SII-SWORD/CoKE huggingface dataset:
Uncharacterised domain CHP02996, repeat-companion domain (CHP02996_rpt-companion-dom)
Type: Domain

This entry is found in Myxococcus xanthus (strain DK 1622). Most member proteins have extensive repeats similar to the leucine-rich repeat, or another repeat class or a region of low-complexity sequence. This domain is not repeated, and is usually adjacent to the WGR domain.
Regulator of ribonuclease activity A, gammaproteobacteria (RraA_gpbac)
Type: Family

The regulator of ribonuclease activity A (RraA) family includes a number of closely related sequences from bacteria and plants. The Escherichia coli member has been characterised, and its crystal structure determined . It acts as a regulator of the endonuclease RNase E (see

) by binding to it and inhibiting RNA processing .

This entry represents the the gammaproteobacterial members of the RraA family.
Lipopolysaccharide export system protein LptA (LptA)
Type: Family

LptA is required for the translocation of lipopolysaccharide (LPS) from the inner membrane to the outer membrane. May act as a chaperone that facilitates LPS transfer across the aquaeous environment of the periplasm. Interacts specifically with the lipid A domain of LPS . This protein is also known as LptH in Pseudomonas aeruginosa .

The cell envelope of Gram-negative bacteria consists of an inner (IM) and an outer membrane (OM) separated by an aqueous compartment, the periplasm, which contains the peptidoglycan layer. The OM is an asymmetric bilayer, with phospholipids in the inner leaflet and lipopolysaccharides (LPS) facing outward . The OM is an effective permeability barrier that protects the cells from toxic compounds, such as antibiotics and detergents, thus allowing bacteria to inhabit several different and often hostile environments. LPS is responsible for the permeability properties of the OM. LPS consists of the lipid A moiety (a glucosamine-based phospholipid) linked to the short core oligosaccharide and the distal O-antigen polysaccharide chain. The core oligosaccharide can be further divided into an inner core, composed of 3-deoxy-D-mannooctulosanate (KDO) and heptose, and an outer core, which has a somewhat variable structure. LPS is essential in most Gram-negative bacteria, with the notable exception of Neisseria meningitidis. The biogenesis of the OM implies that the individual components are transported from the site of synthesis to their final destination outside the IM by crossing both hydrophilic and hydrophobic compartments. The machinery and the energy source that drive this process are not yet fully understood. The lipid A-core moiety and the O-antigen repeat units are synthesized at the cytoplasmic face of the IM and are separately exported via two independent transport systems, namely, the O-antigen transporter Wzx (RfbX) and the ATP binding cassette (ABC) transporter MsbA that flips the lipid A-core moiety from the inner leaflet to the outer leaflet of the IM . O-antigen repeat units are then polymerised in the periplasm by the Wzy polymerase and ligated to the lipid A-core moiety by the WaaL ligase [see,

,

].

The LPS transport machinery is composed of LptA, LptB, LptC, LptD, LptE. This supported by the fact, that depletion of any of one of these proteins blocks the LPS assembly pathway and results in very similar OM biogenesis defects. Moreover, the location of at least one of these five proteins in every cellular compartment suggests a model for how the LPS assembly pathway is organised and ordered in space .
Ectoine/hydroxyectoine ABC transporter, permease protein EhuD (Ectoine_EhuD)
Type: Family

Members of this entry are presumed to act as permease subunits of ectoine ABC transporters. Operons containing this gene also contain other genes of the ABC transporter and are typically found next to either ectoine utilization or ectoine biosynthesis operons.
Ectoine/hydroxyectoine ABC transporter, permease protein EhuC (Ectoine_EhuC)
Type: Family

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain .

Members of this family are presumed to act as permease subunits of ectoine ABC transporters. Operons containing this gene also contain other genes of the ABC transporter and are typically found next to either ectoine utilization or ectoine biosynthesis operons. Permease subunits EhuC and EhuD are homologues.
XrtA system polysaccharide deacetylase (XrtA_polysacc_deacetyl)
Type: Family

Members of this entry belong to the family of polysaccharide deacetylases. All are found in species that encode the PEP-CTERM/exosortase system XrtA and are predicted to act in protein sorting in a number of Gram-negative bacteria, they are also found near the gene coding region for the XrtA homologue (also known as EpsH) that is the putative exosortase gene .
XrtA system polysaccharide chain length determinant (XrtA_polysacc_chain)
Type: Family

Members of this entry belong to the family of polysaccharide chain length determinant proteins. They are found in species that encode the PEP-CTERM/exosortase system and are predicted to act in protein sorting in a number of Gram-negative bacteria, they are also found near the epsH homologue that is the putative exosortase gene.
Prenyl protease-related (Prenyl_protease-related)
Type: Family

Members of this protein family are fusion proteins of exosortase (N-terminal) and a CAAX prenyl protease domain (C-terminal). Members are restricted to the alpha Proteobacteria. The variant C-terminal protein sequence VPEID-CTERM occurs only in these species, often adjacent .

In eukaryotes, CAAX prenyl protease catalyzes three covalent modifications, including the cleavage and acylation at the C terminus of certain proteins in a process connected to protein sorting. This entry describes a bacterial protein homologous to one domain of the CAAX-processing enzyme. Members of this protein are found in genomes that carry a predicted protein sorting system, PEP-CTERM/exosortase, usually in the vicinity of the EpsH homologue that is the hallmark of the system. The function of this protein is unknown, but it may relate to protein modification.
Tautomerase/MIF superfamily (Tautomerase/MIF_sf)
Type: Homologous_superfamily

Tautomerase superfamily members have a (β-α-β)2 structure in two layers, and use a similar mechanism of action involving an amino-terminal proline as a general base in a ket-enol tautomerisation reaction . Members of this superfamily include macrophage migration inhibitory factor (MIF) and related proteins such as D-dopachrome tautomerase; 4-oxalocrotonoate tautomerase and related enzymes such as trans-3-chloroacrylic acid dehalogenase; and 5-carboxymethyl-2-hydroxymuconate Delta-isomerase (CHMI).

Macrophage migration inhibitory factor (MIF) is a key regulatory cytokine within innate and adaptive immune responses, capable of promoting and modulating the magnitude of the response . MIF is released from T-cells and macrophages, and it can regulate cytokine secretion and the expression of receptors involved in the immune response. MIF has been linked to various inflammatory diseases, such as rheumatoid arthritis and atherosclerosis .

4-Oxalocrotonate tautomerase (4-OT) is a plasmid-encoded enzyme that catalyzes the isomerisation of beta,gamma-unsaturated enones to their alpha,beta-isomers. This enzyme is part of the plasmid-encoded catechol meta-fission pathway, which enables the bacteria to use various aromatic hydrocarbons as their sole sources of carbon and energy .

5-carboxymethyl-2-hydroxymuconate isomerase (CHMI) is a trimeric enzyme involved in the homoprotocatechuate pathway in Escherichia coli . This enzyme catalyses the isomerisation of 5-carboxymethyl-2-hydroxymuconate (CHM) to 5-carboxymethyl-2-oxo-3-hexene-1,6-dioate (COHED).
Rieske iron-sulphur protein (Rieske_Fe-S_prot)
Type: Family

The Rieske subunit can be found in the Ubiquinol-cytochrome c reductase (bc1 complex or complex III) or the cytochrome b6f complex. The Rieske subunit acts by binding either a ubiquinol or plastoquinol anion, transferring an electron to the 2Fe-2S cluster, then releasing the electron to the cytochrome c or cytochrome f haem iron . The 2Fe-2S cluster is bound in the highly conserved C-terminal region of the Rieske subunit.

Ubiquinol-cytochrome c reductase (bc1 complex or complex III) is an enzyme complex of bacterial and mitochondrial oxidative phosphorylation systems. It catalyses the oxidoreduction of the mobile redox components ubiquinol and cytochrome c, generating an electrochemical potential which is linked to ATP synthesis .The complex consists of three subunits in most bacteria, and nine in mitochondria: both bacterial and mitochondrial complexes contain cytochrome b and cytochrome c1 subunits, and an iron-sulphur `Rieske' subunit, which contains a high potential 2Fe-2S cluster . The mitochondrial form also includes six other subunits that do not possess redox centres.

The plant cytochrome b6f is located in the thylakoid membrane and functions in both linear and cyclic electron transport, providing ATP and NADPH for photosynthetic carbon fixation. The cytochrome b6f complex has eight different subunits, six being encoded in the chloroplast genome (PetA [cyt f], PetB [cyt b6], PetD, PetG, PetL, and PetN) and two in the nucleus (PetC [Rieske FeS] and PetM. The complex functions as a dimer . In cyanobacteria, the cytochrome b6f complex contains four large subunits, including cytochrome f, cytochrome b6, the Rieske iron-sulfur protein (ISP), and subunit IV; as well as four small hydrophobic subunits, PetG, PetL, PetM, and PetN .

Proteins in this entry also include arsenite oxidase subunit AioB from Alcaligenes faecalis. It is involved in the detoxification of arsenic .
FERM/acyl-CoA-binding protein superfamily (FERM/acyl-CoA-bd_prot_sf)
Type: Homologous_superfamily

This superfamily represents a structural domain with a core structure consisting of a 3-helical closed bundle with a left-handed twist, in an up-and-down arrangement. This structural motif occurs as subdomain 2 within FERM domains, as well as in acyl-CoA-binding proteins. The FERM domain (band F ezrin-radixin-moesin homology domains) has such a structure, acting as a common membrane-binding module involved in localising proteins to the plasma membrane . Proteins containing FERM include cytoskeletal proteins such as erythrocyte membrane protein 4.1R, talin, and the ezrin-radixin-moesin protein family, as well as several protein tyrosine kinases and phosphatases, and the neurofibromatosis 2 tumour suppressor protein merlin. The ezrin-radixin-moesin protein family function is to crosslink the actin filaments of cytoskeletal structures to the plasma membrane.

In addition, acyl-CoA-binding protein (ACBP) contains a domain with a similar 3-helical bundle structure. ACBP plays an important role in fatty acid metabolism, maintaining a pool of fatty acyl-CoA molecules in the cell .
Membrane-bound alcohol dehydrogenase, cytochrome c subunit (Membr-bd_ADH_cyt_c)
Type: Family

In Acetobacter polyoxogenes, this tri-haem binding cytochrome c is one the two subunits of the membrane-bound alcohol dehydrogenase (ADH) . In other species of the genera Acetobacter, Gluconobacter, and Erwinia, the cytochrome c is one of the three subunits of the membrane-bound gluconate dehydrogenase (GADH) , which mediates the conversion of D-glucose to 2-keto-D-gluconate in the presence of an essential cofactor, pyrroloquinoline quinone; the other two subunits are a flavoprotein and a protein of unknown function.
Enoyl-[acyl-carrier-protein] reductase (NADH) (Enoyl-ACP_Rdtase_NADH)
Type: Family

This entry contains enoyl-[acyl-carrier-protein] reductases (

). They are components of the type II (dissociable) fatty acid synthase system and catalyse the terminal reaction in the fatty acid elongation cycle.

They belong to the short-chain dehydrogenases/reductases (SDR) domain superfamily . Crystal structures of these proteins have been extensively studied .
Ketol-acid reductoisomerase, prokaryotic (KARI_prok)
Type: Family

Ketol-acid reductoisomerases (KARI) catalyses two steps in the biosynthesis of branched-chain amino acids. The reaction involves an Mg2+ dependent alkyl migration followed by an NADPH-dependent reduction of the 2-keto group. There are two groups of KARI enzymes: class I is a short form found in fungi and most bacteria, and class II is a long form found in plants and certain bacteria (although their sequences differ) . However, there has also been a long form found in certain bacteria, but these differ from class II sequences found in plants.

This entry consists of bacterial and archaeal KARI.
Glutamate dehydrogenase (Glu_DH)
Type: Family

This entry represents glutamate dehydrogenases (GDH). The tertiary structure have been solved for the GDHs from Thermotoga maritima and Pyrococcus furiosus, both of which are thermostable because of an ion-pair network in the hinge region . Some GDHs are NADP-specific, such as GdhA from Escherichia coli, which catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate and ammonia . In eukaryotes, NADP-dependent GDHs may be mitochondrial, such as GluD from Dictyostelium discoideum .
Cytochrome c oxidase subunit VII, budding yeast (Cox7_yeast)
Type: Family

Cox7 is the subunit VII of cytochrome c oxidase (Complex IV). Cytochrome c oxidase catalyses the terminal step in the electron transport chain involved in cellular respiration .
Cytochrome c oxidase, subunit VIIa, fungal (Cyt_c_oxidase_su7a_fun)
Type: Family

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In fungi (as in other eukaryotes) this enzyme complex is located in the mitochondrial inner membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptidic subunits. This family includes fungal-type cytochrome-c oxidase, subunit VIIa, also known as cytochrome c oxidase subunit 9, the orthologue of cytochrome c oxidase subunit 6C from mammals .
Glycine/Sarcosine N-methyltransferase (Gly/Sar_N_MeTrfase)
Type: Family

Glycine/Sarcosine N-methyltransferase catalyses the methylation of glycine, sarcosine and dimethylglycine to sarcosine, dimethylglycine and betaine, respectively, with S-adenosylmethionine (AdoMet) acting as the methyl donor .

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.
Sterol O-acyltransferase, ACAT/DAG/ARE types (Oat_ACAT_DAG_ARE)
Type: Family

This entry represents a sterol O-acyltransferase, ACAT/DAG/ARE types. Please see the following relevant references .
Protein kinase, T7-type (Protein_kinase_T7-type)
Type: Family

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

This entry represents a protein encoded by the bacteriophage T7 early gene 0.7. This gene is dispensible in a fast-growing host, but is essential when the host is growing suboptimally. The protein is bifunctional, with the C-terminal third involved in host transcription shut-off, while the N-terminal two-thirds has protein kinase activity and is capable of phosphorylating a number of host cell proteins and itself . Expression of the protein kinase in the host leads to the phosphorylation of host RNAse E and the stabilisation of phage mRNA.
Protein kinase C, alpha/beta/gamma types (Protein_kinase_C_a/b/g)
Type: Family

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

This group represents a protein kinase C, alpha/beta/gamma types.
Protein kinase C, delta/epsilon/eta/theta types (Prot_kin_PKC_delta)
Type: Family

This entry represents the novel protein kinase C (nPKC) family.

The N-terminal regulatory domain of nPKC consists of a C2 domain follows by a double C1 domain (C1A and C1B). The C2 domain does not respond to calcium which makes nPKC diacylglycerol-sensitive but calcium-independent .

PKC is a family of serine- and threonine-specific protein kinases that depend on lipids for activity. They can be activated by calcium but have a requirement for the second messenger diacylglycerol . Members of this family play key regulatory roles in various cellular processes. Currently, there are ten isoforms of PKC which can be classified into classical (alpha, beta I, beta II, gamma), novel (delta, epsilon, eta, theta) and atypical (zeta, iota/lambda) types based on their primary structure and biochemical characteristics . All PKCs contain a C-terminal kinase domain and an N-terminal regulatory domain.
6-phosphofructo-2-kinase Pfk27 (Pfk27)
Type: Family

When compared with bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases, members of this group show similarities only to the kinase domains (

). The protein encoded by PFK27 in Saccharomyces cerevisiae was shown to be a second inducible 6-phosphofructo-2-kinase . Expression of Pfk27 was induced by glucose and sucrose, but not by galactose or maltose, this suggests that sugar transport may be involved in triggering the induction signal .

The 6-phosphofructo-2-kinase domain (

) may not be detected.
DNA-directed RNA polymerase subunit Rpo5/Rpb5 (Arch_Rpo5/euc_Rpb5)
Type: Family

Eukaryotic Rpb5 (POLR2E in mammals) is a common component of RNA polymerases I, II and III. Archaeal Rpo5 (also known as subunit H) is a homologue of Rpb5 . Rpb5 has a bipartite structure consisting of a unique N-terminal region, plus a C-terminal region that is structurally homologous to Rpo5 .

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.