as the DREG-2 protein from Drosophila melanogaster (Fruit fly) which has been identified as a rhythmically (diurnally) regulated gene . This family is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs . The subfamilies are defined based on the location and the observed or predicted fold of a so-called, capping domain, , or the absence of such a domain. This family is a member of subfamily 1A in which the cap domain consists of a predicted α helical bundle found in between the first and second catalytic motifs. A distinctive feature of this family is a conserved tandem pair of tryptophan residues in the cap domain. The most divergent sequences included within the scope of this entry are from plants and have "FW" at this position instead. Most likely, these sequences, like the vast majority of HAD sequences, represent phosphatase enzymes.
HAD-superfamily hydrolase, subfamily IA, CTE7 (HAD-SF_hydro_IA_CTE7)
Type: Family

This family of sequences from archaea and metazoans includes N-acylneuraminate-9-phosphatase Nanp from metazoa and glyceraldehyde 3-phosphate phosphatases from archaea . Pyrococcus species appear to have three different forms of this enzyme, so it is unclear whether all members of this family have the same function. This family is a member of the haloacid dehalogenase (HAD) superfamily of hydrolases which are characterised by three conserved sequence motifs. By virtue of an α helical domain in-between the first and second conserved motif, this family is a member of subfamily IA .
HAD-superfamily hydrolase, subfamily IA, YjjG/PynA (HAD-SF_hydro_IA_YjjG/PynA)
Type: Family

This family is a member of the haloacid dehalogenase (HAD) superfamily of hydrolases which are characterised by three conserved sequence motifs . It includes pyrimidine 5'-nucleotidase YjjG from E. coli, pyrimidine 5'-nucleotidase PynA from Streptococcus pneumoniae and the uncharacterised protein YfnB from B. subtilis. YjjG and PynA have been shown to act as house-cleaning enzymes, cleaving nucleotides with non-canonical nucleotide bases that protect cells against non-canonical pyrimidine derivatives such as 5-fluoro-2'-deoxyuridine monophosphate (5-FdUMP), and prevents the incorporation of potentially mutagenic nucleotides such as 5-bromo-2'-deoxyuridine (5-BrdU) into DNA. They are strictly specific to pyrimidine substrates with 5'-monophosphates and shows no activity against nucleoside di- and triphosphates . By virtue of an α helical domain in-between the first and second conserved motif, this family is a member of subfamily IA.
CD-NTase-associated protein 3 (CAP3)
Type: Family

This family represents a group of proteins found in several proteobacteria, which are part of the CBASS (cyclic oligonucleotide-based antiphage signalling system), providing immunity against bacteriophage. This system is ancestry related with the cGAS-STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase and an effector that is activated by the cyclic oligonucleotides, promoting cell death. The CD-NTase protein synthesises cyclic nucleotides in response to infection, which serve as specific second messenger signals that activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection .

cGAS isopeptidase, also known as CD-NTase-associated protein 3 (CAP3), is part of type II CBASS, which is an isopeptidase of the JAB/JAMM family, a group of deubiquitinase enzymes that remove ubiquitin from target proteins. This protein is necessary for the protection against some phage infection suggesting its ancillary function in CBASS system .
Cobaltochelatase, CobN subunit (Cobalto_CobN)
Type: Family

This family of proteins catalyzes the insertion of cobalt into the corrin ring of hydrogenobyrinic acid a,c-diamide. This aerobic branch of corrin ring synthesis is part of the adenosylcobalamin biosynthetic pathway .
Benzoyl-CoA reductase, subunit A (Benzoyl_CoA_Rdtase_A)
Type: Family

This entry describes A subunit of benzoyl-CoA reductase, a 4-subunit enzyme . Many aromatic compounds are metabolized by way of benzoyl-CoA. This family shows strong sequence similarity to the 2-hydroxyglutaryl-CoA dehydratase alpha chain.
Benzoyl-CoA reductase, subunit B (Benzoyl_CoA_Rdtase_B)
Type: Family

This entry describes describes the B, or beta, subunit of the bcr type of benzoyl-CoA reductase, a 4-subunit enzyme. Many aromatic compounds are metabolized by way of benzoyl-CoA.
Benzoyl-CoA reductase, subunit D (Benzoyl_CoA_Rdtase_D)
Type: Family

This entry describes the D subunit of benzoyl-CoA reductase, a 4-subunit enzyme. Many aromatic compounds are metabolized by way of benzoyl-CoA. This family shows sequence similarity to the A subunit (

) and to the 2-hydroxyglutaryl-CoA dehydratase alpha chain.
Benzoate-CoA ligase family (Benz_CoA_lig)
Type: Family

Characterised members of this protein family include benzoate-CoA ligase , 4-hydroxybenzoate-CoA ligase , 2-aminobenzoate-CoA ligase, etc. Members are related to fatty acid and acetate CoA ligases.
Benzoyl-CoA reductase, subunit C (Benzoyl_CoA_Rdtase_C)
Type: Family

This entry describes C subunit of benzoyl-CoA reductase, a 4-subunit enzyme. Many aromatic compounds are metabolized by way of benzoyl-CoA. This enzyme acts under anaerobic conditions.
Conserved hypothetical protein CHP02270 (CHP02270)
Type: Family

Members are found in Myxococcus xanthus (six members), Geobacter sulfurreducens, and Pseudomonas aeruginosa; a short protein homologous to the N-terminal region is found in Rhizobium loti (Mesorhizobium loti). All sequence are from Proteobacteria. The function is unknown.
Gentisate 1,2 dioxygenase 1 (Gentisate_dOase)
Type: Family

This family consists of gentisate 1,2-dioxygenases, including Gentisate 1,2 dioxygenase 1 from Pseudomonas alcaligenes that exhibits broad substrate specificities towards alkyl and halogenated gentisates. These ring-opening enzymes acts in salicylate degradation that goes via gentisate rather than via catechol. It converts gentisate to maleylpyruvate. Some putative gentisate 1,2-dioxygenases may be excluded from this entry.
Ribosome maturation factor RimM (RimM)
Type: Family

This family consists of the bacterial protein RimM (YfjA, 21K), a 30S ribosomal subunit-binding protein implicated in 16S ribosomal RNA processing. It has been partially characterised in Escherichia coli, is found with other translation-associated genes such as trmD. It is broadly distributed among bacteria, including some minimal genomes such the aphid endosymbiont Buchnera aphidicola. This entry represents the full-length model. A member from Arabidopsis (plant) has additional N-terminal sequence likely to represent a chloroplast transit peptide .
dCTP deaminase (dCTP_deaminase)
Type: Family

Deoxycytidine triphosphate deaminase (dCTP deaminase) is an enzyme involved in nucleotide metabolism. It catalyses the formation of dUTP (deoxyuridine (5'-)triphosphate), which in turn is degraded by dUTPase (dUTP diphosphatase) to produce dUMP (deoxyuridine monophosphate). dUMP is the immediate precursor of thymidine nucleotides .

Members of this family include the Escherichia coli monofunctional deoxycytidine triphosphate deaminase (dCTP deaminase) and a Methanocaldococcus jannaschii (Methanococcus jannaschii) bifunctional dCTP deaminase (

)/dUTP diphosphatase (

) .
2,3-dihydroxybenzoate-AMP ligase (DHB_AMP_lig)
Type: Family

Siderophores are low molecular weight iron-chelating compounds synthesised by many bacteria to aid in the aquisition of this vital trace element . Proteins in this entry are adenylation components of non-ribosomal peptide synthases (NRPSs) involved in the biosynthesis of siderophores. These proteins belong to the AMP-binding family and are mostly thought to activate 2,3-dihydroxybenzoate (DHB) by ligation of AMP from ATP with the release of pyrophosphate (ATP-PPi exchange). Enzymatic studies on the purified enzyme, 2,3DHB-AMP ligase of Escherichia coli, show that 2,3DHB efficiently supports the ATP-PPi exchange while other analogues can replace 2,3DHB, for example: salicyclic acid (o-hydrobenzoate); 2,4DHB and 2,5DHB; though the natural substrate 2,3DHB is by far the most efficient. Substrates such as 2,6DHB and 2,4,6THB do not support the ATP-PPi exchange and suggest significant steric interference by the 6-hyroxy side chain .

The crystal structure of 2,3-dihydroxybenzoate-AMP ligase (

) from Bacillus subtilis has been examined . This protein is composed of a large N-terminal domain (~420 aa) and a more compact C-terminal domain (~110 aa), with an overall "hammer-and-anvil" fold similar to that of firefly luciferase . The active site is located in a deep compartment located at the interface of the domains, with a p-loop thought to be involved in catalysis located at the entrance to the cavity. Relatively little conformational change was observed during catalysis.
YVTN beta-propeller repeat (YVTN_b-propeller_repeat)
Type: Repeat

This entry represents a repeat of about 40 amino acids found in a variety of archaea and bacteria which can be present in up to 14 copies per protein. The archaeal species Methanosarcina mazei (Methanosarcina frisia) contains several predicted surface layer proteins (SLPs) containing tandem copies of this repeat . The crystal structure of one of these proteins (

), containing seven tandem copies of this repeat, was examined. Individually, these repeats form four-stranded β-blades, while the seven copies together form a seven-bladed β-propeller domain. This repeat shows sequence similarity to the WD-40 repeat (

) and may play a similar role, serving as a rigid scaffold for protein interactions.
Phenylacetic acid degradation operon negative regulatory protein PaaX (PaaX_trns_reg)
Type: Family

This transcriptional regulator is always found in association with operons believed to be involved in the degradation of phenylacetic acid . The gene product has been shown to bind to the promoter sites and repress their transcription .
Phenylacetic acid degradation protein PaaN (PaaN-DH)
Type: Family

This enzyme is proposed to act in the ring-opening step of phenylacetic acid degradation which follows ligation of the acid with coenzyme A (by PaaF) and hydroxylation by a multicomponent non-heme iron hydroxylase complex (PaaGHIJK). Gene symbols have been standardised in . This enzyme is related to aldehyde dehydrogenases.
3-hydroxyadipyl-CoA dehydrogenase PaaH (3-OHacyl-CoA_DH_PaaH)
Type: Family

This entry represents the 3-hydroxyacyl-CoA dehydrogenase (also known as PaaH) and related bacterial proteins. PaaH is involved in the degradation of phenylacetic acid, presumably in steps following the opening of the phenyl ring . The sequences included in this entry are all found in possible operons with other related genes such as paaA, paaB, paaD, paaE, paaF and paaN . Some genomes contain these other genes without an apparent paaC in the same operon -possibly in these cases a different dehydrogenase involved in fatty acid degradation may fill in the needed activity.
Phenylacetate degradation probable enoyl-CoA hydratase PaaB (PaaB1)
Type: Family

This family of proteins are found within apparent operons for the degradation of phenylacetic acid . These proteins contain the enoyl-CoA hydratase domain. This activity is consistent with current hypotheses for the degradation pathway which involve the ligation of phenylacetate with coenzyme A (paaF), hydroxylation (paaGHIJK), ring-opening (paaN) and degradation of the resulting fatty acid-like compound to a Krebs cycle intermediate (paaABCDE).
Lytic murein transglycosylase (MltB_2)
Type: Domain

Proteins of this entries are closely related to the MltB family lytic murein transglycosylases described by

and are likewise all proteobacterial, although that family and this one form clearly distinct clades. Several species have one member of each family. Many proteins of this entry(unlike the MltB family) contain an additional C-terminal domain, a putative peptidoglycan binding domain (

), not included in region described by this model. Many sequences appear to contain N-terminal lipoprotein attachment sites, as does Esherichia coli MltB in

.