SII-SWORD/CoKE huggingface dataset:
3-dehydroquinate dehydratase type I (DHquinase_I)
Type: Family

3-dehydroquinate dehydratase (

), or dehydroquinase, catalyzes the conversion of 3-dehydroquinate into 3-dehydroshikimate. It is the third step in the shikimate pathway for the biosynthesis of aromatic amino acids from chorismate. Two classes of dehydroquinases exist, known as types I and II. The best studied type I enzyme is from Escherichia coli (gene aroD) and related bacteria where it is a homodimeric protein. In fungi, dehydroquinase is part of a multifunctional enzyme which catalyses five consecutive steps in the shikimate pathway. A histidine is involved in the catalytic mechanism.

This entry represents the 3-dehydroquinate dehydratase, type I, either as a monofunctional protein or as a domain of a larger, multifunctional protein.
Glycoside hydrolase family 47 (Glyco_hydro_47)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 47

comprises enzymes with only one known activity; alpha-mannosidase (

).

Alpha-mannosidase is involved in the maturation of Asn-linked oligo-saccharides . The enzyme hydrolyses terminal 1,2-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide man(9)(glcnac)(2) in a calcium-dependent manner. The mannose residues are trimmed away to produce, first, man(8)glcnac(2), then a man(5)(glcnac)(2) structure.
Large ribosomal subunit protein bL28, bacterial-type (Ribosomal_bL28_bact-type)
Type: Family

The ribosomal bL28 protein family include proteins from bacteria (also known as L28) and chloroplasts (bL28c).

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 .
Peptidase M35, deuterolysin (Peptidase_M35)
Type: Family

This group of metallopeptidases belong to MEROPS peptidase family M35 (deuterolysin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.

Deuterolysin is a microbial zinc-containing metalloprotease that shows some similarity to thermolysin . The protein is expressed with a possible 19-residue signal sequence, a 155-residue propeptide, and an active peptide of 177 residues . The latter contains an HEXXH motif towards the C terminus, but the other zinc ligands are as yet undetermined .

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
Rotavirus A/C, major capsid protein VP6 (Rotavirus_A/C_VP6)
Type: Family

Rotaviruses consist of three concentric protein shells. The intermediate (middle) protein layer contains VP6, the major internal structural protein. VP6 is the most abundant protein in the virion and is involved in virion assembly, VP6 possesses the ability to interact with VP2, VP4 and VP7 .
Cro/C1-type, helix-turn-helix domain (Cro/C1-type_HTH)
Type: Domain

The cro/C1-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in transcriptional regulators. The domain is named after the transcriptional repressors cro and C1 of temperate bacteriophages 434 and lambda, respectively. Besides in bacteriophages, cro/C1-type regulators are present in prokaryotes and in eukaryotes. The helix-turn-helix DNA-binding motif is generally located in the N-terminal part of these transcriptional regulators. The C-terminal part may contain an oligomerization domain, e.g. C1 repressors and CopR act as dimers, while SinR is a tetramer. The cro/C1-type HTH domain also occurs in combination with the TPR repeat and the C-terminal part of C-5 cytosine-specific DNA methylases contains regions related to the enzymatic function.

Several structures of cro/C1-type transcriptional repressors have been resolved and their DNA-binding domain encompasses five α-helices, of which the extremities are less conserved . The helix-turn-helix motif comprises the second and third helices, the third being called the recognition helix. The HTH is involved in DNA-binding into the major groove, where the recognition helix makes most DNA-contacts. The bacteriophage repressors regulate lysogeny/lytic growth by binding with differential affinity to the operators. These operators show 2-fold symmetry and the repressors bind as dimers. Binding of the repressor to the operator positions the DNA backbone into a slightly bent twist .
Synaptobrevin-like (Synaptobrevin-like)
Type: Family

Synaptobrevin is an intrinsic membrane protein of small synaptic vesicles , specialised secretory organelles of neurons that actively accumulate neurotransmitters and participate in their calcium-dependent release by exocytosis. Vesicle function is mediated by proteins in their membranes, although the precise nature of the protein-protein interactions underlying this are still uncertain . Synaptobrevin may play a role in the molecular events underlying neurotransmitter release and vesicle recycling and may be involved in the regulation of membrane flow in the nerve terminal, a process mediated by interaction with low molecular weight GTP-binding proteins . Synaptic vesicle-associated membrane proteins (VAMPs) from Torpedo californica (Pacific electric ray) and SNC1 from yeast are related to synaptobrevin.
Flocculin (Flocculin)
Type: Repeat

Yeast flocculation protein may be directly involved in the flocculation process . The extensively O-glycosylated protein is probably attached to the membrane by a GPI-anchor.
Opsin lateral eye type (Opsin_lateye)
Type: Family

Opsins are the photoreceptors of animal retinas: vertebrate rhodopsin is found in rod cells and mediates scotopic vision; red, green and blue opsins are found in cone cells and mediate photopic vision. The opsins from the lateral eyes and median ocelli of the horseshoe crab, Limulus polyphemus, are likely to be the visible-wavelength rhodopsins in this animal . In the lateral eye, expression of the opsin gene is restricted to the photoreceptor cells of the ommatidia . Limulus opsins, and closely-related crayfish, mantid and honeybee rhodopsins, are most similar to the opsin from the R1-6 photoreceptors of flies.
Clathrin adaptor, mu subunit (Clathrin_mu)
Type: Family

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport . Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors .

AP (adaptor protein) complexes are found in coated vesicles and clathrin-coated pits. AP complexes connect cargo proteins and lipids to clathrin at vesicle budding sites, as well as binding accessory proteins that regulate coat assembly and disassembly (such as AP180, epsins and auxilin). There are different AP complexes in mammals. AP1 is responsible for the transport of lysosomal hydrolases between the TGN and endosomes . AP2 associates with the plasma membrane and is responsible for endocytosis . AP3 is responsible for protein trafficking to lysosomes and other related organelles . AP4 is less well characterised. AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). For example, in AP1 these subunits are gamma-1-adaptin, beta-1-adaptin, mu-1 and sigma-1, while in AP2 they are alpha-adaptin, beta-2-adaptin, mu-2 and sigma-2. Each subunit has a specific function. Adaptins recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal ear (appendage) domains. Mu recognises tyrosine-based sorting signals within the cytoplasmic domains of transmembrane cargo proteins . One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABA(A) receptors available at the cell surface .

This entry represents the mu subunit of various clathrin adaptors (AP1, AP2 and AP3) . The mu subunit regulates the coupling of clathrin lattices with particular membrane proteins by self-phosphorylation via a mechanism that is still unclear . The mu subunit possesses a highly conserved N-terminal domain of around 230 amino acids, which may be the region of interaction with other AP proteins; a linker region of between 10 and 42 amino acids; and a less well-conserved C-terminal domain of around 190 amino acids, which may be the site of specific interaction with the protein being transported in the vesicle .
Calsequestrin (Calsequestrin)
Type: Family

Calsequestrin is the principal calcium-binding protein present in the sarcoplasmic reticulum of cardiac and skeletal muscle . It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internal calcium store in muscle. Sequence analysis has suggested that calcium is not bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface.

Two forms of calsequestrin have been identified. The cardiac form is present in cardiac and slow skeletal muscle and the fast skeletal form is found in fast skeletal muscle. The release of calsequestrin-bound calcium (through a a calcium release channel) triggers muscle contraction. The active protein is not highly structured, more than 50% of it adopting a random coil conformation . When calcium binds there is a structural change whereby the α-helical content of the protein increases from 3 to 11% . Both forms of calsequestrin are phosphorylated by casein kinase II, but the cardiac form is phosphorylated more rapidly and to a higher degree .
Metallothionein, family 4, echinoidea (Metalthion_4_echinoidea)
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 . An empirical classification into three classes has been proposed by Fowler and coworkers and Kojima . Members of class I are defined to include polypeptides related in the positions of their cysteines to equine MT-1B, and include mammalian MTs as well as from crustaceans and molluscs. Class II groups MTs from a variety of species, including sea urchins,
fungi, insects and cyanobacteria. Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units .

This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Subsequently, a new classification was proposed on the basis of sequence similarity derived from phylogenetic relationships, which basically proposes an MT family for each main taxonomic group of organisms .

Echinoidea (sea urchin, family 4) MTs are 64-67 residue proteins. Members of this family are recognised by the sequence pattern P-D-x-K-C-[V,F]-C-C-x(5)-C-x-C-x(4)-C-C-x(4)-C-C-x(4,6)-C-C located near the N terminus.
The taxonomic range of the members extends to sea urchins (echinodea).
The protein sequence is divided into two structural domains, each containing 9 and 11 Cys residues binding 3 and 4 bivalent metal ions, respectively.
Family 4 includes subfamilies: e1, e2, they are separate phylogenetic groups.
5-Hydroxytryptamine 5A receptor (5HT5A_rcpt)
Type: Family

5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics .

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel , all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family , and they activate an intracellular second messenger cascade to produce their responses.

This entry represents the 5-HT5A receptor, which couples to G proteins and negatively influences cAMP . It has also been shown to function, in part, through the regulation of intracellular Ca2+ mobilisation . In the CNS, the 5-HT5A receptor is found in the cerebral cortex, hippocampus, habenula, olfactory bulb and granular layer of the cerebellum . It may play a role in sleep and serve as an presynaptic serotonin autoreceptor .
Macrophage migration inhibitory factor (Macrophage_inhib_fac)
Type: Family

Macrophage migration inhibitory factor (MIF) is a key regulatory cytokine within innate and adaptive immune responses, capable of promoting and modulating the magnitude of the response . MIF is released from T-cells and macrophages, and acts within the neuroendocrine system. MIF is capable of tautomerase activity, although its biological function has not been fully characterised. It is induced by glucocorticoid and is capable of overriding the anti-inflammatory actions of glucocorticoid . MIF regulates cytokine secretion and the expression of receptors involved in the immune response. It can be taken up into target cells in order to interact with intracellular signalling molecules, inhibiting p53 function, and/or activating components of the mitogen-activated protein kinase and Jun-activation domain-binding protein-1 (Jab-1) . MIF has been linked to various inflammatory diseases, such as rheumatoid arthritis and atherosclerosis .

The MIF homologue D-dopachrome tautomerase (

) is involved in detoxification through the conversion of dopaminechrome (and possibly norepinephrinechrome), the toxic quinine product of the neurotransmitter dopamine (and norepinephrine), to an indole derivative that can serve as a precursor to neuromelanin .
VP6 blue-tongue virus inner capsid protein (Orbi_VP6)
Type: Family

Bluetongue virus VP6 protein binds ATP and exhibits an RNA-dependent ATPase function and a helicase activity that catalyses the unwinding of double-stranded RNA substrates . VP6 from five United States prototype bluetongue virus (BTV) serotypes contain unusually high concentrations of glycine, few aromatic amino acids, but a high concentration of charged amino acids, a characteristic of hydrophilic proteins .

VP6 is an inner capsid protein that surrounds the genomic DS-RNA. Its hydrophilic nature coupled with a capability to bind ss-and ds-RNA, suggests that it interacts directly with the BTV genomic RNA.
Somatotropin/prolactin (Somatotropin/Prolactin)
Type: Family

Somatotropin is a hormone that plays an important role in growth control. It belongs to a family that includes choriomammotropin (lactogen), its placental analogue; prolactin, which promotes lactation in the mammary gland, and placental prolactin-related proteins; proliferin and proliferin related protein; and somatolactin from various fish .
The 3D structure of bovine somatotropin has been predicted using a combination of heuristics and energy minimisation .
Dynamin, GTPase domain (Dynamin_GTPase)
Type: Domain

Membrane transport between compartments in eukaryotic cells requires proteins that allow the budding and scission of nascent cargo vesicles from one compartment and their targeting and fusion with another. Dynamins are large GTPases that belong to a protein superfamily that, in eukaryotic cells, includes classical dynamins, dynamin-like proteins, OPA1, Mx proteins, mitofusins and guanylate-binding proteins/atlastins , and are involved in the scission of a wide range of vesicles and organelles. They play a role in many processes including budding of transport vesicles, division of organelles, cytokinesis and pathogen resistance.

The minimal distinguishing architectural features that are common to all dynamins and are distinct from other GTPases are the structure of the large GTPase domain (300 amino acids) and the presence of two additional domains; the middle domain and the GTPase effector domain (GED), which are involved in oligomerisation and regulation of the GTPase activity.

This entry represents the GTPase domain, containing the GTP-binding motifs that are needed for guanine-nucleotide binding and hydrolysis. The conservation of these motifs is absolute except for the the final motif in guanylate-binding proteins. The GTPase catalytic activity can be stimulated by oligomerisation of the protein, which is mediated by interactions between the GTPase domain, the middle domain and the GED.
Parvovirus coat protein VP2 (Parvovirus_coat)
Type: Domain

Parvoviruses are some of the smallest viruses containing linear, non-segmented single-stranded DNA genomes, with an average genome size of 5000 nucleotides. Parvoviruses have been described that infect a wide range of invertebrates and vertebrates and are well known for causing enteric disease in mammals. Genomes contain two large ORFs: NS1 and VP1; other ORFs are found in some sub-types and different gene products can arise from splice variants and the use of different start codons .

The Parvovirus coat protein VP1 together with VP2 forms a capsomer. Both of these proteins are formed from the same transcript using alternative translation start codons. As a result, VP1 and VP2 differ only in the N terminus region. VP2 is involved in packaging the viral DNA . The mature viron contains three capsid proteins VP1, VP2, and VP3 and a noncapsid protein NS1. VP3 may arise from a third start codon with a favorable translation initiation context which is present at position 3067 in the ChPV genome and which has been described in the goose and Muscovy duck parvoviruses .
Heat shock protein Hsp90 family (Hsp90_fam)
Type: Family

Molecular chaperones, or heat shock proteins (Hsps) are ubiquitous proteins that act to maintain proper protein folding within the cell . They assist in the folding of nascent polypeptide chains, and are also involved in the refolding of denatured proteins following proteotoxic stress. As their name implies, the heat shock proteins were first identified as proteins that were up-regulated under conditions of elevated temperature. However, subsequent studies have shown that increased Hsp expression is induced by a variety of cellular stresses, including oxidative stress and inflammation. Five major Hsp families have been determined, and are categorized according to their molecular size (Hsp100, Hsp90, Hsp70, Hsp60, and the small Hsps). Hsps are involved in a variety of cellular processes that are ATP-dependent. These include: prevention of protein aggregation, protein degradation, protein trafficking, and maintenance of signalling proteins in a conformation that permits activation.

Hsp90 chaperones are unique in their ability to regulate a specific subset of cellular signalling proteins that have been implicated in disease processes, including intracellular protein kinases, steroid hormone receptors, and growth factor receptors .
Uncharacterised protein family UPF0758 (UPF0758)
Type: Family

The function of this family of proteins is not known. A member of this family, YicR, formerly called RadC , is a putative JAMM-family deubiquitinating enzyme .