SII-SWORD/CoKE huggingface dataset:
Indoleamine 2,3-dioxygenase (Indolamine_dOase)
Type: Family

Indoleamine 2,3-dioxgyenase (IDO,

) is a cytosolic heme protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyses the conversion of tryptophan and other indole derivatives to kynurenines. It is widely distributed in human tissues, involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses . The degradative action of IDO on tryptophan leads to cell death by starvation of this essential and relatively scarce amino acid. Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells. IDO also acts as a suppressor of anti-tumor immunity and limits the growth of intracellular pathogens by depriving tryptophan. Elevated IDO1 expression is a hallmark of major viral infections including HIV, HBV, HCV or influenza and also of major bacteria infections . This enzyme has also been associated to protection of the fetus from maternal immune rejection . Indoleamine 2,3-dioxygenase from yeast (BNA2) plays a role in the cellular response to telomere uncapping . IDO is a heme-containing enzyme of about 400 amino acids. Site-directed mutagenesis showed His346 (

) to be essential for haem binding, indicating that this histidine residue may be the proximal ligand. Mutation of Asp274 also compromised the ability of IDO to bind haem, suggesting that Asp274 may coordinate to heme directly as the distal ligand or is essential in maintaining the conformation of the haem pocket .

There are two IDO enzyme catalysing the same reaction, IDO1 and IDO2 which differ in their affinity for tryptophan being IDO2 affinity for tryptophan much lower than that of IDO1. 50% of Caucasians harbor polymorphisms which abolish IDO2 enzymatic activity. IDO2 is expressed in human tumors in an inactive form, thus, tryptophan degradation is entirely provided by IDO1 in these cells . IDO2 may play a role as a negative regulator of IDO1 by competing for heme-binding with IDO1. ALthough low efficiency IDO2 enzymes have been conserved throughout vertebrate evolution, higher efficiency IDO1 enzymes are dispensable in many lower vertebrate lineages . It is suggested that IDO1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals.

Other proteins that are evolutionarily related to IDO include myoglobin from the red muscle of the archaeogastropodic molluscs, Nordotis madaka (Giant abalone) and Sulculus diversicolor . These unusual globins lack enzymatic activity but have kept the heme group.
Nebulin repeat (Nebulin_repeat)
Type: Repeat

The nebulin-like motif or nebulin repeat is a tandemly repeated actin-binding module of about 35 amino acids. The repeat is named after the nebulin protein, which is a large protein specific for vertebrate skeletal muscle that may regulate the length of thin filaments. Nebulin contains about 185 copies of the repeat and those in the central part of nebulin are organised into seven-module super-repeats, which seems to reflect an interaction with tropomysin/troponin . Nebulin repeats occur in metazoan actin-binding proteins, most of which are specific for muscle tissues. Most nebulin repeat proteins contain a C-terminal SH3 domain and/or a N-terminal LIM zinc-binding domain. The repeats in nebulin and nebulette bind filamentous actin (F-actin) and may also associate with tropomyosin and troponin. The nebulin repeat has a predicted α-helical secondary structure and contains a central conserved SXXXY motif .
Glycylpeptide N-tetradecanoyltransferase (NMT)
Type: Family

Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (

) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins . Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement .
Sec7 domain (Sec7_dom)
Type: Domain

Protein containing this domain are highly divergent in their overall sequence, however, they share a common region of roughly 200 amino acids known as the SEC7 domain . The 3D structure of the domain displays several α-helices . It was found to be associated with other domains involved in guanine nucleotide exchange (e.g., CDC25, Dbl) in mammalian guanine-nucleotide-exchange factors .

SEC7 domain containing proteins are guanine nucleotide exchange factors (GEFs) specific for the ADP-rybosylation factors (ARF), a Ras-like GTPases which is important for vesicular protein trafficking. These proteins can be divided into five families, based on domain organisation and conservation of primary amino acid sequence: GBF/BIG, cytohesins,eFA6, BRAGs, and F-box . They are found in all eukaryotes, and are involved in membrane remodelling processes throughout the cell .
Gcp-like domain (Gcp-like_dom)
Type: Domain

This domain was identified in proteins including Kae1 and Gcp (YgjD), which were originally thought to be endopeptidases belonging to the peptidase M22 family . However, there is a lack of experimental evidence to support peptidase activity as a general property, and this has not been confirmed in other orthologues . Recent research indicates that the Kae1 and Gcp proteins are involved in the biosynthesis of N6-threonylcarbamoyl adenosine, a universal modification found at position 37 of tRNAs that read codons beginning with adenine . This domain is also present in Bacillus subtilis YdiC and Escherichia coli YeaZ. These proteins have been recently renamed as TsaB, and have also been shown to be involved in N6-Threonylcarbamoylad enonsine (t(6)A) biosynthesis .
ZU5 domain (ZU5_dom)
Type: Domain

The ZU5 domain is a domain of 90-110 residues present in zona occludens 1 (ZO-1) protein, in unc5-like netrin receptors and in ankyrins. The ZU5 domain is named after the mouse tight junction protein ZO-1 and the C. elegans uncoordinated protein 5 (unc-5) and related Unc5-like netrin receptors. ZU5 domains are found in eukaryotic proteins that in most cases contain a C-terminal death domain. Other domains which can be found N-terminal to a ZU5 domain are ankyrin repeats; Ig-like and TSP1 repeats; PDZ, SH3 and guanylate kinase; or leucine-rich repeats (LRR) . The ZU5 domain can function as a spectrin-binding domain in ankyrins , and participates in induction of apoptosis and binding of melanoma-associated antigen D1 (MAGE-D1/NRAGE) in UNC5H1-3 .
Lipoxygenase (LipOase)
Type: Family

Lipoxygenases ([ec:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes . Sequence data is available for the following lipoxygenases:

Plant lipoxygenases (

). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme .

Mammalian arachidonate 5-lipoxygenase (

).

Mammalian arachidonate 12-lipoxygenase (

).

Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;

).

The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues . Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown to be important for the activity of lipoxygenases.
Acetylcholinesterase, fish/snake (Acylcholinesterase_fish/snake)
Type: Family

Cholinesterase enzymes are members of the broader alpha/beta hydrolase family and can be dividied into two distinct groups: those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases

)

acetylcholine + H
2
O ->choline + acetate

and those that catalyse the conversion of other acylcholines to a choline and a weak acid (cholinesterases

)

an acylcholine + H
2
O ->choline + a carboxylate

Acetylcholinesterase also acts on a variety of acetic esters and catalyses transacetylations. It is the most intensively studied of the cholinesterase enzymes due to its key physiological role in the turnover of the neurotransmitter acylcholine . This enzyme is found in, or attached to, cellular or basement membranes of presynaptic cholinergic neurons and postsynaptic cholinoceptive cells within the neuromuscular junction. Signal transmission at the neuromuscular junction involves the release of acylcholine, its interaction with the acycholine receptor and hydrolysis, all occuring in a period of a few milliseconds. Rapid hydrolysis of the newly released aceytlcholine is vital in order to prevent continuous firing of the nerve impulses . Consistent with its role in this process, acetylcholinesterase has an unusually high turnover number, ensuring that acetylcholine is broken down quickly. There is evidence to suggest that acetylcholinesterase has additional important roles including involvement in neuronal adhesion, the formation of Alzheimer fibrils, and neurite growth .
Phosphatidylinositol-specific phospholipase C, X domain (PLipase_C_PInositol-sp_X_dom)
Type: Domain

Phosphatidylinositol-specific phospholipase C, a eukaryotic intracellular enzyme, plays an important role in signal transduction processes . It catalyzes the hydrolysis of 1-phosphatidyl-D-myo-inositol-3,4,5-triphosphate into the second messenger molecules diacylglycerol and inositol-1,4,5-triphosphate. This catalytic process is tightly regulated by reversible phosphorylation and binding of regulatory proteins . In mammals, there are at least 6 different isoforms of PI-PLC, they differ in their domain structure, their regulation, and their tissue distribution. Lower eukaryotes also possess multiple isoforms of PI-PLC. All eukaryotic PI-PLCs contain two regions of homology, sometimes referred to as the 'X-box' and 'Y-box'. The order of these two regions is always the same (NH2-X-Y-COOH), but the spacing is variable. In most isoforms, the distance between these two regions is only 50-100 residues but in the gamma isoforms one PH domain, two SH2 domains, and one SH3 domain are inserted between the two PLC-specific domains. The two conserved regions have been shown to be important for the catalytic activity. By profile analysis, we could show that sequences with significant similarity to the X-box domain occur also in prokaryotic and trypanosome PI-specific phospholipases C. Apart from this region, the prokaryotic enzymes show no similarity to their eukaryotic counterparts.
Ribosomal protein uL11 (Ribosomal_uL11)
Type: Family

Ribosomal protein uL11, together with proteins L10 and L7/L12, and 23S rRNA, form the L7/L12 stalk on the surface of the large subunit of the ribosome. The homologous eukaryotic cytoplasmic protein uL11 was called in the past 60S ribosomal protein L12, which is distinct from the L12 involved in the formation of the L7/L12 stalk. The C-terminal domain (CTD) of uL11 is essential for binding 23S rRNA, while the N-terminal domain (NTD) contains the binding site for the antibiotics thiostrepton and micrococcin. uL11 and 23S rRNA form an essential part of the GTPase-associated region (GAR). Based on differences in the relative positions of the uL11 NTD and CTD during the translational cycle, uL11 is proposed to play a significant role in the binding of initiation factors, elongation factors, and release factors to the ribosome. Several factors, including the class I release factors RF1 and RF2, are known to interact directly with uL11. In eukaryotes, uL11 has been implicated in regulating the levels of ubiquinated p53 and MDM2 in the MDM2-p53 feedback loop, which is responsible for apoptosis in response to DNA damage. In bacteria, the "stringent response" to harsh conditions allows bacteria to survive, and ribosomes that lack uL11 are deficient in stringent factor stimulation .

Ribosomal protein uL11 (also known as L12 in mammals and yeast) is one of the proteins from the large ribosomal subunit. In Escherichia coli, uL11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial uL11; and mammalian, plant and yeast L12 (YL15). uL11 is a protein of 140 to 165 amino-acid residues and consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of uL11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA . In E. coli, the C-terminal half of uL11 has been shown to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.
Herpesvirus major capsid protein (Herpes_MCP)
Type: Family

The Herpesvirus major capsid protein (MCP) is the principal protein of the icosahedral capsid, forming the main component of the hexavalent and probably the pentavalent capsomeres. The capsid shell consists of 150 MCP hexamers and 12 MCP pentamers. One pentamer is found at each of the 12 apices of the icosahedral shell, and the hexamers form the edges and 20 faces . The MCP can be considered as having three domains: floor, middle and upper. The floor domains form a thin largely continuous layer, or shell, and are the only parts that interact directly to form intercapsomeric connections. They also interact with the internal scaffolding protein during capsid assembly . The remainder of the protein extends radially outward from the capsid producing the hexamer and pentamer capsomere structures. The middle domains are involved in binding to the triplexes that lie between and link adjacent capsomeres . The upper domains form the tops of the hexamer and pentamer towers and are the binding sites for the small capsid protein VP26 in the hexons and for tegument proteins in the pentons.
Neurokinin NK2 receptor (NK2_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 .

Neuropeptide receptors are present in very small quantities in the cell and are embedded tightly in the plasma membrane. The neuropeptides exhibit a high degree of functional diversity through both regulation of peptide production and through peptide-receptor interaction . The mammalian tachykinin system consists of 3 distinct peptides: substance P, substance K and neuromedin K. All possess a common spectrum of biological activities, including sensory transmission in the nervous system and contraction/ relaxation of peripheral smooth muscles, and each interacts with a specific receptor type.

In the periphery, NK2 receptors are found in smooth muscle of the respiratory, gastrointestinal and urogenital systems. NK2 receptors activate the phosphoinositide pathway through a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class.
Solute-binding protein family 5 domain (SBP_5_dom)
Type: Domain

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 domain found in the solute-binding protein family 5.

Family 5 members include:

Periplasmic oligopeptide-binding proteins (oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (oppA, amiA or appA)

Periplasmic dipeptide-binding proteins of Escherichia coli (dppA) and Bacillus subtilis (dppE)

Periplasmic murein peptide-binding protein of E. coli (mppA)

Periplasmic peptide-binding proteins sapA of E. coli, Salmonella typhimurium and Haemophilus influenzae

Periplasmic nickel-binding protein (nikA) of E. coli

Haem-binding lipoprotein (hbpA or dppA) from H. influenzae

Lipoprotein xP55 from Streptomyces lividans

Hypothetical proteins from H. influenzae (HI0213) and Rhizobium sp. (strain NGR234) symbiotic plasmid (y4tO and y4wM)

HTH-type transcriptional regulator SgrR from E. coli. The solute-binding domain is localised in its C-terminal .

Peptidoglycan-binding protein YepA from Agrobacterium fabrum
Large ribosomal subunit protein eL6 (60S_ribosomal_eL6)
Type: Family

This family represents large ribosomal subunit protein eL6 which are found in eukaryotes, including mammalian eL6 (which was previously known as L6 and TAX-responsive enhancer element binding protein 107 ) , Saccharomyces cerevisiae (Baker's yeast) ribosomal protein eL6A/B (also known as YL16A/YL16B); and Mesembryanthemum crystallinum (Common ice plant) eL6 (also known as YL16-like). These proteins have 175 (yeast) to 287 (mammalian) 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 .
Bet v I/Major latex protein (Bet_v_I/MLP)
Type: Domain

This domain is named after Bet v 1, the major birch pollen allergen. Bet v 1 belongs to family 10 of plant pathogenesis-related proteins (PR-10), cytoplasmic proteins of 15-17 kd that are wide-spread among dicotyledonous plants . In recent years, a number of diverse plant proteins with low sequence similarity to Bet v 1 was identified. A classification by sequence similarity yielded several subfamilies related to PR-10 :

Pathogenesis-related proteins PR-10: These proteins were identified as major tree pollen allergens in birch and related species (hazel, alder), as plant food allergens expressed in high levels in fruits, vegetables and seeds (apple, celery, hazelnut), and as pathogenesis-related proteins whose expression is induced by pathogen infection, wounding, or abiotic stress. Hyp-1 (

), an enzyme involved in the synthesis of the bioactive naphthodianthrone hypericin in St. John's wort (Hypericum perforatum) also belongs to this family. Most of these proteins were found in dicotyledonous plants. In addition, related sequences were identified in monocots and conifers.

Cytokinin-specific binding proteins: These legume proteins bind cytokinin plant hormones .

(S)-Norcoclaurine synthases are enzymes catalysing the condensation of dopamine and 4-hydroxyphenylacetaldehyde to (S)-norcoclaurine, the first committed step in the biosynthesis of benzylisoquinoline alkaloids such as morphine .

Major latex proteins and ripening-related proteins are proteins of unknown biological function that were first discovered in the latex of opium poppy (Papaver somniferum) and later found to be upregulated during ripening of fruits such as strawberry and cucumber .

The occurrence of Bet v 1-related proteins is confined to seed plants with the exception of a cytokinin-binding protein from the moss Physcomitrella patens (

).
Sulfatase, N-terminal (Sulfatase_N)
Type: Domain

This entry represents a domain found in sulphatases.