SII-SWORD/CoKE huggingface dataset:
Transforming growth factor beta, conserved site (TGFb_CS)
Type: Conserved_site

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types. TGF-beta-1 is a peptide of 112 amino acid residues derived by proteolytic cleavage from the C-terminal of a precursor protein .

A number of proteins are known to be related to TGF-beta-1 . Proteins from the TGF-beta family are only active as homo- or heterodimer; the two chains being linked by a single disulphide bond. From X-ray studies of TGF-beta-2 , it is known that all the other cysteines are involved in intrachain disulphide bonds. There are four disulphide bonds in the TGF-beta's and in inhibin beta chains, while the other members of this family lack the first bond.

The regulatory cytokine TGF-beta exerts tumour-suppressive effects, but also modulates cell invasion and immune regulation . Misregulation of the TGF-beta signalling pathway can result in tumour development.
Thaumatin, conserved site (Thaumatin_CS)
Type: Conserved_site

Thaumatin is an intensely sweet-tasting protein, 100,000 times sweeter than sucrose on a molar basis found in berries from Thaumatococcus daniellii, a tropical flowering plant known as Katemfe, it is induced by attack by viroids, which are single-stranded unencapsulated RNA molecules that do not code for protein.

Thaumatin consists of about 200 residues and contains 8 disulphide bonds. Like other PR proteins, thaumatin is predicted to have a mainly β structure, with a high content of β-turns and little helix . Several stress-induced proteins of plants have been found to be related to thaumatins:

A maize alpha-amylase/trypsin inhibitor

Two tobacco pathogenesis-related proteins: PR-R major and minor forms,which are induced after infection with viruses

Salt-induced protein NP24 from tomato

Osmotin, a salt-induced protein from tobacco

Osmotin-like proteins OSML13, OSML15 and OSML81 from potato

P21, a leaf protein from soybean

PWIR2, a leaf protein from wheat

Zeamatin, a maize antifungal protein

This protein is also referred to as pathogenesis-related group 5 (PR5), as many thaumatin-like proteins accumulate in plants in response to infection by a pathogen and possess antifungal activity . The proteins are involved in systematically acquired resistance and stress responses in plants, although their precise role is unknown .

This entry represents a conserved site that includes three cysteine residues known to be involved in disulphide bonds.
Urease active site (Urease_AS)
Type: Active_site

Urease (urea amidohydrolase,

) is a nickel-binding enzyme that catalyses the hydrolysis of urea to carbon dioxide and ammonia . Historically, it was the first enzyme to be crystallized (in 1926). It is mainly found in plant seeds, microorganisms and invertebrates. In plants, urease is a hexamer of identical chains. In bacteria , it consists of either two or three different subunits (alpha, beta and gamma).

Urease binds two nickel ions per subunit; four histidine, an aspartate and a carbamated-lysine serve as ligands to these metals; an additional histidine is involved in the catalytic mechanism . The urease domain forms an (α/β)(8) barrel structure with structural similarity to other metal-dependent hydrolases, such as adenosine and AMP deaminase and phosphotriesterase.

This entry represents a conserved region that contains the active site histidine.
Urease alpha subunit, C-terminal (Urease_asu_c)
Type: Domain

This entry describes the C-terminal domain of urease alpha subunit UreC (designated beta or UreB in Helicobacter species).

Urease (

) belongs to MEROPS peptidase family M38 (clan MJ).

Urease (urea amidohydrolase,

) a nickel-binding enzyme that catalyses the hydrolysis of urea to form ammonia and carbamate . It is mainly found in plant seeds, microorganisms and invertebrates. In plants, urease is a hexamer of identical chains, but the subunit composition of urease from different sources varies ; in bacteria it consists of either two or three different subunits (alpha, beta and gamma).

Urease binds two nickel ions per subunit; four histidine, an aspartate and a carbamated-lysine serve as ligands to these metals; an additional histidine is involved in the catalytic mechanism . The urease domain forms an (α/β)(8) barrel structure with structural similarity to other metal-dependent hydrolases, such as adenosine and AMP deaminase (see

) and phosphotriesterase see

). Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction.

In Helicobacter pylori, the gamma and beta domains are fused and called the alpha subunit (

). The catalytic subunit (called beta or B) has the same organisation as the Klebsiella alpha subunit. Jack bean (Canavalia ensiformis) urease has a fused gamma-beta-alpha organisation (

).
Carbohydrate kinase, predicted, conserved site (Carbohydrate_kinase_pred_CS)
Type: Conserved_site

Proteins in this entry are related to Hydroxyethylthiazole kinase (

) and PfkB carbohydrate kinase

implying they are also carbohydrate kinases.

Several uncharacterised proteins have been shown to share regions of similarities, including yeast chromosome XI hypothetical protein YKL151c; Caenorhabditis elegans hypothetical protein R107.2; Escherichia coli hypothetical protein yjeF;
Bacillus subtilis hypothetical protein yxkO; Helicobacter pylori hypothetical protein HP1363; Mycobacterium tuberculosis hypothetical protein MtCY77.05c; Mycobacterium leprae hypothetical protein B229_C2_201; Synechocystis sp. (strain PCC 6803) hypothetical protein sll1433; and Methanocaldococcus jannaschii (Methanococcus jannaschii) hypothetical protein MJ1586. These are proteins of about 30 to 40kDa whose central region is well conserved.
Lipid-binding serum glycoprotein, conserved site (Lipid-bd_serum_glycop_CS)
Type: Conserved_site

This entry represents a conserved sequence region found in the N-terminal domain of several lipid-binding serum glycoproteins. The N- and C-terminal domains of these proteins share a similar two-layer α/β structure, but they show little sequence identity. Proteins containing this N-terminal domain include:

Bactericidal permeability-increasing protein (BPI)

Lipopolysaccharide-binding protein (LBP)

Cholesteryl ester transfer protein (CETP)

Phospholipid transfer protein (PLTP)

Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC)

Bactericidal permeability-increasing protein (BPI) is a potent antimicrobial protein of 456 residues that binds to and neutralises lipopolysaccharides from the outer membrane of Gram-negative bacteria . BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity .
AT hook, DNA-binding motif (AT_hook_DNA-bd_motif)
Type: Conserved_site

AT hooks are DNA-binding motifs with a preference for A/T rich regions. These motifs are found in a variety of proteins, including the high mobility group (HMG) proteins , in DNA-binding proteins from plants and in hBRG1 protein, a central ATPase of the human switching/sucrose non-fermenting (SWI/SNF) remodelling complex .
P-type trefoil, conserved site (P_trefoil_CS)
Type: Conserved_site

A cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins . It is known as either the 'P', 'trefoil' or 'TFF' domain, and contains six cysteines linked by three disulphide bonds with connectivity 1-5, 2-4, 3-6. The domain has been found in a variety of extracellular eukaryotic proteins , including protein pS2 (TFF1), a protein secreted by the stomach mucosa; spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that inhibits gastrointestinal motility and gastric acid secretion; intestinal trefoil factor (ITF) (TFF3); Xenopus laevis stomach proteins xP1 and xP4; Xenopus integumentary mucins A.1 (FIM-A.1 or preprospasmolysin) and C.1 (FIM-C.1), proteins which may be involved in defence against microbial infections by protecting the epithelia from the external environment; Xenopus skin protein xp2 (or APEG); Zona pellucida sperm-binding protein B (ZP-B); intestinal sucrase-isomaltase (

/

), a vertebrate membrane bound, multifunctional enzyme complex which hydrolyses sucrose, maltose and isomaltose; and lysosomal alpha-glucosidase (

).
Glutamyl-tRNA(Gln) amidotransferase, subunit B, conserved site (Gln-tRNA_amidoTrfase_suB_CS)
Type: Conserved_site

Glutamyl-tRNA(Gln) amidotransferase (Gat; [ec:EC 6.3.5]) provides a means of producing correctly charged Gln-tRNA(Gln) through the transamidation of mis-acylated Glu-tRNA(Gln) in organisms which lack glutaminyl-tRNA synthetase . The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). The enzyme is composed of three subunits: A (an amidase), B and C. It also exists in eukaryotes as a protein targeted to the mitochondria.

The heterotrimer GatABC is involved in converting Glu to Gln and/or Asp to Asn, when the amino acid is attached to the appropriate tRNA. In Lactobacillus, GatABC is responsible for producing tRNA(Gln). In Archaea, GatABC is responsible for producing tRNA(Asn), while GatDE is responsible for producing tRNA(Gln). In lineages that include Thermus, Chlamydia, or Acidithiobacillus, the GatABC complex catalyses both tRNA(Gln) and tRNA(Asn).

This entry represents a conserved region located in the N-terminal of the B subunit of glutamyl-tRNA(Gln) amidotransferase.
Aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase, subunit B /E (Asn/Gln-tRNA_amidoTrfase_suB/E)
Type: Family

Glutamyl-tRNA(Gln) amidotransferase (Gat;

) provides a means of producing correctly charged Gln-tRNA(Gln) through the transamidation of mis-acylated Glu-tRNA(Gln) in organisms which lack glutaminyl-tRNA synthetase . The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). The enzyme is composed of three subunits: A (an amidase), B and C. It also exists in eukaryotes as a protein targeted to the mitochondria.

The heterotrimer GatABC is involved in converting Glu to Gln and/or Asp to Asn, when the amino acid is attached to the appropriate tRNA. In Lactobacillus, GatABC is responsible for producing tRNA(Gln). In Archaea, GatABC is responsible for producing tRNA(Asn), while GatDE is responsible for producing tRNA(Gln). In lineages that include Thermus, Chlamydia, or Acidithiobacillus, the GatABC complex catalyses both tRNA(Gln) and tRNA(Asn).

Glutamyl-tRNA(Gln) amidotransferase, subunit E (GatE) is found only in the Archaea. It is part of a heterodimer, with GatD (

), that acts as an amidotransferase on misacylated Glu-tRNA(Gln) to produce Gln-tRNA(Gln) . The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). The GatDE system is specific for glutamate and does not act on aspartate. This function is carried out in bacteria by the GatABC system, which acts both on Asp-tRNA(Asn) and Glu-tRNA(Gln). GatABC orthologues also exist in some archaea, where it coexist with GatDE (GatE being paralogous to GatB); while other archaea only posses GatED and use an asparaginyl-tRNA synthetase to produce Asn-tRNA by direct acylation of the tRNA . The crystal structure of GatED showed tRNA(Gln) recognition by indirect readout based on shape complementarity .

This entry represents aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase subunit B and glutamyl-tRNA(Gln) amidotransferase subunit E.
DNA polymerase, Y-family, little finger domain (DNA_pol_Y-fam_little_finger)
Type: Domain

This entry represents the little finger domain found in Y-family (lesion bypass) DNA polymerases. Y-family polymerases were originally known as UmuC/DinB/Rev1/Rad30 after each branch of the family. These enzymes are characterised by their low-fidelity synthesis on undamaged DNA templates and by their ability to traverse replication-blocking lesions. By contrast, high-fidelity polymerases (such as DNA polymerase III) are sensitive to distortions in the DNA template. As a result, Y-family polymerases can extend primer strands across DNA strand lesions that would otherwise stall replicative polymerases. To minimize mutations through their low fidelity synthesis, these enzymes are regulated, and are thought to interact with processivity factors, β-clamp or proliferating cell nuclear antigen (PCNA), which are also essential for the function of replicative DNA polymerases . Organisms can contain more than one Y-family polymerase, each with a unique DNA damage bypass and fidelity profile. For example, humans posses four Y-family polymerases: DNA polymerases kappa, iota, eta and Rev1. Y-family polymerases show no homology to DNA polymerases from the A-, B-, C-, D- or X-families .
DNA-directed DNA polymerase, family B, conserved site (DNA-dir_DNA_pol_B_CS)
Type: Conserved_site

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases (

) by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used for the
de novo
synthesis of a DNA chain. Even though there are 2 different methods of priming, these are mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation.
HMG box A DNA-binding domain, conserved site (HMG_boxA_CS)
Type: Conserved_site

High mobility group (HMG or HMGB) proteins constitute a family of relatively low molecular weight non-histone components in chromatin. HMG1 and HMG2 are highly similar, and preferentially bind single-stranded DNA and unwind double-stranded DNA. Although they have no sequence specificity, they have a high affinity for bent or distorted DNA, and bend linear DNA. HMG1 and HMG2 contain two DNA-binding HMG-box domains (A and B) that show structural and functional differences, and have a long acidic C-terminal domain rich in aspartic and glutamic acid residues. The acidic tail modulates the affinity of the tandem HMG boxes in HMG1 and 2 for a variety of DNA targets. HMG1 and 2 appear to play important architectural roles in the assembly of nucleoprotein complexes in a variety of biological processes, for example V(D)J recombination, the initiation of transcription, and DNA repair .

This signature identifies HMG box A, which is only found in HMG 1 and 2 proteins whereas the HMG box B is also present in various transcription factors. HMG boxes have unusual DNA binding activity. They bind preferentially to distorted DNAs, such as four-way junctions, kinked cisplatin-modified DNA, DNA bulges, and have the property to bend DNA . They can bind DNA without sequence specificity like in HMG1 and 2 or recognise a specific site.
Acylphosphatase, conserved site (Acylphosphatase_CS)
Type: Conserved_site

Acylphosphatase (

) is an enzyme of approximately 98 amino acid residues that specifically catalyses the hydrolysis of the carboxyl-phosphate bond of acylphosphates , its substrates including 1,3-diphosphoglycerate and carbamyl phosphate . The enzyme has a mainly β-sheet structure with 2 short α-helical segments. It is distributed in a tissue-specific manner in a wide variety of species, although its physiological role is as yet unknown : it may, however, play a part in the regulation of the glycolytic pathway and pyrimidine biosynthesis . There are two known isozymes. One seems to be specific to muscular tissues, the other, called 'organ-common type', is found in many different tissues. A number of bacterial and archebacterial hypothetical proteins are highly similar to that enzyme and that probably possess the same activity.

This entry represents a conserved site found in the acylphosphatase domain. It is also found in an acylphosphatase-like domain in some prokaryotic hydrogenase maturation HypF carbamoyltransferases .
Heavy-metal-associated, conserved site (Heavy-metal-associated_CS)
Type: Conserved_site

Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures.

These proteins provide an important focus for research, some being involved in bacterial resistance to toxic metals, such as lead and cadmium, while others are involved in inherited human syndromes, such as Wilson's and Menke's diseases .

A conserved domain has been found in a number of these heavy metal transport or detoxification proteins . The domain, which has been termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that are probably involved in metal binding.

Structure solution of the fourth HMA domain of the Menke's copper transporting ATPase shows a well-defined structure comprising a four-stranded antiparallel β-sheet and two α-helices packed in an α-β sandwich fold . This fold is common to other domains and is classified as "ferredoxin-like".
Homeobox, conserved site (Homeobox_CS)
Type: Conserved_site

This entry represents a conserved site found in the homeodomain (HD), a protein domain of approximately 60 residues that usually binds DNA. It is encoded by the homeobox sequence , which was first identified in a number of Drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates . Members of this group are transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies . The domain binds DNA through a helix-turn-helix (HTH) structure. The HTH motif is characterised by two α-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure.

The motif is very similar in sequence and structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins, homeotic proteins, etc.). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn which is needed to avoid steric interference of the β-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.
Claudin, conserved site (Claudin_CS)
Type: Conserved_site

This entry represents a conserved region located in an extracellular loop between the first and second transmembrane regions.

Zona occludens (ZO), or tight junctions (TJ), are specialised membrane domains found at the most apical region of polarised epithelial and endothelial cells. They create a primary barrier, preventing paracellular transport of solutes, and restricting the lateral diffusion of membrane lipids and proteins, thus maintaining cellular polarity . They also act as diffusion barriers within plasma membranes, creating and maintaining apical and basolateral membrane domains. Under freeze-fracture electron microscopy, TJs appear as a network of continuous anastomosing intramembranous strands. These strands consist mainly of claudins and occludin (

), which are transmembrane proteins that polymerise within plasma membranes to form fibrils .

Recently, the molecular architecture of tight junctions has begun to be elucidated. One group of proteins thought to be major components of TJs is the claudin family . Immunofluorescence studies have shown that claudins are targeted to and incorporated into tight junctions . Furthermore, when claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native TJs .

The claudin protein family is encoded by at least 17 human genes, with many homologues cloned from other species. Tissue distribution patterns for the claudin family members are distinct. Claudin-1 and -2, for example, are expressed at high levels in the liver and kidney, whereas claudin-3 mRNA is detected mainly in the lung and liver . This suggests that multiple claudin family members may be involved in tight junction strand formation in a tissue-dependent manner.
Tubulin, conserved site (Tubulin_CS)
Type: Conserved_site

Microtubules are polymers of tubulin, a dimer of two 55kDa subunits, designated alpha and beta . Within the microtubule lattice, α-β heterodimers associate in a head-to-tail fashion, giving rise to microtubule polarity. Fluorescent labelling studies have suggested that tubulin is oriented in microtubules with beta-tubulin toward the plus end .

For maximal rate and extent of polymerisation into microtubules, tubulin requires GTP. Two molecules of GTP are bound at different sites, termed N and E. At the E (Exchangeable) site, GTP is hydrolysed during incorporation into the microtubule. Close to the E site is an invariant region rich in glycine residues, which is found in both chains and is thought to control access of the nucleotide to its binding site .

Most species, excepting simple eukaryotes, express a variety of closely- related alpha- and beta-isotypes. A third family member, gamma tubulin, has also been identified in a number of species. Gamma tubulin is found at microtubule-organising centres, such as the spindle poles or the centrosome, suggesting that it is involved in minus-end nucleation of microtubule assembly .

This entry represents the glycine-rich conserved site near the E (Exchangeable) site that controls the access of the nucleotide to its binding site.
Zona pellucida domain, conserved site (ZP_dom_CS)
Type: Conserved_site

The zona pellucida (ZP) domain is a protein polymerisation module of ~260 amino acid module, which is found at the C terminus of many secreted eukaryotic glycoproteins that play fundamental roles in development, hearing, immunity, and cancer . Proteins containing a ZP domain include:

Sperm receptor proteins ZP2 and ZP3. Along with protein ZP1, proteins ZP2 and ZP3 are responsible for sperm-adhesion to the zona pellucida. ZP3 first binds to specific sperm proteins, thus mediating sperm contacts with the oocyte. ZP2 acts as a second sperm receptor reinforcing the interactions. ZP1 cross-links the polymers formed by ZP2 and ZP3.

Zona pellucida sperm-binding protein B (ZP-B) (also known as ZP-X in rabbit and ZP-3 α in pig).

Glycoprotein GP2, the major component of pancreatic secretory granule membranes.

TGF-beta receptor type III (also known as betaglycan). This protein is a proteoglycan that binds to TGF-beta and could be involved in capturing and retaining TGF-beta for presentation to the signalling receptors.

Uromodulin (also known as Tamm-Horsfall urinary glycoprotein). The function of this protein, which is the most abundant in human urine, is not yet clear.

Chicken beta-tectorin, a major glycoprotein of avian tectorial membrane.

Most ZP domain proteins are synthesized as precursors with carboxy-terminal transmembrane domains or glycosyl phosphatidylinositol (GPI) anchors .

The ZP domain contains eight strictly conserved cysteines, which form disulphide bridges. The disulphide bonds within the ZP domains are divided into two groups, suggesting that the ZP domain consists of two subdomains. In addition to the conserved cysteines, only a few aromatic or hydrophobic amino acids are absolutely invariant, probably as a result of structural rather than functional constraints .

This entry represents a conserved site found within the zona pellucida domain, and includes 2 conserved Cys residues.