SII-SWORD/CoKE huggingface dataset:
Phage tail collar domain (Phage_tail_collar_dom)
Type: Domain

This entry is represented by a domain found in Bacteriophage T4, Gp12. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This region is occasionally found in conjunction with

. Most of the proteins appear to be phage tail proteins; however some appear to be involved in other processes. For instance the RhiB protein (

) from Rhizobium leguminosarum may be involved in plant-microbe interactions . A related protein, microcystin related protein (MrpB,

) is involved in the pathogenicity of Microcystis aeruginosa. The finding of this family in a structural component of the phage tail fibre baseplate (

) suggests that its function is structural rather than enzymatic. Structural studies show this region consists of a helix and a loop and three β-strands. This alignment does not catch the third strand as it is separated from the rest of the structure by around 100 residues. This strand is conserved in homologues but the intervening sequence is not. Much of the function of

appears to reside in this intervening region. In the tertiary structure of the phage baseplate this domain forms part of the collar and may bind SO
4
. The long unconserved region maybe due to domain swapping in and out of a loop or due to rapid evolution.
DNA repair metallo-beta-lactamase (DRMBL)
Type: Domain

The metallo-beta-lactamase fold contains five sequence motifs. The first four motifs are found in

and are common to all metallo-beta-lactamases. The fifth motif appears to be specific to function. This entry represents the fifth motif from metallo-beta-lactamases involved in DNA repair .
Domain of unknown function DUF1521 (DUF1521)
Type: Domain

This domain of unknown function is found in a limited set of Bradyrhizobium proteins. There appears to be a periodic -DG- motif in the domain.
Domain of unknown function DUF1522 (DUF1522)
Type: Domain

The function of these proteins is unknown. All are from Bradyrhizobium japonicum.
Bacteriophage phiNM3, A0EWY4 (Phage_phiNM3_A0EWY4)
Type: Family

This entry is represented by Bacteriophage phiNM3,

. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

Members of this family are mainly found in Proteobacteria. The function of these proteins is unknown.
GmrSD restriction endonucleases, C-terminal domain (GmrSD_C)
Type: Domain

This entry (previously known as DUF1524) represents a domain found C-terminal in the GmrSD family of modification-dependent restriction endonucleases including SspE proteins . SspE is a dual-function protein that exerts both N-terminal NTPase and C-terminal DNA nicking nuclease activities to defend against phage infection . SspE has a phosphorothioate (PT) modification-binding preference and utilises epigenetic PT modification to accomplish self-nonself discrimination and to coordinate its NTPase and DNA nicking activities to fight against phages. The domain represented in this entry has a DNA nicking nuclease activity and belongs to HNH nuclease superfamily.

This domain contains a conserved HXXP motif. Proteins containing this domain belong to GmrSD restriction systems, which target and cleave DNA with glucosylated hydroxymethylcytosine (HMC) .
Integrating conjugative element protein, PFL4709 (Integr_conj_element_PFL4709)
Type: Family

This entry represents a group of proteins predominantly found in Gammaproteobacteria. Members belong to extended genomic regions that appear to be spread by conjugative transfer .
Putative conjugal transfer nickase/helicase TraI, C-terminal (TraI_2_C)
Type: Domain

This entry contains proteins some of which are from pathogenic strains of Gammaproteobacteria. Though the function of these proteins is unknown, they could be involved in pathogenesis. This domain is found at the C terminus of proteins that contain a N-terminal metal-dependent phosphohydrolase (HD) region and are considered to be helicases/relaxases .
Uncharacterised protein family, LppY/LpqO (Uncharacterised_LppY/LpqO)
Type: Family

This family is the lppY/lpqO homologue family. They are related to 'probable conserved lipoproteins' LppY and LpqO from Mycobacterium bovis.
D-alanine--D-alanine ligase, C-terminal (Dala_Dala_lig_C)
Type: Domain

This entry represents the C-terminal, catalytic domain of the D-alanine--D-alanine ligase enzyme

. D-Alanine is one of the central molecules of the cross-linking step of peptidoglycan assembly. There are three enzymes involved in the D-alanine branch of peptidoglycan biosynthesis: the pyridoxal phosphate-dependent D-alanine racemase (Alr), the ATP-dependent D-alanine: D-alanine ligase (Ddl), and the ATP-dependent D-alanine:D-alanine-adding enzyme (MurF) .
FTP domain (FTP_domain)
Type: Domain

The fungalysin/thermolysin propeptide (FTP) domain is found in both the bacterial M4 peptidase propeptide and the fungal M36 propeptide. Its exact function is not clear, but it is likely to either inhibit the peptidase, so as to prevent its premature activation, or to have a chaperone activity. Both of these roles have been ascribed to the M4 and M36 propeptides .
G5 domain (G5_dom)
Type: Domain

The G5 domain (named after its conserved glycine residues) is a module of ~80 residues that is found in a variety of enzymes such as Streptococcal IgA peptidases and various glycosyl hydrolases in bacteria. It is found in one to seven copies in association with other domains, such as LysM, bacterial Ig-like, M23 and M26 peptidases, F5/8 type C, vanW or transglycosylase-like. The G5 domain contains a few highly conserved residues. None of these conserved residues are the polar types of amino acids found in active sites, so it seems unlikely this region has an enzymatic function. However, in nearly all cases the G5 domain is associated with a known enzymatic domain. Therefore, the G5 domain may confer localization or substrate specificity on the proteins in which it is found. As a common feature of the proteins containing G5 domains is N-acetylglucosamine binding, it has been suggested that this function might be attributed to the G5 domain. Other alternative functions could be allosteric regulation of the enzymatic domain or cofactor binding .
Glycosyl hydrolase family 67, C-terminal (Glyco_hydro_67_C)
Type: Domain

Alpha-glucuronidases, components of an ensemble of enzymes central to the recycling of photosynthetic biomass, remove the alpha-1,2 linked 4-O-methyl glucuronic acid from xylans. This family represents the C-terminal region of alpha-glucuronidase, which is mainly α-helical. It wraps around the catalytic domain (

), making additional interactions both with the N-terminal domain (

) of its parent monomer and also forming the majority of the dimer-surface with the equivalent C-terminal domain of the other monomer of the dimer .
Glycosyl hydrolase family 67, catalytic domain (Glyco_hydro_67_cat)
Type: Domain

Alpha-glucuronidases, components of an ensemble of enzymes central to the recycling of photosynthetic biomass, remove the alpha-1,2 linked 4-O-methyl glucuronic acid from xylans. This family represents the central catalytic domain of alpha-glucuronidase .
Protein of unknown function DUF5131 (DUF5131)
Type: Family

This is a family of bacterial and phage proteins of unknown function. There are three highly conserved cysteine residues in the disposition Cx6Cxxc, amongst many highly conserved residues.
Signal transduction histidine kinase, HWE region (Sig_transdc_His_kinase_HWE)
Type: Domain

The HWE domain is found in a subset of two-component system kinases, belonging to the same superfamily as

, including Blue-light-activated histidine kinase from Brucela, a photosensitive kinase that is involved in flagella synthesis, exopolysaccharide production, biofilm formation and ultimately increased bacterial virulence upon exposure to light . In , the HWE family was defined by the presence of conserved a H residue and a WXE motifs and was limited to members of the proteobacteria. However, many homologues of this domain lack the WXE motif. Furthermore, homologues are found in a wide range of Gram-positive and Gram-negative bacteria.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.
HPr kinase/phosphorylase, C-terminal (Hpr_kin/Pase_C)
Type: Domain

This entry represents the C-terminal kinase domain of Hpr Serine/threonine kinase (HprK/P). HprK/P is a bifunctional histidine-containing protein kinase/phosphatase, which controls the phosphorylation state of the phosphocarrier protein HPr and regulates the utilization of carbon sources by Gram-positive bacteria. It catalyzes both the ATP-dependent phosphorylation of Ser-46 of HPr and its dephosphorylation by phosphorolysis . This kinase is unusual in that it recognises the tertiary structure of its target and is a member of a novel family unrelated to any previously described protein phosphorylating enzymes . X-ray analysis of the full-length crystalline enzyme from Staphylococcus xylosus at a resolution of 1.95 A shows the enzyme to consist of two clearly separated domains that are assembled in a hexameric structure resembling a three-bladed propeller .
Cell wall hydrolase, SleB (Cell_wall_hydrolase_SleB)
Type: Domain

These enzymes have been implicated in cell wall hydrolysis, most extensively in Bacillus subtilis. For instance

is expressed during sporulation in an inactive form and deposited on the cell outer cortex. During germination the enzyme is activated and hydrolyses the cortex . A similar role is carried out by the partially redundant

.
Seven cysteines, N-terminal (MANSC_N)
Type: Domain

The MANSC (motif at N terminus with seven cysteines) domain is a module with a well-conserved seven cysteine motif that is present at the N terminus of higher multicellular animal membrane and extracellular proteins. It is possible that some of the cysteine residues in the MANSC domain form structurally important disulphide bridges. All of the MANSC-containing proteins contain predicted transmembrane regions and signal peptides. It has been proposed that the MANSC domain in HAI-1 might function through binding with hepatocyte growth factor activator and matriptase .
Type 1 protein phosphatase inhibitor (PPI_Ypi1)
Type: Family

This family includes Saccharomyces cerevisiae type 1 protein phosphatase inhibitor Ypi1 and human protein phosphatase 1 regulatory subunit 11 (Ppp1r11/hcgv), an atypical E3 ubiquitin-protein ligase also known to be a PP1 inhibitor .
Zn-dependent metallo-hydrolase, RNA specificity domain (RMMBL)
Type: Domain

The metallo-beta-lactamase fold contains five sequence motifs. The first four motifs are found in

and are common to all metallo-beta-lactamases. This, the fifth motif , appears to be specific to Zn-dependent metallohydrolases such as ribonuclease J 2 which are involved in the processing of mRNA . This domain adds essential structural elements to the CASP-domain and is unique to RNA/DNA-processing nucleases, showing that they are pre-mRNA 3'-end-processing endonucleases .
DNA-binding recombinase domain (DNA_bind_recombinase_dom)
Type: Domain

The large serine recombinases (LSRs) are DNA-rearranging enzymes that are members of the serine recombinase or resolvase/invertase superfamily. Most resolvases/invertases have a catalytic domain of ~150 residues at their amino terminus, followed by a small, helix-turn-helix (HTH) DNA-binding domain. The LSRs share a similar amino-terminal catalytic domain, but have much larger carboxyl-terminal regions that range in size from ~300 residues to ~550 residues. The C-terminal region of the LSRs is comprised of multiple structural domains and is responsible for coordination of unique LSRs activities. The LSR C-terminal region is composed of two structural domains: a mixed α/β DNA-binding 'recombinase domain' linked to an unusual DNA-binding zinc ribbon domain .

The DNA-binding recombinase domain is moderately well conserved among the LSRs and consists of a four stranded β-sheet embedded in a core 4-helix bundle .
Two component regulator propeller (Reg_prop)
Type: Repeat

A large group of two component regulator proteins appear to have the same N-terminal structure of 14 tandem repeats. These repeats show homology to members of

and

indicating that they are likely to form a β-propeller. This family has been built with artificially high cut-offs in order to avoid overlaps with other β-propeller families. The fourteen repeats are likely to form two propellers; it is not clear if these structures are likely to recruit other proteins or interact with DNA.
RepB plasmid partition (Plasmid_RepB)
Type: Domain

This family includes proteins with sequence similarity to the RepB partitioning protein of the large Ti (tumour-inducing) plasmids of Agrobacterium tumefaciens .
Rho termination factor-like, N-terminal (Rho-like_N)
Type: Domain

The Rho termination factor disengages newly transcribed RNA from its DNA template at certain, specific transcripts. It is thought that two copies of Rho bind to RNA and that Rho functions as a hexamer of protomers . This domain is found to the N terminus of the RNA binding domain (

).
Rho termination factor, RNA-binding domain (Rho_RNA-bd)
Type: Domain

The Rho termination factor disengages newly transcribed RNA from its DNA template at certain, specific transcripts. It is thought that two copies of Rho bind to RNA and that Rho functions as a hexamer of protomers .

The Rho N-terminal domain consists of two subdomains: a three-helix bundle followed by a β-barrel. The β-barrel is an OB-type fold, which is found in a wide variety of single-stranded nucleic acid binding molecules that include cold shock proteins. An indented face on one side of this subdomain forms the primary RNA binding site of Rho .
Holliday junction DNA helicase RuvA, C-terminal (RuvA_C)
Type: Domain

In prokaryotes, RuvA, RuvB, and RuvC process the universal DNA intermediate of homologous recombination, termed Holliday junction. The tetrameric DNA helicase RuvA specifically binds to the Holliday junction and facilitates the isomerization of the junction from the stacked folded configuration to the square-planar structure . In the RuvA tetramer, each subunit consists of three domains, I, II and III, where I and II form the major core that is responsible for Holliday junction binding and base pair rearrangements of Holliday junction executed at the crossover point, whereas domain III regulates branch migration through direct contact with RuvB.

The domain represents the C-terminal domain III of RuvA. This domain plays a significant role in the ATP-dependent branch migration of the hetero-duplex through direct contact with RuvB . Within the Holliday junction, this domain makes no interaction with the DNA.
SecA DEAD-like, N-terminal (SecA_DEAD)
Type: Domain

SecA protein binds to the plasma membrane where it interacts with proOmpA to support translocation of proOmpA through the membrane. SecA protein achieves this translocation, in association with SecY protein, in an ATP-dependent manner . This domain represents the N-terminal ATP-dependent helicase domain.
SecA Wing/Scaffold (SecA_Wing/Scaffold)
Type: Domain

SecA protein binds to the plasma membrane where it interacts with proOmpA to support translocation of proOmpA through the membrane. SecA protein achieves this translocation, in association with SecY protein, in an ATP-dependent manner. This domain is composed of two C-terminal α helical subdomains: the wing and scaffold subdomains.
Tannase/feruloyl esterase (Tannase/feruloyl_esterase)
Type: Family

This family includes fungal tannase and feruloyl esterase . It also includes mono(2-hydroxyethyl) terephthalate hydrolase from the bacterium Ideonella sakaiensis and several bacterial homologues of unknown function.
Uncharacterised domain, helicase/relaxase, putative (Unchr_helicase_relaxase_TraI)
Type: Domain

The members of this family are restricted to the proteobacteria. Some members have been annotated as helicase, conjugative relaxase or nickase. The majority contain an HD domain, which is found in a superfamily of enzymes with a predicted or known phosphohydrolase activity. These enzymes appear to be involved in the nucleic acid metabolism, signal transduction and possibly other functions in bacteria.
Neutral trehalase Ca2+ binding (Trehalase_Ca-bd)
Type: Domain

Neutral trehalases mobilise trehalose accumulated by fungal cells as a protective and storage carbohydrate. This family represents a calcium-binding domain similar to EF hand. Residues 97 and 108 in

have been implicated in this interaction. It is thought that this domain may provide a general mechanism for regulating neutral trehalase activity in yeasts and filamentous fungi .
Tryptophan-rich domain (Trp-rich_dom)
Type: Domain

This entry represents a tryptophan-rich domain found in membrane proteins of Proteobacteria and Cyanobacteria. It is normally found in 2 to 3 copies.
WavE lipopolysaccharide synthesis (WavE)
Type: Family

These proteins are encoded by putative wav gene clusters, which are responsible for the synthesis of the core oligosaccharide (OS) region of Vibrio cholerae lipopolysaccharide .
Two component regulator three Y (Y_Y_Y)
Type: Domain

This region is mostly found at the end of the β-propellers (

) in a family of two component regulators. However they are also found tandemly repeated in

without other signal conduction domains being present. It is named after the conserved tyrosines found in the alignment. The exact function is not known.
Zinc finger, CW-type (Znf_CW)
Type: Domain

This entry represents a CW-type zinc finger motif, named for its conserved cysteine and tryptophan residues. It is predicted to be a highly specialised mononuclear four-cysteine (C4) zinc finger that plays a role in DNA binding and/or promoting protein-protein interactions in complicated eukaryotic processes including chromatin methylation status and early embryonic development. Weak homology to members of

further evidences these predictions. The domain is found exclusively in vertebrates, vertebrate-infecting parasites and higher plants .

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Zinc finger, HypF-type (Znf_HypF)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

Proteins of the HypF family are involved in the maturation and regulation of hydrogenase . In the N terminus they appear to have two zinc finger domains that are similar to those found in the DnaJ chaperone .