SII-SWORD/CoKE huggingface dataset:
O-acetyl-ADP-ribose deacetylase (O-Ac-ADP-ribose_deAcase)
Type: Family

O-acetyl-ADP-ribose deacetylase deacetylates O-acetyl-ADP ribose and down-regulates ribonuclease 3 (RNase III) activity. It acts by interacting directly with the region of the ribonuclease that is required for dimerisation/activation .
FAPy deformylase (FAPy_deformylase)
Type: Family

This entry represents FAPy deformylase (

) , which catalyses the second step of the riboflavin and coenzyme F0 biosynthetic pathway in archaea .
FAD synthase RibL (FAD_synth_RibL)
Type: Family

FAD synthases convert flavin mononucleotide (FMN) to flavin adenine dinucleotide (FAD) by the addition of the AMP portion of ATP. RibL is, currently, the only identified archaeal FAD synthase . This protein is not related to the eukarytoic or bacterial enzymes and contains no known motifs for FMN or FAD binding, suggesting that it contains a novel flavin binding site. Unlike most other FAD synthases, RibL does not catalyse the reverse reaction to produce FMN and ATP from FAD.
Putrescine carbamoyltransferase PtcA (PtcA)
Type: Family

Many bacterial species are capable of utilising agmatine (a decarboxylated derivative of arginine) as an energy source via the agamtine deiminase pathway. Agmatine deiminase converts agmatine to carbamoyl putrescine, which is subsequently phosphorylised to carbamoyl phosphate and putrescine by putrescine carbamoyltransferase . The carbamoyl phosphate is used to generate ATP by phosphorylating ADP, while the putrescine is exchanged with extracellular agmatine by an agmatine/putrescine antiporter.

This entry represents the putrescine carbamoyltransferase from this pathway. It is closely related to the ornithine carbamoyltransferase involved in the analogous arginine utilisation pahtway.
Ornithine carbamoyltransferase (OTCase_ArgI)
Type: Family

Ornithine carbamoyltransferases catalyse the production of citrulline from carbamoyl-phosphate and ornithine . This reaction is part of the arginine biosynthetic pathway, and in some organisms the reaction is also part of the arginine deaminase pathway . In most prokaryotes, and some lower eukaryotes, the enzyme is found in the cytoplasm, but in higher eukaryotes, such as mammals, the enzyme is found in the mitochondrial matrix and functions as part of the urea cycle. In most organisms analysed to date, the enzyme has been shown to consist of a trimer of identical or nonidentical subunits . Extensive similarity has been found within the ornithine carbamoyltransferase family, some of the conserved areas being important in catalysis . The C-terminal region of these enzymes contains a highly conserved Cys residue (in a His-Cys-Lys-Pro motif) implicated in ornithine binding .
Sec-independent protein translocase protein TatE (TatE)
Type: Family

Translocation of proteins across the two membranes of Gram-negative bacteria can be carried out via a number of routes. Most proteins marked for export carry a secretion signal at their N terminus, and are secreted by the general secretory pathway. The signal peptide is cleaved as they pass through the outer membrane. Other secretion systems include the type III system found in a select group of Gram-negative plant and animal pathogens, and the CagA system of Helicobacter pylori .

In some bacterial species, however, there exists a system that operates independently of the Sec pathway . It selectively translocates periplasmic-bound molecules that are synthesised with, or are in close association with, "partner" proteins bearing an (S/T)RRXFLK twin arginine motif at the N terminus. The pathway is therefore termed the Twin-Arginine Translocation or TAT system. Surprisingly, the four components that make up the TAT system are structurally and mechanistically related to a pH-dependent import system in plant chloroplast thylakoid membranes . The gene products responsible for the Sec-independent pathway are called TatA, TatB, TatC and TatE.

TatE is highly related to TatA and these proteins appear to overlap in functionality . Translocation occurred in single mutants of either TatA or TatE, though much less efficiently, but double mutants showed no detectable translocation.
Enoyl reductase FAD binding domain (Eno_Rdtase_FAD-bd_dom)
Type: Domain

This entry represents the C-terminal domain of trans-2-enoyl-CoA reductase that binds to FAD. The activity was characterised in Euglena where an unusual fatty acid synthesis path-way in mitochondria performs a malonyl-CoA independent synthesis of fatty acids leading to accumulation of wax esters, which serve as the sink for electrons stemming from glycolytic ATP synthesis and pyruvate oxidation . The full enzyme catalyses the reduction of enoyl-CoA to acyl-CoA.
Cysteinyl-tRNA synthetase/mycothiol ligase (Cys-tRNA/MSH_ligase)
Type: Family

This entry represents a subgroup of the class-I aminoacyl-tRNA synthetase family. It includes cysteinyl-tRNA synthetase and the related enzyme mycothiol ligase .

Cysteine-tRNA ligase (also known as Cysteinyl-tRNA synthetase) (

) is an alpha monomer and belongs to class Ia . It is highly specific despite not possessing the amino acid editing activity characteristic of many other tRNA ligases .

Mycothiol ligase, also known as L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase, uses ATP to ligate a Cys residue to a mycothiol precursor molecule, in the second to last step in mycothiol biosynthesis .
Trans-2-enoyl-CoA reductase catalytic domain, putative (Enoyl-CoA_Rdtase_cat_dom)
Type: Domain

This entry represents a putative catalytic domain of trans-2-enoyl-CoA reductases (

). In Euglena where the enzyme has been characterised it catalyses the reduction of enoyl-CoA to acyl-CoA in an unusual fatty acid pathway in mitochondria. The whole path performs a malonyl-CoA independent synthesis of fatty acids leading to accumulation of wax esters, which serve as the sink for electrons stemming from glycolytic ATP synthesis and pyruvate oxidation.
DNA gyrase inhibitor GyrI (DNA_gyrase_inhibitor_GyrI)
Type: Family

DNA gyrase, a type II topoisomerase, negatively supercoils DNA and is essential for the survival of bacterial cells. This entry represents GyrI, a protein which inhibits the supercoiling activity of DNA gyrase . The mechanism of this inhibition is not known, but it occurs either before or during DNA binding by the gyrase . GyrI protects cells from the double-strand DNA breaks produced by gyrase inhibitors, such as quinolones, that act by trapping the gyrase-DNA covalent complex. It does not appear to protect against inhibitors that target ATPase activity. GyrI has also been shown to protect cells against alkylating agents that act independently of DNA gyrase, suggesting a more general role in protecting cells against DNA damage .
Protein translocase subunit SecD, archaeal (SecD_arc)
Type: Family

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

This family consists of various archaeal SecD proteins. They show a high degree of structural and functional similarity to their bacterial homologues, despite the different composition of their translocation machineries .
tRNA(Ile2) 2-agmatinylcytidine synthetase TiaS (tRNA_Ile2__agm2C_synt)
Type: Family

TiaS is an archaeal ATP-dependent agmatine transferase that catalyses the formation of 2-agmatinylcytidine (agm2C) at the wobble position (C34) of tRNA(Ile2) . This modified base specifically recognises AUA codons.
tRNA(Met) cytidine acetyltransferase TmcA (tRNA_acetyltr_TmcA)
Type: Family

TmcA catalyses the formation of N(4)-acetylcytidine (ac4C) at the wobble position of tRNA(Met), by using acetyl-CoA as an acetyl donor and either ATP or GTP . This modification is thought to ensure precise recognition of the AUG codon by strengthening C-G base-pair interaction and also prevent misrecognition of the near cognate AUA codon. Structurally, TmcA consists of an RNA helicase module fused with a GCN5-related N-acetyltransferase (GNAT) fold . It has been prososed that an RNA helicase motor driven by ATP hydrolysis is used to deliver the wobble base to the active centre of the GNAT domain.
23S rRNA (guanosine-2-O-)-methyltransferase RlmB (23S_rRNA_MeTrfase_RlmB)
Type: Family

23S rRNA (guanosine-2-O-)-methyltransferase RlmB specifically methylates the ribose of guanosine 2251 in 23S rRNA .
Propionate kinase (Propionate_kinase)
Type: Family

Propionate kinase catalyses this reaction:
ATP propanoate = ADP propanoyl phosphate .
3'-5' ssDNA/RNA exonuclease TatD (Exonuc_TatD)
Type: Family

TatD is a Mg(2+)-dependent 3'-5' exonuclease that not only degrades chromosomal DNA during apoptosis but also processes single-stranded DNA during DNA repair .

In E. coli TatD is encoded by a operon that encodes Tat proteins, including TatA, TatB, and TatC, for protein transport via the Tat (Twin-Arginine Translocation) pathway. However, TatD is not involved in the protein export in the Tat pathway .
ECF transporter transmembrane protein EcfT (EcfT)
Type: Family

Energy-coupling factor (ECF) transporters consist of a substrate-specific component (known as the S component), and an energy-coupling module . The substrate-binding component is a small integral membrane protein which captures specific substrates and forms an active transporter in the presence of the energy-coupling AT module. The energy coupling module is composed of an ATPase typical of the ATP binding cassette (ABC) superfamily (A component) and a characteristic transmembrane protein (T component). Unlike the ABC transporters, an energy coupling module can be shared between multiple different substrate-binding components.

This entry represents the transmembrane component from a number of ECF transporters. The function of this component is not known, but it contains two conserved motifs (I and II) that are important for transporter function . Motif I is essential for intramolecular signaling while motifs I and II together are essential for subunit assembly of modular ECF transporters
Dihydroorotate dehydrogenase, class 1 (Dihydroorotate_DH_1)
Type: Family

Dihydroorotate dehydrogenase (DHOD), also known as dihydroorotate oxidase, catalyses the fourth step in de novo pyrimidine biosynthesis, the stereospecific oxidation of (S)-dihydroorotate to orotate, which is the only redox reaction in this pathway. DHODs can be divided into two mains classes: class 1 cytosolic enzymes found primarily in Gram-positive bacteria, and class 2 membrane-associated enzymes found primarily in eukaryotic mitochondria and Gram-negative bacteria .

The class 1 DHODs can be further divided into subclasses 1A and 1B, which differ in their structural organisation and use of electron acceptors. The 1A enzyme is a homodimer of two PyrD subunits where each subunit forms a TIM barrel fold with a bound FMN cofactor located near the top of the barrel . Fumarate is the natural electron acceptor for this enzyme. The 1B enzyme, in contrast is a heterotetramer composed of a central, FMN-containing, PyrD homodimer resembling the 1A homodimer, and two additional PyrK subunits which contain FAD and a 2Fe-2S cluster . These additional groups allow the enzyme to use NAD(+) as its natural electron acceptor.

The class 2 membrane-associated enzymes are monomers which have the FMN-containing TIM barrel domain found in the class 1 PyrD subunit, and an additional N-terminal α helical domain . These enzymes use respiratory quinones as the physiological electron acceptor.

This entry represents the class 1 enzymes. It includes both type 1B, which uses NAD+ as electron acceptor and 1A, which uses instead fumarate as the electron acceptor .
Protein-export membrane protein SecF, archaeal (SecF_arc)
Type: Family

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

This family consists of various archaeal SecF proteins. They show a high degree of structural and functional similarity to their bacterial homologues, despite the different composition of their translocation machineries .
Rubredoxin (Rubredoxin)
Type: Family

Rubredoxin is a low molecular weight iron-containing bacterial and archaeal protein that is involved in electron transfer , sometimes replacing ferredoxin as an electron carrier .

The 3D structures of a number of rubredoxins have been solved . The fold belongs to the α+β class, with 2 α-helices and 2-3 β-strands. Its active site contains an Fe ion which is co-ordinated by the sulphurs of four conserved cysteine residues forming an almost regular tetrahedron. The conserved cysteines reside on two loops, which are the most conserved regions of the protein. In addition, a ring of acidic residues in the proximity of the [Fe(Cys)4] centre is also well-conserved .
Peptidoglycan biosynthesis protein, SpoVB-type (PG_synth_SpoVB)
Type: Family

This entry represents a group of peptidoglycan biosynthesis proteins including stage V sporulation protein B (SpoVB), sporulation protein YkvU and probable cell division protein YtgP . The integral membrane protein SpoVB has been implicated in the biosynthesis of the peptidoglycan component of the spore cortex in Bacillus subtilis .
7-carboxy-7-deazaguanine synthase-like (7-CO-7-deazaguanine_synth-like)
Type: Family

This entry represents 7-carboxy-7-deazaguanine synthase and related uncharacterised proteins that are thought to have the same function.

7-deazapurines are compounds that contain pyrrolopyrimidine functional groups (similar to purines, but lacking one of the nitrogens in the pentameric ring). These compounds form a structurally diverse class of nucleoside analogues that often possess antibiotic, antineoplastic, or antiviral activities. Examples of 7-deazapurines that are important for cell function include the bacterial/eukaryotic modified tRNA base queuosine and the archaeal modified base archaeosine. 7-cyano-7-deazaguanosine (preQ0) is the precursor for all 7-deazapurines and is produced from GTP in a four-step pathway . 7-carboxy-7-deazaguanine synthase catalyses the third step in this pathway, the conversion of 6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-deazaguanine.
Malonyl CoA-acyl carrier protein transacylase (Malonyl_CoA-ACP_transAc)
Type: Family

Malonyl CoA-acyl carrier protein transacylases transfer the malonyl moiety from coenzyme A to acyl-carrier protein. These include proteins involved in fatty acid biosynthesis (FabD), antibiotic biosynthesis (PksC) and the McdH subunit of malonate decarboxylase .
Nucleolar GTP-binding protein 1 (NOG1)
Type: Family

Nucleolar GTP-binding protein 1 is involved in the biogenesis of the 60S ribosomal subunit . It is found as part of the pre-60S complex in nucleolus .
Purple acid phosphatase (Acid_PPase)
Type: Family

This entry includes purple acid phosphatases (

), which are metal dependent, binding two metal ions. Metal binding ligands and residues involved in resistance to tartrate inhibition are conserved .

Purple acid phosphatase 3, 4, 7, 8 and 17 are found in plants, bind zinc and iron, and the genes are predominantly transcribed in flowers . Purple acid phosphatase 17 (PAP17) is induced in response to phosphate starvation, a condition occurring in phosphate-poor soils, and the plant hormone abscisic acid (ABA) and salt stress. Like mammalian acid phosphatase 5, PAP17 has peroxidation activity .

THis entry also includes Glideosome-associated protein 50 (GAP50) from Plasmodium falciparum, a component of the glideosome complex involved in parasite gliding motility and host cell invasion . Its structures has an overall similarity to purple acid phosphatases. However, it has little homology regarding the nature of the residues in the active site region purple acid phosphatases. While the latter contain a phosphate bridged binuclear Fe-site coordinated by seven side chains with the Fe-ions 3.2 A apart, GAP50 in the crystals has two cobalt ions each with one protein ligand and a distance between the Co2 ions of 18 A . The phosphatase activity of GAP50 is controversial .

Acid phosphatase 5 (ACP5) removes the mannose 6-phosphate recognition marker from lysosomal proteins. The exact site of dephosphorylation is not clear. Evidence suggests dephosphorylation may take place in a prelysosomal compartment as well as in the lysosome . ACP5 belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) co-ordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues .
E3 ubiquitin-protein ligase, SMURF1 type (E3_ub_ligase_SMURF1)
Type: Family

This entry represents a set of E3 ubiquitin-protein ligases which accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates, like SMURF1 , Pub1 and RSP5 . All of them contain a HECT domain .
Nucleolar GTP-binding protein 2, circularly permuted GTPase motif (GNL2_CP_dom)
Type: Domain

This entry represents the circularly permuted GTPase motif of Nucleolar GTP-binding protein 2 (GNL2, also known as NGP-1) from animals and fungi. GNL2 is a GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation .

This group of proteins also includes Nuclear/nucleolar GTPase 2 (NUG2) from plants .
Skp domain superfamily (Skp_dom_sf)
Type: Homologous_superfamily

This superfamily represents the Skp (also known as OmpH) domain, named after the Skp protein which functions as a periplasmic chaperone for newly synthesised outer-membrane proteins . Three hairpin-shaped α-helical extensions reach out by approximately 60 A from a trimerisation region, which is composed of three intersubunit β-sheets that wind around a central axis. The α-helical extensions approach each other at their distal turns, resulting in a fold that resembles a 'three-pronged grasping forcep'. The overall shape of Skp is reminiscent of the cytosolic chaperone prefoldin, although it is based on a radically different topology. The peculiar architecture, with apparent plasticity of the prongs and distinct electrostatic and hydrophobic surface properties, supports the recently proposed biochemical mechanism of this chaperone: formation of a Skp(3)-Omp complex protects the outer membrane protein from aggregation during passage through the bacterial periplasm.
Importin subunit alpha (Importin_alpha)
Type: Family

The exchange of macromolecules between the nucleus and cytoplasm takes place through nuclear pore complexes within the nuclear membrane. Active transport of large molecules through these pore complexes require carrier proteins, called karyopherins (importins and exportins), which shuttle between the two compartments.

Members of the importin-alpha (karyopherin-alpha) family can form heterodimers with importin-beta. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Proteins can contain one (monopartite) or two (bipartite) NLS motifs. Importin-alpha contains several armadillo (ARM) repeats, which produce a curving structure with two NLS-binding sites, a major one close to the N terminus and a minor one close to the C terminus.

Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. The N-terminal importin-beta-binding (IBB) domain of importin-alpha contains an auto-regulatory region that mimics the NLS motif . The release of importin-beta frees the auto-regulatory region on importin-alpha to loop back and bind to the major NLS-binding site, causing the cargo to be released .

This entry represents importin alpha.
Flavin transferase ApbE (ApbE)
Type: Family

ApbE is a Mg2+-dependent flavin transferase that catalyses covalent attachment of FMN to a threonine residue in bacterial flavoproteins .
Septin and tuftelin interacting protein (TFP11)
Type: Family

Septin and tuftelin interacting proteins (STIPs) are G-patch domain proteins involved in spliceosome disassembly . The mouse protein, known as TFT11 was originally identified as a protein interacting with tuftelin, one of the presumed enamel matrix proteins . The Drosophila protein STP1 was originally identified as a septin-interacting protein . In both cases these interactions were identified by a yeast two-hybrid system and their function and direct physical association were not characterised. Subsequent studies show that these proteins are widely expressed and function as splicing factors . STIP is essential for embryogenesis in Caenorhabditis elegans .
Rubredoxin-like domain (Rubredoxin-like_dom)
Type: Domain

Rubredoxin is a low molecular weight iron-containing bacterial protein involved in electron transfer , sometimes replacing ferredoxin as an electron carrier . Rubredoxins possess a 45- to 55-residue domain containing one iron atom tetrahedrally coordinated to four cysteinyl residues. Structural analysis of the domains have shown them to be folded into a short three-stranded antiparallel β-sheet and a number of loops .

This entry represents rubredoxin-like domains, which are found in rubredoxins and related proteins, including rubrerythrins, flavorubredoxins and nigerythrins.
Rubredoxin domain (Rubredoxin_dom)
Type: Domain

Rubredoxin is a low molecular weight iron-containing bacterial protein involved in electron transfer , sometimes replacing ferredoxin as an electron carrier . Rubredoxins possess a 45- to 55-residue domain containing one iron atom tetrahedrally coordinated to four cysteinyl residues. Structural analysis of the domains have shown them to be folded into a short three-stranded antiparallel β-sheet and a number of loops .

This entry represents the rubredoxin domain.
Cyclophilin-type peptidyl-prolyl cis-trans isomerase (Cyclophilin-type_PPIase)
Type: Family

Cyclophilins exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity (

), accelerating protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides . They also have protein chaperone-like functions and are the major high-affinity binding proteins for the immunosuppressive drug cyclosporin A (CSA) in vertebrates .

Cyclophilins are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function . They share a common 109 amino acid cyclophilin-like domain (CLD) and additional domains unique to each member of the family. The CLD domain contains the PPIase activity, while the unique domains are important for selection of protein substrates and subcellular compartmentalisation .

This entry represents the cyclophilin peptidyl-prolyl cis-trans isomerase family. The family includes RING-type E3 ubiquitin-protein ligase PPIL2, which is thought to be an inactive PPIase .