SII-SWORD/CoKE huggingface dataset:
Bacterial ice-nucleation, octamer repeat (Ice_nucleatn)
Type: Repeat

Certain Gram-negative bacteria express proteins that enable them to promote nucleation of ice at relatively high temperatures (above -5C) . These proteins are localised at the outer membrane surface and can cause frost damage to many plants. The primary structure of the proteins contains a highly repetitive domain that dominates the sequence. The domain comprises a number of 48-residue repeats, which themselves contain 3 blocks of 16 residues, the first 8 of which are identical. It is thought that the repetitive domain may be responsible for aligning water molecules in the seed crystal.

[.........48.residues.repeated.domain..........]
/ / | | \ \
AGYGSTxTagxxssli AGYGSTxTagxxsxlt AGYGSTxTaqxxsxlt
[16.residues...] [16.residues...] [16.residues...]
Fimbrial-type adhesion domain (Adhesion_dom_fimbrial)
Type: Domain

This domain is found in bacterial proteins that are involved in regulation of length and mediation of adhesion of fimbriae. Fimbriae (also called pili), are polar filaments radiating from the surface of the bacterium to a length of 0.5-1.5 micrometers, that enable bacteria to colonize the epithelium of specific host organs. Fimbriae are also responsible to promote virulence .
NADH:ubiquinone oxidoreductase chain 4, N-terminal (NADH4_N)
Type: Domain

This entry represents the N-terminal domain of ADH:ubiquinone oxidoreductase (complex I) chain 4. This domain is found upstream of

.
EH domain (EH_dom)
Type: Domain

The EH (for Eps15 Homology) domain is a protein-protein interaction module of approximately 95 residues which was originally identified as a repeated sequence present in three copies at the N terminus of the tyrosine kinase substrates Eps15 and Eps15R . The EH domain was subsequently found in several proteins implicated in endocytosis, vesicle transport and signal transduction in organisms ranging from yeast to mammals. EH domains are present in one to three copies and they may include calcium-binding domains of the EF-hand type . Eps15 is divided into three domains: domain I contains signatures of a regulatory domain, including a candidate tyrosine phosphorylation site and EF-hand-type calcium-binding domains, domain II presents the characteristic heptad repeats of coiled-coil rod-like proteins, and domain III displays a repeated aspartic acid-proline-phenylalanine motif similar to a consensus sequence of several methylases .

EH domains have been shown to bind specifically but with moderate affinity to peptides containing short, unmodified motifs through predominantly hydrophobic interactions. The target motifs are divided into three classes: class I consists of the concensus Asn-Pro-Phe (NPF) sequence; class II consists of aromatic and hydrophobic di- and tripeptide motifs, including the Phe-Trp (FW), Trp-Trp (WW), and Ser-Trp-Gly (SWG) motifs; and class III contains the His-(Thr/Ser)-Phe motif (HTF/HSF) . The structure of several EH domains has been solved by NMR spectroscopy. The fold consists of two helix-loop-helix characteristic of EF-hand domains, connected by a short antiparallel β-sheet. The target peptide is bound in a hydrophobic pocket between two α helices. Sequence analysis and structural data indicate that not all the EF-hands are capable of binding calcium because of substitutions of the calcium-liganding residues in the loop .
FMN-dependent dehydrogenase (FMN-dep_DH)
Type: Domain

A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown to be structurally related. These enzymes are:

Lactate dehydrogenase (

), which consists of a dehydrogenase domain and a haem-binding domain called cytochrome b2 and which catalyses the conversion of lactate into pyruvate.

Glycolate oxidase (

) ((S)-2-hydroxy-acid oxidase), a peroxisomal enzyme that catalyses the conversion of glycolate and oxygen to glyoxylate and hydrogen peroxide.

Long chain alpha-hydroxy acid oxidase from rat (

), a peroxisomal enzyme.

Lactate 2-monooxygenase (

) (lactate oxidase) from Mycobacterium smegmatis, which catalyses the conversion of lactate and oxygen to acetate, carbon dioxide and water.

(S)-mandelate dehydrogenase from Pseudomonas putida (gene mdlB), which catalyses the reduction of (S)-mandelate to benzoylformate.

The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the α-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown to be involved in the removal of the proton. The region around this active site residue is highly conserved and contains an arginine residue which is involved in substrate binding.
Geminivirus AR1/BR1 coat protein (GV_A/BR1_coat)
Type: Family

Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name . Most geminiviruses can be divided into 2 subgroups on the basis of host range and/or insect vector: i.e. those that infect dicotyledenous plants and are transmitted by the same whitefly species, and those that infect monocotyledenous plants and are transmitted by different leafhopper vectors.
It has been shown that the 104 N-terminal amino acids of the Maize streak virus coat protein bind DNA non-specifically .
ALB/AFP/VDB (ALB/AFP/VDB)
Type: Family

A number of serum transport proteins are known to be evolutionarily related, including albumin, alpha-fetoprotein, vitamin D-binding protein and afamin . Albumin is the main protein of plasma; it binds water, cations (such as Ca
2+
, Na
+
and K
+
), fatty acids, hormones, bilirubin and drugs - its main function is to regulate the colloidal osmotic pressure of blood. Alphafeto- protein (alpha-fetoglobulin) is a foetal plasma protein that binds various cations, fatty acids and bilirubin. Vitamin D-binding protein binds to vitamin D and its metabolites, as well as to fatty acids. The biological role of afamin (alpha-albumin) has not yet been characterised. The 3D structure of human serum albumin has been determined by X-ray crystallography to a resolution of 2.8A . It comprises three homologous domains that assemble to form a heart-shaped molecule . Each domain is a product of two subdomains that possess common structural motifs . The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. Structurally, the serum albumins are similar, each domain containing five or six internal disulphide bonds, as shown schematically below:

+---+ +----+ +-----+
| | | | | |
xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx
| | | | | |
+-----------------+ +-----+ +---------------+
Prostanoid EP3 receptor (Prostglndn_EP3_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 .

Prostanoids (prostaglandins (PG) and thromboxanes (TX)) mediate a wide variety of actions and play important physiological roles in the cardiovascular and immune systems, and in pain sensation in peripheral systems. PGI2 and TXA2 have opposing actions, involving regulation of the interaction of platelets with the vascular endothelium, while PGE2, PGI2 and PGD2 are powerful vasodilators and potentiate the action of various autocoids to induce plasma extravasation and pain sensation. To date, evidence for at least 5 classes of prostanoid receptor has been obtained. However, identification of subtypes and their distribution is hampered by expression of more than one receptor within a tissue, coupled with poor selectivity of available agonists and antagonists.

EP3 receptors mediate contraction in a wide range of smooth muscles, including gastrointestinal and uterine. They also inhibit neurotransmitter release in central and autonomic nerves through a presynaptic action, and inhibit secretion in glandular tissues (e.g., acid secretion from gastric mucosa, and sodium and water reabsorption in the kidney). mRNA is found in high levels in the kidney and uterus, and in lower levels in the brain, thymus, lung, heart, stomach and spleen. The receptors activate adenylate cyclase via an uncharacterised G-protein, probably of the Gi/Go class.
Small ribosomal subunit protein uS17 (Ribosomal_uS17)
Type: Family

This family includes small ribosomal subunit protein uS17 (formerly known as 30S ribosomal protein S17 and 40S ribosomal protein S11) .

The ribosomal proteins catalyse ribosome assembly and stabilise the rRNA, tuning the structure of the ribosome for optimal function. Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA . The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins. The small ribosomal subunit protein uS17 is known to bind specifically to the 5' end of 16S ribosomal RNA in Escherichia coli (primary rRNA binding protein), and is thought to be involved in the recognition of termination codons. Experimental evidence has revealed that uS17 has virtually no groups exposed on the ribosomal surface.
DNA-directed RNA polymerase subunit RPABC5/Rpb10 (RPABC5/Rpb10)
Type: Family

In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (

) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consists of an oligomeric assemblage of 10 to 13 polypeptides. Archaebacterial subunit Rpo10 (gene rpoN) is a small protein of about 8kDa, it is evolutionary related to a 8.3kDa component shared by all three forms of eukaryotic RNA polymerases (RPABC5, gene Rpb10 in yeast and POLR2J in mammals) as well as to African swine fever virus (ASFV) protein CP80R .

This family includes both archaeal subunit N, also known as Rpo10 following the eukaryotic nomenclature , and eukaryotic Rpb10. There is a conserved region which is located at the N-terminal extremity of these polymerase subunits; this region contains two cysteines that bind a zinc ion .
Copper amine oxidase (Cu_amine_oxidase)
Type: Family

This entry represents a family of copper amine oxidase enzymes.

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .
PB1 domain (PB1_dom)
Type: Domain

The PB1 (Phox and Bem1) domain, comprising about 80 amino acid residues, is conserved among animals, fungi, amoebas, and plants. It functions as a protein binding module through PB1-mediated heterodimerization or homo-oligomerization .
Large ribosomal subunit protein bL34 (Ribosomal_bL34)
Type: Family

Ribosomal protein L34 (also known as Large ribosomal subunit protein bL34) is one of the proteins from the large subunit of the ribosome from bacteria and eukaryotes. It is a small basic protein of 44 to 51 amino-acid residues . L34 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups: Eubacterial L34, Red algal chloroplast L34 and Cyanelle L34.

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 .
Ion-transport regulator, FXYD family (Ion-transport_regulator_FXYD)
Type: Family

The FXYD protein family contains at least seven members in mammals . Two other family members that are not obvious orthologs of any identified mammalian FXYD protein exist in zebrafish. All these proteins share a signature sequence of six conserved amino acids comprising the FXYD motif in the NH2-terminus, and two glycines and one serine residue in the transmembrane domain. FXYD proteins are widely distributed in mammalian tissues with prominent expression in tissues that perform fluid and solute transport or that are electrically excitable.

Initial functional characterisation suggested that FXYD proteins act as channels or as modulators of ion channels however studies have revealed that most FXYD proteins have another specific function and act as tissue-specific regulatory subunits of the Na,K-ATPase . Each of these auxiliary subunits produces a distinct functional effect on the transport characteristics of the Na,K-ATPase that is adjusted to the specific functional demands of the tissue in which the FXYD protein is expressed. FXYD proteins appear to preferentially associate with Na,K-ATPase alpha1-beta isozymes, and affect their function in a way that render them operationally complementary or supplementary to coexisting isozymes.
Adenylate cyclase, class-I (Adenylate_cyclase_1)
Type: Family

Adenylate cyclase is the enzyme responsible for the synthesis of cAMP from ATP. On the basis of sequence similarity, it has been proposed that there are three different classes of adenylate cyclases . Class I cyclases are found in enterobacteria and related Gram-negative bacteria.
Coagulin (Coagulin)
Type: Family

Coagulogen is a gel-forming protein of hemolymph that hinders the spread of invaders by immobilising them . The protein contains a single 175- residue polypeptide chain; this is cleaved after Arg-18 and Arg-46 by a clotting enzyme contained in the hemocyte and activated by a bacterial endotoxin (lipopolysaccharide). Cleavage releases two chains of coagulin, A and B, linked by two disulphide bonds, together with the peptide C . Gel formation results from interlinking of coagulin molecules. The crystal structure of a coagulogen has been revealed. Coagulogen contains a C-terminal domain that has a NGF-like fold .

Mammalian blood coagulation is based on the proteolytically induced polymerisation of fibrinogens. Initially, fibrin monomers noncovalently interact with each other. The resulting homopolymers are further stabilised when the plasma transglutaminase (TGase) intermolecularly cross-links epsilon-(gamma-glutamyl)lysine bonds. In crustaceans, hemolymph coagulation depends on the TGase-mediated cross-linking of specific plasma-clotting proteins, but without the proteolytic cascade. In horseshoe crabs, the proteolytic coagulation cascade triggered by lipopolysaccharides and beta-1,3-glucans leads to the conversion of coagulogen into coagulin, resulting in noncovalent coagulin homopolymers through head-to-tail interaction. Horseshoe crab TGase, however, does not cross-link coagulins intermolecularly. It has been shown that coagulins are cross-linked on hemocyte cell surface proteins called proxins. This indicates that a cross-linking reaction at the final stage of hemolymph coagulation is an important innate immune system of horseshoe crabs .
G protein-coupled receptor, rhodopsin-like (GPCR_Rhodpsn)
Type: Family

This entry represents the G protein-coupled receptor, rhodopsin-like family.

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 .

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 .
Cys/Met metabolism, pyridoxal phosphate-dependent enzyme (Cys/Met-Metab_PyrdxlP-dep_enz)
Type: Family

A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown to be evolutionary related. These enzymes are proteins of about 400 amino-acid residues. The pyridoxal-P group is attached to a lysine residue located in the central section of these enzymes.

One of these enzymes is the sulfhydrylase FUB7 from fungi such as Gibberella and Fusarium. The gene is part of a cluster that mediates the biosynthesis of fusaric acid, a mycotoxin with low to moderate toxicity to animals and humans, but with high phytotoxic properties .

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .