SII-SWORD/CoKE huggingface dataset:
OB-fold nucleic acid binding domain (OB-fold_nuc-bd_dom)
Type: Domain

This entry represents OB-fold domains that bind to nucleic acids. They are found in exonuclease VII (ExoVII) large subunit proteins.

ExoVII is composed of two non-identical subunits . ExoVII is a single-strand-specific exonuclease which degrades ssDNA from both 3-prime and 5-prime ends . ExoVII plays a role in methyl-directed mismatch repair in vivo . ExoVII may also guard the genome from mutagenesis by removing excess ssDNA, since the build up of ssDNA would lead to SOS induction and PolIV-dependent mutagenesis .
Cob(I)alamin adenosyltransferase N-terminal domain (Co_AT_N_dom)
Type: Domain

This domain is found in bacterial sequences, and is approximately 20 amino acids in length. It is found in cob(I)alamin adenosyltransferase, which adenosylates Co(I) in an ATP-dependent manner in the conversion of aquacobalamin to its coenzyme form . This is the third step in this process, after two steps involved in the reduction of Co(III) to Co(I).
Recombinase zinc beta ribbon domain (Zn_ribbon_recom_dom)
Type: Domain

This entry represents a zinc ribbon domain that is likely to be DNA-binding. This domain is found in site-specific recombinase proteins.
Putative sensor domain (Put_sensor_dom)
Type: Domain

This domain is often found at the N terminus of proteins predicted to be two-component system histidine kinases. The N termini of such proteins often function in stimulus sensing.
Zinc knuckle CX2CX3GHX4C (Zn_knuckle_CX2CX3GHX4C)
Type: Domain

This is a zinc-binding domain of the form CxxCxxxGHxxxxC from a variety of different species. It is found in the MPE1 protein from
Saccharomyces cerevisiae
which is a component of the cleavage and polyadenylation factor (CPF) complex important for polyadenylation-dependent pre-mRNA 3'-end formation .
DNA-binding domain, ovate family-like (DNA_bnd_dom_ovate)
Type: Domain

This domain, often found on ovate proteins, binds to single-stranded and double-stranded DNA. Binding to DNA is not sequence-specific .
GxGYxYP putative glycoside hydrolase, C-terminal (GxGYxYP_C)
Type: Domain

This domain can be found in the C-terminal region of a group of putative glycoside hydrolases. This domain contains a characteristic sequence motif, GxGYxYP.
GDYXXLXY protein (GDYXXLXY)
Type: Family

This family of proteins is functionally uncharacterised. Family members are found in bacteria, archaea and eukaryotes and contain a conserved GDYXXLXY motif.
Topoisomerase I C-terminal domain (TopoI_C_dom)
Type: Domain

This domain is found at the C terminus of topoisomerase I.

DNA topoisomerase I (

) is one of the two types of enzyme that catalyze the interconversion of topological DNA isomers. Type I topoisomerases act by catalyzing the transient breakage of DNA, one strand at a time, and the subsequent rejoining of the strands. When a eukaryotic type 1 topoisomerase breaks a DNA backbone bond, it simultaneously forms a protein-DNA link where the hydroxyl group of a tyrosine residue is joined to a 3'-phosphate on DNA, at one end of the enzyme-severed DNA strand. In eukaryotes and poxvirus topoisomerases I, there are a number of conserved residues in the region around the active site tyrosine
Thiopurine S-methyltransferase (Thiopurine_S-MeTrfase)
Type: Family

This family consists of thiopurine S-methyltransferase proteins from both eukaryotes and prokaryotes. Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyses S-methylation of aromatic and heterocyclic sulphydryl compounds, including anticancer and immunosuppressive thiopurines . Thiopurine is commonly used to suppress the immune system in the case of autoimmune disease, inflammatory bowel disease and to prevent transplanted organ rejection . Thiopurine drugs can be toxic to cells but their effect can be mediated by the incorporation of thioguanine nucleotides into DNA .
Zinc knuckle CX2CX4HX4C (Zn_knuckle_CX2CX4HX4C)
Type: Domain

This zinc knuckle is a zinc binding motif composed of the sequence CX2CX4HX4C where X can be any amino acid.
CFTR regulator domain (CFTR_reg_dom)
Type: Domain

Cystic fibrosis transmembrane conductance regulator (CFTR) that belongs to the ATP-binding cassette (ABC) transporter superfamily. It is a member of the ABC-C subfamily, which also contains the SUR receptors and the multidrug- resistance associated proteins (MRP) . The CFTR protein encodes a chloride ion channel, which is controlled by phosphorylation. It has a major role in electrolyte and fluid secretion. CFTR is important in the determination of fluid flow, ion concentration and transepithelial salt transport. Dysfunction of the CFTR channel causes the life-threatening disease, cystic fibrosis, in which trans-epithelial ion transport is disrupted .

This entry represents the CFTR regulator domain .
Inactive transglutaminase fused to 7 transmembrane helices (Transglut_i_TM)
Type: Domain

An inactive transglutaminase domain fused to seven transmembrane helices. The transglutaminase domain is predicted to be extracellularly located. Members of this family are associated in gene neighbourhoods with a pepsin-like peptidase and an ATP-grasp of the RimK-family. The ATP-grasp is predicted to modify the 7TM protein or a cofactor that interacts with it .
RimK-like ATPgrasp N-terminal domain (RLAN_dom)
Type: Domain

An uncharacterised α+β fold domain that is mostly fused to a RimK-like ATP-grasp and is found in bacteria and euryarchaea. Proteins with this domain are almost always associated in gene neighbourhoods with a GNAT-like acetyltransferase fused to a papain-like petidase. Additionally M20-like peptidases, GCS2, 4Fe-4S Ferredoxins, a distinct metal-sulphur cluster protein and ribosomal proteins are found in the gene neighbourhoods. Contextual analysis suggests a role for these in peptide biosynthesis .
7 transmembrane helices usually fused to an inactive transglutaminase (7TM_transglut)
Type: Domain

This domain of seven transmembrane helices is usually fused to an inactive transglutaminase domain. The transglutaminase domain is predicted to be extracellularly located. Proteins with this domain are associated in gene neighbourhoods with a pepsin-like peptidase and an ATP-grasp of the RimK-family. The ATP-grasp is predicted to modify the 7TM protein or a cofactor that interacts with it .
Circularly permuted ATP-grasp type 2 (CP_ATPgrasp_2)
Type: Domain

Circularly permuted ATP-grasp prototyped by Roseiflexus RoseRS_2616 that is associated in gene neighbourhoods with a GCS2-like COOH-NH2 ligase, α/β hydrolase fold peptidase, GAT-II -like amidohydrolase, and M20 peptidase. Members of this family are predicted to be involved in the biosynthesis of small peptides .
Ribosomally synthesized peptide in Bacteroidetes (Bacteroid_pep)
Type: Family

This ribosomally synthesized peptide is usually in the gene neighbourhood of a RimK-like ATP-grasp, and an ABC ATPase fused to a papain-like domain. It is often present in multiple tandem gene copies. The gene contexts suggest that it is modified by the ATP-grasp as in the biosynthesis of microviridin and marinostatin. They might function in defence or development or as peptide antibiotics .
Ribosomally synthesized peptide in Actinomycetes (Actino_peptide)
Type: Family

Ribosomally synthesized peptide that is usually in the gene neighbourhood of a RimK-like ATP-grasp and an aspartyl-O-methylase. Gene contexts suggest that it is further modified by the ATP-grasp and the methylase. It might function in defense or development, or as a peptide antibiotic .
Thg1 C-terminal domain (Thg1_C_dom)
Type: Domain

Thg1 was originally characterised as synthesising the guanine nucleotide at the -1 position of the histidinyl tRNA (HtRNA). Thg1 has also been shown to have polymerase activity, which has been proposed to be the ancestral activity of this enzyme .
Trichome birefringence-like, N-terminal domain (TBL_N)
Type: Domain

This entry represents the N-terminal C-rich predicted sugar binding domain found in Trichome birefringence-like (TBL) proteins from streptophytes. This domain is followed by the TBL PC-Esterase (acyl esterase) domain in PMR5 and ESK1 .
MEDS domain (MEDS_domain)
Type: Domain

The MEDS (MEthanogen/methylotroph DcmR Sensory) domain is prototyped by DcmR and is likely to function with the PocR domain in certain organisms in sensing hydrocarbon derivatives The MEDS domain occurs fused to Histidine Kinase and as standalone version . Sequence analysis shows that it is a catalytically inactive version of the P-loop NTPase domain of the RecA superfamily .
N6-adenosine-methyltransferase MT-A70-like (MT-A70)
Type: Family

METTL3 and METTL14 (methyltransferase-like) form a methyltransferase complex that methylates adenosine residues at the N6 position of some RNAs, forming N6-methyladenosine (m6A). METTL3, also known as MT-A70, is the catalytic subunit of this complex, and accepts S-adenosyl methionine, a donor for methylation . m6A, which is present at internal sites of some mRNAs, affects different aspects of mRNA metabolism such as half-life, splicing, and translation .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
AF2226-like SPOUT RNA methylase fused to THUMP (SPOUT_MTase_fused_to_THUMP)
Type: Family

This entry represents a SPOUT superfamily RNA methylase fused to an RNA-binding THUMP domain .
SUKH-3 immunity protein (SUKH-3)
Type: Family

This family belongs to the SUKH superfamily and functions as immunity proteins in bacterial toxin systems .
SUKH-4 immunity protein (SUKH-4)
Type: Family

This family belongs to the SUKH superfamily and functions as immunity proteins in bacterial toxin systems .
Ataxin 2, SM domain (SM_dom_ATX)
Type: Domain

This SM domain is found in Ataxin-2 . This domain has been shown to interact with RNA helicase DDX6 .

Ataxin-2 has many functions, such as endocytic receptor cycling , translational regulation, embryonic development , energy metabolism and weight regulation . Mutations of the Ataxin-2 gene cause spinocerebellar ataxia 2 (SCA2), a neurodegenerative disorder leading to predominant loss of Purkinje cells in the cerebellum and impairment of motor coordination . In SCA2, expansion of a CAG repeat in exon 1 of the Ataxin-2 (ATXN2) gene causes expansion of a polyQ domain in the ATXN2 protein . ATXN2 has been shown to interact with many proteins. It interacts with multiple RNA-binding proteins (RBPs), staufen, IP3R, RGS8 mRNA, endophilins and CIN85 .
Bd3614-like deaminase (NH3ase_Bd3614-like)
Type: Family

A member of the nucleic acid/nucleotide deaminase superfamily prototyped by Bdellovibrio Bd3614 . They are typified by a distinct N-terminal globular domain. The Bdellovibrio version occurs in a predicted operon with a 23S rRNA G2445-modifying methylase suggesting that it might be involved in RNA editing .
Bd3614-like deaminase, N-terminal (NH3ase_Bd3614-like_N_dom)
Type: Domain

This entry represents a globular domain that occurs in the N-terminal of Bd3614-like deaminases, which are predicted to be involved in RNA editing .
Plasmid replication-relaxation (Replic_Relax)
Type: Family

This family includes proteins which are essential for plasmid replication and plasmid DNA relaxation .
HeH/LEM domain (HeH/LEM_domain)
Type: Domain

This entry represents the HeH/LEM domain. HeH domains form helix-extended loop-helix (HeH) structures.
MacB-like periplasmic core domain (MacB_PCD)
Type: Domain

This entry represents the periplasmic core domain found in a variety of ABC transporters. The structure of this family has been solved for the MacB protein . Some structural similarity was found to the periplasmic domain of the AcrB multidrug efflux transporter.
Exopolysaccharide production protein YjbE (YjbE)
Type: Family

YjbE is part of a four gene operon which is involved in exopolysaccharide production. The expression of YjbE is higher than the rest of the operon yjbEFGH. It appears to be restricted to Enterobacteriaceae .
AurF/CmlI (AurF/CmlI)
Type: Family

AurF is a metalloenzyme which is involved in the biosynthesis of antibiotic aureothin by catalysing the formation of p-nitrobenzoic acid from p-aminobenzoic acid. AurF is a non-heme di-iron monooxygenase which creates nitroarenes via the sequential oxidation of aminoarenes . This entry also includes CmlI from Streptomyces venezuelae. CmlI catalyzes the six-electron oxidation of an aryl-amine precursor of chloramphenicol (NH2-CAM) to yield the aryl-nitro group of chloramphenicol (CAM) .
Major prion protein N-terminal (Prion_N)
Type: Domain

This entry represents the N-terminal region of major prion protein. The proteins consist of mainly α helices found at the C-terminal. Bovine prion has been shown to form a stable helix which inserts in a transmembrane location in the bilayer, with the N -terminal functioning as a cell-penetrating peptide .
Cobalamin biosynthesis protein CobT VWA domain (CobT_VWA_dom)
Type: Domain

This entry represents the VWA domain found in several bacterial cobalamin biosynthesis (CobT) proteins. CobT is involved in the transformation of precorrin-3 into cobyrinic acid .
L-seryl-tRNA selenium transferase N-terminal domain (SelA_trans_N_dom)
Type: Domain

This entry represents the N-terminal domain of L-seryl-tRNA selenium transferase, which catalyses the conversion of seryl-tRNA(Sec) into selenocysteyl-tRNA(Sec) . There is a single completely conserved residue P that may be functionally important.
Choline sulfatase enzyme C-terminal domain (Choline_sulf_C_dom)
Type: Domain

This entry represents the C-terminal domain of choline sulphatase, the enzyme responsible for catalysing the conversion of choline-O-sulphate and, at a lower rate, phosphorylcholine, into choline . There are two completely conserved residues (R and W) that may be functionally important.
Type-F conjugative transfer system protein TraW N-terminal domain (TraW_N_dom)
Type: Domain

This entry represents the N-terminal domain of TraW, an essential component of the F-type conjugative transfer system for plasmid DNA transfer . There is a single completely conserved residue G that may be functionally important.
Cobaltochelatase subunit CobS N-terminal domain (CobS_N_dom)
Type: Domain

This entry represents the N-terminal domain of the CobS subunit of cobaltochelatase. The domain contains two completely conserved residues (P and F) that may be functionally important. Cobaltochelatase belongs to the AAA+ superfamily of proteins and functions in cobalamin biosynthesis .
Polymerase A arginine-rich C-terminal domain (PolyA_pol_arg_C_dom)
Type: Domain

This entry represents the C-terminal domain of polymerase A, which is arginine-rich and is necessary for full functioning of the enzyme .
MnmE, helical domain (MnmE_helical)
Type: Domain

The tRNA modification GTPase MnmE consists of three domains. An N-terminal domain, a helical domain and a GTPase domain which is nested within the helical domain. This entry represents the helical domain .
Putative zinc ribbon domain (Zn_ribbon_dom_put)
Type: Domain

This domain appears to be a zinc binding DNA-binding domain.
Glyoxalase-like domain (Glyoxalase-like_dom)
Type: Domain

This domain is related to the glyoxalase domain (

).
Growth hormone-binding protein (GHBP)
Type: Domain

Growth hormone receptor binding protein is produced either by proteolysis of the growth hormone receptor (GHR) at the cell surface thereby releasing its extracellular domain, the GHBP (growth hormone-binding protein), or, in rodents, by alternative processing of the GHR transcript. The sheddase proteolytic enzyme responsible for the cleavage is TACE (tumour necrosis factor-alpha-converting enzyme) .

Growth hormone (GH) binding to GH receptor is the initial step that leads to the physiological functions of the hormone . The biological effects of GHBP are determined by the serum levels of GH, which can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and have been implicated in diabetic eye and kidney damage .
RING finger family 2, prokaryotic (RING_finger_2_prok)
Type: Family

This entry represents a RING finger family found sporadically in bacteria and archaea, and associated with other components of the ubiquitin-based signaling and degradation system, including ubiquitin and the E1 and E2 proteins. The bacterial versions contain transmembrane helices .
Metal binding domain, predicted (Metal-bd_dom_prd)
Type: Domain

A predicted metal-binding domain that is found in gene-neighbourhood associations with genes encoding components of the bacterial homologues of the ubiquitin modification pathway including the E1, E2, JAB metallopeptidase and ubiquitin proteins. The domain is characterised by a conserved motif with a CxxxxxEYHxxxxH signature.
Double zinc ribbon (DZR)
Type: Domain

This entry represents a pair of zinc ribbon domains found in diverse sequences including double zinc ribbon and ankyrin repeat-containing protein 1 from Danio rerio (Dzank1) and similar sequences from animals and uncharacterised proteins from bacteria and archaea. Dzank1 is required for the intracellular transport of organelles and vesicles, and is essential for the photoreceptor's outer segments formation, maintenance and function .
Leucine rich repeat 4 (Leu-rich_rpt_4)
Type: Repeat

This entry represents 2 copies of a leucine rich repeat.
Trafficking protein particle complex subunit 11, C-terminal (TRAPPC11_C)
Type: Domain

This entry represents a domain found in the C-terminal of TRAPPC11 (trafficking protein particle complex subunit 11) protein. TRAPPC11 is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage .
MobA-like NTP transferase (MobA-like_NTP_Trfase)
Type: Domain

This entry represents a wide range of NTP transferase domains, including the NTP transferase domain of MobA protein (Molybdopterin-guanine dinucleotide biosynthesis protein A).
Acetyl-CoA dehydrogenase-like C-terminal domain (Acyl-CoA_dh-like_C_dom)
Type: Domain

This domain appears to be the very C-terminal region of many bacterial acetyl-CoA dehydrogenases.
Pab87 octamerisation domain (Pab87_oct)
Type: Domain

This domain was first characterised as the C-terminal domain of Pab87 serine protease from Pyrococcus abyssi . The domain is reported to play a crucial role in Pab87 octamerisation and active site compartmentalisation. Its up-and-down 8-stranded β-barrel 3D structure is reminiscent of the one found in lipocalins.
Glycosyl hydrolase family 80, chitosanase (Glyco_hydro_80_chitosanase)
Type: Family

This is a small family of bacterial chitosanases .
Toxin Ibs (Toxin_Ibs)
Type: Family

The Ibs (induction brings stasis) proteins are a family of toxic peptides. Their expression is inhibited by the Sib antisense RNAs, which act as antitoxins .
Toxin Fst (Toxin_Fst)
Type: Family

Fst (faecalis plasmid stabilisation toxin), also known as RNA I, is a toxic peptide. Its N terminus forms a transmembrane α helix, its C terminus is disordered and is likely to be cytosolic. Its translation is inhibited by the antisense RNA, RNA II, which acts as an antitoxin .
Cadherin-like beta-sandwich-like domain (Cadherin-like_domain)
Type: Domain

This domain is found in several bacterial, metazoan and chlorophyte algal proteins. A profile-profile comparison recovered the cadherin domain and a comparison of the predicted structure of this domain with the crystal structure of the cadherin showed a congruent seven stranded secondary structure. The domain is widespread in bacteria and seen in the firmicutes, actinobacteria, certain proteobacteria, bacteroides and chlamydiae with an expansion in Clostridium. In contrast, it is limited in its distribution in eukaryotes suggesting that it was derived through lateral transfer from bacteria. In prokaryotes, this domain is widely fused to other domains such as FNIII (Fibronectin Type III), TIG, SLH (S-layer homology), discoidin, cell-wall-binding repeat domain and alpha-amylase-like glycohydrolases. These associations are suggestive of a carbohydrate-binding function for this cadherin-like domain.
Methyl-CpG binding protein 2/3, C-terminal domain (MeCpG-bd_2/3_C_dom)
Type: Domain

This domain is found at the C-terminal of the methyl-CpG-binding domain (MBD) containing proteins MBD2 and MBD3 . The latter was shown to not bind directly to methyl-CpG DNA but rather interact with components of the NuRD/Mi2 complex , an abundant deacetylase complex.

Methylation at CpG dinucleotide, the most common DNA modification in eukaryotes, has been correlated with gene silencing associated with various phenomena such as genomic imprinting, transposon and chromosome X inactivation, differentiation, and cancer. Effects of DNA methylation are mediated through proteins which bind to symmetrically methylated CpGs. Such proteins contain a specific domain of ~70 residues, the methyl-CpG-binding domain (MBD), which is linked to additional domains associated with chromatin, such as the bromodomain, the AT hook motif, the SET domain, or the PHD finger. MBD-containing proteins appear to act as structural proteins, which recruit a variety of histone deacetylase (HDAC) complexes and chromatin remodelling factors, leading to chromatin compaction and, consequently, to transcriptional repression. The MBD of MeCP2, MBD1, MBD2, MBD4 and BAZ2 mediates binding to DNA, in case of MeCP2, MBD1 and MBD2 preferentially to methylated CpG. In case of human MBD3 and SETDB1 the MBD has been shown to mediate protein-protein interactions .
PapC, N-terminal domain (PapC_N)
Type: Domain

Bacteiral pili are assembled using the chaperone usher system. In E. coli this is composed of the chaperone PapD and the usher PapC. This domain represents the N-terminal domain from PapC and its homologues. This domain is involved in substrate binding .
Phloem protein 2-like (PP2-like)
Type: Family

Phloem protein 2 (PP2) is one of the most abundant and enigmatic proteins in the phloem sap. PP2 is translocated in the assimilate stream where its lectin activity or RNA-binding properties can exert effects over long distances. PP2-like genes have been identified in many plant species, indicating a wide distribution of PP2 genes in the plant kingdom .

This entry represents PP2 and PP2-like proteins.
Glycoside hydrolase family 31, N-terminal domain (Glyco_hydro_31_N_dom)
Type: Domain

This domain is found in proteins that belong to the glycoside hydrolase family 31. The domain appears to be similar to the galactose mutarotase superfamily.
Meiosis-specific protein MEI4 (MEI4)
Type: Family

Meiosis-specific protein MEI4 is required for meiotic induction of recombination, viable spore production and chromosome synapsis. It is a component of the MER2-MEI4-REC114 complex which seems to be required for meiotic double-strand break (DSB) formation . In Schizosaccharomyces pombe it is known as Rec24 .
General stress protein 17M-like domain (GSP17M-like_dom)
Type: Domain

This domain is found in stress induced proteins, mainly from Bacilli. General stress protein 17M or YflT is induced by heat shock, salt stress, oxidative stress, glucose limitation and oxygen limitation . This domain is also found at the N terminus of stress response protein YsnF, induced by phosphate starvation, via the alternative sigma factor sigma-B .
Abhydrolase, bacterial (Abhydrolase_bac)
Type: Family

This is a family of probable bacterial abhydrolases.