SII-SWORD/CoKE huggingface dataset:
Neutrophil cytosol factor P40 (p40phox)
Type: Family

Phagocytes form the first line of defence against invasion by microorganisms. Engulfing of bacteria by neutrophils is accompanied by the consumption of large amounts of oxygen, a so-called respiratory burst. Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic granulomatous disease (CGD), in which patients are predisposed to infection, often from otherwise non-pathogenic bacteria. Regulation of the respiratory burst takes place at the phagocytic vacuole. The process is mediated by NADPH oxidase, which transports electrons across the plasma membrane to form superoxide (an oxygen molecule with an extra electron that is toxic to normal cells) in the vacuole interior. The electrons are carried across the membrane by a short electron transport chain in the form of an unusual flavocytochrome B . To conserve NADPH and avoid the toxic effects of superoxide, the oxidase remains inactive until it receives an appropriate stimulus. Activation involves the participation of a number of cytosolic proteins, some of which attach to the flavocytochrome. P47phox, p67phox and p40phox are specialised components of phagocytic cells. All contain SH3 domains, by means of which they attach to proline-rich regions of other proteins. Upon activation, p40phox translocates to the region of the plasma membrane forming the phagocytic vacuole, where, with phosphorylated p47phox and p67phox, it associates with hydrophilic regions of the flavocytochrome
Myelin P0 protein-related (Myelin_P0-rel)
Type: Family

This entry represents a group of transmembrane proteins, including myelin protein P0, myelin protein zero-like protein 1/2/3, sodium channel subunit beta-2 and v-set and immunoglobulin domain-containing protein 1.

Myelin protein P0 is required for normal myelination in the peripheral nervous system. It mediates adhesion between adjacent myelin wraps and ultimately drives myelin compaction. Mutations in the gene MPZ, encoding myelin protein zero (MPZ), cause inherited neuropathies collectively called Charcot-Marie-Tooth type 1B .

Sodium channel regulatory subunit beta-2 is a regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarisation of excitable membranes .

This entry also includes Junctional adhesion molecule-like (JAML) which is localised at the cell plasma membrane in the areas of cell-cell contacts and is involved in the transmigration of leukocytes within epithelial and endothelial tissues through adhesive interactions with epithelial and endothelial CXADR .
Histamine H1 receptor (Histamine_H1_rcpt)
Type: Family

Histamine plays an important role in a variety of pathophysiological conditions. In allergic conditions, histamine is released from basophils and mast cells and is responsible for symptoms of allergic conditions of the skin and airways. In the gastric mucosa, gastric induced histamine release stimulates parietal cells to secrete gastric acid. In the central nervous system (CNS), histamine is synthesized in specific neurons that are localized in the posterior hypothalamus. These neurons are involved in a variety of important physiological functions, including the regulation of the sleep-wake cycle, cardiovascular control, regulation of the hypothalamic pituitary adrenal-axis, learning and memory .

Histamine exerts its biological effects by binding to and activating four distinct separate rhodopsin-like G protein-coupled receptors-histamine H1 receptor, histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Each of the histamine receptors produce a functional response, but their mechanism differs. The H1 receptor couples to Gq/11 stimulating phospholipase C, whereas the H2 receptor interacts with Gs to activate adenylyl cyclase . The H3 and H4 receptors couple to Gi proteins to inhibit adenylyl cyclase, and to stimulate MAPK in the case of the H3 receptor .

This entry represents the histamine H1 receptor (also known as HH1R), which plays an important role in allergic responses. As a result, a number of selective receptor antagonists have been developed for the treatment of symptoms associated to allergic and anaphylactic reactions, such as various inflammatory conditions, motion sickness, sleep and appetite suppression . Activation of the H1 receptor increases vascular permeability, stimulates sensory nerves of airways, and promotes chemotaxis of eosinophils, so can cause sneezing, nasal congestion and rhinorrhea. H1 antihistamines can act as inverse agonists, causing a shift in equilibrium of the H1 receptor to the inactivated state when bound to the H1 antihistamine . In the cerebral cortex, activation of H1 receptors leads to inhibition of cell membrane potassium channels, depolarizing the neurons and increases the resistance of the neuronal cell membrane, bringing the cell closer to its firing threshold and increasing the excitatory voltage produced by a given excitatory current. H1 receptor antagonists produce drowsiness because they oppose this action, reducing neuronal excitation . The H1 receptor is widely distributed in the periphery, notably smooth muscle, where it stimulates contraction (vasoconstriction). It is also found in the adrenal medulla, vascular endothelium and heart and throughout the CNS, including the cerebral cortex, spinal cord and cerebellum .
D-galactoside/L-rhamnose binding SUEL lectin domain (Lectin_gal-bd_dom)
Type: Domain

The D-galactoside binding lectin purified from sea urchin (Anthocidaris crassispina) eggs exists as a disulphide-linked homodimer of two subunits; the dimeric form is essential for hemagglutination activity . The sea urchin egg lectin (SUEL) forms a new class of lectins. Although SUEL was first isolated as a D-galactoside binding lectin, it was latter shown that it binds to L-rhamnose preferentially . L-rhamnose and D-galactose share the same hydroxyl group orientation at C2 and C4 of the pyranose ring structure.

A cysteine-rich domain homologous to the SUEL protein has been identified in the following proteins :

Plant beta-galactosidases (

) (lactases).

Mammalian latrophilin, the calcium independent receptor of alpha-latrotoxin (CIRL). The galactose-binding lectin domain is not required for alpha-latratoxin binding .

Human lectomedin-1.

Rhamnose-binding lectin (SAL) from catfish (Silurus asotus, Namazu) eggs. This protein is composed of three tandem repeat domains homologous to the SUEL lectin domain. All cysteine positions of each domain are completely conserved .

The hypothetical B0457.1, F32A7.3A and F32A7.3B proteins from Caenorhabditis elegans.

The human KIAA0821 protein.
Blue (type 1) copper domain (BlueCu_1)
Type: Domain

The small blue proteins are single-domain proteins. The domain consists of a β-sheet sandwich, composed of eight strands in two sheets, and has predominantly antiparallel β-strand topology . This entry represents the blue copper domain.

Blue (type 1) copper proteins constitute a diverse class of proteins, including small blue proteins and multicopper oxidases. They bind copper and are characterised by an intense electronic absorption band near 600 nm .

The most well known members of this class of proteins are the small blue proteins, which includes azurins and plastocyanins. It is a group of monomeric proteins which contain one copper ion per molecule. The plant chloroplastic plastocyanins exchange electrons with cytochrome c6, and the distantly related bacterial azurins exchange electrons with cytochrome c551. This group also includes amicyanin from bacteria such as Methylobacterium extorquens or Paracoccus versutus (Thiobacillus versutus) that can grow on methylamine; auracyanins A and B from Chloroflexus aurantiacus ; blue copper protein from Alcaligenes faecalis; cupredoxin (CPC) from Cucumis sativus (Cucumber) peelings ; cusacyanin (basic blue protein; plantacyanin, CBP) from cucumber; halocyanin from Natronomonas pharaonis (Natronobacterium pharaonis) , a membrane associated copper-binding protein; pseudoazurin from Pseudomonas; rusticyanin from Thiobacillus ferrooxidans ; stellacyanin from Rhus vernicifera (Japanese lacquer tree); umecyanin from the roots of Armoracia rusticana (Horseradish); and allergen Ra3 from ragweed. This pollen protein is evolutionary related to the above proteins, but seems to have lost the ability to bind copper.
Glutamyl/glutaminyl-tRNA synthetase (Glu/Gln-tRNA-synth)
Type: Family

Glutamate-tRNA ligase (also known as glutamyl-tRNA synthetase;

) is a class I aminoacyl-tRNA synthetase. This enzyme shares similarities with glutaminyl-tRNA synthetase in terms of structure and catalytic properties. Glutamyl-tRNA synthetase (GluRS) and glutaminyl-tRNA synthetase (GlnRS) are grouped in the GlxRS subclass because of the shared evolutionary pathway of their catalytic domains. The catalytic domain of Glx subfamily is believed to be more ancient, having evolved from a common GluRS ancestor that contained only the catalytic domain. Anticodon binding domains of extant bacterial and eukaryotic/archeal GlxRS appeared independently at a later stage, with the anticodon-binding domain of bacterial GlnRS being acquired by an unique horizontal gene transfer event from the eukaryotic kingdom .

Bacterial GluRS are divided into two groups -discriminatory GluRS (D-GluRS) and non-discriminatory GluRS (ND-GluRS). While D-GluRS exclusively catalyses the transfer of Glu to tRNA(Glu), the ND-GluRS can also glutamylate tRNA(Gln) forming Glu-tRNAGln. The misacylated product is then transformed to Gln-tRNA(Gln) by an enzyme known as glutamyl-tRNA(Gln) amidotransferase. The bacterial GluRS structure consists of four domains. The N-terminal half (domains 1 and 2) contains the 'Rossman fold' typical for class I aminoacyl-tRNA synthetases and resembles the corresponding part of GlnRS, whereas the C-terminal half exhibits a GluRS-specific structural features .

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 .
Major surface glycoprotein G (G_prot)
Type: Family

Respiratory synctial virus (RSV) has two major virion envelope proteins, the fusion F and major attachment G glycoproteins, which are the two viral neutralisation antigens . This entry represents the major surface glycoprotein G from RSV. G glycoprotein interacts with host CX3CR1, the receptor for the CX3C chemokine fractalkine, to modulate the immune response and facilitate infection . There are two versions of the G protein: the full length G protein (mG), which is anchored by a transmembrane domain near the N terminus; the secreted version (sG), which lacks the transmembrane domain due to an alternative initiation of translation . The secreted version-sG helps the virus evade antibody-mediated restriction of replication by acting as an antigen decoy .
GTP cyclohydrolase II, RibA (RibA)
Type: Family

GTP cyclohydrolase II (also known as ribA) catalyses the first committed step in the biosynthesis of riboflavin (vitamin b2). The enzyme converts GTP to 2,5-diamino-6-beta-ribosyl-4(3H)-pyrimidinone 5'-phosphate (APy), formate and pyrophosphate, and requires magnesium as a cofactor. In numerous bacteria and in plants, GTP cyclohydrolase II occurs in the C-terminal of a bifunctional enzyme known as ribBA, which also comprises an N-terminal 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBP_synthase, also known as RibB) (

). RibB catalyses the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate .

A paralogous protein is encoded in the genome of Streptomyces coelicolor, which converts GTP to 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (FAPy), an activity that has otherwise been reported for unrelated GTP cyclohydrolases III .
SNAP-25 domain (SNAP-25_dom)
Type: Domain

This entry represents a domain found in the SNAP-25 family members. SNAP-25 (synaptosome-associated protein 25kDa) proteins are components of SNARE complexes, which are proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex (the SNARE or core complex) that brings the synaptic vesicle and plasma membranes together. The SNAREs constitute a large family of proteins that are characterised by 60-residue sequences known as SNARE motifs (

), which have a high propensity to form coiled coils and often precede carboxy-terminal transmembrane regions. The synaptic core complex is formed by four SNARE motifs (two from SNAP25 and one each from synaptobrevin and syntaxin 1) that are unstructured in isolation but form a parallel four-helix bundle on assembly. The crystal structure of the core complex revealed that the helix bundle is highly twisted and contains several salt bridges on the surface, as well as layers of interior hydrophobic residues. However, a polar layer in the centre of the complex is formed by three glutamines (two from SNAP25 and one from syntaxin 1) and one arginine (from synaptobrevin) .

Members of the SNAP-25 family contain a cluster of cysteine residues that can be palmitoylated for membrane attachment .
Dopamine receptor family (Dopamine_rcpt)
Type: Family

Dopamine receptors are members of the rhodopsin-like G-protein coupled receptor family and are prominent in the vertebrate central nervous system (CNS). Dysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders , including social phobia , Tourette's syndrome , Parkinson's disease , schizophrenia , neuroleptic malignant syndrome , attention-deficit hyperactivity disorder (ADHD) and drug and alcohol dependence . As a result, dopamine receptors are common drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors .

There are at least five different known subtypes of dopamine receptors designated D1, D2, D3, D4 and D5 . They are distinguished by their G-protein coupling, ligand specificity, anatomical distribution and physiological effects. Dopamine receptors are divided into two further subfamilies. The D1-like family consists of D1 and D5 receptors, which couple to Gs and mediate excitatory neurotransmission. The D2-like family, meanwhile, consists of D2, D3 and D4 receptors, which couple to Gi/Go and mediate inhibitory neurotransmission. Although dopamine receptors are widely distributed in the brain, they are found in different locations that have different receptor type densities, presumably reflecting different functional roles . D1 and D2 receptor subtypes are found at 10-100 times the levels of the D3, D4, D5 subtypes .

This entry represents the dopamine receptor family.
Peptidase S3, togavirin (Peptidase_S3)
Type: Domain

Togavirin, also known as Sindbis virus core endopeptidase, is a serine protease resident at the N terminus of the p130 polyprotein of togaviruses . The endopeptidase signature identifies the peptidase as belonging to the MEROPS peptidase family S3 (togavirin family, clan PA(S)). The polyprotein also includes structural proteins for the nucleocapsid core and for the glycoprotein spikes . Togavirin is only active while part of the polyprotein, cleavage at a Trp-Ser bond resulting in total lack of activity . Mutagenesis studies have identified the location of the His-Asp-Ser catalytic triad, and X-ray studies have revealed the protein fold to be similar to that of chymotrypsin .
Adenovirus fibre protein (Adeno_fibre)
Type: Family

Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised . Viral infection commences with recognition of host cell receptors by means of specialised proteins on viral surfaces. The adenovirus fibre protein `knob domain' at the C terminus is one such receptor-binding protein subunit. The crystal structure of the knob domain reveals a trimeric organisation, each subdomain folded into 2 functionally distinct β-sheets. The V sheet is highly conserved, and provides contact surfaces in the formation of the trimer, while the R sheet is more variable, and may play a role in viral-receptor interactions. The overall shape of the trimer resembles a 3-bladed propeller, with a central surface depression and 3 valleys formed by the symmetry-related R sheets. Sequence comparison of different types of adenovirus fibre protein suggests an overall similarity in the structure of the knob domain. The main conserved regions lie in the central surface depression around the 3-fold symmetry axis . The N terminus of the protein contains the 'shaft' region.
Photosystem antenna protein-like (PS_antenna-like)
Type: Family

This entry represents the intrinsic antenna proteins CP43 (PsbC) and CP47 (PsbB) found in the reaction centre of PSII. These polypeptides bind to chlorophyll a and beta-carotene and pass the excitation energy on to the reaction centre . This entry also includes the iron-stress induced chlorophyll-binding protein CP43' (IsiA), which evolved in cyanobacteria from a PSII protein to cope with light limitations and stress conditions. Under iron-deficient growth conditions, CP43' associates with PSI to form a complex that consists of a ring of 18 or more CP43' molecules around a PSI trimer, which significantly increases the light-harvesting system of PSI. IsiA can also provide photoprotection for PSII .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .
Glycoside hydrolase, family 29 (Glyco_hydro_29)
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 .

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.