SII-SWORD/CoKE huggingface dataset:
Ribulose bisphosphate carboxylase large subunit, type II (RuBisCO_lsuII)
Type: Family

Ribulose bisphosphate carboxylase (RuBisCO) catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate .

Members of the Rubisco family can be divided into 4 subgroups, form I-IV , which differ in their taxonomic distribution and subunit composition . A number of subtle interactions near the active site and the carboxyl terminus account for functional differences between the different forms of Rubiscos found in nature . Form II Rubiscos contain only large subunits and are found in some photosynthetic proteobacteria, chemoautotrophic bacteria, and certain dinoflagellate algae .
2-phosphoglycerate kinase (2PKG)
Type: Family

Analysis of the metabolome of a number of methanogenic archaea revealed that they produced a number of unusual compounds of low molecular weight, one of which was cyclic 2,3-diphosphoglycerate (cDPG). This has been found to occur in several methanogens in high concentrations of up to 1 Molar. The highest intracellular concentrations of cDPG were detected in the hyperthermophilic methanogens Methanothermus fervidus (optimal growth temperature, 83 degrees C) and Methanopyrus kandleri (optimal growth temperature, 98 degrees C). Additionally, the intracellular concentration of cDPG increases with temperature up to the optimal growth temperature in M. fervidus. It has been proposed that cDPG is either used an energy store and/or is involved in the process of thermoadaption .
3'-5' exoribonuclease YhaM (3'-5'_exoribonuclease_YhaM)
Type: Family

Exoribonucleases are enzymes that degrade RNA by removing terminal nucleotides from either the 5' end or 3' end of various RNA. This entry represents YhaM, which shows 3'-5' exoribonuclease activity .
NAD(P)H-quinone oxidoreductase, subunit N (NAD(P)H-quinone_OxRdtase_su_N)
Type: Family

NAD(P)H-quinone oxidoreductase (NDH-1) shuttles electrons from an unknown electron donor, via FMN and iron-sulphur (Fe-S) centres, to quinones in the respiratory and/or the photosynthetic chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. It couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient. Cyanobacterial NDH-1 also plays a role in inorganic carbon-concentration. NDH-1 can be composed of about 15 different subunits, although different subcomplexes with different compositions have been identified which probably have different functions.

This entry represents subunit N.
3-phenylpropionate/cinnamic acid dioxygenase, alpha subunit (HcaE)
Type: Family

Phenylpropanoid compounds are widely available in natural environments, and they can originate from putrefaction of proteins in soil or as breakdown products of several constituents of plants, such as lignin, various oils, and resins. Microbial catabolism of phenylpropanoid compounds plays an important role not only in the natural degradative cycle of these aromatic molecules but also in their industrial applications such as wine making, aging, and storage. In particular, degradation of cinnamic acid (CI), 3-phenylpropionic acid (PP), and their hydroxylated derivatives has been reported in several bacteria, including Pseudomonas species , Arthrobacter species , Escherichia coli (strain K12) , and Rhodococcus globerulus .

This entry represent the alpha subunit of PP/CI dioxygenase.
Tyrosine recombinase XerD-like (Tyrosine_recombinase_XerD-like)
Type: Family

Phage integrases are enzymes that mediate unidirectional site-specific recombination between two DNA recognition sequences, the phage attachment site, attP, and the bacterial attachment site, attB . Integrases may be grouped into two major families, the tyrosine recombinases and the serine recombinases, based on their mode of catalysis. Tyrosine family integrases, such as Bacteriophage lambda integrase, utilise a catalytic tyrosine to mediate strand cleavage, tend to recognise longer attP sequences, and require other proteins encoded by the phage or the host bacteria.

The recombinases Cre from phage P1, XerD from Escherichia coli and Flp from yeast are members of the tyrosine recombinase family, and have a two-domain motif resembling that of lambda integrase, as well as sharing a conserved binding mechanism . The structural fold of their catalytic core domains resemble that of Lambda integrase

This entry contains XerD-like putative tyrosine recombinases from the Streptococcaceae family.
Interleukin-1 conserved site (IL-1_CS)
Type: Conserved_site

Interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis . Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors . The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location . The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA).

The crystal structures of IL1A and IL1B have been solved, showing them to share the same 12-stranded β-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors . The β-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel β-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

The Vaccinia virus genes B15R and B18R each encode proteins with N-terminal hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain . These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors . A similar gene product from Cowpox virus (CPV) has also been shown to specifically bind murine IL-1 beta .

This entry represents the Interleukin-1 conserved region in the C-terminal section.
Ribulose bisphosphate carboxylase, large chain, active site (RuBisCo_large_chain_AS)
Type: Active_site

Ribulose bisphosphate carboxylase (RuBisCO) catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. RuBisCO consists of a large catalytic unit and a small subunit of undetermined function. In plants, the large subunit is coded by the chloroplastic genome while the small subunit is encoded in the nuclear genome. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate .

This entry represents the active site which includes both the active site residue and the metal ligand, and which is specific to RuBisCO large chains.
N-acetylglucosamine-binding protein A (GlcNAc-bd_A)
Type: Family

This entry represents the N-acetylglucosamine-binding protein A (GbpA) of various pathogenic bacteria, including Vibrio cholerae, which is the etiologic agent of cholera in humans. GbpA binds to chitin and specifically to the chitin monomer N-acetylglucosamine (GlcNAc), a sugar residue that is also found on the surface of epithelial cells. Intestinal colonization of V. cholerae occurs in a stepwise fashion, initiating with attachment to the small intestinal epithelium . This attachment is followed by expression of the toxin co-regulated pilus, microcolony formation, and cholera toxin production.
Protein of unknown function UPF0741 (UPF0741)
Type: Family

This entry contains bacterial proteins with no known function.
Phosphoglycerol transferase I (OpgB)
Type: Family

Phosphoglycerol transferase I (OpgB) transfers a phosphoglycerol residue from phosphatidylglycerol to the membrane-bound nascent glucan backbones for the biosynthesis of osmoregulated periplasmic glucan (OPG) . Members of this protein family are found in Proteobacteria.
Type I toxin-antitoxin system, SymE toxin (TypeI_TA_SymE)
Type: Family

SymE (SOS-induced yjiW gene with similarity to MazE) belongs to type I toxin-antitoxin systems, and it is an SOS-induced toxin. It inhibits cell growth, decreases protein synthesis and increases RNA degradation. It may play a role in the recycling of RNAs damaged under SOS response-inducing conditions. Its translation is repressed by the antisense RNA SymR, which acts as an antitoxin .
Glutathione-regulated potassium-efflux system protein KefB (K_H_efflux_KefB)
Type: Family

The CPA2 family is a moderately large family (over 100 sequenced members) from bacteria, archaea and eukaryotes. Among the functionally well-characterised members of the family are (1) the KefB/KefC K+ efflux proteins of Escherichia coli which may be capable of catalysing both K+/H+ antiport and K+ uniport, depending on conditions , (2) the Na+/H+ antiporter of Enterococcus hirae and (3) the K+/H+ antiporter of Saccharomyces cerevisiae. It has been proposed that under normal physiological conditions, these proteins may function by essentially the same mechanism .

KefC and KefB of E. coli are responsible for glutathione-gated K+ efflux . Each of these proteins consists of a transmembrane hydrophobic N-terminal domain, and a less well-conserved C-terminal hydrophilic domain. Each protein interacts with a second protein encoded by genes that overlap the gene encoding the primary transporter. The KefB ancillary protein is YheR. The ancillary proteins stimulate transport activity about 10-fold . They are important for cell survival during exposure to toxic metabolites, possibly because they can release K+, allowing H+ uptake. Activation of the KefB or KefC K+ efflux system only occurs in the presence of glutathione and a reactive electrophile such as methylglyoxal or N-ethylmaleimide. Formation of the methylglyoxal-glutathione conjugate, S-lactoylglutathione, is catalysed by glyoxalase I, and S-lactoylglutathione activates KefB and KefC . H+ uptake (acidification of the cytoplasm) accompanying or following K+ efflux may serve as a further protective mechanism against electrophile toxicity . Inhibition of transport by glutathione is enhanced by NADH .
Uncharacterised protein family UPF0367 (UPF0367)
Type: Family

This entry describes proteins of unknown function.
Putative HTH-type transcriptional regulator, archaea (Arc_TR_HTH)
Type: Family

This is a family of archaeal proteins that contain a cro/C1-type HTH domain.
The cro/C1-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in transcriptional regulators. The domain is named after the transcriptional repressors Cro and C1 of temperate bacteriophages 434 and lambda, respectively. Besides the bacteriophages, cro/C1-type regulators are present in prokaryotes and in eukaryotes.
Uncharacterised protein family UPF0509 (UPF0509)
Type: Family

This entry represents a group of uncharacterised proteins.

This protein family includes YciZ from Escherichia coli and similar short sequences encoded by small open reading frames (smORFs) from gammaproteobacteria .
Ribulose bisphosphate carboxylase large subunit, type I (RuBisCO_lsuI)
Type: Family

Ribulose bisphosphate carboxylase (RuBisCO) catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. RuBisCO consists of a large catalytic unit and a small subunit of undetermined function. In plants, the large subunit is coded by the chloroplastic genome while the small subunit is encoded in the nuclear genome. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate .

Members of the Rubisco family can be divided into 4 subgroups, form I-IV , which differ in their taxonomic distribution and subunit composition . Form I is the most abundant class, present in plants, algae, and bacteria, and forms large complexes composed of 8 large and 8 small subunits.
LPS-assembly protein LptD (LipoPS_assembly_LptD)
Type: Family

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 .

LptD forms a complex with LptE, which is involved in the assembly of LPS in the outer leaflet of the outer membrane. It determines N-hexane tolerance and is involved in outer membrane permeability as well as being ssential for envelope biogenesis .
Transcription regulator HTH, HdfR (Tscrpt_reg_HTH_HdfR)
Type: Family

The LysR-type transcriptional regulators (LTTRs) form one of the largest and most diverse families of bacterial regulators. These proteins are widely distributed and contribute to various aspects of bacterial metabolism and physiology. LTTRs are typically homotetramers, with each subunit consisting of an N-terminal DNA-binding domain

and a C-terminal effector-binding domain connected by a long helix

LTTRs generally function as dual-function repressor-activators, often negatively regulating their own expression while activating other genes . They respond to cellular signals by binding small-molecule ligands (effectors), which induce conformational changes altering DNA interactions and contact with RNA polymerase .

Some well-studied members of the LysR family include :

AmpR: regulator of β-lactamase expression

CatM and CatR: involved in aromatic compound degradation

CysB: regulator of cysteine biosynthesis

MetR: methionine biosynthesis regulator

NhaR: sodium/proton antiporter regulator

The hdfR gene encodes a LysR family protein. HdfR is able to bind to the flhDC promoter, indicating that HdfR is a transcriptional regulator for the flagellar master operon. Furthermore, the expression of the hdfR gene was shown to be negatively regulated by H-NS .
Uncharacterised protein family UPF0758, conserved site (UPF0758_CS)
Type: Conserved_site

UPF0758 was previously known as the radC family. The name was assigned according to the radC102 mutant of E. coli which was later demonstrated to be an allele of the transcription-repair-coupling factor recG . It has been described as a putative JAMM-family deubiquitinating enzyme, but its function remains to be determined .
Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site (Cyclophilin-type_PPIase_CS)
Type: Conserved_site

Cyclophilins exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity (

), accelerating protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides . They also have protein chaperone-like functions and are the major high-affinity binding proteins for the immunosuppressive drug cyclosporin A (CSA) in vertebrates .

Cyclophilins are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function . They share a common 109 amino acid cyclophilin-like domain (CLD) and additional domains unique to each member of the family. The CLD domain contains the PPIase activity, while the unique domains are important for selection of protein substrates and subcellular compartmentalisation .

This entry represents a conserved site in the central part of these enzymes.
Cadherin conserved site (Cadherin_CS)
Type: Conserved_site

Cadherins are a group of transmembrane proteins that serve as the major adhesion molecules located within adherens junctions. They can regulate cell-cell adhesion through their extracellular domain and their cytosolic domains connect to the actin cytoskeleton by binding to catenins . These proteins preferentially interact with themselves in a homophilic manner in connecting cells; thus acting as both receptor and ligand. They may play an important role in the sorting of different cell types during morphogenesis, histogenesis and regeneration. They may also be involved in the regulation of tight and gap junctions, and in the control of intercellular spacing. Cadherins are evolutionary related to the desmogleins which are component of intercellular desmosome junctions involved in the interaction of plaque proteins.

Structurally, cadherins comprise a number of domains: classically, these include a signal sequence; a propeptide of around 130 residues; a single transmembrane domain and five tandemly repeated extracellular cadherin domains, 4 of which are cadherin repeats, and the fifth contains 4 conserved cysteines and a C-terminal cytoplasmic domain . However, proteins are designated as members of the broadly defined cadherin family if they have one or more cadherin repeats. A cadherin repeat is an independently folding sequence of approximately 110 amino acids that contains motifs with the conserved sequences DRE, DXNDNAPXF, and DXD. Crystal structures have revealed that multiple cadherin domains form Ca2+-dependent rod-like structures with a conserved Ca2+-binding pocket at the domain-domain interface. Cadherins depend on calcium for their function: calcium ions bind to specific residues in each cadherin repeat to ensure its proper folding, to confer rigidity upon the extracellular domain and is essential for cadherin adhesive function and for protection against protease digestion.
Frataxin conserved site (Frataxin_CS)
Type: Conserved_site

This conserved site covers a conserved region in the central section of these proteins.

The eukaryotic proteins in this entry include Frataxin, the protein that is mutated in Friedreich's ataxia , and related sequences. Friedreich's ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the gene encoding Frataxin (FRDA). Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human Frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat) .

The bacterial proteins in this entry are iron-sulphur cluster (FeS) metabolism CyaY proteins homologous to eukaryotic Frataxin. Partial Phylogenetic Profiling suggests that CyaY most likely functions as part of the ISC system for FeS cluster biosynthesis, and is supported by experimental data in some species .
Synapsin, pre-ATP-grasp domain (Synapsin_pre-ATP-grasp_dom)
Type: Domain

This entry represents the pre-ATP-grasp structural domain found in synapsins, which precedes the ATP-grasp domain. The structure of the pre-ATP-grasp domain consists of α/β/α in three layers, and is possibly a rudiment form of the Rossmann-fold. This domain can have a substrate-binding function.

The synapsins are a family of neuron-specific phosphoproteins that coat synaptic vesicles and are involved in the binding between these vesicles and the cytoskeleton (including actin filaments). The family comprises 5 homologous proteins Ia, Ib, IIa, IIb and III. Synapsins I, II, and III are encoded by 3 different genes. The a and b isoforms of synapsin I and II are splice variants of the primary transcripts .

Synapsin I is mainly associated with regulation of neurotransmitter release from presynaptic neuron terminals . Synapsin II, as well as being involved in neurotransmitter release, has a role in the synaptogenesis and synaptic plasticity responsible for long term potentiation . Recent studies implicate synapsin III with a developmental role in neurite elongation and synapse formation that is distinct from the functions of synapsins I and II .

Structurally, synapsins are multidomain proteins, of which 3 domains are common to all the mammalian forms. The N-terminal `A' domain is ~30 residues long and contains a serine residue that serves as an acceptor site for protein kinase-mediated phosphorylation. This is followed by the `B' linker domain, which is ~80 residues long and is relatively poorly conserved. Domain `C' is the longest, spanning approximately 300 residues. This domain is highly conserved across all the synapsins (including those from Drosophila) and is possessed by all splice variants. The remaining six domains, D-I, are not shared by all the synapsins and differ both between the primary transcripts and the splice variants.