SII-SWORD/CoKE huggingface dataset:
PH-BEACH domain (PH-BEACH_dom)
Type: Domain

This entry represents a domain with a fold similar to that of the PH (pleckstrin homology) domain, despite displaying little sequence homology with canonical PH domains. Furthermore, this domain is incapable of binding phospholipids . This domain is found preceding the BEACH domain in beige-like and BEACH-domain containing proteins.

The BEACH domain is found in eukaryotic proteins that have diverse cellular functions ranging from lysosomal traffic to apoptosis and cytokinesisin vesicle trafficking, membrane dynamics, and receptor signaling. The name BEACH is derived from BEige And Chediak-Higashi syndrome.
Trans-sialidase, domain 3 (Trans_sialidase_dom3)
Type: Homologous_superfamily

This entry represents a β-barrel domain found in bacterial trans-sialidase NanA, NanB and in the leech sialidase . Both act as intramolecular trans-sialidases. Trans-sialidases are responsible for the transfer of previously cleaved sialic acid to other glyconjugates.
Sortase domain superfamily (Sortase_dom-sf)
Type: Homologous_superfamily

This superfamily represents the β barrel structural domain found in sortases, which are cysteine transpeptidases involved in protein sorting activities.
ATP synthase subunit alpha, N-terminal domain-like superfamily (ATP_synth_asu-like_sf)
Type: Homologous_superfamily

In F-ATPases, there are three copies each of the alpha and beta subunits that form the catalytic core of the F1 complex, while the remaining F1 subunits (gamma, delta, epsilon) form part of the stalks. There is a substrate-binding site on each of the alpha and beta subunits, those on the beta subunits being catalytic, while those on the alpha subunits are regulatory. The alpha and beta subunits form a cylinder that is attached to the central stalk. The alpha/beta subunits undergo a sequence of conformational changes leading to the formation of ATP from ADP, which are induced by the rotation of the gamma subunit, itself is driven by the movement of protons through the F0 complex C subunit . In V- and A-ATPases, the alpha/A and beta/B subunits of the V1 or A1 complex are homologous to the alpha and beta subunits in the F1 complex of F-ATPases, except that the alpha subunit is catalytic and the beta subunit is regulatory.

The alpha/A and beta/B subunits can each be divided into three regions, or domains, centred around the ATP-binding pocket, and based on structure and function, where the central region is the nucleotide-binding domain (

) .

This superfamily represents a closed β-barrel domain with Greek-key topology. It is found at the N terminus of the alpha/A subunits. This β barrel closely resembles folds found in riboflavin synthase .
Peptidase M42, domain 2 (Peptidase_M42_dom2)
Type: Homologous_superfamily

This entry represents the β barrel structural domain (sometimes annotated as domain 2) found in bacterial M42 peptidases.
Uncharacterised protein family UPF0066, conserved site (UPF0066_cons_site)
Type: Conserved_site

This conserved site is found in proteins belonging to the uncharacterised protein family UPF0066. It is found in the central part of the tsaA-like domain (

).
TrmO-like, N-terminal domain (TrmO-like_N)
Type: Domain

TrmO (also known as TsaA or YaeB) is a RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs. It has a unique single-sheeted β-barrel structure and represent a new category of AdoMet-dependent methyltransferases .

The following uncharacterised proteins have been shown to be evolutionary related and to contain a TrmO-like β barrel structural domain domain:

Agrobacterium tumefaciens Ti plasmid protein virR.

Pseudomonas aeruginosa protein rcsF.

Archaeoglobus fulgidus hypothetical protein AF0241.

Archaeoglobus fulgidus hypothetical protein AF0433.

Methanococcus jannaschii hypothetical protein MJ1583.

Methanobacterium thermoautotrophicum hypothetical protein MTH1797.

Mammalian Nef-associated protein 1 (NAP1).

The crystal structure of Haemophilus influenzae TrmO has been solved. In addition to the N-terminal β-barrel methyltransferase domain it has a C-terminal domain containing the conserved sequence motif DPRxxY .
YmcC-like superfamily (YmcC_sf)
Type: Homologous_superfamily

This superfamily represents the β-barrel structural domain found in YmcC-related proteins, which belong to the DUF2886 family.
AttH-like domain superfamily (AttH-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a β barrel domain found in bacterial AttH proteins, as well as in survival factors, such as survival factor 1 (Svf1)

.
Acetoacetate decarboxylase domain superfamily (ADC_dom_sf)
Type: Homologous_superfamily

Acetoacetate decarboxylase (ADC) is involved in solventogenesis in certain bacteria, which occurs at the end of the exponential growth phase when there is a metabolic switch from classical sugar fermentation with the production of acetate and butyrate to the re-internalisation and oxidation of these acids to acetate and butanol . In Clostridium, Spo0A controls the switch from acid to solvent production. A Spo0A-binding motif occurs in the gene encoding ADC .

This superfamily represents the β-barrel structural domain found in acetoacetate decarboxylases.
YqcC-like domain (YqcC-like_dom)
Type: Domain

This entry represents the structural domain found in the N-terminal of some tRNA pseudouridine synthase C proteins, as well as other uncharacterised proteins.
YheA/YmcA-like domain superfamily (YheA/YmcA-like_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found in a number of proteins including YlbF and YmcA, which are involved in the formation of biofilms .
BART domain (BART_dom)
Type: Domain

This domain is found in ADP-ribosylation factor-like 2 (ARF2) binding protein, also known as BART. BART binds specifically to ARF2.GTP with a high affinity. However, it does not bind to ARF2.GDP. It is thought that this specific interaction is due to BART being the first identified ARF2-specific effector. The function is not completely characterised . BART is predominantly cytosolic but can also be found to be associated with mitochondria. BART is also involved in binding to the adenine nucleotide transporter ANT1 .

The interactions between ARL2 and BART involve a conserved N-terminal LLxIL motif of ARL2 . This domain is also found in CFAP36/CCDC104, a protein renamed as BARTL1. The BART-like domain of CCDC104/BARTL1 recognizes an LLxILxxL motif at the N-terminal amphipathic helix of ARL3 .
DsbB-like superfamily (DsbB-like_sf)
Type: Homologous_superfamily

Disulphide bonds contribute to folding, maturation, stability, and regulation of proteins, in particular those localized out of the cytosol. Oxidation of selected pairs of cysteines to disulphide in vivo requires cellular factors present in the bacterial periplasmic space or in the endoplasmic reticulum of eukaryotic cells .

The disulfide bond formation protein B (DsbB) is a component of the pathway that leads to disulphide bond formation in periplasmic proteins of Escherichia coli and other bacteria. The DsbB protein oxidises the periplasmic protein DsbA which in turn oxidises cysteines in other periplasmic proteins in order to make disulphide bonds . DsbB acts as a redox potential transducer across the cytoplasmic membrane. It is a membrane protein which spans the membrane four times with both the N- and C-termini of the protein are in the cytoplasm. Each of the periplasmic domains of the protein has two essential cysteines. The two cysteines in the first periplasmic domain are in a Cys-X-Y-Cys configuration that is characteristic of the active site of other proteins involved in disulphide bond formation, including DsbA and protein disulphide isomerase .

The structure of DsbB contains four transmembrane (TM) helices with both termini oriented toward the cytoplasm. The four TM segments are arranged into a four-helix-bundle configuration. In addition to these TM helices, a short helix with a horizontal axis exists in the periplasmic region .
YP001051499.1-like domain superfamily (YP001051499.1-like_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found in a family of uncharacterised proteins including protein YP_001051499.1 from Shewanella baltica.
tRNA-specific 2-thiouridylase MnmA-like, central domain superfamily (MnmA-like_central_sf)
Type: Homologous_superfamily

This entry represents the central PRC-barrel domain of tRNA-specific 2-thiouridylase MnmA and similar proteins from bacteria and eukaryotes. MnmA catalyses the 2-thiolation of uridine at the wobble position (U34) of tRNA, leading to the formation of s2U34 .
Ferredoxin, chloroplast transit peptide (Ferredoxin_transit_pept)
Type: Domain

This entry represent the N-terminal transit peptide of a number of algal petF genes. The peptide is removed during transit into the chloroplast lumen.
Bacteriocin, class IIa, conserved site (Bacteriocin_IIa_CS)
Type: Conserved_site

Many Gram-positive bacteria produce ribosomally synthesized antimicrobial peptides, often termed bacteriocins. One important and well studied class of bacteriocins is the class IIa or pediocin-like bacteriocins produced by lactic acid bacteria. All class IIa bacteriocins are produced by food-associated strains, isolated from a variety of food products of industrial and natural origins, including meat products, dairy products and vegetables. Class IIa bacteriocins are all cationic, display anti-Listeria activity, and kill target cells by permeabilizing the cell membrane .

Class IIa bacteriocins contain between 37 and 48 residues. Based on their primary structures, the peptide chains of class IIa bacteriocins may be divided roughly into two regions: a hydrophilic, cationic and highly conserved N-terminal region, and a less conserved hydrophobic/amphiphilic C-terminal region. The N-terminal region contains the conserved Y-G-N-G-V/L 'pediocin box' motif and two conserved cysteine residues joined by a disulphide bridge. It forms a three-stranded antiparallel β-sheet supported by the conserved disulphide bridge. This cationic N-terminal β-sheet domain mediates binding of the class IIa bacteriocin to the target cell membrane. The C-terminal region forms a hairpin-like domain that penetrates into the hydrophobic part of the target cell membrane, thereby mediating leakage through the membrane. The two domains are joined by a hinge, which enables movement of the domains relative to each other .
YopX-like, C-terminal (YopX-like_C)
Type: Homologous_superfamily

This superfamily represents the β barrel domain found in bacterial YopX and related proteins. It is found towards the C terminus.
DUF1653-like domain (DUF1653-like_dom)
Type: Domain

This entry represents the structural domain found in DUF1653, a protein family of unknown function.
Bacteriocin class IIa domain superfamily (Bacteriocin_IIa_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in class II bacteriocins. It consists of a well-defined central helical structure and a disordered N terminus, as described for carnobacteriocin B2, a type IIa bacteriocin .
DOPA-like superfamily (DOPA-like_sf)
Type: Homologous_superfamily

This superfamily represents the α/β plait structural domain found in DOPA dioxygenases and related proteins.
Bacteriophage M13, G8P, capsid domain superfamily (Phage_M13_G8P_capsid_dom_sf)
Type: Homologous_superfamily

This superfamily represents the capsid domain of the Inoviridae. The type example is bacteriophage M13 Gp8 (capsid or major coat protein); which forms the baseplate structural protein. It consists largely of an α-helix with a slight curve .
Protein translocase SecE domain superfamily (Prot_translocase_SecE_dom_sf)
Type: Homologous_superfamily

The Sec61 complex (eukaryotes) or SecY complex (prokaryotes) forms a conserved heterotrimeric integral membrane protein complex and forms a protein-conducting channel that allows polypeptides to be transferred across (or integrated into) the endoplasmic reticulum (eukaryotes) or across the cytoplasmic membrane (prokaryotes) . This complex is composed of alpha, beta and gamma subunits. The alpha-subunits (Sec61-alpha in mammals, Sec61p in Saccharomyces cerevisiae, SecY in bacteria and archaea) and gamma-subunits (Sec61-gamma in mammals, Sss1p in S. cerevisiae, SecE in bacteria and archaea) show significant sequence conservation.

The gamma or SecE subunit consists of two α-helices. The N-terminal helix lies on the cytoplasmic surface of the membrane. This helix is amphipathic with the hydrophobic surface pointing towards the membrane, contacting the C-terminal part of the alpha-subunit. This helix is followed by a short β-strand. The second helix is a long, curved transmembrane helix that crosses the membrane at approximately a 35 degrees angle with respect to the plane of the membrane .
Mitochondrial outer membrane translocase complex, Tom20 domain superfamily (Tom20_dom_sf)
Type: Homologous_superfamily

The mitochondrial protein translocase (MPT) family, which brings nuclearly encoded preproteins into mitochondria, is very complex with 19 currently identified protein constituents. These proteins include several chaperone proteins, four proteins of the outer membrane translocase (Tom) import receptor, five proteins of the Tom channel complex, five proteins of the inner membrane translocase (Tim) and three "motor" proteins .

The Tom complex performs multiple functions in a coordinated manner. Tom20, Tom37, Tom70, and Tom72 function as redundant receptor proteins, while Tom40 constitutes a protein conducting channel with the aid of Tom22 . Tom20 functions as a general import receptor for mitochondrial proteins and passes them onto the Tom40 channel .

This superfamily represents the structural domain of Tom20 that binds to mitochondrial precursor proteins. It consists of five α-helices. This first four form a well-defined structure with an internal hydrophobic core .
START-like domain superfamily (START-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents an α/β sandwich structural domain found in a wide variety of protein families, including STAR-related lipid transfer proteins and homeobox-leucine zipper proteins.

START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins . StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation . Expression of the protein in the absence of hormone stimulation is sufficient to induce steroid production, suggesting that this protein is required in the acute regulation of steroidogenesis. Representatives of the START domain family have been shown to bind different ligands such as sterols (StAR protein) and phosphatidylcholine (PC-TP). Ligand binding by the START domain can also regulate the activities of other domains that co-occur with the START domain in multidomain proteins such as Rho-gap, the homeodomain, and the thioesterase domain .
Sec7, C-terminal domain superfamily (Sec7_C_sf)
Type: Homologous_superfamily

The Sec7 domain was named after the first protein found to contain such a region . It has been shown to be linked with guanine nucleotide exchange function . The 3D structure of the domain displays several α-helices . It was found to be associated with other domains involved in guanine nucleotide exchange (e.g., CDC25, Dbl) in mammalian factors .

This superfamily represents the α orthogonal structural domain which is found at the C terminus of the Sec7 domain (

).
Mitochondrial carrier protein domain superfamily (MCP_dom_sf)
Type: Homologous_superfamily

This superfamily represents a structural domain found in mitochondrial carrier proteins.

A variety of substrate carrier proteins involved in energy transfer are found in the inner mitochondrial membrane or are integral to the membranes of other eukaryotic organelles such as the peroxisome . Such proteins include:

ADP/ATP carrier protein (ADP/ATP translocase)

2-oxoglutarate/malate carrier protein

Phosphate carrier protein

Tricarboxylate transport protein (or citrate transport protein)

Graves disease carrier protein

Yeast mitochondrial proteins MRS3 and MRS4

Yeast mitochondrial FAD carrier protein

And many others

These mitochondrial carrier proteins share a tripartite structure, consisting of up to three tandem repeats of a domain approximately 100 residues in length . Each domain contains two transmembrane (TM) regions, resulting in a total of six TM domains. Sequence analysis has shown that the TM regions and their adjacent hydrophilic loops are more highly conserved than other parts of the protein, with five of the six TM domains followed by the conserved motif (D/E)-Hy(K/R), where Hy denotes a hydrophobic residue . Structurally, these domains contain six α-helices that form a compact transmembrane unit. This structure exhibits a deep depression on the side facing the space between the inner and outer mitochondrial membranes, resembling a channel-like conformation . It is suggested that substrates bind at the bottom of this cavity, and translocation occurs through a conformational change from a 'pit' to a 'channel' structure.
S-adenosyl-L-methionine-dependent methyltransferase, MraW, recognition domain superfamily (SAM-dep_MeTrfase_MraW_recog)
Type: Homologous_superfamily

This domain superfamily is found inserted into bacterial SAM-dependent methyltransferases and is thought to be involved in methyl acceptor selectivity. In contrast with recognition domains found in other methyltransferases, it is inserted into the centre of the protein sequence and has an α orthogonal structure rather than a simple loop or single α-helix .
Translation Initiation factor eIF- 4e-like (TIF_eIF4e-like)
Type: Homologous_superfamily

Eukaryotic translation initiation factor 4E (eIF-4E) is a protein that binds to the cap structure of eukaryotic cellular mRNAs. eIF-4E recognises and binds the 7-methylguanosine-containing (m7Gppp) cap during an early step in the initiation of protein synthesis and facilitates ribosome binding to a mRNA by inducing the unwinding of its secondary structures. A tryptophan in the central part of the sequence of human eIF-4E seems to be implicated in cap-binding .

This entry includes a group of eIF4E-like protein. These proteins consist of a curved eight-stranded antiparallel β-sheet, decorated with three helices on the convex face and three smaller helices inserted in connecting loops .
Baseplate-like, two-layer sandwich fold (Baseplate-like_2-layer_sand)
Type: Homologous_superfamily

This entry represents an α/β two layer sandwich found in baseplate proteins and related sequences.
DNA recombination and repair protein RecA, C-terminal, superfamily (RecA_C_sf)
Type: Homologous_superfamily

The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response . In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs . RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage .

RecA is a protein of about 350 amino-acid residues. Its sequence is very well conserved among eubacterial species. It is also found in the chloroplast of plants . RecA-like proteins are found in archaea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filament visualised by X-ray crystallography, β-strand 3, the loop C-terminal to β-strand 2, and α-helix D of the core domain form one surface that packs against α-helix A and β-strand 0 (the N-terminal domain) of an adjacent monomer during polymerisation . The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between β-strand 1 and α-helix C. The Escherichia coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (also referred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another nucleotide binding motif, the Walker B box is found at β-strand 4 in the RecA structure. The Walker B box is characterised by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP binding interactions are contributed by the amino acid residues at β-strand 2 and the loop C-terminal to that strand, all of which are greater than 90% conserved among bacterial RecA proteins.

This superfamily represents the C-terminal domain, which forms an α/β two layer sandwich .
Ornithine cyclodeaminase, N-terminal (ODC_N)
Type: Homologous_superfamily

This entry represents the N-terminal domain of the ornithine cyclodeanimase family. This is an α/β two layer sandwich domain. Members of this family includes ornithine cyclodeanimase , alanine dehydrogenase from Archaeoglobus and human cytosolic 3,5,39-triiodo-L-thyronine-binding protein, also called mu-crystallin or CRYM . The function of this domain in ornithine cyclodeaminases, in combination with the C terminus, is responsible for substrate binding. This is a dimerisation domain of alanine dehydrogenase and CRYM.
Uncharacterised protein MG237, central domain (Uncharacterised_MG237_central)
Type: Homologous_superfamily

This entry represents the central domain found in hypothetical protein mg237 .
Uncharacterised protein MG237, N-terminal (Uncharacterised_MG237_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of hypothetical protein mg237 and homologues. It consists of four α helices .
Radical SAM, alpha/beta horseshoe (rSAM_horseshoe)
Type: Homologous_superfamily

Radical SAM domains catalyze diverse reactions, including unusual methylations, isomerization, sulphur insertion, ring formation, anaerobic oxidation and protein radical formation. Evidence exists that these proteins generate a radical species by reductive cleavage of S:-adenosylmethionine (SAM) through an unusual Fe-S centre .

This entry represents radical SAM domains that form an α/β horseshoe structure .