SII-SWORD/CoKE huggingface dataset:
NET domain (NET_dom)
Type: Domain

The bromodomain and extraterminal (BET) proteins are a class of transcriptional regulators whose members can be found in animals, plants and fungi. BET proteins are involved in diverse cellular phenomena such as meiosis, cell-cycle control, and homeosis and have been suggested to modulate chromatin structure and affect transcription via a sequence-independent mechanism. BET proteins are defined as having one (plants) or two (animals/yeast) bromodomains and an Extra Terminal (ET) domain. The ET domain consists of three separate regions, only one of which, the N-terminal ET (NET) domain is conserved in all BET proteins. The function of the NET domain is assumed to be protein binding .

The structure of the NET domain comprises three α-helices and a characteristic loop region of an irregular but well-defined structure. The NET structure has an acidic patch that forms a continuous ridge with a hydrophobic cleft. which may interact with other proteins and/or DNA .

Some proteins known to contain a NET domain include:

Human RING3 (now designated Brd2)

Murine MCAP (now designated Brd4)

Drosophila Fsh

Yeast Bdf1 and Bdf2

Arabidopsis imbibition-inducible (IMB1), whichplays a role in abscisic acid (ABA) and phytochrome A (phyA) mediated responses of seed germination.
YcgL domain (YcgL_dom)
Type: Domain

YcgL represents a conserved class of small proteins widespread in gammaproteobacteria. The YcgL domain contains two α-helices and four β-strands in the sequential arrangement β1-β2-α1-β3-α2-β4 as a 3-layer (α/β/α) sandwich .
Nonstructural protein 10, zinc-binding domain, arterivirus (NSP10_Av_ZBD)
Type: Domain

Nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) feature the most complex genetic organization among plus-strand RNA viruses. Their
replicase genes encode an exceptionally large number of nonstructural protein domains which mediate the key functions required for genomic RNA synthesis (replication) and subgenomic RNA (sgRNA) synthesis (transcription). They encode a nonstructural protein, called NSP10 in arteriviruses (Av) and NSP13 in coronaviruses (CoV) , that is comprised of a C-terminal nucleoside triphosphate-binding/helicase (Hel) motif and a N-terminal cysteine-rich zinc-binding domain (ZBD). The ZBD is critically involved in nidovirus replication and transcription, modulating the ATPase/helicase activity in cis . In SARS-CoV, it has been shown that NSP12 directly interacts with NSP13 and enhances its helicase activity .

The ZBD is comprised of about 80 to 100 residues, including 12 to 13 conserved Cys/His residues. It consists of a RING-like module and treble-cleft zinc finger, together coordinating three Zn atoms. The N-terminal RING-like module has a notable binuclear structure with a cross-brace topology involving 6 Cys and 2 His residues that coordinate two zinc ions. The C-terminal zinc finger of ZBD adopts a treble-cleft fold distinct from that of
the RING module. It coordinates one Zn ion with a C[H/C]C[C/H] pattern .

This entry represents the ZBD domain from NSP10 of arteriviruses.
NPH3 domain (NPH3_dom)
Type: Domain

The NRL (for NPH3/RPT2-Like) family is formed by signaling molecules specific to higher plants. Several regions of sequence and predicted structural conservation define members of the NRL family, with three domains being most notable: an N-terminal BTB domain, a centrally located NPH3 domain, and a C-terminal coiled coil domain. The function of the NPH3 domain is not yet known .

Some proteins known to contain a NPH3 domain include:

Arabidopsis non-phototropic hypocotyl 3 (NPH3), may function as an adapter or scaffold protein in plants.

Arabidopsis root-phototropisme 2 (RPT2), a signal transducer involved in phototropic response and stomatal opening in association with phototropin 1 (phot1).

Phototropic-responsive NPH3 family protein NPY1-5, which may act as a substrate-specific adapters of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. They play an essential role in auxin-mediated organogenesis and in root gravitropic responses through the control of PIN proteins .

Oriza coleoptile phototropism 1 (CPT1), the rice orthologue of NPH3. It is required for phototropism of coleoptiles and lateral translocation of auxin.

This entry represents the NPH3 domain.
DOCKER domain (DOCKER_dom)
Type: Domain

Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, gene
expression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotide exchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with an
adjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct and smaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cell migration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DOCKER domain (also termed the DHR-2 or CZH2 domain) .

The DOCK-type C2 domain is located toward the N terminus . The DOCKER domain is a GEF catalytic domain of ~400 residues situated within the C terminus. The structure of the DOCKER domain differs from that of other GEF catalytic domains. It is organised into three lobes of roughly equal size (lobes A, B, and C), with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. Lobe A is formed from an antiparallel array of α helices. Through extensive contacts with lobe B, lobe A stabilises the DHR2 domain. Lobe B adopts an unusual architecture of two antiparallel β sheets disposed in a loosely packed orthogonal arrangement, whereas lobe C comprises a four-helix bundle .

This entry represents the DOCKER domain.
Kininogen-type cystatin domain (Kininogen-type_cystatin_dom)
Type: Domain

The cystatin superfamily consists of a large group of cystatin domain-containing proteins, most of which are reversible and tight-binding inhibitors of the papain (C1) and legumain (C13) families of cysteine proteases . Kininogens are multifunctional and multidomain glycoproteins related to cystatins. Kininogens ubiquitously exist in vertebrates, including mammals, birds, amphibians, and fishes. They vary extremely in both structure and function among different taxa of animals, in particular between mammals and amphibians. Kininogens contain a bradykinin domain and one (in lampreys), two (in fishes) or three (in mammals, birds, and amphibians) cystatin domain(s). Although mammalian kininogens harbour three cystatin domains only two of them are tight-binding inhibitors of cysteine cathepsins, which belong to the papain-like cysteine proteases. A Q-x-V-x-G motif is the canonical binding site for cysteine proteinases in mammals .

This entry represents the kininogen-type cystatin domain.
Voltage-dependent channel domain superfamily (Volt_channel_dom_sf)
Type: Homologous_superfamily

Voltage-dependent cation (K+, Na+ and Ca2+) channels allow ion conduction in response to changes in cell membrane voltage. This superfamily represents a four helix bundle domain found in voltage-dependent channels .
AbrB-like transcriptional regulator (AbrB-like)
Type: Family

This family of DNA-binding proteins is likely to act as a transcriptional regulator . This family does not include E. coli AbrB (

).
DNA topoisomerase I, C-terminal (TopoI_C)
Type: Homologous_superfamily

Type I topoisomerases (type IB isomerases) relax positive and negative supercoils and are very important in DNA replication. The C-terminal segment of this enzyme constitutes the catalytic domain. The catalytic domain contains five amino acids, conserved in all eukaryotic type IB topoisomerases. Its structure consists of ten α helices and a three-strand β sheet, and resembles the catalytic domains of site-specific recombinases that act via a topoisomerase IB-like mechanism .

This entry represents the carboxyl lobe of the catalytic domain (domain 2), and consists of four α-helices (helices 6-10).
Methylthioribose-1-phosphate isomerase, N-terminal (M1Pi_N)
Type: Homologous_superfamily

Methylthioribose-1-phosphate isomerase, an enzyme of the methionine salvage pathway, catalyses the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P) .

The enzyme can be divided into two domains, the N-terminal domain and the C-terminal domain. The N-terminal domain folds into a three-stranded antiparallel β-sheet followed by five α-helices .
GNAT acetyltransferase YdfB-like (GNAT_acetyltra_YdfB-like)
Type: Family

Several members of this family are annotated as being Zwittermicin A resistance proteins, whereas others are listed as being GNAT acetyltransferases, including the uncharacterised N-acetyltransferase YdfB from Bacillus subtilis. The family has similarities to the GNAT acetyltransferase family.
YMGG-like Gly-zipper (Gly-zipper_YMGG)
Type: Domain

This entry represents a YMGG-like Gly-zipper.
tRNA modification GTPase MnmE domain 2 (MnmE_dom2)
Type: Homologous_superfamily

MnmE, also called TrmE and previously designated ThdF (thiophene and furan oxidation protein), is a GTPase involved in tRNA modification to create 5-methylaminomethyl-2-thiouridine in the wobble position of some tRNAs . This protein and GidA form an alpha2/beta2 heterotetramer.
Zinc finger, RING-type, eukaryotic (Znf-RING_euk)
Type: Domain

This zinc-finger is typical of ubiquitin ligases from eukaryotes . This domain can also be found in Tripartite motif-containing proteins (TRIM), including TRIM5 from humans, a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses .
Mg296-like, C-terminal (Mg296-like_C)
Type: Homologous_superfamily

MPN423 is an homologue of MG296. Its function is unknown, but each molecule consists of five α-helical segments . This superfamily represents the C-terminal domain of MG296 and homologues.
Phytase-like domain (Phytase-like_dom)
Type: Domain

This is a repeated domain that carries several highly conserved Glu and Asp residues, indicating the likelihood that the domain incorporates the enzymic activity of the PLC-like phosphodiesterase part of the proteins.
Ribbon-helix-helix domain (RHH_dom)
Type: Domain

A number of bacterial proteins contain this ribbon-helix-helix domain, which is likely to be DNA-binding.
DKNYY family (DKNYY)
Type: Family

This family represents a group of proteins found enriched in fusobacteria. These proteins contain many repeats of a DKNXXYY motif. The repeats are spaced at about 35 amino acid residues intervals. These proteins are likely to be associated with the membrane. The specific function of these proteins is unknown.
ZAR1/RTP1-5-like, 3CxxC-type zinc finger (ZAR1/RTP1-5-like_Znf-3CxxC)
Type: Domain

This is a domain with several pairs of CxxC motifs, referred to as 3CxxC-type zinc finger which is found in 3CxxC-type zinc finger proteins, such as zygote arrest protein 1 (ZAR1) and its homologues, ZAR1-like proteins, and receptor-transporting proteins 1-5 (RTP1-5). Only one pair of cysteines is associated with a highly conserved histidine residue.

ZAR1 is essential for female fertility and oocyte-to-embryo transition by coordinating maternal mRNA storage, translation and degradation . It is a mRNA-binding protein that mediates formation of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes . This entry represents the C-terminal zinc-finger which interacts with mRNAs .

Mammalian RTP1 and RTP2 are accessory proteins to mammalian odorant receptors (ORs) and play significant roles in the translocation of ORs to the plasma membrane. They are expressed in the olfactory sensory neurons and facilitate OR trafficking to the cell-surface membrane and ligand-induced responses in heterologous cells . The functions of RTP3, RTP4 and RTP5 are not clear.
Cyclic nucleotide-regulated ion channel, N-terminal (Nucleotide_channel_N)
Type: Homologous_superfamily

This superfamily represents a four helix bundle domain found at the N terminus of cyclic nucleotide-regulated ion channel .
Cardiolipin synthase N-terminal (CLS_N)
Type: Domain

This domain is often found at the very N terminus of proteins from the phospholipase D family, cardiolipin synthase subfamily. However, this domain is also found on its own in a large number of cases in proteins described as uncharacterised.
LytR/CpsA/Psr regulator, C-terminal domain (LytR/CpsA/Psr_C)
Type: Domain

This domain often appears at the C terminus of

, in members of the LytR/CpsA/Psr regulatory protein family. Proteins containing this domain include lcpA from Corynebacterium glutamicum, Cell envelope integrity protein Cei and Vesiculogenesis and immune response regulator virR, both from Mycobacterium tuberculosis. IcpA is involved in cell wall biosynthesis . Cei and virR both contribute to cell envelope integrity .
Putative zinc-finger (Znf_put)
Type: Domain

This is a putative zinc-finger found in some anti-sigma factor proteins.
Runx, central domain superfamily (Runx_central_dom_sf)
Type: Homologous_superfamily

This superfamily represents the central domain of Runx (also known as AML1, CBF- alpha, PEBP2) protein. This domain lies between the N-terminal Runt domain

and the C-terminal

domains. Proteins containing this domain include RUNX1/2/3 (Runt-related transcription factor 1/2/3) from Chordata (chordates).
Outer membrane protein, beta-barrel domain (Beta-barrel_OMP)
Type: Domain

This domain is found in a wide range of outer membrane proteins. This domain assumes a membrane bound β-barrel fold. It is part of a Pfam clan that includes other outer membrane protein β-barrel domains.
Ribosomal uL15, N-terminal (Rbsml_uL15_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of the 50S ribosomal protein uL15 and 60S ribosomal protein uL15 (also known as L27a). uL15 binds to the 23S rRNA.

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 .
Cytochrome b/b6-like domain superfamily (Cytb/b6-like_sf)
Type: Homologous_superfamily

Cytochrome b/b6 is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part. Cytochrome b/b6 non-covalently binds two haem groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two haem groups .
Ku70, bridge and pillars domain superfamily (Ku70_bridge/pillars_dom_sf)
Type: Homologous_superfamily

This superfamily represent the bridge and pillars domain of Ku70 . Proteins containing this domain are Ku70 from eukaryotes. Ku70 is involved in the repair of DNA double-strand breaks by non-homologous end-joining .
Beta-1,4-mannosyltransferase Bre-3/Egh (B_mannosylTrfase_Bre-3/Egh)
Type: Family

Beta-1,4-mannosyltransferase Bre-3 is the Caenorhabditis elegans the homologue of Drosophila egghead (Egh). They are glycosyltransferases with a proposed role in glycosphingolipid biosynthesis in a four component glycosylation pathway that is functionally conserved between nematodes and insects and that it is involved in resistance to bacterial toxins . Bre-3 is involved in susceptibility to pore-forming crystal toxins in conjunction with bre-1, bre-2, bre-4 and bre-5 and it is also involved in resistance to the nematotoxic C. cinerea galectin Cgl2 . This protein plays a role in determining brood size .
Endoglucanase F, domain 3 (Endoglucanase_F_dom3)
Type: Homologous_superfamily

This entry represents a structurally irregular domain found in endoglucanase F . Proteins containing this domain include endoglucanases and exoglucanases. They are involved in the cellulose catabolic process.
rRNA small subunit methyltransferase F, RNA-binding PUA-like domain (Nol1_Nop2_Fmu_2)
Type: Domain

This entry represents the second of two C-terminal domains found on bacterial methyltransferase RsmF that modifies the 16S ribosomal RNA. It has some structural similarity to the RNA-binding PUA domains suggesting that it is involved in RNA recognition. It lies downstream of the catalytic centre of this methyltransferase .
Transcription factor zinc-finger (TF_Znf)
Type: Domain

This entry represents a zinc-finger domain.
Virus scaffolding protein, C-terminal (Virus_scaffolding_prot_C)
Type: Homologous_superfamily

This superfamily represents the coat protein-binding C-terminal domain of the scaffolding protein from P22-like viruses . Bacteriophage scaffolding protein is required for successful condensation of DNA within the capsid. The scaffolding protein is lost from the structure during packaging .
Cytochrome-c3 hydrogenase, C-terminal (Cytochrome-c3_hydrogenase_C)
Type: Domain

This entry represents the C-terminal domain of periplasmic [NiFe] hydrogenase small subunit, hydrogenase-1 small chain and uptake hydrogenase small subunit.
Winged helix DNA-binding domain (WH_DNA-bd_dom)
Type: Domain

This entry represents a winged helix DNA-binding domain found in some uncharacterised proteins.
DsrEFH-like (DsrEFH-like)
Type: Homologous_superfamily

DsrE, DsrF, DsrH are part of a gene cluster involved in intracellular sulfur reduction in purple sulfur bacteria . In E. coli, the DsrEFH homologue TusBCD interacts with the DsrC homologue TusE in a sulfur relay system during 2-thiouridine biosynthesis .

DsrE, DsrF and DsrH form a soluble multimeric protein DsrEFH, which is an alpha2beta2gamma2-structured holoprotein .
Catenin binding domain superfamily (Catenin-bd_sf)
Type: Homologous_superfamily

This superfamily represents the catenin binding domain. Proteins containing this domain include cadherins, desmocollins, desmoglein and transcription factor 7-like proteins .

Cadherins and catenins play important roles in the adherents junctions in animal cells. The cadherin-catenin complex is responsible for coupling Ca(2+)-dependent intercellular junctions with actin dynamics and signalling pathways. Desmosomal cadherins are TM protein components of desmosomes (for review, see ), whose extracellular cadherin repeats are responsible for adhesion and whose intracellular regions interact with intermediate filaments via desmosomal plaque proteins plakoglobin, plakobilin and desmoplakin. They are believed to play a wider role in regulation of epithelial differentiation . Two sub-families of desmosomal cadherin have been identified, desmocollin (DSC) and desmoglein (DSG).
SecD export protein N-terminal TM domain (SecD-TM)
Type: Domain

This domain appears to be the fist transmembrane region of the SecD export protein. SecD is directly involved in protein secretion and important for the release of proteins that have been translocated across the cytoplasmic membrane . This domain is also found in modulator protein MzrA, which modulates the activity of the EnvZ/OmpR two-component regulatory system .
Delta antigen, N-terminal (Delta_antigen_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal coiled coil domain of the delta antigen from the hepatitis D virus (HDV). The hepatitis delta antigen dimerises through this anti-parallel coiled coil domain. Dimers then associate further to form octamers through residues in the coiled-coil domain and residues C-terminal to this domain. This domain may play a role in binding the viral RNA .
YidB-like (YidB-like)
Type: Homologous_superfamily

YidB is a bacterial uncharacterised protein found in a number of pathogenic species. The yidB gene of Shigella flexneri and Escherichia coli is located between yidA and gyrB genes which are involved in DNA processing, therefore it might be have functions associated with DNA. The structure of YidB from Shigella flexneri shows distant structural similarity to eukaryotic homeodomain proteins .
Manganese catalase, C-terminal (Mn_catalase_C)
Type: Homologous_superfamily

This superfamily represents a C-terminal domain found in a number of non-haem Manganese-catalases, which are found in several bacterial species . The domain lies the C-terminal to the four-helix bundle catalytically active domain .
PNPase/RNase PH domain superfamily (PNPase/RNase_PH_dom_sf)
Type: Homologous_superfamily

Polynucleotide phosphorylase (PNPase) is a polyribonucleotide nucleotidyl transferase

that degrades mRNA in prokaryotes. Polynucleotide phosphorylase and the Ribonuclease PH (RNase PH) family possess a common domain represented by this entry. This suggests similar structures and mechanisms of action for these 3'-->5' phosphorolytic enzymes . In the case of PNPase, the core domain is found duplicated .
GroEL-like apical domain superfamily (GroEL-like_apical_dom_sf)
Type: Homologous_superfamily

Chaperonins are large cylindrical structures that transiently enclose a partially folded polypeptide and allow it to continue folding in a sequestered environment. Chaperonins are grouped into two families: group I chaperonins, found in eubacteria (e.g. GroEL in Escherichia coli) and eukaryotic organelles of eubacterial descent (e.g. Cpn60 in mitochondria and chloroplasts), and group II chaperonins, found in archaea and the eukaryotic cytosol (CCT or TCP-1 complex) . Both groups share a common monomer architecture of three domains: an equatorial domain that carries ATPase activity, an intermediate domain, and an apical domain, involved in substrate binding .

This superfamily represents the apical domain.