SII-SWORD/CoKE huggingface dataset:
Bacterial Death-like domain 3 (bDLD3)
Type: Domain

This bacterial adaptor domain of the Death-domain fold is involved in protein-protein interactions in biological conflict systems. bDLDs show a characteristic architectural pattern. One copy is always fused, typically to the N- or C-terminal, of a core component of a biological conflict system; examples include VMAP and iSTAND. Further copies of the same bDLD are fused to either effector or signal-transducing domains, or additional Effector-associated domains (EADs). bDLD pairs are frequently observed together on the genome in conserved gene neighborhoods, but can also be severed from such neighborhoods and located in distant regions, indicating the bDLD-bDLD coupling approximates the advantages of collinear transcription. bDLD3 is closest in sequence and likely progenitor of the metazoan Death-superfamily. bDLD3 shows a greater diversity of contextual associations in conflict systems in comparison to bDLD1 and bDLD2 .
Bacterial Death-like domain 2 (bDLD2)
Type: Domain

This bacterial adaptor domain of the Death-domain fold is involved in protein-protein interactions in biological conflict systems. bDLDs show a characteristic architectural pattern. One copy is always fused, typically to the N- or C-terminal, of a core component of a biological conflict system; examples include VMAP and iSTAND. Further copies of the same bDLD are fused to either effector or signal-transducing domains, or additional Effector-associated domains (EADs). bDLD pairs are frequently observed together on the genome in conserved gene neighbourhoods, but can also be severed from such neighbourhoods and located in distant regions, indicating the bDLD-bDLD coupling approximates the advantages of collinear transcription .
Bacterial Death-like domain 1 (bDLD1)
Type: Domain

This bacterial adaptor domain of the Death-domain fold is involved in protein-protein interactions in biological conflict systems. bDLDs show a characteristic architectural pattern. One copy is always fused, typically to the N- or C-terminal, of a core component of a biological conflict system; examples include VMAP and iSTAND. Further copies of the same bDLD are fused to either effector or signal-transducing domains, or additional Effector-associated domains (EADs). bDLD pairs are frequently observed together on the genome in conserved gene neighbourhoods, but can also be severed from such neighbourhoods and located in distant regions, indicating the bDLD-bDLD coupling approximates the advantages of collinear transcription .
Single-stranded-DNA-specific exonuclease RecJ, C-terminal domain, deinococcus (RecJ_C_deino)
Type: Domain

This domain is found at the C terminus of Single-stranded-DNA- specific exonuclease RecJ from Deinococci. This protein has four domains that form a molecule with an O-like structure . The fourth domain (this entry) binds the C-terminal region of Single-stranded DNA-binding protein to efficiently process broken DNA ends for homologous recombination .
Bride of doubletime-like, TPR domain (Bdbt-like_TPR)
Type: Domain

This domain is found at the C-terminal of Bride of doubletime from Drosophila melanogaster (Bdbt,

) and similar proteins predominantly from arthropods. Bdbt is a mediator of the effects of the kinase doubletime on the key circadian transcriptional regulator period. This entry represents the α-helical TPR domain . It is normally found associated with

.
Meiotic recombination protein REC102 (REC102)
Type: Family

This entry represents a family of proteins from Saccharomycetales, including Meiotic recombination protein REC102 from Saccharomyces cerevisiae. REC102 protein is required for formation of the SPO11-mediated double-strand breaks (DSBs) that initiate meiotic recombination. It may mediate the interaction between SPO11 subunits during meiosis . It is also needed for homologue chromosome pairing, synaptonemal complex formation, and for the proper timing of the first meiotic division. It is not required for mitosis and mitotic DNA repair mechanisms.
Bc2l-C, N-terminal domain (Bc2l-C_N)
Type: Domain

This domain is found at the N-terminal of Lectin from Burkholderia cenocepacia (Bc2l-C) and similar sequences from proteobacteria. Bc2l-C is a soluble lectin involved in bacterial adhesion and subsequent deadly infection to the host. It has two domains: a C-terminal domain

and this domain, which adopts a compact jellyroll architecture composed of 11 β-strands and a short helix. It shows specificity for fucosylated human histo-blood group epitopes H-type 1, Lewis b, and Lewis Y .
Bbp16 (Bbp16)
Type: Family

This protein family includes Bbp16 from Bordetella phage BPP-1 and similar proteins from tailed bacteriophages and prophages, mainly found in proteobacteria. Bbp16, which adopts a dimeric configuration, is essential for forming infectious phage particles. This cement protein has a jelly roll fold with two β-sheets, each consisting of four antiparallel strands .
Restriction endonuclease, type II, NgoFVII, C-terminal B3-like DNA-binding domain (RE_NgoFVII_C)
Type: Domain

This entry represents the RIFT related C-terminal domain of Type II restriction enzyme NgoFVII from Neisseria gonorrhoeae, which is known to recognise GCSGC while the cleavage site is still unknown) restriction endonuclease .
BAHCC1-like, Tudor domain (BAHCC1-like_Tudor)
Type: Domain

This entry represents the Tudor domain found in BAHCC1 and TNRC18 from mammals and winged eye, the orthologue from Drosophila . BAHCC1, may function as a transcriptional regulator. BAHCC1 contains a Tudor domain and a C-terminal BAH domain. This protein specifically recognises H3K27me3 through its BAH module (

) and enforces silencing of H3K27me3-demarcated genes in mammalian cells .

TNRC18 is thought to enable chromatin binding activity, however, its function is not yet unknown.

Winged eye is a factor that induces eye-to-wing transdetermination upon overexpression in eye imaginal discs. It induces various histone modifications and enhances the methylation of Lys9 on histone H3 (H3K9) . This domain may be implicated in the interactions with methylated histone.
Rod-determining factor A (RdfA)
Type: Family

This entry represents a family of proteins from halobacteria, including Rod-determining factor A (RdfA) from Haloferax volcanii (

). RdfA is required for the formation of rods under specific growth conditions, and is therefore involved in motility . Protein members of this family possess four highly conserved cysteine residues at the C-terminal that could potentially be involved in zinc binding.
Bag6, BAG-similar domain (Bag6_BAGS)
Type: Domain

Bag6 (BCL2-associated athanogene cochaperone 6) is part of a cytosolic protein quality control complex involved in the post- translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane, in the mislocalised protein degradation pathway and in the endoplasmic reticulum- associated degradation. The BAG-similar domain, found at the C- terminal end of this protein, plays a role in the interaction with the other members of the complex, Ubl4A and TRC35. This domain shows three helices in an extended conformation that differ from the three-helix bundle fold of the canonical BAG domain (

) .
Avirulence protein AvrRps4-like, C-terminal domain (AvrRps4-like_C)
Type: Domain

This domain is found in the C-terminal of Avirulence protein from Pseudomonas syringae (AvrRps4,

) and in similar sequences from plant pathogenic bacteria. AvrRps4, a causal agent of bacterial blight in pea, is a type III secretion system effector protein that triggers triggers RPS4 (resistance to P. syringae 4)-dependent immunity in resistant accessions of Arabidopsis. This domain folds into an antiparallel α-helical coiled-coil structure .
AvrRps4 family type III secretion system effector (AvrRps4)
Type: Family

This entry includes Avirulence protein from Pseudomonas syringae (AvrRps4) and in similar sequences from plant pathogenic bacteria. AvrRps4, a causal agent of bacterial blight in pea, is a type III secretion system effector protein that triggers triggers RPS4 (resistance to P. syringae 4)-dependent immunity in resistant accessions of Arabidopsis .
DNA-binding protein Rap1, C-terminal, S.pombe (Rap1_C_Sp)
Type: Domain

DNA-binding protein Rap1 is involved in protecting chromosome ends in fission yeast and its C-terminal domain (RCT) structurally resembles the first 3-helix bundle found in yeast and human RAP1 RCT. S. pombe RAP1 lacks direct DNA-binding activity and is localised to telomeres via Taz1 . This entry represents the C-terminal domain of Rap1 from S. pombe.
Bacterial transglutaminase-like, N-terminal domain (Bact_transglu_N_2)
Type: Domain

This domain is found at the N-terminal of a group of transglutaminases and similar sequences from bacteria. This domain is often found associated to

. Its structure resembles that of

.
Selenocysteine-specific elongation factor, third winged helix domain (SelB_WH_3rd)
Type: Domain

This domain is found in Selenocysteine-specific elongation factor from Escherichia coli (SelB) and similar bacterial sequences. SelB is a translation factor necessary for the incorporation of selenocysteine into proteins. The C-terminal region of this protein in bacteria shows four winged-helix (WH) domains arranged in tandem, which form two globular structures. This entry represents the third WH domain. Each WH domain has an α/β structure consisting of three α-helices and a twisted three-stranded antiparallel β-sheet .
Alpha-rhamnosidase-like, N-terminal domain, bacteroidetes (Rhamnosid-like_N_bacteroidetes)
Type: Domain

This domain is found in a group of alpha-rhamnosidases predominantly from Bacteroidetes, including the putative alpha-rhamnosidase from Bacteroides thetaiotaomicron, whose structure shows similarity with a galactose-binding domain.
Metallo-beta-lactamase-like, C-terminal domain (B_lactamase-like_C)
Type: Domain

This domain is found in Metallo-beta-lactamase-like protein from Thermus thermophilus (TTHA1429) and similar bacterial enzymes. This domain is often found C-terminal to

.
Acidianus two-tailed virus, ORF273 protein (ATV_ORF273)
Type: Family

Acidianus two-tailed virus (ATV) develops two tails to infect extremely thermophilic and acidophilic archaea. This entry represents one of its proteins, ORF273, which adopts a tetramer assembly and shows flexible loops and surface pockets in an α-β structure typical of hyper thermostable folds .
Avirulence protein ATR1, WY-domain (ATR1_WY-dom)
Type: Domain

Avirulence protein ATR1 is a secreted effector that acts as an elicitor of hypersensitive response (HR) specifically on plants. It activates the N-terminal Toll-interleukin-1 receptor (TIR) domain of Arabidopsis NLR RPP1 . This entry represents the C-terminal helical domain, referred to as the WY-domain .
MvdD-like, pre-ATP grasp domain (MvdD-like_ATPgrasp)
Type: Domain

The pair of ATP-grasp proteins MvdD and MvdC (microviridin D and C), as well as an acetyltransferase, produce microviridin K, an example of a RiPP (ribosomally synthesised and posttranslationally modified peptide). Microviridins are peptidase inhibitors. This domain represents the pre-ATP grasp domain .
F1F0-ATP synthase delta subunit, C-terminal domain, metazoan (ATPD_C_metazoa)
Type: Domain

F-type ATPases consist of two structural domains, F1 containing the extramembranous catalytic core, and F0 which contains the membrane proton channel. This entry includes ATP synthase subunit delta from animals (called epsilon in bacteria or chloroplast ATPase), which interacts with subunit C from F0 which is important for connecting the rotor of F1 (gamma subunit) to the rotor of F0 C subunit). This entry represents the C-terminal α-helical domain which is likely to act as an inhibitor of ATPase activity .
F1F0-ATP synthase subunit delta, C-terminal domain, fungi (ATPD_C_fung)
Type: Domain

F-type ATPases consist of two structural domains, F1 containing the extramembranous catalytic core, and F0 which contains the membrane proton channel. This entry includes ATP synthase subunit delta from fungi (called epsilon in bacteria or chloroplast ATPase), which interacts with subunit C from F0 which is important for connecting the rotor of F1 (gamma subunit) to the rotor of F0 (C subunit). This entry represents the C-terminal α-helical domain which is likely to act as an inhibitor of ATPase activity .
Autophagy protein ATG5, UblA domain (ATG5_UblA)
Type: Domain

Autophagy protein ATG5 is involved in autophagic vesicle formation. It is conjugated with ATG12, acting as an E3-like ubiquitin enzyme required for lipidation of ATG8 family proteins and their association to the vesicle membranes. This is the N-terminal ubiquitin-like domain, termed UblA, from autophagy protein ATG5 . ATG5 comprises two ubiquitin-like domains (UblA and UblB) that flank a helix-rich domain (HBR). Both UblA and UblB comprise a five-stranded sheet and two-helices.
Autophagy protein ATG5, alpha-helical bundle region (ATG5_HBR)
Type: Domain

Autophagy protein ATG5 is involved in autophagic vesicle formation. It is conjugated with ATG12, acting as an E3-like ubiquitin enzyme required for lipidation of ATG8 family proteins and their association to the vesicle membranes. ATG5 comprises two ubiquitin-like domains (UblA and UblB) that flank a helix-rich domain. This domain represents the α-helical bundle region (HBR) of AT5 which consists of three α-helices . This region contains the Lys residue required for conjugation with ATG12 .
ATG1-like, MIT domain 2 (ATG1-like_MIT2)
Type: Domain

These proteins consist of a kinase domain at the N-terminal (

) and two tandem microtubule interacting and transport (MIT) domains (tMIT) at the C-terminal which, in ATG1, mediates the interaction with ATG13 . In ULK1-2, MIT domain control the regulatory function and localisation of the proteins and also mediate interactions with additional autophagy proteins . This is the C-terminal MIT domain (MIT2).

Members of this entry are Serine/threonine-protein kinases, including Atg1 from yeasts, Unc-51 from C. elegans and Ulk1-2 from humans.

Atg1 is required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway .

Ulk1-2 are involved in autophagy in response to starvation . Ulk1 and Ulk2 regulate filopodia extension and branching of sensory axons. They are important for axon growth, playing an essential role in neurite extension of cerebellar granule cells .

Unc-51 is important for axonal elongation and axonal guidance . It is required for either the maintenance of axons (membrane turnover) or for an unknown neuronal function. C elegans worms lacking Unc-51 exhibit various abnormalities in axonal elongation and axonal structures. Unc-51 could also help control cell size along with Bec-1, as mutations in their corresponding genes results in a reduction in small body size without affecting cell number . Unc-51 is also a component of the Unc-51/Atg-13 complex that is probably recruited by lgg-1 to preautophagosomes and is required for autophagosome formation .
Apoptosis-stimulating of p53 protein 2-like, RA domain (ASPP2-like_RA)
Type: Domain

This domain is found at the N-terminal of human Apoptosis-stimulating of p53 protein 2 (ASPP2) and similar sequences mainly from vertebrates. ASPP2 plays a central role in regulation of apoptosis and cell growth via its interactions with proteins such as TP53. This domain shows a mixed twisted β-sheet and α-helices that pack on one side of the β-sheet, with similarity to a Ras-association (RA) domain .
RAD51D, N-terminal domain (RAD51D_N)
Type: Domain

DNA repair protein RAD51 homolog 4 (RAD51D) plays an important role in DNA repair by homologous recombination (HR) and together with other RAD51 paralogues, RAD51B, RAD51C, XRCC3 and XRCC2, helps recruiting RAD51 to the break site . This entry represents the N-terminal domain of human RAD51D and similar proteins from animals. This domain is essential for protein-protein interaction with XRCC2 and consists of four short helices flanked by long N- and C-terminal tails . It can bind DNA, preferentially ssDNA .
Ras association domain-containing protein 8, RA domain (RASSF8_RA)
Type: Domain

RASSF8, also termed carcinoma-associated protein HOJ-1, is a member of the N-terminal RASSF7-10 protein family. RASSF7-10 has an RA-domain at the N-terminal and lacks a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that is found in members of the RASSF1-6 family . The RA domain of N-terminal RASSF proteins family has the β-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RASSF8 has been described as a potential tumor suppressor. RASSF8 might have a role in the regulation of cell-cell adhesion and cell growth .
Ras association domain-containing protein 8/10, RA domain (RASSF8/10_RA)
Type: Domain

This entry includes RASSF8 and RASSF10, members of the N-terminal RASSF7-10 protein family. RASSF7-10 has an RA-domain at the N-terminal and lacks a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that is found in members of the RASSF1-6 family. The RA domain of N-terminal RASSF proteins family has the β-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RASSF8 has been described as a potential tumor suppressor. RASSF8 might have a role in the regulation of cell-cell adhesion and cell growth. RASSF10 is one of the N-terminal RASSF proteins, characterised by an RA domain in the N terminus. It is expressed in a range of tissues, and has been shown to function as a tumour suppressor in a number of studies .

This entry represents the RA domain of RASSF8/10.

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .
Q4D059-like (Q4D059-like)
Type: Family

This protein family represents a group of proteins from related kinetoplastid parasites found in Trypanosomatidae, including the functionally uncharacterised Q4D059 from Trypanosoma cruzi (

). Q4D059 shows a parallel/ anti-parallel three-stranded β-sheet packed against four helical regions .
Primosomal protein N'-like, winged helix (PriA-like_WH)
Type: Domain

This domain is found in Primosomal protein N' from Escherichia coli (PriA) and similar proteins from Enterobacterales. PriA is a DNA helicase involved in the restart of stalled replication forks, which are lethal in bacteria if left unrepaired. This entry represents the circularly permuted winged helix (WH) domain, which is located towards the N-terminal of the protein and can bind DNA in isolation .

Primosomal protein N', also known as ATP-dependent helicase PriA, is a component of the primosome, which is involved in replication, repair, and recombination. PriA serves as a sensor/stabiliser for an arrested replication fork, which is lethal in bacteria if left unrepaired and eventually promotes restart of DNA replication through the assembly of a primosome. It also serves as a checkpoint protein that prevents the replicase from advancing in a strand displacement reaction on forks that do not contain a functional replicative helicase . This protein shows a modular arrangement in which its central helicase core is surrounded by several DNA-binding elements, including a 3'DNA-binding domain

at the N-terminal. This domain is usually followed by a circularly permuted winged helix (WH) domain

. At the C-terminal, there is a Cys-rich region (CRR) domain

, which is embedded within the C-terminal helicase lobe

, followed by the C-terminal domain (CTD)

.
Ppx/GppA phosphatase, C-terminal (Ppx_GppA_C)
Type: Domain

Ppx/GppA phosphatases belong to ASKHA (acetate and sugar kinases, Hsp70, actin) which has an N-terminal (

) nucleotide-binding domain (domains I/II), domain III which corresponds to the catalytic phosphohydrolase domain with the common helical fold and domain IV . This entry represents the C-terminal region that includes domains III and IV.
Exopolyphosphatase, C-terminal (Ppx_C)
Type: Domain

This domain is found at the C-terminal end of Exopolyphosphatase from Agrobacterium fabrum (Ppx) and similar proteins mainly found in alphaproteobacteria. It is usually found associated with

.
Asparagine--tRNA ligase, N-terminal domain (AsnRS_N)
Type: Domain

This domain is found at the N-terminal domain of the eukaryotic cytoplasmic protein Asparagine--tRNA ligase (AsnRS, also known as NARS1). AsnRS is essential for protein translation and has been related to autoimmune and neurological diseases. Unlike its bacterial homologues, this protein has a conserved N-terminal extension, represented in this entry, connected by an unstructured tether to the part of the enzyme that has homologues within eukaryotes and prokaryotes: an anticodon-binding domain (

), a hinge region (HR), and a catalytic domain (

).

This domain folds into two α-helices and three β-strands that form a parallel/antiparallel mixed β-sheet and has a characteristic lysine-rich helical motif that interacts with tRNA. It also shows chemokine activity through its interaction with C-C chemokine receptor 3 (CCR3) and the promotion of NRS-CCR3-mediated proinflammatory signalling .
Protection of telomeres protein 1, C-terminal insertion domain (POT1_C_insert)
Type: Domain

Protection of telomeres protein 1 (POT1) is responsible for binding to and protecting the 3' single-stranded DNA (ssDNA) overhang at most eukaryotic telomeres . This entry represents an insertion domain found at the C-terminal of POT1 and similar sequences from vertebrates. It is described as Holliday junction resolvase-like domain (HJRL) in .
PorZ, N-terminal beta-propeller domain (PorZ_N)
Type: Domain

This domain is found at the N-terminal of PorZ (also known as Immunoreactive 84kD antigen PG93) from Porphyromonas gingivalis and in similar proteins predominantly found in Bacteroidetes. PorZ is an essential component of the type-IX secretion system (T9SS) machinery. It consists of three domains. This entry represents the first domain, which folds into a seven-stranded β-propeller .
Cip1-like, core domain (Cip1-like_core)
Type: Domain

This entry represents a domain found in Cip1 from Hypocrea jecorina and similar fungal and bacterial sequences. Cip1 is a cellulose induced protein with a carbohydrate binding module (

) connected via a linker region to a domain with yet unknown function (this entry). This domain shows a β-sandwich jelly-roll fold with two antiparallel β-sheets that consist on eight and seven strands and pack on top of one another. Structural analysis suggest it may function as a lyase . In some proteins, this domain is found associated with

.
Selenocysteine-specific elongation factor, domain III, archaea (SelB_III_arc)
Type: Domain

Selenocysteine-specific elongation factor (SelB) is a transcription factor necessary for the incorporation of selenocysteine into proteins. This entry represents domain III of archaeal SelB, which adopts a β-barrel fold and is homologous to domain III of EF-Tu .