SII-SWORD/CoKE huggingface dataset:
Mediator of RNA polymerase II, subunit Med31 superfamily (Med31_sf)
Type: Homologous_superfamily

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

This entry includes subunit Med31 of the Mediator complex and the Saccharomyces cerevisiae homologue, Soh1. Soh1 is responsible for the repression of temperature sensitive growth of the Hpr1 mutant and has been found to be a component of the RNA polymerase II transcription complex. Soh1 not only interacts with factors involved in DNA repair, but transcription as well. Thus, the Soh1 protein may serve to couple these two processes .

Med31 is organised as a four helix bundle and with the N-terminal part of subunit Med7 forms a submodule of the middle module of the mediator core which is unique in structure and function. In vivo, Med7N/31 has a predominantly positive function on the expression of a specific subset of genes, including genes involved in methionine metabolism and iron transport .
DNA replication factor Cdt1, C-terminal WH domain superfamily (Cdt1_C_WH_dom_sf)
Type: Homologous_superfamily

In eukaryotic replication licensing, Cdt1 plays a key role by recruiting the MCM2-7 complex onto the origin of chromosome. This entry represents the C-terminal domain of Cdt1 which is the most conserved region of Cdt1, essential for licensing and directly interacts with the MCM2-7 complex . This region contains a WHD (winged helix domain), a typical DNA recognition motif . The winged-helix fold is conserved throughout several other licensing factors, suggesting that they evolved from a common ancestor. In mouse Cdt1, the main role of the WH motif is to interact with MCM2-7 rather than with the DNA, as other winged-helix domains.
UPF0302, N-terminal domain superfamily (UPF0302_N_sf)
Type: Homologous_superfamily

This N-terminal domain is found in a group of uncharacterised proteins that belong to the UPF0302 family.
Phosphorylated adapter RNA export protein, RNA-binding domain superfamily (PHAX_RNA-binding_sf)
Type: Homologous_superfamily

The phosphorylated adaptor for RNA export (PHAX) protein transports U3 snoRNA from the nucleus after transcription . This entry represents the highly conserved U3 snoRNA-binding domain of PHAX, which is characterised by having two pairs of adjacent glycines with the sequence motif GGx12GG. This domain adopts a novel helical fold and binds non-specific single-stranded RNA and comprises five α-helices linked by short loops containing 1 to 4 residues, apart from helices alpha3 and 4 that are linked by 13 residues. The fold is unique to this kind of RNA binding domains which show no structural homology with other RNA-binding domains .
Ubiquitin carboxyl-terminal hydrolase 37, pleckstrin homology-like domain superfamily (USP37-like_PH_sf)
Type: Homologous_superfamily

This pleckstrin homology (PH)-like domain can be found at the N terminus of some ubiquitin carboxyl-terminal hydrolases, including USP26, USP29 and USP37. USP37 antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), resulting in promoting S phase entry . USP26 is a regulator of androgen receptor (AR) signaling . Both USP26 and USP37 are critical for double-strand breaks repair by homologous recombination . USP29 plays a role in apoptosis and oxidative stress .

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner . They share little sequence conservation, but all have a common fold, which is electrostatically polarized.
Desulfoferrodoxin, N-terminal domain superfamily (Desulfoferrodoxin_N_sf)
Type: Homologous_superfamily

Desulfoferrodoxin (class I) is a homodimeric protein, with each protomer comprised of two domains, the N-terminal desulforedoxin (DSRD) domain and C-terminal superoxide reductase-like (SORL) domain. Each domain has a distinct iron centre: the DSRD iron centre I, Fe(S-Cys)4; and the SORL iron centre II, Fe[His4Cys(Glu)] .

This entry represents the N-terminal desulforedoxin (DSRD) domain superfamilly. It has a similar fold to the rubredoxin metal binding domain.
Costars domain superfamily (Costars_sf)
Type: Homologous_superfamily

This entry represents the Costars domain superfamily.

This domain is found both alone (in the costars family of proteins) and at the C terminus of actin-binding Rho-activating protein (ABRA). It binds to actin, and in muscle regulates the actin cytoskeleton and cell motility . It has a winged helix-like fold consisting of three α-helices and four antiparallel β strands. Unlike typical winged helix proteins it does not bind to DNA, but contains a hydrophobic groove which may be responsible for interaction with other proteins .
TEA/ATTS domain superfamily (TEA/ATTS_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in the Transcriptional enhancer factor (TEF) and in the Conidiophore development regulator aba.

The TEA domain is a DNA-binding region of about 66 to 68 amino acids that has been named after the two proteins that originally defined the domain: TEF-1 and AbaA. The TEA domain is located toward the N terminus of eukaryotic transcription factors of the TEA/ATTS family. It shows a three-helix bundle with a homeodomain fold . Two α-helices are nearly anti-parallel and pack on either side of the third one, which is the DNA-recognition helix of the TEA domain. Phosphorylation of one or both of the two conserved serines found on the DNA-binding surface could interfere with DNA-binding activity, by introducing electrostatic repulsion and/or steric hindrance, and help regulate the transcription factor activity of the proteins .
Large ribosomal subunit protein eL36 domain superfamily (Ribosomal_eL36_sf)
Type: Homologous_superfamily

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. The eL36 (also known as L36e) ribosomal family consists of mammalian , Caenorhabditis elegans and Drosophila L36, Candida albicans L39, and yeast YL39 ribosomal proteins .

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 .
PHD finger protein 12, MRG binding domain superfamily (PHF12_MRG-bd_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in PHF12 (PHD finger protein 12, also known as Pf1) binds to the MRG domain of mortality factor 4-like protein 1 (MORF4L1, also known as MRG15) . In mammals, the corepressor Sin3B, the histone deacetylase HDAC1, MRG15 and Pf1 form a complex that plays important roles in regulation of transcription .
BldD-like, C-terminal domain superfamily (BldD-like_C_sf)
Type: Homologous_superfamily

The Streptomyces transcription factor BldD represses the transcription of ~170 sporulation genes during vegetative growth. It binds and is regulated by the second messenger 3',5'-cyclic diguanylic acid (c-di-GMP) .

This entry represents the C-terminal domain of BldD from Streptomyces venezuelae (

) and similar proteins found in Actinobacteria. This domain shows two β-α-α repeats and a short C-terminal helix. It is responsible for the binding of the protein to the second messenger 3',5'-cyclic diguanylic acid (c-di-GMP) .
NVL2, N-terminal domain superfamily (NLV2_N_sf)
Type: Homologous_superfamily

This superfamily represents a domain found at the N terminus of nuclear valosin-containing protein (VCP)-like protein 2 (NVL2). This domain adopts a three helix fold resembling part of a winged helix motif and binds to nucleolin, a multifunctional phosphoprotein ubiquitously distributed in the nucleolus, nucleus and cytoplasm of the cell .
EYA domain superfamily (EYA_dom_sf)
Type: Homologous_superfamily

The Eyes absent proteins are members of a conserved regulatory network implicated in the development of the eye, muscle, kidney and ear. Eyes absent is a nuclear transcription factor, acting through interaction with homeodomain-containing Sine oculis (also known as Six) proteins. Eyes absent is also a protein tyrosine phosphatase , It does not resemble the classical tyrosine phosphatases that use cysteine as a nucleophile and proceed by means of a thiol-phosphate intermediate. Rather, Eyes absent is the prototype for a class of protein tyrosine phosphatases that use a nucleophilic aspartic acid in a metal-dependent reaction. Furthermore, the phosphatase activity of Eyes absent contributes to its ability to induce eye formation in drosophila. Thus, Eyes absent belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily and appears to act as a nuclear transcriptional coactivator with intrinsic phosphatase activity.

The Eyes absent proteins contain a divergent 200-300 residue long N-terminal region and a conserved C-terminal domain of approximately 270 residues, the EYA domain, which is critical for activity and believed to participate in protein-protein interactions .
Cell division control protein 73, C-terminal domain superfamily (CDC73_C_sf)
Type: Homologous_superfamily

CDC73 is an RNA polymerase II accessory factor , and forms part of the Paf1 complex that has roles in post-initiation events . More specifically, crystal structure analysis shows the C terminus to be a Ras-like domain that adopts a fold that is highly similar to GTPases of the Ras superfamily. The C-terminal domain contains a large but comparatively flat surface of highly conserved residues, devoid of ligand. Deletion of the Cdc73 C-domain significantly reduces Paf1C occupancy on active genes, which means that the Cdc73 C-domain plays a role in promoting association of Paf1C with chromatin .

The canonical nucleotide binding pocket is altered in CDC73, and there is no nucleotide ligand, but it contributes to histone methylation and Paf1 complex (Paf1C) recruitment to active genes. Thus, together with Rtf1, it combines to couple Paf1C to elongating polymerase .
TRF2-interacting telomeric protein/Rap1, C-terminal domain superfamily (Rap1_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the protein Rap-1, which plays a distinct role in silencing at the silent mating-type loci and telomeres . The Rap-1 C terminus adopts an all-helical fold. Rap1 carries out its function by recruiting the Sir3 and Sir4 proteins to chromatin via its C-terminal domain . Rap1 is otherwise known as TRF2-interacting protein, as it is one of the six subunit components of the Shelterin complex. Shelterin protects telomere ends from attack by DNA-repair mechanisms .
Kinesin-like protein Kif23, Arf6-interacting domain superfamily (Kif23_Arf-bd_sf)
Type: Homologous_superfamily

The C-terminal region of kinesin-like protein Kif23 (also known as MKLP1) is necessary for the interaction with the small GTPase Arf6. MKLP1 is a Flemming body-localising protein essential for cytokinesis. The Arf6-MKLP1 complex plays a crucial role in cytokinesis by connecting the microtubule bundle and membranes at the cleavage plane .
NFRKB winged helix-like domain superfamily (NFRKB_winged_sf)
Type: Homologous_superfamily

This winged helix-like domain is found in nuclear factor related to kappa-B-binding (NFRKB) protein. This winged helix-like domain is however not involved in DNA binding but is instead thought to be involved in protein-protein interactions .
3-deoxy-D-manno-octulosonic-acid transferase, N-terminal domain superfamily (Glycos_transf_N_sf)
Type: Homologous_superfamily

3-deoxy-D-manno-octulosonic-acid transferase (WaaA, KdtA) is involved in lipopolysaccharide biosynthesis. It catalyses the transfer of two 3-deoxy-D-manno-octulosonate (Kdo) residues from CMP-Kdo to lipid IV(A), the precursor of lipid A . WaaA consists of two Rossmann-like domains. This superfamily represents the N-terminal domain, which is the acceptor-substrate binding domain. Structurally, it consists of 7 α-helices and 5 β-strands .
RPN13, DEUBAD domain superfamily (RPN13_DEUBAD_sf)
Type: Homologous_superfamily

This entry represents the DEUBiquitinase ADaptor (DEUBAD) domain from RPN13 (ADRM1), located at its C-terminal, that binds to the UCH37-like domain (ULD) of the deubiquitinase UCH37 . This interaction is required for DUB activity activation.

Its structure consists of eight α-helices that form a helical bundle surrounding a compact hydrophobic core . It has a modular architecture with the core formed by helices 1-4, primarily responsible for binding to ULD, and accessory elements that lead to full activation, or inhibition, of the UCH activity .
DNA-binding recombinase domain superfamily (DNA_bind_recomb_sf)
Type: Homologous_superfamily

The large serine recombinases (LSRs) are DNA-rearranging enzymes that are members of the serine recombinase or resolvase/invertase superfamily. Most resolvases/invertases have a catalytic domain of ~150 residues at their amino terminus, followed by a small, helix-turn-helix (HTH) DNA-binding domain. The LSRs share a similar amino-terminal catalytic domain, but have much larger carboxyl-terminal regions that range in size from ~300 residues to ~550 residues. The C-terminal region of the LSRs is comprised of multiple structural domains and is responsible for coordination of unique LSRs activities. The LSR C-terminal region is composed of two structural domains: a mixed α/β DNA-binding 'recombinase domain' linked to an unusual DNA-binding zinc ribbon domain .

The DNA-binding recombinase domain is moderately well conserved among the LSRs and consists of a four stranded β-sheet embedded in a core 4-helix bundle .
Threonine dehydratase, ACT-like domain superfamily (TD_ACT-like_sf)
Type: Homologous_superfamily

Threonine deaminase (threonine dehydratase, TD) is the first enzyme on the pathway for the biosynthesis of isoleucine. TD is organized into two domains. The larger N-terminal domain is considered the catalytic domain as it contains the essential pyridoxal phosphate cofactor. The C-terminal regulatory domain folds as an eight-stranded antiparallel sheet. The holoenzyme is a homotetramer in which the intersubunit contacts lie between pairs of C-terminal regulatory domains and pairs of N-terminal domains .

The ACT domain is a 90 amino acid long domain, which has been named after three of the allosterically regulated enzymes in which it is found: aspartate kinase, chorismate mutase and TyrA (prephenate dehydrogenase) . The ACT domain is found in a variety of contexts and is proposed to be a structurally conserved regulatory domain involved in the binding of small ligands, such as amino acids. There is a close structural and functional relationship between the regulatory domain of TD and the ACT domain .
Protein-tyrosine phosphatase receptor IA-2, ectodomain superfamily (Receptor_IA-2_ectodomain_sf)
Type: Homologous_superfamily

IA-2 (also known as PTPRN or ICA512) and phogrin (also known as PTPRN2, IA-2b, IAR or ICAAR) are homologous protein-tyrosine phosphatase (PTP) receptors. They have a signal peptide, an ectodomain, a single-pass transmembrane region, and a single intracellular PTP domain. Processing of pro IA-2 by furin-like hormone convertases produces mature IA-2, which lacks the signal peptide and an adjacent fragment (residues 1-448). Upon exocytosis, the cytoplasmic domain of IA-2 is cleaved and moves to the nucleus where it enhances transcription of the insulin gene . The mature ectodomain of IA-2 participates in adhesion to the extracellular matrix and is self-proteolysed in vitro by reactive oxygen species, which may be a new shedding mechanism .
MITD1, C-terminal phospholipase D-like domain superfamily (MITD1_C_sf)
Type: Homologous_superfamily

The C-terminal domain of the MIT domain-containing proteins contains an unanticipated phospholipase d fold (PLD fold) that binds avidly to phosphoinositide-containing membranes. MITD1 is a ESCRT-III binding protein involved in cytokinesis .
GPAT, N-terminal domain superfamily (GPAT_N_sf)
Type: Homologous_superfamily

Stromal glycerol-3-phosphate acyltransferases (GPAT) are responsible for the selective incorporation of saturated and unsaturated fatty-acyl chains into chloroplast membranes, which is an important determinant of a plant's ability to tolerate chilling temperatures . This entry represents the N-terminal four α helical bundle found in these proteins.
Nucleocapsid, C-terminal superfamily (Nucleocapsid_C_sf)
Type: Homologous_superfamily

Arenaviridae are single stranded RNA viruses. The arenaviridae S RNAs that have been characterised include conserved terminal sequences, an ambisense arrangement of the coding regions for the precursor glycoprotein (GPC) and nucleocapsid (N) proteins and an intergenic region capable of forming a base-paired "hairpin" structure. The mature glycoproteins that result are G1 and G2 and the N protein .

The C-terminal domain of the nucleocapsid protein (that encapsulates the viral ssRNA) in arenaviridae has an RNaseH-like fold. This domain contains 3'-5' exoribonuclease activity involved in suppressing interferon induction . It forms a typical α/β/α sandwich architecture and contains a CCHE zinc-binding site near the 3'-5' exonuclease active site.
TrpR-like superfamily (TrpR-like_sf)
Type: Homologous_superfamily

The Trp repressor (TrpR) binds to at least five operators in the Escherichia coli genome, repressing gene expression. The operators at which it binds vary considerably in DNA sequence and location within the promoter; when bound to the Trp operon it recognises the sequence 5'-ACTAGT-3' and acts to prevent the initiation of transcription. The TrpR controls the trpEDCBA (trpO) operon and the genes for trpR, aroH, mtr and aroL, which are involved in the biosynthesis and uptake of the amino acid tryptophan . The repressor binds to the operators only in the presence of L-tryptophan, thereby controlling the intracellular level of its effector; the complex also regulates Trp repressor biosynthesis by binding to its own regulatory region. TrpR acts as a dimer that is composed of identical 6-helical subunits, where four of the helices form the core of the protein and intertwine with the corresponding helices from the other subunit.
Bypass of forespore C, C-terminal domain superfamily (BofC_C_sf)
Type: Homologous_superfamily

BofC (bypass of forespore C) protein acts negatively on inter-compartmental signalling of pro-sigma(K) processing in the sigma(K)-checkpoint of Bacillus subtilis. This is achieved through its interaction with SpoIV inhibiting autoproteolysis of the latter which leads to a delay in proteolytic cleavage of pro-sigma(K) . BofC is a monomer made up of two domains, an N-terminal and a C-terminal domain.
Bypass-of-forespore C, N-terminal domain superfamily (BOFC_N_sf)
Type: Homologous_superfamily

Bypass of forespore C (BofC) is a monomer made up of two domains, an N-terminal and a C-terminal domain. The N-terminal domain of BofC is composed of a four-stranded β-sheet covered by an α-helix. The β-sheet has a beta2-beta1-beta4-beta3 topology, where strands beta1 and beta2 and strands beta3 and beta4 are connected by β-turns, whereas strands beta2 and beta3 are joined by an α-helix that runs across one face of the β-sheet. This domain is similar to the third immunoglobulin G-binding domain of protein G from Streptococcus, the latter belonging to a large and diverse group of cell surface-associated proteins that bind to immunoglobulins. It has been hypothesised that this domain may be a mediator of protein-protein interactions involved in proteolytic events at the cell surface .
RNA polymerase Rpb1, funnel domain superfamily (Rpb1_funnel_sf)
Type: Homologous_superfamily

RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This entry represents the funnel domain. The funnel domain contains the binding site for some elongation factors .
Non-structural protein NSP4, C-terminal superfamily, coronavirus (NSP4_C_sf_CoV)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the coronavirus nonstructural protein NSP4. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. Together with NSP3, NSP4 may play critical functions during viral RNA synthesis and double membrane vesicle formation . It has been shown that in betacoronavirus, the coexpression of NSP3 and NSP4 results in a membrane rearrangement to induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), playing a critical role in SARS-CoV replication. There are two well conserved amino acid residues (H120 and F121) in NSP4 among betacoronavirus, which were demonstrated to be essential for membrane rearrangements during interaction with NSP3. This suggests that the specific details of the interaction between these two proteins varies among different coronavirus . This predominantly α-helical domain may be involved in protein-protein interactions .