SII-SWORD/CoKE huggingface dataset:
RNA polymerase III subunit RPC82-related, helix-turn-helix (RNA_pol_III_RPC82-rel_HTH)
Type: Domain

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

This family consists of several DNA-directed RNA polymerase III polypeptides which are related to the Saccharomyces cerevisiae (Baker's yeast) RPC82 protein. RNA polymerase C (III) promotes the transcription of tRNA and 5S RNA genes. In S. cerevisiae, the enzyme is composed of 15 subunits, ranging from 10kDa to about 160kDa . This region is probably a DNA-binding helix-turn-helix.
Global transcriptional regulator CodY, C-terminal (GTP_trans_reg_CodY_C)
Type: Domain

This entry represents the C-terminal helix-turn-helix domain found in several bacterial GTP-sensing transcriptional pleiotropic repressor CodY proteins. CodY has been found to repress the dipeptide transport operon (dpp) of Bacillus subtilis in nutrient-rich conditions . The CodY protein also has a repressor effect on many genes in Lactococcus lactis during growth in milk .
M protein trans-acting positive regulator (MGA) HTH domain (HTH_Mga_DNA-bd_dom)
Type: Domain

Mga is a DNA-binding protein that activates the expression of several important virulence genes in group A streptococcus in response to changing environmental conditions. It appears to contain two DNA-binding domains that are required for direct activation of the Mga virulence regulon in vivo . This entry represents the Mga DNA binding domain, which also appears to be found in other regulatory proteins.
Cathepsin propeptide inhibitor domain (I29) (Prot_inhib_I29)
Type: Domain

This entry represents a peptidase inhibitor domain, which belongs to MEROPS peptidase inhibitor family I29. The domain is also found at the N terminus of a variety of peptidase precursors that belong to MEROPS peptidase subfamily C1A; these include cathepsin L, papain, and procaricain (

) . It forms an α-helical domain that runs through the substrate-binding site, preventing access. Removal of this region by proteolytic cleavage results in activation of the enzyme. This domain is also found, in one or more copies, in a variety of cysteine peptidase inhibitors such as salarin .
Kinin peptide (Kinin_peptide)
Type: Family

This entry represents neuropeptides that are the first members of the insect kinin-family isolated from the American cockroach. Their occurrence in the retrocerebral complex suggests a physiological role as a neurohormone. The C-terminal sequence Phe-X-Ser-Trp-Gly-NH2 characterised the peptides as members of the insect kinin family. Data suggest a possible involvement of insect kinins in water-balance by regulating the osmoregulation. Insect kinins also mediate visceral muscle contractile activity (myotropic activity) . These peptides have lengths ranging from 6 to 14 amino acids .
Leader peptide, Arg-2/CPA1 (Leader_Arg2_CPA1)
Type: Family

In this family there are leader peptides involved in the regulation of the glutaminase subunit (small subunit) of arginine-specific carbamoyl phosphate synthetase. In Neurospora crassa it is a small upstream ORF of 24 codons above the arg-2 locus . In yeast it is the leader peptide of the CPA1 gene. The 5' region of CPA1 mRNA contains a 25 codon upstream open reading frame. The leader peptide, the product of the upstream open reading frame, plays an essential, negative role in the specific repression of CPA1 by arginine .
Leader peptide, Erm (Leader_Erm)
Type: Family

These short proteins are leader peptides (15-19 amino acids) of erm genes that code for resistance determinants in Staphylococcus aureus .
Leader peptide, tryptophan-operon (Leader_Trp_op)
Type: Family

The tryptophan operon regulatory region of Citrobacter freundii (leader transcript) encodes a 14-residue peptide containing characteristic tandem tryptophan residues. It is about 10 nucleotides shorter than those of Escherichia coli and Salmonella typhimurium .
Leucophaea maderae tachykinin-related peptide (Lem_TRP)
Type: Family

These peptides are designated Leucophaea maderae (Madeira cockroach) tachykinin-related peptides (Lem TRPs). Some were isolated from the midgut of L. maderae, whereas others appear to be brain specific. The Lem TRPs of the brain are myotropic and induce increases in the amplitude and frequency of spontaneous contractions and tonus of hindgut muscle in L. maderae . They were also isolated from brain-corpora, cardiaca-corpora, allata-suboesophageal ganglion extracts of Locusta migratoria (Migratory locust). They stimulate visceral muscle contractions of the oviduct and the foregut of L. migratoria .
LGFP (LGFP)
Type: Repeat

This 54 amino acid repeat is found in many hypothetical proteins. Several hypothetical proteins from Corynebacterium glutamicum (Brevibacterium flavum) and Corynebacterium efficiens along with PS1 protein contain this repeat region. The N-terminal region of PS1 contains an esterase domain which transfers corynomycolic acid. The C-terminal region consists of 4 tandem LGFP repeats. It is hypothesised that the PS1 proteins in Corynebacterium, when associated with the cell wall, may be anchored via the LGFP tandem repeats that may be important for maintaining cell wall integrity. Deletion of

protein results in a 10-fold increase in the cell volume of the organism and infers the corresponding involvement of the protein in the cell shape formation . The secondary structure of each repeat is predicted to comprise two β-strands and one α-helix.
Lipin/Ned1/Smp2 (LNS2) (LNS2)
Type: Domain

This domain is found in lipins and lipin homologues from Saccharomyces cerevisiae (Smp2) and from Schizosaccharomyces pombe (Ned1) . Smp2 (also known as PAH1) is involved in plasmid maintenance and respiration and has been identified as a Mg2+-dependent phosphatidate phosphatase (

) that contains a haloacid dehalogenase (HAD)-like domain . Lipin proteins are phosphatidate phosphatases which catalyse the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in triacylglycerol synthesis . They are involved in adipose tissue development and insulin resistance .
Leucine-rich repeat-containing N-terminal, plant-type (LRR_N_plant-typ)
Type: Domain

This domain is often found at the N terminus of tandem leucine rich repeats, mainly in plant proteins.

Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape . LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions .Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response .

Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel β sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the β-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear" segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins.
3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with α-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions . Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20-to 30-residue repeats .
LVIVD (LVIVD)
Type: Repeat

This repeat is found in bacterial and archaeal cell surface proteins, many of which are hypothetical. The secondary structure corresponding to this repeat is predicted to comprise 4 β-strands, which may associate to form a β-propeller. The repeat copy number varies from 2-14. This repeat is sometimes found with the PKD domain

.
Mad3/Bub1 homology region 1 (Mad3/Bub1_I)
Type: Domain

Proteins containing this domain are checkpoint proteins involved in cell division. This region has been shown to be essential for the binding of Bub1 and Mad3 to Cdc20 .
Mastoparan (Mastoparan)
Type: Family

Mastoparans are a family of tetradecapeptides from wasp venom that have been shown to directly activate GTP-binding regulatory proteins. These peptides show selectivity among G proteins: they strongly activate Go and Gi but not Gs or Gt. The peptides of this family are composed by 14 amino acids but they can assume different structures .
Mastoparan peptide (Mastoparan_peptide)
Type: Family

Mastoparan (MP) peptides I, II and III are extracted from the venom gland of Protopolybia exigua (Neotropical social wasp) . They are tetradecapeptides presenting from seven to ten hydrophobic amino acid residues and from two to four lysine residues in their primary sequences. These peptides cause the degranulation of mast cells.
Cobalamin-independent methionine synthase MetE, N-terminal (Cbl-indep_Met_Synth_N)
Type: Domain

Cobalamin-independent methionine synthase, MetE, catalyses the synthesis of the amino acid methionine by the transfer of a methyl group from methyltetrahydrofolate to homocysteine . The N-terminal and C-terminal domains of MetE together define a catalytic cleft in the enzyme. The N-terminal domain is thought to bind the substrate, in particular, the negatively charged polyglutamate chain. The N-terminal domain is also thought to stabilise a loop from the C-terminal domain.
Methyltransferase type 11 (Methyltransf_11)
Type: Domain

This entry represents a methyltransferase domain found in a large variety of SAM-dependent methyltransferases including, but not limited to:

Arsenite methyltransferase (

) which converts arsenical compounds to their methylated forms

Biotin synthesis protein bioC, which is involved in the early stages of biotin biosynthesis

Arginine N-methyltransferase 1, an arginine-methylating enzyme which acts on residues present in a glycine and argine-rich domain and can methylate histones

Hexaprenyldihydroxybenzoate methyltransferase (

), a mitochondrial enzyme involved in ubiquinone biosynthesis

A probable cobalt-precorrin-6Y C(15)-methyltransferase thought to be involved in adenosylcobalamin biosynthesis

Sterol 24-C-methyltransferase (

), shown to participate in ergosterol biosynthesis

3-demethylubiquinone-9 3-methyltransferase (

) involved in ubiquinone biosynthesis

Structural studies show that this domain forms the Rossman-like α-β fold typical of SAM-dependent methyltransferases .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Methyltransferase type 12 (Methyltransf_12)
Type: Domain

Methyl transfer from the ubiquitous donor S-adenosyl-L-methionine (SAM) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalysed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.

This entry represents a methyltransferase domain found in a large variety of SAM-dependent methyltransferases including, but not limited to:

Fatty acid synthase (

), a biosynthetic enzyme catalysing the formation of long-chain fatty acids

Glycine N-methyltransferase (

) which catalyses the SAM-dependent methylation of glycine to form sarcosine and may play a role in regulating the methylation potential of the cell

A polyketide synthase, important for the synthesis of chaetoviridin A and chaetomugilin A in the fungus Chaetomium

Fungal non-reducing polyketide synthases, such as ausA and otaA

Structural studies show that this domain forms the Rossman-like α-β fold typical of SAM-dependent methyltransferases .
Kinetochore-associated protein Dsn1/Mis13 (Dsn1/Mis13)
Type: Family

This entry represents the kinetochore-associated protein Dsn1/Mis13.

In Saccharomyces cerevisiae, Dsn1 acts as essential component of the kinetochore MIND complex, which is required for the spindle checkpoint and kinetochore integrity. MIND plays a role in establishing a bipolar spindle-kinetochore interaction by joining kinetochore subunits contacting DNA to those contacting microtubules .

In Schizosaccharomyces pombe, Mis13 acts as a component of the NMS (Ndc80-MIND-Spc7) super complex which has a role in kinetochore function during late meiotic prophase and throughout the mitotic cell cycle. It is required for correct segregation of chromosomes and for maintaining the inner centromere structure .
Small ribosomal subunit protein mS33 (Ribosomal_mS33)
Type: Family

This entry represents the small ribosomal subunit protein mS33 from eukaryotes, previously known as S27 in yeast and S33 in humans . It is a small 106 residue protein. The evolutionary history of the mitoribosomal proteome that is encoded by a diverse subset of eukaryotic genomes, reveals an ancestral ribosome of alpha-proteobacterial descent that more than doubled its protein content in most eukaryotic lineages. Several new MRPs have originated via duplication of existing MRPs as well as by recruitment from outside of the mitoribosomal proteome .

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 .
E3 ubiquitin-protein ligase substrate receptor Mms22, budding yeast (Mms22_budding_yeast)
Type: Family

Mms22 is a substrate targeting component of a cullin-RING-based E3 ubiquitin-protein ligase complex Rtt101(Mms1-Mms22), a complex that promotes replication through damaged DNA . Mms22 may play an important role for the stabilisation of protein components at the replication fork during replication stress and thereby function to prevent fork collapse and promote the resumption of DNA synthesis .
Mur ligase, central (Mur_ligase_cen)
Type: Domain

The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria is comprised of a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages:

(1) formation of UDP-N-acetylmuramic acid (UDPMurNAc) from N-acetylglucosamine (GlcNAc).

(2) addition of a short polypeptide chain to the UDPMurNAc.

(3) addition of a second GlcNAc to the disaccharide-pentapeptide building block and transport of this unit through the cytoplasmic membrane and incorporation into the growing peptidoglycan layer.

Stage two involves four key Mur ligase enzymes: MurC (

) , MurD (

) , MurE (

) and MurF (

) . These four Mur ligases are responsible for the successive additions of L-alanine, D-glutamate, meso-diaminopimelate or L-lysine, and D-alanyl-D-alanine to UDP-N-acetylmuramic acid . All four Mur ligases are topologically similar to one another, even though they display low sequence identity. They are each composed of three domains: an N-terminal Rossmann-fold domain responsible for binding the UDPMurNAc substrate; a central domain (similar to ATP-binding domains of several ATPases and GTPases); and a C-terminal domain (similar to dihydrofolate reductase fold) that binds the incoming amino acid . Residues found in the three domains (the Asp50, Lys130 (GKT motif), and Glu174 residues, MurC numbering) are involved in the catalytic process . The conserved sequence motifs found in the four Mur enzymes also map to other members of the Mur ligase family, including folylpolyglutamate synthetase, cyanophycin synthetase and the capB enzyme from Bacillales .

This entry represents the central domain from all four stage 2 Mur enzymes: UDP-N-acetylmuramate-L-alanine ligase (MurC), UDP-N-acetylmuramoylalanine-D-glutamate ligase (MurD), UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase (MurE), and UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase (MurF). This entry also includes folylpolyglutamate synthase that transfers glutamate to folylpolyglutamate and cyanophycin synthetase that catalyses the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin) .
Glycosyl hydrolase family 98, putative carbohydrate-binding module (Glyco_hyd_98_carb-bd)
Type: Domain

This entry represents a putative carbohydrate binding module (NPCBM) domain found at the N terminus of glycosyl hydrolase family 98 proteins .

Proteins containing this domain include CpGH98 from C. perfringens. It specifically hydrolyses fucose-containing trisaccharides from the glycotopes of blood groups A and B and is implicated for the infectivity and virulence of this pathogen . CpGH98 has a central TIM barrel catalytic domain, in which putative catalytic residues may be tentatively identified, and an N-terminal novel putative carbohydrate binding module (NPCBM) .

NPCBM domains found in bacterial conflict systems are predicted to interact with invasive molecules and recruit downstream effectors .
Ribonuclease B, N-terminal OB domain (RNase_B_OB_dom)
Type: Domain

This domain includes the N-terminal OB domain found in ribonuclease B proteins in one or two copies.
Transcriptional repressor PaaX-like, C-terminal (PaaX_C)
Type: Domain

This entry represents the C-terminal domain of the Transcriptional repressor PaaX from Escherichia coli and similar bacterial proteins. PaaX is involved in metabolism of phenylacetic acid . This protein is involved in the regulation of expression of a group of proteins known to participate in the metabolism of phenylacetic acid .
Pal1 cell morphology (Pal1)
Type: Family

Pal1 is a membrane associated protein that is involved in the maintenance of cylindrical cellular morphology. It localises to sites of active growth. Pal1 physically interacts and displays overlapping localisation with the Huntingtin-interacting-protein (Hip1)-related protein Sla2p/End4p . Fission yeast Pal1 is involved in cellular morphogenesis and cell wall integrity .