SII-SWORD/CoKE huggingface dataset:
Telomerase reverse transcriptase, TEN domain (TERT_TEN)
Type: Domain

This entry represents the N-terminal domain of Telomerase reverse transcriptase from Tetrahymena thermophila (TERT), named the TEN domain. TERT is the catalytic component of the telomerase, a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme . The TEN domain is able to bind both RNA and telomeric DNA and contributes towards telomerase catalysis. Its structure consists of a core β-sheet surrounded by seven α-helices and a short β-hairpin .
WD repeat-containing protein 72-like (WDR72-like)
Type: Family

This family includes WD repeat-containing protein 7 and WD repeat-containing protein 72 (WDR7/72). The function of WDR7 is currently unknown.

WD repeat-containing protein 72 (WDR72) plays a major role in the formation of tooth enamel, particularly during the maturation phase of amelogenesis, where it is essential for normal enamel matrix formation and the clearance of enamel proteins . WDR72 may also be involved in the localisation of the calcium transporter SLC24A4 to the ameloblast cell membrane. These proteins share a distinct domain architecture comprising one or two β-propellers followed by an α-solenoid domain

, an evolutionarily conserved structure common among proteins that form membrane coat complexes, dating back to the early eukaryotic endomembrane system .
Excisionase Xis (Xis_Gifsy_1-like)
Type: Family

Members of this family are excisionases such as Xis from the Gifsy-1 prophage of Salmonella enterica and are found exclusively in Enterobacterales. Excision of the Gifsy-I phage requires three proteins, the Gifsy-I integrase (Int), the Gifsy-I excisionase (Xis) protein, and host encoded Integration Host Factor (IHF). Gifsy-I Xis is involved in the regulation of the Gifsy-I phage excision and interacts with the Gifsy-I Int protein .
HxsD-related (HxsD-rel)
Type: Family

This entry represents a group of prokaryotic proteins. Members of this family resemble HxsD, although they are usually shorter. HxsD is a possible chaperone of a radical SAM-catalysed peptide modification system. Members of this family often are found in the context of other Hxs system proteins, suggesting it may be one of a pair of chaperones in those systems.
Type 4 adapter protein IcmW (IcmW)
Type: Family

This entry represents the IcmW protein (

) from Legionella pneumophila and similar proteins found mainly in Legionellales. IcmW is a component of the Dot/Icm secretion machinery and play an important role in the injection of bacterial effector proteins into eukaryotic host cells . IcmW exists in a stable complex with IcmS and in its absence it is rapidly degraded . The IcmS-IcmW complex is involved in the recognition and Dot/Icm-dependent translocation of substrate proteins during Legionella infection of host cells .

The structure of the IcmS-IcmW complex was determined showing that these proteins form a 1:1 heteromeric complex in order to bind effector substrates . The IcmS-IcmW complex function as an inseparable integral component of the DotL-T4CP complex in the bacterial inner membrane. The structure of the DotL-IcmS-IcmW complex revealed extensive and highly stable interactions between DotL and IcmS-IcmW .
Probable CBASS effector molecule IK1_05631-like (IK1_05631-like)
Type: Family

This entry represents a family of prokaryotic proteins, including the probable CBASS effector molecule IK1_05631 (

) from Bacillus cereus. CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophages . Some members of this group are predicted pore-forming effectors found in conserved genome contexts with diverse nucleotide synthetases including the SMODS (Second Messenger Oligonucleotide or Dinucleotide Synthetases) .
Type 4 apparatus protein DotM-llike (DotM-like)
Type: Family

This entry represents Type 4 apparatus protein DotM (

) from Legionella pneumophila and similar proteins mainly from gammaproteobacteria. DotM is a component of the Dot/Icm type 4B secretion system (T4BSS), which is used to inject bacterial effector proteins into eukaryotic host cells . The T4BS systems are encoded by a large gene cluster named dot/icm. Three components of this system, DotL, DotM, and DotN, form the "coupling complex", which serves as a platform for recruitment of effector proteins .

The structure of DotM was determined as a part of the membrane-embedded T4 coupling complex (T4CC). The T4CC includes the DotL ATPase, the DotM and DotN proteins, the chaperone module IcmSW, and DotY and DotZ proteins (

) . In the T4CC complex, DotLMNYZ form hetero-pentameric core from which the flexible IcmSW module protrudes . DotM forms the interacting surface for recruitment of acidic Glu-rich motif-containing effectors .
Glycosyl-hydrolase 114-associated domain (GH114_assoc)
Type: Domain

This entry represents a domain often found N-terminal to the TIM-barrel domain of GH114 glycosyl-hydrolases (

). It is predicted to adopt a β-sandwich.
Avirulence protein (AvrXv3-like)
Type: Family

This entry represents Avirulence protein AvrXv3, a type III secretion system effector from Xanthomonas euvesicatoria (

), and similar proteins found mainly in gammaproteobacteria. The expression of this protein is controlled by the hypersensitivity and pathogenicity (hrp) regulatory system. AvrXv3 possess transcription activation activity in yeast, and the domain located at the C terminus of this protein is responsible for this activity .
TonB, proline-rich region (TonB_pro-rich)
Type: Domain

This entry represents proline-rich segment of Protein TonB from Escherichia coli and similar sequences from enterobacterales. TonB is critical for the uptake of siderophores through the outer membrane using chemiosmotic energy. This region adopts in a PPII-like conformation . This implies that the proline-rich segment of TonB possesses a length of more than 15 nm, sufficient to span the periplasm of Gram-negative bacteria.
Plasmid stabilization protein StbA-like (StbA-like)
Type: Family

This entry represents the plasmid stabilisation protein StbA and related proteins found mainly in Enterobacterales. StbA is encoded within the stbABC operon and is required for plasmid stability. StbA and StbB control conjugation and both are considered part of an atypical plasmid stabilisation system that reconciles two modes: a maintenance mode (replication and segregation) and a propagation mode (conjugation) .
Plasmid transfer protein HtdO-like (HtdO-like)
Type: Family

This entry represents the plasmid transfer protein HtdO from Serratia marcescens (

,

), Salmonella enterica (

,

) and similar proteins from Enterobacterales.
DotY, N-terminal domain (DotY_N)
Type: Domain

This entry represents the N-terminal domain of DotY, which is responsible for interaction with DotZ . DotY and DotZ are integral parts of the T4CC and play significant roles in the translocation of effectors into eukaryotic host cells. They are unique to the Legionella genus. .

DotY is a component of membrane-embedded T4 coupling complex (T4CC), which consists of the DotL ATPase, the DotM and DotN proteins, and DotY and DotZ. The DotLMNYZ hetero-pentamer and plays an essential role in the recruitment and delivery of effectors to the Type IV secretion (T4S) machinery in Legionella pneumophila, a bacterial pathogen that utilizes a T4S system to inject effector proteins into human macrophages.
Type III secretion system effector XopP-like (XopP-like)
Type: Family

This entry represents the Type III secretion system effector XopP and related proteins found in beta- and gammaproteobacteria. XopP is a highly conserved core-effector protein produced by X. campestris, the causal agent of black rot disease of crucifers such as Brassica spp., radish, and turnip. This protein is essential for virulence and inhibits the function of the host-plant exocyst complex by direct targeting of Exo70B, a subunit of the exocyst complex, which plays a significant role in plant immunity . XopP interferes with exocyst-dependent exocytosis and efficiently inhibits the host's pathogen-associated molecular pattern (PAMP)-triggered immunity
Type III toxin-antitoxin system, toxin TenpN-like (TenpN-like)
Type: Family

This family represents the TenpN-like toxin component of a bacterial type III toxin-antitoxin (TA) system, which consists of a ribonuclease (RNase) toxin that processes its structured and specific cognate RNA antitoxin, which in turn then directly inhibits the toxin. TA systems have been associated with many important phenotypes, like phage resistance, maintenance of genomic islands, and formation of bacterial persister cells .
VapC-like, PIN domain (PIN_VapC-like)
Type: Domain

This entry represents the PIN domain found in cyanobacterial proteins distantly related to VapC.

VapC is a PIN-domain ribonuclease toxin from prokaryotic VapBC toxin-antitoxin (TA) systems. VapB is a transcription factor-like protein antitoxin acting as an inhibitor. Other members of the VapC-like nuclease family include FitB toxin of the FitAB TA system, eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1 .

The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN (PilT N terminus) domain indicate its active centre, consisting of three highly conserved catalytic residues which coordinate metal ions, in some members, additional metal coordinating residues can be found. Some members of the superfamily lack several of these key catalytic residues. The PIN active site is geometrically similar in the active centre of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons .
Nuclear envelope-associated protein 1-4 (NEAP1-4)
Type: Family

This family represents a group of plants proteins, including nuclear envelope-associated proteins (NEAP) that interact with other proteins of the nuclear envelope. In Arabidopsis thaliana, this family comprises three genes AtNEAP1-3 expressed ubiquitously and a pseudogene AtNEAP4 . These proteins consist of coiled-coils and localise to the nuclear periphery where they form part of stable protein complexes. They are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, which are involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex.
RpoE leader peptide (RseD)
Type: Family

This entry represents the rpoE leader peptide from Escherichia coli (RseD) and similar proteins from enterobacterales. RseD is a short protein whose stop codon overlaps with the start codon of downstream rpoE, the gene for the extracytoplasmic stress response sigma factor RpoE. A premature stop codon at position 12 results in decreased expression of RpoE, thus they are translationally coupled . It participates in the CrsA-mediated fine-tuning of the stress response. The corresponding locus in Klebsiella pneumoniae appears to be split into an upstream and a downstream peptide.
Outer membrane protein GjpA-like (GjpA-like)
Type: Family

This entry represents the homologues of outer membrane protein GjpA found mainly in Mycobacteriales. GjpA was first identified in Gordonia jacobaea strain MV-1 as an outer membrane channel-forming protein . GjpA is likely involved in the import and export of negatively charged molecules across the cell wall.
SMC5-SMC6 complex localization factor protein 1, BRCT domain (BRCT_SLF1)
Type: Domain

SLF1, also termed Smc5/6 localization factor 1, or ankyrin repeat domain-containing protein 32 (ANKRD32), or BRCT domain-containing protein 1 (BRCTD1), plays a role in the DNA damage response (DDR) pathway by regulating post replication repair of UV-damaged DNA and genomic stability maintenance. It is a component of the SLF1-SLF2 complex that acts as a link between RAD18 and the SMC5-SMC6 complex at replication-coupled interstrand cross-links (ICL) and DNA double-strand break (DSB) sites on chromatin during DNA repair in response to stalled replication forks. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is missing in this group.
TopBP1, eighth BRCT domain (TopBP1_BRCT_8)
Type: Domain

This entry corresponds to the eighth BRCT domain found in TopBP1. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this group.

TopBP1, also known as DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response, acting as a scaffold protein . It binds double-stranded DNA breaks and nicks as well as single-stranded DNA . It has been shown to activate the ATR-ATRIP complex . TopBP1 contains eight copies of BRCT domain which specifically recognise and bind phosphorylated proteins, bringing proteins together into functional combinations .
Chp1, chromodomain (CD_Chp1-like)
Type: Domain

Chromodomain-containing protein 1 (Chp1) is required for RNA interference-dependent heterochromatin formation in fission yeast and it is a member of the RNA-induced transcriptional silencing (RITS) complex which maintains the heterochromatin regions, playing a role in stabilizing microtubules which allows accurate chromosome segregation .

This entry represents the chromodomain (CD) of the Chp1 component which binds the histone H3 lysine 9 methylated tail (H3K9me) and the core of the nucleosome . Chromodomain is a conserved region usually of about 50 amino acids, found in a variety of chromosomal proteins, which appears to play a role in the functional organization of the eukaryotic nucleus.
Chp1, SPOC domain (SPOC_Chp1p)
Type: Domain

This entry represents the SPOC domain of Chp1 that is involved in developmental signaling and has also been proposed to be a phosphorylation binding module .

Chromodomain-containing protein 1 (Chp1) is required for RNA interference-dependent heterochromatin formation in fission yeast. Chp1 is a member of the RNA-induced transcriptional silencing (RITS) complex which maintains the heterochromatin regions and plays a role in stabilizing microtubules which allows accurate chromosome segregation .
Nitrogenase MoFe cofactor biosynthesis protein NifE-like (NifE-like)
Type: Family

This entry represents Nitrogenase iron-molybdenum cofactor biosynthesis protein NifE from Azotobacter vinelandii and similar prokaryotic proteins. NifE may play a role in the biosynthesis of the prosthetic group of nitrogenase (FeMo cofactor).

The enzyme responsible for nitrogen fixation, the nitrogenase, shows a high degree of conservation of structure, function, and amino acid sequence across wide phylogenetic ranges. All known Mo-nitrogenases consist of two components, component I (also called dinitrogenase, or Fe-Mo protein), an alpha2beta2 tetramer encoded by the nifD and nifK genes, and component II (dinitrogenase reductase, or Fe protein) a homodimer encoded by the nifH gene which has an Fe4S4 cluster bound between the subunits and two ATP-binding domains. The Fe protein supplies energy by ATP hydrolysis, and transfers electrons from reduced ferredoxin or flavodoxin to component 1 for the reduction of molecular nitrogen to ammonia . Nitrogenase contains two unusual rare metal clusters; one of them is the iron molybdenum cofactor (FeMo-co), which is considered to be the site of dinitrogen reduction and whose biosynthesis requires the products of the nifNE operon and of some other nif genes . It has been proposed that nifNE might serve as a scaffold upon which FeMo-co is built and then inserted into component I .
Lysophospholipid acyltransferase 7/Porcupine-like (LPLAT_7/PORCN-like)
Type: Family

This entry represents a group of eukaryotic proteins, including human Lysophospholipid acyltransferase 7 (LPLAT 7) and Protein-serine O-palmitoleoyltransferase porcupine (PORCN).

LPLAT 7 catalyses the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodelling pathway also known as the Lands cycle . Alterations on its expression are associated to brain developmental disorders, fatty liver disease and hepatocellular and renal cancers. Its structure is mainly α-helical, with 11 transmembrane (TM) helical segments linked by short intervening helices (IH) and loops .

PORCN acts as a key regulator of the Wnt signalling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins . This protein shows a similar structural configuration to LPLAT7, with 11 TMs, 6 (IH) and 2 β-strands .
DML1/Misato (DML1/Misato)
Type: Family

This entry represents a group of eukaryotic proteins, including Misato from Drosophila melanogaster (MST) and its homologues such as protein DML1 from fungi and protein misato homolog 1 (MSTO1) from mammals.

Misato from Drosophila and DML1p from fungi are descendants of an ancestral tubulin-like protein, and exhibit regions with similarity to members of a GTPase family that includes eukaryotic tubulin and prokaryotic FtsZ . DML1p and Misato have been co-opted into a role in mtDNA inheritance in yeast, and into a cell division-related mechanism in flies, respectively. DML1p might additionally function in the partitioning of the mitochondrial organelle itself, or in the segregation of chromosomes, thereby explaining its essential requirement.

DML1 is involved in the partitioning of the mitochondrial organelle and mitochondrial DNA (mtDNA) inheritance . MST is required for mitotic spindle assembly and viability and for tubulin polymerization and stability .

MSTO1 is involved in the regulation of mitochondrial distribution and morphology .
It is required for mitochondrial fusion and mitochondrial network formation .
Serine hydroxymethyltransferase-like (Ser_HO-MeTrfase-like)
Type: Family

This entry includes serine hydroxymethyltransferases, transaldolases and other uncharacterised proteins.

Serine hydroxymethyltransferase is a pyridoxal phosphate (PLP) requiring enzyme whose physiological role is to catalyse the formation of single carbon groups for a number of biosynthetic pathways. It catalyses the reversible interconversion of serine and glycine with tetrahydrofolate serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules. Serine hydroxymethyltransferase adopts an α/β structure consisting of a mixed β-sheet and α-helices packed on both sides of it .

This entry also includes L-threonine:uridine-5'-aldehyde transaldolase and fluorothreonine transaldolase. L-threonine:uridine-5'-aldehyde transaldolase is involved in the biosynthesis of the capuramycin-type nucleoside antibiotic A-102395 . This enzyme catalyses the condensation of L-threonine and uridine-5'-aldehyde to form 5'-C-glycyluridine . Fluorothreonine transaldolase catalyses the final step in 4-fluorothreonine biosynthesis. Mediates a L-threonine/fluoroaceldehyde to 4-fluoro-L-threonine/acetaldehyde crossover reaction. It can also convert chloroacetaldehyde into 4-chloro-L-threonine .
5-hydroxytryptamine 3 receptor, transmembrane domain (LGIC_TM_5-HT3)
Type: Domain

This entry represents the transmembrane (TM) domain of the serotonin 5-HT3 receptors . The transmembrane region consists of four transmembrane-spanning α-helical segments (M1-M4) that are linked by loops. The intracellular loop that links M1 and M2 determines the ion selectivity of the channel.

The 5-HT3 channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems. Like other ligand gated ion channels, the 5-HT3 receptor consists of five subunits arranged around a central ion conducting pore, which is permeable to Na+, K+, and Ca2+ ions. Binding of the neurotransmitter 5-hydroxytryptamine (serotonin) to the 5-HT3 receptor opens the channel, which then leads to an excitatory response in neurons, and the rapidly activating, desensitizing, inward current is predominantly carried by Na+ and K+ ions . This receptor is most closely related by homology to the nicotinic acetylcholine receptor (nAChR) . Five subunits have been identified for this family: 5-HT3A, 5-HT3B, 5-HT3C, 5-HT3D, and 5-HT3E, encoded by HTR3A-E genes. Only 5-HT3A subunits are able to form functional homomeric receptors, whereas the 5-HT3B, C, D, and E subunits form heteromeric receptors with 5-HT3A. Different receptor subtypes are important mediators of nausea and vomiting during chemotherapy, pregnancy, and following surgery, while some contribute to neuro-gastroenterologic disorders such irritable bowel syndrome (IBS) and eating disorders as well as comorbid psychiatric conditions . 5-HT3 receptor antagonists are established treatments for emesis and IBS, and are beneficial in the treatment of psychiatric diseases .
ORC1/DEAH AAA+ ATPase domain (AAA_22)
Type: Domain

This entry represents a number of closely related AAA+ ATPase domains from proteins involved in diverse processes such as DNA replication, DNA transposition and mRNA splicing. Amongst the proteins containing this domain are Origin recognition complex (ORC) subunits , Transposon Tn7 transposition protein TnsC , cell division control proteins and pre-mRNA-splicing factor ATP-dependent RNA helicases .
Large ribosomal subunit protein bL20, conserved site (RIBOSOMAL_L20_CS)
Type: Conserved_site

This entry represents a conserved site found in the central section of Large ribosomal subunit protein bL20 (also known as Ribosomal protein L20) which is one of the proteins from the large ribosomal subunit. In Escherichia coli, L20 is known to bind directly to the 23S rRNA. Based on sequence
similarities, this entry groups:

- Eubacterial L20.

- Algal and plant chloroplast L20.

- Cyanelle L20.

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 .