SII-SWORD/CoKE huggingface dataset:
ClpP/crotonase-like domain superfamily (ClpP/crotonase-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a ClpP/crotonase-like domain formed from repeated β/β/α units, which comprises two perpendicular β-sheet surrounded by α-helices. Proteins containing this domain can be classified into four structural families :

The Clp protease, Clp subunit family.

The tail-specific protease, catalytic domain family. Members include tricorn proteases.

The crotonase-like family.

The biotin-dependent carboxylase carboxyltransferase domain family. Members include the acetyl-coenzyme A carboxylase carboxyl transferase subunits.
Lipoprotein localisation LolA/LolB/LppX (LolA/LolB/LppX)
Type: Homologous_superfamily

LppX is a lipoprotein required for the translocation of complex lipids to the outer membrane of Mycobacterium tuberculosis. Its structure consists of a U-shaped β-half-barrel with a large hydrophobic cavity . LppX shares a similar fold with the periplasmic molecular chaperone LolA and the outer membrane lipoprotein LolB, which are involved in the localisation of lipoproteins to the outer membrane of Gram-negative bacteria .
Heat shock protein 70kD, peptide-binding domain superfamily (HSP70_peptide-bd_sf)
Type: Homologous_superfamily

Members of the 70-kilodalton heat-shock protein (HSP70) family promote protein folding both constitutively and in response to stress. These proteins have two functional units: a substrate-binding unit, and an adenosine triphosphatase unit. The substrate-binding unit of DnaK consists of a β-sandwich domain followed by α-helical segments. The α-helical domain stabilises the complex, but does not contact the peptide directly .

This superfamily represents peptide-binding β-sandwich domain from DnaK and other
HSP70 proteins.
Heat shock protein 70kD, C-terminal domain superfamily (HSP70_C_sf)
Type: Homologous_superfamily

Members of the 70-kilodalton heat-shock protein (HSP70) family promote protein folding both constitutively and in response to stress. These proteins have two functional units: a substrate-binding unit, and an adenosine triphosphatase unit. The substrate-binding unit of DnaK consists of a β-sandwich domain followed by α-helical segments. The α-helical domain stabilises the complex, but does not contact the peptide directly .

This superfamily represents the C-terminal α-helical subdomain of the substrate-binding unit from DnaK and other HSP70 proteins.
Immunoprotective extracellular, immunoglobulin-like domain superfamily (Immunoprotect_excell_Ig-like)
Type: Homologous_superfamily

This superfamily represents an immunoglobulin-like domain found in immunogenic proteins MPB63/MPT63 and in a group of related proteins that fall into the antigen MPT63/MPB63 (immunoprotective extracellular protein) superfamily, such as uncharacterised lipoprotein YjhA (

).
Domain of unknown function DUF4352 (DUF4352)
Type: Domain

This immunoglobulin-like domain can be found in a group of proteins that fall into the antigen MPT63/MPB63 (immunoprotective extracellular protein) superfamily, such as uncharacterised lipoprotein YjhA (

).
Metallo-dependent phosphatase-like (Metallo-depent_PP-like)
Type: Homologous_superfamily

This entry represents a domain found in metallo-dependent phosphatases. Proteins containing this domain include:

Purple acid phosphatases .

DNA double-strand break repair nucleases .

5'-nucleotidases (syn. UDP-sugar hydrolase).

Protein serine/threonine phosphatase.

Phosphoesterase-related proteins.

TT1561-like proteins.

YfcE-like proteins.

Hypothetical protein aq_1666.

DR1281-like proteins.

TTHA0625-like proteins.

GpdQ-like proteins.

ADPRibase-Mn-like proteins.

Metallophosphatases (MPPs), also known as metallophosphoesterases, phosphodiesterases (PDEs), binuclear metallophosphoesterases, and dimetal-containing phosphoesterases (DMPs), represent a diverse superfamily of enzymes with a conserved domain containing an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues .
Viral coat protein subunit (Viral_coat)
Type: Homologous_superfamily

The domain that participates in the formation of icosahedral virus shell exhibits a fold with two flanking twisted β-sheets, each consisting of 4 antiparallel β-strands, that is called the 8-stranded jelly roll β-barrel motif . In the Norwalk virus, a human calicivirus, the capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has this classical eight-stranded β-sandwich motif .
dUTPase-like (dUTPase-like)
Type: Domain

This entry represents a distorted barrel domain found in deoxyuridine triphosphate nucleotidohydrolases and CTP deaminases.
Nucleophile aminohydrolases, N-terminal (Ntn_hydrolases_N)
Type: Homologous_superfamily

The N-terminal of the nucleophile aminohydrolase (Ntn hydrolases) provides two catalytic groups, nucleophile and proton donor. Ntn hydrolases use the side chain of the amino-terminal residue, incorporated in a β-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon. The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome. All the enzymes share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing .

Some nucleophile aminohydrolases include:

ATP-dependent protease subunit HslV

Glutamine--fructose-6-phosphate aminotransferase [isomerizing]

Proteasome subunits

Amidophosphoribosyltransferase

Related proteins
Ribokinase-like (Ribokinase-like)
Type: Homologous_superfamily

This superfamily represents a domain found in phosphotransferases that have an alcohol group as an acceptor ([ec:2.7.1.-]). However, 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase (HMPP kinase) catalyses two phosphorylation reactions: one to a hydroxymethyl group of hydroxymethyl pyrimidine (HMP) and the second to the phosphomethyl group of HMPP . The common structural feature for the enzymes in this superfamily is a central eight-stranded sheet that is flanked by eight structurally conserved helices, five on one side and three on the other . The active site is located in a shallow groove along one edge of the sheet, with the phosphate acceptor hydroxyl group and -phosphate of ATP close together in the middle of the groove, and substrate and ATP binding at the ends .
Phosphoribosyltransferase-like (PRTase-like)
Type: Homologous_superfamily

This superfamily represents a phosphoribosyltransferase-like domain. Proteins containing this domain include phosphoribosyltransferases (PRTases) , phosphoribosylpyrophosphate synthetase-like proteins and some uncharacterised proteins.
Alpha/Beta hydrolase fold (AB_hydrolase_fold)
Type: Homologous_superfamily

This entry represent the α/β hydrolase superfamily that brings together enzymes with a common structural fold but diverse catalytic functions. This superfamily is characterised by a core structure composed of a central β-sheet consisting of 5-8 strands, connected by α-helices to form an α/β/α sandwich.

The α/β hydrolase fold is common to a number of hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is an α/β-sheet (rather than a barrel), containing 8 strands connected by helices . The enzymes are believed to have diverged from a common ancestor, preserving the arrangement of the catalytic residues. All have a catalytic triad, the elements of which are borne on loops, which are the best conserved structural features of the fold. Esterase (EST) from Pseudomonas putida is a member of the α/β hydrolase fold superfamily of enzymes .

In most of the family members the β-strands are parallel, but some have an inversion of the first strands, which gives it an antiparallel orientation. The catalytic triad residues are presented on loops. One of these is the nucleophile elbow and is the most conserved feature of the fold. Some other members lack one or all of the catalytic residues. Some members are therefore inactive but others are involved in surface recognition. The ESTHER database gathers and annotates all the published information related to gene and protein sequences of this superfamily .
Alpha/beta hydrolase fold-5 (AB_hydrolase_5)
Type: Domain

The α/β hydrolase fold is common to a number of hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is an α/β-sheet (rather than a barrel), containing 8 strands connected by helices . The enzymes are believed to have diverged from a common ancestor, preserving the arrangement of the catalytic residues. All have a catalytic triad, the elements of which are borne on loops, which are the best conserved structural features of the fold. Esterase (EST) from Pseudomonas putida is a member of the α/β hydrolase fold superfamily of enzymes .

In most of the family members the β-strands are parallel, but some have an inversion of the first strands, which gives it an antiparallel orientation. The catalytic triad residues are presented on loops. One of these is the nucleophile elbow and is the most conserved feature of the fold. Some other members lack one or all of the catalytic residues. Some members are therefore inactive but others are involved in surface recognition. The ESTHER database gathers and annotates all the published information related to gene and protein sequences of this superfamily .
PIN-like domain superfamily (PIN-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain sharing protein structural similarity with the PIN domain. This domain can also be found in the N-terminal of the 5'3'-exonuclease, which has a 3-layer α/β/α core structure and contains an α-helical arch .

PIN domains are small protein domains identified by the presence of three strictly conserved acidic residues. Apart from these three residues, there is poor sequence conservation . PIN domains are found in eukaryotes, eubacteria and archaea. In eukaryotes they are ribonucleases involved in nonsense mediated mRNA decay and in processing of 18S ribosomal RNA . In prokaryotes, they are the toxic components of toxin-antitoxin (TA) systems, their toxicity arising by virtue of their ribonuclease activity. The PIN domain TA systems are now called VapBC TAs(virulence associated proteins), where VapB is the inhibitor and VapC, the PIN-domain ribonuclease toxin .
Thiamin diphosphate-binding fold (THDP-binding)
Type: Homologous_superfamily

This entry represents the thiamin diphosphate-binding fold found in pyruvate dehydrogenases, branched chain alpha-keto acid decarboxylases, phosphoketolases and the pyrimidine binding region of transketolases . There are two different functional modules of this fold: pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. Two Pyr and two PP modules can assemble together in a conserved heterotetrameric core that binds two THDP coenzyme molecules.
Class I glutamine amidotransferase-like (Class_I_gatase-like)
Type: Homologous_superfamily

Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group . The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified : class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). In class I glutamine amidotransferases, a triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity . Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.

This entry also include the DJ-1/PfpI protein that contains a catalytic triad or dyad different from the class I GAT triad.

This superfamily represents the class I glutamine amidotransferase-like domain.
S-adenosyl-L-methionine-dependent methyltransferase superfamily (SAM-dependent_MTases_sf)
Type: Homologous_superfamily

This entry represents S-adenosyl-L-methionine-dependent methyltransferases (SAM MTase). Methyltransferases transfer a methyl group from a donor to an acceptor. SAM-binding methyltransferases utilise the ubiquitous methyl donor SAM as a cofactor to methylate proteins, small molecules, lipids, and nucleic acids. All SAM MTases contain a structurally conserved SAM-binding domain consisting of a central seven-stranded β-sheet that is flanked by three α-helices per side of the sheet .

A review published in 2003 divides all methyltransferases into 5 classes based on the structure of their catalytic domain (fold):

class I: Rossmann-like α/β

class II: TIM β/α-barrel α/β

class III: tetrapyrrole methylase α/β

class IV: SPOUT α/β

class V: SET domain all β

Another paper based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:

class VI: transmembrane all-α

class VII: DNA/RNA-binding 3-helical bundle all-α

class VIII: SSo0622-like α+β

class IX: thymidylate synthetase α+β

The vast majority of methyltransferases belong to the Rossmann-like fold (Class I) which consists in a seven-stranded β-sheet adjoined by α-helices. The β-sheet contains a central topological switch-point resulting in a deep cleft in which SAM binds. Class I methyltransferases display two conserved positions, the first one is a GxGxG motif (or at least a GxG motif) at the end of the first β-strand which is characteristic of a nucleotide-binding site and is hence used to bind the adenosyl part of SAM, the second conserved position is an acidic residue at the end of the second β-strand that forms one hydrogen bond to each hydroxyl of the SAM ribose part. The core of these enzymes is composed by about 150 amino acids that show very strong spatial conservation .
Ribosomal protein eL30-like superfamily (Ribosomal_eL30-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in eL30/eL8 (also known as L30e and L7ae, respectively) ribosomal proteins , the N-terminal domain in a variety of bacterial and mitochondrial RNA 2'-O ribose methyltransferases and the C-terminal domain of the release factor eRF1 .
Enolase C-terminal domain-like (Enolase_C-like)
Type: Domain

This entry represents the C-terminal domain of the enolase, which adopts a TIM barrel fold that contains a metal binding site . Proteins containing this domain also include D-glucarate dehydratase-like proteins and some uncharacterised proteins .
PLP-binding barrel (PLP-binding_barrel)
Type: Homologous_superfamily

This entry represents the PLP (pyridoxal 5'-phosphate)-binding barrel that can be found at the N terminus of alanine racemase-like proteins and members of the Orn/Lys/Arg decarboxylase class-II family of proteins.

The molecular structure of alanine racemase from Bacillus stearothermophilus was determined by X-ray crystallography to a resolution of 1.9 A . The alanine racemase monomer is composed of two domains, an eight-stranded α/β barrel at the N terminus, and a C-terminal domain essentially composed of β-strands. The pyridoxal 5'-phosphate (PLP) cofactor lies in and above the mouth of the α/β barrel and is covalently linked via an aldimine linkage to a lysine residue, which is at the C terminus of the first β-strand of the α/β barrel.
CDC48 domain 2-like superfamily (CDC48_domain_2-like_sf)
Type: Homologous_superfamily

This superfamily represents the CDC48 domain 2-like domain, which can be found in the N-terminal of the peroxisome biogenesis factor 1 and the domain 2 of the AAA ATPases.

CDC48 from yeasts is an AAA ATPase that is involved in protein export from the endoplasmic reticulum to the cytoplasm .

Peroxisome biogenesis factor 1, also known as peroxin-1 or PEX1, is a component of the peroxisomal protein import machinery. In addition to its role in import, PEX1 together with PEX6, mediates the ATP-dependent relocation and recycling of the peroxisomal targeting signal-1 (PTS1) import receptor PEX5 from the peroxisomal membrane to the cytosol .
Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase (Glyas_Bleomycin-R_OHBP_Dase)
Type: Homologous_superfamily

The entry represents a domain containing a β-α-β(3) motif found in a group of metalloenzymes. The β-α-β(3) motif provides a metal coordination environment for these enzymes, which catalyse different reactions, including isomerisations (glyoxalase I), epimerisations (methylmalonyl-CoA epimerase), oxidative cleavage of C-C bonds (extradiol dioxygenase), and nucleophilic substitutions (fosfomycin resistance proteins) .
HotDog domain superfamily (HotDog_dom_sf)
Type: Homologous_superfamily

The HotDog superfamily represents a domain found in thioesterases and thiol ester dehydratase-isomerases. This domain is also known as the 'hot dog' fold from the study of the structure of Escherichia coli beta-hydroxydecanoyl thiol ester dehydrase (FabA) . It contains the seven-stranded antiparallel β-sheet 'bun', which wraps around a five-turn α-helical 'sausage'. Proteins containing this domain include numerous prokaryotic, archaeal and eukaryotic proteins involved in several related, but distinct, catalytic activities, from metabolic roles such as thioester hydrolysis in fatty acid metabolism, to degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. It also includes FapR, a non-catalytic bacterial homologue that is involved in transcriptional regulation of fatty acid biosynthesis .
Chitinase insertion domain superfamily (Chitinase_insertion_sf)
Type: Homologous_superfamily

This superfamily represents the chitinase insertion domain (CID) that is found in chitinases or chitinase-like proteins. It is composed of five or six anti-parallel β-strands and one α-helix and it inserts between the seventh α-helix and seventh β-strand of the TIM barrel . The CID domain forms a wall alongside the TIM barrel substrate-binding cleft of chitinase which increases the depth of the cleft. Family 18 chitinases (also known as glycosyl hydrolase 18 family) can be classified into three subfamilies: A, B, and C. The CID domain can be found in the subfamily A, but is absent in the subfamily B .
Ubiquitin-like domain superfamily (Ubiquitin-like_domsf)
Type: Homologous_superfamily

Ubiquitin (Ub) and Ub-like proteins are typified by a β-grasp fold. Ub-like proteins (Ubl) such as Nedd8 and SUMO are also covalently linked to target polypeptides, just as Ub itself. This fold is also found in Ub-related domains, such as the UBX domain and Ras-binding domain (RBD) .
YebC-like (YebC-like)
Type: Homologous_superfamily

This domain is found in uncharacterised proteins, including E. coli protein YebC (

), a probable transcriptional regulator, and Aq1575 from Aquifex aeolicus. This protein reveals a monomer consisting of three domains arranged along a pseudo threefold symmetry axis .
Protein of unknown function DUF4661 (DUF4661)
Type: Family

Proteins in this family are typically between 281 and 302 amino acids in length. They are found in mammals.
Immunity protein 49 (Imm49)
Type: Family

This entry represents a predicted immunity protein with an all α-helical fold and a conserved proline residue. These proteins are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-REAse-1 or Tox-REase-6 families .
Immunity protein 48 (Imm48)
Type: Family

This entry represents a predicted immunity protein with an all α-helical fold and a conserved HRG motif. These proteins are present in heterogeneous polyimmunity loci in polymorphic toxin systems .
Immunity protein 47 (Imm47)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved KxGDxxK motif. These proteins are present in heterogeneous polyimmunity loci in polymorphic toxin systems .
Immunity protein 45 (Imm45)
Type: Domain

This entry represents a predicted immunity protein with an α+β fold and a conserved C-terminal tryptophan residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-ColE3 family .
Immunity protein 44 (Imm44)
Type: Family

This entry represents a predicted immunity protein with an α+β fold. These proteins are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-URI1, Tox-URI2 or Tox-ParBL1 families . The gene for this toxin is also found in heterogeneous polyimmunity loci that show variations in structure even between closely related strains.
Immunity protein 43 (Imm43)
Type: Domain

This entry represents a predicted immunity domain with an α+β fold with conserved tryptophan, proline, aspartate, serine and arginine residues. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-AHH family of HNH/Endonuclease VII fold nucleases . The gene for this toxin is also found in heterogeneous polyimmunity loci.
Immunity protein 40 (Imm40)
Type: Domain

This entry represents a predicted immunity protein with an α+β fold and conserved phenylalanine and tryptophan residues and a GGD motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox19 family .
Immunity protein 39 (Imm39)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and conserved GR, and GxK motifs. These proteins are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-URI2 family of nucleases .
Immunity protein 35 (Imm35)
Type: Domain

This entry represents a predicted immunity protein with an α+β fold and a conserved tryptophan residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a protease domain such as Tox-PL1 and Ntox40. In some instances, it is also fused to a papain-like toxin, ADP-ribosyl glycohydrolase and a S8-like peptidase . Based on these associations the domain is likely to be a protease inhibitor.
Immunity protein 32 (Imm32)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved histidine residue. These proteins are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox12 or Ntox37 or Notx 7 families .
Immunity protein 30 (Imm30)
Type: Domain

This entry represents a predicted immunity protein with a mostly α-helical fold and a conserved DxG motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-SHH family of HNH/Endonuclease VII fold nucleases .
Immunity protein 25 (Imm25)
Type: Domain

This entry represents a predicted immunity protein with an α+β fold. Proteins containing this domain are present in heterogeneous polyimmunity loci of polymorphic toxin systems .
Immunity protein 19 (Imm19)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved HxxRN motif. These proteins are present in heterogeneous polyimmunity loci in polymorphic toxin systems .
Immunity protein 17 (Imm17)
Type: Family

This entry represents a predicted immunity protein with two transmembrane helices, and a WxW motif and a conserved arginine between the two helices. These proteins are present in heterogeneous polyimmunity loci in polymorphic toxin systems .