SII-SWORD/CoKE huggingface dataset:
Lamin tail domain superfamily (Lamin_tail_dom_sf)
Type: Homologous_superfamily

Intermediate filaments (IF) are primordial components of the cytoskeleton and the nuclear envelope . They generally form filamentous structures 8 to 14 nm wide. IF proteins are members of a very large multigene family of proteins which has been subdivided in five major subgroups, type I: acidic cytokeratins, type II: basic cytokeratins, type III: vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin, type IV: neurofilaments L, H and M, alpha-internexin and nestin, and type V: nuclear lamins A, B1, B2 and C. The lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane that may provide a framework for the nuclear envelope and may interact with chromatin.

All IF proteins are structurally similar in that they consist of a central rod domain arranged in coiled-coil α-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins. The C-terminal domain has been characterised for the lamins .

The lamin-tail domain (LTD), which has an immunoglobulin (Ig) fold, is found in nuclear lamins and several bacterial proteins where it occurs with membrane associated hydrolases of the metallo-beta-lactamase, synaptojanin, and calcineurin-like phosphoesterase superfamilies .
Peptidyl-tRNA hydrolase superfamily (Pept_tRNA_hydro_sf)
Type: Homologous_superfamily

Peptidyl-tRNA hydrolase (

) (PTH) is a bacterial enzyme that cleaves peptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the ribosome during protein synthesis . Bacterial PTH has been found to be evolutionary related to a yeast protein . This enzyme is interesting as a potential target for the discovery of new antimicrobial agents as it is critical for the viability of bacteria [

}. It folds into a single α/β globular domain with seven β-strands forming a twisted mixed central β-sheet, surrounded by a total of six helices .

This group also contains chloroplast RNA splicing 2 (CRS2), which is closely related nuclear-encoded protein required for the splicing of nine group II introns in chloroplasts .

The structure of hydrolases consists of three layers (α/β/α) with mixed sheets of five strands where the strand 4 is antiparallel to the rest, and contains crossover loops.
Tobacco mosaic virus-like, coat protein superfamily (TMV-like_coat_sf)
Type: Homologous_superfamily

This superfamily contains virus coat proteins. Examples include those from Tobacco mosaic virus (TMV), Cucumber green mottle mosaic virus and Ribgrass mosaic virus (RMV).

In order to establish infections, viruses must be delivered to the cells of potential hosts and must then engage in activities that enable their genomes to be expressed and replicated. With most viruses, the events that precede the onset of production of progeny virus particles are referred to as the early events and, in the case of positive-strand RNA viruses, they include the initial interaction with and entry of host cells and the release (uncoating) of the genome from the virus particles. The uncoating process in TMV may involve the bidirectional release of coat protein subunits from the viral RNA which may be mediated by cotranslational and coreplicational disassembly mechanisms .

The TMV particle is assembled from its constituent coat protein and RNA by a complex process. The protein forms an obligatory intermediate (a cylindrical disk composed of two layers of protein units), which recognises a specific RNA hairpin sequence. This mechanism simultaneously fulfils the physical requirement for nucleating the growth of the helical particle and the biological requirement for specific recognition of the viral DNA . TMV has a four-helical up-and-down bundle fold.
Cytochrome c oxidase, subunit VIa superfamily (Cyt_c_oxidase_su6a_sf)
Type: Homologous_superfamily

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptidic subunits. One of these subunits is known as VIa in vertebrates and fungi. Mammals have two tissue-specific isoforms of VIa, a liver (VIa-L) and a heart and skeletal muscle isoform (VIa-H). Mammalian VIa-H induces a slip in CcO (decrease in proton/electron stoichiometry) at high intramitochondrial ATP/ADP ratios, while VIa-L induces a permanent slip in CcO, depending on the presence of cardiolipin and palmitate . Only one form is found in fish .
Ribosomal protein S3, C-terminal domain superfamily (Ribosomal_S3_C_sf)
Type: Homologous_superfamily

Ribosomal protein S3 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S3 is known to be involved in the binding of initiator Met-tRNA. This family of ribosomal proteins includes S3 from bacteria, algae and plant chloroplast, cyanelle, archaebacteria, plant mitochondria, vertebrates, insects, Caenorhabditis elegans and yeast . This entry is the C-terminal domain. This domain has two layers (α/β) with antiparallel β-sheets.
BRCT domain superfamily (BRCT_dom_sf)
Type: Homologous_superfamily

The breast cancer susceptibility gene contains at its C terminus two copies of a conserved domain that was named BRCT for BRCA1 C terminus. This domain of about 95 amino acids is found in a large variety of proteins involved in DNA repair, recombination and cell cycle control . The BRCT domain is not limited to the C-terminal of protein sequences and can be found in multiple copies or in a single copy as in RAP1 and TdT. Some data indicate that the BRCT domain functions as a protein-protein interaction module.

The structure of the first of the two C-terminal BRCT domains of the human DNA repair protein XRCC1 has been determined by X-ray crystallography, it comprises a four-stranded parallel β-sheet surrounded by three α-helices, which form an autonomously folded domain .
Iron dependent repressor, metal binding and dimerisation domain superfamily (Fe_dep_repressor_sf)
Type: Homologous_superfamily

The diphtheria toxin repressor protein (DTXR) is a member of this group . In Corynebacterium diphtheriae where it has been studied in some detail this protein acts as an iron-binding repressor of diphtheria toxin gene expression and may serve as a global regulator of gene expression. DTXR comprises an N-terminal DNA-binding domain, an interface domain (which contains two metal-binding sites) and a third, very flexible C-terminal domain. The second domain is responsible for dimerization and metal binding. The N terminus may be involved in iron binding and may associate with the Tox operator. Binding of DTXR to Tox operator requires a divalent metal ion such as cobalt, ferric, manganese and nickel whereas zinc shows weak activation .

The dimerisation domain is composed of six helices, each one containing a homodimer of 3-helical domains.
RuBisCO large subunit, N-terminal domain superfamily (RuBisCO_lsu_N_sf)
Type: Homologous_superfamily

Ribulose bisphosphate carboxylase (RuBisCO) catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate .
Superoxide dismutase-like, copper/zinc binding domain superfamily (SOD-like_Cu/Zn_dom_sf)
Type: Homologous_superfamily

Superoxide dismutases (SODs) are ubiquitous metalloproteins that prevent damage by oxygen-mediated free radicals by catalysing the dismutation of superoxide into molecular oxygen and hydrogen peroxide . Superoxide is a normal by-product of aerobic respiration and is produced by a number of reactions, including oxidative phosphorylation and photosynthesis. The dismutase enzymes have a very high catalytic efficiency due to the attraction of superoxide to the ions bound at the active site .

There are three forms of superoxide dismutase, depending on the metal cofactor: Cu/Zn (which binds both copper and zinc), Fe and Mn types. The Fe and Mn forms are similar in their primary, secondary and tertiary structures, but are distinct from the Cu/Zn form . Prokaryotes and protists contain Mn, Fe or both types, while most eukaryotic organisms utilise the Cu/Zn type. The Cu/Zn form has an immunoglobulin-like β-sandwich fold.

Defects in the human SOD1 gene causes familial amyotrophic lateral sclerosis (Lou Gehrig's disease). Cytoplasmic and periplasmic SODs exist as dimers, whereas chloroplastic and extracellular enzymes exist as tetramers. Structural analysis supports the notion of independent functional evolution in prokaryotes (P-class) and eukaryotes (E-class) .
Decaprenyl diphosphate synthase-like superfamily (UPP_synth-like_sf)
Type: Homologous_superfamily

In prokaryotes, undecaprenyl diphosphate synthase (UPP synthase or di-trans-poly-cis-decaprenylcistransferase (

)), catalyzes the formation of the carrier lipid undecaprenyl pyrophosphate (UPP) in bacterial cell wall peptidoglycan biosynthesis from isopentenyl pyrophosphate (IPP) . Cis (Z)-Isoprenyl diphosphate synthase (cis-IPPS) catalyzes the successive 1'-4 condensation of the IPP molecule to trans,trans-farnesyl diphosphate (FPP) or to cis,trans-FPP to form long-chain polyprenyl diphosphates. A few can also catalyze the condensation of IPP to trans-geranyl diphosphate to form the short-chain cis,trans- FPP. cis-IPPS form homodimers and are mechanistically and structurally distinct from trans-IPPS, which lack the DDXXD motifs, yet require Mg
2+
for activity. Homologues are also found in archaebacteria and include a number of uncharacterised proteins including some from yeasts.

The structure of diphosphate synthase has three layers (α/β/α) with parallel β-sheet of six strands.

This entry also matches related enzymes that transfer alkyl groups, such as dehydrodolichyl diphosphate synthase from eukaryotes, which catalyzes the formation of the polyisoprenoid glycosyl carrier lipid dolichyl monophosphate.
MoaB/Mog-like domain superfamily (MoaB/Mog-like_dom_sf)
Type: Homologous_superfamily

MoaB/Mog domain, also known as Cnx1G domain, is found in the bacterial molybdenum cofactor (Moco) biosynthesis protein MoaB/Mog and N-terminal of the eukaryotic MoCF biosynthesis proteins, such as the Drosophila protein cinnamon, the Arabidopsis protein cnx1 and the mammal protein gephyrin . These proteins are involved in the final steps of Moco synthesis. In E. coli two proteins, MogA and MoeA are essential for Mo insertion into molybdopterin, while in plants and animals one fusion protein with two domains (G and E domains) fulfils this function. The G domain of Cnx1 and gephyrin shares similarity with MoaB/Mog, while their E domain displays similarities to the sulfurtransferase rhodanese (homologous to E. coli MoeA/chlE) . Structurally, MogA is folded into a compact molecule with α/β/α architecture and forms a trimer . The Cnx1G domain has been shown to bind molybdopterin .

This domain is also found in N-terminal of the FAD synthases belonging to a family that catalyses the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme . CinA from Thermus thermophilus is shown to have both nicotinamide mononucleotide deamidase and ADP-ribose pyrophosphatase activities, with ADP-ribose pyrophosphatase activity attributed to the N-terminal domain .

The structure of the MoaB/Mog domain has three layers (α/β/α) with mixed β-sheet of five strands where the strand 5 is antiparallel to the rest.
Bulb-type lectin domain superfamily (Bulb-type_lectin_dom_sf)
Type: Homologous_superfamily

A bulb lectin super-family (Amaryllidaceae, Orchidaceae and Aliaceae) contains a ~115-residue-long domain whose overall three dimensional fold is very similar to that of :

Dictyostelium discoideum comitin, an actin binding protein

Curculigo latifolia curculin, a sweet tasting and taste-modifying protein

This domain generally binds mannose, but in at least one protein, curculin, it is apparently devoid of mannose-binding activity.
Bromodomain-like superfamily (Bromodomain-like_sf)
Type: Homologous_superfamily

Bromodomains are found in a variety of mammalian, invertebrate and yeast DNA-binding proteins . Bromodomains are highly conserved α-helical motifs that can specifically interact with acetylated lysine residues on histone tails . In some proteins, the classical bromodomain has diverged to such an extent that parts of the region are either missing or contain an insertion (e.g., mammalian protein HRX, Caenorhabditis elegans hypothetical protein ZK783.4, yeast protein YTA7). The bromodomain may occur as a single copy, or in duplicate.

This domain is present in proteins involved in a wide range of functions such as acetylating histones, remodelling chromatin, and recruiting other factors necessary for transcription, thus playing a critical role in the regulation of transcription .
Pterin 4 alpha carbinolamine dehydratase superfamily (PCD_sf)
Type: Homologous_superfamily

DCoH has a β(2)-α-β(2)-α fold arranged in two α/β layers.

Pterin 4 alpha carbinolamine dehydratase is also known as DCoH. DCoH is the dimerisation cofactor of hepatocyte nuclear factor 1 (HNF-1) that functions as both a transcriptional coactivator and a pterin dehydratase . X-ray crystallographic studies have shown that the ligand binds at four sites per tetrameric enzyme, with little apparent conformational change in the protein.
SpoA-like superfamily (SpoA-like_sf)
Type: Homologous_superfamily

Proteins of the surface presentation of antigen (SpoA) group are involved in a secretory pathway responsible for the surface presentation of invasion plasmid antigen needed for the entry of Salmonella and other species into mammalian cells .They could play a role in preserving the translocation competence of the IPA antigens and are required for secretion of the three IPA proteins .

The SpoA structure is composed of a segment-swapped dimer forming two identical conjoint barrels fold and is topologically similar to the FMN-binding split barrel.

This entry represents the C-terminal region of Flagellar motor switch proteins FliN and FliM and similar proteins mainly found in bacteria. This domain seems to play a key role in flagellation .
Ribonuclease T2-like superfamily (RNase_T2-like_sf)
Type: Homologous_superfamily

Ribonuclease T2 (RNase T2) is a widespread family of secreted RNases found in every organism examined thus far. This family includes RNase Rh, RNase MC1, RNase LE, and self-incompatibility RNases (S-RNases) . Plant T2 RNases are expressed during leaf senescence in order to scavenge phosphate from ribonucleotides. They are also expressed in response to wounding or pathogen invasion. S-RNases are thought to prevent self-fertilization by acting as selective cytotoxins of "self" pollen. Generally, RNases have two distinct binding sites: the primary site (B1 site) and the subsite (B2 site), for nucleotides located at the 5'- and 3'- terminal ends of the sissile bond, respectively.

The fungal ribonucleases T2 from Aspergillus oryzae, M from Aspergillus saitoi and Rh from Rhizopus niveus are structurally and functionally related 30 Kd glycoproteins that cleave the 3'-5' internucleotide linkage of RNA via a nucleotide 2',3'-cyclic phosphate intermediate (

). Two histidines residues have been shown to be involved in the catalytic mechanism of RNase T2 and Rh. These residues and the region around them are highly conserved in a number of other RNAses that have been found to be evolutionary related to these fungal enzymes.

The structure of ribonuclease T2 is composed of an α+β fold.
ARID DNA-binding domain superfamily (ARID_dom_sf)
Type: Homologous_superfamily

The AT-rich interaction domain (ARID) is an ~100-amino acid DNA-binding module found in a large number of eukaryotic transcription factors that regulate cell proliferation, differentiation, and development . The ARID domain appears as a single-copy motif and can be found in association with other domains, such as JmjC, JmjN, Tudor and PHD-type zinc finger .

The basic structure of the ARID domain appears to be a series of six α-helices separated by β-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. Based on primary sequence homology, they can be partitioned into three structural classes:

Minimal ARID proteins that consist of a core domain formed by six α-helices;

ARID proteins that supplement the core domain with an N-terminal α-helix;

Extended-ARID proteins, which contain the core domain and additional α-helices at their N-and C-termini.

Minimal ARIDs are distributed in all eukaryotes, while extended ARIDs are restricted to metazoans. The ARID domain binds DNA as a monomer, recognising the duplex through insertion of a loop and an α-helix into the major groove and by extensive non-specific anchoring contacts to the adjacent sugar-phosphate backbone .

Some proteins known to contain an ARID domain are listed below:

Eukaryotic transcription factors of the jumonji family.

Mammalian Bright, a B-cell-specific trans-activator of IgH transcription.

Mammalian PLU-1, a protein that is upregulated in breast cancer cells.

Mammalian RBP1 and RBP2, retinoblastoma-binding factors.

Mammalian Mrf-1 and Mrf-2, transcriptional modulators of the cytomegalovirus major intermediate-early promoter.

Drosophila melanogaster dead ringer protein, a transcriptional regulatory protein required for early embryonic development.

Yeast SWI1 protein, from the SWI/SNF complex involved in chromatin remodelling and broad aspects of transcription regulation.

Drosophila melanogaster Osa. It is structurally related to SWI1 and associates with the brahma complex, which is the Drosophila equivalent of the SWI/SNF complex.
Elongation factor EF1B gamma, C-terminal domain superfamily (EF1B_G_C_sf)
Type: Homologous_superfamily

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .

This entry represents a conserved domain superfamily. This domain is usually found near the C terminus of EF1B-gamma chains, a peptide of 410-440 residues. The gamma chain appears to play a role in anchoring the EF1B complex to the beta and delta chains and to other cellular components.
1, 4-beta cellobiohydrolase superfamily (Beta_cellobiohydrolase_sf)
Type: Homologous_superfamily

O-Glycosyl hydrolases (

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

The 1,4-beta cellobiohydrolase superfamily plays a central role in the recycling of plant biomass. The biological conversion of cellulose to glucose generally requires three types of hydrolytic enzymes: Endoglucanases, which cut internal beta-1,4-glucosidic bonds; exocellobiohydrolases that cut the dissaccharide cellobiose from the non-reducing end of the cellulose polymer chain; and beta-1,4-glucosidases, which hydrolyze the cellobiose and other short cello-oligosaccharides to glucose.
Leukocidin/porin MspA superfamily (Leukocidin/porin_MspA_sf)
Type: Homologous_superfamily

This entry represents a structural domain consisting of a β-sandwich fold with an immunoglobulin-like Greek-key topology, and a β-ribbon arm that forms an oligomeric transmembrane barrel. This domain is found in pore-forming proteins, including porin MspA, as well as the exotoxins haemolysin and leukocidin. MspA is a membrane porin produced by Mycobacteria, allowing hydrophilic nutrients to enter the bacterium . Haemolysins attack blood cell membranes and cause cell rupture by forming water-filled homoheptameric transmembrane pores. Leukocidin consists of two polypeptides, F and S, and form pores in polymorphonuclear leukocytes .
Disintegrin domain superfamily (Disintegrin_dom_sf)
Type: Homologous_superfamily

Disintegrins are a family of small proteins from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion . Integrin receptors are involved in cell-cell and cell-extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet-platelet bridges, which are essential in thrombosis and haemostasis. Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor-glycoprotein complex of activated platelets. Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and collagen . The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant .

Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin , schistatin , echistatin , elegantin, eristicophin, flavoridin , halysin, kistrin, tergeminin, salmosin and triflavin.

Disintegrin-like proteins are found in various species ranging from slime mold to humans. Some other proteins known to contain a disintegrin domain are:

Some snake venom zinc metalloproteinases consist of an N-terminal catalytic domain fused to a disintegrin domain. Such is the case for trimerelysin I (HR1B), atrolysin-e (Ht-e) and trigramin. It has been suggested that these proteinases are able to cleave themselves from the disintegrin domains and that the latter may arise from such a post-translational processing.

The beta-subunit of guinea pig sperm surface protein PH30 . PH30 is a protein involved in sperm-egg fusion. The beta subunit contains a disintegrin at the N-terminal extremity.

Mammalian epididymial apical protein 1 (EAP I) . EAP I is associated with the sperm membrane and may play a role in sperm maturation. Structurally, EAP I consists of an N-terminal domain, followed by a zinc metalloproteinase domain, a disintegrin domain, and a large C-terminal domain that contains a transmembrane region.