SII-SWORD/CoKE huggingface dataset:
Autoinducer synthase (Autoind_synthase)
Type: Family

Bacterial species have many methods of controlling gene expression and cell growth. Regulation of gene expression in response to changes in cell density is termed quorum sensing . Quorum-sensing bacteria produce, release and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. Once a threshold of these molecules is reached, a signal transduction cascade is triggered that ultimately leads to behavioural changes in the bacterium . Autoinducers are thus clearly important mediators of molecular communication.

Conjugal transfer of Agrobacterium octopine-type Ti plasmids is activated by octopine, a metabolite released from plant tumours . Octopine causes conjugal donors to secrete a pheromone, Agrobacterium autoinducer (AAI), and exogenous AAI further stimulates conjugation. The putative AAI synthase and an AAI-responsive transcriptional regulator have been found to be encoded by the Ti plasmid traI and traR genes, respectively. TraR and TraI are similar to the LuxR and LuxI regulatory proteins of Vibrio fischeri, and AAI is similar in structure to the diffusable V. fischeri autoinducer, the inducing ligand of LuxR. TraR activates target genes in the presence of AAI and also activates traR and traI themselves, creating two positive-feedback loops. TraR-AAI-mediated activation in wild-type Agrobacterium strains is enhanced by culturing on solid media, suggesting a possible role in cell density sensing .

Production of light by the marine bacterium V. fischeri and by recombinant hosts containing cloned lux genes is controlled by the density of the culture . Density-dependent regulation of lux gene expression has been shown to require a locus consisting of the luxR and luxI genes.

In these and other Gram-negative bacteria, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) acts as the autoinducer by binding to transcriptional regulatory proteins and activating them . OHHL and related molecules, such as N-butanoyl- (BHL), N-hexanoyl- (HHL) and N-oxododecanoyl- (PAI) homoserine lactones, are produced by a family of proteins that share a high level of sequence similarity.

Proteins which currently members of this family include:

luxI from V. fischeri.

ahyI and asaI from Aeromonas species, which synthesize BHL and whose targets are ahyR and asaR respectively.

carI from Erwinia carotovora. The target of OHHL is carR which activates genes involved in the biosynthesis of carbapenem antibiotics.

eagI from Enterobacter agglomerans. The target of OHHL is not yet known.

esaI from Erwinia stewartii.

expI from Erwinia carotovora.

lasI from Pseudomonas aeruginosa, which synthesizes PAI and whose target is lasR which activates the transcription of the elastase gene.

rhlI (or vsmI) from P. aeruginosa, which synthesizes BHL and HHL and whose target is rhlR.

swrI from Serratia liquefaciens, which synthesizes BHL.

yenI from Yersinia enterocolitica.
Histidinol dehydrogenase, conserved site (Histidinol_DH_CS)
Type: Conserved_site

Histidinol dehydrogenase (

) (HDH) catalyses the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants, the four-electron oxidation of L-histidinol to histidine.

In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His . The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules . By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme . A Cys residue has been implicated in the catalytic mechanism of the second oxidative step .

In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyzes three different steps of histidine biosynthesis; and in plants it is expressed as nuclear encoded protein precursor which is exported to the chloroplast .
Calcitonin peptide-like (Calcitonin_peptide-like)
Type: Domain

Calcitonin is a 32 amino acid polypeptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in the blood, by promoting the incorporation of these ions in the bones. This is the alpha type. Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP), beta type. CGRP induces vasodilatation in a variety of vessels, including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.

Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids that selectively inhibits insulin-stimulated glucose utilisation and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. Structurally, IAPP is closely related to CGRP.

Calcitonin receptor-stimulating peptide 1 stimulates cAMP production via the calcitonin receptor.

Two conserved cysteines in the N-terminal of these peptides are known to be involved in a disulphide bond. The C-terminal residue of all three peptides is amidated.

xCxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxx-NH(2)
| | Amide group
+-----+

'C': conserved cysteine involved in a disulphide bond.
NADH:ubiquinone oxidoreductase, subunit 1/F420H2 oxidoreductase subunit H (NADH_UbQ_OxRdtase_su1/FPO)
Type: Family

This entry represents subunit 1 NADH:ubiquinone oxidoreductase . Among the many polypeptide subunits that make up complex I, there are fifteen which are located in the membrane part, seven of which are encoded by the mitochondrial and chloroplast genomes of most species. The most conserved of these organelle-encoded subunits is known as subunit 1 (gene ND1 in mitochondrion, and NDH1 in chloroplast) and seems to contain the ubiquinone binding site.

The ND1 subunit is highly similar to subunit 4 of Escherichia coli formate hydrogenlyase (gene hycD), subunit C of hydrogenase-4 (gene hyfC). Paracoccus denitrificans NQO8 and Escherichia coli nuoH NADH-ubiquinone oxidoreductase subunits also belong to this family .

This entry also includes the archaeal F420H2 oxidoreductase subunit H (FPO). FPO shuttles electrons from F420H2, via FAD and iron-sulphur (Fe-S) centres, to quinones in the F420H2:heterodisulphide oxidoreduction chain. The immediate electron acceptor for the enzyme in this species is believed to be methanophenazine. Couples the redox reaction to proton translocation (for every two electrons transferred, 0.9 hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient.
Lysyl oxidase (Lysyl_oxidase)
Type: Family

Lysyl oxidase (

) (LOX) is an extracellular copper-dependent enzyme that catalyses the oxidative deamination of peptidyl lysine residues in precursors of various collagens and elastins, yielding alpha-aminoadipic-delta-semialdehyde. The deaminated lysines are then able to form semialdehyde cross-links, resulting in the formation of insoluble collagen and elastin fibres in the extracellular matrix .

The active site of LOX resides towards the C terminus: this region also binds a single copper atom in an octahedral coordination complex involving at least 3 His residues . Four histidine residues are clustered in a central region of the enzyme. This region is thought to be involved in cooper-binding and is called the 'copper-talon' .
Voltage gated sodium channel, alpha subunit (Na_channel_asu)
Type: Family

Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in most
electrically excitable cells . They may exist in 3 states : the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.

There are nine pore-forming alpha subunit of voltage-gated sodium channels consisting of four membrane-embedded homologous domains (I-IV), each consisting of six α-helical segments (S1-S6), three cytoplasmic loops connecting the domains, and a cytoplasmic C-terminal tail. The S6 segments of the four domains form the inner surface of the pore, while the S4 segments bear clusters of basic residues that constitute the channel's voltage sensors .

Cation channels are transport proteins responsible for the movement of cations through the membrane. These proteins contain 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms as a tetramer in the membrane.
Pyruvate kinase (Pyr_Knase)
Type: Family

Pyruvate kinase (

) (PK) catalyses the final step in glycolysis , the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP:

ADP + phosphoenolpyruvate = ATP + pyruvate

The enzyme, which is found in all living organisms, requires both magnesium and potassium ions for its activity. In vertebrates, there are four tissue-specific isozymes: L (liver), R (red cells), M1 (muscle, heart and brain), and M2 (early foetal tissue). In plants, PK exists as cytoplasmic and plastid isozymes, while most bacteria and lower eukaryotes have one form, except in certain bacteria, such as Escherichia coli, that have two isozymes. All isozymes appear to be tetramers of identical subunits of ~500 residues.

PK helps control the rate of glycolysis, along with phosphofructokinase (

) and hexokinase (

). PK possesses allosteric sites for numerous effectors, yet the isozymes respond differently, in keeping with their different tissue distributions . The activity of L-type (liver) PK is increased by fructose-1,6-bisphosphate (F1,6BP) and lowered by ATP and alanine (gluconeogenic precursor), therefore when glucose levels are high, glycolysis is promoted, and when levels are low, gluconeogenesis is promoted. L-type PK is also hormonally regulated, being activated by insulin and inhibited by glucagon, which covalently modifies the PK enzyme. M1-type (muscle, brain) PK is inhibited by ATP, but F1,6BP and alanine have no effect, which correlates with the function of muscle and brain, as opposed to the liver.

The structure of several pyruvate kinases from various organisms have been determined . The protein comprises three-four domains: a small N-terminal helical domain (absent in bacterial PK), a β/α-barrel domain, a β-barrel domain (inserted within the β/α-barrel domain), and a 3-layer α/β/α sandwich domain.
F-actin-capping protein subunit beta (CAPZB)
Type: Family

The F-actin capping protein binds in a calcium-independent manner to the fast growing ends of actin filaments (barbed end) and thereby restricts its growth. The F-actin capping protein is a heterodimer composed of two unrelated subunits: alpha and beta. Neither of the subunits shows sequence similarity to other filament-capping proteins .

This entry represents the beta subunit (CAPZB), which is a protein of about 280 amino acid residues whose sequence is well conserved in eukaryotic species . In Drosophila mutations in the alpha and beta subunits cause actin accumulation and subsequent retinal degeneration . In humans CAPZB is part of the WASH complex that controls the fission of endosomes .
T-box transcription factor (TF_T-box)
Type: Family

Transcription factors of the T-box family are required both for early cell-fate decisions, such as those necessary for formation of the basic vertebrate body plan, for differentiation and organogenesis and also have been associated to multiple aspects of development and in adult terminal cell-type differentiation in different animal lineages . The T-box is defined as the minimal region within the T-box protein that is both necessary and sufficient for sequence-specific DNA binding, all members of the family so far examined bind to the DNA consensus sequence TCACACCT and function as transcriptional repressors and/or activators . The T-box is a relatively large DNA-binding domain, generally comprising about a third of the entire protein (17-26kDa) .

These genes were uncovered on the basis of similarity to the DNA binding domain of Mus musculus (Mouse) Brachyury (T) gene product, which similarity is the defining feature of the family. The Brachyury gene is named for its phenotype, which was identified 70 years ago as a mutant mouse strain with a short blunted tail. The gene, and its paralogues, have become a well-studied model for the family, and hence much of what is known about the T-box family is derived from the murine Brachyury gene.

Consistent with its nuclear location, Brachyury protein has a sequence-specific DNA-binding activity and can act as a transcriptional regulator . Homozygous mutants for the gene undergo extensive developmental anomalies, thus rendering the mutation lethal . The postulated role of Brachyury is as a transcription factor, regulating the specification and differentiation of posterior mesoderm during gastrulation in a dose-dependent manner .

T-box proteins tend to be expressed in specific organs or cell types, especially during development, and they are generally required for the development of those tissues, for example, Brachyury is expressed in posterior mesoderm and in the developing notochord, and it is required for the formation of these cells in mice .
Glycoside hydrolase family 9 (Glyco_hydro_9)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 9

comprises enzymes with several known activities; endoglucanase (

); cellobiohydrolase (

). These enzymes were formerly known as cellulase family E.
Porin, Gram-negative type (Porin_Gram-ve)
Type: Family

Porins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts, where they form ion-selective channels for small hydrophilic molecules (up to ~600 D) . X-ray structure analyses of several bacterial porins have revealed a large 16-stranded anti-parallel β-barrel structure enclosing the transmembrane pore, by contrast with all other integral membrane proteins described to date, which are α-helical. Three subunits form a trimer; the 3-fold axis is approximately parallel to the barrel axes and is assumed to be perpendicular to the membrane plane.

From the range of porins now known, similarities have been observed between porins from different species, and between porins of different specificity within the same species. But most porins cannot be related to each other on the basis of sequence alone, and this is reflected in the lengths of the known porin sequences, which range from 282-483 residues/monomer.

This entry represents porins from Gram-negative bacteria.
Prepro-orexin (Orexin)
Type: Family

Orexins (also known as hypocretins) are neuropeptides that are specifically localised to the hypothalamus. They are thought to interact with autonomic, neurendocrine and neuroregulatory systems, and play an important role in the regulation of feeding behaviour . When applied to hypothalamic neurones, these peptides are neuroexcitatory, which action is probably mediated by their binding to a new family of G-protein-coupled receptors (orexin receptors 1 and 2), which were previously orphan .

To date, two orexins have been characterised (orexin-A and -B), both encoded by a single mRNA transcript (prepro-orexin or hypocretin neuropeptide precursor, whose product is represented in this entry): orexin-A is a 33-residue peptide with two intramolecular disulphide bonds in the N-terminal region; and orexin-B is a linear 28-residue peptide. These peptides have 46% identity at the amino acid sequence level, and show some similarity to the glucagon/vasoactive intestinal polypeptide/secretin peptide family.
Large ribosomal subunit protein bL33 (Ribosomal_bL33)
Type: Family

Ribosomal protein bL33 is one of the proteins from the large ribosomal subunit. In Escherichia coli, bL33 has been shown to be on the surface of 50S subunit. L33 belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups:

Eubacterial bL33.

Algal and plant chloroplast bL33c.

Cyanelle bL33.

Animal bL33m.

Fungal bL33m (also known as MRPL39).

bL33 is a small protein of 49 to 66 amino-acid residues.

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 bL35 (Ribosomal_bL35)
Type: Family

This entry represents the large ribosomal subunit protein bL35. Members of this family are predominantly found in bacteria and some plant and fungal species.

This entry represents the large ribosomal subunit protein bL35, previously known as L35, a basic protein of 60 to 70 amino-acid residues . Like many basic polypeptides, it completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes . This family of ribosomal proteins includes proteins from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants .

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 .
Chloramphenicol acetyltransferase (Cmp_AcTrfase)
Type: Family

Chloramphenicol acetyltransferase (CAT) (

) catalyzes the acetyl-CoA dependent acetylation of chloramphenicol (Cm), an antibiotic which inhibits prokaryotic peptidyltransferase activity. Acetylation of Cm by CAT inactivates the antibiotic. A histidine residue, located in the C-terminal section of the enzyme, plays a central role in its catalytic mechanism.

The crystal structure of the type III enzyme from Escherichia coli with chloramphenicol bound has been determined. CAT is a trimer of identical subunits (monomer Mr 25,000) and the trimeric structure is stabilised by a number of hydrogen bonds, some of which result in the extension of a β-sheet across the subunit interface. Chloramphenicol binds in a deep pocket located at the boundary between adjacent subunits of the trimer, such that the majority of residues forming the binding pocket belong to one subunit while the catalytically essential histidine belongs to the adjacent subunit. His195 is appropriately positioned to act as a general base catalyst in the reaction, and the required tautomeric stabilisation is provided by an unusual interaction with a main-chain carbonyl oxygen .