SII-SWORD/CoKE huggingface dataset:
Chromo-like domain superfamily (Chromo-like_dom_sf)
Type: Homologous_superfamily

This entry represents a chromo (CHRromatin Organization MOdifier) structural domain, which consists of an SH3-like β-barrel capped by a C-terminal helix. Chromo domains are conserved modules of around 60 amino acids that are implicated in the recognition of lysine-methylated histone tails and nucleic acids. Chromo domains were originally identified in Drosophila modifiers of variegation, proteins that alter the structure of chromatin to the condensed morphology of heterochromatin. Domains with a chromo domain structural fold include:

Chromo domain, which lacks the first strand of the SH3-like β-barrel.

Shadow chromo domain, in which the first strand of the SH3-like β-barrel is altered by insertions.

Chromo barrel domain, which is a typical SH3-like β-barrel fold (similar sequence motif to the canonical chromo domain).

Histone-like DNA-binding proteins from Archaea .

Chromo domains can be found in various nuclear proteins, including heterochromatin protein 1 (HP1) (N-terminal chromo domain and C-terminal chromo shadow domain), where the chromo domain recognises histone tails with specifically methylated lysines ; polycomb protein Pc, which is essential for maintaining the silencing state of homeotic genes during development (chromo domain important for chromatin targeting) ; histone methyltransferase clr4, which regulates silencing and switching at the mating-type loci and to affect chromatin structure at centromeres ; and the ATP-dependent helicase CHD1, which regulates ATP-dependent nucleosome assembly and mobilisation through conserved double chromo domains and a SWI2/SNF2 helicase/ATPase domain .

Chromo barrel domains are found in various histone acetyltransferases, such as MYST1 from Mus musculus (Mouse) and MOF from Drosophila melanogaster (Fruit fly) . This domain can also be found in the human mortality factor 4-like protein, MRG15.
PSI domain (PSI)
Type: Domain

This domain is found in several different extracellular receptors, including plexins, which are involved in the development of neural and epithelial tissues ; in semaphorins, which regulate axon guidance, immune function and angiogenesis ; in integrins, which are important Metazoan adhesion receptors that transmit conformational change bidirectionally across the membrane (integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane) ; and in hepatocyte growth factor receptor, which plays important roles in normal development and in tumour growth and metastasis .
Deoxyribonuclease I (DNase_I)
Type: Family

This entry represents DNaseI and related proteins such as DNase gamma.

Deoxyribonuclease I (DNase I) (

) is a vertebrate enzyme which catalyzes the endonucleolytic cleavage of double-stranded DNA to 5'- phosphodinucleotide and 5'-phosphooligonucleotide end-products. DNase I is an enzyme involved in DNA degradation; it is normally secreted outside of the cell but seems to be able to gain access to the nucleus where it is involved in cell death by apoptosis .

As shown in the following schematic representation, DNase I is a glycoprotein of about 260 residues with two conserved disulphide bonds.

+-+ +--------+
| | | |
xxxxxxxxxxxxxxxxx#xxxxxxCxCxxxxx#xxxxxxxxxCxxxxxxxxCxxxxxxxxxxxxx

'C': conserved cysteine involved in a disulphide bond.
'#': active site residue.

DNase I has a pH-optimum around 7.5 and requires calcium and magnesium for full activity. It causes single strand nicks in duplex DNA. A proton acceptor-donor chain composed of a histidine and a glutamic acid produce a nucleophilic hydroxyl ion from water, which cleaves the 3'-P-O bond . DNase I forms a 1:1 complex with G-actin, resulting in the inhibition of DNase activity and loss of the ability of G-actin to polymerise into fibres . DNase I has been used in the treatment of lung problems in patients with cystic fibrosis: here it acts by degrading DNA found in purulent lung secretions, reducing their viscosity and making it easier for the patient to breathe .

The sequence of DNase I is evolutionary related to that of human muscle-specific DNase-like protein and human proteins DHP1 and DHP2. However, the first disulphide bond of DNase I is not conserved in these proteins.
Homoserine dehydrogenase (HDH)
Type: Family

This entry represents a family of homoserine dehydrogenases mainly found in bacteria.

Homoserine dehydrogenase (

) catalyses the third step in the aspartate pathway; the NAD(P)-dependent reduction of aspartate beta-semialdehyde into homoserine . Homoserine is an intermediate in the biosynthesis of threonine, isoleucine, and methionine. The enzyme can be found in a monofunctional form, in some bacteria and yeast, or a bifunctional form consisting of an N-terminal aspartokinase domain and a C-terminal homoserine dehydrogenase domain, as found in bacteria such as Escherichia coli and in plants. Structural analysis of the yeast monofunctional enzyme (

) indicates that the enzyme is a dimer composed of three distinct regions; an N-terminal nucleotide-binding domain, a short central dimerisation region, and a C-terminal catalytic domain . The N-terminal domain forms a modified Rossman fold, while the catalytic domain forms a novel α-β mixed sheet.

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see .
Glycerol dehydrogenase (Glycerol_DH)
Type: Family

This entry represents two distinct enzymes: bacterial NAD-linked glycerol dehydrogenase and archaeal glycerol-1-phosphate dehydrogenase. NAD-linked glycerol dehydrogenase converts glycerol to glycerone and s NADH during glycerol metabolism . Glycerol-1-phosphate dehydrogenase is responsible for the formation of the archaeal-specific glycerophosphate backbone of phospholipids, G-1-P, from glycerone phosphate . This is the key step in the in biosynthesis of archaeal enantiomeric phospholipids, .

There is similarity in the structure of these enzymes despite the differences in substrate specificity and biological role .
Ketol-acid reductoisomerase, plant (KetolA_reductoisomerase_plant)
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 group represents a ketol-acid reductoisomerase, plant type.
Ketol-acid reductoisomerase, fungi (KetolA_reductoisomerase_fun)
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 group represents a ketol-acid reductoisomerase, fungal type.
Aldehyde oxidase/xanthine dehydrogenase-like (Ald_Oxase/xanthine_DH-like)
Type: Family

This entry includes aldehyde oxidases (AOXs) and xanthine dehydrogenases (XDHs). They are both molybdenum cofactor (Moco) containing enzymes . AOX catalyses the reaction:

aldehyde + H(2)O + O(2) = a carboxylic acid + H2O2

It binds 2 2Fe-2S clusters uses FAD and molybdopterin as cofactors. XDH has the same cofactors and some of them can be converted from the dehydrogenase form (D) to the oxidase form (O). This can be done irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups . This enzyme catalyses three reactions:

Xanthine + H2O + NAD+= urate + NADH

Hypoxanthine + H2O + NAD+= xanthine + NADH

Xanthine + H2O + O2 = urate + H2O2

In Arabidopsis thaliana, the molybdenum cofactor sulfurase ABA3 is needed for post-translational activation of aldehyde oxidase and xanthine dehydrogenase. It does this by transferring a sulfur atom to the desulfo-molybdenum cofactor of these enzymes .
Protochlorophyllide reductase, ChlB, light independent (Protochlorophyllide_Rdtase)
Type: Family

This group represents a light independent protochlorophyllide reductase (DPOR) chain ChlB. DPOR is important for chlorophyll synthesis in the dark for some algae, lower plants, and gymnosperms, but not for angiosperms. The enzyme consists of three subunits encoded by the chlB, chlL, and chlN genes in the plastid genome .
NAD-dependent glutamate dehydrogenase, eukaryotes (NAD-GDH_euk)
Type: Family

This protein family represents fungal NAD-dependent glutamate dehydrogenases, including the NAD-specific glutamate dehydrogenases from Neurospora crassa and Saccharomyces cerevisiae (DHE2) . These enzymes catalyse the reversible oxidative deamination of glutamate to ketoglutarate and ammonia.
Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase, bacterial/archaeal (Glu/Phe/Leu/Val/Trp_DH_bac/arc)
Type: Family

Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

Glutamate dehydrogenases (

,

, and

) (GluDH) are enzymes that catalyse the NAD-and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate . GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction -this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha-keto acids . In rice, glutamate dehydrogenase 3 is mitochondrial.

Leucine dehydrogenase (

) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues . Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.

Phenylalanine dehydrogenase (

) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate .

Valine dehydrogenase (

) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate .

L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ .

This group represents glutamate/phenylalanine/leucine/valine/tryptophan dehydrogenases found in a number of bacteria and archaea.
Methyl coenzyme M reductase, alpha subunit (Me_CoM_Rdtase_asu)
Type: Family

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .

This group represents the alpha subunit of methyl coenzyme M reductase, also called coenzyme-B sulfoethylthiotransferase (

). This enzyme, with alpha, beta, and gamma subunits, catalyses the last step in methanogenesis. Several methanogens have encode two such enzymes, designated I and II; this model does not separate the isozymes.
Polyphenol oxidase (Polyphenol_oxidase)
Type: Family

This group represents a polyphenol oxidase, plant type.
NAD-reducing hydrogenase, HoxS gamma subunit (NAD-red_Hydgase_HoxS_gsu)
Type: Family

This entry represents the NAD-reducing hydrogenase HoxS gamma subunit (also known as HoxU).
Subunits alpha and gamma of HoxS constitute a diaphorase sub-complex that binds a [2Fe2S] cluster, FMN and a series of [4Fe4S] clusters [

,

, .
Nitrilotriacetate monooxygenase component A/pristinamycin IIA synthase subunit A (NTA_MOA)
Type: Family

This entry represents a distinctive clade, in which all characterised members are FMN-binding, within the larger family of luciferase-like monooxygenases (LLM), among which there are both FMN- and F420-binding enzymes. A well-characterised member is Nitrilotriacetate monooxygenase, component A from Aminobacter aminovorans, where nitrilotriacetate is a chelating agent used in detergents. This protein family also includes Dimethyl-sulfide monooxygenase from Hyphomicrobium sulfonivorans, Dibenzothiophene desulfurization enzyme A from Rhodococcus sp. and Long-chain alkane monooxygenase from Geobacillus thermodenitrificans .
Monophenol monooxygenase, fungi (Monophenol_mOase_fun)
Type: Family

This entry includes tyrosinases and polyphenol oxidases from fungi .
Nitrogen fixation, NifU (N_fixation_NifU)
Type: Family

The nitrogen fixation protein NifU is required for full activation of the metalloenzyme nitrogenase, the catalytic component of biological nitrogen fixation. In Azotobacter vinelandii, it is a homodimer; each subunit contains one 2Fe-2S cluster , which is proposed to have a redox function involving the release of Fe for the biosynthesis of the Fe-S cluster at the labile rubredoxin-like site .
Acetyl-CoA decarbonylase/synthase complex, gamma subunit (AcylCoA_decarb/synth_gsu)
Type: Family

This group represents the gamma subunit of acetyl-CoA decarbonylase/synthase (ACDS), a complex catalysing the reversible cleavage of acetyl-CoA. Depending on the direction of the reaction this complex allows either growth on acetate as sole carbon and energy source, or autotrophic growth from carbon dioxide/carbon monoxide .

The ACDS complex contains five subunits, among which beta possesses an Ni-Fe-S active-site metal cluster, the A-cluster, at which reaction with acetyl-CoA takes place, generating an acetyl-enzyme species poised for C-C bond cleavage . The ACDS complex is made up of alpha, epsilon, beta, gamma and delta chains with a probable stoichiometry of (alpha(2)epsilon(2))(4)-beta(8)-(gamma(1)delta(1))(8).

Titration experiments indicate that two electrons are required for activation of the enzyme in the process of forming the enzyme-acetyl intermediate .
Phosphatidylethanolamine N-methyltransferase, fungi (Phosphatid-EA_MeTrfase_fun)
Type: Family

This family consists of phosphatidylethanolamine N-methyltransferases from Fungi. Phosphatidylethanolamine N-methyltransferase (CHO2) catalyses the first step in the conversion of phosphatidylethanolamine to phosphatidylcholine during the methylation pathway of phosphatidylcholine biosynthesis .

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.
Methylphosphotriester-DNA alkyltransferase, AdaA (Me-P-triester_DNA_alkyl-Trfase)
Type: Family

Methylphosphotriester-DNA alkyltransferase AdaA is involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. It repairs the methylphosphotriester lesions in DNA by a direct and irreversible transfer of the methyl group to one of its own cysteine residues .
Bifunctional regulatory protein Ada (Bifunct_regulatory_prot_Ada)
Type: Family

This group represents the bifunctional regulatory protein Ada.
Glycerol-3-phosphate O-acyltransferase, chloroplast (G3P_O-acylTrfase_chlp)
Type: Family

Glycerol-3-phosphate (1)-acyltransferase(G3PAT) catalyzes the incorporation of an acyl group from either acyl-acyl carrier proteins (acylACPs) or acyl-CoAs into the sn-1 position of glycerol 3-phosphate to yield 1-acylglycerol-3-phosphate . Glycerol-3-phosphate (G3P) plays an important role in carbohydrate and lipid metabolic processes .
DNA alpha-glucosyltransferase (DNA_alpha-glucosyltransferase)
Type: Family

The T4 bacteriophage of E.coli protects its DNA via two glycosyltransferases which glucosylate 5-hydroxymethyl cytosines (5-HMC) using UDP-glucose. These two proteins are the retaining alpha-glucosyltransferase (AGT) and the inverting beta-glucosyltransferase (BGT) .

This entry represents AGT and similar proteins from Uroviricota. AGT catalyses the transfer of glucose from uridine diphosphoglucose to 5-hydroxymethyl cytosine of T4 DNA to yield glucosyl 5-hydroxymethyl cytosine . This protein adopts the GT-B fold and binds both the sugar donor and acceptor to the C-terminal domain. There is evidence for a role of AGT in the base-flipping mechanism and for its specific recognition of the acceptor base . AGT interacts with the clamp protein gp45 . The modification performed by this enzyme protects the phage genome against its own nucleases, the host restriction endonuclease system and against the host CRISPR-Cas9 defence system .
Ecdysteroid UDP-glucosyltransferase (Ecdysteroid_UDP-Glc_Trfase)
Type: Family

Ecdysteroid UDP-glucosyltransferase catalyses the transfer of glucose from UDP-glucose to ecdysteroids .
NAD--protein ADP-ribosyltransferase Alt-like (Phage_T4_Alt-like)
Type: Family

This entry represents a family of NAD-protein ADP-ribosyltransferases found in Myoviridae (phages with contractile tails). It includes the ALT protein from the bacteriophage T4

Protein ADP-ribosylation is an important posttranslational modification catalyzed by a group of enzymes known as ADP-ribosyltransferases (ADP-RTs) . ADP-RTs transfer single or multiple ADP-ribose moieties from NAD to a specific amino acid residue within a target protein, forming mono ADP-ribosylation or poly ADP-ribosylation (PARylation) . ADP-ribosylation changes the electrostatic potential of a target protein by introducing two phosphate groups and may affect protein-DNA as well as protein-protein interactions . Protein ADP-ribosylation plays versatile roles in multiple biological processes.

Bacteriophage T4 codes for three ADP-ribosyltransferases: Alt, ModA, and ModB. The ADP-ribosylating activity of each is directed to a specific set of host proteins. Among the three phage-encoded T4 mono-ADP-RTs, the Alt protein has the broadest range of target proteins, which include one of the two alpha subunits of host RNA polymerase .The T4 Alt protein initially acts as a structural component of the phage head. At the time of infection, it enters the host cell with phage DNA and immediately displays enzymatic activity .
Dihydropteroate synthase, predicted (Dihydropteroate_synthase_prd)
Type: Family

This group represents a group of predicted dihydropteroate synthases found mostly in the Campylobacterales.
Thiamine-phosphate synthase, cyanobacterial/bacterial (TMP_synthase_cyanobac_bac)
Type: Family

This group represents a predicted thiamine-phosphate synthase from cyanobacteria and bacteria.

Thiamine phosphate synthase (TPS) catalyzes the substitution of the pyrophosphate of 2-methyl-4-amino-5- hydroxymethylpyrimidine pyrophosphate by 4-methyl-5- (beta-hydroxyethyl)thiazole phosphate to yield thiamine phosphate in the thiamine biosynthesis pathway .
Serine-protein kinase PrkA/YeaG (PrkA/YeaG)
Type: Family

This entry represents YeaG, PrkA and similar proteins in bacteria.

ATP-dependent protease PrkA proteins are bacterial and archaeal serine kinases, approximately 630 residues in length. They possesses the A-motif of nucleotide-binding proteins and exhibit distant homology to eukaryotic protein kinases .

Serine/threonine kinase YeaG plays a role in bacterial adaptation to sustained nitrogen starvation . It may function by indirectly repressing the transcription of two toxin-antitoxin modules, MqsR/MqsA and DinJ/YafQ, which in turn positively influence the expression of rpoS, the master regulator of the general stress response . In vitro, YeaG exhibits autokinase and casein kinase activity , and can also specifically phosphorylate an unidentified 65 kDa cytoplasmic protein. Additionally, it has been shown to phosphorylate the isocitrate lyase AceA in the presence of malate, suggesting a possible regulatory role during the metabolic shift from glucose to malate .
Mitogen-activated protein (MAP) kinase kinase kinase, MLK1-4 (MLK1-4)
Type: Family

This entry represents mitogen-activated protein kinase kinase kinase MAP3K9 (MLK1), MAP3K10 (MLK2), MAP3K11 (MLK3) and MAP3K21 (MLK4), which form part of the mixed lineage kinase (MLK) family .
Homeobox protein Pitx/unc30 (Homeobox_Pitx/unc30)
Type: Family

This entry represents the Pitx/unc30 homeobox proteins, which act as transcriptional regulators.