SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein bL36 (Ribosomal_bL36)
Type: Family

Ribosomal protein bL36 (also known as L36) is the smallest protein from the large subunit of the prokaryotic ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities can be grouped into: bacterial L36; algal and plant chloroplast L36; Cyanelle L36; fungal and animal L36. L36 is a small basic and cysteine-rich protein of around 40 amino-acid residues probably involved in late assembly of the 50S particle, in vitro translation and cell growth. This protein shows a zinc-binding CxxC motif. Its paralogue encoded by ykgO (as named in Escherichia coli), lacks the zinc-binding site and replaces RpmJ when zinc availability is low .

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 .
Retroviral Vif (Viral infectivity) protein (Vif)
Type: Family

The virion infectivity factor (vif) is an accessory protein, which is essential for HIV replication in host cells. Vif of Human immunodeficiency virus 1 (HIV-1) affects the infectivity of virus particles to T lymphocytes and macrophages (in some cases increasing the infectivity of HIV-1 particles by 100- to 1000-fold), but has no direct effect on transcription, translation or virus release. Vif antibodies are found in the sera of patients at all levels of HIV-1 infection, indicating that vif is expressed in natural infections
in vivo
. Other lentiviruses, including Simian immunodeficiency virus (SIV-cpz), Visna/Maedi virus, and Feline immunodeficiency virus (FIV), have vif open reading frames, suggesting vif plays an essential role during natural infections . The expression of vif in BHK-21 cells has been shown to be linked to a modification of the C terminus of gp41env, which modification is inhibited by trans-epoxysuccinyl-L-leucylamido-(4-guanidio)butane (E64), a specific inhibitor of cysteine proteases . Coupled with sequence analysis and the effects of point mutations in vif, it has been suggested that vif could be a cysteine protease. Virions produced in the absence of Vif have abnormal core morphology and those produced in primary T cells carry immature core proteins and low levels of mature capsid .

In humans, HIV-1 Vif hijacks cellular E3 ligase components containing CUL5, RBX2, ELOB, ELOC and CBFbeta, to poly-ubiquitinate antiviral cellular factors, APOBEC3 proteins . In sheep and goats, Caprine arthritis encephalitis virus (CAEV) Vif is responsible for degradation of oaA3Z2-Z3 .
Glycoprotein hormone alpha chain (Glyco_hormone)
Type: Family

Glycoprotein hormones (or gonadotropins) are a family of proteins, which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin(TSH) placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function . The hormones LH, FSH and TSH are secreted by the anterior pituitary gland, while hCG and eCG are secreted by the placenta . All these hormones consist of two glycosylated chains (alpha and beta). The alpha subunit is common to each protein dimer (well conserved within species, but differing between them ), and a unique beta subunit, which confers biological specificity . The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulphide bonds , as shown in the following schematic representation.

+---------------------------+
+----------+| +-------------|--+
| || | | |
xxxxCxCxxxxxxCxCCxxxxxxxxxxxxxCCxxxxxxxxxxCxCxxCx
| | | |
+------|-----------------+ |
| |
+----------------------------+

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

Intracellular levels of free alpha subunits are greater than those of the mature glycoprotein, implying that hormone assembly is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated .
Reverse transcriptase domain (RT_dom)
Type: Domain

The use of an RNA template to produce DNA, for integration into the host genome and exploitation of a host cell, is a strategy employed in the replication of retroid elements, such as the retroviruses and bacterial retrons. The enzyme catalysing polymerisation is an RNA-directed DNA-polymerase, or reverse trancriptase (RT) (

). Reverse transcriptase occurs in a variety of mobile elements, including retrotransposons, retroviruses, group II introns , bacterial msDNAs, hepadnaviruses, and caulimoviruses.

Retroviral reverse transcriptase is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. The discovery of retroelements in the prokaryotes raises intriguing questions concerning their roles in bacteria and the origin and evolution of reverse transcriptases and whether the bacterial reverse transcriptases are older than eukaryotic reverse transcriptases .

Several crystal structures of the reverse transcriptase (RT) domain have been determined .
Cation-independent mannose-6-phosphate receptor repeat (CIMR_rpt)
Type: Repeat

The cation-independent mannose-6-phosphate receptor is a multi-functional transmembrane glycoprotein whose major function is to bind and transport M6P-bearing glycoproteins from the trans-Golgi network or the cell surface to lysosomes. It appears to mediate the uptake and processing of M6P-containing cytokines and peptide hormones, such as transforming growth factor-beta, leukemia inhibitory factor, and proliferin . It also binds and internalizes the insulin-like growth factor II .
Glutelin (Glutelin)
Type: Family

Glutelins are major storage proteins that aggregate in protein bodies in the endosperm of Zea mays (Maize) . They comprise the second largest protein fraction in Maize endosperm (zeins being the largest), and show sequence similarities to other cereal storage proteins, such as gliadins, glutenins, hordeins, etc. Glutelins have a well-defined structure, including an N-terminal region containing varying numbers of repeats of the sequence PPPHVL ; a Gln rich region that can be separated into 2 domains; and a Cys rich C-terminal domain that shows some regions of internal similarity. Glutelins have been shown to exhibit structural similarity to other cereal storage proteins, including a beta-reverse turn region which forms a loose helix-like domain.
GPCR fungal pheromone B alpha receptor (GPCR_Pheromne_B_alpha_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 .

GPCR Fungal pheromone mating factor receptors form a distinct family of G-protein-coupled receptors, and are also known as Class D GPCRs.

The Fungal pheromone mating factor receptors STE2 and STE3 are integral membrane proteins that may be involved in the response to mating factors on the cell membrane . The amino acid sequences of both receptors contain high proportions of hydrophobic residues grouped into 7 domains,in a manner reminiscent of the rhodopsins and other receptors believed tointeract with G-proteins. However, while a similar 3D framework has been proposed to account for this, there is no significant sequence similarity either between STE2 and STE3, or between these and the rhodopsin-type family: the receptors thereofore bear their own unique '7TM' signatures which is why they have been given their own GPCR group: Class D Fungal mating pheromone receptors.

The STE3 gene in Saccharomyces cerevisiae is the cell-surface receptor that binds the 13-residue lipopeptide a-factor. Several related fungal pheromone receptor sequences are known: these include pheromone B alpha 1 and B alpha 3, and pheromone B beta 1 receptors from Schizophyllum commune; pheromone receptor 1 from Ustilago hordei; and pheromone receptors 1 and 2 from Ustilago maydis. Members of the family share about 20% sequence identity.

The multiallelic mating type locus B alpha-1 of S. commune encodes a pheromone receptor and putative pheromone genes . Analysis of this locus has provided evidence that pheromones and pheromone receptors govern recognition of self versus non-self, and sexual development in this homobasidiomycetous fungus .

This entry represents pheromone B alpha type receptors.
5-Hydroxytryptamine 2B receptor (5HT2B_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.

The 5-HT2 receptors mediate many of the central and peripheral physiologic functions of 5-hydroxytryptamine. The original 5HT2 receptor (now renamed as the 5-HT2A receptor) was initially classified according to its ability to display micromolar affinity for 5-HT, to be labelled with [3H]spiperone and by its susceptibility to 5-HT antagonists. At least 3 members of the 5HT2 receptor subfamily exist (5-HT2A, 5-HT2B, 5-HT2C), all of which share a high degree of sequence similarity and couple to Gq/G11 to stimulate the phosphoinositide pathway and elevate cytosolic calcium. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitisation to tactile stimuli and mediation of some of the effects of phenylisopropylamine hallucinogens. 5-HT2 receptors display functional selectivity in which the same agonist in different cell types or different agonists in the same cell type can differentially activate multiple, distinct signalling pathways .

The 5-HT2B receptor has been shown to be distributed in a range of tissues, including human gut, brain and the cardiovascular system . In the cardiovascular system the 5-HT2B receptor regulates cardiac structure and function . 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valve fibroblasts , which, with chronic overstimulation, can lead to a severe valvulopathy. In addition, the 5-HT2B receptor has been shown to be involved in pulmonary hypertension via vasoconstriction . As a result 5-HT2B antagonists have been developed as treatments for chronic heart disease . In the CNS the 5-HT2B receptor has been shown to be involved in presynaptic inhibition, leading to behavioural effects , since it is important to the normal regulation of serotonin levels in the blood plasma and abnormal release produced by drugs such as MDMA .
Cysteine-rich flanking region, C-terminal (Cys-rich_flank_reg_C)
Type: Domain

Leucine-rich repeats (LRR, see

) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape . LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions . Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response.

LRRs are often flanked by cysteine-rich domains: an N-terminal LRR domain (

) and a C-terminal LRR domain. This entry represents the C-terminal LRR domain.
AsnC-type HTH domain (AsnC-type_HTH_dom)
Type: Domain

The asnC-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 60 amino acids present in transcription regulators of the asnC/lrp family. This family of prokaryotic regulators is named after Escherichia coli asnC and Leucine-responsive Regulatory Protein (lrp), which are a regulator of asparagine synthesis and a global regulator of various operons, respectively . AsnC/lrp-like proteins are present in bacteria and archaea . The DNA-binding asnC-type HTH domain occurs usually in the N-terminal part. The C-terminal part can contain an effector-binding domain and/or an oligomerisation domain.
Extradiol ring-cleavage dioxygenase, class I /II (Xdiol_ring_cleave_dOase_1/2)
Type: Conserved_site

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes (

) use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) . These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues. Extradiol dioxygenases are usually homo-multimeric, bind one atom of ferrous ion per subunit and have a subunit size of about 33kDa. Extradiol dioxygenases can be divided into three classes. Class I and II enzymes show sequence similarity, with the two-domain class II enzymes having evolved from a class I enzyme through gene duplication. As a result, the class II enzymes are composed of two domains with approximately the same folding pattern as each other. Class III enzymes (

,

) are different in sequence and structure, but they do share several common active-site characteristics with the class II enzymes, in particular the coordination sphere and the disposition of the putative catalytic base are very similar. This entry represents the dioxygenase domain found in class I and class II extradiol enzymes.

Enzymes that belong to the extradiol class II family include catechol 2,3-dioxygenase (2,3-CTD) (

) and biphenyl-2,3-diol 1,2-dioxygenase (BphC) (

).
Non-structural protein NS2B, flavivirus (Flavi_NS2B)
Type: Domain

Pathogenic members of the flavivirus family [E1], including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The genome encodes three structural proteins found in the mature virion (C, prM, and E) and seven "non-structural" (i.e., not part of the virion architecture) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) . Full-length NS3 is a bifunctional protein. The N-terminal 175 residues comprise a chymotrypsin-like protease, "NS3pro", while the C-terminal portion is a helicase ("NS3hel"). The NS2B protein, which is located in the polypeptide precursor immediately upstream of the NS3pro domain, functions as the cofactor for NS3pro. A 35-48 residue central portion is required for protease activity in vitro, while N- and C-terminal flanking hydrophobic regions are predicted to anchor the NS2B-NS3 complex into the host endoplasmic reticulum membrane. The two component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication . The NS3pro domain forms peptidase family S7 (flavivirus family) of clan PA [E2].

The NS3pro has a classical serine protease catalytic triad (His, Asp, and Ser). The enzymatic activity of NS3pro is enhanced by interacting with the
central 40 amino acid of NS2B which acts as an essential cofactor. The NS3pro domain has an overall structure of two barrels made of six β-sheets each, with the active site located in the cleft between the barrels. The NS2B hydrophilic core cofactor contributes one of the N-terminal β-sheets .

This entry represents NS2B protein.
Death domain (Death_dom)
Type: Domain

The death domain (DD) is a homotypic protein interaction module composed of a bundle of six α-helices. DD is related in sequence and structure to the death effector domain (DED, see

) and the caspase recruitment domain (CARD, see

), which work in similar pathways and show similar interaction properties . DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins . Within these proteins, the DD domains can be found in combination with other domains, including: CARDs, DEDs, ankyrin repeats (

), caspase-like folds, kinase domains, leucine zippers, leucine-rich repeats (LRR) (

), TIR domains (

), and ZU5 domains (

) .

Some DD-containing proteins are involved in the regulation of apoptosis and inflammation through their activation of caspases and NF-kappaB, which typically involves interactions with TNF (tumour necrosis factor) cytokine receptors . In humans, eight of the over 30 known TNF receptors contain DD in their cytoplasmic tails; several of these TNF receptors use caspase activation as a signalling mechanism. The DD mediates self-association of these receptors, thus giving the signal to downstream events that lead to apoptosis. Other DD-containing proteins, such as ankyrin, MyD88 and pelle, are probably not directly involved in cell death signalling. DD-containing proteins also have links to innate immunity, communicating with Toll family receptors through bipartite adapter proteins such as MyD88 .
Pterin-binding domain (Pterin-binding_dom)
Type: Domain

The ~250-residue pterin-binding domain has been shown to adopt a (β/α)8 barrel fold, which has the overall shape of a distorted cylinder. It has eight α-helices stacked around the outside of an inner cylinder of parallel β-strands. The pterin ring binds at the bottom of the (β/α)8 barrel in a polar cup-like region that is relatively solvent exposed and fairly negatively charged. The pterin ring is partially buried within the (β/α)8 barrel. The pterin binding residues are highly conserved and include aspartate and asparagine residues located at the C terminus of the β-strands of the barrel, which are predicted to form hydrogen bonds with the nitrogen and oxygen atoms of the pterin ring .

Some proteins known to contain a pterin-binding domain are listed below:

Prokaryotic and eukaryotic B12-dependent methionine synthase (MetH) (

), a large, modular protein that catalyses the transfer of a methyl group from methyltetrahydrofolate (CH3-H4folate) to Hcy to form methionine, using cobalamin as an intermediate methyl carrier.

Prokaryotic and eukaryotic dihydropteroate synthase (DHPS) (

). It catalyses the condensation of para-aminobenzoic acid (pABA) with 7,8-dihydropterin-pyrophosphate (DHPPP), eliminating pyrophosphate to form 7,8-dihydropteroate which is subsequently converted to tetrahydrofolate.

Moorella thermoacetica 5-methyltetrahydrofolate corrinoid/iron sulphur protein methyltransferase (MeTr). It transfers the N5-methyl group from CH3-H4folate to a cob(I)amide centre in another protein, the corrinoid iron sulphur protein.
Glycoside hydrolase family 17 (Glyco_hydro_17)
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 17

comprises enzymes with several known activities; endo-1,3-beta-glucosidase (

); lichenase (

); exo-1,3-glucanase (

). Currently these enzymes have only been found in plants and in fungi.
Inhibin, beta A subunit (Inhibin_betaA)
Type: Family

Inhibins and activins are glycoproteins, secreted by the gonads, that belong to the transforming growth factor beta family . They participate in differentiation and growth of diverse cell types. Inhibin inhibits secretion of follicle-stimulating hormone by the pituitary .

Inhibin has two isoforms, A and B, with the same alpha subunit but different beta subunits. Inhibin A is a dimer of alpha and beta A subunits, inhibin B is a dimer of alpha and beta B subunits.

Activin A is a dimer of beta A subunits, activin AB is a dimer of beta A and beta B chains.