SII-SWORD/CoKE huggingface dataset:
ZipA, C-terminal FtsZ-binding domain (ZipA_FtsZ-bd_C)
Type: Domain

This entry represents the ZipA C-terminal domain. ZipA, a membrane-anchored protein, is an essential cell division protein involved in septum formation . FtsA and the C-terminal domain of ZipA bind FtsZ, a homologue of eukaryotic tubulins and a major component of the bacterial septal ring , at the prospective division site. This is followed by the sequential addition of FtsK, FtsQ, FtsL, FtsW, FtsI, and FtsN . ZipA contains three domains: a short N-terminal membrane-anchored domain, a central P/Q domain that is rich in proline and glutamine and a C-terminal domain, which comprises almost half the protein. The structure of the C-terminal domain is an α-β fold with three α helices and a β sheet of six antiparallel β strands. The major loops protruding from the β sheet surface are thought to form a binding site for FtsZ .
Outer membrane protein assembly factor BamE domain (BamE_dom)
Type: Domain

This domain is found in bacterial outer membrane lipoproteins probably involved in maintaining the structural integrity of the cell envelope , including Outer membrane protein assembly factor BamE from Vibrio cholerae (also known as SmpA). The lipid attachment site is a conserved N-terminal cysteine residue sometimes found adjacent to the OmpA domain (

).

Proteins containing this domain also includes TpgA from Acinetobacter sp. TpgA forms a complex with AtaA, anchoring it to the outer membrane (OM) .
High frequency lysogenization protein HflD (HflD)
Type: Family

When bacteriophage lambda infects to the Escherichia coli cell, it undergoes either lytic growth or lysogenization. The lambda CII protein is a key determinant in the lysis-lysogeny decision. Escherichia coli HflD is a factor that may sequesters CII from the target promoters and recruits it to the membrane where the FtsH protease is localized .
Translocation and assembly module TamB, C-terminal domain (TamB_C)
Type: Domain

This entry represents the C-terminal domain in TamB proteins mainly found in bacteria and plants.

TamB is an integral inner membrane protein that forms a complex, the translocation and assembly module or TAM , with the outer membrane protein, TamA. TAM is responsible for the efficient secretion of the adhesin protein Ag43 in E.coli K-12 .
Sulphur transfer protein DsrC/TusE (DsrC/TusE)
Type: Family

Members of this protein family include TusE, a partner to TusBCD in a sulphur relay system for 2-thiouridine biosynthesis, a tRNA base modification process . Other members are DsrC , a functionally similar protein in species where the sulphur relay system exists primarily for sulphur metabolism , rather than tRNA base modification. Some members of this family are known explicitly as the gamma subunit of sulphite reductases.
Uncharacterised protein family UPF0250, YbeD-like (UPF0250_YbeD-like)
Type: Family

This family includes UPF0250 protein YbeD from Escherichia coli and similar prokaryotic proteins. YbeD shows structural homology to the regulatory domain from 3-phosphoglycerate dehydrogenase, which suggests a role in the allosteric regulation of lipoic acid biosynthesis or the glycine cleavage system . The protein has been shown to play an important role in enduring high-temperature stress .
Serglycin (Serglycin)
Type: Family

Serglycin was first identified as an intracellular proteoglycan expressed by hematopoietic cells. All inflammatory cells highly synthesize serglycin and store it in granules, where it interacts with numerous inflammatory mediators, such as proteases, chemokines, cytokines, and growth factors. Later serglycin was found to be expressed by various non-hematopoietic cell types, such as tumour cells. Serglycin promotes the aggressive phenotype of tumours and confers resistance against drugs and complement system attack .

Human serglycin consists of a small core protein containing eight serine/glycine repeats. Each serine of this repeat region is a potential GAG attachment site .
Smg (Smg)
Type: Family

This entry represents the Smg family of bacterial proteins. Their function is unknown.
Fe(II) trafficking protein YggX (Fe_traffick_prot_YggX)
Type: Family

The protein represented by this entry, YggX, serves to protect Fe-S clusters from oxidative damage . The effect is two-fold: proteins that rely on Fe-S clusters do not become inactivated, and the release of free iron and hydrogen peroxide--a DNA damaging agent--is prevented. These observations are consistent with the hypothesis that YggX chelates free iron, and recent experiments show that YggX can indeed bind Fe(II) in vitro and in vivo . Furthermore, YggX has a positive effect on the action of at least one Fe(II)-responsive protein. The combined actions of YggX is reminiscent of iron trafficking proteins , and YggX is therefore proposed to play a role in Fe(II) trafficking . In Escherichia coli, YggX was shown to be under the transcriptional control of the redox-sensing SoxRS system .
Protein of unknown function DUF496 (DUF496)
Type: Family

Members of this family are uncharacterised proteins.
DNA polymerase III chi subunit, HolC (DNA_pol3_chi)
Type: Family

The DNA polymerase III holoenzyme (

) is the polymerase responsible for the replication of the Escherichia coli chromosome. The holoenzyme is composed of the DNA polymerase III core, the sliding clamp, and the DnaX clamp loading complex. The DnaX complex contains either the tau or gamma product of gene dnax, complexed to delta.delta and to chi psi. Chi forms a 1:1 heterodimer with psi. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta allowing a functional clamp-loading complex to form at physiological subunit concentrations. Psi is responsible for the interaction with DnaX (gamma/tau), but psi is insoluble unless it is in a complex with chi . Members of this protein family are mainly found in proteobacteria.
Ribonuclease toxin, BrnT, of type II toxin-antitoxin system (BrnT_toxin)
Type: Family

BrnT is a ribonuclease toxin of a type II toxin-antitoxin system that exhibits a RelE-like fold. The antitoxin that neutralises this toxin is (

). BrnT is found in bacteria, archaea, bacteriophage, and plasmids. BrnT-BrnA forms a 2:2 tetrameric complex and autoregulates its own expression, which is induced by a number of different environmental stresses. Expression of BrnT alone results in cessation of bacterial growth which can be rescued after subsequent expression of BrnA .
Ysc84 actin-binding domain (Ysc84_actin-binding)
Type: Domain

This entry corresponds to proteins having the Ysc84 actin binding domain (YAB). This 184 amino acid domain lies at the N terminus of the Saccharomyces cerevisiae (Baker's yeast) protein Ysc84 (

). It is essential for the organisation of the actin cytoskeleton, and interacts with the Arp2/3 complex . Homologous domains are found across a range of species. In fungi and vertebrates the domain is at the N terminus, while there is an SH3 domain at the C terminus. In plants the domain seems to be at the C terminus and in association with a FYVE domain. Interestingly, the domain is absent in invertebrates.

The domain is also found in prokaryotes, where presumable it is also involved in protein binding, perhaps to the prokaryotic homologue of actin .
Protein CONTINUOUS VASCULAR RING 1-like (COV1-like)
Type: Family

This entry includes COV1 from Arabidopsis and uncharacterised proteins from bacteria and archaea. COV1 is an integral membrane protein involved in the regulation of vascular patterning in the stem, probably by negatively regulating the differentiation of vascular tissue .
Protein of unknown function DUF507 (DUF507)
Type: Family

This entry represents a bacterial protein of unknown function.
Bacteriocin, class IId (Bacteriocin_IId)
Type: Family

Bacteriocins are produced by bacteria to inhibit the growth of similar or closely related bacterial strains. The class II bacteriocins are small heat-stable proteins for which disulphide bonds are the only modification to the peptide.

Lactococcin A and B are class-IId bacteriocins (one-peptide non-pediocin-like bacteriocin) .
Protein of unknown function DUF508 (DUF508)
Type: Family

This is a family of uncharacterised proteins from Caenorhabditis elegans.
Peptidyl-arginine deiminase, Porphyromonas-type (Peptidyl-Arg-deiminase_porph)
Type: Family

Peptidyl-arginine deiminase (PAD) enzymes catalyse the deimination of the guanidino group from carboxy-terminal arginine residues of various peptides to produce ammonia. PAD from Porphyromonas gingivalis (Bacteroides gingivalis) (PPAD) appears to be evolutionarily unrelated to mammalian PAD (

), which is a metalloenzyme. PPAD is thought to belong to the same superfamily as aminotransferase and arginine deiminase, and to form an α/β propeller structure. This family has previously been named PPADH (Porphyromonas peptidyl-arginine deiminase homologues) . The predicted catalytic residues in PPAD (

) are Asp130, Asp187, His236, Asp238 and Cys351 . These are absolutely conserved with the exception of Asp187 which is absent in two family members. PPAD is also able to catalyse the deimination of free L-arginine, but has primarily peptidyl-arginine specificity. It may have a FMN cofactor .
Putative uroporphyrinogen-III C-methyltransferase HemX (HemX)
Type: Family

This is a family of bacterial putative uroporphyrinogen-III C-methyltransferase proteins. It forms one of the members of a complex of proteins involved in the biogenesis of the inner membrane in E.coli. Uroporphorphyrin-III C-methyltransferase (HemX) is a single spanning inner membrane protein that regulates the activity of NAD(P)H:glutamyl-tRNA reductase (HemA) in the tetrapyrrole biosynthesis pathway .
N-end aminoacyl transferase, N-terminal (N-end_Aminoacyl_Trfase_N)
Type: Domain

This entry represents the N-terminal region of aminoacyl-transferases found in both eukaryotic (Arginine-tRNA-protein transferase) and prokaryotic (Aspartate/glutamate leucyltransferase) enzymes.

Arginine-tRNA-protein transferase catalyses the post-translational conjugation of arginine to the N terminus of a protein. In eukaryotes, this functions as part of the N-end rule pathway of protein degradation by conjugating a destabilising amino acid to the N-terminal aspartate or glutamate of a protein, targeting the protein for ubiquitin-dependent proteolysis . In Saccharomyces cerevisiae, Cys20, 23, 94 and/or 95 are thought to be important for activity . Of these, only Cys 94 appears to be completely conserved in this family.

Aspartate/glutamate leucyltransferase (also known as bacterial protein transferase or Bpt) functions in the N-end rule pathway of protein degradation where it conjugates Leu from its aminoacyl-tRNA to the N-termini of proteins containing an N-terminal aspartate or glutamate. This protein shows sequence similarity to the eukaryotic N-end rule pathway component arginyl-transferase Ate1 .
N-end rule aminoacyl transferase, C-terminal (N-end_Aminoacyl_Trfase_C)
Type: Domain

This entry represents the C-terminal region of aminoacyl-transferases found in both eukaryotic (Arginine-tRNA-protein transferase) and prokaryotic (Aspartate/glutamate leucyltransferase) enzymes.

Arginine-tRNA-protein transferase catalyses the post-translational conjugation of arginine to the N terminus of a protein. In eukaryotes, this functions as part of the N-end rule pathway of protein degradation by conjugating a destabilising amino acid to the N-terminal aspartate or glutamate of a protein, targeting the protein for ubiquitin-dependent proteolysis . In Saccharomyces cerevisiae, Cys20, 23, 94 and/or 95 are thought to be important for activity . Of these, only Cys 94 appears to be completely conserved in this family.

Aspartate/glutamate leucyltransferase (also known as bacterial protein transferase or Bpt) functions in the N-end rule pathway of protein degradation where it conjugates Leu from its aminoacyl-tRNA to the N-termini of proteins containing an N-terminal aspartate or glutamate. This protein shows sequence similarity to the eukaryotic N-end rule pathway component arginyl-transferase Ate1 .
Ribosomal RNA large subunit methyltransferase J (RlmJ)
Type: Family

Ribosomal methyltransferase RlmJ (YhiR) specifically methylates the adenine in position 2030 of 23S rRNA . Nascent 23S rRNA seems to be the natural substrate. RlmJ seems to be required for the utilisation of extracellular DNA as the sole source of carbon and energy .
ApaG domain (ApaG_domain)
Type: Domain

The apaG domain is a ~125 amino acids domain present in bacterial apaG proteins and in eukaryotic F-box proteins. The domain is named after the bacterial apaG protein, of which it forms the core. The domain also occurs in the C-terminal part of eukaryotic proteins with an N-terminal F-box domain. The Salmonella typhimurium apaG domain protein corD is involved in Co(2+) resistance and Mg(2+) efflux. Tertiary structures from different apaG proteins show a fold of several β-sheets. The apaG domain may be involved in protein-protein interactions which could be implicated in substrate-specificity .
Ubiquinone biosynthesis accessory factor UbiK (UbiK)
Type: Family

UbiK is an accessory factor required for efficient ubiquinone (coenzyme Q) biosynthesis under aerobic conditions. It forms a complex with the UQ biogenesis factor UbiJ .
Putative exonuclease, RdgC (RdgC)
Type: Family

Members of the RdgC family may have exonuclease activity. RdgC is required for efficient pilin variation in Neisseria gonorrhoeae, suggesting that it may be involved in recombination reactions . In Escherichia coli, RdgC is required for growth in recombination-deficient exonuclease-depleted strains. Under these conditions, RdgC may act as an exonuclease to remove collapsed replication forks, in the absence of the normal repair mechanisms .
SAB domain (SAB_dom)
Type: Domain

This presumed domain is found in proteins containing FERM domains

. This domain is found to bind to both spectrin and actin, hence the name SAB (Spectrin and Actin Binding) domain .
ISC system FeS cluster assembly, IscX (ISC_FeS_clus_asmbl_IscsX)
Type: Family

Iron-sulphur (FeS) clusters are important cofactors for numerous proteins involved in electron transfer, in redox and non-redox catalysis, in gene regulation, and as sensors of oxygen and iron. These functions depend on the various FeS cluster prosthetic groups, the most common being [2Fe-2S] and [4Fe-4S] . FeS cluster assembly is a complex process involving the mobilisation of Fe and S atoms from storage sources, their assembly into [Fe-S] form, their transport to specific cellular locations, and their transfer to recipient apoproteins. So far, three FeS assembly machineries have been identified, which are capable of synthesising all types of [Fe-S] clusters: ISC (iron-sulphur cluster), SUF (sulphur assimilation), and NIF (nitrogen fixation) systems.

The ISC system is conserved in eubacteria and eukaryotes (mitochondria), and has broad specificity, targeting general FeS proteins . It is encoded by the isc operon (iscRSUA-hscBA-fdx-iscX). IscS is a cysteine desulphurase, which obtains S from cysteine (converting it to alanine) and serves as a S donor for FeS cluster assembly. IscU and IscA act as scaffolds to accept S and Fe atoms, assembling clusters and transfering them to recipient apoproteins. HscA is a molecular chaperone and HscB is a co-chaperone. Fdx is a [2Fe-2S]-type ferredoxin. IscR is a transcription factor that regulates expression of the isc operon. IscX (also known as YfhJ) appears to interact with IscS and may function as an Fe donor during cluster assembly .

This entry represents IscX proteins (also known as hypothetical protein YfhJ) that are part of the ISC system. IscX is active as a monomer. The structure of YfhJ is an orthogonal α-bundle . YfhJ is a small acidic protein that binds IscS, and contains a modified winged helix motif that is usually found in DNA-binding proteins . YfhJ/IscX can bind Fe, and may function as an Fe donor in the assembly of FeS clusters
Protein of unknown function DUF529 (DUF529)
Type: Repeat

This entry represents a repeated region found in proteins from Theileria species. The repeat is normally about 70 residues long and contains a conserved aromatic residue in the middle.
Stringent starvation protein B (SspB)
Type: Family

Escherichia coli stringent starvation protein B (SspB), is thought to enhance the specificity of degradation of tmRNA-tagged proteins by the ClpXP protease. The tmRNA tag, also known as ssrA, is an 11-aa peptide added to the C terminus of proteins stalled during translation, targets proteins for degradation by ClpXP and ClpAP. SspB is a cytoplasmic protein that specifically binds to residues 1-4 and 7 of the tag. Binding of SspB enhances degradation of tagged proteins by ClpX, and masks sequence elements important for ClpA interactions, inhibiting degradation by ClpA . However, more recent work has cast doubt on the importance of SspB in wild-type cells . SspB is encoded in an operon whose synthesis is stimulated by carbon, amino acid, and phosphate starvation. SspB may play a special role during nutrient stress, for example by ensuring rapid degradation of the products of stalled translation, without causing a global increase in degradation of all ClpXP substrates .
Protein-tyrosine phosphatase-like, PTPLA (Tyr_Pase-like_PTPLA)
Type: Family

Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;

) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation . The PTP superfamily can be divided into four subfamilies :

(1) pTyr-specific phosphatases

(2) dual specificity phosphatases (dTyr and dSer/dThr)

(3) Cdc25 phosphatases (dTyr and/or dThr)

(4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

Receptor-like, which are transmembrane receptors that contain PTPase domains

Non-receptor (intracellular) PTPases

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif . Functional diversity between PTPases is endowed by regulatory domains and subunits.

This family includes the mammalian protein tyrosine phosphatase-like protein, PTPLA. A significant variation of PTPLA from other protein tyrosine phosphatases is the presence of proline instead of catalytic arginine at the active site. It is thought that PTPLA proteins have a role in the development, differentiation, and maintenance of a number of tissue types .
Hamartin (Hamartin)
Type: Family

This family includes the hamartin protein which is thought to function as a tumour suppressor. The hamartin protein interacts with the tuberin protein

. Tuberous sclerosis complex (TSC) is an autosomal dominant disorder and is characterised by the presence of hamartomas in many organs, such as brain, skin, heart, lung, and kidney. It is caused by mutation in either TSC1 or TSC2 tumour suppressor genes. TSC1 encodes a protein, hamartin, containing two coiled-coil regions, which have been shown to mediate binding to tuberin. The TSC2 gene codes for tuberin

.
Peptidase M28 (Peptidase_M28)
Type: Domain

This domain is found in metallopeptidases belonging to the MEROPS peptidase family M28 (aminopeptidase Y, clan MH) and in non-peptidase homologues such as transferrin receptor proteins. Members containing this domain, also contain a transferrin receptor-like dimerisation domain (

) and a protease-associated PA domain (

).

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
LPS-assembly lipoprotein LptE (LPS_assembly_LptE)
Type: Family

The cell envelope of Gram-negative bacteria consists of an inner (IM) and an outer membrane (OM) separated by an aqueous compartment, the periplasm, which contains the peptidoglycan layer. The OM is an asymmetric bilayer, with phospholipids in the inner leaflet and lipopolysaccharides (LPS) facing outward . The OM is an effective permeability barrier that protects the cells from toxic compounds, such as antibiotics and detergents, thus allowing bacteria to inhabit several different and often hostile environments. LPS is responsible for the permeability properties of the OM. LPS consists of the lipid A moiety (a glucosamine-based phospholipid) linked to the short core oligosaccharide and the distal O-antigen polysaccharide chain. The core oligosaccharide can be further divided into an inner core, composed of 3-deoxy-D-mannooctulosanate (KDO) and heptose, and an outer core, which has a somewhat variable structure. LPS is essential in most Gram-negative bacteria, with the notable exception of Neisseria meningitidis. The biogenesis of the OM implies that the individual components are transported from the site of synthesis to their final destination outside the IM by crossing both hydrophilic and hydrophobic compartments. The machinery and the energy source that drive this process are not yet fully understood. The lipid A-core moiety and the O-antigen repeat units are synthesized at the cytoplasmic face of the IM and are separately exported via two independent transport systems, namely, the O-antigen transporter Wzx (RfbX) and the ATP binding cassette (ABC) transporter MsbA that flips the lipid A-core moiety from the inner leaflet to the outer leaflet of the IM . O-antigen repeat units are then polymerised in the periplasm by the Wzy polymerase and ligated to the lipid A-core moiety by the WaaL ligase [see,

,

].

The LPS transport machinery is composed of LptA, LptB, LptC, LptD, LptE. This supported by the fact, that depletion of any of one of these proteins blocks the LPS assembly pathway and results in very similar OM biogenesis defects. Moreover, the location of at least one of these five proteins in every cellular compartment suggests a model for how the LPS assembly pathway is organised and ordered in space .

LptE forms a complex with LptD, which is involved in the assembly of LPS in the outer leaflet of the outer membrane . LptE interacts with LptD while this protein is being assembled by the β-barrel assembly machine . In Neisseria, LptE does not have a direct role in LPS transport, suggesting that the Lpt system does not function in a completely conserved manner in all Gram-negative bacteria .
Inner membrane protein YebE (YebE)
Type: Family

Some family members may be secreted or integral membrane proteins. This entry includes the inner membrane protein YebE from Escherichia coli.