SII-SWORD/CoKE huggingface dataset:
Pseudouridine synthase I, TruA (PsdUridine_synth_TruA)
Type: Family

This entry represents pseudouridine synthase I (TruA) from prokaryotes and tRNA pseudouridine synthase 1 (Pus1) from eukaryotes, which belongs to the TruA family. TruA from Escherichia coli modifies positions uracil-38, U-39 and/or U-40 in tRNA . TruA contains one atom of zinc essential for its native conformation and tRNA recognition and has a strictly conserved aspartic acid that is likely to be involved in catalysis . This protein adopts a dimeric assembly and shows two positively charged, RNA-binding clefts along their surface. Each cleft contains a highly conserved aspartic acid located at its centre. The structural domains have a topological similarity to those of other RNA-binding proteins, though the mode of interaction with tRNA appears to be unique. Pus1 from Saccharomyces cerevisiae acts at positions 27 and 28 of tRNAs, at positions 34 and 36 of intron-containing precursor tRNA(Ile), at position 35 in the intron-containing tRNA(Tyr) and at position 44 in U2 snRNA . This enzyme also catalyses pseudouridylation of mRNAs .

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.
Influenza RNA-dependent RNA polymerase subunit PB1 (RNA_pol_PB1_influenza)
Type: Family

Influenza RNA-dependent RNA polymerase is composed of three subunits;
P1 (or PB1), P2 (or PA), and P3 (or PB2).
There are two separate domains in the influenza virus PB1 protein involved in the interaction with the PB2 and PA subunits . PB1 is the core of the complex and accounts for the polymerase activity .
Aminoacyl-tRNA synthetase, class I, conserved site (aa-tRNA-synth_I_CS)
Type: Conserved_site

This entry represents a conserved sequence in their N-terminal section of class I aminoacyl-tRNA synthetases.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
Dopamine D1 receptor (Dopamine_D1_rcpt)
Type: Family

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

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

This entry represents the dopamine D1 receptor, also known as D(1A) dopamine receptor. The receptors are found in greatest abundance in the caudate-putamen, nucleus accumbens and olfactory tubercle, with lower levels in the frontal cortex, habenula, amygdala, hypothalamus and thalamus. In the periphery, binding sites are found in the kidney, heart, liver and parathyroid gland. In humans, the pulmonary artery expresses D1, D2, D4, and D5 receptor subtypes, which may account for vasodilatory effects of dopamine in the blood . In rats, dopamine D1 receptors are present on the smooth muscle of the blood vessels in most major organs and have been shown to have vasodilation effects . They are also present on the juxtaglomerular apparatus and on renal tubules .
G-protein coupled receptor 143 (GPR143)
Type: Family

G-protein coupled receptor 143 (also known as ocular albinism type 1, OA1) is a receptor for tyrosine, L-DOPA and dopamine. After binding to L-DOPA, it stimulates Ca2+ influx into the cytoplasm, increases secretion of the neurotrophic factor SERPINF1 and relocalises beta arrestin at the plasma membrane; this ligand-dependent signaling occurs through a G(q)-mediated pathway in melanocytic cells .
Parathyroid hormone/parathyroid hormone-related protein (PTH/PTH-rel)
Type: Family

Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Parathyroid hormone-related protein (PTH-rP) is structurally related to PTH and seems to play a physiological role in lactation, possibly as a hormone for the mobilisation and/or transfer of calcium to the milk. It also regulates chondrocytic differentiation and endochondral bone formation .

PTH and PTH-rP bind to the same G-protein coupled receptor.

This entry represents parathyroid hormone and parathyroid hormone-related protein.
Atypical chemokine receptor 3 (ACKR3)
Type: Family

Just like classical chemokine receptors, atypical chemokine receptors (ACKRs) are seven-transmembrane-helix (7TM) receptors that bind chemokines . However, they lack the canonical DRYLAIV motif necessary for GPCR coupling to G proteins and induction of classical signalling pathways. Instead, ACKRs internalise their chemokine ligands, which may subsequently affect chemokine availability. The ACKR family comprises five members: Duffy Antigen Receptor for Chemokines (DARC, ACKR1), D6 (ACKR2), CXCR7 (ACKR3), CCRL1 (ACKR4) and CCRL2 (ACKR5) .

Atypical chemokine receptor 3 (ACKR3), previously known as CXC chemokine receptor 7 (CXCR7), is regarded as a scavenger for CXCL12 and, to a lesser extent, for CXCL11 . Unlike other CXC chemokine receptors, ACKR3 does not elicit classical chemokine receptor signalling via typical G protein-mediated pathways , but instead induces beta-arrestin recruitment, leading to ligand internalisation and activation of MAPK signaling pathway .

ACKR3/CXCR7 has been identified on memory B cells and in mammals is found in bone, brain, heart and kidney . It has been shown to act as a novel coreceptor for several immunodeficiency virus strains, which infect brain-derived cells . Studies in zebrafish have also revealed a critical role in vascular formation and angiogenesis during development . ACKR3/CXCR7 is a functional receptor for CXCL12 in astrocytomas/glioblastomas and mediates resistance to drug-induced apoptosis . It has been shown to promote growth of tumors formed from breast and lung cancer cells .
Opioid receptor (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. The receptors are found in the CNS and certain smooth muscles: mu-opioid receptors are believed to mediate analgesia, hypothermia, respiratory depression, miosis, bradycardia, nausea, euphoria and physical dependence, beta-endorphin being the most potent endogenous ligand; delta-receptors mediate analgesia; and kappa-opioid receptors are believed to mediate analgesia, sedation, miosis and diuresis, dynorphin being the most potent endogenous ligand.

A human placental protein that binds opioid ligands with moderate affinity has been provisionally classified as an opioid receptor. However, it is not selective for kappa-ligands and is 93% similar to the human NK3 tachykinin receptor, although it doesn't bind tachykinins.
HMW glutenin (Glutenin)
Type: Family

Gluten is the protein component of wheat flour. It consists of numerous proteins, which are of two different types responsible for different physical properties of dough: the glutenins, which are primarily responsible for the elasticity, and the gliadins, which contribute to the extensibility.

The glutenins are of two different types, termed low (LMW) and high molecular weight (HMW) subunits . The glutenin high molecular weight subunits are classified as elastomeric proteins, because the glutenin network can withstand significant deformations without breaking, and return to the original conformation when the stress is removed. Elastomeric proteins differ considerably in amino acid sequence, but they are all polymers whose subunits consist of elastomeric domains, composed of repeated motifs, and non-elastic domains that mediate cross-linking between the subunits. The elastomeric domain motifs are all rich in glycine residues in addition to other hydrophobic residues. High molecular weight glutenin subunits have an extensive central elastomeric domain, flanked by two terminal non-elastic domains that form disulphide cross-links. The central elastomeric domain is characterised by the following three repeated motifs: PGQGQQ, GYYPTS[P/L]QQ, GQQ. It possesses overlapping β-turns within and between the repeated motifs, and assumes a regular helical secondary structure with a diameter of approx. 1.9 nm and a pitch of approx. 1.5 nm .
X opioid receptor (X_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. The receptors are found in the CNS and certain smooth muscles: mu-opioid receptors are believed to mediate analgesia, hypothermia, respiratory depression, miosis, bradycardia, nausea, euphoria and physical dependence, beta-endorphin being the most potent endogenous ligand; delta-receptors mediate analgesia; and kappa-opioid receptors are believed to mediate analgesia, sedation, miosis and diuresis, dynorphin being the most potent endogenous ligand.

The X-receptor is closely related to opioid receptors, on grounds of both sequence and function, although it is not a typical opioid receptor . X-receptors are found in many regions of the brain and spinal cord, particularly limbic and hypothalamic structures. They are believed to represent a new class of opioid receptors, with a potential role in modulating various brain functions, including instinctive behaviours and emotions .
ATP synthase protein 8, metazoa (ATP8_metazoa)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

This entry represents subunit 8 found in the F0 complex of mitochondrial F-ATPases from Metazoa. This subunit appears to be an integral component of the stator stalk in yeast mitochondrial F-ATPases . The stator stalk is anchored in the membrane, and acts to prevent futile rotation of the ATPase subunits relative to the rotor during coupled ATP synthesis/hydrolysis. This subunit may have an analogous function in Metazoa. Subunit 8 differs in sequence between Metazoa, plants (

) and fungi (

).
Neuromodulin (Neuromodulin)
Type: Family

Neuromodulin (also known as growth-associated protein 43 or GAP-43) is a component of the motile growth cones. It is membrane protein whose expression is widely correlated with successful axon elongation . It is a crucial component of an effective regeneration response in the nervous system . Although its function is uncertain, the N-terminal region is well conserved and contains both a calmodulin binding domain, and sites for acylation, membrane attachment and protein kinase C phosphorylation. Structure predictions suggest that the C-terminal region may exist as an extended, negatively-charged rod with some similarity to the side arms of neurofilaments, indicating that the biological role of neuromodulin may depend on its ability to form a dynamic membrane-cytoplasm-calmodulin complex .
Lysophospholipase patatin, conserved site (LysoPLipase_patatin_CS)
Type: Conserved_site

Lysophospholipase NTE1 was identified in yeast as an endoplasmic reticulum integral membrane protein that acts as a phospholipase B, catalysing the double deacylation of phosphatidylcholine to glycerophosphocholine . Phosphatidylcholine is the major phospholipid component of eukaryotic membranes. NTE1 plays an important role in membrane lipid homeostasis, and is responsible for the rapid phosphatidylcholine turnover in response to inositol, elevated temperatures, or when choline is present in the growth medium. NTE1-mediated phosphatidylcholine deacylation is strongly affected by Sec14p, a component of the yeast secretory machinery involved in lipid metabolism and vesicular trafficking.

The mammalian and Drosophila homologues of NTE1, neuropathy target esterase and swiss cheese, respectively, have been implicated in normal brain development . The absence of these proteins is associated with increased cytoplasmic vesicularisation and multi-layered membrane stacks.

NTE1 contains two cyclic nucleotide-binding domains and a patatin domain. This entry represents the patatin domain.
Superoxide dismutase, copper/zinc binding domain (SOD_Cu_Zn_dom)
Type: Domain

Superoxide dismutases (SODs) are ubiquitous metalloproteins that prevent damage by oxygen-mediated free radicals by catalysing the dismutation of superoxide into molecular oxygen and hydrogen peroxide . Superoxide is a normal by-product of aerobic respiration and is produced by a number of reactions, including oxidative phosphorylation and photosynthesis. The dismutase enzymes have a very high catalytic efficiency due to the attraction of superoxide to the ions bound at the active site .

There are three forms of superoxide dismutase, depending on the metal cofactor: Cu/Zn (which binds both copper and zinc), Fe and Mn types. The Fe and Mn forms are similar in their primary, secondary and tertiary structures, but are distinct from the Cu/Zn form . Prokaryotes and protists contain Mn, Fe or both types, while most eukaryotic organisms utilise the Cu/Zn type.

Defects in the human SOD1 gene causes familial amyotrophic lateral sclerosis (Lou Gehrig's disease). Cytoplasmic and periplasmic SODs exist as dimers, whereas chloroplastic and extracellular enzymes exist as tetramers. Structural analysis supports the notion of independent functional evolution in prokaryotes (P-class) and eukaryotes (E-class) .
Archaeal/bacterial/fungal rhodopsins (Arc/bac/fun_rhodopsins)
Type: Family

Bacterial rhodopsins are a family of bacterial opsins. They are retinal-binding proteins that provide light-dependent ion transport and sensory functions to a family of halophilic bacteria . They are integral membrane proteins believed to contain seven transmembrane (TM) domains, the last of which contains the attachment point for retinal binding (a conserved lysine).

Fungal rhodopsins are membrane-embedded photoreceptors characterised by seven transmembrane helices and a retinal chromophore. They are widely distributed across fungal species, forming large multigene families . These proteins exhibit diverse functions, including light-driven proton pumping, green light sensing, and involvement in signalling pathways. Fungal rhodopsins are particularly prevalent in plant-associated and phytopathogenic fungi .
Pancreatic ribonuclease (RNaseA)
Type: Family

Pancreatic ribonucleases (RNaseA) are pyrimidine-specific endonucleases found in high quantity in the pancreas of certain mammals and of some reptiles . Specifically, the enzymes are involved in endonucleolytic cleavage of 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates. Ribonuclease can unwind the DNA helix by complexing with single-stranded DNA; the complex arises by an extended multi-site cation-anion interaction between lysine and arginine residues of the enzyme and phosphate groups of the nucleotides. Other proteins belonging to the pancreatic RNAse family include: bovine seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases ; liver-type ribonucleases ; angiogenin, which induces vascularisation of normal and malignant tissues; eosinophil cationic protein , a cytotoxin and helminthotoxin with ribonuclease activity; and frog liver ribonuclease and frog sialic acid-binding lectin. The sequence of pancreatic RNases contains four conserved disulphide bonds and three amino acid residues involved in the catalytic activity.