SII-SWORD/CoKE huggingface dataset:
Thioredoxin domain (Thioredoxin_domain)
Type: Domain

This entry represents the thioredoxin domain.

Thioredoxins are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of two cysteine thiol groups to a disulphide, accompanied by the transfer of two electrons and two protons. The net result is the covalent interconversion of a disulphide and a dithiol. In the NADPH-dependent protein disulphide reduction, thioredoxin reductase (TR) catalyses the reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulphide; reduced thioredoxin then directly reduces the disulphide in the substrate protein .

Thioredoxin is present in prokaryotes and eukaryotes and the sequence around the redox-active disulphide bond is well conserved. All thioredoxins contain a cis-proline located in a loop preceding β-strand 4, which makes contact with the active site cysteines, and is important for stability and function . Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulphide isomerase DsbA, and the N-terminal domain of glutathione transferase . Thioredoxins have a β-α unit preceding the motif common to all these proteins.

A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, most of them are protein disulphide isomerases (PDI). PDI (

) is an endoplasmic reticulum multi-functional enzyme that catalyses the formation and rearrangement of disulphide bonds during protein folding . All PDI contains two or three (ERp72) copies of the thioredoxin domain, each of which contributes to disulphide isomerase activity, but which are functionally non-equivalent . Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide isomerase activity . The various forms of PDI which are currently known are:

PDI major isozyme; a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase (

), as a component of oligosaccharyl transferase (

), as thyroxine deiodinase (

), as glutathione-insulin transhydrogenase (

) and as a thyroid hormone-binding protein

ERp60 (ER-60; 58 Kd microsomal protein). ERp60 was originally thought to be a phosphoinositide-specific phospholipase C isozyme and later to be a protease.

ERp72.

ERp5.

Bacterial proteins that act as thiol:disulphide interchange proteins that allows disulphide bond formation in some periplasmic proteins also contain a thioredoxin domain. These proteins include:

Escherichia coli DsbA (or PrfA) and its orthologs in Vibrio cholerae (TtcpG) and Haemophilus influenzae (Por).

E. coli DsbC (or XpRA) and its orthologues in Erwinia chrysanthemi and H. influenzae.

E. coli DsbD (or DipZ) and its H. influenzae orthologue.

E. coli DsbE (or CcmG) and orthologues in H. influenzae.

Rhodobacter capsulatus (Rhodopseudomonas capsulata) (HelX), Rhiziobiacae (CycY and TlpA).
PAS fold (PAS_fold)
Type: Domain

PAS domains are involved in many signalling proteins where they are used as a signal sensor domain . PAS domains appear in archaea, bacteria and eukaryotes. Several PAS-domain proteins are known to detect their signal by way of an associated cofactor. Heme,
flavin, and a 4-hydroxycinnamyl chromophore are used in different proteins. The PAS domain was named after three proteins that it occurs in:

Per- period circadian protein

Arnt- Ah receptor nuclear translocator protein

Sim- single-minded protein.

PAS domains are often associated with PAC domains

. It appears that these domains are directly linked, and that together they form the conserved 3D PAS fold. The division between the PAS and PAC domains is caused by major differences in sequences in the region connecting these two motifs . In human PAS kinase, this region has been shown to be very flexible, and adopts different conformations depending on the bound ligand . Probably the most surprising identification of a PAS domain was that in EAG-like K

-channels .
Band 3 cytoplasmic domain (Band3_cytoplasmic_dom)
Type: Domain

This entry contains the cytoplasmic domain of the Band 3 anion exchange proteins that exchange Cl-/HCO3-. Band 3 constitutes the most abundant polypeptide in the red blood cell membrane, comprising 25% of the total membrane protein. The cytoplasmic domain of band 3 functions primarily as an anchoring site for other membrane-associated proteins. Included among the protein ligands of cdb3 are ankyrin, protein 4.2, protein 4.1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphofructokinase, aldolase, hemoglobin, hemichromes, and the protein tyrosine kinase (p72syk) .
Alpha-amylase, plant (A-amylase_pln)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

This entry represents a subfamily of alpha-amylase proteins that are found in plants.
Alpha-amylase, thermostable (A-amylase_thermo)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

This entry represents a subfamily of alpha-amylase proteins that are highly thermostable. Studies on amylases with different thermostabilities have revealed several structural and dynamic features that can affect thermal adaptation . One of these features is the number of calcium-binding sites that the enzyme contains, with extra calcium-binding sites contributing to structural stability .
Alpha-amylase-like (A-amylase-like)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

This entry includes alpha-amylases and related proteins .
Glycosyl hydrolase, all-beta (Glyco_hydro_b)
Type: Homologous_superfamily

This entry represents the all-β domain superfamily that is found in several members of the glycosyl hydrolase family 13 and other glycosyl hydrolases. It is usually located C-terminal to the catalytic β/α barrel domain. The structure of this domain has been found to be a Greek key β-sheet fold .

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
Immunoglobulin-like fold (Ig-like_fold)
Type: Homologous_superfamily

This superfamily represents domains with an immunoglobulin-like (Ig-like) fold, which consists of a β-sandwich of seven or more strands in two sheets with a Greek-key topology. Ig-like domains are one of the most common protein modules found in animals, occurring in a variety of different proteins. These domains are often involved in interactions, commonly with other Ig-like domains via their β-sheets . Domains within this fold-family share the same structure, but can diverge with respect to their sequence. Based on sequence, Ig-like domains can be classified as V-set domains (antibody variable domain-like), C1-set domains (antibody constant domain-like), C2-set domains, and I-set domains (antibody intermediate domain-like). Proteins can contain more than one of these types of Ig-like domains. For example, in the human T-cell receptor antigen CD2, domain 1 (D1) is a V-set domain, while domain 2 (D2) is a C2-set domain, both domains having the same Ig-like fold .

Domains with an Ig-like fold can be found in many, diverse proteins in addition to immunoglobulin molecules. For example, Ig-like domains occur in several different types of receptors (such as various T-cell antigen receptors), several cell adhesion molecules, MHC class I and II antigens, as well as the hemolymph protein hemolin, and the muscle proteins titin, telokin and twitchin.
Carbohydrate-binding-like fold (Carb-bd-like_fold)
Type: Homologous_superfamily

This superfamily represents domains with a carbohydrate-binding-like fold, which consists of a seven-stranded β-sandwich with a Greek key topology, although some members may have 1-2 extra strands. These domains are present as carbohydrate-binding modules in a number of glycosyl hydrolases, often at the C-terminal end, as well as in rhamnogalacturonase B (RhgB), where it occurs as a central domain .
Aldolase-type TIM barrel (Aldolase_TIM)
Type: Homologous_superfamily

This entry represents the TIM β/α barrel found in aldolase and in related proteins. This TIM barrel usually covers the entire protein structure. Proteins containing this TIM barrel domain include class I aldolases, class I DAHP synthases, class II fructose-bisphosphate aldolases (FBP aldolases), and 5-aminolevulinate dehydratase (a hybrid of classes I and II aldolases) .
Acyl-CoA dehydrogenase/oxidase, N-terminal (AcylCoA_DH/ox_N)
Type: Domain

The monomeric enzyme is folded into three domains of approximately equal size, where the N-terminal domain is all-α, the middle domain is an open (5,8) barrel, and the C-terminal domain is a four-helical bundle. The constituent families differ in the numbers of C-terminal domains. This entry represents the N-terminal α-helical domain found in medium chain acyl-CoA dehydrogenases, as well as in the related peroxisomal acyl-CoA oxidase-II enzymes. Acyl-CoA oxidase (ACO;

) catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids .

Acyl-CoA dehydrogenases (

) are a family of flavoproteins that catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with the concomitant reduction of enzyme-bound FAD. Different family members share a high sequence identity, catalytic mechanisms, and structural properties, but differ in the position of their catalytic bases and in their substrate binding specificity. Butyryl-CoA dehydrogenase prefers short chain substrates, medium chain-and long-chain acyl-CoA dehydrogenases prefer medium and long chain substrates, respectively, and Isovaleryl-CoA dehydrogenase prefers branched-chain substrates.
S100/CaBP-9k-type, calcium binding, subdomain (S100_Ca-bd_sub)
Type: Domain

The calcium-binding domain found in S100 and CaBP-9k proteins is a subfamily of the EF-hand calcium-binding domain . S100s are small dimeric acidic calcium and zinc-binding proteins abundant in the brain, with S100B playing an important role in modulating the proliferation and differentiation of neurons and glia cells . S100 proteins have two different types of calcium-binding sites: a low affinity one with a special structure, and a 'normal' EF-hand type high-affinity site.

Calbindin-D9k (CaBP-9k) also belong to this family of proteins, but it does not form dimers. CaBP-9k is a cytosolic protein expressed in a variety of tissues. Although its precise function is unknown, it appears to be under the control of the steroid hormones oestrogen and progesterone in the female reproductive system . In the intestine, CaBP-9k may be involved in calcium absorption by mediating intracellular diffusion .

This entry represents a subdomain of the calcium-binding domain found in S100, CaBP-9k, and related proteins.
Hemocyanin/hexamerin (Hemocyanin/hexamerin)
Type: Family

Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and insect hexamerins (storage proteins) are homologous gene products, although the latter do not bind oxygen .

Haemocyanins are found in the haemolymph of many invertebrates. They are divided into 2 main groups, arthropodan and molluscan. These have structurally similar oxygen-binding centres, which are similar to the oxygen-binding centre of tyrosinases, but their quaternary structures are arranged differently. The arthropodan proteins exist as hexamers comprising 3 heterogeneous subunits (a, b and c) and possess 1 oxygen-binding centre per subunit; and the molluscan proteins exist as cylindrical oligomers of 10 to 20 subunits and possess 7 or 8 oxygen-binding centres per subunit . Although the proteins have similar amino acid compositions, the only real similarity in their primary sequences is in the region corresponding to the second copper-binding domain, which also shows similarity to the copper-binding domain of tyrosinases.
Phosphotransferase system, mannose family IIA component (PTS_EIIA_man)
Type: Domain

Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains. The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of Escherichia coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this family can transport sorbose, fructose and N-acetylglucosamine.
Dwarfin (Dwarfin)
Type: Family

This family of proteins was first identified in Caenorhabditis elegans , Smad proteins that act as intracellular signal transducers and transcriptional modulators activated by TGF-beta and regulates the entry into a developmentally arrested larval state known as dauer, in response to non-favorable environmental conditions. Mammalian dwarfins are phosphorylated in response to TGF-beta and are implicated in control of cell growth . The dwarfin family also includes the Drosophila protein MAD that is required for the function of decapentaplegic (DPP) and may play a role in DPP signalling. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Dpp .
RNA 3'-terminal phosphate cyclase, insert domain (RNA3'-term_phos_cycl_insert)
Type: Domain

RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea. RNA 3'-terminal phosphate cyclase (

) catalyses the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA.

ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate

These enzymes might be responsible for production of the cyclic phosphate RNA ends that are known to be required by many RNA ligases in both prokaryotes and eukaryotes.

RNA cyclase is a protein of from 36 to 42kDa. The best conserved region is a glycine-rich stretch of residues located in the central part of the sequence and which is reminiscent of various ATP, GTP or AMP glycine-rich loops.

The crystal structure of RNA 3'-terminal phosphate cyclase shows that each molecule consists of two domains. The larger domain contains three repeats of a folding unit comprising two parallel α helices and a four-stranded β sheet; this fold was previously identified in translation initiation factor 3 (IF3). The large domain is similar to one of the two domains of 5-enolpyruvylshikimate-3-phosphate synthase and UDP-N-acetylglucosamine enolpyruvyl transferase. The smaller insert domain disrupts the large domain, and uses a similar secondary structure element with different topology, observed in many other proteins such as thioredoxin . Although the active site of this enzyme could not be unambiguously assigned, it can be mapped to a region surrounding His309, an adenylate acceptor, in which a number of amino acids are highly conserved in the enzyme from different sources .
RNA 3'-terminal phosphate cyclase/enolpyruvate transferase, alpha/beta (RNA3'P_cycl/enolpyr_Trfase_a/b)
Type: Homologous_superfamily

This superfamily represents an α/β domain consisting of alternating β-strands and α helices in two layer. This domain is found in RNA 3'-terminal phosphate cyclase (RPTC), where it occurs as a duplication of three repeats of this fold packed together around a pseudo three-fold axis . RNA cyclases are a family of RNA-modifying enzymes that catalyse the ATP-dependent conversion of the 3'-phosphate to the 2',3'-cyclic phosphodiester at the end of RNA. These cyclases contain an insert α/β domain with a thioredoxin topology (

).

This domain is also found in enolpyruvate transferase, where it occurs as a duplication of six repeats of this fold organised into two RPTC-like domains . Enolpyruvate transferase is the first enzyme in bacterial peptidoglycan biosynthesis, catalysing the transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetyl-glucosamine.
Porin, Gram-negative type, conserved site (Porin_Gram-ve_CS)
Type: Conserved_site

Porins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts, where they form ion-selective channels for small hydrophilic molecules (up to ~600 D) . X-ray structure analyses of several bacterial porins have revealed a large 16-stranded anti-parallel β-barrel structure enclosing the transmembrane pore, by contrast with all other integral membrane proteins described to date, which are α-helical. Three subunits form a trimer; the 3-fold axis is approximately parallel to the barrel axes and is assumed to be perpendicular to the membrane plane.

From the range of porins now known, similarities have been observed between porins from different species, and between porins of different specificity within the same species. But most porins cannot be related to each other on the basis of sequence alone, and this is reflected in the lengths of the known porin sequences, which range from 282-483 residues/monomer.

This entry represents a conserved region found in porins from Gram-negative bacteria. It is located in the C-terminal part of these proteins and spans two putative transmembrane β strands.
DNA/RNA-binding protein Alba (DNA/RNA-bd_Alba)
Type: Family

The DNA/RNA-binding protein Alba binds double-stranded DNA tightly but without sequence specificity. It binds rRNA and mRNA in vivo, and may play a role in maintaining the structural and functional stability of RNA, and, perhaps, ribosomes. It is distributed uniformly and abundantly on the chromosome. Alba has been shown to bind DNA and affect DNA supercoiling in a temperature dependent manner . It is regulated by acetylation (alba = acetylation lowers binding affinity) by the Sir2 protein. Alba is proposed to play a role in establishment or maintenance of chromatin architecture and thereby in transcription repression. For further information see .
Maltooligosyl trehalose synthase, domain 4 (Maltooligo_trehalose_synth_4)
Type: Homologous_superfamily

Maltooligosyl trehalose synthase (

) is one of two enzymes in the coupled trehalose biosynthesis system in the archaea Sulfolobus acidocaldarius . This enzyme catalyses the conversion of maltopentaose to maltotriosyltrehalose, which is further hydrolysed by maltooligosyl trehalose trehalohydrolase to produce trehalose and maltotriose .