SII-SWORD/CoKE huggingface dataset:
HTH APSES-type DNA-binding domain superfamily (HTH_APSES_sf)
Type: Homologous_superfamily

The APSES (ASM-1, Phd1, StuA, EFG1, and Sok2) domain is a ~110-residue sequence-specific DNA-binding domain found in a family of fungal transcription factors and other DNA-binding proteins. The APSES domain is found associated with ankyrin repeats (see

,

) and a heterodimerization domain .

The APSES domain consists of a six-stranded β-sheet segment folded against two pairs of α-helices in the topology of the winged helix-turn-helix (HTH) family of proteins . The αA/αB helical pair corresponds to the HTH motif . Some proteins known to contain an APSES domain are listed below:

Saccharomyces cerevisiae (Baker's yeast) Mlu-1 box binding protein (MBP1,

); Mlu-1 and Swi6 together make up the transcription factor complex MBF (Mlu-1-binding factor), which binds to the Mlu1 cell-cycle box (MCB) elements found in the promoters of many DNA synthesis genes .

Schizosaccharomyces pombe (Fission yeast) cell division cycle-related proteins res1/sct1 (

) and res2/pct1 (

), which are homologous to MBP1.

S. pombe start control protein cdc10 (

).

Emericella nidulans (Aspergillus nidulans) cell pattern formation-associated protein stuA (

). It regulates the transformation of undifferentiated hyphal elements into a complex multicellular structure.

S. cerevisiae transcription factor PHD1 (

).

S. cerevisiae protein SOK2 (

). It represses the transition from unicellular growth to pseudohyphae.

Candida albicans (Yeast) enhanced filamentous growth protein (EFG1,

)).

Neurospora crassa ascospore maturation 1 protein (Asm-1,

). It has a role in spore maturation.

S. pombe bouquet formation protein 4 (

), which is a nuclear membrane protein that connects telomeres to the nuclear envelop (NE) during both vegetative growth and meiosis. Bqt4 does not seem to bind DNA, but acts as an adaptor between Bqt3 and Rap1 .
DNA integrity scanning protein, DisA, N-terminal domain superfamily (DNA_integrity_DisA_N_sf)
Type: Homologous_superfamily

Cyclic di-AMP (c-di-AMP) is a bacterial secondary messenger molecule, which is associated with various physiological functions. It is involved in several important cellular processes, such as cell wall metabolism, maintenance of DNA integrity, ion transport, transcription regulation, and allosteric regulation of enzyme function. The 120-amino acid-long diadenylate cyclase (DAC) domain converts two ATP or ADP molecules into one c-di-AMP molecule. The majority of DAC domain-containing proteins are found in bacterial species, but a small number are also present in archaea of the phylum Euryarchaeota. In bacteria, DAC domain proteins are most frequently found in Gram-positive bacteria belonging to the phyla Firmicutes and Actinobacteria, including pathogenic bacteria such as Listeria monocytogenes or
Staphylococcus aureus
. Compared with the majority of bacterial species which encode only one DAC enzyme, members of the genus
Bacillus
generally encode three DAC domain-containing proteins: DisA, CdaA (previously named YbbP in the genus
Bacillus
or DacA in other genera) and CdaS (previously named YojJ in the genus
Bacillus
or DacB in others) .

The DAC domain exhibits an overall globular α/β fold with the long N-terminally located helix (alpha1) flanking the core. A slightly twisted central β-sheet, made up of seven mixed-parallel and antiparallel β-strands, forms the core globular part. Both sides of the β-sheets are flanked by a total of five α-helices (alpha1-alpha5), resulting in the observed globular shape .

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. The DAC domain is the first and is a globular, nucleotide-binding region; the next 146-289 residues constitute the DisA-linker family,

that consists of an elongated bundle of three α helices (alpha-6, alpha-10, and alpha-11), one side of which carries an additional three helices (alpha7-9), which thus forms a spine like-linker between domains 1 and 3. The C-terminal residues, of domain 3, are represented by family HHH,

the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis.
Monooxygenase component MmoB/DmpM superfamily (mOase_MmoB_DmpM_sf)
Type: Homologous_superfamily

This entry includes monooxygenase component MmoB methane monooxygenase (

) regulatory protein B and Phenol hydroxylase (

) protein component P2 (DmpM). When MmoB is present at low concentration it converts methane monooxygenase from an oxidase to a hydroxylase and stabilises intermediates required for the activation of dioxygen . DmpM lacks redox co-factors and is required for optimal turnover of Phenol hydroxylase . Phenol hydroxylase catabolises phenol and some of its methylated derivatives in the first step of phenol biodegradation, and is required for growth on phenol. The multicomponent enzyme is made up of P0, P1, P2, P3, P4 and P5 polypeptides.

The common structure for these proteins consists of a corner-like structure formed by two sheets and filled in with 2-3 helices.
Histidine kinase/HSP90-like ATPase superfamily (HATPase_C_sf)
Type: Homologous_superfamily

This domain superfamily is found in several ATP-binding proteins, including: histidine kinase , DNA gyrase B, topoisomerases , heat shock protein HSP90 , phytochrome-like ATPases and DNA mismatch repair proteins. The fold of this domain consists of two layers, α/β, which contains an 8-stranded mixed β-sheet.
Signal recognition particle, SRP54 subunit, M-domain superfamily (Signal_recog_part_SRP54_M_sf)
Type: Homologous_superfamily

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

This entry represents the M domain superfamily of the 54kDa SRP54 component, a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species.

These proteins include Escherichia coli and Bacillus subtilis ffh protein (P48), which seems to be the prokaryotic counterpart of SRP54; signal recognition particle receptor alpha subunit (docking protein), an integral membrane GTP-binding protein which ensures, in conjunction with SRP, the correct targeting of nascent secretory proteins to the endoplasmic reticulum membrane; bacterial FtsY protein, which is believed to play a similar role to that of the docking protein in eukaryotes; the pilA protein from Neisseria gonorrhoeae, the homologue of ftsY; and bacterial flagellar biosynthesis protein flhF.
L27 domain superfamily (L27_dom_sf)
Type: Homologous_superfamily

The L27 domain is a ~50-amino acid module, initially identified in the Lin-2 and Lin-7 proteins, that exists in a large family of animal scaffold proteins . The L27 domain is a specific protein-protein interaction module capable of forming heteromeric complexes that can integrate multiple scaffold proteins into supramolecular assemblies required for establishment and maintenance of cell polarity. The L27 domain can be found as a single occurrence or as a duplication in association with other domains such as PDZ, SH3, the guanylate kinase domain or the serine/threonine protein kinase domain.

The main features of the L27 domain are conserved negatively charged residues and a conserved aromatic amino acid . Study of individual L27 domains revealed largely unfolded domains that require the formation of obligate heterodimers to achieve well-folded structures. Each L27 domain is composed of three helices. The two L27 domains heterodimerize by building a compact structure consisting of a four-helix bundle formed by the first two helices of each L27 domain and one coiled-coil formed by the third helix of each domain .
SBP domain superfamily (SBP_sf)
Type: Homologous_superfamily

SBP (for SQUAMOSA-pROMOTER BINDING PROTEIN) domain is a sequence specific DNA-binding domain found in plant proteins . Members of family probably function as transcription factors involved in the control of early flower development . They share a highly conserved DNA-binding domain that contains two zinc-binding sites. Among the 11 possible ligands for the zinc atoms that are conserved in the SBP zinc finger, only 8 are used. The SBP zinc finger follows the general pattern C-x4-C-x16-C-x2-[HC]-x15-C-x2-C-x3-H-x11-C. Three other histidines are well conserved but not involved in zinc binding .

In vitro experiments show that the SBP zinc finger preferentially binds the consensus sequence -TNCGTACAA- . However, little is known of the physiological functions of these putative transcriptional regulators beyond their ability to bind DNA.

The solution structure of the SBP zinc finger has been solved . The first four Cys or His coordinate one zinc ion and the last four coordinate the other. It can be viewed as two structural subdomains, each subdomain containing a single zinc-binding pocket. The N-terminal subdomain consists of two short α helices whereas the C-terminal one contains a three-stranded antiparallel β-sheet.
Nucleoid-associated protein YbaB-like domain superfamily (YbaB-like_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily of DNA-binding proteins. It is restricted to bacteria and plants. Members of this family form homodimers which bind DNA via a tweezer-like structure . The conformation of the DNA is changed when bound to these proteins . In bacteria, these proteins may play a role in DNA replication-recovery following DNA damage . The plant form contains an additional N-terminal region that may serve as a transit peptide and shows a close relationship to the cyanobacterial member, suggesting that it is a chloroplast protein.

The crystal structure YbaB from Haemophilus influenzae revealed a tight dimer with a three-layer structure (β/α/β) .
Uracil-DNA glycosylase-like domain superfamily (Uracil-DNA_glycosylase-like_sf)
Type: Homologous_superfamily

This entry represents various uracil-DNA glycosylases and related DNA glycosylases (

), such as uracil-DNA glycosylase , thermophilic uracil-DNA glycosylase , G:T/U mismatch-specific DNA glycosylase (Mug) , and single-strand selective monofunctional uracil-DNA glycosylase (SMUG1) . These proteins have a 3-layer α/β/α structure.

Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosylic bond, initiating the base excision repair pathway. Uracil in DNA can arise either through the deamination of cytosine to form mutagenic U:G mispairs, or through the incorporation of dUMP by DNA polymerase to form U:A pairs . These aberrant uracil residues are genotoxic . The sequence of uracil-DNA glycosylase is extremely well conserved in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses .
Avidin-like superfamily (Avidin-like_sf)
Type: Homologous_superfamily

Avidin is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.

Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin. The three-dimensional structures of both streptavidin and avidin have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site.

Fibropellins I and III are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see

), followed by a variable number of EGF repeats and a C-terminal avidin-like domain.
Carbamoyl-phosphate synthetase, large subunit oligomerisation domain superfamily (CarbamoylP_synth_lsu_oligo_sf)
Type: Homologous_superfamily

This entry represents the oligomerisation domain superfamily found in the large subunit of carbamoyl phosphate synthases as well as in certain other carboxy phosphate domain-containing enzymes. This domain forms a primarily α-helical fold .
RNA polymerase Rpb7-like, N-terminal domain superfamily (RNA_pol_Rpb7-like_N_sf)
Type: Homologous_superfamily

The eukaryotic RNA polymerase subunits RPB4 and RPB7 form a heterodimer that reversibly associates with the RNA polymerase II core, being involved in initiation complex formation . Archaeal cells contain a single RNAP made up of about 12 subunits, displaying considerable homology to the eukaryotic RNAPII subunits. The RPB4 and RPB7 homologues are called subunits F and E, respectively, and have been shown to form a stable heterodimer. While the RPB7 homologue is reasonably well conserved, the similarity between the eukaryotic RPB4 and the archaeal F subunit is barely detectable .

This entry represents the N-terminal, heterodimerisation domain superfamily of RPB7 and homologues. This domain has a β-α-β(2) fold arranged in two layers (α/β) with antiparallel β-sheet.
Large ribosomal subunit protein uL13 superfamily (Ribosomal_uL13_sf)
Type: Homologous_superfamily

The structure of the uL13 domain is composed of three layers (α/β/α) with parallel β-sheet of four strands.

Ribosomal protein uL13 is one of the proteins from the large ribosomal subunit . In Escherichia coli, uL13 is known to be one of the early assembly proteins of the 50S ribosomal subunit. uL13 proteins were previously known as L13 from bacteria,	L16 from yeast and L13A from human.

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 .
Alpha-D-phosphohexomutase, C-terminal domain superfamily (A-D-PHexomutase_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain superfamily of alpha-D-phosphohexomutase enzymes.

The alpha-D-phosphohexomutase superfamily is composed of four related enzymes, each of which catalyses a phosphoryl transfer on their sugar substrates: phosphoglucomutase (PGM), phosphoglucomutase/phosphomannomutase (PGM/PMM), phosphoglucosamine mutase (PNGM), and phosphoacetylglucosamine mutase (PAGM) . PGM (

) converts D-glucose 1-phosphate into D-glucose 6-phosphate, and participates in both the breakdown and synthesis of glucose . PGM/PMM (

;

) are primarily bacterial enzymes that use either glucose or mannose as substrate, participating in the biosynthesis of a variety of carbohydrates such as lipopolysaccharides and alginate . Both PNGM (

) and PAGM (

) are involved in the biosynthesis of UDP-N-acetylglucosamine .
Aspartate/ornithine carbamoyltransferase superfamily (Asp/Orn_carbamoylTrfase_sf)
Type: Homologous_superfamily

This domain superfamily contains two related enzymes:

Aspartate carbamoyltransferase (

) (ATCase) catalyses the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the
de novo
biosynthesis of pyrimidine nucleotides . In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals ) that also catalyses other steps of the biosynthesis of
pyrimidines.

Ornithine carbamoyltransferase (

) (OTCase) catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine (the arginine deaminase pathway).

It has been shown that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies , to be implicated in binding the phosphoryl group of carbamoyl phosphate.
Ta1353-like superfamily (Ta1353-like_sf)
Type: Homologous_superfamily

The structure of a member of this superfamily from the hyperthermophilic archaeon Pyrobaculum aerophilum contains a modified histidine residue which is interpreted as stable phosphorylation. In vitro binding studies confirmed that adenosine and AMP but not ADP or ATP bind to the protein . The core structure of this domain is composed of β-α-β(2)-α-β-α-β fold arranged in three layers (α/β/α) with antiparallel β-sheet of five strands.
Phycobilisome degradation protein NblA superfamily (NblA_sf)
Type: Homologous_superfamily

In the cyanobacterium Synechococcus species PCC 7942 (

), nblA triggers degradation of light-harvesting phycobiliproteins in response to deprivation nutrients including nitrogen, phosphorus and sulphur. The mechanism of nblA function is not known, but it has been hypothesised that nblA may act by disrupting phycobilisome structure, activating a protease or tagging phycobiliproteins for proteolysis. Members of this domain superfamily have also been identified in the chloroplasts of some red algae. The structure of the nblA domain is composed of four helices arranged as dimer of identical α-hairpin subunits with open bundle.
ATPase, V1 complex, subunit F superfamily (ATPase_V1_fsu_sf)
Type: Homologous_superfamily

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents subunit F in the V1 complex of V-ATPases and Na(+)-translocating ATPase in Enterococcus hirae. Subunit F is a 16kDa protein that is required for the assembly and activity of V-ATPase, and has a potential role in the differential targeting and regulation of the enzyme for specific organelles. This subunit is not necessary for the rotation of the ATPase V1 rotor, but it does promote catalysis . In Enterococcus hirae, Na(+)-translocating ATPase extrudes sodium ions from the cytoplasm and generates the Na+ electrochemical gradient by using the energy of ATP . Structurally, the subunit F is composed of three layers (α/β/α) with parallel β-sheet of four strands.