SII-SWORD/CoKE huggingface dataset:
DeoR-like transcriptional repressor, C-terminal sensor domain (DeoR-like_C)
Type: Domain

DeoR-like transcription repressors occur in diverse bacteria and archaea, as regulators of sugar and nucleoside metabolic systems. The effector molecules for DeoR-like regulators are generally phosphorylated intermediates of the relevant metabolic pathway.

The C-terminal sensor domain of DeoR-like transcription repressors represents a catalytically inactive version of the ISOCOT fold, but retains the substrate binding site . This sensor domain binds the inducer and often acts as an oligomerization domain. It senses diverse sugar derivatives such as deoxyribose nucleoside (in the case of DeoR), tagatose phosphate (LacR), galactosamine (AgaR), myo-inositol (Bacillus IolR) and L-ascorbate (UlaR) . GlpR controls both fructose and glucose metabolic enzymes through transcriptional repression of the glpR-pfkB operon and kdgK1 during growth on glycerol .
Translation elongation factor EF1B, beta/delta subunit, guanine nucleotide exchange domain (EF1B_bsu/dsu_GNE)
Type: Domain

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .

This entry represents the guanine nucleotide exchange domain of the beta (EF-1beta, also known as EF1B-alpha) and delta (EF-1delta, also known as EF1B-beta) chains of EF1B proteins from eukaryotes and archaea. The beta and delta chains have exchange activity, which mainly resides in their homologous guanine nucleotide exchange domains, found in the C-terminal region of the peptides. Their N-terminal regions may be involved in interactions with the gamma chain (EF-1gamma).
Translation elongation factor EFTs/EF1B, dimerisation (Transl_elong_EFTs/EF1B_dimer)
Type: Domain

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .

This entry represents the C-terminal dimerisation domain found primarily in EF-Tu (EF1A) proteins from bacteria, mitochondria and chloroplasts.
ESCRT-II complex, Vps25 subunit, N-terminal winged helix (ESCRT-II_cplx_Vps25-sub_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal winged helix domain of the vps25 subunit (vacuolar protein sorting-associated protein 25) of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs) . ESCRT-II recruits the transport machinery for protein sorting at MVB . In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo .

ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps35 .
Glutathione synthase, alpha-helical (Glutathione_synthase_a-hlx)
Type: Homologous_superfamily

This superfamily represents an α-helical domain found in glutathione synthetase (

) (GSS), a homodimeric enzyme that catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to phosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis, the first step being catalysed by gamma-glutamylcysteine synthetase . In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, and increased rate of haemolysis and defective function of the central nervous system.
Acyl transferase domain (Acyl_transferase_dom)
Type: Domain

This entry represents the acyl transferase domain in polyketide synthase (PKS) enzymes mainly found in bacteria and eukaryotes.

Enzymes like bacterial malonyl CoA-acly carrier protein transacylase (

) and eukaryotic fatty acid synthase (

) that are involved in fatty acid biosynthesis belong to this group . Also included are the polyketide synthases 6-methylsalicylic acid synthase (

), a multifunctional enzyme that involved in the biosynthesis of patulin and conidial green pigment synthase (

) and several non-reducing polyketide synthases.
CAP domain (CAP_dom)
Type: Domain

This entry represents the CAP domain common to all members of the CAP superfamily. The CAP domain forms a unique 3 layer α-β-α fold with some, though not all, of the structural elements found in proteases .

The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily proteins are found in a wide range of organisms, including prokaryotes and non-vertebrate eukaryotes , The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilisation. The overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences . The Ca2-chelating function would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how

blocks the Ca2 transporting ryanodine receptors.
Diadenylate cyclase (C-di-AMP_synthase)
Type: Family

Diadenylate cyclase catalyses the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol by bacterial pathogens, such as Listeria monocytogenes. This compound triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity . Apart from a role in the establishment of bacterial infection, c-di-AMP seems to be involved in coordinating bacterial growth, cell wall stability, and responses to stress .

This entry includes CdaA and CdaS from Bacillus subtilis . CdaA produces the c-di-AMP that is required for cell wall homeostasis . CdaS contains an N-terminal domain that consists of two α-helices and a C-terminal catalytically active diadenylate cyclase (DAC) domain. The cyclic di-AMP formed by CdaS is required for efficient germination .
Chromate transporter, long chain (Chr_Tranpt_l_chain)
Type: Family

This entry represents the long chain chromate transporters . The protein reduces chromate accumulation and is essential for chromate resistance. They appear to have arisen from a gene fusion event of two short chain transporters .
Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding (MethylDNA_cys_MeTrfase_DNA-bd)
Type: Domain

Synonym(s): 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase

This entry represents the DNA binding region of 6-O-methylguanine-DNA methyltransferases.

The repair of DNA containing O6-alkylated guanine is carried out by DNA-[protein]-cysteine S-methyltransferase (

). The major mutagenic and carcinogenic effect of methylating agents in DNA is the formation of O6-alkylguanine. The alkyl group at the O-6 position is transferred to a cysteine residue in the enzyme . This is a suicide reaction since the enzyme is irreversibly inactivated and the methylated protein accumulates as a dead-end product. Most, but not all of the methyltransferases are also able to repair O-4-methylthymine. DNA-[protein]-cysteine S-methyltransferases are widely distributed and are found in various prokaryotic and eukaryotic sources .
Glutathione synthase, N-terminal, eukaryotic (Glutathione_synthase_N_euk)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in eukaryotic glutathione synthetase (

) (GSS), a homodimeric enzyme that catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to phosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis, the first step being catalysed by gamma-glutamylcysteine synthetase . In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, and increased rate of haemolysis and defective function of the central nervous system. The N-terminal domain has a 2-layer α/β structure.
Phosphoesterase, HXTX (Phosphoesterase_HXTX)
Type: Domain

This entry represents a domain found in a number of known and predicted phosphoesterases. These include bacterial and archaeal 2',5' RNA ligases, and a family of predicted phosphoesterases known as the YjcG family. The 2',5' RNA ligases perform a reversible, ATP-independent 2'-5'-ligation of what is presumably a non-phyiological substrate: half-tRNA splice intermediates from an intron-containing yeast tRNA . The physiological substrate(s) in prokaryotes may include small 2',5'-link-containing oligonucleotides, perhaps with regulatory or biosynthetic roles. This domain contains a conserved HXTX motif which is thought to be important for catalytic activity, as it is in the related enzyme cyclic nucleotide phosphodiesterase (CPDase) . In 2',5' RNA ligase this domain is duplicated, with the two conserved motifs forming the proposed active site, which is analogous to that of CPDase .
DNA primase, small subunit, eukaryotic/archaeal (DNA_primase_ssu_euk/arc)
Type: Family

This entry represents the eukaryotic and archaeal DNA primase small subunit proteins known as PRIM1 and PriS, respectively , and does not include bacterial or viral proteins. Bacterial DNA primase adopts a different fold to archaeal and eukaryotic primases . In human, PRIM1 deficiency has been associated with primordial dwarfism syndrome .

DNA primase synthesizes the RNA primers for the Okazaki fragments in lagging strand DNA synthesis. Eukaryotic and archaeal DNA primase is a heterodimer of large (p58) and small catalytic (p48) subunits . The large subunit only exists in archaeal and eukaryotic primases, plays an important role in primase activity as it stabilizes the small catalytic subunit and, probably, interacts with the template DNA and the first initiating NTP .
Formylmethanofuran: tetrahydromethanopterin formyltransferase Ftr (ForMFR_H4MPT_ForTrfase)
Type: Family

Formylmethanofuran:tetrahyromethanopterin formyltransferase (Ftr) is involved in C1 metabolism in methanogenic archaea, sulphate-reducing archaea and methylotrophic bacteria. It catalyses the following reversible reaction:

N-formylmethanofuran + 5,6,7,8-tetrahydromethanopterin = methanofuran + 5-formyl-5,6,7,8-tetrahydromethanopterin

Ftr from the thermophilic methanogen Methanopyrus kandleri (optimum growth temperature 98 degrees C) is a hyperthermophilic enzyme that is absolutely dependent on the presence of lyotropic salts for activity and thermostability. The crystal structure of Ftr reveals a homotetramer composed essentially of two dimers. Each subunit is subdivided into two tightly associated lobes both consisting of a predominantly antiparallel β sheet flanked by α helices forming an α/β sandwich structure. The approximate location of the active site was detected in a region close to the dimer interface . Ftr from the mesophilic methanogen Methanosarcina barkeri and the sulphate-reducing archaeon Archaeoglobus fulgidus have a similar structure .

In the methylotrophic bacterium Methylobacterium extorquens, Ftr interacts with three other polypeptides to form an Ftr/cyclohydrolase complex which catalyses the hydrolysis of formyl-tetrahydromethanopterin to formate during growth on C1 substrates .
Bacteriophage regulatory protein, Rha family (Phage_regulatory_Rha)
Type: Family

This entry represents a family of proteins which are encoded in temperate phages and bacterial prophage regions. They include the product of the late operon rha gene from lambdoid phage phi-80. The presence of this gene interferes with the infection of bacterial strains lacking the integration host factor that regulates the rha gene. Rha is thought to function as a phage regulatory protein .
CRISPR-associated protein, Csx11 (CRISPR-assoc_prot_Csx11)
Type: Family

Members of this uncommon, sporadically distributed Cas protein family are large (>900 amino acids) and strictly associated, so far, with CRISPR-associated (Cas) gene clusters. Nearby Cas genes always include members of the RAMP superfamily and the six-gene CRISPR-associated RAMP module. Species in which it is found, so far, include three archaea (Methanosarcina mazei, Methanosarcina barkeri and Methanobacterium thermoautotrophicum) and two bacteria (Thermodesulfovibrio yellowstonii DSM 11347 and Sulfurihydrogenibium azorense).

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Type II toxin-antitoxin system RelE/ParE-like toxin, predicted (TypeIITA-like_toxin_pred)
Type: Family

Members of this protein family are small, generally only 100 amino acids in length. The gene is almost invariably the upstream member of a gene pair, where the downstream member is a predicted DNA-binding protein. These gene pairs, when found on the bacterial chromosome, are often located within prophage regions, but are also found in integrated plasmid regions and near housekeeping genes. Analysis suggests that the gene pair may serve as an addiction module.

Member of this family from cyanobacterium Synechocystis 6803 is predicted to be a component of a putative Type II TA system .
Uncharacterized protein HI1420 (HI1420)
Type: Family

Members of this bacterial protein family are small, at roughly 100 amino acids. The gene is almost invariably the downstream member of a gene pair. It is a predicted DNA-binding protein from a clade within the helix-turn-helix family. These gene pairs, when found on the bacterial chromosome, are located often with prophage regions, but also both in integrated plasmid regions and in housekeeping gene regions. Analysis suggests that the gene pair may serve as an addiction module.
Pteridine reductase (Pteridine_reductase)
Type: Family

Pteridine reductase is an enzyme used by trypanosomatids (including Trypanosoma cruzi and Leishmania major) to obtain reduced pteridines by salvage rather than biosynthetic pathways. Enzymes in T. cruzi described as pteridine reductase 1 (PTR1) and pteridine reductase 2 (PTR2) have different activity profiles. PTR1 is more active with fully oxidized biopterin and folate than with reduced forms, while PTR2 reduces dihydrobiopterin and dihydrofolate but not oxidized pteridines. T. cruzi PTR1 and PTR2 are more similar to each other in sequence than either is to the pteridine reductase of L. major, and all are included in this family.
TraI/TrwC, conjugative relaxase domain (TraI/TrwC_relax)
Type: Domain

This is the conjugative relaxase domain found in the N-terminal region of TraI and TrwC . TrwC is a relaxase-helicase that acts in plasmid R388 conjugation . The relaxase domain has DNA cleavage and strand transfer activities. Members of this family are typically found near other genes characteristic of conjugative plasmids and appear to identify integrated plasmids when found in bacterial chromosomes.
Alkaline phosphatase-like protein PglZ (PglZ)
Type: Family

This family includes the Alkaline phosphatase-like protein PglZ from Bacillus cereus and Escherichia coli, putative phosphatases and core proteins of a type 1 BREX system. BREX systems (bacteriophage exclusion) provide immunity against bacteriophage. This system allows phage adsorption but prevents phage DNA replication, without degradation of the phage DNA. Methylation of bacterial DNA by PglX probably guides self/non-self discrimination .
Lon-like protease BrxL-like (BrxL-like)
Type: Family

This family includes Lon-like protease BrxL from Bacillus cereus and similar proteins. BrxL is part of a type 1 BREX system. BREX systems (bacteriophage exclusion) provide immunity against bacteriophage, a system that allows phage adsorption but prevents phage DNA replication, without degradation of the phage DNA . Methylation of bacterial DNA by PglX probably guides self/non-self discrimination. When the brxA-brxB-brxC-pglX and pglZ-brxL operons are transformed into a susceptible B.subtilis strain (BEST7003) they confer resistance to bacteriophages SPbeta, SP16, Zeta, phi3T and SP02 and partial protection to phages SP01 and SP82G (these include lytic and temperate phage). This entry also includes few uncharacterised viral proteins.
Arsenate reductase, glutathione/glutaredoxin type (Arsenate_reductase_gluta)
Type: Family

This entry represents a novel form of arsenate reductase, including Synechocystis sp. ArsC, which belongs to a family that, though related to thioredoxin-dependent arsenate reductases, uses the glutathione/glutaredoxin system for reduction .
Arsenate resistance ArsH (Arsenate-R_ArsH)
Type: Family

Members of this protein family occur in arsenate resistance operons that include at least two different types of arsenate reductase. ArsH is not required for arsenate resistance in some systems. This family belongs to the larger family of NADPH-dependent FMN reductases (

). ArsH from the cyanobacterium Synechocystis sp. PCC 6803 is an efficient NADPH-dependent quinone reductase .
Arsenate reductase ArsC (Arsenate_reductase_ArsC)
Type: Family

This family describes the well-studied thioredoxin-dependent arsenate reductase of Staphylococcus aureus plasmid pI258 and other mechanistically similar arsenate reductases. The mechanism involves an intramolecular disulphide bond cascade, and aligned members of this family have four absolutely conserved Cys residues. This group of arsenate reductases belongs to the low-molecular weight protein-tyrosine phosphatase family, as does a group of glutathione/glutaredoxin type arsenate reductases (

). At least two other, non-homologous groups of arsenate reductases involved in arsenical resistance are also known. This enzyme reduces arsenate to arsenite, which may be more toxic but which is more easily exported .
tRNA adenylyltransferase (tRNA_adenylyltransferase)
Type: Family

The enzyme tRNA adenylyltransferase, also called tRNA-nucleotidyltransferase and CCA-adding enzyme, can add or repair the required CCA triplet at the 3 -end of tRNA molecules. Genes encoding tRNA include the CCA tail in some but not all bacteria, and this enzyme may be required for viability. Members of this family represent a distinct clade within the larger family

(tRNA nucleotidyltransferase/poly(A) polymerase family protein). The example from Streptomyces coelicolor was shown to act as a CCA-adding enzyme and not as a poly(A) polymerase.
Arsenite oxidase subunit AioA/Iodate reductase subunit IdrA, large subunit (AioA/IdrA_lsu)
Type: Family

This entry represents a group of prokaryotic molybdopterin-containing oxidoreductases, including Arsenite oxidase subunit AioA from Alcaligenes faecalis and Iodate reductase subunit IdrA from Pseudomonas sp. AioA is the large subunit of an arsenite oxidase complex in which the small subunit is a Rieske protein. This enzyme acts in energy metabolism by arsenite oxidation, rather than detoxification by reduction of arsenate to arsenite prior to export . Its homologue IdrA is thought to catalyse the reduction of iodate (IO3-) to hypoiodous acid (HIO) and H2O2, using a reduced cytochrome c as the electron donor .
Arsenite oxidase subunit AioB/Iodate reductase subunit IdrB, small subunit (AioB/IdrB_ssu)
Type: Family

This entry represents a group of prokaryotic molybdopterin-containing oxidoreductases, including Arsenite oxidase subunit AioB from Alcaligenes faecalis and Iodate reductase subunit IdrB from Pseudomonas sp. AioB is the small subunit of an arsenite oxidase complex. It is a Rieske protein and appears to rely on the Tat (twin-arginine translocation) system to cross the membrane. Although this enzyme could run in the direction of arsenate reduction to arsenite in principle, the relevant biological function is arsenite oxidation for energy metabolism, not arsenic resistance . IdrB, a Rieske-type protein with a [2Fe-2S]-binding motif, is involved in iodate respiration .
Azurin (Azurin)
Type: Family

Azurin is a blue copper-binding protein in the plastocyanin/azurin family. It serves as a redox partner to enzymes such as nitrite reductase or arsenite oxidase. The most closely related copper-binding proteins to this family are auracyanins, as in Chloroflexus aurantiacus, which have similar redox activities.

The copper of Azurin is tetrahedrally coordinated by a cysteine, 2 histidines, and a methionine residue . The electron transfer reactions are carried out with the Cu centre transitioning between the oxidized Cu(II) form and the reduced Cu(I) form. Azurin can function as a tumor suppressor; it forms a complex with p53 that triggers apoptosis in various human cancer cells .
Guanosine pentaphosphate synthetase I/polyribonucleotide nucleotidyltransferase (GPSI/PNP)
Type: Family

The of the characterisation of two proteins from Streptomyces coelicolor has been presented . The protein in this family was shown to have poly(A) polymerase activity and may be responsible for polyadenylating RNA in this species. It has also been shown that a nearly identical plasmid-encoded protein from Streptomyces antibioticus is a bifunctional enzyme that acts also as a guanosine pentaphosphate synthetase .