SII-SWORD/CoKE huggingface dataset:
Linker histone H1/H5, domain H15 (Histone_H1/H5_H15)
Type: Domain

Histone proteins have central roles in both chromatin organisation (as structural units of the nucleosome) and gene regulation (as dynamic components that have a direct impact on DNA transcription and replication). Eukaryotic DNA wraps around a histone octamer to form a nucleosome, the first order of compaction of eukaryotic chromatin. The core histone octamer is composed of a central H3-H4 tetramer and two flanking H2A-H2B dimers. Each of the core histone contains a common structural motif, called the histone fold, which facilitates the interactions between the individual core histones.

In addition to the core histones, there is a "linker histone" called H1 (or H5 in avian species). The linker histones present in all multicellular eukaryotes are the most divergent group of histones, with numerous cell type- and stage-specific variant. Linker histone H1 is an essential component of chromatin structure. H1 links nucleosomes into higher order structures. Histone H5 performs the same function as histone H1, and replaces H1 in certain cells. The structure of GH5, the globular domain of the linker histone H5 is known . The fold is similar to the DNA-binding domain of the catabolite gene activator protein, CAP, thus providing a possible model for the binding of GH5 to DNA.

The linker histones, which do not contain the histone fold motif, are critical to the higher-order compaction of chromatin, because they bind to internucleosomal DNA and facilitate interactions between individual nucleosomes. In addition, H1 variants have been shown to be involved in the regulation of developmental genes. A common feature of this protein family is a tripartite structure in which a globular (H15) domain of about 80 amino acids is flanked by two less structured N- and C-terminal tails. The H15 domain is also characterised by high sequence homology among the family of linker histones. The highly conserved H15 domain is essential for the binding of H1 or H5 to the nucleosome. It consists of a three helix bundle (I-III), with a β-hairpin at the C terminus. There is also a short three-residue stretch between helices I and II that is in the β-strand conformation. Together with the C-terminal β-hairpin, this strand forms the third strand of an antiparallel β-sheet .

Proteins known to contain a H15 domain are:

Eukaryotic histone H1. The histones H1 constitute a family with many variants, differing in their affinity for chromatin. Several variants are simultaneously present in a single cell. For example, the nucleated erythrocytes of birds contain both H1 and H5, the latter being an extreme variant of H1.

Eukaryotic MHYST family of histone acetyltransferase. Histone acetyltransferases transfer an acetyl group from acetyl-CoA to the epsylon- amino group of lysine within the basic NH2-termini of histones, which bind the acidic phosphates of DNA .

This entry represents the H15 domain.
Linker histone H1/H5 (H1/H5)
Type: Family

Histone proteins have central roles in both chromatin organisation (as structural units of the nucleosome) and gene regulation (as dynamic components that have a direct impact on DNA transcription and replication). Eukaryotic DNA wraps around a histone octamer to form a nucleosome, the first order of compaction of eukaryotic chromatin. The core histone octamer is composed of a central H3-H4 tetramer and two flanking H2A-H2B dimers. Each of the core histone contains a common structural motif, called the histone fold, which facilitates the interactions between the individual core histones.

In addition to the core histones, there is a "linker histone" called H1 (or H5 in avian species). The linker histones present in all multicellular eukaryotes are the most divergent group of histones, with numerous cell type- and stage-specific variant. Linker histone H1 is an essential component of chromatin structure. H1 links nucleosomes into higher order structures. Histone H5 performs the same function as histone H1, and replaces H1 in certain cells. The structure of GH5, the globular domain of the linker histone H5 is known . The fold is similar to the DNA-binding domain of the catabolite gene activator protein, CAP, thus providing a possible model for the binding of GH5 to DNA.

The linker histones, which do not contain the histone fold motif, are critical to the higher-order compaction of chromatin, because they bind to internucleosomal DNA and facilitate interactions between individual nucleosomes. In addition, H1 variants have been shown to be involved in the regulation of developmental genes. A common feature of this protein family is a tripartite structure in which a globular (H15) domain of about 80 amino acids is flanked by two less structured N- and C-terminal tails. The H15 domain is also characterised by high sequence homology among the family of linker histones. The highly conserved H15 domain is essential for the binding of H1 or H5 to the nucleosome. It consists of a three helix bundle (I-III), with a β-hairpin at the C terminus. There is also a short three-residue stretch between helices I and II that is in the β-strand conformation. Together with the C-terminal β-hairpin, this strand forms the third strand of an antiparallel β-sheet .

Histone H5 is a nuclear protein involved in the condensation of nucleosome chains into higher order structures. In this respect, it performs the same function as histone H1, and replaces H1 in certain cells. The structure of GH5, the globular domain (residues 22-100) of the linker histone H5, has been solved. The fold is similar to the DNA-binding domain of the catabolite gene activator protein, CAP, thus providing a possible model for the binding of GH5 to DNA. The structure comprises 3 α-helices and 2 short β-strands .
Ion transport domain (Ion_trans_dom)
Type: Domain

This domain is found in sodium, potassium, and calcium ion channels proteins. The proteins have 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some Na channel proteins the domain is repeated four times, whereas in others (e.g. K channels) the protein forms a tetramer in the membrane. A bacterial structure of the protein is known for the last two helices but is not included in the Pfam family due to it lacking the first four helices.

This domain is also found in Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1/2/3 that upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) .
Large ribosomal subunit protein uL13 (Ribosomal_uL13)
Type: Family

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 .
Large ribosomal subunit protein uL13, bacterial-type (Ribosomal_uL13_bac-type)
Type: Family

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. This entry represents ribosomal protein uL13 from bacteria, mitochondria and chloroplasts.

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 .
KOW (KOW)
Type: Domain

The KOW (Kyprides, Ouzounis, Woese) motif is found in a variety of ribosomal proteins and the bacterial transcription antitermination proteins NusG .
Large ribosomal subunit protein uL24, conserved site (Ribosomal_uL24_CS)
Type: Conserved_site

This entry represents a conserved site found in the large ribosomal subunit protein uL24 family.

Ribosomal protein uL24 is one of the proteins from the large ribosomal subunit. uL24 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:

Eubacterial uL24.

Plant chloroplast uL24 (nuclear-encoded).

Red algal uL24.

Vertebrate uL24 (known as L26).

Yeast uL24 (known as L26 (YL33)).

Archaebacterial HmaL24 (HL15).

A probable ribosomal protein from Sulfolobus acidocaldarius .

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 .
Major facilitator, sugar transporter-like (MFS_sugar_transport-like)
Type: Family

This entry represents a subfamily of the major facilitator superfamily. Members in this family include sugar transporters, which are responsible for the binding and transport of various carbohydrates, organic alcohols, and acids in a wide range of prokaryotic and eukaryotic organisms . Most but not all members of this family catalyse sugar transport .
Sugar transporter, conserved site (Sugar_transporter_CS)
Type: Conserved_site

This entry represents two conserved sites. The first is centered on a G-R-[KR] motif. The second is based on a number of conserved residues which are located at the end of the fourth transmembrane segment and in the short loop region between the fourth and fifth segments.

The sugar transporters belong to a superfamily of membrane proteins responsible for the binding and transport of various carbohydrates, organic alcohols, and acids in a wide range of prokaryotic and eukaryotic organisms . These integral membrane proteins are predicted to comprise twelve membrane spanning domains. It is likely that the transporters have evolved from an ancient protein present in living organisms before the divergence into prokaryotes and eukaryotes . In mammals, these proteins are expressed in a number of organs .
Aerolysin (Aerolysn)
Type: Family

Aerolysin is a cytolytic toxin exported by Aeromonas hydrophila, a Gram-negative bacterium associated with diarrhoeal diseases and deep wound infections . The mature toxin binds to eukaryotic cells and aggregates to form holes (approximately 3 nm in diameter) leading to the destruction of the membrane permeability barrier and osmotic lysis. The structure of proaerolysin has been determined to 2.8A resolution and shows the protoxin to adopt a novel fold . Images of an aerolysin oligomer derived from electron microscopy have helped to construct a model of the protein and to outline a mechanism by which it might insert into lipid bilayers to form ion channels .
Aerolysin/haemolysin toxin, conserved site (Aerolysin/haemolysin_CS)
Type: Conserved_site

Aerolysin is a cytolytic toxin exported by the Gram-negative Aeromonas bacteria . The mature toxin binds to eukaryotic cells and aggregates to form holes (approximately 3 nm in diameter) leading to the destruction of the membrane permeability barrier and osmotic lysis. Staphylococcus aureus also exports a cytotoxin, alpha-toxin, whose biological activity is similar to that of aerolysin. The sequences of both toxins are not similar except for a stretch of ten residues rather well conserved.
Nucleotidyl transferase domain (NTP_transferase_dom)
Type: Domain

Nucleotidyl transferases transfer nucleotides from one compound to another. This domain is found in a number of enzymes that transfer nucleotides onto phosphosugars .
ADP-glucose pyrophosphorylase, conserved site (ADP_Glu_pyroP_CS)
Type: Conserved_site

ADP-glucose pyrophosphorylase (glucose-1-phosphate adenylyltransferase) (

) catalyzes a very important step in the biosynthesis of alpha 1,4-glucans (glycogen or starch) in bacteria and plants: synthesis of the activated glucosyl donor, ADP-glucose, from glucose-1-phosphate and ATP.

ADP-glucose pyrophosphorylase is a tetrameric allosterically regulated enzyme. It is a homotetramer in bacteria while in plant chloroplasts and amyloplasts, it is a heterotetramer of two different, yet evolutionary related, subunits.

There are a number of conserved regions in the sequence of bacterial and plant ADP-glucose pyrophosphorylase subunits.
Flagellar transport protein FliP (FliP)
Type: Family

This model describes bacterial flagellar biogenesis protein fliP, which is one of the genes within the motility locus on the bacterial chromosome that is involved in structure and function of bacterial flagellum. It was demonstrated that mutants in fliP locus were non-flagellated and non-motile, while revertants were flagellated and motile. In Escherichia coli and related proteins the fliP protein probably plays a role in the transport of flagellar proteins. FliP is a protein of about 30 Kd which contains three or four transmembrane regions. Proteins evolutionary related to fliP have been found in a wide range of bacteria (mopC, hrcR, hrpW, spaP, yscR, etc.) and are involved in a variety of signal-peptide independent secretion systems.
Type III secretion system inner membrane P protein (T3SS_IM_P)
Type: Family

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior . There have been four secretion systems described in animal enteropathogens such as Salmonella and Yersinia, with further sequence similarities in plant pathogens like Ralstonia and Erwinia. The type III secretion system is of great interest as it is used to transport virulence factors from the pathogen directly into the host cell and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis . However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of the flagellum itself , type III subunits in the outer membrane translocate secreted proteins through a channel-like structure. It is believed that the family of type III inner membrane proteins are used as structural moieties in a complex with several other subunits , including the ATPase necessary for driving the secretion system.

One such set of inner membrane proteins, termed "P" here for nomenclature purposes, includes the Salmonella and Shigella SpaP, the Yersinia YscR, the Erwinia HrcR, and the Xanthamonas Pro2 genes , as well as several FliP flagellar biosynthesis genes . FliP is an ~30Kd protein containing three or four transmembrane (TM) regions.
Methylthiotransferase (Methylthiotransferase)
Type: Family

The methylthiotransferase (MTTase) or miaB-like family is named after the (dimethylallyl)adenosine tRNA MTTase miaB protein, which catalyses a C-H to C-S bond conversion in the methylthiolation of tRNA. A related bacterial enzyme RimO performs a similar methylthiolation, but on a protein substrate. RimO acts on the ribosomal protein S12 and forms a separate MTTase subfamily. The miaB-subfamily includes mammalian CDK5 regulatory subunit-associated proteins and similar proteins in other eukaryotes. Two other subfamilies, yqeV and CDKAL1, are named after a Bacillus subtilis and a human protein, respectively. While yqeV-like proteins are found in bacteria, CDKAL1 subfamily members occur in eukaryotes and in archaebacteria .

The likely MTTases from these 4 subfamilies contain an N-terminal MTTase domain, a central radical generating fold and a C-terminal TRAM domain (see

). The core forms a radical SAM fold (or AdoMet radical), containing a cysteine motif CxxxCxxC that binds a [4Fe-4S] cluster . A reducing equivalent from the [4Fe-4S]+ cluster is used to cleave S-adenosylmethionine (SAM) to generate methionine and a 5'-deoxyadenosyl radical. The latter is thought to produce a reactive substrate radical that is amenable to sulphur insertion . The N-terminal MTTase domain contains 3 cysteines that bind a second [4Fe-4S] cluster, in addition to the radical-generating [4Fe-4S] cluster, which could be involved in the thiolation reaction. The C-terminal TRAM domain is not shared with other radical SAM proteins outside the MTTase family. The TRAM domain can bind to RNA substrate and seems to be important for substrate recognition. The tertiary structure of the central radical SAM fold has six β/α motifs resembling a three-quarter TIM barrel core . The N-terminal MTTase domain might form an additional [β/α]2 TIM barrel unit .
Ribosomal protein uS12 methylthiotransferase RimO (Ribosomal_uS12_MeSTrfase_RimO)
Type: Family

In many bacterial species ribosmal protein uS12 is posttranslationally modified by the methylthiolation of the aspartate residue at position 88. The enzyme responsible for this modification is RimO, a radical S-adenoslymethionine protein .
Alpha-D-phosphohexomutase superfamily (Alpha-D-phosphohexomutase_SF)
Type: Family

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 .
Alpha-D-phosphohexomutase, C-terminal (A-D-PHexomutase_C)
Type: Domain

This entry represents the C-terminal domain 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 .