SII-SWORD/CoKE huggingface dataset:
Aspartyl/asparaginy/proline hydroxylase (Asp/Arg/Pro-Hydrxlase)
Type: Domain

Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes. Proline 3-hydroxylase (P3H) hydroxylates proline at position 3, the first of a 2-OG oxygenase catalysing oxidation of a free alpha-amino acid. The structure of proline 3-hydroxylase contains the conserved motifs present in other 2-OG oxygenases including a jelly roll strand core and residues binding iron and 2-oxoglutarate, consistent with divergent evolution within the extended family. PH3 folds into two domains, an
N-terminal domain containing 10 β strands and a C-terminal helical domain. The N-terminal domain contains the distorted jelly roll β sheet core . A similar domain is also found in aspartyl/asparaginyl beta-hydroxylase, which hydroxylates one aspartic or asparagine residue in certain epidermal growth factor-like domains of a number of proteins .
Gas vesicle protein G (GvpG)
Type: Family

Gas vesicles are intracellular, protein-coated, and hollow organelles found in cyanobacteria and halophilic archaea. They are permeable to ambient gases by diffusion and provide buoyancy, enabling cells to move upwards in water to access oxygen and/or light. This family represents Gas vesicle protein G from Streptomyces sp. and similar prokaryotic proteins involved in the formation of gas vesicles .
Gas vesicle protein K (GvpK)
Type: Family

Gas vesicles are intracellular, protein-coated, and hollow organelles found in cyanobacteria and halophilic archaea. They are permeable to ambient gases by diffusion and provide buoyancy, enabling cells to move upwards in liquid to access oxygen and/or light. This family represents Gas vesicle protein K from Streptomyces sp. (GvpK) and similar prokaryotic proteins involved in the formation of gas vesicles .
Mobile element transfer (SpdB)
Type: Family

This family is found in proteins involved in transferring a group of integrating conjugative DNA elements, such as pSAM2 from Streptomyces ambofaciens during mating . Their precise role is not known.
TcmA/NAT10, helicase domain (TcmA/NAT10_helicase)
Type: Domain

This domain contains a P-loop (Walker A) motif, suggesting that it has ATPase activity, and a Walker B motif. It is found in NAT10 from eukaryotes and TmcA from prokaryotes. In NAT10, this domain catalyses the formation of N4-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs . In TmcA, it may function as an RNA helicase motor (driven by ATP hydrolysis) which delivers the wobble base to the active centre of the GCN5-related N-acetyltransferase (GNAT) domain .

The bacterial tRNA(Met) cytidine acetyltransferase (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 . RNA cytidine acetyltransferas (NAT10) are RNA cytosine acetyltransferases with specificity toward both 18S rRNA and tRNAs and contain additional putative nuclear and nucleolar localisation signals (NLS and NoLS respectively) .
Transcription elongation factor 1 (Elf1)
Type: Family

Transcription elongation factor 1 (Elf1) is a transcription elongation factor implicated in the maintenance of proper chromatin structure in actively transcribed regions .
FlgN-like protein (FlgN-like)
Type: Family

Flagella synthesis protein FlgN is an export chaperone involved in flagellar synthesis . FlgN consists of a 4 long helices bundle, where the last helix is shorter than the three others. FlgN is required for the export of the hook-filament junction proteins, FlgK and FlgL. It is required for both swimming and swarming motility in B. subtilis .
Pep3/Vps18/deep orange, beta-propeller domain (Pep3_Vps18)
Type: Domain

This domain is found N-terminal in a number of proteins identified as being involved in Golgi function and vacuolar sorting. The molecular function of this region is unknown. Proteins containing this domain also contain a C-terminal ring finger domain.
DNA-directed RNA polymerase III subunit RPC4 (RPC4)
Type: Family

This entry represents a component of the RNA polymerase III (Pol III) complex
, which catalyse the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates .
Type II secretion system protein GspL (T2SS_protein-GspL)
Type: Family

This family consists of general secretion pathway protein L sequences from several Gram-negative bacteria. GspL is predicted to contain a large cytoplasmic domain and has been shown to interact with the autophosphorylating cytoplasmic membrane protein GspE. It is thought that the tri-molecular complex of GspL, GspE and GspM might be involved in regulating the opening and closing of the secretion pore and/or transducing energy to the site of outer membrane translocation .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Type IV pilus inner membrane component PilN (PilN)
Type: Family

PilN forms a stable heterodimer with PilO through interaction of their periplasmic domains, being essential for the assembly of a functional complex. PilN requires PilO for a proper folding and they depend on each other for their stability . PilN also interacts with PilM causing conformational changes that allow PilM monomerisation.

This entry also includes Type II secretion system protein L. Type II secretion (T2S) and type IV pilus systems share evolutionary origins, being structurally and functionally related . DNA utilization protein HofN from E.coli is also included in this entry. It is involved in DNA uptake and DNA utilisation as a carbon and energy source, conferring competitive advantage. This protein is encoded by a gene homologue to com genes in Haemophilus influenzae, involved in pilus biogenesis, protein secretion, competence-transformation, and twitching motility .

Bacterial type IV pili are surface filaments critical for diverse biological processes including surface and host cell adhesion, colonisation, biofilm formation, twitching motility, DNA uptake during natural transformation and virulence . The proteins necessary to form the type IV pili inner-membrane complex, are included in the pilMNOPQ operon which encodes the cytoplasmic actin-like protein PilM, PilN, PilO, the periplasmic lipoprotein PilP and the outer-membrane secretin PilQ. The inner-membrane PilM/N/O/P complex is required for the optimal function of the outer-membrane secretin PilQ. This cluster is highly conserved across the type IV pilus-producing bacterial species, and all of these proteins have been shown to be essential for twitching motility .
1,2-phenylacetyl-CoA epoxidase, subunit A/C (PaaA_PaaC)
Type: Family

This family includes PaaA and PaaC proteins, which are part of a catabolic pathway of phenylacetic acid . E. coli PaaA and PaaC are components of 1,2-phenylacetyl-CoA epoxidase multicomponent enzyme system which catalyses the reduction of phenylacetyl-CoA (PA-CoA) to form 1,2-epoxyphenylacetyl-CoA. PaaA is the catalytic subunit involved in the incorporation of one atom of molecular oxygen into phenylacetyl-CoA, while PaaC may be essential for structural integrity of the alpha subunit .
Erythromycin esterase (Emycin_Estase)
Type: Family

This entry contains erythromycin esterase, which shares conserved active site residues of the Tiki/TraB family. Erythromycin esterases (EreA and EreB) disrupt erythromycin via the hydrolysis of the macrolactone ring. A critical catalytic histidine acts as a general base in the activation of a water molecule. Macrolides act by inhibiting bacterial protein synthesis by binding at the exit tunnel of ribosomal subunit 50s, blocking the translation of the polypeptide. Erythromycin esterase, typically found in integrons and transposons, confers antibiotic resistance through the disruption of the drug ring structure. EreB substrate profile is substantially broader than that for EreA, being able to also metabolize semisynthetic derivatives such as azalide azithromycin .
ResB-like domain (ResB-like_domain)
Type: Domain

This domain is found in a number of known and suspected cytochrome c biogenesis proteins, including ResB . Mutations in ResB indicate that they are essential for growth . ResB is predicted to be a transmembrane protein.
Isocyanide synthase/Spore wall maturation protein DIT1 (Isocyanide_synthase_DIT1)
Type: Family

Isocyanide synthases are required for the biosynthesis of isocyanides (or isonitriles), a class of microbial secondary metabolites that can be cytotoxic, antibacterial, and antiprotozoal .

L-tyrosine isonitrile synthase from the Gammaproteobacteria Xenorhabdus nematophila participates in the biosynthesis of rhabduscin, a tyrosine derivative which is a potent inhibitor of phenoloxidase, a key component of the insect's innate immune system .

L-tryptophan isonitrile synthase AmbI1/2 from the Cyanobacteria Fischerella ambigua is involved in the biosynthesis of ambiguines, a family of hapalindole-type alkaloids .

This entry also includes Spore wall maturation protein DIT1 from Saccharomyces cerevisiae is involved in the synthesis of dityrosine . Dityrosine is a sporulation-specific component of the Saccharomyces cerevisiae ascospore wall that is essential for the resistance of the spores to adverse environmental conditions.

is involved in the biosynthesis of pyoverdine .
SHI protein family (SHI)
Type: Family

This entry represents a group of plant proteins, including protein SHORT INTERNODES (SHI) and its paralogues from Arabidopsis. In Arabidopsis, the SHI family comprises ten members. They contain a RING finger-like zinc finger motif. SHI may act as a negative regulator of GA responses through transcriptional control binding directly to the 5'-T/GCTCTAC-3' DNA motif found in the promoter regions . In rice, it regulates tillering and panicle branching by modulating SPL14/IPA1 transcriptional activity on the downstream TB1 and DEP1 target genes .
AbrB family (AbrB_fam)
Type: Family

AbrB is a multipass membrane protein that is probably involved in the regulation of alkylation damage induced protein AidB in Escherichia coli .
Lanthionine synthetase C-like (LANC-like)
Type: Family

The C-terminal of the lantibiotic biosynthesis protein LanM is homologous to LanC . LanC-like protein 1 (included in this family) has been shown to function as a glutathione transferase, and as such has been renamed to Glutathione S-transferase LANCL1 .

The LanC-like protein superfamily encompasses a highly divergent group of peptide-modifying enzymes, including the eukaryotic and bacterial lanthionine synthetase C-like proteins (LanC) ; subtilin biosynthesis protein SpaC from Bacillus subtilis ; epidermin biosynthesis protein EpiC from Staphylococcus epidermidis ; nisin biosynthesis protein NisC from Lactococcus lactis ; GCR2 from Arabidopsis thaliana ; and many others.

The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution . The globular structure is characterised by an all-α fold, in which an outer ring of helices envelops an inner toroid composed of 7 shorter, hydrophobic helices. This 7-fold hydrophobic periodicity has led several authors to claim various members of the family, including eukaryotic LanC-1 and GCR2, to be novel G protein-coupled receptors ; some of these claims have since been corrected .
Ribosomal RNA processing protein 8 (RRP8)
Type: Family

Ribosomal RNA processing protein 8 (Rrp8) is a nucleolar Rossman-fold like methyltransferase. In yeast, it is involved in pre-rRNA cleavage at site A2 and is responsible for a base methylation of the 25S rRNA . In humans it is also known as nucleomethylin (NML), and it is important for mediating the assembly of the energy-dependent nucleolar silencing complex (eNoSC), which regulates rRNA transcription in response to glucose deprivation . NML represses rDNA transcription by promoting H3K9 methylation and establishing heterochromatin across the rDNA .
Paraflagellar rod (Flagellar_rod)
Type: Family

This family consists of several eukaryotic paraflagellar rod component proteins. The eukaryotic flagellum represents one of the most complex macromolecular structures found in any organism and contains more than 250 proteins . In addition to its locomotive role, the flagellum is probably involved in nutrient uptake since receptors for host low-density lipoproteins are localised on the flagellar membrane as well as on the flagellar pocket membrane .
Major outer membrane precursor, Legionella pneumophila-type (Major_OMP_Legionella)
Type: Family

This family consists of major outer membrane protein precursors from Legionella pneumophila and other bacteria.
Photosystem II PsbM (PSII_PsbM)
Type: Family

This entry represents the low molecular weight transmembrane protein PsbM found in PSII. PsbM is one of the most hydrophobic proteins in the thylakoid membrane. The function of this protein is unknown.

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .
Protein of unknown function DUF694 (DUF705)
Type: Family

This family contains uncharacterised baculoviral proteins.
Inositol oxygenase (Inositol_oxygenase)
Type: Family

Inositol oxygenase (

) is involved in the biosynthesis of UDP-glucuronic acid (UDP-GlcA), providing nucleotide sugars for cell-wall polymers. It may be also involved in plant ascorbate biosynthesis .
TM2 domain (TM2)
Type: Domain

This domain is composed of a pair of transmembrane α helices connected by a short linker. The function of this domain is unknown, however it occurs in a wide range or protein contexts.
Type II secretion system protein GspE, N-terminal (T2SS_GspE_N)
Type: Domain

This domain is found at the N-terminal of the Type II secretion secretion system protein E (GspE) and type IV pilus extensin ATPase PilB and near the C-terminal of the glycosyltransferase NfrB. A variant of this domain, called MshEN, binds cyclic di-GMP , which modulates the activity of the respective protein. The structure of this domain is now known .

Proteins containing this domain are typically involved in Type IV pilus biogenesis (e.g.

), though some are involved in other processes; for instance aggregation in Myxococcus xanthus (e.g.

) .
RNA polymerase Rpc34 (RNA_pol_Rpc34)
Type: Family

The family comprises a subunit specific to RNA Pol III, the tRNA specific polymerase. The C34 subunit of Saccharomyces cerevisiae RNA Pol III is part of a subcomplex of three subunits which have no counterpart in the other two nuclear RNA polymerases. This subunit interacts with TFIIIB70 and therefore participates in Pol III recruitment .
Capsule polysaccharide biosynthesis (Capsule_polysaccharide_synth)
Type: Family

This family includes export proteins involved in capsule polysaccharide biosynthesis, such as KpsS

and LipB

. Capsule polysaccharide modification protein lipB/A is involved in the phospholipid modification of the capsular polysaccharide and is a strong requirement for its translocation to the cell surface. The capsule of Neisseria meningitidis serogroup B and of other meningococcal serogroups and other Gram-negative bacterial pathogens, are anchored in the outer membrane through a 1,2-diacylglycerol moiety. The lipA and lipB genes are located on the 3' end of the ctr operon. lipA and lipB do not encode proteins responsible for diacylglycerophosphatidic acid substitution of the meningococcal capsule polymer, but they are required for proper translocation and surface expression of the lipidated polymer .

KpsS is an unusual sulphate-modified form of the capsular polysaccharide in Rhizobium loti (Mesorhizobium loti). Many plants, including R. loti, enter into symbiotic relationships with bacteria that allow survival in nutrient-limiting environments. KpsS functions as a fucosyl sulphotransferase in vitro. The kpsS gene product shares no significant amino acid similarity with previously identified sulphotransferases . Sulphated cell surface polysaccharides are required for optimum nodule formation but limit growth rate and nodule colonisation in M. loti .
DSS1/SEM1 (DSS1_SEM1)
Type: Family

This family includes yeast Sem1 and its mammalian homologue, DSS1.

Sem1/DSS1 (also known as rpn15) is a component of lid subcomplex of 26S proteasome regulatory subunit . Besides being a subunit of the 26S proteasome, Sem1/DSS1 associates with other protein complexes . It is a component of the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation .
MOFRL domain (MOFRL)
Type: Domain

The MOFRL(multi-organism fragment with rich Leucine) domain is found in bacteria and eukaryotes. The function of this domain is not clear, although it exists in some putative enzymes such as reductases and kinases.
Large ribosomal subunit protein eS32 (Ribosomal_eS32)
Type: Family

This entry represents the large ribosomal subunit protein eS32 (previously known as eL41), which associates with the ribonucleoprotein particles of the 60S subunit late in the ribosomal maturation process. eS32 is encoded by the smallest known open reading frame and in yeast is composed of only 24 amino acids, 17 of which are arginine or lysine.

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 .
DNA damage-inducible protein DinB (DinB)
Type: Family

This entry represents the DinB family, and includes DinB from Bacillus subtilis. DNA damage-inducible genes (dinA, dinB, and dinC) in Bacillus subtilis are coordinately regulated and together compose a global regulatory network that has been termed the SOS-like or SOB regulon .
Cell division protein ZapA-like (Cell_div_ZapA-like)
Type: Family

This entry represents a structural domain found in the cell division protein ZapA, as well as in related proteins. This domain has a core structure consisting of two layers alpha/beta, and has a long C-terminal helix that forms dimeric parallel and tetrameric antiparallel coiled coils . ZapA interacts with FtsZ, where FtsZ is part of a mid-cell cytokinetic structure termed the Z-ring that recruits a hierarchy of fission related proteins early in the bacterial cell cycle. ZapA drives the polymerisation and filament bundling of FtsZ, thereby contributing to the spatio-temporal tuning of the Z-ring.
GTP cyclohydrolase III (GTP_CycHdrlase_3)
Type: Family

GTP cyclohydrolase (GCH) III from Methanocaldococcus jannaschi catalyses the conversion of GTP to 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (FAPy). The reaction requires two bound magnesium ions for the catalysis and is activated by monovalent cations such as potassium and ammonium. The enzyme is a tetramer of identical subunits; each monomer is composed of an N- and a C-terminal domain that adopt nearly superimposible structures, suggesting that the protein has arisen by gene duplication .
Uncharacterised protein family UPF0210 (UPF0210)
Type: Family

The proteins in this family are functionally uncharacterised. The proteins are around 450 amino acids long and includes Streptococcus pneumoniae Sp0239 (

) and similar uncharacterised proteins. Sp0239 is structurally similar to ribonucleotide reductase (RNR) and pyruvate formate lyase (PFL), which are believed to have diverged from a common ancestor. RNR and PFL possess a ten-stranded α/β barrel domain that hosts the active site, and are radical enzymes. RNRs are found in all organisms and provide the only mechanism by which nucleotides are converted to deoxynucleotides. PFL is an essential enzyme in anaerobic bacteria that catalyses the conversion of pyruvate and CoA to acteylCoA and formate.