SII-SWORD/CoKE huggingface dataset:
Transcriptional repressor TraM superfamily (Tscrpt_rep_TraM_sf)
Type: Homologous_superfamily

Members of this superfamily of transcriptional repressors adopt a T-shaped structure, with a core composed of two antiparallel α-helices. These proteins can be divided into two parts, a globular head and an elongated tail, and they negatively regulate conjugation and the expression of tra genes by antagonising traR/AAI-dependent activation .
Matrilin, coiled-coil domain superfamily (Matrilin_CC_sf)
Type: Homologous_superfamily

This entry represents a short domain found the matrilin (cartilage matrix) proteins. It forms a coiled coil structure and contains a single cysteine residue at its start which is likely to form a di-sulphide bridge with a corresponding cysteine in an upstream EGF domain, thereby spanning the VWA domain of the protein (

). This domain is likely to be responsible for protein trimerisation .

The Matrilin proteins are major components of the extracellular matrix, primarily found in cartilage. These proteins play a crucial role in the formation of extracellular filamentous networks and matrix assembly. Proteins such as Matrilin-1, Matrilin-2, Matrilin-3, and Matrilin-4 can form various oligomeric structures, including homooligomers and heterooligomers, which contribute to their functional diversity. They interact with other extracellular matrix proteins like COMP and collagen, facilitating the structural integrity and function of cartilage. Matrilin-1, also known as cartilage matrix protein, is specifically involved in non-articular cartilage and binds to collagen, further emphasising its role in maintaining cartilage structure .
Activator of Hsp90 ATPase, Aha1 (Aha1)
Type: Homologous_superfamily

Aha1 is a co-chaperone that binds to the chaperone Hsp90 stimulating its ATPase activity. Aha1 adopts a secondary structure consisting of an N-terminal α-helix leading into a four-stranded meandering antiparallel β-sheet, followed by a C-terminal α-helix. The two α helices are packed together, with the β-sheet curving around them. The N-terminal domain of Aha1 interacts with Hsp90 and stimulates its ATPase activity .
PUB-like domain superfamily (PUB-like_dom_sf)
Type: Homologous_superfamily

The PUB (also known as PUG) domain is found in peptide N-glycanase where it functions as a AAA ATPase binding domain . This domain is also found on other proteins linked to the ubiquitin-proteasome system.

It has α(2)-β-α(2)-α(2)-α fold. It is composed of a cluster of helices with a small antiparallel β-sheet on one side. It presents topological similarity to the fold of an extended R3H domain.
MG296-like superfamily (MG296-like_sf)
Type: Homologous_superfamily

MG296 is an uncharacterised protein of 129 residues expressed in bacteria. It consists of three identical chains of five α helices. Two copies of each chain associate into a complex of six units of possible biological significance but of unknown function.
Her-1 superfamily (Her-1_sf)
Type: Homologous_superfamily

Her-1 adopts an all-helical structure with two subdomains: residues 19-80 comprise a left-handed three-helix bundle with an overhand connection between the second and third helices, whilst residues 81-164 comprise a left-handed anti-parallel four-helix bundle in which the first helix consists of four consecutive turns of 3-10-helix. Fourteen Cys residues are conserved in all known HER-1 sequences and form seven disulphide bonds. The protein dictates male development in Caenorhabditis elegans, probably by playing a direct role in cell signalling during C. elegans sex determination. It also inhibits the function of tra-2a .
Superantigen MAM (MAM_sf)
Type: Homologous_superfamily

Mycoplasma arthritidis-derived mitogen (MA-Mit) adopts a completely α-helical structure consisting of ten α-helices arranged in two orthogonal bundles. MA-Mit is a superantigen that can activate large fractions of T cells bearing particular TCR V-beta elements. Two MA-Mit molecules form an asymmetric dimer and cross-link two MHC antigens to form a dimerised MA-Mit-MHC complex .
Glutamyl-tRNA reductase, N-terminal domain superfamily (GluRdtase_N_sf)
Type: Homologous_superfamily

Delta-aminolevulinic acid (ALA) is the obligatory precursor for the synthesis of all tetrapyrroles including porphyrin derivatives such as chlorophyll and heme. ALA can be synthesized via two different pathways: the Shemin (or C4) pathway which involves the single step condensation of succinyl-CoA and glycine and which is catalyzed by ALA synthase and via the C5 pathway from the five-carbon skeleton of glutamate. The C5 pathway operates in the chloroplast of plants and algae, in cyanobacteria, in some eubacteria and in archaebacteria .

The initial step in the C5 pathway is carried out by glutamyl-tRNA reductase (GluTR) which catalyzes the NADP-dependent conversion of glutamate- tRNA(Glu) to glutamate-1-semialdehyde (GSA) with the concomitant release of tRNA(Glu) which can then be recharged with glutamate by glutamyl-tRNA synthetase .

This entry represents the N-terminal domain superfamily of glutamyl-tRNA reductase (

) . The enzyme requires NADPH as a cofactor. This domain has a Ferredoxin-like fold, which consits of an α+β sandwich with antiparallel β-sheet. This N-terminal domain is the catalytic domain .
Fungal immunomodulatory protein FIP-Fve superfamily (FIP_sf)
Type: Homologous_superfamily

FIP-Fve (Fungal Immunomodulatory Protein Fve) is a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity . It stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and oedema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and haemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve adopts a tertiary structure consisting of an immunoglobulin-like β-sandwich, with seven strands arranged in two β sheets, in a Greek-key topology. It forms a non-covalently linked homodimer containing no Cys, His or Met residues; dimerisation occurs by 3-D domain swapping of the N-terminal helices and is stabilised predominantly by hydrophobic interactions .
Exoribonuclease, PH domain 2 superfamily (ExoRNase_PH_dom2_sf)
Type: Homologous_superfamily

The PH (phosphorolytic) domain is responsible for 3'-5' exoribonuclease activity, although in some proteins this domain has lost its catalytic function. An active PH domain uses inorganic phosphate as a nucleophile, adding it across the phosphodiester bond between the end two nucleotides in order to release ribonucleoside 5'-diphosphate (rNDP) from the 3' end of the RNA substrate.

PH domains can be found in bacterial/organelle RNases and PNPases (polynucleotide phosphorylases) , as well as in archaeal and eukaryotic RNA exosomes , the later acting as nano-compartments for the degradation or processing of RNA (including mRNA, rRNA, snRNA and snoRNA). Bacterial/organelle PNPases share a common barrel structure with RNA exosomes, consisting of a hexameric ring of PH domains that act as a degradation chamber, and an S1-domain/KH-domain containing cap that binds the RNA substrate (and sometimes accessory proteins) in order to regulate and restrict entry into the degradation chamber . Unstructured RNA substrates feed in through the pore made by the S1 domains, are degraded by the PH domain ring, and exit as nucleotides via the PH pore at the opposite end of the barrel .

This entry represents the phosphorolytic (PH) domain 2 superfamily. This domain has a core 3-layer α/β/α structure. It is found in bacterial/organelle PNPases and in archaeal/eukaryotic exosomes .
GTP-binding protein OBG, C-terminal domain superfamily (GTP-bd_prot_GTP1/OBG_C_sf)
Type: Homologous_superfamily

Obg subfamily proteins (also known as ObgE, YhbZ and CgtA) are conserved P- loop GTPases, that are involved in a wide range of cellular processes, including sporulation, cellular differentiation, ribosome assembly, DNA replication, chromosome segregation, and stringent response in eubacteria and plant chloroplasts. Obg subfamily proteins have three domains: the Obg fold, the G domain, and the Obg C-terminal (OCT) domain. A potential role of the OCT domain in the regulation of the nucleotide-binding state has been suggested . The OCT domain structure contains a four-stranded β-sheet and three α-helices flanked by an additional β-strand .
Erythronolide synthase, docking domain superfamily (DEBS_docking_sf)
Type: Homologous_superfamily

Docking domains are found in prokaryotic erythronolide synthase. They adopt a structure consisting of a bundle of four α-helices, and mediate homodimerisation of the protein, stabilising the resulting complex .
WIBG, N-terminal domain superfamily (WIBG_N_sf)
Type: Homologous_superfamily

Partner of Y14 and mago (PYM, also known as WIBG) is a key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmarks for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation .

The N-terminal domain of PYM adopts a small globular all-β-domain structure, with a three-stranded β-sheet and a contiguous β-hairpin. It binds to both Mago and Y14 .
Integrin beta tail domain superfamily (Integrin_bsu_tail_dom_sf)
Type: Homologous_superfamily

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.

This entry represents the tail domain of the integrin beta subunit. It forms a four-stranded β-sheet that contains parallel and antiparallel strands and faces an α helix found at the N terminus of this domain . Interactions between the α-helix and the β-sheet are mostly hydrophobic and involve a disulphide bond. The rear of the β sheet is covered with a long A-B loop.
Large ribosomal subunit protein eL32 superfamily (Ribosomal_eL32_sf)
Type: Homologous_superfamily

eL32 is a protein from the large ribosomal subunit that contains a surface-exposed globular domain and a finger-like projection that extends into the RNA core to stabilize the tertiary structure. eL32 does not appear to play a role in forming the A (aminacyl), P (peptidyl) or E (exit) sites of the ribosome, but does interact with 23S rRNA, which has a "kink-turn" secondary structure motif. eL32 is overexpressed in human prostate cancer and has been identified as a stably expressed housekeeping gene in macrophages of human chronic obstructive pulmonary disease (COPD) patients. In Schizosaccharomyces pombe, eL32 has also been suggested to play a role as a transcriptional regulator in the nucleus. Found in archaea and eukaryotes .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Sema domain superfamily (Semap_dom_sf)
Type: Homologous_superfamily

The Sema domain occurs in semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in plexins , receptors for multiple classes of semaphorins, in hepatocyte growth factor receptor, and in viral proteins .

The Sema domain is characterised by a conserved set of cysteine residues, which form four disulphide bonds to stabilise the structure. The Sema domain fold is a variation of the β propeller topology, with seven blades radially arranged around a central axis. Each blade contains a four-stranded (strands A to D) antiparallel β sheet. The inner strand of each blade (A) lines the channel at the centre of the propeller, with strands B and C of the same repeat radiating outward, and strand D of the next repeat forming the outer edge of the blade. The large size of the Sema domain is not due to a single inserted domain but results from the presence of additional secondary structure elements inserted in most of the blades. The Sema domain uses a 'loop and hook' system to close the circle between the first and the last blades. The blades are constructed sequentially with an N-terminal β-strand closing the circle by providing the outermost strand (D) of the seventh (C-terminal) blade. The β-propeller is further stabilised by an extension of the N terminus, providing an additional, fifth β-strand on the outer edge of blade 6 .
XPC-binding domain superfamily (XPC-bd_sf)
Type: Homologous_superfamily

This domain adopts a structure consisting of four α-helices, arranged in an array. It binds specifically and directly to the xeroderma pigmentosum group C protein (XPC) to initiate nucleotide excision repair .
Proteinase inhibitor I13, potato inhibitor I superfamily (Prot_inh_pot1_sf)
Type: Homologous_superfamily

This family of proteinase inhibitors belong to MEROPS inhibitor family I13, clan IG. They inhibit peptidases of the S1 (

) and S8 (

) families . Potato inhibitor type I sequences are not solely restricted to potatoes but are found in other plant species for example: barley endosperm chymotrypsin inhibitor , and pumpkin trypsin inhibitor. Apart from leeches, e.g.Hirudo medicinalis (Medicinal leech), homologues are not found in metazoa . In general, the proteins have retained a specificity towards chymotrypsin-like and elastase-like proteases. Structurally these inhibitors are small (60 to 90 residues) and in contrast with other families of protease inhibitors, they lack disulphide bonds. The inhibitor is a wedge-shaped molecule, its pointed edge formed by the protease-binding loop, which contains the scissile bond. The loop binds tightly to the protease active site, subsequent cleavage of the scissile bond causing inhibition of the enzyme .

The inhibitors (designated type I and II) are synthesised in potato tubers, increasing in concentration as the tuber develops. Synthesis of the inhibitors throughout the plant is also induced by leaf damage; this systemic response being triggered by the release of a putative plant hormone.

Examples found in the bacteria and archaea are probable false positives.
Endoplasmic reticulum resident protein 29, C-terminal domain superfamily (ERp29_C_sf)
Type: Homologous_superfamily

ERp29 (also known as ERp28 and ERp31) is a ubiquitously expressed endoplasmic reticulum protein found in mammals . This protein has an N-terminal thioredoxin-like domain, which is homologous to the domain of human protein disulphide isomerase (PDI). ERp29 may help mediate the chaperone function of PDI. The C-terminal Erp29 domain has a 5-helical bundle fold. ERp29 is thought to form part of the thyroglobulin folding complex .
Photosystem I reaction centre subunit VIII superfamily (PSI_PsaI_sf)
Type: Homologous_superfamily

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

This entry represents subunit VIII (PsaI) of the photosystem I (PSI) reaction centre. PSI is located, along with photosystem II (PSII), in the thylakoid photosynthetic membranes of plants, green algae and cyanobacteria. The crystal structure of PSI from the thermophilic cyanobacterium Synechococcus elongatus (Thermosynechococcus elongatus) has 12 protein subunits and 127 cofactors comprising 96 chlorophylls, 2 phylloquinones, 3 4Fe4S clusters, 22 carotenoids, 4 lipids, and a putative calcium ion . PsaI consists of a single transmembrane helix, and has a crucial role in aiding normal structural organisation of PsaL within the PSI complex and the absence of PsaI alters PsaL organisation, leading to a small, but physiologically significant, defect in PSI function . PsaL encodes a subunit of PSI and is necessary for trimerisation of PSI. PsaL may constitute the trimer-forming domain in the structure of PSI .
Beta-trefoil domain superfamily (BTD_sf)
Type: Homologous_superfamily

This DNA-binding domain superfamily adopts a β-trefoil fold, that is, a capped β-barrel with internal pseudo threefold symmetry. In the DNA-binding protein LAG-1, it also is the site of mutually exclusive interactions with NotchIC (and the viral protein EBNA2) and corepressors (SMRT/N-Cor and CIR) .
Thiol-activated cytolysin superfamily (Thiol_cytolysin_sf)
Type: Homologous_superfamily

Thiol-activated cytolysins are toxins produced by a variety of Gram-positive bacteria and are characterised by their ability to lyse cholesterol-containing membranes, their reversible inactivation by oxidation and their capacity to bind to cholesterol. All these proteins contain a single cysteine residue, located in their C-terminal section, which has been shown to be essential for the binding to cholesterol.
SAP domain superfamily (SAP_dom_sf)
Type: Homologous_superfamily

The SAP motif is a 35-residue motif, which has been named after SAF-A/B, Acinus and PIAS, three proteins known to contain it. The SAP motif is found in a variety of nuclear proteins involved in transcription, DNA repair, RNA processing or apoptotic chromatin degradation. As the sap motif of SAF-A has been shown to be essential for specific DNA binding activity, it has been proposed that it could be a DNA-binding motif .

A multiple alignment of the SAP motif reveals a bipartite distribution of strongly conserved hydrophobic, polar and bulky amino acids separated by a region that contains a glycine. Secondary structure predictions suggest that the SAP motif could form two α helices separated by a turn .

Some proteins known to contain a SAP motif are listed below:

Vertebrate scaffold attachment factors A and B (SAF-A/B). These two proteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind to AT-rich chromosomal region. It has been proposed that they couple RNA metabolism to nuclear organisation . The SAF-A protein is cleaved by caspase-3 during apoptosis .

Mammalian Acinus, a protein which induces apoptotic chromatin condensation after cleavage by caspase-3 . Acinus also contains a RNA-recognition motif.

Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT) family. These proteins interact with phosphorylated STAT dimers and inhibit STAT mediated gene activation. Deletion of the first 50 amino acid residues containing the SAP domain allows the interaction of PIAS1 with STAT1 monomer .

Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein that catalyzes the poly(ADP-ribosyl)ation of proteins. It is involved in responses to mild and severe oxidative stresses, by mediating DNA repair and programmed cell death processes, respectively . PARP is tightly bound to chromatin or nuclear matrix.

Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.

Yeast THO1 protein. It could be involved in the regulation of transcriptional elongation by RNA polymerase II .

Animal Ku70. Together with Ku86, it forms a DNA ends binding complex that is involved in repairing DNA double-strand breaks.

Yeast RAD18, a protein involved in DNA repair.

Neurospora crassa UVS-2, the homologue of RAD18.
Adenovirus DNA-binding, N-terminal domain superfamily (Adenovirus_DNA-bd_N_sf)
Type: Homologous_superfamily

This entry represents the N terminus of the C-terminal domain of the Adenovirus DNA-binding protein, a multi functional protein involved in DNA replication and transcription control . Its structure has four helices with a partly open bundle.
Thiol-activated cytolysin, alpha-beta domain superfamily (Thiol_cytolysin_ab_sf)
Type: Homologous_superfamily

Thiol-activated cytolysins are toxins produced by a variety of Gram-positive bacteria and are characterised by their ability to lyse cholesterol-containing membranes, their reversible inactivation by oxidation and their capacity to bind to cholesterol. All these proteins contain a single cysteine residue, located in their C-terminal section, which has been shown to be essential for the binding to cholesterol.