SII-SWORD/CoKE huggingface dataset:
Flagellar transcriptional activator FlhD (Flagellar_FlhD)
Type: Family

This family consists of several bacterial flagellar transcriptional activator (FlhD) proteins. FlhD combines with FlhC to form a regulatory complex in Escherichia coli . This complex has been shown to be a global transcriptional regulator involved in many cellular processes as well as a flagellar transcriptional activator .

The FlhD protein is dimeric. The dimer is tightly coupled, with an intimate contact surface, implying that the dimer does not easily dissociate. The FlhD monomer is predominantly α-helical .
Carbonic anhydrase, alpha-class (Carbonic_anhydrase_a-class)
Type: Family

Carbonic anhydrases (CA:

) are zinc metalloenzymes which catalyse the reversible hydration of carbon dioxide to bicarbonate . The alpha-CAs are found predominantly in animals but also in bacteria and green algae. There are at least 15 isoforms found in mammals, which can be subdivided into cytosolic CAs (CA-I, CA-II, CA-III, CA-VII and CA XIII), mitochondrial CAs (CA-VA and CA-VB), secreted CAs (CA-VI), membrane-associated (CA-IV, CA-IX, CA-XII and CA-XIV) and those without CA activity, the CA-related proteins (CA-RP VIII, X and XI).
Clp protease proteolytic subunit /Translocation-enhancing protein TepA (ClpP/TepA)
Type: Family

This entry includes peptidases from the MEROPS peptidase family S14, including ClpP endopeptidase and translocation-enhancing protein TepA.

ClpP is an ATP-dependent protease that cleaves a number of proteins, such as casein and albumin . It exists as a heterodimer of ATP-binding regulatory A and catalytic P subunits, both of which are required for effective levels of protease activity in the presence of
ATP , although the P subunit alone does possess some catalytic activity. Proteases highly similar to ClpP have been found to be encoded in the genome of bacteria, metazoa, some viruses and in the chloroplast of plants. A number of the proteins in this family are classified as non-peptidase homologues as they have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for catalytic activity.
Large ribosomal subunit protein uL13, conserved site (Ribosomal_uL13_CS)
Type: Conserved_site

This entry represents a conserved region located in the C-terminal section of uL13 proteins.

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 .
Peptidyl-prolyl cis-trans isomerase Fpr3/Fpr4-like (PPIase_Fpr3/Fpr4-like)
Type: Family

FK506-binding proteins (FKBPs) are a particular class of peptidyl-prolyl cis-trans isomerases (PPIases) (

) . This entry represents a group of nuclear FK506-binding proteins that act as histone chaperones. They each containing an extended acidic domain in addition to the conserved FK506-binding/peptidylprolyl isomerase (PPIase) domain. The PPIase domain has been shown to regulate histone H3 methylation, while the acidic domain has been shown to facilitate histone deposition and may regulate rDNA silencing .
Prokineticin domain (Prokineticin_domain)
Type: Domain

The prokineticin family includes prokinectin itself and related proteins such as BM8 and the AVIToxins. The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. It has been shown that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock .

The prokinectin domain is found in the prokinectin family and the hainantoxins, where it comprises the whole length of the protein. This domain is also found at the C terminus of some members of the Dickkopf family.
Archease domain (Archease_dom)
Type: Domain

The archease superfamily of proteins are represented in all three domains of life. Archease genes are generally located adjacent to genes encoding proteins involved in DNA or RNA processing and therefore have been predicted to be modulators or chaperones involved in DNA or RNA metabolism. Many of the roles of archeases remain to be established experimentally.

The function of one of the archeases from the hyperthermophile Pyrococcus abyssi has been determined. The gene encoding the archease (PAB1946) is located in a bicistronic operon immediately upstream from a second open reading frame (PAB1947), which encodes a tRNA m5C methyltransferase. The methyl transferase catalyses m5C formation at several cytosine's within tRNAs with preference for C49; the specificity of the methyltransferase reaction being increased by the archease. The archease protects the tRNA (cytosine-5-)-methyltransferase PAB1947 against aggregation and increases its specificity. The archease exists in monomeric and oligomeric states, with only the oligomeric forms able to bind the methyltransferase .

The function of this family of archeases as chaperones is supported by structural analysis of

from Methanobacterium thermoautotrophicum, which shows homology to heat shock protein 33, which is a chaperone protein that inhibits the aggregation of partially denatured proteins .

Structurally, the archeases are composed of a single three layer β-α-β sandwich domain similar to those found in other chaperones.
Large ribosomal subunit protein eL20 domain (Ribosomal_eL20_dom)
Type: Domain

This entry includes the large ribosomal subunit protein eL20 from archaea (previously known as 50S ribosomal protein L18A) and eukaryotes (also known as L20 and 60S ribosomal protein L18a) .
Large ribosomal subunit protein uL4 domain superfamily (Ribosomal_uL4_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in the large ribosomal subunit protein uL4 (also known as L4/L1). Its structure consists of three layers (α/β/α) with parallel β-sheet of four strands.

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 .
Small ribosomal subunit protein uS19, superfamily (Ribosomal_uS19_SF)
Type: Homologous_superfamily

The signatures in this entry match the structural unit of the ribosomal S19 family.

The small subunit ribosomal proteins can be categorised as: primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins. The small ribosomal subunit protein S19 contains 88-144 amino acid residues. In Escherichia coli, S19 is known to form a complex with S13 that binds strongly to 16S ribosomal RNA. Experimental evidence has revealed that S19 is moderately exposed on the ribosomal surface, and is designated a secondary rRNA binding protein. S19 belongs to a family of ribosomal proteins that includes: eubacterial S19; algal and plant chloroplast S19; cyanelle S19; archaebacterial S19; plant mitochondrial S19; and eukaryotic S15 ('rig' protein).

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 .
UbiE/COQ5 methyltransferase, conserved site (UbiE/COQ5_MeTrFase_CS)
Type: Conserved_site

A number of methyltransferases have been shown to share regions of similarities . Apart from the ubiquinone/menaquinone biosynthesis methyltransferases (for example, the C-methyltransferase from the ubiE gene of Escherichia coli), the ubiquinone biosynthesis methyltransferases (for example, the C-methyltransferase from the COQ5 gene of Saccharomyces cerevisiae) and the menaquinone biosynthesis methyltransferases (for example, the C-methyltransferase from the MENH gene of Bacillus subtilis), this family also includes methyltransferases involved in biotin and sterol biosynthesis and in phosphatidylethanolamine methylation.
CYTH domain (CYTH_domain)
Type: Domain

The entry represents the CYTH domain. The bacterial CyaB like adenylyl cyclase and the mammalian thiamine triphosphatases (ThTPases) define a superfamily of catalytic domains called the CYTH (CyaB, thiamine triphosphatase) domain that is present in all three superkingdoms of life . Proteins containing this domain act on triphosphorylated substrates and require at least one divalent metal cation for catalysis .

The catalytic core of the CYTH domain is predicted to contain an α+β scaffold with 6 conserved β-strands and 6 conserved α-helices. The CYTH domains contains several nearly universally conserved charged residues that are likely to form the active site. The most prominent of these are an EXEXK motif associated with strand-1 of the domain, two basic residues in helix-2, a K at the end of strand 3, an E in strand 4, a basic residue in helix-4, a D at the end of strand 5 and two acidic residues (typically glutamates) in strand 6. The presence of around 6 conserved acidic positions in the majority of the CYTH domains suggests that it coordinates two divalent metal ions. Both CyaB and ThTPase have been shown to require Mg(2+) ions for their nucleotide cyclase and phosphatase activities. The four conserved basic residues in the CYTH domain are most probably involved in the binding of acidic phosphate moieties of their substrates. The conservation of these two sets of residues in the majority of CYTH domains suggests that most members of this group are likely to possess an activity dependent on two metal ions, with a preference for nucleotides or related phosphate-moiety -bearing substrates. The proposed biochemical activity, and the arrangement of predicted strands in the primary structure of the CYTH domain imply that they may adopt a barrel or sandwich- like configuration, with metal ions and the substrates bound in the central cavity .
Ras guanine nucleotide exchange factor domain superfamily (Ras_GEF_dom_sf)
Type: Homologous_superfamily

Small GTPases of the Ras family alternate between 2 conformations induced by the binding of either GTP or GDP. Guanine nucleotide exchange factors (GEFs) induce the dissociation of GDP to allow association of the more abundant GTP. The Ras-like family of small GTPases includes, among others, Ras, Rap1, R-ras, and Ral. The family is characterised by similarities in the effector domain. The Ras GTPase Rap1 is activated rapidly in response to activation of a variety of receptors. Rap1 activation is mediated by several second messengers, including calcium, diacylglycerol, and cAMP. GEFs have been identified that mediate these effects. One such GEF is Epac, an exchange protein directly activated by cAMP, which represents a novel cAMP-induced, protein kinase A-independent pathway .

This superfamily represents a multihelical domain found in Ras GEFs. It can be subdivided in two domains: Ras GEF catalytic domain (

) and Ras GEF N-terminal domain (

). In the nucleotide exchange factor Son of sevenless (SOS), both of these domains are required for the Ras specific nucleotide exchange activity, and both of them together are referred to as SOS-cat .
RNA polymerase subunit RPB10 (RNA_pol_su_RPB10)
Type: Homologous_superfamily

The RNA polymerase subunit RPB10 displays a high level of conservation across archaea and eukaryota. Structure determination of this subunit reveals a zinc-bundle topology, consisting of three α-helices stabilised by a zinc ion .
Platelet-derived growth factor, conserved site (PD_growth_factor_CS)
Type: Conserved_site

This entry represents a conserved site found in PDGF and VEGF families, amongst others, that includes four of the eight cysteines conserved in the sequences of these proteins. In PDGF, these cysteines are known to be involved in intra and inter-chain disulphide bonds .

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked
homodimers, but only PDGFA and B can form functional heterodimers. PDGFRs also function as homo- and heterodimers. All known PDGFs have characteristic 'PDGF domains', which include eight conserved cysteines that are involved in inter- and intramolecular bonds. Alternate splicing of the A chain transcript can give rise to two different forms that differ only in their C-terminal extremity. The transforming protein of Woolly monkey sarcoma virus (WMSV) (Simian sarcoma virus), encoded by the v-sis oncogene, is derived from the B chain of PDGF.

PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal .

Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis . VEGF is a potent mitogen in embryonic and somatic angiogenesis with a unique specificity for vascular endothelial cells. VEGF forms homodimers and exists in 4 different isoforms. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended.

PDGF is structurally related to a number of other growth factors which also form disulphide-linked homo- or heterodimers. A cysteine knot motif is a common feature of this domain .
Impact family (Impact)
Type: Family

The Impact protein is a translational regulator that ensures constant high levels of translation under amino acid starvation. It acts by interacting with Gcn1/Gcn1L1, thereby preventing activation of Gcn2 protein kinases (EIF2AK1 to 4) and subsequent down-regulation of protein synthesis. It is evolutionary conserved from eukaryotes to archaea .
Ribosome recycling factor domain (Ribosome_recyc_fac_dom)
Type: Domain

The ribosome recycling factor or ribosome release factor (RRF) dissociates ribosomes from mRNA after termination of translation, and is essential for bacterial growth . Thus ribosomes are 'recycled' and ready for another round of protein synthesis.

This entry represents a domain found in ribosome recycling factors.
Isoleucine-tRNA ligase, type 1 (Ile-tRNA-ligase_type1)
Type: Family

Isoleucine-tRNA ligase (also known as Isoleucyl-tRNA synthetase)(

) is an alpha monomer that belongs to class Ia. The enzyme, isoleucine-tRNA ligase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the ligase itself rapidly hydrolyses only the valylated products as shown from the crystal structures.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

In eukaryotes, two forms of isoleucine-tRNA synthetase exist, a cytoplasmic form and a mitochondrial form . Type 1 includes bacterial and mitochondrial (gene iars2) isoleucine-tRNA ligases.