SII-SWORD/CoKE huggingface dataset:
Dihydroorotase, conserved site (Dihydroorotase_CS)
Type: Conserved_site

This group contains a number of protein families, example are:

Archaeal and bacterial dihydroorotase (

) (DHOase)

Allantoinase (

)

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 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 .

Allantoinase (

) is the enzyme that hydrolyzes allantoin into allantoate. In yeast (gene DAL1) , it is the first enzyme in the allantoin degradation pathway; in amphibians and fishs it catalyzes the second step in the degradation of uric acid. The sequence of allantoinase is evolutionary related to that of DHOases.
Glycoside hydrolase, family 24 (Glyco_hydro_24)
Type: Family

Glycoside hydrolase family 24

comprises enzymes with only one known activity; lysozyme (

).

This entry includes Bacteriophage lambda lysozyme and Escherichia coli endolysin . Lysozyme helps to release mature phage particles from the cell wall by breaking down the peptidoglycan. The enzyme hydrolyses the 1,4-beta linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of prokaryotic cell walls. E. coli endolysin also functions in bacterial cell lysis and acts as a transglycosylase. The Bacteriophage T4 lysozyme structure contains two domains, the interface between which forms the active-site cleft. The N terminus of the two domains undergoes a 'hinge-bending' motion about an axis passing through the molecular waist . This mobility is thought to be important in allowing access of substrates to the enzyme active site.

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.
DNA binding HTH domain, Fis-type (HTH_Fis)
Type: Domain

The Factor for Inversion Stimulation (FIS) protein is a regulator of bacterial functions, and binds specifically to weakly related DNA sequences
. It activates ribosomal RNA transcription, and is involved in upstream activation of rRNA promoters. The protein has been shown to play a role in the regulation of virulence factors in both Salmonella typhimurium and Escherichia coli . Some of its functions include inhibition of the initiation of DNA replication from the OriC site, and promotion of Hin-mediated DNA inversion.

In its C-terminal extremity, FIS encodes a helix-turn-helix (HTH) DNA-binding motif, which shares a high degree of similarity with other HTH
motifs of more primitive bacterial transcriptional regulators, such as the nitrogen assimilation regulatory proteins (NtrC) from species like Azotobacter, Rhodobacter and Rhizobium. This has led to speculation that both evolved from a single common ancestor .

The 3-dimensional structure of the E. coli FIS DNA-binding protein has been determined by means of X-ray diffraction to 2.0A resolution . FIS is composed of four α-helices tightly intertwined to form a globular dimer with two protruding HTH motifs. The 24 N-terminal amino acids are poorly defined, indicating that they might act as `feelers' suitable for DNA or protein (invertase) recognition . Other proteins belonging to this subfamily include:

E. coli: atoC, hydG, ntrC, fhlA, tyrR,

Rhizobium spp.: ntrC, nifA, dctD
Elicitin (Elicitin)
Type: Family

Elicitins are small, highly-conserved proteins secreted by phytopathogenic fungi belonging to the phytophthora species . They are toxic proteins reponsible for inducing a necrotic and systemic hypersensitive response in plants from the solanaceae and cruciferae families. Leaf necrosis provides immediate control of fungal invasion and induces systemic acquired resistance; both responses mediate basic protection against subsequent pathogen inoculation.

Members of this family share a high level of sequence similarity, but they differ in net charge, dividing them into two classes: alpha and beta . Alpha-elicitins are highly acidic, with a valine residue at position 13, whereas beta-elicitins are basic, with a lysine at the same position. Residue 13 is known to be involved in the control of necrosis and, being exposed, is thought to be involved in ligand/receptor binding . Phenotypically, the two classes can be distinguished by their necrotic properties: beta-elicitins are 100-fold more toxic and provide better subsequent protection .
Glycosyl transferase, family 9 (Glyco_trans_9)
Type: Family

Glycosyltransferase family 9

comprises enzymes with two known activity; lipopolysaccharide N-acetylglucosaminyltransferase (

), heptosyltransferase (

).

Heptosyltransferase I is thought to add L-glycero-D-manno-heptose to the inner 3-deoxy-D-manno-octulosonic acid (Kdo) residue of the lipopolysaccharide core . Heptosyltransferase II is a glycosyltransferase involved in the synthesis of the inner core region of lipopolysaccharide . Lipopolysaccharide is a major component of the outer leaflet of the outer membrane in Gram-negative bacteria. It is composed of three domains; lipid A, Core oligosaccharide and the O-antigen. These enzymes transfer heptose to the lipopolysaccharide core .

This family includes bacterial autotransporter heptosyltransferases (BAHTs) .

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.
Hydroxymethylglutaryl-CoA reductase, class I/II (HMG_CoA_Rdtase)
Type: Family

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).
3-hydroxyisobutyrate dehydrogenase-related, conserved site (3-OH-isobutyrate_DH-rel_CS)
Type: Conserved_site

This entry identifies a conserved site in reductases/dehydrogenases.

3-hydroxyisobutyrate dehydrogenase (

) catalyses the NAD-dependent, reversible oxidation of 3-hydroxbutyrate to methylmalonate . In eukaryotes, it is a homodimeric mitochondrial protein involved in valine catabolism. In Pseudomonas aeruginosa (gene mmsB), it is involved in the distal valine metabolic pathway.

2-hydroxy-3-oxopropionate reductase (

) catalyses the NAP(P)H dependent reduction of 2-hydroxy-3-oxopropionate (tartronate semialdehyde) to D-glycerate.

6-phosphogluconate dehydrogenase (

) catalyses the NADP-dependent decarboxylation of 6-phosphogluconate to D-ribulose 5-phosphate and CO
2
.
DNA topoisomerase, type IIA, domain A (Topo_IIA_dom_A)
Type: Domain

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils .

This entry represents a domain found in type IIA topoisomerases, such as bacterial DNA topoisomerase IV (C subunit, ParC), bacterial DNA gyrases (A subunit, GyrA), and mammalian DNA toposiomerases II. DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA topology by catalysing the concerted breakage and rejoining of DNA strands during normal cellular growth .

In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N- and C-terminal regions correspond to gyrB and gyrA, respectively; this topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions (differs between eukaryotic and bacterial enzymes), domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA .

Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication . Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.
Opsin, pineal type (Opsin_pineal)
Type: Family

Recently, a non-visual opsin (designated P-opsin or pinopsin) has been isolated from Gallus gallus (Chicken) pineal gland . Environmental light signals reset the phase of the endogenous circadian pacemaker that controls the rhythmic production of melatonin via this protein . Sharing ~45% identity with retinal opsins, pinopsin is thought to have diverged early in opsin evolution . The protein is maximally sensitive to light of wavelength ~500nm and produces a slow, prolonged photo-transduction response consistent with the non-visual function of pineal photo-reception.
Class I peroxidase (Peroxidase_I)
Type: Family

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. They are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, fungal, plant and bacterial peroxidases can be viewed as members of a superfamily consisting of 3 major classes. Class I, the intracellular peroxidases, includes yeast cytochrome c peroxidase (CCP), ascorbate peroxidase (AP) and bacterial catalase-peroxidases .

In chloroplasts of higher plants, oxygen consumption in the absence of electron acceptors is accompanied by production of H2O2 and activated forms of oxygen. Chloroplasts contain several protective systems (such as superoxide dismutase (SOD), alpha-tocopherol and carotenoids), which are effective against various forms of activated oxygen. However, they lack catalase, and the disposal of H2O2 is accomplished by other means.

Ascorbic acid is a strong antioxidant that is effective in scavenging superoxide (O2-'), hydroxyl (OH') radicals and singlet oxygen. It can also remove H2O2 in the following reaction:

Ascorbate + H2O2 -->dehydroascorbate + 2 H2O

Ascorbate peroxidase (AP) is the main enzyme responsible for hydrogen peroxide removal in the chloroplasts and cytosol of higher plants.

The 3D structure of pea cytosolic ascorbate peroxidase has an overall fold virtually identical to that of CCP . The protein consists of 2 all-alpha domains, between which is embedded the haem group. The most pronounced difference between the AP and CCP structures is the absence of an antiparallel β-hairpin between the G and H helices in the AP molecule.
SecY/SEC61-alpha family (SecY/SEC61-alpha)
Type: Family

This family consists of the protein translocase subunit SecY and protein transport protein Sec61 subunit alpha (Sec61a).

Sec61a is part of the Sec61 complex, which plays a crucial role in the insertion of secretory and membrane polypeptides into the ER. It is required for assembly of membrane and secretory proteins.

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion . The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic domains . Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices.
Fibroblast growth factor family (Fibroblast_GF_fam)
Type: Family

Fibroblast growth factors (FGFs) are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types . FGFs are mitogens, which stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. The function of FGFs in developmental processes include mesoderm induction, anterior-posterior patterning, limb development, and neural induction and development. In mature tissues, they are involved in diverse processes including keratinocyte organisation and wound healing . FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects . Fibroblast growth factors are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction. FGFs have internal pseudo-threefold symmetry (β-trefoil topology) . There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules . They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 , which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active .
Major capsid L1 (late) protein, Papillomavirus (Capsid_L1_Papillomavir)
Type: Family

This entry represents the major late capsid protein L1 from Papillomaviruses, such as Human papillomavirus (HPV) . Papillomaviruses are members of the papovavirus superfamily. More than 70 different types of papillomavirus have been discovered in humans, some of which have been shown to cause genital carcinomas and cutaneous warts . The viruses contain a circular dsDNA genome surrounded by an icosahedral capsid (non-enveloped). Two proteins are involved in capsid formation: a major (L1) and a minor (L2) protein, in the approximate proportion 95:5%. L1 forms a pentameric assembly unit of the viral shell in a manner that closely resembles VP1 from polyomaviruses. Intermolecular disulphide bonding holds the L1 capsid proteins together . L1 capsid proteins can bind via its nuclear localisation signal (NLS) to karyopherins Kapbeta(2) and Kapbeta(3) and inhibit the Kapbeta(2) and Kapbeta(3) nuclear import pathways during the productive phase of the viral life cycle . Surface loops on L1 pentamers contain sites of sequence variation between HPV types.
Lymphocyte-specific protein (Lymphspecific)
Type: Family

Human and mouse LSP1 proteins consist of two domains: an N-terminal acidic domain and a C-terminal basic domain . The C-terminal domains are highly conserved and include several putative Ser/Thr phosphorylation sites . Immunoprecipitation of LSP1 from 32P-orthophosphate-loaded cells indicates that LSP1 is a phosphoprotein . The N-terminal domain of mouse LSP1 contains two putative Ca2(+)-binding sites, but these are not conserved in human LSP1; nevertheless, a different Ca2(+)-binding site may exist in the human protein, indicating functional rather than strict sequence conservation of the two proteins .

Although the precise function of LSP is unclear, it is an F-actin binding protein thought to be involved in transmembrane signal transduction via its postulated calcium-binding function (although evidence for the existence of the calcium-binding sites is weak). The expression pattern of LSP1 is highly restricted. Non-lymphoid cell lines or normal mouse tissues such as brain, lung, liver, skeletal muscle, kidney or testis do not express the protein, and it appears that its expression in the hematopoietic system is restricted to the lymphocyte, macrophage and neutrophil lineages .
Hantavirus nucleocapsid protein (Hanta_nucleocap)
Type: Family

Hantaviruses are ssRNA negative-strand viruses. The nucleocapsid protein is an internal protein of the virus particle .
Lipoprotein LPP20 (Lipo_LPP20)
Type: Family

This entry represents LPP20, which belongs to the non-essential class of lipoproteins .
tRNA uridine 5-carboxymethylaminomethyl modification enzyme MnmG-related (MnmG-rel)
Type: Family

MnmG (also known as GidA) is a tRNA modification enzyme found in bacteria and mitochondria. Though its precise molecular function of these proteins is not known, it is involved in the 5-carboxymethylaminomethyl modification of the wobble uridine base in some tRNAs . Sequence variations in the human mitochondrial protein may influence the severity of aminoglycoside-induced deafness .

This entry includes MnmG and related proteins, such as the methylenetetrahydrofolate--tRNA-(uracil-5-)-methyltransferase enzyme TrmFO.
Protein kinase C-like, phorbol ester/diacylglycerol-binding domain (PKC_DAG/PE)
Type: Domain

This entry represents the N-terminal region of PKC, known as C1. It has been shown to bind PE and DAG in a phospholipid and zinc-dependent fashion . The C1 region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain, which is about 50 amino-acid residues long, and which is essential for DAG/PE-binding. The DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.

Protein kinase C (PKC) is a family of serine/threonine protein kinases found in eukaryotic organisms, including humans, animals, and fungi. These enzymes play crucial roles in various signal transduction cascades, regulating cellular processes such as gene expression, protein secretion, cell proliferation, and inflammatory responses . PKCs are activated by second messengers, primarily diacylglycerol (DAG) . The PKC family comprises multiple isozymes, categorised into three subfamilies: conventional, novel, and atypical, based on their second messenger requirements . Structurally, PKCs consist of a regulatory domain and a catalytic domain connected by a hinge region . The regulatory domain typically contains C1

and C2 domain, which are responsible for DAG and calcium binding. The catalytic domain

, highly conserved among PKC isozymes, contains the ATP- and substrate-binding sites.
DapA-like (DapA-like)
Type: Family

Dihydrodipicolinate synthase (

) (DHDPS, DapA) catalyses, in higher plants, some fungi and bacteria (gene dapA), the first reaction specific to the biosynthesis of lysine and of diaminopimelate . DHDPS is responsible for the condensation of aspartate semialdehyde and pyruvate by a ping-pong mechanism in which pyruvate first binds to the enzyme by forming a Schiff-base with a lysine residue .

Other proteins are structurally related to DHDPS and probably also act via a similar catalytic mechanism :

Escherichia coli N-acetylneuraminate lyase (EC 4.1.3.3) (gene nanA), which catalyses the condensation of N-acetyl-D-mannosamine and pyruvate to form N-acetylneuraminate.

Trans-o-hydroxybenzylidenepyruvate hydratase-aldolase.

D-4-deoxy-5-oxoglucarate dehydratase.

Rhizobium meliloti protein mosA , which is involved in the biosynthesis of the rhizopine 3-o-methyl-scyllo-inosamine.

Thermoproteus tenax 2-dehydro-3-deoxy-D-gluconate/2-dehydro-3-deoxy-phosphogluconate aldolase (KdgA) .