SII-SWORD/CoKE huggingface dataset:
Nociceptin (Nociceptin)
Type: Family

Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptide itself. Three types of precursor are known: preproenkephalin A (gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin; and prepronocipeptin (gene PNOC), whose processing produces nociceptin (orphanin FQ) and two other potential neuropeptides.

Sequence analysis reveals that the conserved N-terminal region of the precursors contains 6 cysteines, which are probably involved in disulphide bond formation. It is speculated that this region might be important for neuropeptide processing .

Nociceptin (or orphanin FQ) is a natural agonist of opioid receptor-like receptor . The peptide is derived from the prepronociceptin precursor, whose gene is predominantly transcribed in the central nervous system (brain and spinal cord) and, weakly, in the ovary (the sole peripheral organ that expresses the gene) . Studies on Rattus norvegicus (Rat) and Mus musculus (Mouse) nociceptin suggest that the protein functions not only as a neuropeptide precursor but also as an important component in neuronal differentiation .
Outer membrane protein, OmpA (OmpA)
Type: Family

The OmpA outer membrane proteins in this group all contain the OmpA-like transmembrane domain at the N-terminal and the conserved bacterial outer membrane protein domain at the C-terminal. The outer membrane protein A of Escherichia coli (OmpA), is one of the most studied proteins in this group . It has a multifunctional role. OmpA is required for the action of colicins K and L and for the stabilisation of mating aggregates in conjugation. OmpA may be involved in the maintenance of the position of the peptidoglycan cell wall in the periplasm by non-covalent interaction with TolR . These proteins are implicated as a secondary receptor for a number of T-even like phages, for example, during phage Sf6 infection, it requires both lipopolysaccharide and OmpA . In addition, OmpA can act as a porin with low permeability that allows slow penetration of small solutes .
Integrin beta subunit, VWA domain (Integrin_bsu_VWA)
Type: Domain

This domain corresponds to the integrin beta VWA domain.

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [

]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [

]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) . This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [

], [

],

]. Finally, this is followed by the β-ankle TM domain [

] and a cytoplasmic tail [

] .

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.
Flagellar hook-associated protein 1 (FlgK)
Type: Family

Within the bacterial flagellum, the basal-body rod, the hook, the hook- associated proteins (HAPs), and the helical filament together constitute an axial substructure whose elements share structural features and a common export pathway . This entry represents the hook-associated protein 1 (HAP1, also known as FlgK) . The structure of FlgK from Burkholderia pseudomallei has been revealed .
Pyrrolo-quinoline quinone repeat domain (PQQ_rpt_dom)
Type: Domain

This entry represents a β-propeller composed of the so-called PQQ repeats and found in a group of functionally diverse proteins.

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 . A number of bacterial quinoproteins belong to this family.

Enzymes in this group contain repeats composing a β propeller.
cGMP-dependent kinase (cGMP_dep_kinase)
Type: Family

Guanosine cyclase 3',5'-dependent protein kinases are known to play a role in smooth muscle relaxation, ion fluxes in kidneys and intestines, and neuronal function. The predominant form of cGMP-dependent protein kinase is a dimer of identical 75kDa subunits, although larger subunits of 86 and 130kDa have been found . The enzyme is kept in an inactive form by the interaction of the catalytic domain of one subunit with the region on the other subunit that precedes the cGMP binding domain. Each subunit contains two cGMP-binding regions, found together in the sequence: binding of two molecules of cGMP precipitates a conformational change in the active site that allows the substrate to bind.

Although cGMP-and cAMP-dependent protein kinases are similar both in structure and sequence around the nucleotide binding site, and in the method of activation and inactivation, there are some basic contrasts. The major difference is that all of the functional domains of the cGMP-dependent enzymes are found on a single polypeptide chain, whereas cAMP-dependent protein kinases have separate regulatory (cAMP binding) and catalytic chains.
Formyl transferase, N-terminal (Formyl_transf_N)
Type: Domain

A number of formyl transferases belong to this group. Methionyl-tRNA formyltransferase transfers a formyl group onto the amino terminus of the acyl moiety of the methionyl minoacyl-tRNA. The formyl group appears to play a dual role in the initiator identity of N-ormylmethionyl-tRNA by promoting its recognition by IF2 and by impairing its binding to EFTU-GTP. Formyltetrahydrofolate dehydrogenase produces formate from formyl-tetrahydrofolate. This is the N-terminal domain of these enzymes and is found upstream of the C-terminal domain (

).

The trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase catalyses the second, third and fifth steps in de novo purine biosynthesis. The glycinamide ribonucleotide transformylase belongs to this group.
V-ATPase proteolipid subunit C-like domain (ATPase_proteolipid_c-like_dom)
Type: Domain

The F-ATPases (or F1F0-ATPases) and V-ATPases (or V1V0-ATPases) are each composed of two linked complexes: the F1 or V1 complex contains the catalytic core that synthesizes/hydrolyses ATP, and the F0 or V0 complex that forms the membrane-spanning pore. The F- and V-ATPases all contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis .

In V-ATPases, there are three proteolipid subunits (c, c' and c'') that form part of the proton-conducting pore, each containing a buried glutamic acid residue that is essential for proton transport, and together they form a hexameric ring spanning the membrane .

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.
Ribonuclease PH, bacterial-type (RNase_PH_bac-type)
Type: Family

Prokaryotic ribonuclease PH (

) (RNase PH) is a phosphorolytic exoribonuclease that participates in tRNA maturation by removing nucleotide residues following the -CCA terminus of tRNA . It also has synthetic activity, adding nucleotides to the ends of RNA molecules by using nucleoside diphosphates as substrates . RNase PH forms a homohexameric ring .

Interestingly, E. coli MG1655 and W3110 strains contains the rph-1 allele, encoding a truncated catalytically inactive RNase PH protein. These truncated proteins are also included in this entry .
Osteocalcin/matrix Gla protein (Osteocalcin/MGP)
Type: Family

Bone gamma-carboxyglutamic acid protein (BGP), also known as osteocalcin, and matrix gamma-carboxyglutamic acid protein (MGP) are the only vitamin K-dependent proteins that have been isolated from bone. MGP is a small protein found in bone, dentin and cartilage. It contains five gamma-carboxyglutamic acid (Gla) residues (formed by post-translational modification of glutamic acid by vitamin K-dependent carboxylase) and a single disulphide bond. BGP is a 49 residue protein found in bone. It contains three Gla residues and a single disulphide bond. There is little similarity between these vitamin K-dependent bone proteins and the blood coagulation proteins, though they are believed to have diverged from a common ancestor .
Amicyanin/Pseudoazurin (Amicyanin/Pseudoazurin)
Type: Family

Based on their primary sequences and their unique metabolic role, amicyanins are considered as a distinct subclass of cupredoxins, although they appear to be closely related to the plant plastocyanins .

The structure of amicyanin is a β-sandwich, built from nine β-strands. The copper atom is located between three loops on one end of the molecule. Two of these loops contribute the copper ligands. The other three ligands are located on the loop between strands 8 and 9. The structure departs from the general cupredoxin fold in having a 21-residue N-terminal extension, which forms an extra β-strand, and it shows significant differences between strands 5 and 7 (this forms a helix in azurin and an acidic patch in plastocyanin).

Pseudoazurin, also called cupredoxin, is a small, blue periplasmic protein with a single bound copper atom. Pseudoazurin is related to plastocyanins . Several examples of pseudoazurin are encoded by a neighbouring gene for, or have been shown to transfer electrons to, copper-containing nitrite reductases (

) of the same species .

Pseudoazurin has been identified as an electron donor to the denitrification pathway. For example, pseudoazurin acts as an electron donor to cytochrome c peroxidase and N2OR from Paracoccus pantotrophus , and to the copper containing nitrite reductase that catalyzes the second step of denitrification . It has been shown that pseudoazurin dramatically enhances the reaction profile of nitrite reduction by Paracoccus pantotrophus cytochrome cd1 and facilitates release of the product nitric oxide. The ability of this small redox protein to interact with a multitude of structurally different partners has been attributed to the hydrophobic character of the binding surface.
Plastocyanin (Plastocyanin)
Type: Family

Blue or 'type-1' copper proteins are small proteins which bind a single copper atom and which are characterised by an intense electronic absorption band near 600 nm . The most well known members of this class of proteins are the plant chloroplastic plastocyanins, and the distantly related bacterial azurins, which exchange electrons with cytochrome c551. Plastocyanin participates in electron transfer between the cytochrome b6f complex and photosystem I. Many cyanobacteria and eukaryotic algae can synthesise both plastocyanin and its functional analog cytochrome c6, depending on bioavailabilities of copper and iron, respectively .

Plastocyanin participates in electron transfer between P700 and the cytochrome b/f complex in photosystem I .
Annexin A1 (ANX1)
Type: Family

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner . The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) . Annexins are absent from yeasts and prokaryotes .

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long . Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication .

This entry represents Annexin A1, which inhibits phospholipase A2, either in response to inflammation, or following dephosphorylation by protein kinases involved in the signal transduction pathway. The protein may also associate with the cell cytoskeleton by binding to actin fibres.
Annexin A2 (ANX2)
Type: Family

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner . The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) . Annexins are absent from yeasts and prokaryotes .

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long . Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication .

This entry represents annexin A2 that binds two calcium ions and inhibits phospholipase A2, following dephosphorylation by protein kinases involved in the signal transduction pathway. They may also cross-link plasma membrane phospholipids with actin and the cytoskeleton, and possibly play a part in exocytosis, since they are also involved in granule aggregation and membrane fusion.
Annexin A3 (ANX3)
Type: Family

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner . The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) . Annexins are absent from yeasts and prokaryotes .

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long . Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication .

This entry represents Type III annexins that inhibit phospholipase A2 activity, and also play a role in inositol phosphate metabolism, cleaving the cyclic bond of inositol-1,2-cyclic phosphate to yield inositol-1-phosphate.
Annexin A4 (ANX4)
Type: Family

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner . The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) . Annexins are absent from yeasts and prokaryotes .

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long . Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication .

This entry represents Type IV class annexins that have not been identified in all species known to possess annexins, but are thought to be required for the budding of clathrin-coated pits. Annexin IV localises to the apical membrane of epithelial cells. It modifies membrane bilayers by increasing rigidity, reducing permeability to water and H+ ions, promoting vesicle aggregation and regulating ion conductances .
Annexin A5 (ANX5)
Type: Family

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner . The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) . Annexins are absent from yeasts and prokaryotes .

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long . Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication .

This entry represents Type V annexin that behaves as an anticoagulant, acting as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation casacade. It may also act as a form of calcium channel.