SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein uL11, C-terminal domain superfamily (Ribosomal_uL11_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of uL11. The domain consists of a three-helical bundle and a short parallel two-stranded β-ribbon, with an overall α3-β4-α4-α5-β5 topology. All five secondary structure elements contribute to a conserved hydrophobic core. The domain is characterised by two extended loops that are disordered in the absence of the RNA but have defined structures in the complex .

Ribosomal protein uL11 (also known as L12 in mammals and yeast) is one of the proteins from the large ribosomal subunit. In Escherichia coli, uL11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial uL11; and mammalian, plant and yeast L12 (YL15). uL11 is a protein of 140 to 165 amino-acid residues and consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of uL11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA . In E. coli, the C-terminal half of uL11 has been shown to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.
Ankyrin repeat-containing domain superfamily (Ankyrin_rpt-contain_sf)
Type: Homologous_superfamily

This entry represents the ankyrin repeat-containing domain. These domains contain multiple repeats of a β(2)-α(2) motif. The ankyrin repeat is one of the most common protein-protein interaction motifs in nature. Ankyrin repeats are tandemly repeated modules of about 33 amino acids. They occur in a large number of functionally diverse proteins mainly from eukaryotes. The few known examples from prokaryotes and viruses may be the result of horizontal gene transfers . The repeat has been found in proteins of diverse function such as transcriptional initiators, cell-cycle regulators, cytoskeletal, ion transporters and signal transducers. The ankyrin fold appears to be defined by its structure rather than its function since there is no specific sequence or structure which is universally recognised by it.
F0F1 ATP synthase delta/epsilon subunit, N-terminal (ATPsynth_dsu/esu_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal β-sandwich domain of F1F0-ATP synthase subunits delta (in mitochondrial ATPase) and epsilon (in bacteria or chloroplast ATPase) . The interaction site of subunit C of the F0 complex with the delta or epsilon subunit of the F1 complex may be important for connecting the rotor of F1 (gamma subunit) to the rotor of F0 (C subunit) . In bacterial species, the delta subunit is the equivalent of the oligomycin sensitive subunit (OSCP,

) in metazoans. The C-terminal domain of the epsilon subunit appears to act as an inhibitor of ATPase activity .
SRCR-like domain superfamily (SRCR-like_dom_sf)
Type: Homologous_superfamily

The scavenger receptor cysteine-rich (SRCR) domain is an ancient and highly conserved domain of about 110 residues which is found in diverse secreted and cell-surface proteins, like the type I scavenger receptor, the speract receptor, CD5/Ly-1, CD6, or complement factor I . Tandem repeats of SRCR domains are common in the membrane bound proteins. Most SRCR domains have six to eight cysteines that participate in intradomain disulfide bonds. SRCR domains have been subdivided into two groups, A and B, primarily on the differences in the spacing pattern between the cysteine residues . Besides type I scavenger receptor, this domain can also be found in the N-terminal of hepsin .

The core structure of SRCR has a β-x-α-β-loop-β fold.
TGF-beta binding (TB) domain superfamily (TB_dom_sf)
Type: Homologous_superfamily

The transforming growth factor beta family of cytokines, are potent and multifunctional signalling molecules. Prior to ligand receptor binding there exist extracellular regulators that target these cytokines and facilitate the formation of morphogen gradients that control developmental processes. Some of these proteins that are known to sequester latent TGF-beta contains a conserved domain, the TGF-beta binding (TB) domain.

The domain is characterised by 8 conserved cysteine residues, which include an unusual cysteine triplet . The TB fold is globular with six β-strands and two α-helices . The pairing of the eight cysteines is 1-3, 2-6, 4-7, and 5-8, creating a fairly rigid structure. In follistatin and in the first repeat of fibrillin and LTBPs the last disulphide bridge is absent.

Proteins containing a TB domain include:

Vertebrate fibrillin-1, 2 and 3. Fibrillins form tissue-specific and temporally regulated microfibril networks. They are implicated in the regulation of TGF-beta signalling.

Vertebrate latent TGF-beta binding proteins (LTBPs) 1, 2, 3 and 4 LTBPs regulate TGF-beta signalling by forming a latent complex with the cleaved TGF-beta proproteins.

Vertebrate follistatin. It is an extracellular antagonist of various TGF-beta proteins. The TB domain of follistatin mimic a type I receptor of TGF-beta and binds TGF-beta which leads to the formation of a receptor-ligand-antagonist complex .
ERV/ALR sulfhydryl oxidase domain superfamily (ERV/ALR_sulphydryl_oxid_sf)
Type: Homologous_superfamily

The ~100-residue ERV/ALR sulphydryl oxidase domain is a versatile module adapted for catalysis of disulphide bond formation in various organelles and biological settings. The ERV/ALR sulphydryl oxidase domain has a Cys-X-X-Cys dithiol/disulphide motif adjacent to a bound FAD cofactor, enabling transfer of electrons from thiol substrates to non-thiol electron acceptors. ERV/ALR family members differ in their N- or C-terminal extensions, which typically contain at least one additional disulphide bond, the hypothesised 'shuttle' disulphide. In yeast ERV1, a mitochondrial enzyme, the shuttle disulphide is N-terminal to the catalytic core; in yeast ERV2, present in the endoplasmic reticulum, it is C-terminal. The N- and C-terminal extensions can be entire domains, such as the thioredoxin-like domains (

) or short segments that do not seem to be distinct domains. Proteins of the ERV/ALR family are encoded by all eukaryotes and cytoplasmic DNA viruses (poxviruses, African swine fever virus, iridoviruses, and Paramecium bursaria Chlorella virus 1) .

The ERV/ALR sulphydryl oxidase domain contains a four-helix bundle (helices α1-α4) and an additional single turn of helix (α5) packed perpendicular to the bundle . The FAD prosthetic group is housed at the mouth of the 4-helix bundle and communicates with the pair of juxtaposed cysteine residues that form the proximal redox active site .
DNA polymerase, Y-family, little finger domain superfamily (DNA_pol_Y-fam_lit_finger_sf)
Type: Homologous_superfamily

This entry represents the little finger domain superfamily found in Y-family (lesion bypass) DNA polymerases. Y-family polymerases were originally known as UmuC/DinB/Rev1/Rad30 after each branch of the family. These enzymes are characterised by their low-fidelity synthesis on undamaged DNA templates and by their ability to traverse replication-blocking lesions. By contrast, high-fidelity polymerases (such as DNA polymerase III) are sensitive to distortions in the DNA template. As a result, Y-family polymerases can extend primer strands across DNA strand lesions that would otherwise stall replicative polymerases. To minimize mutations through their low fidelity synthesis, these enzymes are regulated, and are thought to interact with processivity factors, β-clamp or proliferating cell nuclear antigen (PCNA), which are also essential for the function of replicative DNA polymerases . Organisms can contain more than one Y-family polymerase, each with a unique DNA damage bypass and fidelity profile. For example, humans posses four Y-family polymerases: DNA polymerases kappa, iota, eta and Rev1. Y-family polymerases show no homology to DNA polymerases from the A-, B-, C-, D- or X-families .
Nucleoside-specific channel-forming protein, Tsx-like superfamily (Channel_Tsx-like_sf)
Type: Homologous_superfamily

The tsx gene of Escherichia coli encodes an outer membrane protein, Tsx, which constitutes the receptor for colicin K and Bacteriophage T6, and functions as a substrate-specific channel for nucleosides and deoxy-nucleosides . The protein contains 294 amino acids, the first 22 of which are characteristic of a bacterial signal sequence peptide. The putative mature form of Tsx contains 272 residues with a calculated Mr of 31418. The Tsx sequence shows an even distribution of charged residues and lacks extensive hydrophobic stretches . Tsx shows no significant similarities to the channel-forming proteins OmpC, OmpF, PhoE and LamB from the E. coli outer membrane.

This entry also contains related proteins of unknown function.
Oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase superfamily (OHCU_decarboxylase_sf)
Type: Homologous_superfamily

The proteins in this entry are OHCU decarboxylase, an enzyme of the purine catabolism that catalyses the conversion of OHCU into S(+)-allantoin ; it is the third step of the conversion of uric acid (a purine derivative) to allantoin. Step one is catalysed by urate oxidase (

) and step two is catalysed by hydroxyisourate hydrolase (

).
LysM domain superfamily (LysM_dom_sf)
Type: Homologous_superfamily

The LysM (lysin motif) domain is a small globular domain, approximately 40 amino acids long. It is a widespread protein module involved in binding peptidoglycan in bacteria and chitin in eukaryotes. The domain was originally identified in enzymes that degrade bacterial cell walls , but proteins involved in many other biological functions also contain this domain. It has been reported that the LysM domain functions as a signal for specific plant-bacteria recognition in bacterial pathogenesis . Many of these enzymes are modular and are composed of catalytic units linked to one or several repeats of LysM domains. LysM domains are found in bacteria and eukaryotes .

Structurally, the LysM domain has a β-α(2)-β fold with antiparallel strands (

).
PG1857-like superfamily (PG1857-like_sf)
Type: Homologous_superfamily

This protein of unknown function of approx.120 residues consists of three β strands and five α helices, thought to fold into a homo-dimer.
Smr-associated-like superfamily (Smr_assoc-like_sf)
Type: Homologous_superfamily

Proteins with this domain are uncharacterised, but may be involved in DNA mismatch repair. The domain is similar to the Smr domain (

).
NE0471-like, N-terminal (NE0471-like_N)
Type: Homologous_superfamily

Several proteins in this superfamily are annotated as being putative molybdopterin-guanine dinucleotide biosynthesis proteins, but this has not been confirmed. Members of this superfamily also include proteins containing the N-terminal domain of the bacteria NE0471 protein. The function of these proteins is not known.
Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain superfamily (AK/P_DHK_N_sf)
Type: Homologous_superfamily

Catabolism and synthesis of leucine, isoleucine and valine are finely balanced, allowing the body to make the most of dietary input but removing excesses to prevent toxic build-up of their corresponding keto-acids. Regulating the activity of the branched-chain alpha-ketoacid dehydrogenase (BCDH) complex is the primary means by which these processes are coordinated. BCDH kinase regulates BCDH by phosphorylation, thereby inactivating it when synthesis is required.

The N-terminal domain of the alpha-ketoacid dehydrogenase kinase has a bromodomain-like fold, which consists of four helices arranged in bundle with minor mirror variant of up-and-down topology.
YkyA-like superfamily (YkyA-like_sf)
Type: Homologous_superfamily

The YkyA superfamily of proteins contain a lipoprotein signal and a hydrolase domain. They are similar to cell wall binding proteins and might also be recognisable by a host immune defence system. It is thus likely that they function in pathways important for pathogenicity .
Ribosome maturation protein SBDS, N-terminal domain superfamily (Ribosome_mat_SBDS_N_sf)
Type: Homologous_superfamily

Proteins containing this domain are highly conserved in species ranging from archaea to vertebrates and plants , including several Shwachman-Bodian-Diamond syndrome (SBDS, OMIM 260400) proteins from both mouse and humans. Shwachman-Diamond syndrome is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. It is characterised by bone marrow failure and leukemia predisposition. Members of this superfamily play a role in RNA metabolism . In yeast Sdo1 is involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with the EF-2-like GTPase RIA1 (EfI1), it triggers the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating TIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. This data links defective late 60S subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition .

A number of uncharacterised hydrophilic proteins of about 30kDa share regions of similarity. These include,

Mouse protein 22A3.

Saccharomyces cerevisiae chromosome XII hypothetical protein YLR022c.

Caenorhabditis elegans hypothetical protein W06E11.4.

Methanocaldococcus jannaschii (Methanococcus jannaschii) hypothetical protein MJ0592.
Translation initiation factor 3 (IF-3), N-terminal domain superfamily (T_IF-3_N_sf)
Type: Homologous_superfamily

Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit . The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal 30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 .

The IF-3 N-terminal domain has an ubiquitin-like fold, which consists of a β(2)-α-β(2) fold with mixed β-sheet.
Translation initiation factor 3 (IF-3), C-terminal domain superfamily (T_IF-3_C_sf)
Type: Homologous_superfamily

Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit . The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal 30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 .

The C-terminal domain of IF-3 has a β-α-β-α-β(2) fold arranged into two layers with mixed sheet and strand 4 antiparallel to the rest.
Large ribosomal subunit protein uL6-like, alpha-beta domain superfamily (Ribosomal_uL6-like_a/b-dom_sf)
Type: Homologous_superfamily

This α-β domain found duplicated in ribosomal uL6 proteins consists of two β-sheets and one α-helix packed around single core .

Large ribosomal subunit protein uL6 was previously known as L6. In Escherichia coli, it is located in the aminoacyl-tRNA binding site of the peptidyltransferase centre, and is known to bind directly to 23S rRNA. It belongs to a family of ribosomal proteins, including L6 from bacteria, cyanelles (structures that perform similar functions to chloroplasts, but have structural and biochemical characteristics of Cyanobacteria) and mitochondria; and L9 from mammals, Drosophila, plants and yeast. L6 contains two domains with almost identical folds, suggesting that is was derived by the duplication of an ancient RNA-binding protein gene. Analysis reveals several sites on the protein surface where interactions with other ribosome components may occur, the N terminus being involved in protein-protein interactions and the C terminus containing possible RNA-binding sites .

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 .
Frizzled cysteine-rich domain superfamily (Frizzled_dom_sf)
Type: Homologous_superfamily

This entry represents the frizzled domain superfamily.

The frizzled (fz) domain is an extracellular domain of about 120 amino acids.It was first identified in the alpha-1 chain of type XVIII collagen and in members of the Frizzled family of seven transmembrane (7TM) proteins which act as receptors for secreted Wingless (Wg)/Wnt glycoproteins . In addition to these proteins, one or two copies of the fz domain are also found in:

The Frzb family; secreted frizzled-like proteins.

Smoothened; another 7TM receptor involved in hedgehog signaling.

Carboxpeptidase Z (CPZ).

Transmembrane serine protease corin (atrial natriuretic peptide-converting enzyme).

Two receptor tyrosine kinases (RTKs) subfamilies, the Ror family and the muscle-specific kinase (MuSK) family.

As the fz domain contains 10 cysteines which are largely conserved, it has also been called cysteine-rich domain (CRD) . The fz domain also contains several other highly conserved residues, for example, a basic amino acid follows C6, and a conserved proline residues lies four residues C-terminal to C9 . The crystal structure of a fz domain shows that it is predominantly α-helical with all cysteines forming disulphide bonds. In addition to helical regions, two short β-strands at the N terminus form a minimal β-sheet with the second β sheet passing through a knot created by disulphide bonds .

Several fz domains have been shown to be both necessary and sufficient for Wg/Wnt ligand binding, strongly suggesting that the fz domain is a Wg/Wnt interacting domain .
Large ribosomal subunit protein bL9, C-terminal domain superfamily (Ribosomal_bL9_C_sf)
Type: Homologous_superfamily

This entry represents the large ribosomal subunit protein bL9. In Escherichia coli, bL9 is known to bind directly to the 23S rRNA. It belongs to a family of ribosomal proteins grouped on the basis of sequence similarities .

The crystal structure of Bacillus stearothermophilus bL9 shows the 149-residue protein comprises two globular domains connected by a rigid linker . Each domain contains an rRNA binding site, and the protein functions as a structural protein in the large subunit of the ribosome. The C-terminal domain consists of two loops, an α-helix and a three-stranded mixed parallel, anti-parallel β-sheet packed against the central α-helix. The long central α-helix is exposed to solvent in the middle and participates in the hydrophobic cores of the two domains at both ends.

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 .