SII-SWORD/CoKE huggingface dataset:
Cytochrome oxidase maturation protein cbb3-type (Cyt_oxidase_maturation_cbb3)
Type: Family

Cytochrome cbb3 oxidases are found almost exclusively in Proteobacteria, and represent a distinctive class of proton-pumping respiratory haem-copper oxidases (HCO) that lack many of the key structural features that contribute to the reaction cycle of the intensely studied mitochondrial cytochrome c oxidase (CcO). Expression of cytochrome cbb3 oxidase allows human pathogens to colonise anoxic tissues and agronomically important diazotrophs to sustain nitrogen fixation .

Genes encoding a cytochrome cbb3 oxidase were initially designated fixNOQP (ccoNOQP), the ccoNOQP operon is always found close to a second gene cluster, known as fixGHIS (ccoGHIS) whose expression is necessary for the assembly of a functional cbb3 oxidase. On the basis of their derived amino acid sequences each of the four proteins encoded by the ccoGHIS operon are thought to be membrane-bound. It has been suggested that they may function in concert as a multi-subunit complex, possibly playing a role in the uptake and metabolism of copper required for the assembly of the binuclear centre of cytochrome cbb3 oxidase.
Phosphotransferase system, IIA component fructose subfamily (PTS_IIA_fruc)
Type: Domain

The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The PTS Fructose-Mannitol (Fru) family is a large and complex family which includes several sequenced fructose and mannitol-specific permeases as well as several putative PTS permeases of unknown specificities. The fructose permeases of this family phosphorylate fructose on the 1-position. Those of family 4.6 phosphorylate fructose on the 6-position. The Fru family PTS systems typically have 3 domains, IIA, IIB and IIC, which may be found as 1 or more proteins. The fructose and mannitol transporters form separate phylogenetic clusters in this family.

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates and coupled with translocation across the cell membrane, makes the PTS a link between the uptake and metabolism of sugars.

The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred via a signal transduction pathway, to enzyme I (EI) which in turn transfers it to a phosphoryl carrier, the histidine protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease, a membrane-bound complex known as enzyme 2 (EII), which transports the sugar to the cell. EII consists of at least three structurally distinct domains IIA, IIB and IIC . These can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).
Phosphotransferase system, glucitol/sorbitol-specific IIA component (PTS_IIA_glucitol/sorbitol-sp)
Type: Family

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates and coupled with translocation across the cell membrane, makes the PTS a link between the uptake and metabolism of sugars.

The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred via a signal transduction pathway, to enzyme I (EI) which in turn transfers it to a phosphoryl carrier, the histidine protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease, a membrane-bound complex known as enzyme 2 (EII), which transports the sugar to the cell. EII consists of at least three structurally distinct domains IIA, IIB and IIC . These can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

This family consists only of glucitol-specific transporters, and occur both in Gram-negative and Gram-positive bacteria. The system in Escherichia coli consists of a IIA protein, and a IIBC protein. This family is specific for the IIA component.
Phosphotransferase system, mannitol-specific enzyme IIC (PTS_IIC_mtl)
Type: Domain

Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The Fru family is a large and complex family which includes several sequenced fructose and mannitol-specific permeases as well as several putative PTS permeases of unknown specificities.The Fru family PTS systems typically have 3 domains, IIA, IIB and IIC, which may be found as 1 or more proteins. The fructose and mannitol transporters form separate phylogenetic clusters in this family.

This group is specific for the IIC domain of the mannitol PTS transporters.
Phosphotransferase system, maltose/glucose-specific subfamily IIC component (PTS_maltose/Glc_sub_IIC)
Type: Domain

Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.
The Glc family includes permeases specific for glucose, N-acetylglucosamine and a large variety of alpha-and beta-glucosides. However, not all b-glucoside PTS
permeases are in this class, as the cellobiose (Cel) beta-glucoside PTS permease is in the Lac family.

Several of the Escherichia coli PTS permeases in the Glc family lack their own IIA domains and instead use the glucose IIA protein (IIAglc or Crr). Most of these permeases have the B and C domains linked together in a single polypeptide chain, and a cysteyl residue in the IIB domain is phosphorylated by direct phosphoryl transfer from IIAglc(his~P). Those permeases which lack a IIA domain include the maltose (Mal), arbutin-salicin-cellobiose (ASC), trehalose (Tre), putative glucoside (Glv) and sucrose (Scr) permeases of E. coli. Most, but not all Scr permeases of other bacteria also lack a IIA domain. This entry is specific for the IIC domain of this type of Glc family PTS transporters.
Phosphotransferase system, sorbose subfamily IIB component (PTS_IIB_sorbose-sp)
Type: Domain

Bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains . The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of Escherichia coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine. The active site histidine receives a phosphate group from the IIA subunit and transfers it to the substrate . This entry is specific for the IIB components of this family of PTS transporters .
Dihydroorotase homodimeric type (DHOdimr)
Type: Family

Dihydroorotase belongs to MEROPS peptidase family M38 (clan MJ), where it is classified as a non-peptidase homologue. DHOase catalyses the third step in the
de novo
biosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity .

In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In the metazoa, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila melanogaster and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis . The DHOase domain is located in the central part of this polyprotein. In yeast, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.

The comparison of DHOase sequences from various sources shows that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold .

This family represents the homodimeric form of dihydroorotase

. It is found in bacteria, plants and fungi; URA4 of yeast is a member of this group of sequences.
Dihydroorotase (DHOase)
Type: Family

Dihydroorotase belongs to MEROPS peptidase family M38 (clan MJ), and includes peptides classified as a non-peptidase homologues. DHOase catalyses the third step in the
de novo
biosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity .

In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila melanogaster and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis . The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.

The comparison of DHOase sequences from various sources shows that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold .

Dihydroorotase 'multifunctional complex type'

, in contrast to the homodimeric type of dihydroorotase found in Escherichia coli, tends to appear in a large multifunctional complex with aspartate transcarbamoylase. Homologous domains appear in multifunctional proteins of higher eukaryotes. In some species, including Pseudomonas putida and Pseudomonas aeruginosa, this protein is inactive but is required as a non-catalytic subunit of aspartate transcarbamoylase (ATCase). In these species, a second, active dihydroorotase is also present.
8-amino-7-oxononanoate synthase, Archaea/Proteobacteria type (AONS_Archaea/Proteobacteria)
Type: Family

8-amino-7-oxononanoate synthase (AONS) is a pyridoxal 5'-phosphate-dependent enzyme, which catalyses the decarboxylative condensation of L-alanine with pimeloyl-CoA to form 8(S)-amino-7-oxononanoate. This is the first committed step in biotin biosynthesis :
6-carboxyhexanoyl-CoA + L-alanine = 8-amino-7-oxononanoate + CoA + CO2

The enzyme is a symmetrical homodimer with a tertiary structure and active site organisation similar to, but distinct from, those of other PLP-dependent enzymes with known structures. AONS is a critical PLP-binding lysine at the end of a deep cleft that allows access to the pantothenate arm of pimeloyl-CoA. There is a cluster of positively charged residues at the entrance to this cleft, which forms a putative diphosphate binding site for CoA . Trifluoroalanine irreversibly inhibits this enzyme .

This entry represents 8-amino-7-oxononanoate synthases mainly from Proteobacteria and Archaea. Some members are from Firmicutes and are also covered in (

).
Epithelial sodium channel, chordates (ENaC_chordates)
Type: Family

The epithelial Na+ channel (ENaC) proteins consist of sodium channels from animals and has no recognizable homologues in other eukaryotes or bacteria. The vertebrate ENaC proteins from epithelial cells cluster tightly together on the phylogenetic tree: voltage-insensitive ENaC homologues are also found in the brain. Eleven sequenced Caenorhabditis elegans proteins, including the degenerins (

), are distantly related to the vertebrate proteins as well as to each other.
Apoptosis regulator, Bcl-2/ BclX (Bcl2/BclX)
Type: Family

Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes . At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.

Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 . Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily . Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.

Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans . In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.
Degenerin (Deg-1)
Type: Family

The Caenorhabditis elegans mec-4 gene encodes a subunit of a candidate mechano-sensitive ion channel that plays a critical role in touch reception . The product is a mechano-sensory protein (degenerin). At least some of the proteins in this group form part of a mechano-transducing complex for touch sensitivity. Others include the acid-sensing ion channels, ASIC1-3 that are homo- or hetero-oligomeric neuronal H+-gated channels that mediate pain sensation in response to tissue acidosis. Mammalian ENaC (

) is important for the maintenance of Na+ balance and the regulation of blood pressure. Three homologous ENaC subunits, a, b and g, have been shown to assemble to form the highly Na+-selective channel.
Calcium-activated chloride channel protein, chordata (CLCA_chordata)
Type: Family

This entry represents a family of Ca(2+)-regulated chloride channels (CLCA) which includes bovine, murine and human proteins . Each CLCA exhibits a distinct, often overlapping, tissue expression pattern. With the exception of the truncated, secreted protein hCLCA3 , they are synthesized as an approximately 125kDa precursor transmembrane glycoprotein that is rapidly cleaved into 90 and 35kDa subunits. The human proteins have been shown to affect a large number of cell functions including chloride conductance, epithelial secretion, cell-cell adhesion, apoptosis, cell cycle control, mucus production in asthma, and blood pressure. The CLCA proteins expressed on the luminal surface of lung vascular endothelia (bCLCA2; mCLCA1; hCLCA2) serve as adhesion molecules for lung metastatic cancer cells, mediating vascular arrest and lung colonization. Expression of hCLCA2 in normal mammary epithelium is consistently lost in human breast cancer and in all tumorigenic breast cancer cell lines. Re-expression of hCLCA2 in human breast cancer cells abrogates tumorigenicity in nude mice, implying that hCLCA2 acts as a tumour suppressor in breast cancer.
Translocation protein Sec62 (Sec62)
Type: Family

Members of the NSCC2 family have been sequenced from various yeast, fungal and animals species including Saccharomyces cerevisiae, Drosophila melanogaster and Homo sapiens. These proteins are the Sec62 proteins, believed to be associated with the Sec61 and Sec63 constituents of the general protein secretary systems of yeast microsomes. They are also the non-selective cation (NS) channels of the mammalian cytoplasmic membrane. The yeast Sec62 protein has been shown to be essential for cell growth. The mammalian NS channel proteins have been implicated in platelet derived growth factor(PGDF) dependent single channel current in fibroblasts. These channels are essentially closed in serum deprived tissue-culture cells and are specifically opened by exposure to PDGF. These channels are reported to exhibit equal selectivity for Na+, K+ and Cs+ with low permeability to Ca2+, and no permeability to anions.
Transaldolase type 1 (Transaldolase_1)
Type: Family

Transaldolase (

) catalyses the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34kDa whose sequence has been well conserved throughout evolution. A lysine has been implicated in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.

This entry represents trasnaldolase type 1, which is found in bacteria, metazoa and fungi. The enzyme is found in the non-oxidative branch of the pentose phosphate pathway and forms a dimer in solution .
Transaldolase type 3B/Fructose-6-phosphate aldolase (Transaldolase_3B/F6P_aldolase)
Type: Family

This entry includes transaldolases type 3B and fructose-6-phosphate aldolase. They share a high degree of structural similarity and sequence identity.

Transaldolase (

) catalyses the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34kDa whose sequence has been well conserved throughout evolution. A lysine has been implicated in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.

Fructose-6-phosphate aldolase was originally thought to be transaldolases or transaldolase-related proteins. However, they perform a novel reaction, the cleavage or formation of fructose 6-phosphate .
Transaldolase type 2 (Transaldolase_2)
Type: Family

Transaldolase (

) catalyses the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34kDa whose sequence has been well conserved throughout evolution. A lysine has been implicated in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.

This entry represents transaldolases type 2, which is found in bacteria and plants.
Phosphoribosylformylglycinamidine cyclo-ligase (PurM_cligase)
Type: Family

The purine biosynthetic pathway in prokaryotes enlists eleven enzymes, six of which use ATP. Enzymes 5 and 6 of this pathway, formylglycinamide ribonucleotide (FGAR) amidotransferase (PurL) and aminoimidazole ribonucleotide (AIR) synthetase (PurM or AIRS) utilise ATP to activate the oxygen of an amide within their substrate toward nucleophilic attack by a nitrogen. PurM (also known as phosphoribosyl-aminoimidazole synthetase or phosphoribosylformylglycinamidine cyclo-ligase) uses the product of PurL, formylglycinamidine ribonucleotide (FGAM) and ATP to make AIR, ADP and P(i) . The N-terminal domain of PurM is related to the ATP-binding domains of hydrogen expression/formation protein HypE, the AIR synthases, selenophosphate synthetase (SelD), and FGAM synthase and is thought to bind ATP .
Multidrug resistance protein (Multidrug-R)
Type: Family

Multidrug resistance proteins are molecular pumps that participate in a low energy shock adaptive response in some bacteria. They mediate cellular resistance to toxicants such as cycloheximide (CYH), 4-nitroquinoline N-oxide (4-NQO), cadmium, and hydrogen peroxide in yeast .