SII-SWORD/CoKE huggingface dataset:
DNA-binding HTH domain, TetR-type, conserved site (DNA-bd_HTH_TetR-type_CS)
Type: Conserved_site

The TetR-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 60 residues present in the TetR family of prokaryotic transcription regulators. Several of these bacterial regulators are repressors of genes and operons for membrane transport and cell envelope permeability. The family is named after the TetRacycline repressor TetR of enterobacteria found on Tn10 and other transposons and plasmids. The 'helix-turn-helix' DNA-binding motif is located in the N-terminal extremity of these transcriptional regulators . The C-terminal part of TetR-type regulators contains several regions that can be involved in (1) binding of inducers, which can be drugs, and (2) oligomerisation. The TetR and camR proteins are dimers, whilst qacR binds its operator as a pair of dimers and ethR seems to bind as an octamer . TetR-type transcription regulators include several bacterial regulators of drug export systems that protect pathogenic bacteria against antibiotics, antiseptics, disinfectants and host-encoded antimicrobials .
Putative metal-dependent hydrolase YfiT (Put_metal_dep_hydrolase_YfiT)
Type: Family

This entry is represented by YfiT, which is a 19kDa polypeptide from Bacillus subtilis, belonging to a small sequence family with members predominantly from Gram-positive bacteria. The crystal structure of YfiT in complex with Ni(2+) has been determined to a resolution of 1.7 A . YfiT exists as a dimer and binds Ni(2+) in a 1:1 stoichiometry. The protein has an unusual four-helix bundle topology and coordinates Ni(2+) in an octahedral geometry with three conserved histidines and three waters. Although there is no similarity in their overall structures, the coordination geometry of the metal and the residues that constitute the putative active site in YfiT are similar to those of metalloproteases such as thermolysin. YfiT may therefore function as a metal-dependent hydrolase.
Bifunctional protein Aas (Aas)
Type: Family

This entry represents a bifunctional enzyme which possesses 2-acylglycerophosphoethanolamine acyltransferase and acyl synthetase activity. It is responsible for regeneration of phosphatidylethanolamine from 2-acyl-glycero-3-phosphoethanolamine (2-acyl-GPE) formed by transacylation reactions or degradation by phospholipase A1 .
Anti-adapter protein, IraD (Anti-adapt_IraD)
Type: Family

This entry represents the bacterial anti-adapter protein IraD (inhibitor of RssB after DNA damage) family. It inhibits RpoS proteolysis by regulating RssB activity, thereby increasing the stability of the sigma stress factor RpoS during oxidative stress. Its effect on RpoS stability is due to its interaction with RssB, which probably blocks the interaction of RssB with RpoS, and the consequent delivery of the RssB-RpoS complex to the ClpXP protein degradation pathway which inhibits RpoS proteolysis by regulating RssB adaptor activity .
Amino acid/peptide transporter family, dipeptide permease D (AA/pep_transptr_DtpD)
Type: Family

The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The amino acid/peptide transporter family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analysis of a number of recently discovered peptide transport proteins . This family consists of bacterial proton-dependent oligopeptide transporters, although they are found in yeast, plants and animals. They function by proton symport in a 1:1 stoichiometry, which is variable in different species. Structurally, these transporters present a conserved architecture consisting of 14 transmembrane α-helices with N-terminal and C-terminal six-helix bundles connected by two transmembrane α-helices (HA and HB) .

This entry represents a family of probable proton-dependent permeases that transport dipeptides.
Amino acid/peptide transporter family, dipeptide/tripeptide permease B (AA/pep_transptr_DtpB)
Type: Family

The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The amino acid/peptide transporter family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analysis of a number of recently discovered peptide transport proteins . This family consists of bacterial proton-dependent oligopeptide transporters, although they are found in yeast, plants and animals. They function by proton symport in a 1:1 stoichiometry, which is variable in different species. Structurally, these transporters present a conserved architecture consisting of 14 transmembrane α-helices with N-terminal and C-terminal six-helix bundles connected by two transmembrane α-helices (HA and HB) .

This entry represents a family of proton-dependent permeases that transport di- and tripeptides.
Chromo domain, conserved site (Chromodomain_CS)
Type: Conserved_site

The CHROMO (CHRromatin Organization MOdifier) domain is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation. These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, the chromo domain has been shown to be important for chromatin targeting.

Proteins that contain a chromo domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain followed by a region termed the chromo shadow domain, with weak but significant sequence similarity to the N-terminal chromo domain , eg. Drosophila and human heterochromatin protein Su(var)205 (HP1). The second class includes proteins with a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigen and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.

Functional dissections of chromo domain proteins suggests a mechanistic role for chromo domains in targeting chromo domain proteins to specific regions of the nucleus. The mechanism of targeting may involve protein-protein and/or protein/nucleic acid interactions. Hence, several line of evidence show that the HP1 chromo domain is a methyl-specific histone binding module, whereas the chromo domain of two protein components of the drosophila dosage compensation complex, MSL3 and MOF, contain chromo domains that bind to RNA in vitro .

The high resolution structures of HP1-family protein chromo and chromo shadow domain reveal a conserved chromo domain fold motif consisting of three β-strands packed against an α-helix. The chromo domain fold belongs to the OB (oligonucleotide/oligosaccharide binding)-fold class found in a variety of prokaryotic and eukaryotic nucleic acid binding protein .

This entry represents a conserved site in the chromo domain.
Chromo domain (Chromo_domain)
Type: Domain

The CHROMO (CHRromatin Organization MOdifier) domain is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation. These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, the chromo domain has been shown to be important for chromatin targeting.

Proteins that contain a chromo domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain followed by a region termed the chromo shadow domain, with weak but significant sequence similarity to the N-terminal chromo domain , eg. Drosophila and human heterochromatin protein Su(var)205 (HP1). The second class includes proteins with a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigen and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.

Functional dissections of chromo domain proteins suggests a mechanistic role for chromo domains in targeting chromo domain proteins to specific regions of the nucleus. The mechanism of targeting may involve protein-protein and/or protein/nucleic acid interactions. Hence, several line of evidence show that the HP1 chromo domain is a methyl-specific histone binding module, whereas the chromo domain of two protein components of the drosophila dosage compensation complex, MSL3 and MOF, contain chromo domains that bind to RNA in vitro .

The high resolution structures of HP1-family protein chromo and chromo shadow domain reveal a conserved chromo domain fold motif consisting of three β-strands packed against an α-helix. The chromo domain fold belongs to the OB (oligonucleotide/oligosaccharide binding)-fold class found in a variety of prokaryotic and eukaryotic nucleic acid binding protein .
Nucleoside triphosphatase NudI (Nucleoside_triphosphatase_NudI)
Type: Family

This entry represents a family of Nudix hydrolases that catalyse the hydrolysis of nucleoside triphosphates, with a preference for pyrimidine deoxynucleoside triphosphates (dUTP, dTTP and dCTP) .
Cation efflux pump FieF (Cation_efflux_FieF)
Type: Family

The ferrous iron efflux (FieF) proteins are members of the cation diffusion facilitator (CDF) family of membrane-bound transporters. These are divalent metal cation transporters that, in addition to their involvement in iron detoxification in Escherichia coli, FieF proteins are also able to transport Zn2 and Cd2 in a proton-dependent manner .
2-oxoglutarate dehydrogenase E1 component, bacterial (2oxoglutarate_DH_E1_bac)
Type: Family

2-oxoglutarate dehydrogenase is a key enzyme in the TCA cycle, converting 2-oxoglutarate, coenzyme A and NAD(+) to succinyl-CoA, NADH and carbon dioxide . This activity of this enzyme is tightly regulated and it is a major determinant of the metabolic flux through the TCA cycle. This enzyme is composed of multiple copies of three different subunits: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) which is often shared with similar enzymes such as pyruvate dehydrogenase . The E2 component forms a large multimeric core which binds the peripheral E1 and E3 subunits. The substrate is transferred between the active sites of the different subunits by a lipoyl moiety, bound to a lysine residue from the E2 polypeptide.

The E1 subunit of 2-oxoglutarate dehydrogenase catalyses the decarboxylation of this compound in a thiamine pyrophosphate-dependent manner, transferring the resultant succinyl group onto the liposyl moiety bound to the E2 subunit. The E1 ortholog from Corynebacterium glutamicum (Brevibacterium flavum) is unusual in having an N-terminal extension that resembles the E2 component of 2-oxoglutarate dehydrogenase enzyme.

This entry contains bacterial 2-oxoglutarate dehydrogenase E1 components, mainly from Gram-positive bacteria.
Regulator of RNA polymerase sigma(70) subunit, Rsd (Sigma70_reg_Rsd)
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. They are responsible for switching between sigma 70 to sigma S during the transition from exponential growth to stationary phase .
3-(3-hydroxy-phenyl)propionate/3-hydroxycinnamic acid hydroxylase (3-HPP/3HCI_hydroxylase)
Type: Family

3-(3-hydroxy-phenyl)propionate/3-hydroxycinnamic acid hydroxylase catalyzes the insertion of one atom of molecular oxygen into position 2 of the phenyl ring of 3-(3-hydroxyphenyl)propionate (3-HPP) and hydroxycinnamic acid (3HCI) .
Type III secretion system flagellar brake protein YcgR (T3SS_YcgR)
Type: Family

This entry represents YcgR a member of the T3SS. It acts as a flagellar brake, regulating swimming and swarming in a bis-(3'-5') cyclic diguanylic acid (c-di-GMP)-dependent manner. Increasing levels of c-di-GMP lead to decreased motility. YcgR binds 1 c-di-GMP dimer per subunit.

YcgR is composed of two domains: an N-terminal domain of unknown function and a C-terminal PilZ domain. The PilZ domain binds c-di-GMP in vitro with an affinity that is high enough to allow it to respond to small changes in intracellular c-di-GMP levels. This domain organisation is conserved in a large number of proteobacteria. Therefore, the function of YcgR in motility control is likely to be conserved.
D-tagatose-bisphosphate aldolase, class II, subunit KbaY (TagBP_ald_KbaY)
Type: Family

Escherichia coli and other enteric bacteria contain two closely related D-tagatose 1,6-bisphosphate (TagBP)-specific aldolases - KbaYZ (also known as AgaYZ) and GatYZ. Unlike other class II aldolases, which are homodimeric enzymes, KbaYZ and GatYZ are heterodimers, and are comprised of subunits KbaY/GatY and GatY/GatZ.

The KbaY/GatY subunits alone are sufficient to show aldolase activity and contain most or all of the residues that have been identified as essential for substrate/product recognition and catalysis in class II aldolases . However, subunits GatZ/KbaZ are required for full activity and for good in vivo and in vitro stability.

This entry represents D-tagatose-1,6-bisphosphate aldolase catalytic subunit KbaY.
2,3-dihydroxyphenylpropionate/2,3-dihydroxicinnamic acid 1,2-dioxygenase (DHPP/DHXA_dioxygenase)
Type: Family

This entry represents 2,3-dihydroxyphenylpropionate/2,3-dihydroxicinnamic acid 1,2-dioxygenase. This enzyme catalyzes the non-heme iron(II)-dependent oxidative cleavage of 2,3-dihydroxyphenylpropionic acid and 2,3-dihydroxicinnamic acid into 2-hydroxy-6-ketononadienedioate and 2-hydroxy-6-ketononatrienedioate, respectively .
Chloride channel, voltage-gated, ClcB (Cl-channel_volt-gated_ClcB)
Type: Family

Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport .

The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata , and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains . Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm .

This entry represents bacterial voltage-gated chloride channel of the ClcB type. ClcB probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response .
2-hydroxy-6-oxononadienedioate/2-hydroxy-6-oxononatrienedioate hydrolase (MhpC_alpha/beta_hydrolase)
Type: Family

2-hydroxy-6-oxononadienedioate/2-hydroxy-6-oxononatrienedioate hydrolase catalyzes the cleavage of the C5-C6 bond of 2-hydroxy-6-oxononadienedioate and 2-hydroxy-6-oxononatrienedioate, a dienol ring fission product of the bacterial meta-cleavage pathway for degradation of phenylpropionic acid . The purified enzyme is a dimeric protein requiring no cofactors for catalytic activity .
Protein-disulfide oxidoreductase DsbI (DiS_OxRdtase_Dsbl)
Type: Family

This group of proteins belongs to the DsbI subfamily of the DsbB family. DsbI is required for disulfide bond formation in some proteins. It is part of a redox system composed of DsbI and DsbL that mediates formation of an essential disulfide bond in arylsulfate sulfotransferase AssT .
2-keto-4-pentenoate hydratase (Keto_pentenoate-hydratase)
Type: Family

2-keto-4-pentenoate hydratase catalyzes the conversion of 2-hydroxypentadienoic acid (enolic form of 2-oxopent-4-enoate) to 4-hydroxy-2-ketopentanoic acid. It uses divalent metal ions as cofactor, with optimum activity obtained with Mn2+ .
Inositol 2-dehydrogenase/D-chiro-inositol 3-dehydrogenase (MI/DCI_dehydrogenase)
Type: Family

Inositol 2-dehydrogenase catalyses the oxidation of myo-inositol (MI) to 2-keto-myo-inositol (2KMI or 2-inosose). In firmicutes (Gram-positive bacteria), the enzyme also shows D-chiro-inositol 3-dehydrogenase activity and is involved in the oxidation of D-chiro-inositol (DCI) to 1-keto-D-chiro-inositol (1KDCI) .
Serpin, conserved site (Serpin_CS)
Type: Conserved_site

This entry represents a conserved site for the Serpin family of proteins, centred on a well conserved Pro-Phe sequence which is found ten to fifteen residues on the C-terminal side of the reactive bond.

Serpins (SERine Proteinase INhibitors) belong to MEROPS inhibitor family I4, clan ID. Most serpin family members are indeed serine protease inhibitors, but several have additional cross-class inhibition functions and inhibit cysteine protease family members such as the caspases and cathepsins . Others, such as ovalbumin, are incapable of protease inhibition and serve other functions .
Serpin domain (Serpin_dom)
Type: Domain

This entry represents the structural domain of serpins.

Serpins (SERine Proteinase INhibitors) belong to MEROPS inhibitor family I4, clan ID. Most serpin family members are indeed serine protease inhibitors, but several have additional cross-class inhibition functions and inhibit cysteine protease family members such as the caspases and cathepsins . Others, such as ovalbumin, are incapable of protease inhibition and serve other functions .
RNA 3'-terminal phosphate cyclase domain (RNA3'_phos_cyclase_dom)
Type: Domain

RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea. Type 1 RNA 3'-terminal phosphate cyclases (

) catalyse the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA:

ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate

The physiological function of the cyclase is not known, but the enzyme could be involved in the maintenance of cyclic ends in tRNA splicing intermediates or in the cyclisation of the 3' end of U6 snRNA .

A second subfamily of RNA 3'-terminal phosphate cyclases (type 2) that do not have cyclase activity have been identified in eukaryotes. They are localised to the nucleolus and are involved in ribosomal modification .

The crystal structure of RNA 3'-terminal phosphate cyclase shows that each molecule consists of two domains. The larger domain contains three repeats of a folding unit comprising two parallel α helices and a four-stranded β sheet; this fold was previously identified in translation initiation factor 3 (IF3). The large domain is similar to one of the two domains of 5-enolpyruvylshikimate-3-phosphate synthase and UDP-N-acetylglucosamine enolpyruvyl transferase. The smaller domain uses a similar secondary structure element with different topology, observed in many other proteins such as thioredoxin . Although the active site of this enzyme has not been unambiguously assigned, it can be mapped to a region surrounding His309, an adenylate acceptor, in which a number of amino acids are highly conserved in the enzyme from different sources .
Small ribosomal subunit protein uS7 domain (Ribosomal_uS7_dom)
Type: Domain

This entry represents the uS7 structural domain, which consists of a bundle of six helices and an extended β hairpin between helices 3 and 4, with two or more RNA-binding sites on its surface .

This entry includes the small ribosomal subunit protein uS7, formerly referred to as 30S ribosomal proteins S7 (bacterial, archaeal, plastid, mitochondrial), and eukaryotic 40S ribosomal proteins S5 (cytoplasmic) . 30S ribosomal protein S7 contacts ribosomal proteins S9 and S11. It is also one of the primary rRNA binding proteins - it binds directly to 16S rRNA - where it nucleates assembly of the head domain of the 30S subunit . S7 is located at the subunit interface close to the decoding centre, where it has been shown to contact mRNA. It has also been shown to contact tRNA in both the P and E sites; it probably blocks exit of the E site tRNA.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .