SII-SWORD/CoKE huggingface dataset:
ATP-binding cassette subfamily C member 9 (ABCC9)
Type: Family

ATP-binding cassette subfamily C member 9 (ABCC9, also known as the sulphonylurea receptor SUR2)
is an atypical member of the ABC transporter family. Although it has the requisite domains to function as a transporter, it is a regulator of a potassium channel to which it is directly coupled in a hetero-octameric complex . Mutations in ABCC9 cause Cantu syndrome (CS), a distinct multiorgan disease, potentially via enhanced KATP channel activity .
Viral small hydrophobic protein (SH)
Type: Family

The mumps virus SH protein is a membrane protein and not essential for virus growth . Its function is unknown.
PDZ domain (PDZ)
Type: Domain

PDZ domains (also known as Discs-large homologous regions (DHR) or GLGF)) are found in diverse signalling proteins in bacteria, yeasts, plants, insects and vertebrates . PDZ domains can occur in one or multiple copies and are nearly always found in cytoplasmic proteins. They bind either the carboxyl-terminal sequences of proteins or internal peptide sequences . In most cases, interaction between a PDZ domain and its target is constitutive, with a binding affinity of 1 to 10 microns. However, agonist-dependent activation of cell surface receptors is sometimes required to promote interaction with a PDZ protein. PDZ domain proteins are frequently associated with the plasma membrane, a compartment where high concentrations of phosphatidylinositol 4,5-bisphosphate (PIP2) are found. Direct interaction between PIP2 and a subset of class II PDZ domains (syntenin, CASK, Tiam-1) has been demonstrated.
Quinoprotein dehydrogenase, conserved site (Quinoprotein_DH_CS)
Type: Conserved_site

This entry represents two conserved regions found in mainly proteobacterial PQQ dehydrogenases.

Pyrrolo-quinoline quinone (PQQ) is a redox coenzyme, which serves as a cofactor for a number of enzymes (quinoproteins) and particularly for some bacterial dehydrogenases .
Bulb-type lectin domain (Bulb-type_lectin_dom)
Type: Domain

A bulb lectin super-family (Amaryllidaceae, Orchidaceae and Aliaceae) contains a ~115-residue-long domain whose overall three dimensional fold is very similar to that of :

Dictyostelium discoideum comitin, an actin binding protein

Curculigo latifolia curculin, a sweet tasting and taste-modifying protein

This domain generally binds mannose, but in at least one protein, curculin, it is apparently devoid of mannose-binding activity.
Type II/IV secretion system domain (T2SS/T4SS_dom)
Type: Domain

This entry contains both type II and type IV pathway secretion proteins from bacteria. Proteins in this entry include VirB11 ATPase (

), which is a subunit of the Agrobacterium tumefaciens transfer DNA (T-DNA) transfer system, a type IV secretion pathway required for delivery of T-DNA and effector proteins to plant cells during infection .

The type II protein secretion system (T2SS) is a sophisticated multi-protein machinery containing 12-15 different proteins . Historically, this system was described as the main terminal branch (MTB) of the general secretory pathway (GSP), but this nomenclature is now on obsolete .
Urotensin II (Urotensin_II)
Type: Family

Urotensin II (UII) is a vasoactive somatostatin-like or cortistatin-like peptide hormone. However, despite the apparent structural similarity to these peptide hormones, they are not homologous to UII. Urotensin II was first identified in fish spinal cord but later found in humans and other mammals . In fish, UII is secreted at the back part of the spinal cord, in a neurosecretory centre called uroneurapophysa, and is involved in the regulation of the renal and cardiovascular systems . In mammals, urotensin II is the most potent mammalian vasoconstrictor identified to date and causes contraction of arterial blood vessels, including the thoracic aorta .

This entry represents urotensin II.
Pyrokinin, conserved site (Pyrokinin_CS)
Type: Conserved_site

Pyrokinins are insect neuropeptides that mediate visceral muscle contractile activity (myotropic activity) . They share an amide-blocked C-terminal pentapeptide sequence that is sufficient to elicit a significant myotropic activity. Pheromonotropin which controls sex pheromone production also belongs to this group .
Truncated hemoglobin (Hemoglobin_trunc)
Type: Family

This entry represents a group of haemoglobin-like proteins found in eubacteria, cyanobacteria, protozoa, algae and plants, but not in animals or yeast. These proteins have a truncated 2-over-2 rather than the canonical 3-over-3 α-helical sandwich fold . They include:

HbN (or GlbN): a truncated haemoglobin-like protein that binds oxygen cooperatively with a very high affinity and a slow dissociation rate, which may exclude it from oxygen transport. It appears to be involved in bacterial nitric oxide detoxification and in nitrosative stress .

Cyanoglobin (or GlbN): a truncated haemoprotein found in cyanobacteria that has high oxygen affinity, and which appears to serve as part of a terminal oxidase, rather than as a respiratory pigment .

HbO (or GlbO): a truncated haemoglobin-like protein with a lower oxygen affinity than HbN. HbO associates with the bacterial cell membrane, where it significantly increases oxygen uptake over membranes lacking this protein. HbO appears to interact with a terminal oxidase, and could participate in an oxygen/electron-transfer process that facilitates oxygen transfer during aerobic metabolism .

Glb3: a nuclear-encoded truncated haemoglobin from plants that appears more closely related to HbO than HbN. Glb3 from Arabidopsis thaliana (Mouse-ear cress) exhibits an unusual concentration-independent binding of oxygen and carbon dioxide .

The truncated haemoglobin (trHb) family branches into three main groups, designated as type I, II and III and named as HbN, HbO and HbP, respectively. The trHbO gene (also known as glbO) has been predicted as the ancestral gene, with group I and group III genes appearing as a result of duplication and transfer events. There is an accumulating evidence suggests that trHbs may be implicated in functions other than oxygen delivery .
Bromodomain (Bromodomain)
Type: Domain

Bromodomains are found in a variety of mammalian, invertebrate and yeast DNA-binding proteins . Bromodomains are highly conserved α-helical motifs that can specifically interact with acetylated lysine residues on histone tails . In some proteins, the classical bromodomain has diverged to such an extent that parts of the region are either missing or contain an insertion (e.g., mammalian protein HRX, Caenorhabditis elegans hypothetical protein ZK783.4, yeast protein YTA7). The bromodomain may occur as a single copy, or in duplicate.

This domain is present in proteins involved in a wide range of functions such as acetylating histones, remodelling chromatin, and recruiting other factors necessary for transcription, thus playing a critical role in the regulation of transcription .
Heat-stable enterotoxin, STa (Heat-stable_enterotox_STa)
Type: Family

This entry represents a group of heat-stable enterotoxins, such as STa from Escherichia coli, which is the cause of acute diarrhoea in infants and travellers in developing countries. The mature STa protein is a 19-residue peptide containing three disulphide bridges that are functionally important. STa contains an N-terminal signal peptide composed of two domains, Pre and Pro, involved in extracellular toxin release, and a core enterotoxigenic domain . STa binds to and activates the guanylate cyclise C intestinal receptor, causing an increase in the intracellular levels of cyclic guanosine monophosphate (cGMP) .
Flagellin (Flagellin)
Type: Family

Bacterial flagella are responsible for motility and chemotaxis . They comprise a basal body, a hook and a filament, the latter accounting for 98% of the mass . Flagellin is the subunit protein that polymerises to form the flagella , the subunits being transported through the centre of the filament to the tip, where they then polymerise . Both the N- and C- termini of the subunit protein, which are α-helical in structure , are required to mediate polymerisation. Although no export or assembly, consensus sequences have been identified: Ala, Val, Leu, Ile, Gly, Ser, Thr, Asn, Gln and Asp tend to make up around 90% of the sequence, Cys and Trp being absent .

Flagellin plays a role in the activation of innate and adaptive immunity. It is an specific ligand for Toll-like receptor 5 (TLR5) in the host, which has lead to great interest to use it as adjuvant for vaccines . The protein is also recognised by the intracellular NAIP5/NLRC4 inflammasome receptor .
Peptidase A22A, presenilin 2 (Pept_A22A_PS2)
Type: Family

This group of aspartic peptidases belong to MEROPS peptidase family A22 (presenilin family, clan AD): subfamily A22A, the type example being presenilin 1 from Homo sapiens (Human).

Presenilins are polytopic transmembrane (TM) proteins, mutations in which are associated with the occurrence of early-onset familial Alzheimer's disease, a rare form of the disease that results from a single-gene mutation . The physiological functions of presenilins are unknown, but they may be related to developmental signalling, apoptotic signal transduction, or processing of selected proteins, such as the beta-amyloid precursor protein(beta-APP). There are a number of subtypes which belong to this presenilin family. That presenilin homologues have been identified in species that do not have an Alzhemier's disease correlate suggests that they may have functions unrelated to the disease, homologues having been identified in mouse, Drosophila melanogaster, Caenorhabditis elegans and other members of the eukarya including plants.
Importin-beta, N-terminal domain (Importin-beta_N)
Type: Domain

This entry represents the N-terminal domain of importin-beta (also known as karyopherins-beta) that is important for the binding of the Ran GTPase protein .

Members of the importin-beta (karyopherin-beta) family can bind and transport cargo by themselves, or can form heterodimers with importin-alpha. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Importin-beta is a helicoidal molecule constructed from 19 HEAT repeats. Many nuclear pore proteins contain FG sequence repeats that can bind to HEAT repeats within importins , which is important for importin-beta mediated transport.

Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. As a result, the N-terminal auto-inhibitory region on importin-alpha is free to loop back and bind to the major NLS-binding site, causing the cargo to be released . There are additional release factors as well.
SOCS box domain (SOCS_box)
Type: Domain

The SOCS box was first identified in SH2-domain-containing proteins of the suppressor of cytokines signalling (SOCS) family but was later also found in:

the WSB (WD-40-repeat-containing proteins with a SOCS box) family,

the SSB (SPRY domain-containing proteins with a SOCS box) family,

the ASB (ankyrin-repeat-containing proteins with a SOCS box) family,

and ras and ras-like GTPases .

The SOCS box found in these proteins is an about 50 amino acid C-terminal domain composed of two blocks of well-conserved residues separated by between 2 and 10 non-conserved residues . The C-terminal conserved region is an L/P-rich sequence of unknown function, whereas the N-terminal conserved region is a consensus BC box , which binds to the Elongin BC complex . It has been demonstrated that this association couple bound proteins to the ubiquitination or proteasomal compartments .
Methylated-DNA-[protein]-cysteine S-methyltransferase, active site (MethylDNA_cys_MeTrfase_AS)
Type: Active_site

Synonym(s): 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase, Methylated-DNA-[protein]-cysteine S-methyltransferase.

This entry represents the active site of 6-O-methylguanine-DNA methyltransferases.

The repair of DNA containing O6-alkylated guanine is carried out by DNA-[protein]-cysteine S-methyltransferase (

). The major mutagenic and carcinogenic effect of methylating agents in DNA is the formation of O6-alkylguanine. The alkyl group at the O-6 position is transferred to a cysteine residue in the enzyme . This is a suicide reaction since the enzyme is irreversibly inactivated and the methylated protein accumulates as a dead-end product. Most, but not all of the methyltransferases are also able to repair O-4-methylthymine. DNA-[protein]-cysteine S-methyltransferases are widely distributed and are found in various prokaryotic and eukaryotic sources .
Impact, N-terminal (Impact_N)
Type: Domain

The Impact protein is a translational regulator that ensures constant high levels of translation under amino acid starvation. It acts by interacting with Gcn1/Gcn1L1, thereby preventing activation of Gcn2 protein kinases (EIF2AK1 to 4) and subsequent down-regulation of protein synthesis. It is evolutionary conserved from eukaryotes to archaea .

This entry represents the N-terminal domain of the Impact proteins.
GPCR fungal pheromone mating factor, STE3 (GPCR_STE3)
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.

This entry represents the STE3-type family of fungal pheromone mating factor receptors. The STE3 gene of Saccharomyces cerevisiae (Baker's yeast) 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.
Nickel-dependent hydrogenase, large subunit (Ni-dep_hyd_lsu)
Type: Family

Hydrogenases are enzymes that catalyse the reversible oxidation of hydrogen and are important in anaerobic metabolism. There are various types of metal-containing hydrogenases and can be broadly divided into three groups: Fe ('iron only') hydrogenases; Ni-Fe hydrogenases; and Ni-Fe-Se hydrogenases .

The [NiFe] and [NiFeSe] hydrogenases are heterodimer that consist of a small subunit (S) that contains a signal peptide and a large subunit (L). All the known large subunits seem to be evolutionary related ; they contain two Cys-x-x-Cys motifs; one at their N-terminal end; the other at their C-terminal end. These four cysteines are involved in the binding of nickel . In the [NiFeSe] hydrogenases the first cysteine of the C-terminal motif is a selenocysteine which has experimentally been shown to be a nickel ligand .
Glycosyl transferase family 10 (Glyco_trans_10)
Type: Family

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

Glycosyltransferase family 10 (

) comprises enzymes with two known activities; galactoside 3(4)-L-fucosyltransferase (

) and galactoside 3-fucosyltransferase (

).

The galactoside 3-fucosyltransferases display similarities with the alpha-2 and alpha-6-fucosyltranferases . The biosynthesis of the carbohydrate antigen sialyl Lewis X (sLe(x)) is dependent on the activity of an galactoside 3-fucosyltransferase. This enzyme catalyses the transfer of fucose from GDP-beta-fucose to the 3-OH of N-acetylglucosamine present in lactosamine acceptors .
Bradykinin receptor B2 (Brdyknn_2_rcpt)
Type: Family

Bradykinins are a family of short, structurally similar peptides that activate sensory fibres, contract venous smooth muscle, stimulate release of cytokines, induce connective tissue proliferation and mediate endothelium-dependent vasodilation . Bradykinin antagonists are used in the treatment of inflammation, asthma, mild pain and endotoxic shock.

Bradykinin receptors are members of the seven transmembrane, rhodopsin-like G-protein coupled receptor family and are widespread in peripheral tissues. There are two bradykinins receptor subtypes: B1 and B2. It has also been proposed there could be further subtypes of the bradykinin receptor, including a tracheal B3 receptor but these, as yet have not been confirmed .

This entry represents bradykinin receptor B2, which is the predominant subtype and is ubiquitously and constitutively expressed in healthy tissues . The B2 receptor mediates slow contraction of various smooth muscles including veins, intestine, uterus, trachea and lung, inducing endothelium-dependent relaxation of arteries and arterioles, and stimulates natriuresis/diuresis in kidney . Both B1 and B2 receptors are involved in the induction and maintenance of cytokine-induced hyperalgesia, but B2 receptor to a lesser extent . The B2 receptor couples to Gq and Gi, Gq stimulates phospholipase C to increase intracellular free calcium and Gi inhibits adenylate cyclase . Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways . The B2 receptor also forms a complex with angiotensin converting enzyme (ACE) , and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and the kinin-kallikrein system (KKS) .
Copper centre Cu(A) (Copper_CuA)
Type: Binding_site

The Cu(A) centre contains a mixed valence binuclear copper binding site formed of about 50 amino acids containing two cysteines and histidines and one glutamate and methionine . The Cu(A) centre has been identified in subunit II of cytochrome c oxidase and nitrous oxide reductase .

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain and is involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. The enzyme complex consists of 3-4 subunits (prokaryotes) to up to 13 polypeptides (mammals). Subunit II (see

,

) transfers the electrons from cytochrome c to the catalytic subunit I. It provides the substrate-binding site and contains a Cu(A) centre that is probably the primary acceptor in cytochrome c oxidase.

Nitrous oxide reductase (

) (gene nosZ) of Pseudomonas is part of the bacterial respiratory system which is activated under anaerobic conditions in the presence of nitrate or nitrous oxide. NosZ is a periplasmic homodimer that contains a dinuclear copper centre, probably located in a 3-dimensional fold similar to the cupredoxin-like fold that has been suggested for the copper-binding site of subunit II .
Peptidase M12A (Peptidase_M12A)
Type: Domain

This group of metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin 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 and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH .

The astacin (

) family of metalloendopeptidases encompasses a range of proteins found in hydra to humans, in mature and developmental systems . Their functions include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins . The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the protease domain. They are either secreted from cells, or are associated with the plasma membrane .

The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains . The zinc ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 histidine residues, a tyrosine and a water molecule (which is also bound to the carboxylate side chain of Glu93) . The N-terminal domain comprises 2 α-helices and a 5-stranded β-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake venom proteases; they cleave peptide bonds in polypeptides such as insulin B chain and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity .