SII-SWORD/CoKE huggingface dataset:
11-S seed storage protein, plant (11S_seedstore_pln)
Type: Family

Plant seed storage proteins, whose principal function appears to be the major nitrogen source for the developing plant, can be classified, on the basis of their structure, into different families. 11S-type globulins are non-glycosylated proteins which form hexameric structures . Each of the subunits in the hexamer is itself composed of an acidic and a basic chain derived from a single precursor and linked by a disulphide bond. This structure is shown in the following representation.

+-------------------------+
| |
xxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxxxNGxCxxxxxxxxxxxxxxxxxxxxxxx
|------Acidic-subunit-------------||-----Basic-subunit------|
|-----------------About-480-to-500-residues-----------------|

'C': conserved cysteine involved in a disulphide bond.

Members of the 11-S family include pea and broad bean legumins, oil seed rape cruciferin, rice glutelins, cotton beta-globulins, soybean glycinins, pumpkin 11-S globulin, oat globulin, sunflower helianthinin G3, etc. This family represents the precursor protein which is cleaved into the two chains. These proteins contain two β-barrel domains. This family is a member of the 'cupin' superfamily on the basis of their conserved barrel domain ('cupa' is the Latin term for a small barrel).
Cupin 1 (Cupin_1)
Type: Domain

This entry represents the conserved β-barrel fold of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel). This family contains 11S and 7S plant seed storage proteins, and germins. Plant seed storage proteins provide the major nitrogen source for the developing plant .

This domain can also be found as a central component of many microbial proteins including certain types of phosphomannose isomerase, polyketide synthase, epimerase, and dioxygenase .
Alpha amylase (Alpha_amylase)
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.

Alpha-amylases, which belong to glycoside hydrolase family 13, are 1,4-alpha-D-glucan glucanohydrolases, which degrade both the branched and unbranched forms of starch by cleaving the internal alpha-1,4 bonds connecting the glucose monomers. The products of these reactions are maltose and maltotriose, which are further degraded to glucose by maltases. One atom of calcium is required to bind to each protein molecule to allow it to function, but excess calcium can inhibit activity by binding to amino acids that are required for the catalytic activity of the enzyme.
Glycosyl hydrolase family 13, catalytic domain (GH13_cat_dom)
Type: Domain

Enzymes containing this domain, such as alpha-amylase, belong to family 13 (

) of the glycosyl hydrolases. The maltogenic alpha-amylase is an enzyme that catalyses the hydrolysis of (1-4)-alpha-D-glucosidic linkages in polysaccharides so as to remove successive alpha-maltose residues from the non-reducing ends of the chains in the conversion of starch to maltose. Other enzymes include neopullulanase, which hydrolyses pullulan to panose, and cyclomaltodextrinase, which hydrolyses cyclodextrins.

This entry represents the catalytic domain found in several protein members of this family. It has a structure consisting of an 8-stranded α/β barrel that contains the active site, interrupted by a ~70 amino acid calcium-binding domain protruding between β-strand 3 and α-helix 3, and a carboxyl-terminal β-barrel domain .

Family GH13 is the major glycoside hydrolase family acting on substrates containing α-glucoside linkages. GH13 contains hydrolases, transglycosidases, and isomerases ; noticeably, animal amino acid transporters , which have no glycosidase activity , are also GH13 members. The enzymes are found in a very wide range of organisms from all kingdoms. The GH13 enzymes have a wide range of different preferred substrates and products. For example, the α-amylases prefer polysaccharides of the α-1,4-glucan type, such as amylose and amylopectin, but are also able to attack the supramolecular structures represented by starch granules and glycogen particles. Among thousands of sequences and ~30 different enzyme specificities many are closely related to each other; GH13 therefore has officially been subdivided into almost 40 subfamilies . In general, the GH13 members are multidomain proteins with catalytic (β/α)8-barrel (i.e. TIM-barrel) domain (called domain A) having a small domain B (usually varying in length and of irregular structure) . Some of these enzymes include:

α-amylase

oligo-1,6-glucosidase

α-glucosidase

pullulanase

cyclomaltodextrinase

maltotetraose-forming α-amylase

isoamylase

dextran glucosidase

trehalose-6-phosphate hydrolase

maltohexaose-forming α-amylase

)

maltotriose-forming α-amylase

maltogenic amylase

neopullulanase

malto-oligosyltrehalose trehalohydrolase

limit dextrinase

amylosucrase

sucrose phosphorylase

cyclomaltodextrin glucanotransferase (CGTase)

4-α-glucanotransferase

isomaltulose synthase

trehalose synthase

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.
Alpha-amylase/branching enzyme, C-terminal all beta (A-amylase/branching_C)
Type: Domain

This entry represents the all-β C-terminal domain that is found in members of the glycosyl hydrolase 13 family, such as alpha-amylases and 1,4-alpha-glucan branching enzyme. This domain forms a Greek key β-barrel fold in these enzymes .

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

Branching enzyme catalyses the formation of alpha-1,6 branch points in either glycogen or starch. It has an important role in the determination of the structure of starch in plants and of glycogen in animals and bacteria .
DNA photolyase, N-terminal (DNA_photolyase_N)
Type: Domain

The photolyase/cryptochrome family consists of flavoproteins that perform various functions using blue-light photons as an energie source. It is present in all three domains of life, that is, archaea, eubacteria, and eukaryotes, and hence has arisen very early during evolution to protect genomes against the genotoxic effects of ultraviolet light originating from the sun. The photolyase/cryptochrome family is divided into two major groups: photolyases and cryptochromes. Photolyases repair cytotoxic and mutagenic UV-induced photolesions in DNA in many species from bacteria to plants and animals by using a light-dependent repair mechanism. It involves light absorption, electron transfer from an excited reduced and deprotanated FADH(-) to the flipped-out photolesion, followed by the fragmentation of the photolesions. Cryptochromes are highly related proteins that generally no longer repair damaged DNA, but function as photoreceptors. Cryptochromes regulate growth and development in plants and the circadian clock in animals .

Both photolyases and cryptochromes have a bilobal architecture consisting of two domains: an N-terminal α/β domain that may contain a light- harvesting chromophore to additionally broaden their activity spectra and a C- terminal α-helical catalytic domain comprising the light-sensitive FAD cofactor. Diverse classes of antenna chromophores likes 5,10- methenyltetrahydrofolate (MTHF), 8-hydroxydeazaflavin, FMN or FAD have been identified in some photolyase/cryptochrome to broaden their activity spectra, whereas many others apparently lack any bound antenna chromophores.

This entry represents the photolyase/cryptochrome α/β domain. It adopts a dinucleotide binding fold with a five-stranded parallel β sheet flanked on both sides by α helices .
Tumour necrosis factor domain (TNF_dom)
Type: Domain

The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities :

Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.

Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo .

T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.

CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells.

CD30L, a cytokine which induces proliferation of T cells.

FASL, a cytokine involved in cell death .

4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.

OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production .

TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis .

TNF-alpha is synthesised as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-beta, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-alpha is a secreted protein.

All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.
Tumour necrosis factor (TNF)
Type: Family

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.
DNA polymerase III epsilon subunit, exonuclease domain (DnaQ)
Type: Domain

All proteins in this entry for which functions are known are components of the DNA polymerase III complex (epsilon subunit). There is, however, an outgroup that includes paralogs in some gammaproteobacteria and the N-terminal region of DinG from some low GC Gram-positive bacteria.
RidA family (RidA)
Type: Family

This entry represents part of the RidA subfamily. Its members include 2-iminobutanoate/2-iminopropanoate deaminase from mammal and bacteria (RidA) and the yeast Protein HMF1 (YER057C). However, this entry does not include RutC, which is represented in

.

Mammal RidA, also known as UK114 antigen homolog, catalyses the hydrolytic deamination of enamine/imine intermediates that form during the course of normal metabolism . It also promotes endoribonucleolytic cleavage of some transcripts by promoting recruitment of the ribonuclease P/MRP complex . Bacterial RidA, also known as YjgF, is also involved in the isoleucine biosynthesis . Besides, yeast HMF1 is involved in maintenance of the mitochondrial genome .

The YjgF/YER057c/UK114 family (also known as the Rid family) of proteins is conserved in all domains of life . A phylogenetic analysis applied by Lambrecht
et al.
has divided the Rid family into a widely distributed archetypal RidA (YjgF) subfamily and seven other subfamilies (Rid1 to Rid7) that are largely confined to bacteria and often co-occur in the same organism with RidA and each other . Although the family members share high levels of protein sequence and structure similarity, their functions vary widely across different species .

Structurally, these proteins are homotrimers with clefts between the monomeric subunits that are proposed to have some functional relevance .

This family includes:

YjgF (also known as RidA or 2-iminobutanoate/2-iminopropanoate deaminase), which displays enamine/imine deaminase activity and can accelerate the release of ammonia from reactive enamine/imine intermediates of the pyridoxal 5'-phosphate-dependent threonine dehydratase (IlvA)

the yeast growth inhibitor YER057c (protein HMF1) that appears to play a role in the regulation of metabolic pathways and cell differentiation

the mammalian 14.5kDa translational inhibitor protein UK114, also known as L-PSP (liver perchloric acid-soluble protein), with endoribonucleolytic activity that directly affects mRNA translation and can induce disaggregation of the reticulocyte polysomes into 80 S ribosomes

RutC from E. coli, which is essential for growth on uracil as sole nitrogen source and is thought to reduce aminoacrylate peracid to aminoacrylate

YabJ from B. subtilis, which is required for adenine-mediated repression of purine biosynthetic genes
2Fe-2S ferredoxin, iron-sulphur binding site (2Fe2S_fd_BS)
Type: Binding_site

Ferredoxins are iron-sulphur proteins that mediate electron transfer in a range of metabolic reactions ; they can be classified into several subgroups according to the nature of their iron-sulphur cluster(s). One group, originally found in chloroplast membranes, has been termed 'chloroplast-type' or 'plant-type' and includes ferredoxins from plants, algae, archaea, rhodobacter, and a toluene-degrading pseudomonas. Here, the active centre is a 2Fe-2S cluster, where the irons are tetrahedrally coordinated by both inorganic sulphurs and sulphurs provided by 4 conserved Cys residues . In chloroplasts, 2Fe-2S ferredoxins function as electron carriers in the photosynthetic electron transport chain and as electron donors to various cellular proteins. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase .

Several oxidoreductases contain redox domains similar to 2Fe-2S ferredoxins, including ferredoxin/ferredoxin reductase components of several bacterial aromatic di- and monooxygenases, phenol hydroxylase, methane monooxygenase, vanillate demethylase oxidoreductase, phthalate dioxygenase reductase, bacterial fumarate reductase iron-sulphur protein, eukaryotic succinate dehydrogenase, and xanthine dehydrogenase. 3D structures are known for a number of 2Fe-2S ferredoxins and for the ferredoxin reductase/ferredoxin fusion protein phthalate dioxygenase reductase . The fold belongs to the α + β class, with 3 helices and 4 strands forming a barrel-like structure and an extruded loop containing 3 of the 4 cysteinyl residues of the iron-sulphur cluster.

In the 2Fe-2S ferredoxins, four cysteine residues bind the iron-sulphur cluster. Three of these cysteines are clustered together in the same region of the protein. This sequence covers the three cysteine residues involved in iron-sulphur binding.
Bacterial-type extracellular solute-binding protein (SBP)
Type: Family

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight family clusters , which generally correlate with the nature of the solute bound. This entry represents the family 1.
Maltose/Cyclodextrin ABC transporter, substrate-binding protein (Maltose/Cyclodextrin-bd)
Type: Family

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

This entry includes maltodextrin binding proteins and cyclodextrin-binding proteins (also known as galactooligosaccharide-binding proteins) from bacteria and archaea.

Maltodextrin binding protein (MBP) is the primary component of bacterial high-affinity active transport and chemotaxis . It is a monomeric protein, with 2 globular domains separated by a 2- or 3-stranded hinge. MBP binds and transports linear oligosaccharides (of up to 7 glucosyl units), as well as 2 cyclic maltodextrins which, although binding tightly, cannot be transported nor initiate a chemotactic response . It is thought that the hinge region is critical for the correct functioning of MBP, not just in the binding and recognition of sugars,
but also in allowing and maintaining the integrity of initiation of both active transport and chemotaxis .

The cyclodextrin-binding protein CYCB (also known as galactooligosaccharide-binding protein GANS) from Bacillus subtilis has been characterised. It is part of the ABC transporter complex GanPQS involved in the uptake of galactooligosaccharides and it has a role in galactan degradation .
Solute-binding family 1, conserved site (SBP_1_CS)
Type: Conserved_site

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight families or clusters, which generally correlate with the nature of the solute bound.

This entry represents a conserved site found in the extracellular solute-binding protein family 1 members from Gram-positive bacteria, Gram-negative bacteria and archaea.
Histidine biosynthesis protein (His_biosynth)
Type: Family

Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteins involved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called His6 and His7 in eukaryotes and HisA and HisF in prokaryotes. HisA is a phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (

), involved in the fourth step of histidine biosynthesis. The bacterial HisF protein is a cyclase which catalyses the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during the sixth step of histidine biosynthesis. The yeast His7 protein is a bifunctional protein which catalyses an amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the ribonucleotide used for purine biosynthesis. The enzyme also catalyses the cyclization reaction that produces D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis.
HisA, bacterial (HisA_bact_arch)
Type: Family

1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase (

), also known as Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase or HisA, catalyses the fourth step in histidine biosynthesis. HisA from Lactococcus lactis was found to be inactive . The putative HisA from Thermotoga maritima, is a conspicuous outlier to the set of all other HisA, including experimental HisA from the bacterium Escherichia coli and the Archaeaon Methanococcus voltae. Neighbour joining shows HisA from Thermotoga maritima to be within the HisA family (with HisF as an outgroup) but with a long branch.
Cytokinin glycosidase (Glycosidase)
Type: Domain

These enzymes correspond to Agrobacterium rolC and were characterised along with rolB. RolB and rolC were originally classified as glycoside hydrolase family 40 and 41 respectively. RolB has subsequently been shown to have tyrosine phosphatase activity.
Glycoside hydrolase, family 41 (Glyco_hydro_41)
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.

Family 41 encompasses cytokinin-beta-glucosidases. These enzymes hydrolyse cytokinin glucosides, liberating free cytokinins and contribute to root- inducing activity .