SII-SWORD/CoKE huggingface dataset:
YlxR domain (YlxR_dom)
Type: Domain

This entry represents a domain found in YlxR from Bacillus subtilis, its homologue SP0554 from Streptococcus pneumoniae (

) and in other bacterial proteins. YlxR regulate metabolic gene expression . SP0554 revealed an α+β fold with a large positively charged patch on one side of the protein, that could have evolved from a glucocorticoid receptor-like zinc finger domain .
Putative helix-turn-helix protein, YlxM/p13-like (UPF0122)
Type: Family

Members of this family are predicted to contain a helix-turn-helix motif, for example residues 37-55 in Mycoplasma mycoides p13 (

). Genes encoding family members are often part of operons that encode components of the SRP pathway, and this protein may regulate the expression of an operon related to the SRP pathway .
Putative neutral zinc metallopeptidase (Zn_peptidase_2)
Type: Family

Members of this family of bacterial proteins are described as hypothetical proteins or zinc-dependent proteases. The majority have a HExxH zinc-binding motif characteristic of neutral zinc metallopeptidases, however there is no evidence to support their function as metallopeptidases.
Transcriptional regulator PAI 2-type (TR_PAI2-type)
Type: Family

In Bacillus subtilis, family member

, PAI 2, is involved in the negative regulation of protease synthesis and sporulation . Its structure has been solved .
F-box associated (FBA) domain (F-box-assoc_dom)
Type: Domain

F-box proteins have a bipartite structure: they contain a carboxy-terminal
domain that interacts with substrates and a 42-48 amino-acid F-box domain which binds to the protein Skp1. A subset of F-box proteins is
characterised by a ~180-residue carboxy-terminal region, which has been called
the F-box-associated (FBA) domain . A FBA domain has also been identified
in the catfish, tilapia, and zebrafish nonspecific cytotoxic cell receptor
proteins (NCCRP-1), which do not contain the F-box domain. NCCRP-1 may
function as an antigen recognition molecule and, as such, may participate in
innate immunity in teleosts . The FBA domain is likely to be a
glycoprotein-binding module .
Pimeloyl-ACP methyl esterase BioG (BioG)
Type: Family

This protein family includes Pimeloyl-ACP methyl esterase BioG from Haemophilus influenzae

and similar bacterial proteins. This enzyme is involved in the biosynthesis of pymeloyl-ACP and, hence, in biotin biosynthesis. It is organised into a a core domain formed by a seven-stranded β-sheet and a lid domain consisting of four α-helices .
PrpF-like (PrpF-like)
Type: Family

PrpF is a protein found in the 2-methylcitrate pathway. It is structurally similar to DAP epimerase and proline racemase. This protein is an aconitate- isomerise converting trans-aconitate to cis-aconitate .
Protein of unknown function DUF454 (DUF454)
Type: Family

This entry includes YbaN from Escherichia coli. It is an inner membrane protein.
Protein of unknown function DUF455 (DUF455)
Type: Family

This is a family of uncharacterised proteins.
Protein of unknown function DUF456 (DUF456)
Type: Family

This is a family of putative membrane proteins.
YdjM inner membrane (YdjM-like)
Type: Family

This is a family of putative LexA-binding proteins. Members are predicted to be membrane-bound metal-dependent hydrolases that may be acting as phospholipases. It is a member of the SOS network, that rescues cells from UV and other DNA-damage. Expression of YdjM is regulated by LexA .
Bacteriophage KVP40, Orf299 (Phage_KVP40_Orf299)
Type: Family

This entry is represented by Bacteriophage KVP40, Orf299. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This is a family of uncharacterised, mainly bacterial, proteins. While the functions of these proteins are unknown, an analysis has suggested that they may form a novel family within the RNASE H-like superfamily . These proteins appear to contain all the core secondary structural elements of the RNase H-like fold and share several conserved, possible active site, residues. It was suggested, therefore, that they function as nucleases. From the taxonomic distibution of these proteins it was further inferred that they may play a role in DNA repair under stressful conditions.
MukB, N-terminal domain (MukB_N_dom)
Type: Domain

This is the N-terminal region of MukB. MukB is involved in the segregation and condensation of prokaryotic chromosomes. MukE (

) along with MukF (

) interact with MukB in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli . The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC . ScpA (

) and ScpB (

) have little sequence similarity to MukE or MukF, though they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.
Protein of unknown function DUF459 (DUF459)
Type: Family

This is a putative periplasmic protein and a member of the SGNH-family of hydrolases, a diverse family of lipases and esterases. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely resembles the Ser-His-Asp(Glu) triad found in other serine hydrolases .
Protein of unknown function DUF460 (DUF460)
Type: Family

This is an archaeal protein of unknown function.
Restriction endonuclease, type I, HsdR, N-terminal (Restrct_endonuc_type1_HsdR_N)
Type: Domain

This entry represents the N-terminal domain found in the R subunit (HsdR) of type I enzymes. The type I enzyme represented is EcoKI, which recognises the DNA sequence 5'-AACN6GTGC-3'; the R protein (HsdR) is required for both nuclease and ATPase activity .

This domain is often found adjacent to a methylase domain (

) in restriction endonucleases or methylases. In one of the proteins,

, it is adjacent to a helicase domain (

) in a putative restriction endonuclease.

Type I restriction endonucleases are components of prokaryotic DNA restriction-modification mechanisms that protects the organism against invading foreign DNA. Type I enzymes have three different subunits subunits -M (modification), S (specificity) and R (restriction) -that form multifunctional enzymes with restriction (

), methylase (

) and ATPase activities . The S subunit is required for both restriction and modification and is responsible for recognition of the DNA sequence specific for the system. The M subunit is necessary for modification, and the R subunit is required for restriction. These enzymes use S-Adenosyl-L-methionine (AdoMet) as the methyl group donor in the methylation reaction, and have a requirement for ATP. They recognise asymmetric DNA sequences split into two domains of specific sequence, one 3-4 bp long and another 4-5 bp long, separated by a nonspecific spacer 6-8 bp in length. Cleavage occurs a considerable distance from the recognition sites, rarely less than 400 bp away and up to 7000 bp away. Adenosyl residues are methylated, one on each strand of the recognition sequence. These enzymes are widespread in eubacteria and archaea. In enteric bacteria they have been subdivide into four families: types IA, IB, IC and ID.

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.
Copper chaperone PCuAC (PCuAC)
Type: Family

CuA is a dinuclear copper site within the soluble domain of subunit II (Cox2) of bacterial and eukaryotic cytochrome c oxidases (CcOs), whose function is to convey electrons from a soluble cytochrome c to the catalytic heme a3-CuB centre of CcO. The proper assembly of the CuA site is essential for the catalytic machinery of a functional oxidase. In prokaryotes two protein families have been proposed to be involved in CuA site formation, with a key role in the delivery of metal ions to the CuA site. The first includes proteins that are able to bind Cu(I) through methionine and histidine residues arranged in a highly conserved H(M)X(10)MX(21)HXM motif 5 (referred to as periplasmic CuA chaperone, PCu(A)C). The second consists of the Sco proteins, whose mechanism of action in CuA assembly as thioredoxins or metallochaperones is still debated. These proteins (PCuAC and Sco) are often found in the same bacterial operon, and most of the identified operons that encode Sco also contain a gene for Cox2 .

PCu(A)C is a periplasmic copper chaperone. It selectively inserts Cu(I) ions into subunit II of Thermus thermophilus ba3 oxidase to generate a native Cu(A) site. Its role may be to capture and transfer copper to two other copper chaperones, PrrC and Cox11, which in turn deliver Cu(I) to cytochrome c oxidase .
Elongation factor P hydroxylase (EpmC)
Type: Family

This family catalyses the final step in the elongation factor P modification pathway. It hydroxylates Lys-34 of elongation factor P. Members of this family have a conserved HEXXH motif, suggesting they are putative peptidases of zincin fold .
Anti-sigma-28 factor, FlgM (FlgM)
Type: Family

FlgM binds and inhibits the activity of the transcription factor sigma 28. Inhibition of sigma 28 prevents the expression of genes from flagellar transcriptional class 3, which include genes for the filament and chemotaxis. Correctly assembled basal body-hook structures export FlgM, relieving inhibition of sigma 28 and allowing expression of class 3 genes. NMR studies show that free FlgM is mostly unfolded, which may facilitate its export. The C-terminal half of FlgM adopts a tertiary structure when it binds to sigma 28. All mutations in FlgM that prevent sigma 28 inhibition affect the C-terminal domain and is the region thought to constitute the binding domain. A minimal binding domain has been identified between Glu 64 and Arg 88 in Salmonella typhimurium (

).The N-terminal portion remains unstructured and may be necessary for recognition by the export machinery .
Ras-like GTPase YcjX (YcjX-like)
Type: Family

This family represents a group of proteins related to Ras-like GTPase YcjX. The crystal structure of YcjX from Shewanella oneidensis has now been solved, and shows it to be a Ras-like GTP-binding protein that binds GTP and GDP, and has an intrinsic GTPase activity. YcjX utilises a non-canonical switch 2' motif not found in any other G protein .
Protein of unknown function DUF468 (DUF468)
Type: Family

This is a family of uncharacterised yeast proteins.
Nitrogenase MoFe maturation protein, NifZ (Nitrogenase_MoFe_mat_NifZ)
Type: Family

NifZ is a short protein is found in the nif (nitrogen fixation) operon. It is required for the maturation of the nitrogenase MoFe protein. In the absence of NifZ, only one of the two P-clusters of the MoFe protein is matured to the ultimate [8Fe-7S] structure. The other P-cluster site in the protein contains a [4Fe-4S] cluster pair, suggesting that NifZ is specifically required for the formation of the second P-cluster .
YggL 50S ribosome-binding protein (YggL_50S_bp)
Type: Family

YggL from E.coli was recently characterised and it interacts with ribosome subunits 50S and 70S. It is a 50S-binding protein likely to be involved in particle assembly. It is a small protein extremely conserved in Gammaproteobacteria but also present in orders Burkholderiales and Neisseriales from Betaproteobacteria .
Protein of unknown function DUF473 (DUF473)
Type: Family

This is a family of uncharacterised archaeal proteins.
Protein of unknown function DUF474 (DUF474)
Type: Family

This is a family of uncharacterised archaeal/bacterial proteins.They are predicted to be integral membrane proteins with several transmembrane segments.
BFD-like [2Fe-2S]-binding domain (BFD-like_2Fe2S-bd_dom)
Type: Domain

The two Fe ions are each coordinated by two conserved cysteine residues. This domain occurs alone in small proteins such as bacterioferritin-associated ferredoxin (BFD,

). The function of BFD is not known, but it may be a general redox and/or regulatory component involved in the iron storage or mobilisation functions of bacterioferritin in bacteria . This domain is also found in nitrate reductase proteins in association with the nitrite and sulphite reductase 4Fe-4S domain (

), nitrite/sulphite reductase ferredoxin-like half domain (

). It is also found in NifU nitrogen fixation proteins, in association with NifU-like N-terminal domain (

) and C-terminal domain (

).
Protein of unknown function DUF465 (DUF465)
Type: Family

Family members are found in small bacterial proteins, and also in the heavy chains of fungal proteins that contain the domain kinesin, in which this region is located C-terminal of the motor domain. Members of this family may form coiled coil structures .
Schlafen, AlbA_2 domain (Schlafen_AlbA_2_dom)
Type: Domain

This entry represents the AlbA clan of DNA-binding domains.

This is the AlbA_2 domain from the Schlafen (SLFN) family of proteins which are important in cell differentiation and defense against viruses . This domain is present at the N-terminal of all SLFN proteins and includes the SLFN box, a sequence unique to these proteins that may form a dimer interface . The AlbA_2 domain is RNA-binding and RNase region as it contains the highly conserved catalytic glutamic acid residues .
Cysteine protease Prp (Peptidase_Prp)
Type: Family

This is a family of cysteine proteases that are found to cleave the N terminus extension of ribosomal subunit L27 in eubacteria. Proteins in this family are distinguished by a pair of invariant histidine and cysteine residues with conserved spacing that form the classic catalytic dyad of a cysteine protease . Staphylococcus aureus depends on L27 cleavage by Prp for ribosome function, being a target for antibiotic development .
Selenoprotein, putative (Sel_put)
Type: Family

This entry includes a group of putative selenoproteins from Proteobacteria, Actinobacteria and Firmicutes. The invariant cysteine at the C terminus is encoded by a TGA Sec codon in some Epsilonproteobacteria, suggesting a redox activity for the protein .
Protein of unknown function DUF475 (DUF475)
Type: Family

This entry contains proteins that are predicted to be an integral membrane proteins with multiple transmembrane domains.
MlaA lipoprotein (MlaA)
Type: Family

Intermembrane phospholipid transport system lipoprotein MlaA is a component of the Mla pathway, an ABC transport system that functions to maintain the asymmetry of the outer membrane . MlaA, also known as VacJ, is required for the intercellular spreading of Shigella flexneri. It is attached to the outer membrane by a lipid anchor .
Protein of unknown function DUF478 (DUF478)
Type: Family

This family contains uncharacterised protein encoded on Trypanosomal kinetoplast minicircles.
Bacterial virulence protein VirB8 (VirB8)
Type: Domain

VirB8 is a bacterial virulence protein with cytoplasmic, transmembrane, and periplasmic regions. It is thought that it is a primary constituent of a DNA transporter. The periplasmic region interacts with VirB9, VirB10, and itself . It is required for stabilisation of VirB3 (an inner membrane protein) . This family also includes the conjugal transfer protein family TrbF, a family of proteins known to be involved in conjugal transfer. The TrbF protein is thought to compose part of the pilus required for transfer .
Acyl carrier protein phosphodiesterase (ACP_PD)
Type: Family

This entry contains the Escherichia coli gene yajB, now renamed acpH, which encodes an ACP hydrolase. AcpH converts holo-ACP to apo-ACP by hydrolytic cleavage of the phosphopantetheine prosthetic group from ACP .

A mutant E. coli strain having a total deletion of the acpH grows normally, showing that phosphodiesterase activity is not essential for growth, although it is required for turnover of the ACP prosthetic group in vivo. AcpH is found only in Gram-negative organisms suggesting that it plays a role in some aspect of lipid metabolism that is unique to these organisms. The most obvious of which is biosynthesis of lipid A. Because AcpH is a hydrolase, it could possibly be an editing enzyme that intercepts acyl-ACPs that would give an inappropriate lipid A structure if used as acyl donors .
Protein of unknown function DUF480 (DUF480)
Type: Family

This family consists of several proteins of uncharacterised function.
Protein of unknown function DUF481 (DUF481)
Type: Family

This family includes several proteins of uncharacterised function.
Peptidogalycan biosysnthesis/recognition (FemAB-like)
Type: Family

This is a family of both bacterial and plant proteins with responsibility for building interpeptide bridges in peptidoglycan. Such a function is feasible for bacteria but less likely for the plant members of this family. Perhaps the plant-members are using homologous proteins to recognise bacterial peptidoglcans as part of their innate immune system .
Protein of unknown function DUF484 (DUF484)
Type: Family

This family consists of several proteins of uncharacterised function.
Protein of unknown function DUF485 (DUF485)
Type: Family

This family includes several putative integral membrane proteins.
Protein of unknown function DUF486 (DUF486)
Type: Family

This family contains several proteins of uncharacterised function. The family is represented in the Transport classification database as 2.A.7.34, though the exact nature of what is transported is not known.
Protein of unknown function DUF488 (DUF488)
Type: Family

This family includes several proteins of uncharacterised function.
Chemotaxis phosphatase, CheZ (Chemotax_Pase_CheZ)
Type: Family

This family represents the bacterial chemotaxis phosphatase, CheZ. This protein forms a dimer characterised by a long four-helix bundle, composed of two helices from each monomer. CheZ dephosphorylates CheY in a reaction that is essential to maintain a continuous chemotactic response to environmental changes. It is thought that CheZ's conserved residue Gln 147 orientates a water molecule for nucleophilic attack at the CheY active site.
Chorismate--pyruvate lyase (Chorismate--pyruvate_lyase)
Type: Family

Chorismate--pyruvate lyase catalyses the first step in ubiquinone synthesis, the removal of pyruvate from chorismate, to yield 4-hydroxybenzoate in Escherichia coli and other Gram-negative bacteria . The yeast Saccharomyces cerevisiae can synthesize ubiquinone from either chorismate or tyrosine , however this enzyme is found only in bacteria. Its activity does not require metal cofactors .
Ethanolamine utilisation protein EutH (EutH)
Type: Family

Protonated ethanolamine does not enter cells, while uncharged ethanolamine diffuses freely across the membrane. External concentrations of the two forms vary with the pH. It has been shown in Salmonella enterica that EutH is a membrane protein that facilitates diffusion of protonated ethanolamine . It is involved in bacterial survival and replication in acidified macrophage vacuoles .
Penicillin-binding protein activator LpoA (LpoA)
Type: Family

This entry represents penicillin-binding protein activators LpoA. It has been suggested that penicillin-binding protein activator acts as a regulator of peptidoglycan synthesis that is essential for the function of penicillin-binding protein 1A (PBP1a).
Glucan biosynthesis, periplasmic, MdoG C-terminal (Glucan_biosyn_MdoG_C)
Type: Domain

Membrane-derived oligosaccharides (MDO) are members of a family of glucans found in the periplasmic space of Gram-negative bacteria. MdoG has been shown to be necessary for the synthesis of MDO , but its exact function is not known yet. MdoD, an MdoG paralog, is a twin-arginine-dependent periplasmic protein that controls osmoregulated periplasmic glucan backbone structures . This entry represents the functional portion of the protein and excludes the N-terminal signal sequence.
Type IV pilus inner membrane component PilO (PilO)
Type: Family

Bacterial type IV pili are surface filaments critical for diverse biological processes including surface and host cell adhesion, colonisation, biofilm formation, twitching motility, DNA uptake during natural transformation and virulence . The proteins necessary to form the type IV pili inner-membrane complex, are included in the pilMNOPQ operon which encodes the cytoplasmic actin-like protein PilM, PilN, PilO, the periplasmic lipoprotein PilP and the outer-membrane secretin PilQ. The inner-membrane PilM/N/O/P complex is required for the optimal function of the outer-membrane secretin PilQ. This cluster is highly conserved across the type IV pilus-producing bacterial species, and all of these proteins have been shown to be essential for twitching motility .

This entry represents type IV pilus inner membrane component PilO, which is necessary for proper folding of PilN. PilO and PilN depend on each other for stability and the periplasmic domains of them interact to form a stable heterodimer, which is essential for the assembly of a functional complex .
Type IV pilus inner membrane component PilP (PilP)
Type: Family

Bacterial type IV pili are surface filaments critical for diverse biological processes including surface and host cell adhesion, colonisation, biofilm formation, twitching motility, DNA uptake during natural transformation and virulence . The proteins necessary to form the type IV pili inner-membrane complex, are included in the pilMNOPQ operon which encodes the cytoplasmic actin-like protein PilM, PilN, PilO, the periplasmic lipoprotein PilP and the outer-membrane secretin PilQ. The inner-membrane PilM/N/O/P complex is required for the optimal function of the outer-membrane secretin PilQ. This cluster is highly conserved across the type IV pilus-producing bacterial species, and all of these proteins have been shown to be essential for twitching motility .

The PilP family are periplasmic proteins involved in the biogenesis of type IV pili . The N-terminal domain of PilP interacts with the periplasmic regions of PilNO, while the C-terminal beta-domain of PilP interacts with the N0 domain of PilQ, connecting PilO to the secretin PilQ .

This entry also includes competence protein D (comD) from Haemophilus influenzae which is encoded in the homologous operon comA/B/C/D/E.
Regulator of RNA polymerase sigma(70) subunit, Rsd/AlgQ (Sigma70_reg_Rsd_AlgQ)
Type: Family

This family includes bacterial transcriptional regulators that are thought to act through an interaction with the conserved region 4 of the sigma(70) subunit of RNA polymerase . The Pseudomonas aeruginosa homologue, AlgQ, positively regulates virulence gene expression and is associated with the mucoid phenotype observed in P. aeruginosa isolates from cystic fibrosis patients.