SII-SWORD/CoKE huggingface dataset:
HAD hydrolase, TIGR01548 family (HAD-SF_TIGR01548)
Type: Family

This entry represents a small and phylogenetically curious clade of sequences. Sequences are found from Halobacterium (an archaeon), Nostoc and Synechococcus (cyanobacteria) and Phytophthora (a stramenophile eukaryote). 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 . 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 (by PSI-PRED) indicate membership in subfamily IA. All but the Halobacterium sequence currently found are annotated as "Imidazoleglycerol-phosphate dehydratase", however, the source of the annotation could not be traced and significant homology could not be found between any of these sequences and known IGPD's.
HAD hydrolase, subfamily IA (HAD-SF_hydro_IA)
Type: Family

The Haloacid Dehalogenase (HAD) 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. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions.

The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an α-helical bundle. Subfamily IA and IB are separated based on an apparent phylogenetic bifurcation. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA.

NOTE: Three variant models were created by TIGRFAMs with some overlap among them to cover subfamily IA. This serves the purpose of eliminating the overlap with models of more distantly related HAD subfamilies caused by an overly broad single model.
Death on curing protein (Doc)
Type: Family

This entry represents death-on-curing (Doc) proteins mostly from bacteria and archaea.

Bacterial toxin-antitoxin (TA) system (or "addiction module") composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect . TA system plays a role in the adaptation of prokaryotes to stress conditions, the persistence phenomenon, programmed cell death and addiction to phages and mobile elements .
Bacteriophage P2, capsid (Phage_P2_GpN)
Type: Family

This entry represents Capsid proteins from Bacteriophage P2 (GpN) and similar proteins from tailed bacteriophages and bacterial prophages mainly among Proteobacteria.

GpN undergoes proteolytic cleavage into three products:

Minor capsid protein H1, a 39 kDa protein

Minor capsid protein H2, 38.6 kDa

Major capsid protein N*, 36.7 kDa

The capsid of P4, the satellite phage of P2, consists of those same gene products encoded by P2, although in this case the resulting capsids are smaller than those usually formed by P2 alone. P2 procapsid have a dextro HK97 fold with T = 7 symmetry .
Type II toxin-antitoxin system, antitoxin Phd/YefM (Antitoxin_Phd/YefM)
Type: Family

Members of this family act as antitoxins in type II toxin-antitoxin systems . When bound to their toxin partners, they can bind DNA via the N terminus and repress the expression of operons containing genes encoding the toxin and the antitoxin .
Formate dehydrogenase-N, alpha subunit (Formate-DH-alph_fdnG)
Type: Family

This family of sequences describe a subset of formate dehydrogenase alpha chains found mainly in proteobacteria but also in Aquifex aeolicus. The alpha chain contains domains for molybdopterin dinucleotide binding and molybdopterin oxidoreductase. The holo-enzyme also contains beta and gamma subunits of 32 and 20kDa. The enzyme catalyzes the oxidation of formate (produced from pyruvate during anaerobic growth) to carbon dioxide with the concomitant release of two electrons and two protons. The electrons are utilised mainly in the nitrate respiration by nitrate reductase . In Escherichia coli and Salmonella typhi, there are two forms of the formate dehydrogenase, one induced by nitrate which is strictly anaerobic (fdn), and one induced during the transition from aerobic to anaerobic growth (fdo). This subunit is one of only three proteins in E. coli which contains selenocysteine .
Phage-associated protein HI1409 (Phage-assoc_HI1409)
Type: Family

This family of uncharacterised proteins is found in prophage regions of a number of bacterial genomes, including Haemophilus influenzae, Xylella fastidiosa, Salmonella typhi, and Enterococcus faecalis.

This family includes sequences mainly from proteobacteria and firmicutes, such as Abc1, a protein that counteracts or regulates the endogenous CBASS (cyclic oligonucleotide-based antiphage signalling system) antiviral defense system. It is a phosphodiesterase that enables metal-independent hydrolysis of the host cyclic di- and trinucleotide CBASS signals such as 3'3'-cGAMP, 3'3'cUA, and 3'3'3'-cAAA .
Rhamnosyltransferase (RhaTrfase)
Type: Family

This subfamily is composed of sequences from the gammaproteobacteria that function as L-rhamnosyltransferases in the synthesis of their respective surface polysaccharides. Rhamnolipids are glycolipids containing mono- or di- L-rhamnose molecules. Rhamnolipid synthesis occurs by sequential glycosyltransferase reactions involving two distinct rhamnosyltransferase enzymes. In Pseudomonas aeruginosa, the synthesis of mono-rhamnolipids is catalyzed by rhamnosyltransferase 1, and proceeds by a glycosyl transfer reaction catalyzed by rhamnosyltransferase 2 to yield di-rhamnolipids .
Myb domain, plants (Myb_dom_plants)
Type: Domain

This DNA-binding domain is restricted to (but common in) plant proteins, many of which also contain a response regulator domain. The domain appears related to the Myb-like DNA-binding domain .
Putative phage terminase, small subunit, P27 family (Phage_term_ssu_P27)
Type: Family

This group of sequences are a family of phage (and integrated prophage) putative terminase small subunit sequences. Members tend to be encoded by the gene adjacent to the phage terminase large subunit gene.
Squalene synthase-like (Squal_synth-like)
Type: Family

This family of sequences describe farnesyl-diphosphate farnesyltransferase, also known as squalene synthase, as found in eukaryotes. This family is related to phytoene synthases. Tentatively identified archaeal homologues lack the C-terminal predicted transmembrane region universally conserved among members of this family and therefore are not included in this group.

This family also includes squalene synthase-like (SSL) proteins from green algae. SSL-3 (Botryococcene synthase) produces botryococcene when coexpressed with SSL-1 (Presqualene diphosphate synthase). SSL-3 has no activity with farnesyl diphosphate as substrate . SSL-2 (Botryococcus squalene synthase) produces squalene when coexpressed with SSL-1 and bisfarnesyl ether .
Phage HK97 gp6-like (Phage_HK97_gp6-like)
Type: Family

This group of sequences represents small (~100 amino acids) hypothetical proteins found in phage (such as gp6 from phage HK97) and in putative prophage regions of a number of bacterial genomes. Gp6 from HK97 is a protein the crystallizes into an oligomeric ring, consistent with its role as a phage head-tail connector protein in long-tailed phages.
Glycogen debranching enzyme, archaeal type (Glycogen_debranch_arc)
Type: Family

These sequences are largely uncharacterised archaeal proteins which include those from Methanosarcina acetivorans and Sulfolobus solfataricus. The group also contains sequences from the Gram-positive bacterium Clostridium perfringens and from cyanobacterial species. All the sequences display weak relatedness to the characterised eukaryotic glycogen debranching enzyme of Saccharomyces cerevisiae (Baker's yeast).
Formate dehydrogenase accessory protein (Formate_DH_accessory)
Type: Family

This entry contains formate dehydrogenase accessory protein FdhE and its homologues, found largely in proteobacteria, where the fdhE genes are almost always genetically-linked to the structural genes for formate dehydrogenases . FdhE is required for the assembly of formate dehydrogenase although not present in the final complex. In E.coli, FdhE interacts with the catalytic subunits of the respiratory formate dehydrogenases. FdhE is an iron-binding rubredoxin that can adopt monomeric and homodimeric forms. E.coli FdhE interacts with the catalytic subunits, FdnG and FdoG, of the Tat-dependent respiratory formate dehydrogenases. Site-directed mutagenesis has shown that conserved cysteine motifs are essential for the physiological activity of the FdhE protein and are also involved in Fe(III) ligation. The iron likely is redox active, suggesting that the switch from aerobic to anaerobic conditions may be important in modulating FdhE function. Alternatively, FdhE may be involved in an electron transfer reaction, similar to other rubredoxins .
S-layer protein (S_layer_MJ)
Type: Family

These sequences represent one of several families of proteins associated with the formation of prokaryotic S-layers. Members of this family are found in archaeal species, including Pyrococcus horikoshii (split into two tandem reading frames), Methanocaldococcus jannaschii (Methanococcus jannaschii), and related species. Some local similarity can be found to other S-layer protein families.
Homeodomain, ZF-HD class (Homeodomain_ZF_HD)
Type: Domain

This entry represents a class of homeobox domain that differs substantially from the typical homeobox domain described in

. It is found in both C4 and C3 plants .
ZF-HD homeobox protein, Cys/His-rich dimerisation domain (ZF_HD_homeobox_Cys/His_dimer)
Type: Domain

The homeodomain (HD) is a 60-amino acid DNA-binding domain found in many transcription factors. HD-containing proteins are found in diverse organisms such as humans, Drosophila, nematode worms, and plants, where they play important roles in development. Zinc-finger-homeodomain (ZF- HD) subfamily proteins have only been identified in plants, and likely play plant specific roles. ZF-HD proteins are expressed predominantly or exclusively in floral tissue, indicating a likely regulatory role during floral development . The ZF-HD class of homeodomain proteins may also be involved in the photosynthesis-related mesophyll-specific gene expression of phosphoenolpyruvate carboxylase in C4 species and in pathogen signaling and plant defense mechanisms .

These proteins share three domains of high sequence similarity: the homeodomain (II) located at the carboxy-terminus, and two other segments (Ia and Ib) located in the amino-terminal part. These N-terminal domains contain five conserved cysteine residues and at least three conserved histidine residues whose spacing ressembles zinc-binding domains involved in dimerization of transcription factors. Although the two domains contain at least eight potential zinc-binding amino-acids, the unique spacing of the conserved cysteine and histidine residues within domain Ib suggests that both domains form one rather than two zinc finger structures. The two conserved motifs Ia and Ib constitute a dimerization domain which is sufficient for the formation of homo- and heterodimers .
S-layer family duplication domain (S_layer-rel_Mac)
Type: Domain

This entry represents a domain found tandemly duplicated in two proven archaeal S-layer glycoproteins, MA0829 from Methanosarcina acetivorans C2A and MM1976 from Methanosarcina mazei Go1 , as well as in several paralogues of those L-layer proteins from both species. Members of the family show regions of local similarity to another known family of archaeal S-layer proteins (

). Some members of this family, including the proven S-layer proteins, have the archaeosortase A target motif, PGF-CTERM (

), at the protein C terminus.
Ovate protein family, C-terminal (Ovate_C)
Type: Domain

This domain in found towards the C terminus in the Oval family of transcriptional repressors. These proteins are important regulators of growth and development in plants .
Casparian strip membrane protein (CASP/CASPL)
Type: Family

This family consists of CASP and CASP-like proteins. In vascular plants Casparian strips span the cell wall of adjacent endodermal cells to form a tight junction that blocks extracellular diffusion . Casparian Strip Membrane Domain Proteins (CASPs) are four-membrane-span proteins that recruit the lignin polymerisation machinery necessary for the deposition of Casparian strips in the endodermis. CASP-like proteins (CASPLs) are found in all major divisions of land plants as well as in green algae. In Arabidopsis, CASPLs show specific expression in a variety of cell types .
Protein MIZU-KUSSEI 1-like, plant (MIZ1-like_pln)
Type: Family

This entry includes Arabidopsis MIZU-KUSSEI 1 (MIZ1), which is an essential protein for hydrotropism in roots. It can be regulated by light signal and ABA signalling .
PLAC8 motif-containing protein (PLAC_motif_containing)
Type: Family

This entry represents a group of cys-rich proteins, including cornifelin and PLAC8 from animals, MCA (MID1-COMPLEMENTING ACTIVITY) and PCR (PLANT CADMIUM RESISTANCE) from Arabidopsis and cell number regulators from maize .

Cornifelin is part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia . PLAC8 is required for white adipocyte differentiation in vitro and cell number control in vivo .

Plant transports in this entry include MCA1, MCA2 and PCR1-12. MCA1 and MCA2 mediate Ca2+ uptake , while PCR2 is a zinc exporter involved in both zinc extrusion and long-distance zinc transport .
Protein MS5 (MS5)
Type: Family

These sequences comprise a paralogous family of proteins predominantly found in Brassicaceae. Length heterogeneity within the family is attributable partly to a 21-residue repeat present in from zero to three tandem copies. One member of the family, protein MS5, has been shown to be important for progression of meiosis during early prophase and is essential for pairing of homologues. It is preferentially expressed in reproductive organs . The structure of MS5 revealed that it adopts a cystatin-like fold that consists of a central α-helix and four- or five-stranded antiparallel β-sheets that wrap around it .
tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase MiaB (MiaB_methiolase)
Type: Family

This entry represents the MiaB enzyme and homologues that are responsible for the modification of the isopentenylated adenine-37 base of most bacterial and eukaryotic tRNAs that read codons beginning with uracil (all except tRNA(I,V) Ser). Adenine-37 is next to the anticodon on the 3' side in these tRNA's, and lack of modification at this site leads to an increased spontaneous mutation frequency. Isopentenylated A-37 is modified by methylthiolation at position 2 leading to the formation of 2-methylthio-N6-(dimethylallyl)adenosine, either by MiaB alone or in concert with a separate methylase yet to be discovered . MiaB contains two 4Fe-4S clusters which are labile under oxidizing conditions . One cluster is coordinated with three cysteines and an exchangeable S-adenosyl-L-methionine, the other is thought to be the sulfur donor. The second cluster has a polysulfide group bound to it, which is methylated in the first reaction step. Concurrently, the SAM-[4Fe-4S] cluster forms the 5'-dAdo radical, which abstracts a hydrogen atom from the substrate, which is then methylthiolated by the methylated polysulfide group . Additionally, the sequence is homologous to the biotin synthetase, BioB, which utilises both an iron-sulfur cluster and S-adenosym methionine (SAM) to generate a radical which is responsible for initiating the insertion of sulfur into the substrate . It is reasonable to surmise that the methyl group of SAM becomes the methyl group of the product, but this has not been shown, and the possibility of a separate methylase exists. These enzymes contain a TRAM domain which is believed to be responsible for binding to tRNAs. The enzyme from Thermotoga maritima has been cloned, expressed, spectroscopically characterised and shown to complement the E. coli MiaB enzyme .
N-acetyltransferase RimI/Ard1 (AcTrfase_RimI/Ard1)
Type: Family

Members of this entry belong to the GCN5-related N-acetyltransferase (GNAT) superfamily. This entry covers prokaryotes and the archaea. It contains RimI, which catalyses the acetylation of the N-terminal alanine of ribosomal protein bS18 and Ard1, an N-terminal protein acetyltransferase from Sulfolobus that has relaxed sequence specificity .
Oligosaccharide amylase (Oligosac_amylase)
Type: Family

The name of this type of amylase is based on the characterisation of an glucoamylase family enzyme from Thermoactinomyces vulgaris. The T. vulgaris enzyme was expressed in E. coli and, like other glucoamylases, it releases beta-D-glucose from starch. However, unlike previously characterised glucoamylases, this T. vulgaris amylase hydrolyzes maltooligosaccharides (maltotetraose, maltose) more efficiently than starch, indicating that it belongs to a class of glucoamylase-type enzymes with oligosaccharide-metabolising activity .
MiaB-like tRNA modifying enzyme, archaea/eukaryota (MiaB-like_arc_euk)
Type: Family

This clade of sequences is closely related to MiaB, a modifier of isopentenylated adenosine-37 of certain eukaryotic and bacterial tRNAs (see

). Sequence alignments suggest that this family of sequences perform the same chemical transformation as MiaB, perhaps on a different (or differently modified) tRNA base substrate. This clade represents a subfamily that spans the archaea and eukaryotes. The only archaeal miaB-like genes are in this group of sequences .
MiaB-like tRNA modifying enzyme, bacteria (MiaB-like_bact)
Type: Family

This entry represents a group of bacterial tRNA modifying enzymes, including tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase from	Natranaerobius thermophilus (MiaB) and Threonylcarbamoyladenosine tRNA methylthiotransferase MtaB from Bacillus subtilis. Members of this family are closely related to MiaB, a modifier of isopentenylated adenosine-37 of certain eukaryotic and bacterial tRNAs (see

). Sequence alignments suggest that these sequences perform the same chemical transformation as MiaB, perhaps on a different (or differently modified) tRNA base substrate .
Nitrate reductase, alpha subunit (NarG)
Type: Family

The nitrate reductase enzyme complex allows bacteria to use nitrate as an electron acceptor during anaerobic growth. The enzyme complex is a heterotrimer consisting of alpha, beta and gamma subunits . The alpha subunit contains a molybdenum cofactor, the beta subunit contains [Fe-S] clusters while the gamma subunit contains haem and is membrane bound. The alpha and beta subunits form a membrane extrinsic catalytic dimer which is bound to the membrane by the gamma subunit, which is a b-type cytochrome that receives electrons from the quinone pool and transfers them to the beta subunit. The three subunits form a stable "flower"-shaped structure , where the gamma subunit anchors the alpha and beta subunits to the membrane through predominantly hydrophobic interactions. The structure is further stabilised by the presence of a phosphatidylglycerol molecule that is bound by all three subunits. The alpha subunit uses a Mo-bisMGD cofactor for catalytic activity and, like other proteins that bind this cofactor, forms four α-β domains grouped around the cofactor. Interaction with the other catalytic subunit occurs along an extensive, buried interface.
Formate dehydrogenase iron-sulphur subunit, Proteobacteria (Formate_DH_bsu_Proteobacteria)
Type: Family

The sequences in this group represent the beta subunit of the gammaproteobacterial formate dehydrogenase. This subunit contains four 4Fe-4S clusters and is involved in transmitting electrons from the alpha subunit (

) at the periplasmic space to the gamma subunit which spans the cytoplasmic membrane . In addition to the gammaproteobacteria, a sequence from Aquifex aeolicus falls within this group. This appears to be the case for the alpha, gamma and epsilon (accessory protein

) chains as well.
Formate dehydrogenase, gamma subunit (Formate_DH_gsu)
Type: Family

These sequences represent the gamma chain of the gammaproteobacteria (and Aquifex aeolicus) formate dehydrogenase. This subunit is integral to the cytoplasmic membrane, consisting of 4 transmembrane helices, and receives electrons from the beta subunit. The entire Escherichia coli formate dehydrogenase N (nitrate-inducible form) has been crystallized and its structure determined . The gamma subunit contains two cytochromes, haem b(P) and haem b(C) near the periplasmic and cytoplasmic sides of the membrane respectively. The electron acceptor quinone binds at the cytoplasmic haem histidine ligand. NiFe-hydrogenase and thiosulphate reductase contain homologous gamma subunits, and these are found in this group.
Citrate lyase, alpha subunit (Citrate_lyase_asu)
Type: Family

These sequences, from both Gram-positive and Gram-negative bacteria, represent the alpha subunit of the holoenzyme citrate lyase composed of alpha (

), beta, and acyl carrier protein subunits in a stoichiometric relationship of 6:6:6. Citrate lyase is an enzyme which converts citrate to oxaloacetate. In bacteria, this reaction is involved in citrate fermentation. The alpha subunit catalyzes the reaction Acetyl-CoA + citrate = acetate + (3S)-citryl-CoA. The proteins from Lactococcus lactis subsp. lactis (Streptococcus lactis) and Klebsiella pneumoniae has been experimentally characterised .
Peptidase C58, YopT-type domain (Peptidase_C58_Yopt)
Type: Domain

This group of sequences are characterised by a cysteine protease domain, corresponding to MEROPS peptidase family C58 (clan CA), found in proteins of bacteria that include plant pathogens (Pseudomonas syringae), root nodule bacteria, and intracellular pathogens (e.g. Yersinia pestis, Haemophilus ducreyi, Pasteurella multocida, Chlamydia trachomatis) of animal hosts. The domain features a catalytic triad of Cys, His, and Asp. Sequences can be extremely divergent outside of a few well-conserved motifs. YopT, a virulence effector protein of Y. pestis, cleaves and releases host cell Rho GTPases from the membrane, thereby disrupting the actin cytoskeleton. Members of the family from pathogenic bacteria are likely to be pathogenesis factors .
Helicase Cas3, CRISPR-associated, core (Helicase_Cas3_CRISPR-ass_core)
Type: Domain

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 highly conserved core region found in the Cas3 family of proteins. These proteins are found in association with CRISPR repeat elements in a broad range of bacteria and archaea . Cas3 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. Cas3 proteins have motifs characteristic of helicases from superfamily 2 and contain a DEAD/DEAH box region and a conserved C-terminal domain. Some but not all Cas3 family members have an N-terminal HD domain region (

), although these sequences are not included within this group. These Cas proteins may be involved in DNA metabolism or gene expression .