SII-SWORD/CoKE huggingface dataset:
Mannosyl-glycoprotein endo-beta-N-acetylglucosamidase-like domain (MGlyc_endo_b_GlcNAc-like_dom)
Type: Domain

This domain is found in many different proteins including mannosyl-glycoprotein endo-beta-N-acetylglucosamidase (

). It is also found in flagellar protein J (

), which has been shown to hydrolyse peptidoglycan .
Gnk2-homologous domain (GNK2)
Type: Domain

Ginkbilobin-2 (Gnk2) is an antifungal protein found in the endosperm of Ginkgo seeds, which inhibits the growth of phytopathogenic fungi such as Fusarium oxysporum. Gnk2 has considerable homology (~85%) to embryo-abundant proteins (EAP) from the gymnosperms Picea abies and P. glauca. Plant EAP are expressed in the late stage of seed maturation and are involved in protection against environmental stresses such as drought. The sequence of Gnk2 is also 28-31% identical to the extracellular domain of cysteine-rich receptor-like kinases (CRK) from the angiosperm Arabidopsis. The CRK members are induced by pathogen infection and treatment with reactive oxygen species or salicylic acid and are involved in the hypersensitive reaction, which is a typical system of programmed cell death. In addition, there are at least 60 genes in Arabidopsis encoding the cysteine-rich secreted proteins (CRSP) with an Gnk2-homologous domain. Therefore, the proteins with a Gnk2-homologous domain are regarded as one of the largest protein superfamilies, although the role of the conserved Gnk2-homologous domain remains unclear . The Gnk2-homologous domain is composed of two α-helices and a five stranded β-sheet, which forms a compact single-domain architecture with an α+β-fold. It contains a C-X(8)-C-X(2)-C motif. Cysteine residues form three intramolecular disulphide bridges: C1-C5, C2-C3, and C4-C6 .
Ribosomal RNA small subunit methyltransferase H (RsmH)
Type: Family

RsmH (previously known as MraW) is a methyltransferase responsible for one of the two methylations (N4-methylation) of C1402 in Escherichia coli 16S rRNA. The N4, 2'-O-dimethylcytidine (m4Cm) at position 1402 of the 16S rRNA directly interacts with the P-site codon of the mRNA. These conserved methyl-modifications may play a role in fine-tuning the shape and function of the P-site, thus increasing decoding fidelity .
Lysine-tRNA ligase (Lys-tRNA-ligase)
Type: Family

Lysine-tRNA ligase (also known as Lysyl-tRNA synthetase) (

) is an alpha 2 homodimer that belong to both class I and class II. In eubacteria and eukaryota lysine-tRNA ligases belong to class II in the same family as aspartyl tRNA ligase. The class Ic lysine-tRNA ligase family is present in archaea and in a number of bacterial groups that include the alphaproteobacteria and spirochaetes. A refined crystal structures shows that the active site of LysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding .

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
tRNA methyltransferase, Trm1 (Trm1)
Type: Family

Trm1 (

) dimethylates a single guanine residue at position 26 of a number of tRNAs using S-adenosyl-L-methionine as donor of the methyl groups . In Saccharomyces cerevisiae, Trm1 is required for the modification of both mitochondrial and cytoplasmic tRNAs . This family also includes the related TRMT1-like protein from Mus musculus, which may play a role in motor coordination and exploratory behaviour , and similar mammal sequences.
Small ribosomal subunit protein eS31 (Ribosomal_eS31)
Type: Domain

This entry represents the eS31 (also known as S27a) ribosomal domain from both archaea and eukaryotes. In eukaryotes, the 40S ribosomal protein eS31 is synthesized as a C-terminal extension of ubiquitin (

), and this fusion protein is known as UBS27 . The eS31 domain comprises the C-terminal half of the protein. The synthesis of ribosomal proteins as extensions of ubiquitin promotes their incorporation into nascent ribosomes by a transient metabolic stabilisation and is required for efficient ribosome biogenesis . The ribosomal extension protein eS31 contains a basic region that is proposed to form a zinc finger; its fusion gene is proposed as a mechanism to maintain a fixed ratio between ubiquitin necessary for degrading proteins and ribosomes a source of proteins .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Frataxin/CyaY (Frataxin/CyaY)
Type: Family

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 .
IPT domain (IPT_dom)
Type: Domain

The IPT (Ig-like, plexins, transcription factors) domain has an immunoglobulin like fold . These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. The Ron tyrosine kinase receptor shares with the members of its subfamily (Met and Sea) a unique functional feature: the control of cell dissociation, motility, and invasion of extracellular matrices (scattering) .
Floricaula/leafy protein (FLO_LFY)
Type: Family

This family consists of various plant development proteins which are homologues of Floricaula (FLO) and leafy (LFY) proteins which are floral meristem identity proteins.

FLO and LFY proteins are floral meristem identity proteins . Mutations in the sequences of these proteins affect flower and leaf development. LFY has been shown to bind semi-palindromic 19-bp DNA elements through its highly conserved C-terminal DNA-binding domain (DBD). In addition to its well-characterised DBD, LFY possesses a second conserved domain at its amino terminus (LFY-N). Crystallographic structure determination shows that LFY-N is a sterile alpha motif (SAM) domain that mediates LFY oligomerisation. It allows LFY to bind to regions lacking high-affinity LFY-binding sites and to access closed chromatin regions. Experiments revealed that altering the capacity of LFY to oligomerize compromised floral function. It has been suggested that the biochemical properties of the SAM domain are evolutionarily conserved in all plant species .
ACT domain (ACT_dom)
Type: Domain

The ACT domain is found in a variety of contexts and is proposed to be a conserved regulatory binding fold. ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. The archetypical ACT domain is the C-terminal regulatory domain of 3-phosphoglycerate dehydrogenase (3PGDH), which folds with a ferredoxin-like topology. A pair of ACT domains form an eight-stranded antiparallel sheet with two molecules of allosteric inhibitor serine bound in the interface. Biochemical exploration of a few other proteins containing ACT domains supports the suggestions that these domains contain the archetypical ACT structure .

Most of the proteins in which it is found are involved in amino acid and purine metabolism:

aspartokinases

chorismate mutases

prephenate dehydrogenases (TyrA)

prephenate dehydratases

homoserine dehydrogenases

malate dehydrogenases

phosphoglycerate dehydrogenases

phenylalanine and tryptophan-4-monooxygenases

phosphoribosylformylglycinamidine synthase (PurQ)

uridylyl transferase and removing enzyme (GlnD)

GTP pyrophosphokinase/phosphohydrolase (SpoT/RelA)

tyrosine and phenol metabolism operon regulators (TyrR)

several uncharacterised proteins from archaea, bacteria and plants that contain from one to four copies of this domain .
START domain (START_lipid-bd_dom)
Type: Domain

START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins . StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation . Expression of the protein in the absence of hormone stimulation is sufficient to induce steroid production, suggesting that this protein is required in the acute regulation of steroidogenesis. Representatives of the START domain family have been shown to bind different ligands such as sterols (StAR protein) and phosphatidylcholine (PC-TP). Ligand binding by the START domain can also regulate the activities of other domains that co-occur with the START domain in multidomain proteins such as Rho-gap, the homeodomain, and the thioesterase domain .
Pollen allergen Poa p IX/Phl p VI (Poa_pIX/Phl_pVI)
Type: Domain

Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

Proteins in this family belong to the Poa p (Poa pratensis or Kentucky bluegrass) IX and Phl p (Phleum pratense) VI allergen family, and include allergens with the following designations: Lol p 5, Pha a 5, Phl p 6, and Poa p 9. Phl p 5b has been shown to possess ribonuclease activity . Grass pollen allergens are one of the major causes of type I allergies (including allergic rhinoconjunctivitis, allergic bronchial asthma and hayfever), afflicting 15-20% of a genetically predisposed population .
DeoC/FbaB/LacD aldolase (DeoC/FbaB/LacD_aldolase)
Type: Family

This entry represents diverse aldolases, such as deoxyribose-phosphate aldolase, tagatose 1,6-diphosphate aldolase, fructose-bisphosphate aldolase class 1, 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate synthase, 2-amino-4,5-dihydroxy-6-one-heptanoic acid-7-phosphate synthase, phospho-2-dehydro-3-deoxyheptonate aldolase, and 6-deoxy-5-ketofructose 1-phosphate synthase, etc.

Aldolases play important roles in essential metabolic pathways, such as gluconeogenesis and glycolysis. They are classified with respect to their catalytic mechanism into two classes: class I adolases are are characterised by formation of covalent Schiff base intermediates, while class II aldolases are metallodependent enzymes and use a divalent transition metal ion to polarize the substrate ketose .

Fructose-1,6-bisphosphate (FBP) aldolase (EC 4.1.2.13) catalyzes the reversible aldol condensation of glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) yielding FBP. Two distinct classes of FBP aldolases occur in nature,Class I FBP aldolases form a Schiff-base intermediate between the carbonyl substrate (FBP and DHAP), whereas Class II FBP aldolases depend on divalent metal ions to stabilise the carbanion intermediate .

Tagatose 1,6-diphosphate aldolase is a class I aldolase. It catalyses the reversible cleavage of four diastereoisomers (fructose 1,6-bisphosphate (FBP), psicose 1,6-bisphosphate, sorbose 1,6-bisphosphate, and tagatose 1,6-bisphosphate) to dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate with high catalytic efficiency .

This entry also includes Divergent deoxyribose-phosphate aldolase-like protein (DPA) that was shown to interact with actin depolymerizing factor (ADF) to enhance the actin filament dynamics . This protein is inactive on 2-deoxyribose 5-phosphate and may have diverged to the point of losing deoxyribose-phosphate aldolase enzymatic activity .
Lipase EstA/Esterase EstB (Lipase_EstA/Esterase_EstB)
Type: Family

This family represents lipase estA and extracellular esterase estB. Lipase estA (also known as lipase LipA) was initially identified in Bacillus subtilis as a lipase that was active toward p-nitrophenyl esters and triacylglycerides, displaying a marked preference for esters with C8 acyl groups . A second, secreted lipase (LipB) was then identified in Pseudomonas fluorescens . However, it is likely that this second enzyme functions as an esterase, rather than a lipase . It has therefore been renamed extracellular esterase estB.
Trypsin Inhibitor-like, cysteine rich domain (TIL_dom)
Type: Domain

This domain is found in proteinase inhibitors, as well as in many extracellular proteins. The domain typically contains ten cysteine residues that form five disulphide bonds. The cysteine residues that form the disulphide bonds are 1-7, 2-6, 3-5, 4-10 and 8-9 .
Fungal lipase-type domain (Fungal_lipase-type)
Type: Domain

This entry represents a domain with an α/β hydrolase fold found in a group of proteins from eukaryotes and bacteria, including Feruloyl esterase A from Aspergillus niger , Triacylglycerol lipase OBL1 from Arabidopsis thaliana , human Diacylglycerol lipase-alpha , Toxin TseL from Vibrio cholerae . It is similar to that found in fungal lipases .
Thiazole biosynthetic enzyme Thi4 family (Thi4_fam)
Type: Family

Thiamine (vitamin B1) can be synthesised de novo in prokaryotes, plants and fungi. In eukaryotes, THI4 is involved in the biosynthesis of the thiamine precursor thiazole, and is repressed by thiamine .

Archaea harbour structural homologues of both the bacterial (ThiS-ThiF) and eukaryotic (THI4) proteins for thiazole synthesis. Most archaea have homologues that cluster to the THI4 family of proteins, but lack the conserved cysteine residue of the yeast THI4p that is required for sulfur transfer in formation of the thiazole ring. Instead, they have a histidine residue that is well conserved. Initially, these archaeal histidine-cointaining THI4 homologues were reported to convert ribose-1,5-bisphosphate (R15P) into ribulose-1,5-bisphosphate, the substrate of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) , but this may not be correct and their function remains unknown . On the other hand, archaeal THI4 homologues with a conserved catalytic cysteine are linked to thiamine biosynthesis .

This family is represented by THI4 and also includes chloroplastic thiamine thiazole synthase Thi1 and prokaryotic proteins.
Adenovirus small t-antigen, E1B 19kDa protein (Adenovir_t-Ag_E1B_19kDa)
Type: Family

This family consists of adenovirus E1B 19kDa protein or small t-antigen. The E1B 19kDa protein inhibits E1A induced apoptosis and hence prolongs the viability of the host cell . It can also inhibit apoptosis mediated by tumour necrosis factor alpha and Fas antigen . E1B 19kDa blocks apoptosis by interacting with and inhibiting the p53-inducible and death-promoting Bax protein . The E1B region of adenovirus encodes two proteins E1B 19kDa the small t-antigen as found in this family and E1B 55kDa the large t-antigen which is not found in this family; both of these proteins inhibit E1A induced apoptosis .
Dienelactone hydrolase (Dienelactn_hydro)
Type: Domain

Dienelactone hydrolases play a crucial role in chlorocatechol degradation via the modified ortho cleavage pathway. Enzymes induced in 4-fluorobenzoate-utilizing bacteria have been classified into three groups on the basis of their specificity towards cis- and trans-dienelactone . Some proteins contain repeated small fragments of this domain (for example rat kan-1 protein).
Myosin tail (Myosin_tail)
Type: Domain

Muscle contraction is caused by sliding between the thick and thin filaments of the myofibril. Myosin is a major component of thick filaments and exists as a hexamer of 2 heavy chains , 2 alkali light chains, and 2 regulatory light chains. The heavy chain can be subdivided into the N-terminal globular head and the C-terminal coiled-coil rod-like tail , although some forms have a globular region in their C-terminal. There are many cell-specific isoforms of myosin heavy chains, coded for by a multi-gene family . Myosin interacts with actin to convert chemical energy, in the form of ATP, to mechanical energy . The 3-D structure of the head portion of myosin has been determined and a model for actin-myosin complex has been constructed .

This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament . It contains skip residues that confers local relaxation surrounding them and allows the transition of the coiled-coil to a nonclose-packed structure . The coiled-coil region provides the structural backbone of the thick filament .
Potato leaf roll virus readthrough protein (PLrV_ORF5)
Type: Family

This family consists mainly of the Potato leafroll virus (PLrV) read through protein also known as the minor capsid protein. This is generated via a readthrough of open reading frame 3, the coat protein, allowing transcription of open reading frame 5 to give an extended coat protein with a large C-terminal addition or read through domain .

The read through protein is essential for the circulative aphid transmission of PLrV and Beet western yellows virus . The N-terminal region of the luteovirus readthrough domain determines virus binding to Buchnera GroEL and is essential for virus persistence in the aphid .
Glycine cleavage system H-protein (GCV_H)
Type: Family

This is a family of glycine cleavage H-proteins, part of the glycine cleavage system (GCS) found in bacteria, archaea, and the mitochondria of eukaryotes. GCS is a multienzyme complex consisting of 4 different components (P-, H-, T- and L-proteins) which catalyzes the oxidative cleavage of glycine . The H-protein shuttles the methylamine group of glycine from the P-protein (glycine dehydrogenase) to the T-protein (aminomethyltransferase) via a lipoyl group, attached to a completely conserved lysine residue .
Transglutaminase-like (Transglutaminase-like)
Type: Domain

This domain is found in many proteins known to have transglutaminase activity, i.e. which cross-link proteins through an acyl-transfer reaction between the gamma-carboxamide group of peptide-bound glutamine and the ε-amino group of peptide-bound lysine, resulting in a epsilon-(gamma-glutamyl)lysine isopeptide bond. Transglutaminases have been found in a diverse range of species, from bacteria to mammals. The enzymes require calcium binding and their activity leads to post-translational modification of proteins through acyl-transfer reactions, involving peptidyl glutamine residues as acyl donors and a variety of primary amines as acyl acceptors, with the generation of proteinase resistant isopeptide bonds .
Glutamate synthase domain (Glu_synthdom)
Type: Domain

Ferredoxin-dependent glutamate synthase (GltS) has been implicated in a number of functions including photorespiration in Arabidopsis where it may also play a role in primary nitrogen assimilation in roots . GltS is a complex iron-sulfur flavoprotein that catalyzes the reductive synthesis of L-glutamate from 2-oxoglutarate and L-glutamine via intramolecular channelling of ammonia, a reaction in the plant, yeast and bacterial pathway for ammonia assimilation. It is a multifunctional enzyme that functions through three distinct active centres, carrying out L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor .

This domain is expressed as a separate subunit in the glutamate synthase alpha subunit from archaebacteria, or part of a large multidomain enzyme in other organisms. It contains a putative FMN binding site and Fe-S cluster .