SII-SWORD/CoKE huggingface dataset:
Serum amyloid A protein (Serum_amyloid_A)
Type: Family

The serum amyloid A (SAA) proteins comprise a family of vertebrate amphipathic α-helical apolipoproteins that associate predominantly with high density lipoproteins (HDL) . They play a role in the mobilisation of cholesterol for tissue repair and regeneration . The synthesis of these proteins is greatly increased (as much as a 1000 fold) in inflammation, being a major acute phase reactant together with C-reactive protein. They act as cytokine-like proteins that are involved in cell-cell communication and in inflammatory, immunologic, neoplastic and protective pathways . Prolonged elevation of plasma SAA levels, as in chronic inflammation, results in a pathological condition, called amyloidosis, which affects the liver, kidney and spleen and which is characterised by the highly insoluble accumulation of SAA in these tissues. During chronic inflammation, SAA association with HDL can change its protein and lipid composition which abrogates the HDL anti-atherogenic properties, contributing to a pro-atherogenic state .
Interleukin-10 (IL-10)
Type: Family

Interleukin 10 (IL-10) is a secreted 17-21kDa protein that is non- glycosylated in humans but exists as a non-covalent homodimer. IL-10 is secreted by some types of T-lymphocyte, B-lymphocytes and macrophages late after antigen activation. Generally, IL-10 inhibits T-cell and natural killer cell synthesis of other cytokines at the transcriptional level, indirectly, by affecting macrophages. These cytokines include interferon-gamma, IL-2, IL-3, tumour necrosis factor and granulocyte-macrophage colony-stimulating factor (GM-CSF). The mechanism of IL-10 induced inhibition appears to involve a reduction in the abundance of the macrophage surface molecules that directly stimulate T-cells and natural killer cells. Proteins encoded by viruses such as Epstein-Barr virus and equine herpes virus show a high degree of sequence identity to IL-10. These proteins are thought to be involved in evasion of host immune responses. The IL-10 molecule is a tight dimer of 2 interpenetrating subunits that form a V-shaped structure. Each half of the structure consists of 6 α-helices (4 from 1 subunit and 2 from the other). Four of the helices form an up-up-down-down bundle, which is observed in all other helical cytokines. The overall topology resembles interferon-gamma.

This entry represents interleukin-10.
Ribonuclease P (RNase_P)
Type: Family

Ribonuclease P (

) (RNase P) is a site specific endonuclease that generates mature tRNAs by catalysing the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5'-terminus. It can also cleave other RNA substrates such as 4.5S RNA. In bacteria RNase P is known to be composed of two components: a large RNA (about 400 base pairs) encoded by rnpB, and a small protein (119 to 133 amino acids) encoded by rnpA. The RNA moiety of RNase P carries the catalytic activity; the protein component plays an auxiliary, but essential, role in vivo by binding to the 5'-leader sequence and broadening the substrate specificity of the ribozyme. The sequence of rnpA is not highly conserved, however there is, in the central part of the protein, a conserved basic region.
Gamma-glutamyltranspeptidase (GGT_peptidase)
Type: Family

Gamma-glutamyltranspeptidase (

) (GGT) catalyses the transfer of the gamma-glutamyl moiety of glutathione to an acceptor that may be an amino acid, a peptide or water (forming glutamate). GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione and drug and xenobiotic detoxification . In prokaryotes and eukaryotes, it is an enzyme that consists of two polypeptide chains, a heavy and a light subunit, processed from a single chain precursor by an autocatalytic cleavage. The active site of GGT is known to be located in the light subunit. The sequences of mammalian and bacterial GGT show a number of regions of high similarity . Pseudomonas cephalosporin acylases (

) that convert 7-beta-(4-carboxybutanamido)-cephalosporanic acid (GL-7ACA) into 7-aminocephalosporanic acid (7ACA) and glutaric acid are evolutionary related to GGT and also show some GGT activity . Like GGT, these GL-7ACA acylases, are also composed of two subunits. This entry also includes the highly similar Scoloptoxin SSD14 from Scolopendra dehaani. SSD14 (which is also cleaved into alpha and beta subunits) has been shown to induce human platelet aggregation .

As an autocatalytic peptidase GGT belongs to MEROPS peptidase family T3 (gamma-glutamyltransferase family, clan PB(T)). The active site residue for members of this family and family T1 is C-terminal to the autolytic cleavage site. The type example is gamma-glutamyltransferase 1 from Escherichia coli.
Neuraxin/MAP1B repeat (MAP1B_neuraxin)
Type: Repeat

In microtubule-associated protein 1B (MAP1B) the basic region containing the KKEE and KKEVI motifs is responsible for the interaction between MAP1B and microtubules
in vivo
. This region bears no sequence relationship to the microtubule binding domains of kinesin, MAP2, or tau . Neuraxin is a putative structural protein of the rat central nervous system that is immunologically related to microtubule-associated protein 5 (MAP5). Neuraxin may be implicated in neuronal membrane-microtubule interactions .

Both proteins contain a region that consists of 12 tandem repeats of a 17 residues motif.
Antifreeze protein, type I (Antifreeze_1)
Type: Family

Marine teleosts from polar oceans can be protected from freezing in icy sea-water by serum antifreeze proteins (AFPs) or glycoproteins (AFGPs) : these function by binding to, and preventing the growth of, ice crystals within the fish and depressing the non-equilibrium freezing point to below that of the melting point.

Despite functional similarity, antifreeze proteins are structurally diverse and include glycosylated and at least 3 non-glycosylated forms: the AFGP of nototheniids and cods are polymers of a tripeptide repeat, Ala-Ala-Thr, with a disaccharide attached to the threonine residue; type I AFPs are found in flounder and sculpin; type II AFPs of sea-raven, smelt and herring are Cys-rich proteins; and type III AFPs, found in eel pouts, are rich in β-structure. Non-homologous antifreeze proteins have also been identified in insects and plants .

Type I AFPs are Ala-rich, amphiphilic, α-helical proteins . The ice-binding sites of all AFPs are relatively flat and hydrophobic and have an uninterupted section of alanines running the length of the approximately 16.5A helix repeat. Based on the energy-minimised structure , a model has been proposed to describe the binding of the protein to ice crystals, whereby the protein binds to an ice nucleation structure, in a zipper-like fashion, via hydrogen bonding of the methyl-group of threonine side chains (with an 11-residue period) to oxygen atoms in the ice lattice. The growth of ice crystals is thus stopped, or retarded, and the freezing point depressed. The high lysince content of these peptides may serve to promote the solubility of these proteins.
Mu opioid receptor (Mu_opioid_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

The term opioid refers to a class of substance that produces its effects via the major classes of opioid receptor, termed mu, delta and kappa. In the CNS, the mu opioid receptor is found in the cerebral cortex, thalamus, hypothalamus, periaqueductal grey, interpeduncular nucleus and median raphe. In the periphery, it is found in the myenteric plexus, and in certain smooth muscles, e.g. mouse vas deferens. Mu opioid receptors are believed to mediate analgesia, hypothermia, respiratory depression, miosis, bradycardia, nausea, euphoria and physical dependence. Beta-endorphin is the most potent endogenous ligand.
Proton-dependent oligopeptide transporter family (POT_fam)
Type: Family

The proton-dependent oligopeptide transporter (POT) family (also known as the peptide transport (PTR) family) is made up of a group of energy-dependent transporters found in organisms as diverse as bacteria and humans. The POT family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analyses of peptide transport proteins . They seem to be mainly involved in the intake of small peptides . However, some family members are nitrate permeases and others are involved in histidine transport .
Small ribosomal subunit protein bS1 (Ribosomal_bS1)
Type: Family

The small ribosomal subunit protein bS1 (also known as 30S ribosomal protein S1) contains the S1 domain that has been found in a large number of RNA-associated proteins. bS1 is a prominent component of the Escherichia coli ribosome and is most probably required for translation of most, if not all, natural mRNAs in E. coli in vivo . It binds mRNA upstream of the Shine-Dalgarno (SD) sequence and helps its binding to the 30S ribosomal subunit. It acts as an RNA chaperone to unfold structured mRNA on the ribosome but is not essential for mRNAs with strong SDs and little 5'-UTR structure, thus it may help fine-tune which mRNAs that are translated . This protein is also able to unwind dsRNA by binding to transiently formed ssRNA regions .

Unique among ribosomal proteins, the primary structure of bS1 contains six repeating contiguous OB-folds . There are flexible regions between the OB domains permitting free movement of the domains relative to each other.

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 .
Glycoside hydrolase family 27/36, conserved site (Glyco_hydro_27/36_CS)
Type: Conserved_site

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) web site. Families 27 (

) and 36 (

) encompasses alpha-galactosidases and alpha-N-acetylgalactosaminidases.

Alpha-galactosidase (

) (melibiase) catalyses the hydrolysis of melibiose into galactose and glucose. In man, the deficiency of this enzyme is the cause of Fabry's disease (X-linked sphingolipidosis). Alpha-galactosidase is present in a variety of organisms. There is a considerable degree of similarity in the sequence of alpha-galactosidase from various eukaryotic species. Escherichia coli alpha-galactosidase (gene melA), which requires NAD and magnesium as cofactors, is not structurally related to the eukaryotic enzymes; by contrast, an Escherichia coli plasmid encoded alpha-galactosidase (gene rafA) contains a region of about 50 amino acids which is similar to a domain of the eukaryotic alpha-galactosidases.

Alpha-N-acetylgalactosaminidase (

) catalyses the hydrolysis of terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides. In man, the deficiency of this enzyme is the cause of Schindler and Kanzaki diseases. The sequence of this enzyme is highly related to that of the eukaryotic alpha-galactosidases.

This entry represents a conserved site in families 27 and 36. It contains two conserved aspartic acid residues which could be involved in the catalytic mechanism.
GPCR, family 3, metabotropic glutamate receptor 6 (GPCR_3__mGluR6)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length . Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors . As these receptors regulate many important physiological processes they are potentially promising targets for drug development.

The metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca
2+
intracellular signalling pathway . At least eight sub-types of metabotropic receptor (GRM1-8) have been identified in cloning studies. The sub-types differ in their agonist pharmacology and signal transduction pathways.

GRM6 is restrictedly expressed in retinal ON bipolar cells and, on the basis of its agonist selectivity, may have a key physiological role in certain inherited eye
diseases .
Large ribosomal subunit protein uL16, bacterial-type (Ribosomal_uL16_bact-type)
Type: Family

Ribosomal protein uL16 is one of the proteins from the large ribosomal subunit from bacteria and its homologues from chloroplast and mitochondria. In Escherichia coli, uL16 is known to bind directly the 23S rRNA and to be located at the A site of the peptidyltransferase centre. uL16 is a protein of 133 to 185 amino-acid residues.

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 .
Phosphoribosylglycinamide synthetase (PRibGlycinamide_synth)
Type: Family

Phosphoribosylglycinamide synthetase (

) (GARS) (phosphoribosylamine glycine ligase) catalyses the second step in the
de novo
biosynthesis of purine. The reaction catalysed by phosphoribosylglycinamide synthetase is the ATP-dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide:

ATP + 5-phosphoribosylamine + glycine = ADP + P
i
+ 5'-phosphoribosylglycinamide

In bacteria, GARS is a monofunctional enzyme (encoded by the purD gene). In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5,7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) . In higher eukaryotes, GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART), forming GARS-AIRS-GART .
High mobility group protein HMGA (HMGA)
Type: Family

This entry represents the HMGA family, whose members contain DNA-binding domains, also known as AT hooks due to their ability to interact with the narrow minor groove of AT-rich DNA sequences. They play an important role in chromatin organisation .

The high mobility group (HMG) proteins are the most abundant and ubiquitous nonhistone chromosomal proteins. They bind to DNA and to nucleosomes and are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair. They can be grouped into three families: HMGB (HMG 1/2), HMGN (HMG 14/17) and HMGA (HMG I/Y). The characteristic domains are: AT-hook for the HMGA family, the HMG Box for the HMGB family, and the nucleosome-binding domain (NBD) for the members of the HMGN family .
Kappa casein (Casein_kappa)
Type: Family

Kappa-casein is a mammalian milk protein involved in a number of important physiological processes . In the gut, the ingested protein is split into an insoluble peptide (para kappa-casein) and a soluble hydrophilic glycopeptide (caseinomacropeptide). Caseinomacropeptide is responsible for increased efficiency of digestion, prevention of neonate hypersensitivity to ingested proteins, and inhibition of gastric pathogens.
Granulin (Granulin)
Type: Domain

Metazoan granulins are a family of cysteine-rich peptides of about 6 Kd which may have multiple biological activity. A precursor protein (known as acrogranin) potentially encodes seven different forms of granulin (grnA to grnG) which are probably released by post-translational proteolytic processing. Granulins are evolutionary related to PMP-D1, a peptide extracted from the pars intercerebralis of migratory locusts . A schematic representation of the structure of a granulin is shown below:

xxxCxxxxxCxxxxxCCxxxxxxxxCCxxxxxxCCxxxxxCCxxxxxCxxxxxxCx

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

In plants a granulin domain is often associated with the C terminus of cysteine proteases belong to the MEROPS peptidase family C1, subfamily C1A (papain).
Histone-like DNA-binding protein (Hist_DNA-bd)
Type: Family

Bacteria synthesise a set of small, usually basic proteins of about 90 residues that bind DNA and are known as histone-like proteins . Examples include the HU protein in Escherichia coli which is a dimer of closely related alpha and beta chains and in other bacteria can be a dimer of identical chains. HU-type proteins have been found in a variety of eubacteria, cyanobacteria and archaebacteria, and are also encoded in the chloroplast genome of some algae . The integration host factor (IHF), a dimer of closely related chains which seem to function in genetic recombination as well as in translational and transcriptional control is found in enterobacteria and viral proteins include the African Swine fever virus protein Pret-047 (also known as A104R or LMW5-AR) .

The exact function of these proteins is not yet clear but they are capable of wrapping DNA and stabilising it from denaturation under extreme environmental conditions. The structure is known for one of these proteins . The protein exists as a dimer and two "β-arms" function as the non-specific binding site for bacterial DNA.