SII-SWORD/CoKE huggingface dataset:
Haemagglutinin-neuraminidase (Hemagglutn-neuramid)
Type: Family

This entry represents the haemagglutinin-neuraminidase (HN) glycoprotein found in a variety of paramyxoviruses (negative-stranded RNA viruses), including Mumps virus, Human parainfluenza virus 3, and the avian pathogen Newcastle disease virus. Some paramyxoviruses have two surface glycoproteins, HN and a fusion protein (F). HN is a multi-functional protein with three distinct functions: a receptor-binding (haemagglutinin) activity, a receptor-destroying (neuraminidase) activity, and a membrane fusion activity that fuses the viral envelope to the host cell membrane in order to infect the cell. The fusion activity involves an interaction between HN and the fusion protein. In other viruses, such as influenza A and B viruses, haemagglutinin and neuraminidase occur as separate glycoproteins.

The haemagglutinin-neuraminidase glycoprotein has a six-bladed β-propeller structure, and bears structural similarity to influenza A and B virus neuraminidase, bacterial neuraminidase, trypanosomal neuraminidase and transialidase .
Alpha-L-fucosidase, metazoa-type (FUC_metazoa-typ)
Type: Family

O-Glycosyl hydrolases family 29 (

) encompasses alpha-L-fucosidases (

) , which is a lysosomal enzyme responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Alpha-L-fucosidase is responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.

Fucosylated glycoconjugates are involved in numerous biological events, making alpha-l-fucosidases, the enzymes responsible for their processing, critically important. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterised by rapid neurodegeneration, resulting in severe mental and motor deterioration . The enzyme is a hexamer and displays a two-domain fold, composed of a catalytic (β/α)(8)-like domain and a C-terminal β-sandwich domain .

Drosophila melanogaster spermatozoa contains an alpha-l-fucosidase that might be involved in fertilisation by interacting with alpha-l-fucose residues on the micropyle of the eggshell . In human sperm, membrane-associated alpha-l-fucosidase is stable for extended periods of time, which is made possible by membrane domains and compartmentalisation. These help preserve protein integrity .

This entry represents a subgroup of alpha-L-fucosidases found in metazoa, fungi and bacteria.
Beta-agarase (Beta_agarase)
Type: Family

Beta-agarase is a glycosyl hydrolase family 16 (GH16) member that hydrolyzes the internal beta-1,4-linkage of agarose, a hydrophilic polysaccharide found in the cell wall of Rhodophyceaea, marine red algae . Agarose is a linear chain of galactose units linked by alternating L-alpha-1,3-and D-beta-1,4-linkages that are additionally modified by a 3,6-anhydro-bridge. Agarose forms thermo-reversible gels that are widely used in the food industry or as a laboratory medium. While beta-agarases are also found in two other families derived from the sequence-based classification of glycosyl hydrolases (GH50, and GH86) the GH16 members are most abundant .
1, 4-beta cellobiohydrolase (Beta_cellobiohydrolase)
Type: Family

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.

The 1,4-beta cellobiohydrolase family plays a central role in the recycling of plant biomass. The biological conversion of cellulose to glucose generally requires three types of hydrolytic enzymes: Endoglucanases, which cut internal beta-1,4-glucosidic bonds; exocellobiohydrolases that cut the dissaccharide cellobiose from the non-reducing end of the cellulose polymer chain; and beta-1,4-glucosidases, which hydrolyze the cellobiose and other short cello-oligosaccharides to glucose.
Endo-beta-N-acetylglucosaminidase (Endo-Fsp)
Type: Family

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.

This group represents an endo-beta-N-acetylglucosaminidase (

) that cleaves asparagine-linked oligomannose and hybrid, but not complex, oligosaccharides from glycoproteins . It belongs to glycosyl hydrolase family 18.
S-Adenosylmethionine lyase (S-AdoMet_lyase)
Type: Family

This entry represents S-Adenosylmethionine lyases (

), which catalyse the hydrolysis of S-adenosyl-L-methionine, cleaving it to form L-homoserine and methylthioadenosine. This enzyme is produced by Bacteriophage T3, which infects Escherichia coli cells. SAM hydrolase can remove S-adenosylmethionine from the E. coli cell, thereby inhibiting a variety of SAM-related activities, such as dam and dcm methylase-directed DNA modifications and the synthesis of spermidine from putrescine . It inhibits the host S-adenosylmethionine synthase METK/MAT which prevents methylation of the viral genome . Expression of SAM hydrolase in T3-transformed E. coli induces the met regulon by cleaving the SAM co-repressor to form 5'-methylthioadenosine, which is then cleaved to produce 5-methylthioribose .
Isochorismatase (Isochorismatase)
Type: Family

This entry includes a group of isochorismatase, including EntB from E. coli, PhzD from Pseudomonas fluorescens and VibB from Vibrio cholerae serotype O1.

EntB is involved in the second stage of enterobactin biosynthesis. It has a molecular weight of 35kDa, and is believed to possess bifunctional activity. Deletion studies involving EntB- mutants have shown that it is essential for virulence .

PhzD is involved in the biosynthesis of the antibiotic phenazine, a nitrogen-containing heterocyclic molecule having important roles in virulence, competition and biological control .
Epoxide hydrolase (Epoxide_hydrolase)
Type: Family

This entry includes epoxide hydrolase 1 (EPHX1) from mammals and juvenile hormone epoxide hydrolase (JHEH) from insects. EPHX1 is a conserved biotransformation enzyme for converting epoxides to diols and has been linked to several human diseases including cancer . JHEH catalyzes juvenile hormone hydrolysis .
Peptidase M10B (Pept_M10B)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

Proteins in this entry are metalloendopeptidases belong to the MEROPS peptidase family M10 (subfamily M10B, clan MA). They include serralysin, epralysin, mirabilysin, aeruginolysin and other related peptidases.
The peptidase unit is found at the N terminus while in this entry it is found at the C terminus and forms a corkscrew. It is thought to be important for secretion of the protein through the bacterial cell wall. Proteins in this entry contain a calcium ion binding domain.
Proteasome subunit beta 4 (Proteasome_beta4)
Type: Family

This group represents the beta type-4 subunit (MEROPS identifier T01.987) from the proteasome endopeptidase complex, which is one of the non-peptidase subunits. This subunit is known as beta type-7 in fungi.

The 20S proteasome, multisubunit proteolytic complex, is the central enzyme of non-lysosomal protein degradation in both the cytosol and nucleus . It is composed of 28 subunits arranged as four homoheptameric rings that stack on top of one another forming an elongated α-β-β-α cylinder with a central cavity . The proteasome alpha and beta subunits are members of the N-terminal nucleophile (Ntn)-hydrolase superfamily . Three of the beta subunits (beta1, beta2 and beta5) have an N-terminal threonine residue exposed as a nucleophile in peptide bond hydrolysis . Eukaryotes have 7 alpha and 7 beta proteasome subunits while archaea have one of each .
Histidine biosynthesis trifunctional-protein (Histidine_synth_trifunct)
Type: Family

This group represents a histidine biosynthesis trifunctional protein.
Riboflavin biosynthesis protein RibBA (Riboflavin_synth_RibBA)
Type: Family

This group represents the riboflavin biosynthesis protein RibBA which has both GTP cyclohydrolase II and 3,4-dihydroxy-2-butanone 4-phosphate synthase activities .
Arsenical pump ATPase, ArsA/GET3 (ATPase_ArsA/GET3)
Type: Family

This entry represents GET3 proteins in eukaryotes and ArsA proteins in bacteria and related pump proteins such as BagB.

Active extrusion is a common mechanism for the detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. This is particularly important for arsenic extrusion because of its prevalence in the environment and its potential to cause health and environmental problems. In prokaryotes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems. ArsA from Escherichia coli is the catalytic subunit of the ArsAB extrusion pump, providing resistance to arsenite and antimonite. This pump consists of a soluble ATPase (ArsA) and a membrane channel (ArsB). Maintenance of a low intracellular concentration of oxidation produces resistance to the toxic agents. A third protein, ArsC, expands the substrate specificity to allow for arsenate resistance. ArsC reduces arsenate to arsenite, which is subsequently pumped out of the cell . ArsA contains two nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony. Binding of metalloids to the pump stimulates the ATPase activity .

Homologues of the bacterial ArsA ATPase are found in eukaryotes, where they have several recognised functions unrelated to arsenic resistance . Caenorhabditis elegans homologue Asna-1 is required for defence against arsenite and antimonite toxicity , and may be also involved in insulin signaling . The homologue in yeast, GET3/Arr4, is part of the GET complex and not only is involved in stress tolerance to metals and heat , but also specifically recognises transmenbrane domains of tail-anchored (TA) proteins destined for the secretory pathway . Archaeal GET3 homologues have also been discovered, suggesting that that archaea may possess a TA protein targeting pathway similar to that in eukaryotes .
Phosphoribosylaminoimidazole carboxylase, fungi/plant (Ade2_fungi/plant)
Type: Family

The novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N5-carboxy-AIR (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (class I PurE). In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II PurE) .
Anthranilate synthase component 2 (Anthranilate_synth_II)
Type: Family

This entry represents a trifunctional tryptophan biosynthesis protein found in some yeast. In Neurospora crassa the anthranilate synthase complex catalyses the first, third and fourth enzymatic reactions of the committed pathway of tryptophan biosynthesis. This heterotetrameric complex (alpa2/beta2) is composed of a monofunctional alpha-subunit or component I (the trp-2 gene product), which catalyses the formation of anthranilate using ammonia rather than glutamine, and a beta-subunit or component II (the trp-1 gene product), which is a trifunctional polypeptide bearing the glutamine amidotransferase (TrpG), indole-3-glycerol-phosphate synthase (TrpC), and phosphoribosylanthranilate isomerase (TrpF) activities .
Peptidyl-prolyl cis-trans isomerase E (PPIE)
Type: Family

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 the peptidyl-prolyl cis-trans isomerase E family of enzymes, which are a type of cyclophilin. In addition to their PPIase activity and role in protein folding, PPIase E family members also possess RNA-binding activity and may be involved in pre-mRNA splicing .
Mannose-6-phosphate isomerase (Mannose-6-P_Isomerase)
Type: Family

Mannose-6-phosphate isomerase or phosphomannose isomerase (

) (PMI) is the enzyme that catalyses the interconversion of mannose-6-phosphate and fructose-6-phosphate. In eukaryotes PMI is involved in the synthesis of GDP-mannose, a constituent of N-and O-linked glycans and GPI anchors and in prokaryotes it participates in a variety of pathways, including capsular polysaccharide biosynthesis and D-mannose metabolism. PMI's belong to the cupin superfamily whose functions range from isomerase and epimerase activities involved in the modification of cell wall carbohydrates in bacteria and plants, to non-enzymatic storage proteins in plant seeds, and transcription factors linked to congenital baldness in mammals . Three classes of PMI have been defined .

This group represents a mannose-6-phosphate isomerase.
DNA ligase, bacteriophage T7-type (DNA_ligase_T7)
Type: Family

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (

), the other NAD (

), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination .

This group represents the ATP-dependent DNA ligase from Escherichia phage T7 and similar proteins predominantly found in tailed bacteriophages.
Protease inhibitor with pacifastin repeats (Prtase-inh_pacifastin)
Type: Family

This entry represents a group of protease inhibitors with pacifastin repeats, including Serine protease inhibitor 2 from the migratory grasshopper Melanoplus sanguinipes, Serine protease inhibitor I/II from Gryllus gregarius (Schistocerca gregaria) and U-reduvitoxin-Pr21 from the red spot assassin bug Platymeris rhadamanthus .
Proteinase inhibitor A/B (Prot_inh_API-A/B)
Type: Family

This small family of proteins from plants includes proteinase inhibitors A and B from Sagittaria sagittifolia (Arrowhead) and a trypsin/chymotrypsin inhibitor from Alocasia macrorrhizos (Giant taro) . They belong to the MEROPS inhibitor family I3, clan IC.
Transcription factor GAMYB-like (GAMYB-like)
Type: Family

The GAMYB protein from rice is a transcriptional activator of gibberellin-dependent alpha-amylase expression in aleurone cells. It plays an important role in floral organ development and is essential for pollen development .

This entry also includes MYB33 and MYB65 proteins from Arabidopsis. They are transcriptional activator of alpha-amylase expression that binds to 5'-CAACTGTC-3' motif in target gene promoter . Together with MYB65, MYB33 facilitates anther and tapetum development .
Transforming protein C-ets (Transform_prot_C-ets)
Type: Family

C-ets transcription factors are highly conserved members of the ets gene family, with amino acid similarity to the v-ets oncogene of the avian leukemia virus, E26 . They bind to unique DNA sequences, either alone or by association with other proteins .
Transcription factor, GA-binding, alpha subunit (TF_GA-bd_asu)
Type: Family

This group represents the DNA-binding alpha subunit of the GA-binding trancription factor. This transcritipon factor interacts with purine repeats and may play a role in embryonic development .
Disks large 1-like (DLG1-like)
Type: Family

This entry represents the disks large 1 (DLG1) proteins, including DLG1 from flies and DLG1/2/3/4 from vertebrates. DLG1 is an essential multidomain scaffolding protein required for normal development . It may play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation . Members of this group are involved in synaptic plasticity associated with NMDA receptor signalling
Cell division protein Cdc6/18 (Cdc6/18)
Type: Family

This group represents the cell division control protein Cdc6 and Cdc18, which are essential initiation factors for DNA replication .

Cdc6 appears to have an important and perhaps unique dual role in S phase, it is first required for the initiation of DNA replication and then actively participates in the suppression of nuclear division. It interacts with the origin recognition complex (ORC). It targeted for degradation by the E3 ubiquitin ligase complex SCF (Cdc4) .

Cdc18 is part of the checkpoint control that prevents mitosis from occurring until S phase is completed. It plays a key role in coupling S phase to start and mitosis. It acts at the initiation of DNA replication and plays a major role in controlling the onset of S-phase. Together with orp1, it is involved in the maintenance of replication forks and activation of cds1-dependent S-phase checkpoint .
Protohaem IX farnesyltransferase, mitochondria (Protohaem_IX_farnesylTrfase_mt)
Type: Family

This entry represents protohaem IX (haem A) farnesyltransferase (

), the product of the COX10 gene. This enzyme occurs in the mitochondrial membrane and catalyses the first step in the conversion of protohaem to the haem A prosthetic groups of the enzyme, namely the conversion of protohaem IX and farnesyl diphosphate to haem O. Haem O and/or haem A are specifically synthesised for the haem-copper respiratory oxidases . Deficiencies in COX10 are a cause of Leigh syndrome (LS) , which is a severe neurological disorder characterised by bilaterally symmetrical necrotic lesions in subcortical brain regions .
Pro-epidermal growth factor (Pro-epidermal_GF)
Type: Family

This group represents a pro-epidermal growth factor.
Transforming protein, StpA/StpB (Transforming_StpA/StpB)
Type: Family

This group represents a transforming proteins StpA/StpB.
Transforming growth factor-beta (TGF-beta)
Type: Family

The transforming growth factors-beta constitute a family of multi-functional cytokines that regulate cell growth and differentiation . Many cells synthesise TGF-beta, and essentially all have specific receptors for this peptide . TGF-beta regulates the actions of many other peptide growth factors and determines a positive or negative direction of their effects.
Frog skin active peptide family (FSAP)
Type: Family

This entry represents the frog skin active peptide (FSAP) family, whose members include dermaseptin, phylloseptin, brevinin, caerin and ocellatin-PT1-8 but excludes other ocellatins. They are highly potent antimicrobial peptides with a large spectrum of activity .
Thyroglobulin (Thyroglobulin)
Type: Family

This entry represents mammalian thyroglobulin.
Mating-type protein ALPHA1, Saccharomycetales (ALPHA1_Saccharomycetales)
Type: Family

This entry represents the transcription activators mating-type alpha1, such as HMLalpha1 and MATalpha1. Initiation of meiosis in Saccharomyces cerevisiae (Baker's yeast) is regulated by mating type and nutritional conditions that restrict meiosis to diploid cells grown under starvation conditions . Saccharomyces mating-type (MAT) switching occurs by gene conversion using one of two donors, HMLalpha and HMRa .
Mating factor alpha (Mating_factor_a)
Type: Family

This group represents a mating factor alpha from Saccharomycetales (budding yeasts) . The alpha-factor is produced by the haploid cells of the alpha mating type, and acts on cells of the opposite mating type (type a). The alpha-pheromone reversibly arrests the growth of these cells in the early G1 period of the cell cycle, which has been suggested to be a method of synchronisation of the two haploid cell cycles prior to mating.
Alpha-defensin (Alpha-defensin)
Type: Family

Mammalian alpha-defensins are expressed primarily in leukocytes and epithelia. They play an important role in the innate and adaptive immune response to microbial infection. There are six cysteine residues and one glycine residue, for an atypical SS-bulge, which are totally conserved in the otherwise diverse sequences of all known mammalian alpha-defensins. There is also a conserved pair of oppositely charged residues (Arg/Glu) that form a salt bridge across a protruding loop in the molecule. The primary function of the salt bridge in HD5 is to ensure correct processing of proHD5 and subsequent stabilisation of mature alpha-defensin in vivo .

Human neutrophil alpha-defensins (HNPs) are synthesized in vivo as inactive precursor proteins, i.e. preproHNPs. A series of sequential proteolytic events excise the N-terminal inhibitory pro peptide, leading to defensin maturation and storage in azurophilic granules . Human alpha-defensin-1 (HNP1) is a small antimicrobial peptide, which is cytotoxic to tumour cells in vitro and shows inhibitory activity for pathologic neovascularisation in vivo. Intracellularly expressed HNP1 induces tumour cell apoptosis, consequently inhibiting its growth. It might be involved in the host immune response to tumours and as such is a promising basis for HNP1-based gene therapy for cancer .
Beta/delta-agatoxin family (Beta/delta-agatoxin_fam)
Type: Family

The beta/delta-agatoxins are a family of spider proteins that act as insecticidal neurotoxins. The family includes mu-agatoxins, U3-agatoxins and delta-amaurobitoxins. They act by modifying presynaptic voltage-gated sodium channels (Nav), inducing spastic paralysis when injected into insect prey .
Neurotoxin, TxP-I (Neurotoxin_TxP-I)
Type: Family

This group represents a neurotoxin TxP-I.
Neurotoxin 3, Actiniidae (Neurotoxin_3_Actiniidae)
Type: Family

This group represents a neurotoxin 3, Actiniidae type . The structure of Anemonia sulcata toxin III (ATX III) has been determined .