SII-SWORD/CoKE huggingface dataset:
S-locus glycoprotein domain (S_locus_glycoprot_dom)
Type: Domain

In Brassicaceae, self-incompatible plants have a self/non-self recognition system, which involves the inability of flowering plants to achieve self-fertilisation. This is sporophytically controlled by multiple alleles at a single locus (S). There are a total of 50 different S alleles in Brassica oleracea. S-locus glycoproteins, as well as S-receptor kinases, are in linkage with the S-alleles . Most of the proteins within this family contain apple-like domain (

), which is predicted to possess protein- and/or carbohydrate-binding functions.
CUB domain (CUB_dom)
Type: Domain

The CUB domain (for complement C1r/C1s, Uegf, Bmp1) is a structural motif of approximately 110 residues found almost exclusively in extracellular and plasma membrane-associated proteins, many of which are developmentally regulated . These proteins are involved in a diverse range of functions, including complement activation, developmental patterning, tissue repair, axon guidance and angiogenesis, cell signalling, fertilisation, haemostasis, inflammation, neurotransmission, receptor-mediated endocytosis, and tumour suppression . Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin). Proteins containing a CUB domain include:

Mammalian complement subcomponents C1s/C1r, which form the calcium-dependent complex C1, the first component of the classical pathway of the complement system.

Cricetidae sp. (Hamster) serine protease Casp, which degrades type I and IV collagen and fibronectin in the presence of calcium.

Mammalian complement-activating component of Ra-reactive factor (RARF), a protease that cleaves the C4 component of complement.

Vertebrate enteropeptidase (

), a type II membrane protein of the intestinal brush border, which activates trypsinogen.

Vertebrate bone morphogenic protein 1 (BMP-1), a protein which induces cartilage and bone formation and expresses metalloendopeptidase activity.

Sea urchin blastula proteins BP10 and SpAN.

Caenorhabditis elegans hypothetical proteins F42A10.8 and R151.5.

Neuropilin (A5 antigen), a calcium-independent cell adhesion molecule that functions during the formation of certain neuronal circuits.

Fibropellins I and III from Strongylocentrotus purpuratus (Purple sea urchin).

Mammalian hyaluronate-binding protein TSG-6 (or PS4), a serum and growth factor induced protein.

Mammalian spermadhesins.

Xenopus laevis embryonic protein UVS.2, which is expressed during dorsoanterior development.

Several of the above proteins consist of a catalytic domain together with several CUB domains interspersed by calcium-binding EGF domains. Some CUB domains appear to be involved in oligomerisation and/or recognition of substrates and binding partners. For example, in the complement proteases, the CUB domains mediate dimerisation and binding to collagen-like regions of target proteins (e.g. C1q for C1r/C1s). The structure of CUB domains consists of a β-sandwich with a jelly-roll fold. Almost all CUB domains contain four conserved cysteines that probably form two disulphide bridges (C1-C2, C3-C4). The CUB1 domains of C1s and Map19 have calcium-binding sites .
Porphobilinogen deaminase (HemC)
Type: Family

Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway . The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin .

The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (

), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase (

) to charge a tRNA with glutamate, glutamyl-tRNA reductase (

) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase (

) to catalyse a transamination reaction to produce ALA.

The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase,

) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase,

) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase (

) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.

Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (

). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase (

) .

Porphobilinogen deaminase (also known as hydroxymethylbilane synthase,

) functions during the second stage of tetrapyrrole biosynthesis. This enzyme catalyses the polymerisation of four PBG molecules into the tetrapyrrole structure, preuroporphyrinogen, with the concomitant release of four molecules of ammonia. This enzyme uses a unique dipyrro-methane cofactor made from two molecules of PBG, which is covalently attached to a cysteine side chain. The tetrapyrrole product is synthesized in an ordered, sequential fashion, by initial attachment of the first pyrrole unit (ring A) to the cofactor, followed by subsequent additions of the remaining pyrrole units (rings B, C, D) to the growing pyrrole chain . The link between the pyrrole ring and the cofactor is broken once all the pyrroles have been added. This enzyme is folded into three distinct domains that enclose a single, large active site that makes use of an aspartic acid as its one essential catalytic residue, acting as a general acid/base during catalysis . A deficiency of hydroxymethylbilane synthase is implicated in the neuropathic disease, Acute Intermittent Porphyria (AIP) . A deficiency of hydroxymethylbilane synthase alters vegetative and reproductive development and causes lesions in Arabidopsis .
Sulfotransferase domain (Sulfotransferase_dom)
Type: Domain

This entry includes a range of sulfotransferase proteins including flavonol 3-sulfotransferase, aryl sulfotransferases, alcohol sulfotransferases, estrogen sulfotransferases and phenol-sulphate phenol sulfotransferase. These enzymes are responsible for the transfer of sulphate groups to specific compounds and function via an SN2-like mechanism through a trigonal bipyramidal transition state and have important roles in detoxification, hormone regulation, and cell signaling across all kingdoms of life .

The domain adopts a characteristic fold consisting of a central β-sheet flanked by α-helices, with conserved PAPS-binding loop (PSB) and 3' phosphate binding (PB) regions . The domain contains a highly conserved catalytic lysine in the PSB region and a conserved serine in the PB helix .
Proteinase inhibitor I13, potato inhibitor I (Prot_inh_pot1)
Type: Family

This family of proteinase inhibitors belong to MEROPS inhibitor family I13, clan IG. They inhibit peptidases of the S1 (

) and S8 (

) families . Potato inhibitor type I sequences are not solely restricted to potatoes but are found in other plant species for example: barley endosperm chymotrypsin inhibitor , and pumpkin trypsin inhibitor. Apart from leeches, e.g.Hirudo medicinalis (Medicinal leech), homologues are not found in metazoa . In general, the proteins have retained a specificity towards chymotrypsin-like and elastase-like proteases. Structurally these inhibitors are small (60 to 90 residues) and in contrast with other families of protease inhibitors, they lack disulphide bonds. The inhibitor is a wedge-shaped molecule, its pointed edge formed by the protease-binding loop, which contains the scissile bond. The loop binds tightly to the protease active site, subsequent cleavage of the scissile bond causing inhibition of the enzyme .

The inhibitors (designated type I and II) are synthesised in potato tubers, increasing in concentration as the tuber develops. Synthesis of the inhibitors throughout the plant is also induced by leaf damage; this systemic response being triggered by the release of a putative plant hormone.

Examples found in the bacteria and archaea are probable false positives.
Alkyl hydroperoxide reductase subunit C/ Thiol specific antioxidant (AhpC/TSA)
Type: Domain

Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels which mediate signal transduction in mammalian cells. Prxs can be regulated by changes to phosphorylation, redox and possibly oligomerisation states. Prxs are divided into three classes: typical 2-Cys Prxs; atypical 2-Cys Prxs; and 1-Cys Prxs. All Prxs share the same basic catalytic mechanism, in which an active-site cysteine (the peroxidatic cysteine) is oxidised to a sulphenic acid by the peroxide substrate. The recycling of the sulphenic acid back to a thiol is what distinguishes the three enzyme classes. Using crystal structures, a detailed catalytic cycle has been derived for typical 2-Cys Prxs, including a model for the redox-regulated oligomeric state proposed to control enzyme activity .

Alkyl hydroperoxide reductase (Ahp) has two subunits, the small AhpC subunit and the large AhpF subunit . AhpC is responsible for directly reducing organic hydroperoxides in its reduced dithiol form. Thiol specific antioxidant (TSA) is a physiologically important antioxidant which constitutes an enzymatic defence against sulphur-containing radicals and protects the cell against the oxidative stress caused by protein misfolding and aggregation . This entry contains AhpC and TSA, as well as related proteins.
Isochorismatase-like domain (Isochorismatase-like_dom)
Type: Domain

This entry represents a domain found in hydrolase enzymes that belong to the isochorismatase family, including Ureidoacrylate amidohydrolase RutB from Escherichia coli and Nicotinamidase from Saccharomyces cerevisiae. Isochorismatase (also known as 2,3 dihydro-2,3 dihydroxybenzoate synthase) catalyses the conversion of isochorismate, in the presence of water, to 2,3-dihydroxybenzoate and pyruvate . This domain shows a typical helix-sheet-helix sandwich structural architecture, with a central β-sheet made of six parallel strands, three α-helices on one side and two α-helices on the other .
Fungi-IV metallothionein, family 11 (Metalthion_11)
Type: Family

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, nickel, etc. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds . The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects, e.g. low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. Fifteen MT families have been characterised, each family being identified by its number and its taxonomic range.

Fungi-IV (family 11) MTs are proteins of about 55-56 residues, with 9 conserved cysteines. Its members are recognised by the sequence pattern C-X-K-C-x-C-x(2)-C-K-C. The taxonomic range of the members extends to ascomycotina. The protein contains a number of unusual histidine and phenylalanine residues conserved in the N-terminal part of the sequence. This fragment does not contain any Cys. The protein binds to copper ions.
Homoserine kinase (Homoserine_kinase)
Type: Family

Saccharomyces cerevisiae strains containing the erg8-1 mutation are temperature sensitive for growth due to a defect in phosphomevalonate kinase, an enzyme of isoprene and ergosterol biosynthesis. Subcloning and DNA sequencing have defined the functional ERG8 regulon as an 850bp upstream region and an adjacent 1,272bp open reading frame. The deduced ERG8 protein contains 424 residues and shows no similarity to known proteins, except within a putative ATP-binding domain present in many kinases . Enzymes that share the N-terminal Gly/Ser-rich putative ATP-binding region include galactokinase, homoserine kinase, mevalonate kinase and phosphomevalonate kinase. Homoserine kinase is a homodimeric enzyme involved in threonine biosynthesis. Sequence comparison of the yeast enzyme with the corresponding proteins from bacterial sources reveals the presence of several highly conserved regions, the pattern of occurrence of which suggests that the ancestral sequences might have been composed from separate (functional) domains. A block of similar residues, found towards the C terminus, is also present in many other proteins involved in threonine (or serine) metabolism; this motif may therefore represent the binding site for the hydroxy-amino acids. Limited similarity was detected between a motif conserved among the homoserine kinases and consensus sequences found in other mono- or dinucleotide-binding proteins .
Beta-lactamase, class-A (Beta-lactam_class-A)
Type: Family

Beta-lactamase catalyses the opening and hydrolysis of the beta-lactam ring of beta-lactam antibiotics such as penicillins and cephalosporins. There are four groups, classed A, B, C and D according to sequence, substrate specificity, and kinetic behaviour. Class A (penicillinase-type) is the most common . The genes for class A beta-lactamases are widely distributed in bacteria, frequently located on transmissible plasmids in Gram-negative organisms, although an equivalent chromosomal gene has been found in a few species . Class A, C and D beta-lactamases are serine-utilising hydrolases, while class B enzymes utilise a catalytic zinc centre instead. The 3 classes of serine beta-lactamase are evolutionarily related and belong to a superfamily that also includes DD-peptidases and other penicillin-binding proteins . All these proteins contain an S-x-x-K motif, the Ser being the active site residue . Although clearly related, however, the sequences of the 3 classes of serine beta-lactamases vary considerably outside the active site.

This entry represents the Group 2 beta-lactamases, which correspond to the penicillinases and cephalosporinases, which are inhibited by clavulanic acid. They corresponding to the molecular classes A and D reflecting the original TEM and SHV genes. However, because of the increasing number of TEM and SHV derived beta-lactamases, they have been divided into two subclasses, 2a and 2b:

The 2a subgroup contains just penicillinases.

The 2b subgroup contains broad spectrum beta-lactamases, meaning that they are capable of inactivating penicillins and cephalosporins at the same rate. Furthermore, new subgroups were segregated from subgroup 2b based on their activity against certain antibiotics and resistance to clavulanic acid.

Molecular Class D or A Subgroup 2d enzymes inactivate cloxacillin more than benzylpenicillin, with some activity against carbenicillin; these enzymes are poorly inhibited by clavulanic acid, and some of them are extended spectrum beta-lactamases (ESBLs).

The class A and D beta-lactamases belong to MEROPS peptidase family S11 (D-Ala-D-Ala carboxypeptidase A family, clan SE).
Tafazzin (Tafazzin)
Type: Family

This entry includes tafazzin and its homologues, such as Taz1 from yeasts and N-acylphosphatidylethanolamine synthase from plants. Tafazzin is an enzyme involved in the cardiolipin remodelling pathway . The phospholipid cardiolipin is an important component of the inner mitochondrial membrane that is involved in mitochondrial energy production and apoptosis .

In humans tafazzin is expressed at high levels in cardiac and skeletal muscle. As many as 10 isoforms can be present in different amounts in different tissues. Isoforms with hydrophobic N-termini are thought to be membrane anchored, while shorter forms, lacking the hydrophobic stretch, may be cytoplasmic (these latter are found in leukocytes and fibroblasts, but not in heart and skeletal muscle). A central hydrophilic domain may serve as an exposed loop that interacts with other proteins. Defects in the taz gene are the cause of Barth syndrome, a severe inherited disorder, often fatal in childhood. The disease is characterised by cardiac and skeletal myopathy, short stature and neutropenia .

In flies tafazzin is a CoA-independent, acyl-specific phospholipid transacylase with substrate preference for cardiolipin and phosphatidylcholine .

Budding yeast Taz1 is a lyso-phosphatidylcholine acyltransferase that is required for normal phospholipid content of mitochondrial membranes, whose acyl specificity in the reaction relies on lipid chemical composition .
AMP-dependent synthetase/ligase domain (AMP-dep_synth/lig_dom)
Type: Domain

This domain is found in a number of prokaryotic and eukaryotic enzymes, which act via an ATP-dependent covalent binding of AMP to their substrate, share a region of sequence similarity . This region is a Ser/Thr/Gly-rich domain that is further characterised by a conserved Pro-Lys-Gly triplet. This group of enzymes includes luciferase, long chain fatty acid Co-A ligase, long-chain fatty acid transport proteins that also function as acyl-CoA ligases, acetyl-CoA synthetase and various other closely-related synthetases .
Bombesin/neuromedin-B/ranatensin peptide family (Bombesin)
Type: Family

Bombesin-like peptides comprise a large family of peptides which were initially isolated from amphibian skin, where they stimulate smooth muscle contraction. They were later found to be widely distributed in mammalian neural and endocrine cells. The amphibian peptides which belong to this family are currently classified into three subfamilies ; the Bombesin group, which includes bombesin and alytesin; the Ranatensin group, which includes ranatensins, litorin, and Rohdei litorin; and the Phyllolitorin group, which includes Leu(8)- and Phe(8)-phyllolitorins. In mammals and birds two categories of bombesin-like peptides are known , gastrin-releasing peptide (GRP), which stimulates the release of gastrin as well as other gastrointestinal hormones, and neuromedin B (NMB), a neuropeptide that regulates exocrine and endocrine secretions, smooth muscle contraction, saciety, blood pressure, blood glucose, body temperature, and it is thought to play a role in reproduction and in different behavioral responses like stress or fear . Bombesin-like peptides, like many other active peptides, are synthesized as larger protein precursors that are enzymatically converted to their mature forms. The final peptides are eight to fourteen residues long.
Cecropin-like (CecC-like)
Type: Family

This entry represents antimicrobial peptides such as Cecropins, Sarcotoxins, Aedesins, Andropin and related protins from insects. The andropin gene is closely linked to the cecropin gene cluster of Drosophila melanogaster .

Cecropins are potent antibacterial proteins that constitute a main part of the cell-free immunity of insects. Cecropins are small proteins of about 35 amino acid residues active against both Gram-positive and Gram-negative bacteria. They seem to exert a lytic action on bacterial membranes. Cecropins have been given various names, including bactericidin, lepidopteran and sarcotoxin. All of these peptides are structurally related.
Small ribosomal subunit protein eS4 (Ribosomal_eS4)
Type: Family

This family represents the small ribosomal subunit protein eS4 from archaea and eukaryotes. Small ribosomal subunit protein eS4A from yeast is also known as S7/YS6; archaeal members are also known as S4e; and mammalian and plant cytoplasmic proteins were previously known as S4 . Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have 233 to 264 amino acids.

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 .
Proteinase inhibitor I12, Bowman-Birk (Prot_inh_BBI)
Type: Domain

This family of eukaryotic proteinase inhibitors, belongs to MEROPS inhibitor family I12, clan IF. They predominantly inhibit serine peptidases of the S1 family (

) . They play a role in defense response against pathogens and insects, but they also have been studied as therapeutic treatment in cancer and inflammatory disorders . Exceptionally, cowpea trypsin inhibitor inhibits a cathepsin L-like cysteine proteinase CPL-1 from the nematode Heterodera glycines .

The Bowman-Birk inhibitor family is one of the numerous families of serine proteinase inhibitors. They have a duplicated structure and generally possess two distinct inhibitory sites. These inhibitors are primarily found in plants and in particular in the seeds of legumes as well as in cereal grains. In cereals they exist in two forms, one of which is a duplication of the basic structure .
Proteins of the Bowman-Birk inhibitor family of serine proteinase inhibitors interact with the enzymes they inhibit via an exposed surface loop that adopts the canonical proteinase inhibitory conformation. The resulting non-covalent complex renders the proteinase inactive. This inhibition mechanism is common for the majority of serine proteinase inhibitor proteins and many analogous examples are known. A particular feature of the Bowman-Birk inhibitor protein, however, is that the interacting loop is a particularly well-defined disulphide-linked short β-sheet region .