SII-SWORD/CoKE huggingface dataset:
Nitrous oxide reductase, N-terminal (N2O_reductase_N)
Type: Homologous_superfamily

This entry represents the 7-bladed β-propeller domain found in YbhE 6-phosphogluconolactonase, nitrous oxide reductase, and WD repeat-containing proteins.

Nitrous oxide (N2O) reductase (

) is a copper-containing enzyme that catalyses the two-electron reduction of the greenhouse gas N2O to N2 . N2O reductase has two domains: an N-terminal 7-bladed β-propeller domain that contains the CuZ catalytic centre and a C-terminal domain with a cupredoxin fold that is homologous to the CuA domain of bovine cytochrome c oxidase (COXII).

6-phosphogluconolactonases (6PGL)

are cytosolic enzymes found in all organisms that catalyse the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconic acid in the oxidative phase of the pentose phosphate pathway. Trypanosoma brucei and other characterised 6PGL proteins [

] share an α/β hydrolase fold, with both parallel and anti-parallel β-sheets surrounded by eight α-helices . In Escherichia coli (strain K12), 6PGL (YbhE) is characterised by a 7-bladed β-propeller fold

(

) .
Quinoprotein alcohol dehydrogenase-like superfamily (Quinoprotein_ADH-like_sf)
Type: Homologous_superfamily

Quinoprotein alcohol dehydrogenases are a family of proteins found in methylotrophic or autotrophic bacteria. These quinoproteins use pyrroloquinoline quinone as their prosthetic group. There are three types of alcohol dehydrogenases: type I includes methanol dehydrogenase and ethanol dehydrogenase, type II includes soluble quinohaemoprotein with a C-terminal containing haem C, and type III includes quinoprotein alcohol dehydrogenase with a C-terminal cytochrome C domain . These quinoproteins contain an 8-bladed β-propeller motif, which is present in the N-terminal domain of quinoprotein alcohol dehydrogenase, ethanol dehydrogenase, and the heavy chain (alpha subunit) of methanol dehydrogenase (

) .

This entry represents quinoprotein alcohol dehydrogenases as well as some other proteins that share a similar structure, including WD repeat-containing protein and echinoderm microtubule-associated protein-like proteins.
Cytochrome cd1-nitrite reductase-like, haem d1 domain superfamily (Haem_d1_sf)
Type: Homologous_superfamily

Cytochrome cd1 (cyt cd1) nitrite reductase is a dimeric enzyme of the bacterial periplasm that plays a key role in denitrification, the respiratory reduction of nitrite to nitric oxide in the nitrogen cycle. Each subunit of the cyt cd1 dimer contains one cytochrome c and one d1 haem group . The active site contains a specialised d1 haem, where the nitrite substrate is bound and reduced. This d1 haem is bound in an 8-bladed β-propeller, which is also found in some members of the WD40 repeat-containing proteins (

). This superfamily represents the d1 heme binding domain.
Serralysin-like metalloprotease, C-terminal (Serralysin-like_metalloprot_C)
Type: Homologous_superfamily

This entry represents the C-terminal domain of serralysins. The serralysin precursor does not possess a signal peptide, instead the C-terminal domain is required for secretion . This domain is a 21-strand β sandwich known as a "parallel β roll" with the β strands arranged in a right-handed spiral. There are tandem repeats of a GGXGXDX(L/I/FV)X motif, each of which binds a calcium ion .

Serralysin is a bacterial Zn-endopeptidase that acts as a virulence factor to cause tissue damage and anaphylactic response . Many Zn-endopeptidases contain the metal binding motif HexxHxxGxxH; in addition to these coordinated histidine residues, serralysin contains a coordinated tyrosine residue that is unique to the astacin-like Zn enzymes. The Zn-endopeptidases containing the histidine motif are structurally similar to one another, containing an N-terminal catalytic domain that belongs to the zincin family, and a C-terminal β-helix metal-binding domain. These peptidase include the astacin family, snake venom Zn-endopeptidases, the extracellular metalloproteases from Serratia sp., Pseudomonas sp. and Erwinia sp., and the matrixins.
Pectin lyase fold/virulence factor (Pectin_lyase_fold/virulence)
Type: Homologous_superfamily

Microbial pectin and pectate lyases are virulence factors that degrade the pectic components of the plant cell wall . When the backbone of pectin is methylated it is known as pectin and is cleaved by pectin lyase, and when it is demethylated it is known as pectate and is cleaved by pectate lyase. Pectin lyase from Aspergillus niger displays a single-stranded, right-handed parallel β-helix topology (

), where each coil contains three β-strands and three turn regions. Several other virulence factors share this β-helix topology, although they vary in the number of coils, including bacterial pectate lyases, fungal and bacterial galacturonases (such as rhamnogalacturonase and polygalacturonase), chrondroitinase B from Flavobacterium sp., iota-carrageenase from Alteromonas sp., pectin methylesterase (PemA), P22 tailspike protein from Enterobacteria phage P22, and the virulence factor P.69 pertactin from Bordetella pertussis that mediates adhesion to target mammalian cells .
RmlC-like cupin domain superfamily (RmlC_Cupin_sf)
Type: Homologous_superfamily

RmlC (dTDP (deoxythymidine diphosphates)-4-dehydrorhamnose 3,5-epimerase;

) is a dTDP-sugar isomerase enzyme involved in the synthesis of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria . RmlC is a dimer, each monomer being formed from two β-sheets arranged in a β-sandwich, where the substrate-binding site is located between the two sheets of both monomers.

Other protein families contain domains that share this fold, including glucose-6-phosphate isomerase (

); germin, a metal-binding protein with oxalate oxidase and superoxide dismutases activities ; auxin-binding protein ; seed storage protein 7S ; acireductone dioxygenase ; as well as three proteins that have metal-binding sites similar to that of germine, namely quercetin 2,3-dioxygenase (

) , phosphomannose isomerase (

) and homogentisate dioxygenase (

) , the last three sharing a 2-domain fold with storage protein 7s.
Proteinase/amylase inhibitor domain superfamily (Proteinase_amylase_inhib_sf)
Type: Homologous_superfamily

This superfamily includes inhibitors of proteinases and amylases, such as trypsin inhibitors (

) , carboxypeptidase A inhibitors (

) , and alpha-amylase inhibitors (AAI) . The proteins display a knottins-like (small inhibitors, toxins, lectins) disulphide-bound fold, containing a β-hairpin with two adjacent disulphides.
Single hybrid motif (Single_hybrid_motif)
Type: Homologous_superfamily

The single hybrid motif has a β-barrel sandwich hybrid fold, consisting of a sandwich of half-barrel shaped β-sheets. This motif is found in biotinyl/lipoyl-carrier proteins and domains, where the biotin and lipoic acid moieties act as covalently attached coenzyme cofactors in enzymes that catalyse metabolic reactions. For example, this motif can be found in the biotinyl domain of Escherichia coli acetyl-CoA carboxylase , protein H of the glycine cleavage system in Pisum sativum (Garden pea) , the ipoyl domain of dihydrolipoamide acetyltransferase, which is a component of the pyruvate dehydrogenase complex , the lipoyl domain of the 2-oxoglutarate dehydrogenase complex , and the lipoyl domain f the mitochondrial branched-chain alpha-ketoacid dehydrogenase.
Rudiment single hybrid motif (Rudment_hybrid_motif)
Type: Homologous_superfamily

The rudiment single hybrid motif has a β-barrel sandwich hybrid motif, consisting of a sandwich of half-barrel shaped β-sheets. This motif is found in the small domain of cytochrome f , as well as in the C-terminal domain of the biotin carboxylase subunit of acetyl-CoA carboxylase , and its family members, such as glycinamide ribonucleotide synthetase C-terminal domain , N5-carboxyaminoimidazole ribonucleotide synthetase PurK C-terminal domain , and glycinamide ribonucleotide transformylase PurT C-terminal domain .
Duplicated hybrid motif (Dup_hybrid_motif)
Type: Homologous_superfamily

The duplicated hybrid motif is a structural motif that is found in certain glucose-permease-like enzymes, and consists of a half-barrel β-sheet of eight strands that is sandwiched with two 3-stranded β-sheets. Enzymes displaying this motif include domain IIa of the glucose-specific permease from bacteria (

) (

), which is part of the phosphoenolpyruvate:sugar phosphotransfer system (PTS), a bacterial and mycoplasma system responsible for the uptake of some sugars and their concomitant phosphorylation . This structural motif is also found in peptidoglycan hydrolase LytM in Staphylococcus aureus

, a member of peptidase family M23, although it contains an extra N-terminal, non-conserved β-sheet subdomain .
Mss4-like superfamily (Mss4-like_sf)
Type: Homologous_superfamily

This superfamily represents a structural domain with a complex fold consisting of several coiled β-sheets. This domain exists as a duplication, consisting of a tandem repeat of two similar structural motifs. These domains can be found in:

Mss4, which contains a zinc-binding site.

Translationally controlled tumour-associated protein TCTP, which contains an insertion of an α-helix hairpin, and which lacks a zinc-binding site.

The C-terminal MsrB domain of peptide methionine sulphoxide reductase.

Mss4 is a conserved accessory factor for Rab GTPases, which function as ubiquitous regulators of intracellular membrane trafficking . Mss4 acts to promote nucleotide release from exocytic but not endocytic Rab GTPases. Mss4 has a complex fold made of several coiled β-sheets, and consists of a duplication of tandem repeats of two similar structural motifs. It contains a zinc-binding site.

Other proteins that show structure similarity to Mss4 include the translationally controlled tumour-associated proteins TCTPs, which contains an insertion of an α helical hairpin, and lacks the zinc-binding site. TCTPs are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and the human acute allergic response .

The C-terminal MsrB domain of peptide methionine sulphoxide reductase PilB is structurally similar to Mss4. Methionine sulphoxide reductases protect against oxidative damage that can contribute to cell death. The tandem Msr domains (MsrA and MsrB) of the pilB protein from Neisseria gonorrhoeae each reduce different epimeric forms of methionine sulphoxide .
Cyanovirin-N (Cyanovirin-N)
Type: Domain

Cyanovirin-N (CV-N) is an 11kDa protein from the cyanobacterium Nostoc ellipsosporum that displays virucidal activity against several viruses, including human immunodeficiency virus (AIDS). The virucidal activity of CV-N is mediated through specific high-affinity interactions with the viral surface envelope glycoproteins gp120 and gp41, as well as to high-mannose oligosaccharides found on the HIV envelope . In addition, CV-N is active against rhinoviruses, human parainfluenza virus, respiratory syncytial virus, and enteric viruses. The virucidal activity of CV-N against influenza virus is directed towards viral haemagglutinin .

The CV-N domain is evolutionarily conserved and occurs as a protein module in eukaryotes . CV-N has a complex fold composed of a duplication of a tandem repeat of two homologous motifs comprising three-stranded β-sheet and β-hairpins .
Metal-dependent hydrolase, composite domain superfamily (Metal-dep_hydrolase_composite)
Type: Homologous_superfamily

The composite domain of metal-dependent hydrolases has a pseudo-barrel fold that is interrupted by the catalytic β/α barrel domain. This domain is found in a variety of bacterial and fungal enzymes, including: cytosine deaminase, an enzyme that is important in the pyrimidine salvage pathway ; the alpha-subunit of urease, a virulence factor of gastric pathogens such as Helicobacter pylori (Campylobacter pylori) ; D- and L-hydantoinases (dihydropyrimidinase), which catalyse the production of D- and L-amino acids, respectively ; isoaspartyl dipeptidase from Escherichia coli, which functions in protein degradation ; N-acetylglucosamine-6-phosphate deacetylase, which is an enzyme from the biosynthetic pathway to amino-sugar-nucleotides ; and N-acyl-D-amino acid amidohydrolase (D-aminoacylase), involved in the synthesis of D-amino acids .
Ribulose-phosphate binding barrel (RibuloseP-bd_barrel)
Type: Homologous_superfamily

The ribulose-phosphate binding barrel consists of a parallel β-sheet barrel fold containing a phosphate-binding site. Several proteins display this fold, including histidine biosynthesis enzymes, tryptophan biosynthesis enzymes, D-ribulose-5-phosphate 3-epimerase, and decarboxylases .
Hirudin/antistatin (Hirudin/antistatin)
Type: Homologous_superfamily

Leeches, such as Hirudo medicinalis (Medicinal leech), produce a variety of antihaemostatic proteins that act as proteinase inhibitors. These inhibitors are used to aid the leech in feeding upon its host by blocking blood coagulation . Examples of these proteins include hirustasin (inhibitor of tissue kallikrein, trypsin, alpha-chymotrypsin, and granulocyte cathepsin G) , bdellastasin (inhibitor of trypsin, plasmin, and acrosin) , factor Xa inhibitor antistasin (inhibitor of blood coagulation factor Xa) , hirudin (thrombin inhibitor), decorsin (inhibitor of platelet aggregation) and haemadin (thrombin inhibitor) .
Contryphan, conserved site (Contryphan_CS)
Type: Conserved_site

Contryphans are a family of short disulphide constrained peptides isolated from various species of cone shell. They constitute a group of conopeptides that are known to contain an unusual density of post-translational modifications including tryptophan bromination, amidation of the C-terminal residue, leucine and tryptophan isomerisation, proline hydroxylation and glutamic acid γ-carboxylation .
tRNA(Ile)-lysidine/2-thiocytidine synthase, N-terminal (TilS/TtcA_N)
Type: Domain

The structure of tRNA(Ile)-lysidine synthetase consists of an N-terminal dinucleotide-binding fold domain (NTD), and a C-terminal globular domain (CTD). The structure of the NTD closely resembles that of a P-loop "N-type" ATP pyrophosphatase . tRNA(Ile)-lysidine and 2-thiocytidine synthase both belong to the PP-loop superfamily .
Allophycocyanin linker chain (Allophyco_linker_chain)
Type: Homologous_superfamily

This superfamily represents the Allophycocyanin linker chain domain.
Kunitz inhibitor STI-like superfamily (Kunitz_inhibitor_STI-like_sf)
Type: Homologous_superfamily

The Kunitz-type soybean trypsin inhibitor (STI) family consists mainly of proteinase inhibitors from Leguminosae seeds . They belong to MEROPS inhibitor family I3, clan IC. They exhibit proteinase inhibitory activity against serine proteinases; trypsin (MEROPS peptidase family S1,

) and subtilisin (MEROPS peptidase family S8,

), thiol proteinases (MEROPS peptidase family C1,

) and aspartic proteinases (MEROPS peptidase family A1,

) . STI has a beta-Trefoil type fold consisting of a closed barrel and a hairpin triplet, with internal pseudo threefold symmetry.

The C-terminal domain of Clostridium spp. neurotoxins have an overfold that is very similar to that of the Kunitz STI family. The tetanus toxin binds to the gangliosides receptor, GT1b, and is composed of light and heavy chains, where the light chain is responsible for toxicity; the Kunitz-like domain is found on the C-terminal of the heavy chain, and is responsible for binding to sensitive cells .
Mechanosensitive ion channel MscS, C-terminal domain superfamily (MscS_channel_C_sf)
Type: Homologous_superfamily

MscS is a mechanosensitive channel present in the membrane of bacteria, archaea and eukaryote thsat responds both to stretching of the cell membrane and to membrane depolarisation . MscS folds as a homo-heptamer with a cylindrical shape, and can be divided into transmembrane and extra membrane regions: an N-terminal periplasmic region, a transmembrane region, and a C-terminal cytoplasmic region (middle and C-terminal domains) . The MscS family of channels shows diversity in size and sequence between its members; most of the diversity occurs in the size of the transmembrane region, which ranges from three to eleven transmembrane helices, although the three C-terminal helices are conserved.

This superfamily represents the C-terminal domain of MscS, which has an α/β structure and, together with the middle domain, creates a framework that connects to the cytoplasm through distinct openings .
Plasmid maintenance toxin/Cell growth inhibitor (Plasmid_toxin/cell-grow_inhib)
Type: Homologous_superfamily

Bacterial cells remove plasmid-free segregants by the use of toxin/antitoxin systems, where cells that lack plasmids cannot produce the antitoxin required for survival. Several of the toxin components have similar structures, which consists of an SH3-like barrel fold, and contains an inserted β-sheet subdomain and a C-terminal helix, despite often low sequence identities. Toxins that have this structural fold include CcdB from Escherichia coli, a topoisomerase poison that interferes with DNA gyrase activity , PemK-like YdcE from Bacillus subtilis, Kid toxin (Kis antitoxin) from the E. coli R1 plasmid and the MazF toxin (MazE antitoxin) from E. coli .
Nucleotidyltransferase, class I-like, C-terminal (NuclTrfase_I-like_C)
Type: Homologous_superfamily

Nucleotidytransferases can be divided into two classes based on highly conserved features of the nucleotidyltransferase motif . Class I enzymes include eukaryotic poly(A) polymerase (PAP), archaeal tRNA CCA-adding enzyme and possibly DNA polymerase beta, while class II enzymes include eukaryotic and eubacterial tRNA CCA-adding enzymes. This superfamily represents the C-terminal domain of class I nucleotidyltransferases. The C-terminal domain has an α/β sandwich fold, although the archaeal tRNA CCA-adding enzyme has a large insertion; this fold is reminiscent of the RNA-recognition motif fold.
Globular protein, non-globular alpha/beta subunit (Globular_prot_asu/bsu)
Type: Homologous_superfamily

Certain globular proteins from different functional families contain non-globular α+β subunits. These proteins do not form a true superfamily, but share a similar topology in their non-globular subunits. Proteins that display this structure include phycoerythrin alpha subunits (

), which are light-harvesting biliproteins found in cryptomonads , the chaperone-binding domain of the virulence effector SptP from Salmonella typhimurium, which acts to modulate host cellular responses , and the ubiquinol-cytochrome c reductase 8kDa protein (

), an integral membrane protein complex essential to cellular respiration .
Polysaccharide lyase family 8-like, C-terminal (Lyase_8-like_C)
Type: Homologous_superfamily

Proteins containing this C-terminal domain consist of a group of secreted bacterial lyase enzymes capable of acting on a variety of substrates. One such enzyme is hyaluronate lyase, a Streptococcal surface enzyme that degrades hyaluronan and chondroitin, thereby helping to spread the bacteria throughout host tissues . Hyaluronate lyase (

) is a four-domain enzyme containing an N-terminal carbohydrate-binding domain, a spacer domain, a catalytic domain, and a C-terminal domain that modulates access to the catalytic cleft of the enzyme. The C-terminal domain has a β sandwich fold consisting of 10 strands in two sheets. Other bacterial enzymes that display this structure include the C-terminal domain of chondroitin AC lyase (

) , the C-terminal domain of chondroitin ABC lyase (

) , and the C-terminal domain of xanthan lyase (

) . This entry represents the C-terminal domain of hyaluronate lyase, chondroitin AC lyase, chondroitin ABC lyase and xanthan lyase.
HR1 rho-binding domain (HR1_rho-bd)
Type: Domain

This entry also includes Transducer of Cdc42-dependent actin assembly protein (TOCA) family proteins which contains a central HR1 (also known as Rho effector motif class 1, REM-1) which is closely related to Cdc42-interacting protein 4 (CIP4), effectors of the Rho family small G protein Cdc2 .

HR1 was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN) . The first two of these repeats were later shown to bind the small G protein rho known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. This domain contains two long α helices forming a left-handed antiparallel coiled-coil fold termed the antiparallel coiled- coil (ACC) finger domain. The two long helices encompass the basic region and the leucine repeat region, which are identified as the Rho-binding region .
CRAL/TRIO, N-terminal domain (CRAL/TRIO_N_dom)
Type: Domain

This all-α domain is often found N-terminal to CRAL-TRIO domains (

). Its function is unknown.
Malate synthase superfamily (Malate_synth_sf)
Type: Homologous_superfamily

Malate synthase (MS) (

) catalyses the aldol condensation of glyoxylate with acetyl-CoA to form malate as part of the second step of the glyoxylate bypass and an alternative to the tricarboxylic acid cycle in bacteria, fungi and plants. There have been identified two isoforms, A and G (MSA and MSG, respectively) that differ in size and is attributed to an inserted α/β domain in MSG that may have regulatory function . MSA and MSG consist of an N-terminal α-helical clasp domain, a central TIM-barrel domain and a C-terminal helical plug domain. In malate synthases, the TIM β/α-barrel fold and the C-terminal helical domain are well conserved and the cleft between them forms the active site .
Pyridoxal phosphate homeostasis protein (PyrdxlP_homeostasis)
Type: Family

Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is an essential cofactor for nearly 60 Escherichia coli enzymes and 140 human enzymes. It is a highly reactive molecule that is toxic in its free form. The E. coli PROSC, known as yggS, binds to PLP and is involved in PLP homeostasis, supplying this cofactor to apoenzymes while minimizing any toxic side reactions .
Alanine racemase, C-terminal (Ala_racemase_C)
Type: Domain

Alanine racemase (

) plays a role in providing the D-alanine required for cell wall biosynthesis by isomerising L-alanine to D-alanine.

The molecular structure of alanine racemase from Bacillus stearothermophilus (Geobacillus 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-strand. This entry represents the C-terminal domain.
Bacterial Ig-like domain (Big_4)
Type: Domain

This entry represents a bacterial domain with an Ig-like fold. These domains are found in a variety of bacterial surface proteins such as Beta-L-arabinobiosidase and Exo-beta-1,6-galactobiohydrolase.
Exosome-associated factor Rrp47/DNA strand repair C1D (Exosome-assoc_fac/DNA_repair)
Type: Family

The CD1 family of proteins includes exosome-associated cofactor Rrp47, and DNA double-strand repair protein C1D. Both of these proteins are implicated in DNA double-strand repair and in nuclear exosome activity.

Rrp47 functions in nuclear RNA processing. Rrp47 is associated with nuclear exosomes, and with the nuclear exosome-specific 3'-5' exonuclease Rrp6.Rrp47 appears to be a substrate-specific nuclear cofactor that is required for the 3' processing of pre-rRNAs, snoRNAs and snRNAs (specifically U4 and U5) . However, Rrp47 is not required for cytoplasmic exosome mRNA degradation. It also appears to have a role in DNA strand repair.

C1D is an inducible nuclear matrix proteins that interacts with and activates the DNA-dependent protein kinase essential for DNA double-strand repair and V(D)J recombination . C1D can interact with condensin, which is required for DNA repair and replication checkpoint control . C1D also binds to nuclear exosomes and might regulate their functional activities, as it has RNA-binding activity .