SII-SWORD/CoKE huggingface dataset:
BESS motif (BESS_motif)
Type: Domain

The BESS domain has been named after the three proteins that originally defined the domain: BEAF (Boundary element associated factor 32) , Suvar(3)7 and Stonewall ). The BESS domain is 40 amino acid residues long and is predicted to be composed of three α helices, as such it might be related to the myb/SANT HTH domain. The BESS domain directs a variety of protein-protein interactions, including interactions with itself, with Dorsal, and with a TBP-associated factor. It is found in a single copy in Drosophila proteins and is often associated with the MADF domain .

Proteins known to contain a BESS domain include:

Drosophila Boundary element associated factor 32 (BEAF-32).

Drosophila Suppressor of variegation protein 3-7 (Su(var)3-7), which could play a role in chromosome condensation.

Drosophila Ravus, which is homologous to the C-terminal part of Su(var)3-7 .

Drosophila Stonewall (Stwl), a putative transcription factor required for maintenance of female germline stem cells as well as oocyte differentiation.

Drosophila Adf-1, a transcription factor first identified on the basis of its interaction with the alcohol dehydrogenase promoter but that binds the promoters of a diverse group of genes .

Drosophila Dorsal-interacting protein 3 (Dip3). It functions both as an activator to bind DNA in a sequence specific manner and a coactivator to stimulate synergistic activation by Dorsal and Twist .
Recombination endonuclease VII (Endonuclease_7)
Type: Family

This family of proteins which includes Bacteriophage T4 endonuclease VII, Mycobacteriophage D29 gene 59, and other as yet uncharacterised proteins. The T4 endonuclease VII (Endo VII) recognises a broad spectrum of DNA substrates ranging from branched DNAs to single base mismatches. The structure of this enzyme has been resolved and it was found that the monomers form an elongated, intertwined molecular dimer that exibits extreme domain swapping. Two pairs of antiparallel helices which form a novel 'four-helix cross' motif are the major dimerisation elements .
GTF2I-like repeat (GTF2I)
Type: Repeat

This region of sequence similarity is found up to six times in a variety of proteins including general transcription factor II-I (GTF2I). It has been suggested that this may be a DNA binding domain .
Flt3 ligand (Flt3_lig)
Type: Family

The flt3 (fms-related tyrosine kinase 3) ligand is a short chain cytokine with a 4 helical bundle fold. It is a type I membrane protein which stimulates the proliferation of of early hematopoeitic cells, and synergises well with other colony stimulating factors and interleukins.
Conotoxin (Conotoxin)
Type: Family

Cone snail toxins, conotoxins, are small neurotoxic peptides with disulphide connectivity that target ion-channels or G-protein coupled receptors. Based on the number and pattern of disulphide bonds and biological activities, conotoxins can be classified into several families . Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine knot scaffold. The knottin scaffold is a very special disulphide-through-disulphide knot, in which the III-VI disulphide bond crosses the macrocycle formed by two other disulphide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N terminus.

The disulphide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins . The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers . Mu conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu conotoxins target the voltage-gated sodium channels , and are useful probes for investigating voltage-dependent sodium channels of excitable tissues . Alpha conotoxins have two types of cysteine arrangements , and are competitive nicotinic acetylcholine receptor antagonists.
Prokaryotic glutathione synthetase, N-terminal (GSHS_N)
Type: Domain

Prokaryotic glutathione synthetase

(glutathione synthase) catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to orthophosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis. The enzyme is inhibited by 7,8-dihydrofolate, methotrexate and trimethoprim. This domain is the N terminus of the enzyme.
L-fucose/L-arabinose isomerase, C-terminal (Fuc/Ara_isomerase_C)
Type: Homologous_superfamily

L-fucose isomerase (

) converts the aldose L-fucose into the corresponding ketose L-fuculose during the first step in fucose metabolism using Mn2+ as a cofactor. The enzyme is a hexamer, forming the largest structurally known ketol isomerase, and has no sequence or structural similarity with other ketol isomerases. The structure was determined by X-ray crystallography at 2.5 A resolution .
Tim10-like (Tim10-like)
Type: Domain

This domain has four conserved cysteine residues. It is found in proteins Tim8, Tim9, Tim10 and Tim13, which are involved in mitochondrial protein import and seem to be localised to the mitochondrial intermembrane space. The Tim8-Tim13 complex has a complex architecture, similar to the Tim9-Tim10 complex, composed of a hexametric architecture with long helices which look like tentacles extend from a central loop . In each subunit of the Tim9-Tim10 complex, a signature "twin CX3C" motif forms two intramolecular disulfides .

Defects in the Tim8A gene (DDP1) have been shown to be the cause of 2 human syndromes: Mohr-Tranebjaerg syndrome (MTS); also known as dystonia-deafness syndrome (DDS) or X-linked progressive deafness type 1 (DFN-1); and Jensen syndrome (JENSS); also known as opticoacoustic nerve atrophy with dementia.
Prokaryotic glutathione synthetase, ATP-binding (GSHS_ATP-bd)
Type: Domain

Prokaryotic glutathione synthetase

(glutathione synthase) catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to orthophosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis. The enzyme is inhibited by 7,8-dihydrofolate, methotrexate and trimethoprim. This is the ATP-binding domain of the enzyme.
TT viral protein of unknown function (TTvirus_Unk)
Type: Family

Torque teno virus, isolated initially from a Japanese patient with hepatitis of unknown aetiology, has since been found to infect both healthy and diseased individuals and numerous prevalence studies have raised questions about its role in unexplained hepatitis. ORF1 is a large 750 residue protein.
5-carboxymethyl-2-hydroxymuconate isomerase (5-COMe_2-OHmuconate_Isoase)
Type: Family

5-carboxymethyl-2-hydroxymuconate isomerase transforms 5-carboxymethyl-2-hydroxy-muconic acid into 5-oxo-pent-3-ene-1,2,5-tricarboxylic acid during the third step of the homoprotocatechuate catabolic pathway . Homoprotocatechuate (HPC; 3,4-dihydroxyphenylacetate) is catabolized to Krebs cycle intermediates via extradiol (meta-) cleavage and the necessary enzymes are chromosomally encoded in a variety of bacteria . 5-carboxymethyl-2-hydroxymuconate isomerase is probably a dimer of two identical subunits . A comparison of the N-terminal half of the isomerase/decarboxylase sequence from the pathway (both encoded by the gene hpcE), with the second half showed significant similarity. This suggests that a duplication may have occurred to produce a bifunctional gene .
Restriction endonuclease, type II, EcoRI (Restrct_endonuc_II_EcoRI)
Type: Family

This entry represents the P subtype Type II restriction endonuclease EcoRI and its isoschizomer RsrI . Both enzymes require magnesium as a cofactor and recognise the DNA sequence GAATTC and cleaves after G-1 .

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .
Methane monooxygenase, gamma chain (Me_mOase_g)
Type: Family

Methane monooxygenases (

) catalyse the oxidation of methane to methanol in the presence of oxygen and NADH in methanotrophs. It has a broad specificity, hydroxylating many alkanes, and converting alkenes into the corresponding epoxides. In additional reactions, CO is oxidized to CO2, ammonia is oxidized to hydroxylamine, and some aromatic compounds and cyclic alkanes can also be hydroxylated, although more slowly. In Methylococcus capsulatus there are two forms of the enzyme, a soluble and a membrane-bound type. The soluble form consists of 3 components, A, B and C. Protein A is made up of 3 chains, alpha, beta and gamma.

This entry represents the gamma chain of methane monooxygenases. Structurally, the gamma chain contains two domains, each consisting of a three helices arranged in an open bundle topology .
Vitamin B12-dependent methionine synthase, activation domain (VitB12-dep_Met_synth_activ_dom)
Type: Domain

Vitamin B12 dependent methionine synthase

(5-methyltetrahydrofolate--homocysteine S-methyltransferase) catalyses the conversion of 5-methyltetrahydrofolate and L-homocysteine to tetrahydrofolate and L-methionine as the final step in
de novo
methionine biosynthesis. The enzyme requires methylcobalamin as a cofactor. In humans, defects in this enzyme are the cause of autosomal recessive inherited methylcobalamin deficiency (CBLG), which causes mental retardation, macrocytic anemia and homocystinuria. Mild deficiencies in activity may result in mild hyperhomocysteinemia, and mutations in the enzyme may be involved in tumorigenesis. Vitamin B12 dependent methionine synthase is found in prokaryotes and eukaryotes, but in prokaryotes the cofactor is cobalamin.

In Escherichia coli, methionine synthase is a large enzyme composed of four structurally and functionally distinct modules: the first two modules bind homocysteine and tetrahydrofolate, the third module binds the B12 cofactor (

,

), and the C-terminal module (activation domain) binds S-adenosylmethionine. The activation domain is essential for the reductive activation of the enzyme. During the catalytic cycle, the highly reactive cob(I)alamin intermediate can be oxidised to produce an inactive cob(II)alamin enzyme; the enzyme is then reactivated via reductive methylation by the activation domain . The activation domain adopts an unusual α/β fold.
Fumarate reductase type B, transmembrane subunit (Fum_red_B_TM)
Type: Family

Quinol:fumarate reductase (QFR) couples the reduction of fumarate to succinate to the oxidation of quinol to quinone, the opposite reaction to that catalyzed by the related protein, succinate:quinone oxidoreductase (SQR). QFR and SQR complexes are collectively referred to as succinate:quinone oxidoreductases and are predicted to share similar structures, containing either 3 or 4 subunits .

Subunit A (the flavoprotein subunit) contains the site of fumarate reduction and a covalently bound flavin adenine dinucleotide prosthetic group. Subunit B (the iron protein subunit) contains three iron-sulphur centres. Subunit(s) C (and D) (the membrane anchor subunits or cytochrome b subunits) include the membrane-spanning segments and binds haem b molecules . The composition of these hydrophobic, cytochrome B subunits varies depending on the enzyme subtype.

Type A have two polypeptides, with three transmembrane helices each, and contain two protoheme IX molecules (denoted heme bH and heme bL). Type B have one polypeptide with five transmembrane helices and contain heme bH and heme bL. Type C have the same polypeptide arrangement as Type A, but contains only one protoheme IX molecule, corresponding to heme bH. Type D have two polypeptides, with three transmembrane helices each, and are without heme .
Tubulin binding cofactor A (TBCA)
Type: Family

The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP .

This entry represents tubulin binding cofactor A (TBCA) from animal, plants and fungi. Human TBCA functions as a molecular chaperone for beta-tubulin . Budding yeast TBCA, also known as Rbl2, may bind transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic . The sequence identity of Rbl2 and human TBCA is only 32%, they appear to be structurally distinct and may interact with beta-tubulin by different mechanisms .
Formiminotransferase catalytic domain (Formiminotransferase_cat)
Type: Domain

This entry represents the formiminotransferase (FT) domain of formiminotransferase-cyclodeaminase (FTCD), which forms a homodimer, with each protomer being comprised of two subdomains. Each subdomain has the structure consisting of an α/β sandwich with antiparallel β-sheet in the form (β-α-β)x2. Tetrahydrofolate (THF)-dependent glutamate formiminotransferase is involved in the histidine utilization pathway. This enzyme interconverts L-glutamate and N-formimino-L-glutamate. The enzyme is bifunctional as it also catalyzes the cyclodeaminase reaction on N-formimino-THF, converting it to 5,10-methenyl-THF and releasing ammonia; part of the process of regenerating THF. This model covers enzymes from metazoa as well as Gram-positive bacteria and archaea. In humans, deficiency of this enzyme results in a disease phenotype . The crystal structure of the enzyme has been studied in the context of the catalytic mechanism .
Phycoerythrin alpha chain (Phycoerythr_a)
Type: Domain

Cryptophytes are unicellular photosynthetic algae that use a lumenally located light-harvesting system, which is distinct from the phycobilisome structure found in cyanobacteria and red algae. One of the key components of this system is water-soluble phycoerythrin (PE) 545 whose expression is enhanced by low light levels . Phycoerythrin (PE) 545 is a heterodimeric of α(1)α(2)betabeta subunits. Each alpha subunit carries a covalently linked 15,16-dihydrobiliverdin chromophore that probably acts as the final energy acceptor. The architecture of the heterodimer suggests that PE 545 may dock to an acceptor protein via a deep cleft and that energy may be transferred via this intermediary protein to the reaction centre .

The structure of this domain found in the alpha chain is a long β-hairpin and a single α-helix.
Methylamine dehydrogenase light chain (MeN_DH_Ltc)
Type: Family

This family consists of the light chain (small subunit) of methylamine dehydrogenase, a periplasmic enzyme. This subunit contains a tryptophan tryptophylquinone (TTQ) prosthetic group derived from Trp-114 and Trp-165 of the precursor, numbered according to the sequence from Paracoccus denitrificans . The enzyme forms a complex with the type I blue copper protein amicyanin and cytochrome. Electron transfer proceeds from TQQ to the copper and then to the heme group of the cytochrome.
DNA mismatch repair protein MutH (DNA_mismatch_repair_MutH)
Type: Family

MutS, MutL and MutH are the three essential proteins for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli. MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex. Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL .
Carboxypeptidase A inhibitor-like (COpept_A_inh-like)
Type: Domain

In molecular biology, the carboxypeptidase A inhibitor family is a family of proteins which is represented by the well-characterised metallocarboxypeptidase A inhibitor (MCPI) from potatoes, which belongs to the MEROPS inhibitor family I37, clan IE. It inhibits metallopeptidases belonging to MEROPS peptidase family M14, carboxypeptidase A.

Proteins with this domain include metallocarboxypeptidase inhibitor (MCPI) and fruit-specific protein. MCPI may play a defensive role against insect attacks .
Nitrile hydratase alpha/Thiocyanate hydrolase gamma (CN_Hdrtase_a/SCN_Hdrlase_g)
Type: Domain

Nitrile hydratases (

) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, α(2)β(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site . The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide . Fe-and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.

Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia .

The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino-and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase .

This entry represents the structural domain of the alpha subunit of both iron- and cobalt-containing nitrile hydratases; the alpha subunit is a duplication of two structural repeats, each consisting of 4 layers, α/β/β/α . This structure is also found in the related protein, the gamma subunit of thiocyanate hydrolase (SCNase).
FokI, recognition domain, subdomain 2 (FokI_D2)
Type: Domain

Type IIS restriction endonuclease FokI (

) is a member of an unusual class of bipartite restriction enzymes that recognises the double-stranded DNA sequence 5'-GGATG-3' and cleave DNA phosphodiester groups 9 base pairs away on this strand and 13 base pairs away on the complementary strand . FokI contains amino- and carboxy-terminal domains corresponding to the DNA-recognition and cleavage functions, respectively.

The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP .

This entry represents the subdomain D2 of FokI. D1 and D2 make almost all of the base-specific contacts with the DNA .
FokI, recognition domain, subdomain 1 (FokI_D1)
Type: Domain

Type IIS restriction endonuclease FokI (

) is a member of an unusual class of bipartite restriction enzymes that recognises the double-stranded DNA sequence 5'-GGATG-3' and cleave DNA phosphodiester groups 9 base pairs away on this strand and 13 base pairs away on the complementary strand . FokI contains amino- and carboxy-terminal domains corresponding to the DNA-recognition and cleavage functions, respectively.

The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP .

This entry represents the subdomain D1 of FokI. Subdomain D1 of the recognition domain covers the DNA major groove, recognizing base pairs at the 3' end of the recognition sequence (GGATG) .
Scytalone dehydratase (Scytalone_dehydratase)
Type: Family

This entry represents Scytalone dehydratase (SDH) and similar proteins mainly found in the fungi Accomycota. SDH is a member of the group of enzymes involved in fungal melanin biosynthesis . It was first identified in a phytopathogenic fungus, Magnaporthe grisea (Rice blast fungus), which causes rice blast disease . Scytalone dehydratase is a molecular target of inhibitor design efforts aimed at protecting rice plants from fungal disease . This protein family is structurally related to the NTF2 family (

).