SII-SWORD/CoKE huggingface dataset:
Replication initiation protein, N-terminal (RepD-like_N)
Type: Domain

This domain is found at the N-terminal end of Replication initiation protein from Staphylococcus aureus (Rep and RepC, D, E, M, N variants of the pT181 family) and similar sequences from Bacilli. Rep proteins, shows similarity with the extended β-sheet in TATA binding protein (TBP) .

Replication of pT181 family plasmids is initiated when the dimeric Rep protein makes a sequence specific nick in the (+) strand at the double-stranded origin of replication via one of its active sites, resulting in a covalent adduct to the 5' side of the nick. After nicking, the Rep protein assists recruitment of PcrA helicase, which is responsible for unwinding the plasmid during replication .

The Rep proteins possess two related catalytic activities, a type-I topoisomerase-like cleavage activity in which they form a nick in the (+) strand at the origin of replication to initiate DNA synthesis, and a re-ligation activity to join the ends of the parental strand that is displaced during replication .
Phage phiCb5, coat protein (PhiCb5_coat)
Type: Family

This entry represents a family of proteins from Leviviricetes, including Coat protein from Caulobacter phage phiCb5 (

), which consists of an N-terminal loop, a five-stranded β-sheet and a C-terminal arm containing two helices .
Conserved flagellar protein F, immunoglobulin-like domain (FlaF_Ig-like)
Type: Domain

This domain is found in Conserved flagellar protein F from Sulfolobus acidocaldarius (FlaF,

) and similar archaeal proteins. FlaF is essential for archaellum assembly with an extended N-terminal α-helix connected to a globular domain (this entry). This domain adopts a β-sandwich fold with eight anti-parallel β-strands in two sheets and Ig-like topology . FlaF associates with FlaG and this FlaG-FlaF complex is critical for archaellum assembly and motility by anchoring the archaellum to the S-layer .
Transcriptional cofactor Bfc domain (Bfc_dom)
Type: Domain

This domain is found in sequences from insects, including the transcriptional cofactor Bfc from Drosophila melanogaster, which adopts a C2-like fold. Bfc is a transcriptional cofactor involved in efferocytosis. Together with Srp mediates expression of the phagocytic receptor crq/croquemort in response to apoptotic cells, and is up-regulated by crq/croquemort in a positive feedback mechanism. Bfc is also involved in macrophage engulfment and clearance of apoptotic cells during embryogenesis .
DUF5018-related (DUF5018-rel)
Type: Domain

This domain is found in the putative secreted protein BF4250 from Bacteroides fragilis (

) and similar bacterial functionally uncharacterised proteins. It adopts a β-sandwich with a greek key topology

. This domain seems to be related to

.
TraI-like, C-terminal domain (TraI-like_C)
Type: Domain

This entry represents the C-terminal domain of Protein TraI from Escherichia coli and similar sequences mainly found in proteobacteria. TraI is a plasmid-specific component required for the initiation process of transfer DNA synthesis, as part of a specialised nucleoprotein complex - the relaxosome, together with TraH, I, and J. Site- and strand-specific cleavage at the transfer origin is dependent of TraI and TraJ. This domain is predicted to adopt an OB fold-like structure.
TraI-like, middle domain (TraI_M)
Type: Domain

This entry represents a domain found in the middle region of TraI-like proteins mostly from proteobacteria, including

from Methylophaga frappieri. It is found C-terminal to the relaxase domain (

).
RxLR effector PexRD54, WY domain (PexRD54_WY)
Type: Domain

This entry represents homologous WY domains of the RxLR effector PexRD54 from Phytophthora infestans and similar proteins from Peronosporales, water moulds that are mainly associated with plant diseases. PexRD54 is an effector that specifically binds host autophagy protein ATG8CL (from the ATG8 family) to stimulate autophagosome formation and subsequent autophagy and pays a key role in plant immunity . The WY domain is a conserved structural unit consisting of three α-helices and two characteristic hydrophobic amino acids, frequently W (Trp) and Y (Tyr), which contribute to a stable hydrophobic core.
Ubiquitin-like domain, fungal (ULD_fung)
Type: Domain

This entry represents a domain found in a range of fungal proteins. It is predicted to show an ubiquitin like structure.
Integrase p58-like, C-terminal domain (Integrase_p58-like_C)
Type: Domain

This domain is found at the C-terminal end of a group of uncharacterised animal proteins that are similar to Integrase p58, the last chain cleaved from the Transposon Ty3-G Gag-Pol polyprotein from Saccharomyces cerevisiae. This domain, which is associated to

, is also named SH3 domain .
Kinase OspG, kinase domain (OspG_kinase)
Type: Domain

This entry represents the kinase domain of protein kinase OspG, which is involved in down-regulation of the host innate response induced by invasive bacteria . OspG is a an effector kinase that binds host E2 ubiquitin-conjugating enzymes activated with ubiquitin, which enhances its kinase activity, playing a role to suppress the host inflammatory response during invasion and colonisation . Members of this group are mainly found in proteobacteria.
YkoP-like domain (YkoP-like_dom)
Type: Domain

This entry represents a domain that covers the whole length of the sequence in the uncharacterised protein YkoP from Bacillus subtilis, whose structure shows similarity to GNAT family acetyltransferases. This domain is found associated with

in some sequences.
NrS-1 polymerase-like, HBD domain (NrSPol-like_HBD)
Type: Domain

This entry represents the helix bundle domain (HBD) domain of NrS-1 polymerase (NrSPol) which together with the N-terminal Prim/Pol domain, is responsible for DNA polymerization and de novo primer synthesis activities. This domain is critical for the primer synthesis activity of NrS-1 polymerase . Members of this group are found in tailed bacteriophages and prokaryotes.
Predicted hydrolase, N-terminal domain (Pred_hydrolase_N)
Type: Domain

This entry represents a domain found at the N-terminal end in an uncharacterised family of proteins mainly found in actinomycetes, including MT2140 from Mycobacterium tuberculosis, a predicted alpha/beta hydrolase that contains

at the C-terminal end .
FIMAH domain (FIMAH_dom)
Type: Domain

This entry represents a small α-helical bundle domain found in a group of prokaryotic proteins with a large range of different domain architectures, including Alpha-1,2-mannosidase from Neobacillus novalis (

, ). The proteins containing these domains are extracellular enzymes often involved in cell wall processes. The domain, named FIMAH (Found In Many Architectures Helical), is usually found at the C-terminal end of the protein. Its precise function is unknown.
GPI inositol-deacylase, winged helix domain (GPIID_WHD)
Type: Domain

This winged helix domain (WHD) is found in a number of putative GPI inositol-deacylases from fungi, including Vegetative incompatibility protein HET-E-1. This protein is responsible for vegetative incompatibility through specific interactions with different alleles of the unlinked gene, het-c . This domain has detectable sequence similarity to WHDs found in various ATPases. The function of this domain is unknown.
Winged helix domain, variant (WHD)
Type: Domain

This domain is found mainly in uncharacterised bacterial proteins. It is predicted to adopt a globular structure with similarity to MarR family of transcription factors (

). This domain is found usually in combination with AAA+ ATPase domains (

).
Kinesin-like protein KIF2A-like, N-terminal (KIF2A-like_N)
Type: Domain

This domain is found at the N-terminal of human Kinesin-like protein KIF2A and similar animal proteins with a kinesin motor domain (

). KIF2A, which is required for normal progression through mitosis and for normal brain development, is a plus end-directed microtubule-dependent motor protein with microtubule depolymerisation activity. This domain is predicted to adopt an SH3 fold.
Diacylglycerol kinase eta/delta/kappa, helical domain (DGKD_4H)
Type: Domain

This domain is found in diacylglycerol kinase isoenzymes eta (DGKH), delta (DGKD), and kappa (DGKK) . These enzymes play important roles in lipid signaling by converting diacylglycerol to phosphatidic acid. DGKD is a multidomain protein composed of seven globular domains. The domain represented by this entry locates toward the C-terminal and precedes the C-terminal SAM domain (

). It is predicted to adopt an α-helical structure arranged in a four helical bundle.
DNA polymerase-epsilon, zinc finger domain (Znf-DPOE)
Type: Domain

This zinc finger domain is found in the epsilon subunit of eukaryotic DNA polymerase which is involved in DNA synthesis during DNA repair .

This domain is also found in DNA polymerase II large subunit DP2 from archaea, which is the large subunit of a two-subunit archaebacterial replicative DNA polymerase.
E3 ubiquitin-protein ligase listerin, N-terminal domain (Ltn1_N)
Type: Domain

This domain is found at the N-terminal of E3 ubiquitin-protein ligase listerin from Saccharomyces cerevisiae (Ltn1) and similar eukaryotic proteins. Ltn1 is a component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesised nascent chains for proteasomal degradation. This domain is predominantly composed of α-helices that are arranged into HEAT repeats, each consisting of two antiparallel α-helices that pack against each other in a repeating array .
E3 ubiquitin-protein ligase listerin, HEAT repeat region (LTN1_E3_ligase_6th)
Type: Domain

This entry represents a series of HEAT repeats from the LTN1 family of proteins. The LTN1 family consists of E3 ubiquitin-protein ligases that are integral components of the ribosome quality control complex (RQC). The RQC is a ribosome-associated complex responsible for the ubiquitination and subsequent extraction of incompletely synthesized nascent polypeptides for proteasomal degradation. Members of the LTN1 family are recruited to stalled 60S ribosomal subunits, often by NEMF, to mediate the ubiquitination of stalled nascent chains. This ubiquitination event is crucial for the recruitment of VCP/p97 or CDC48, which facilitates the extraction and degradation of the incomplete translation products. In some species, LTN1 proteins also ubiquitinate proteins derived from mRNAs lacking stop codons or translation arrest products induced by specific sequences. Additionally, they may play a role in chromatin function and transcription regulation indirectly.
E3 ubiquitin-protein ligase listerin, ubiquitin conjugating domain (LTN1_UBC)
Type: Domain

This entry represents a domain that structurally resembles the ubiquitin conjugating enzyme domain

and the RWD domain

. This domain is somewhat smaller and apparently lacks the conserved cysteine that is used for ubiquitin conjugation.

This domain is commonly found in the LTN1 family that comprises E3 ubiquitin-protein ligases involved in the ribosome quality control complex (RQC). The RQC is a ribosome-associated complex that targets incompletely synthesized nascent chains for proteasomal degradation. Members of the LTN1 family are responsible for ubiquitinating stalled nascent chains on the 60S ribosomal subunit, a process facilitated by the recruitment of NEMF in some species. This ubiquitination signals the recruitment of cellular machinery such as VCP/p97, TER94/VCP, or CDC48, depending on the organism, to extract and degrade the incomplete translation products. The LTN1 family plays a crucial role in maintaining protein synthesis fidelity by ensuring the removal of defective ribosomal products, thereby preventing the accumulation of potentially toxic protein fragments within the cell.
AglB-like, core domain (AglB-like_core)
Type: Domain

This entry represents the core domain of archaeal oligosaccharyltransferase AglB that transfers oligosaccharide chain from a lipid-linked oligosaccharide (LLO) donor to the asparagine residues in the N-glycosylation sequon, Asn-X-Ser/Thr (X=Pro) . In the archaea AlgB, it occurs alone, rather than in complex as the animal homologue STT3, also included in this entry. This domain adopts a mixed α/β fold and contains a highly conserved WWDYG motif that may be of functional relevance.
Acetolactate synthase small subunit-like, ACT domain (AHAS_small-like_ACT)
Type: Domain

This entry represents the ACT domain found at the N-terminal of acetohydroxyacid synthase isozyme III small subunit (ILVH) from Escherichia coli and at the C-terminal of D-3-phosphoglycerate dehydrogenase , which are closely related . ILVH is the regulatory subunit of acetohydroxyacid synthase (AHAS), an enzyme that catalyses the first step in the biosynthesis of the three branched-chain amino acids .
Alpha-glucan water dikinase, phosphohistidine-like domain (GWD1_pHisD)
Type: Domain

This domain is found in Alpha-glucan water dikinase (GWD1) and its homologues . This enzyme is involved in the incorporation of phosphate into starch-like alpha-V, with preferred C-6 position of glucose units. It acts as an overall regulator of starch mobilisation and it is required for starch degradation.

The domain represented by this entry is predicted to adopt a globular structure consisting of a β-barrel decorated with α-helices. This domain has a significant sequence and structural similarity to phosphohistidine domain found in phosphate dikinases and PEP:sugar phosphotransferases.
Tail protein NMB1110-like, third domain (NMB1110-like_3rd)
Type: Domain

This domain is found in Tail protein, 43 kDa from Neisseria meningitidis (NMB1110) and similar sequences which are related to baseplate hub protein gp44 from Mu bacteriophage. This domain is located C-terminal to

and N-terminal to

.
DC1-like, C-terminal (DC1-like_CT)
Type: Domain

This entry represents a variation of the protein kinase C1 domain (named DC1 for divergent C1 domain) that is characterised by a rich cysteine content, found at the C-terminal of a group of uncharacterised plant proteins. This domain is involved in binding many ligands, which include diacylglycerol, phorbol esters and zinc . This domain is found in association with

.
ComC, supersandwich domain (ComC_SSD)
Type: Domain

This domain is found in ComC from Dictyostelium discoideum and related proteins from Amoebozoa species. It adopts a supersandwich fold with a greater similarity to GLMP luminal domain. ComC mediates a cell adhesion pathway via regulation of the expression of the other intercellular communication genes lagC, and lagD during Dictyostelium development .
Fluoroacetyl-CoA-specific thioesterase-like domain (FlK-like_dom)
Type: Domain

This entry includes fluoroacetyl-CoA-specific thioesterases (FlK), which catalyses the hydrolysis of fluoroacetyl-coenzyme A and provides an effective self-defence mechanism, preventing any fluoroacetyl-coenzyme A formed from being further metabolized to 4-hydroxy-trans-aconitate, an inhibitor of TCA cycle .

This entry represents a HotDog domain that in FIK covers the full length, while in some other members of this entry, this domain can be found in association with other domains, such as

.
Cyanobactin oxidase ThcOx, second domain (ThcOx_dom2)
Type: Domain

Thus entry represents the second peptide-clamp domain described in cianobactin oxidase ThcOx from Cyanothece sp.

. The first one is represented in

and at the C-terminal it contains a nitroreductase domain (

) . In this domain, the binding site is buried by an interaction with the other clamp domain and thus it is unlikely to be active .
Myosin-1, central acidic domain (Myo1_CA)
Type: Domain

This is the CA domain (central acidic domain) found at the C-terminal of myosin-1 from S.pombe and similar fungal sequences . Myo-1 localizes to actin patches which assemble at sites of endocytosis. The CA domain binds and activates Arp2/3, however, this interaction is dispensable for endocytosis. Mammalian orthologues, such as the human Myo1e, do not contain CA domains .
BT_1020-like, structural beta-sandwich domain 1 (BT_1020-like_b-sandwich_1)
Type: Domain

This entry represents the central structural β-sandwich domain 1 found in Six-hairpin glycosidase from Bacteroides thetaiotaomicron (BT_1020,

) and similar uncharacterised proteins mainly found in bacteroidetes .
Mannosylglycerate hydrolase MGH1-like, glycoside hydrolase domain (MGH1-like_GH)
Type: Domain

This entry represents the glycoside hydrolase domain found in Mannosylglycerate hydrolase MGH(1/2) from Selaginella moellendorffii, Glucosidase YgjK and similar sequences from bacteria and eukaryotes. MGH1 catalyses the hydrolysis of alpha-D-mannosyl-glycerate (MG) to D-glycerate and D-mannose . Glucosidase YgjK cleaves the alpha-1,3-glucosidic linkage in nigerose and has a very low activity towards maltooligosaccharides, soluble starch, nigerotriose, kojibiose and trehalose .

This domain is also found in a complex multi-domain architecture in Beta-L-arabinobiosidase that removes L-arabinofuranose-beta-1,2-L-arabinofuranose disaccharide from various substrates such as carrot extensin and potato lectin . It also exists as a standalone domain in Glucosylglycerate hydrolase that catalyses the hydrolysis of glucosylglycerate to glycerate and glucose .
Polysaccharide deacetylase-like (WbmS-like)
Type: Family

This family represents a group of prokaryotic proteins, including the putative polysaccharide deacetylase WbmS from Bordetella bronchiseptica (

), which is involved in O-antigen biosynthesis. It adopts an α-β barrel configuration

.
Macrophage growth locus, subunit A, C-terminal domain (MglA_C)
Type: Domain

This entry represents the C-terminal domain of Macrophage growth locus, subunit A (MglA) from Francisella tularensis (

) and similar sequences from gammaproteobacteria. MglA forms a complex with stringent starvation protein A (SspA) and this complex interacts with both RNA polymerase (RNAP) and the pathogenicity island (FPI) gene regulator to activate FPI transcription .
Conserved oligomeric Golgi complex subunit 2, C-terminal (COG2_C)
Type: Domain

This entry represents the C-terminal region of Conserved oligomeric Golgi complex subunit 2 from yeast, a component of the peripheral membrane COG complex involved in intra-Golgi protein trafficking. This domain adopts a six-helix bundle that seems to play an important structural role in the COG complex .
Active DUF488-N3 subclade (DUF488-N3a)
Type: Domain

This entry represents a subclade of DUF488 domains with degenerate C-terminal core strand. Sometimes it is observed adjacent to the DUF488-s subclade, suggesting it preserves a catalytic activity comparable to other active DUF488 subclades .
Baseplate hub gp41 (E217_GP41)
Type: Family

E217 is a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. Gp41 ia a baseplate cap protein that forms a complex with gp36, gp37 and gp38 proteins. These four proteins are evolutionarily related to the tail tube and adopt a similar fold, consisting of two orthogonally packed β-sheets that form the inner lumen of the tail .
Lytic polysaccharide monooxygenase AA14 (LPMO_AA14)
Type: Family

This entry represents the AA14 family of lytic polysaccharide monooxygenases (LPMOs), mainly found in fungi. These enzymes cleave polysaccharides through an oxidative, instead of hydrolytic, mechanism. Catalysis by LPMOs requires the reduction of the active-site copper from Cu(II) to Cu(I) by a reducing agent and H2O2 or O2 as a cosubstrate . For instance, AA14 family lytic polysaccharide monooxygenase A, is a lytic polysaccharide monooxygenase (LPMO) that has a broad substrate specificity with strong oxidative activity on pure amorphous cellulose and xyloglucan and plays as a bifunctional enzyme to decompose some specific network structures formed between cellulose and hemicellulose in the plant cell walls . It simultaneously oxidizes cellulose, xylan and xyloglucan in natural hemi/cellulosic substrate such as fibrillated eucalyptus pulp, and releases native and oxidized cello-oligosaccharides, xylo-oligosaccharides and xyloglucan oligosaccharides from this substrate .

Proteins in this entry fold into a globular structure, the core of which comprising largely an Ig-like β-sandwich . The active site consists of two histidine and a tyrosine residue, forming the canonical histidine brace exposed at the surface.
Swiss Army Knife, 2H phosphoesterase domain (2H-SAK)
Type: Domain

The Swiss Army Knife class of proteins features a diverse domain repertoire acting to repair RNA damaged in the wake of RNase attacks. 2H-SAK is one such domain, a phosphatase of the rhodanese-phosphatase superfamily. It is predicted to 'clean' RNA ends by removing phosphate groups, preparing them for ligation by their associating RNA ligases .
Diels-Alderase, C-terminal domain (DA_C)
Type: Domain

This domain is found at the C-terminal of a number of fungal Diels-Alderases, including mycB, mpsD and cghA.

Diels-Alderases catalyse different pericyclic [4+2] cycloaddition reactions that synthesise potential pharmaceuticals and mycotoxins . These enzymes consist of two similar β-barrel domains with arrangement similar to AttH. Both domains share some similarity to lipocalins.
Phage tail fiber repeat (Phage_fiber_rpt)
Type: Repeat

This entry represents a lasso-like repeat found in phage tail proteins from tailed bacteriophages and prophages mainly found in flavobacteria.
NACHT conflict system, C-terminal helical domain 2 (NCH2)
Type: Domain

This is an helical domain found at the C-terminal of bacterial NACHT conflict systems .
Plant bHLH transcription factor, ACT-like domain (bHLH-TF_ACT-like_plant)
Type: Domain

This entry represents an ACT-like domain found at the C-terminal of plant transcription factors, such as transcription factor GLABRA 3 from Arabidopsis and the bHLH transcription factor (

) from maize, which is associated with bHLH domains. This domain association is unique to the kingdom Plantae . Phylogenetic analysis show that the association of ACT-like and bHLH domains occurred early in Plantae by recruitment of an ACT-like domain in a common ancestor with widely distributed ACT DOMAIN REPEAT (ACR) genes by an ancestral bHLH gene. The functional significance of this association relies on the homodimer formation of ACT-like domains that negatively affects DNA binding of the associated bHLH domains . For some bHLH transcription factors with the C-terminal ACT-like domain, such as Arabidopsis SPEECHLESS and MUTE, the ACT-like domain serves as heterodimerization selectivity interface.
Lysine-specific demethylase 3A/B, tudor domain (KDM3AB_Tudor)
Type: Domain

This domain is found in Lysine-specific demethylase 3B (KDM3B, also known as JmjC domain-containing histone demethylation protein 2B or JHDM2B), Lysine-specific demethylase 3A (KDM3A, also known as JmjC domain-containing histone demethylation protein 2A or JHDM2A) and related proteins. KDM3B is a histone demethylase that specifically demethylates lysine at position 9 of histone H3 . This enzyme plays a central role in histone code. This domain is predicted to adopt an open β-barrel with an SH3-like topology. It has significant sequence and structural similarity to RDM15 tudor domain that is known to specifically recognise the monomethylation (H3K4me1) mark of lysine at position 4 of histone H3 .
Lysine-specific demethylase 3B, PWWP domain (PWWP_KDM3B)
Type: Domain

This domain is found in Lysine-specific demethylase 3B (KDM3B, also known as JmjC domain-containing histone demethylation protein 2B or JHDM2B), Lysine-specific demethylase 3A (KDM3A, also known as JmjC domain-containing histone demethylation protein 2A or JHDM2A) and related proteins. KDM3B is a histone demethylase that specifically demethylates lysine at position 9 of histone H3 . This enzyme plays a central role in histone code. This domain is predicted to adopt an open β-barrel with an SH3-like topology. It has detectable sequence and structural similarity to PWWP reader domains of LEDGF and ZMYND8 known to recognise the histone H3 methylation marks of lysine at position 36.
Myb-like DNA-binding domain (Myb_DNA-bind_8)
Type: Domain

This entry represents a Myb-like domain. These are short DNA-binding domains.