SII-SWORD/CoKE huggingface dataset:
MAP3K, deoxyribohydrolase domain (DRHyd-ASK)
Type: Domain

Apoptosis signal-regulating kinases (ASK1/2/3 or MAP3K5/6/15) are mitogen-activated protein kinase kinase kinases (MAP3Ks) that mediate cellular responses to redox stress and inflammatory cytokines and play a key role in innate immunity and viral infection. This kind of signalling kinases are regulated by oligomerization and regulatory domains. In its N-terminal there is a thioredoxin-binding domain that negatively regulates activity and a TNF receptor-associated factors (TRAFs)-binding domain which triggers ASK activation and kinase activity. TRAFs-binding domain is composed by 14 helices, which form seven tetratricopeptide repeats (TPRs), followed by a PH-like domain to complete de central regulatory domain of ASK. The central regulatory region promotes ASK1 activity via its PH domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding and kinase domains into close proximity. The PH-like domain, adjacent to the kinase domain, is required together with an intact TPR region for ASK1 activity.

The major role of the central regulatory region is to bring the thioredoxin-binding domain into close proximity to the kinase domain to inhibit its activity .

This is an uncharacterised DRHyd domain observed in MAP3K5/6/15. It potentially generates nucleotide-derived signal recognised by the TPR-S domain found in the same proteins .
MAP3K, HisK-N-like globin domain (HisK-N-like)
Type: Domain

Apoptosis signal-regulating kinases (ASK1/2/3 or MAP3K5/6/15) are mitogen-activated protein kinase kinase kinases (MAP3Ks) that mediate cellular responses to redox stress and inflammatory cytokines and play a key role in innate immunity and viral infection. This kind of signalling kinases are regulated by oligomerization and regulatory domains. In its N-terminal there is a thioredoxin-binding domain that negatively regulates activity and a TNF receptor-associated factors (TRAFs)-binding domain which triggers ASK activation and kinase activity. TRAFs-binding domain is composed by 14 helices, which form seven tetratricopeptide repeats (TPRs), followed by a PH-like domain to complete de central regulatory domain of ASK. The central regulatory region promotes ASK1 activity via its PH domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding and kinase domains into close proximity. The PH-like domain, adjacent to the kinase domain, is required together with an intact TPR region for ASK1 activity.

The major role of the central regulatory region is to bring the thioredoxin-binding domain into close proximity to the kinase domain to inhibit its activity .

This domain represents a predicted non-heme-binding version of the globin domain identified in ASK1/2/3. It displays strongest affinities to the HisK-N family of sensor domains, which inhibit histidine kinase activation required for sporulation in bacteria of the firmicutes lineage. This globin domain is predicted to represent an independent sensory element recognizing a fatty acid or a related membrane-derived molecule which regulates activity of the ASK signalosome in apoptosis .
Predicted novel nucleotide synthetase (Pred_NTSase1)
Type: Family

Conserved genome contexts in NAD -derived nucleotide-activated effector systems predict a function for members of this protein family as a previously-uncharacterised nucleotide synthetase from Proteobacteria .
Prokaryotic STING domain (Prok_STING)
Type: Domain

This entry represents a STING (STimulator of INterferon Gene) sensor domain found in certain prokaryotic nucleotide-activated effector conflict systems, like the CBASS (cyclic oligonucleotide-based antiphage signaling system) which provides immunity against bacteriophage. Binding to a nucleotide activates fused effector proteins in conflict response against invasive elements.

This domain is found in CD-NTase-associated protein 12 and 13, which bind c-di-GMP and 3'-3'-cGAMP, cyclic nucleotides synthesized by the CD-NTase protein in response to infection that serve as specific second messenger signals to activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection . Certain versions in prokaryotes may additionally regulate bacterial ion channels. This domain has been transferred to eukaryotes on multiple occasions, and representatives observed are in animal-choanoflagellate, haptophyte/stramenopile, and fungal lineages .

The crystal structure of this domain in

from Prevotella corporis shows an α/β fold with a central five-stranded β-sheet surrounded by five α-helices and a β-ribbon .
Nucleotidyltransferase-Associated Rossmannoid Fold (NARF)
Type: Domain

This entry represents an inactive bacterial domain, which is a member of the Receiver superfamily of the Rossmonnoid fold. It is predicted to function as a sensor domain in certain nucleotide-activated effector conflict systems. This domain is thought to bind nucleotides synthesized by both the SMODS domain and the CRISPR polymerase (Cpol) domain of the Cas10-like proteins, depending on genome context. N-terminal transmembrane segments are observed, suggesting that nucleotide binding initiates a membrane-perforating and cell-suicide response in conflict .
Bacterial Ig-like domain 14 (Big_14)
Type: Domain

This entry represents a bacterial Ig-like domain that shows some similarity to

, suggesting it may act as a protease inhibitor similar to B. subtilis BsuPI.
KANL3/Tex30, alpha/beta hydrolase-like domain (KANL3/Tex30_Abhydrolase)
Type: Domain

This entry represents an α/β hydrolase-fold domain of the animal KAT8 regulatory NSL complex subunit 3 (KANSL3 or NSL3, also known as testis development protein PRTD) and the testis-expressed sequence 30 proteins.

KAT8 regulatory NSL complex subunit 3 is part of the NSL complex that is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription . The function of the testis-expressed sequence 30 protein is not known.

This entry also includes uncharacterised bacterial proteins.
Tetratricopeptide Repeats-Sensor (TPR-S)
Type: Repeat

This entry represents a sensor domain consisting of 7 TPR repeats forming a tightly-wound solenoid structure harbouring a deep central pocket. The TPR-S binding pocket is lined with several conserved aromatic and polar residues predicted to bind a NAD -derived nucleotide in prokaryotic NAD -derived nucleotide-activated effector conflict systems. It has been acquired at the base of the choanoflagellate-animal lineage as a core component of the ASK signalosome .
Divergent DnaB-like ATPase (divDNAB)
Type: Domain

This domain is found in a divergent DnaB-like helicase of the RecA-ATP-synthase superfamily of P-loop NTPases found in phages, which is characterised by a modified ATP-binding Walker B motif .
Small protein found in certain Dnd DNA modification systems (Sp-DndD)
Type: Family

This entry represents a small protein found in bacteria, that, analogous to an antitoxin, it potentially acts as a negative regulatory component that might sense the presence of invaders by acting as a binding factor or substrate for invader-encoded enzymes like viral peptidases in certain Dnd systems . In some members included in this entry the model represents a domain associated with

.
Type VI secretion system, FHA domain-containing protein, C-terminal domain (T6SS_FHA_C)
Type: Domain

This entry represents a presumed domain found at the C-terminal of a group of proteins thought to be expressed in a Type VI secretion system locus in proteobacteria. These proteins contain an N-terminal FHA domain (

). The function of this domain is unknown.
tRNA-specific 2-thiouridylase MnmA-like, central domain (MnmA-like_central)
Type: Domain

This entry represents the central PRC-barrel domain of tRNA-specific 2-thiouridylase MnmA and similar proteins from bacteria and eukaryotes. MnmA catalyses the 2-thiolation of uridine at the wobble position (U34) of tRNA, leading to the formation of s2U34 .
tRNA-specific 2-thiouridylase MnmA-like, C-terminal domain (MnmA-like_C)
Type: Domain

This entry represents the aminomethyltransferase β-barrel domain found at the C-terminal end of tRNA-specific 2-thiouridylase MnmA and similar proteins from bacteria and eukaryotes. MnmA catalyses the 2-thiolation of uridine at the wobble position (U34) of tRNA, leading to the formation of s2U34 .
Ribosomal RNA small subunit methyltransferase E, methyltransferase domain (RsmE_MTase_dom)
Type: Domain

Methyltransferases (Mtases) are responsible for the transfer of methyl groups between two molecules. The transfer of the methyl group from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms. The reaction is catalysed by Mtases and modifies DNA, RNA, proteins or small molecules, such as catechol, for regulatory purposes. Proteins in this entry belong to the RsmE family of Mtases, this is supported by crystal structural studies, which show a close structural homology to other known methyltransferases .

This group of proteins includes Ribosomal RNA small subunit methyltransferase E (RsmE) from Escherichia coli, which specifically methylates the uridine in position 1498 of 16S rRNA in the fully assembled 30S ribosomal subunit . This enzyme has two distinct but structurally related domains: the N-terminal PUA domain and the conserved MTase domain at the C-terminal end. This protein adopts a dimeric configuration that is functionally critical for substrate binding and catalysis .

This entry represents the C-terminal methyltransferase domain (MTase domain) found in RsmE which shows a deep trefoil knot. This domain is responsible for binding of one AdoMet molecule and for the catalytic process .
Ribosomal RNA small subunit methyltransferase E, PUA-like domain (RsmE_PUA-like)
Type: Domain

Methyltransferases (Mtases) are responsible for the transfer of methyl groups between two molecules. The transfer of the methyl group from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms. The reaction is catalysed by Mtases and modifies DNA, RNA, proteins or small molecules, such as catechol, for regulatory purposes. Proteins in this entry belong to the RsmE family of Mtases, this is supported by crystal structural studies, which show a close structural homology to other known methyltransferases .

This group of proteins includes Ribosomal RNA small subunit methyltransferase E (RsmE) from Escherichia coli, which specifically methylates the uridine in position 1498 of 16S rRNA in the fully assembled 30S ribosomal subunit . This enzyme has two distinct but structurally related domains: the N-terminal PUA domain and the conserved MTase domain at the C-terminal end. This protein adopts a dimeric configuration that is functionally critical for substrate binding and catalysis .

This entry represents the N-terminal PUA (pseudouridine synthases and archaeosine-specific transglycosylases)-like RNA recognition and binding domain found in RsmE. This domain is mainly responsible for recognition of one substrate molecule (the ribosomal RNA fragment and ribosomal protein complex) .
Prokaryotic YEATS domain (pYEATS)
Type: Domain

This entry represents a prokaryotic YEATS domain. pYEATS is fused to diverse effector domains, suggesting that the binding to a ligand activates an effector-based response against an invasive threat. It has been predicted to specifically recognise invader-induced modifications of macromolecules by acyl moieties (e.g. phage-encoded acylations of surface polysaccharides) to unleash the fused effectors through a conformational change .
Small protein from certain CxC ATPase-based DNA modification systems (Sp-CxC)
Type: Family

This entry represents a small protein, that, analogous to an antitoxin, it potentially acts as a negative regulatory component that might sense the presence of invaders by acting as a binding factor or substrate for invader-encoded enzymes like viral peptidases in certain CxC ABC ATPase-based DNA modification systems .
YEATS-Like-Associating Three TM (YLATT)
Type: Domain

This is a conserved, three transmembrane helix-containing domain found fused to certain prokaryotic YEATS domain. Genome context displacement patterns predict an effector role for this domain, as a membrane-perforating, cell-suicide response-enacting domain .
Prokaryotic E2 domain (E2-ntca)
Type: Domain

This is an E2 domain observed in certain prokaryotic ubiquitin systems found as secondary effectors in nucleotide-activated effector conflict systems .
Cysteine-rich domain, C-terminal to E2 domain (E2-Crich)
Type: Domain

This is a cysteine-rich domain observed C-terminal to certain E2 domains (

) which are part of prokaryotic ubiquitin systems found as secondary effector modules in nucleotide-activated effector conflict systems .
MutS2 and Smr-associated SH3 domain (MSSS)
Type: Domain

This entry represents a SH3-like domain associated with the MutS-like ABC ATPase and Smr domains. It has been predicted to play a role in lesion recognition or alternatively in mediating contacts with RNA primers or misincorporated ribonucleotides during DNA repair or interacting with the ribosome at the intersection between DNA repair and ribosome rescue . It is found in several proteins from plants and bacteria, including Endonuclease MutS2.
Methylase-associated X1 (MTaX1)
Type: Domain

This entry represents a globular domain found across several bacterial restriction-modification systems .
ABC-three component system, Middle Component 8 (ABC-3C_MC8)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses. MC8 is a MC unifiable with the HTH fold .
LYR motif-containing protein Cup1-like, N-terminal domain (Cup1-like_N)
Type: Domain

This entry represents a domain found at the N-terminal end of fungal LYR domain-containing proteins, including Cup1 (caffeine unstable phenotype 1, previously known as uncharacterised protein C17G9.13c) from S. pombe . Cup1 is a mitochondrial protein whose silencing by heterochromatin island formation results in caffeine resistance. LYR-motif containing proteins are basic polypeptides carrying a conserved tripeptide L-Y-R (leucine/tyrosine/arginine) sequence close to the N terminus in addition to some basic arginine/lysine residues and a highly-conserved phenylalanine downstream of the LYR motif .
ABC-three component system, Middle Component 6 (ABC-3C_MC6)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses. MC6 is a MC unifiable with the HTH fold .
ATPase RavA, LARA domain (RavA_LARA_dom)
Type: Domain

This entry represents the LARA (LdcI Associating domain of RavA) domain of bacterial regulatory ATPase RavA (Regulatory ATPase variant A) . It adopts an unique fold which consists of a compact antiparallel β-barrel-like structure formed by six β-strands and one α-helix . This domain mediates the interaction between RavA and LdcI (inducible lysine decarboxylase) which form a cage-like complex proposed to assist assembly of specific respiratory complexes in E. coli .
KTSC and Metallopeptidase-like, N-terminal fusion domain (KMPT_N)
Type: Domain

This entry represents an uncharacterised α/β domain N-terminally fused to diverse metallopeptidases (MPTases) and the lysyl tRNA synthetase KTSC RNA-binding domain protein. This domain is currently observed in only the jumbo phages .
ABC-three component system, Middle Component 7 (ABC-3C_MC7)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses. MC7 is a MC unifiable with the HTH fold .
ABC-three component system, Middle Component 5 (ABC-3C_MC5)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses .
ABC-three component system, Middle Component 4 (ABC-3C_MC4)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses .
Mab-21-like, nucleotidyltransferase domain (Mab-21-like_nuc_Trfase)
Type: Domain

This entry represents the N-terminal nucleotidyltransferase domain of Mab-21 and Mab-21 like proteins and related proteins from animals. In Caenorhabditis elegans, these proteins are required for several aspects of embryonic development . This entry also includes inositol 1,4,5-triphosphate receptor-interacting proteins, which are predicted to contain a partial Mab-21 domain .
ABC-three component system, Middle Component 2 (ABC-3C_MC2)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses .
ABC-three component system, Middle Component 1 (ABC-3C_MC1)
Type: Family

Middle Components (MCs) of the ABC-3C biological conflict systems occupy the central position between the catalytic effector and ABC ATPases of the systems. MCs are defined by distinctive patterns of conserved charged residues. As some MCs are HTH domains, they are predicted to function akin to kleisins as DNA-binding partners for the ABC ATPases, assisting in recognition and responding to invasive elements such as DNA viruses .
Mab-21-like, HhH/H2TH-like domain (Mab-21_HhH/H2TH-like)
Type: Domain

This entry represents the C-terminal HhH/H2TH-like domain of Mab-21 and Mab-21-like proteins, and related proteins from animals. In Caenorhabditis elegans, these proteins are required for several aspects of embryonic development . This entry also includes inositol 1,4,5-triphosphate receptor-interacting proteins, which are predicted to contain a partial Mab-21 domain .
SH3 fold domain associated with phage DNA polymerases (SH3DP)
Type: Domain

This is an SH3 fold domain related to nucleic acid binding toxins of uncharacterised function, usually associated with a divergent Family B DNA polymerase in group 1/PhiKZ-like phages .
Divergent Family B DNA polymerase (divDNApol)
Type: Family

This family represents a Divergent Family B DNA polymerase found in PhiKZ/ group 1 phages .
Cyclic-phosphate processing, Receiver domain (cREC_REC)
Type: Domain

This is a divergent version of the Receiver (Rec) domain linked to different NAD /ADPr-processing enzymes. Unlike conventional Rec domains, cREC is never found in two-component Histidine Kinase signalling systems. Instead, it is found in association with NAD -processing systems that generate or recognise cyclic nucleotides. Known Rec domains process phosphoester linkages by means of catalytic aspartate residues that are also conserved in cREC. Accordingly, it is predicted that members of this entry are cADPr or 2'-3' cyclic nucleotide-processing enzymes .
E2-E1 middle domain (E2-E1mid)
Type: Domain

Certain prokaryotic Ubiquitin systems contain this domain between E2 and E1 fusion proteins. Many of these systems are secondary effector modules associating with nucleotide-activated effector systems .
ABC-three component systems, C-terminal domain 9 (ABC-3C_CTD9)
Type: Domain

C-terminal domains (CTDs) of ABC-3C systems, contain distinct patterns of charged and polar residues and are not yet unifiable with known domains. These domains are found at the C-terminal of the effector component of the systems, which are upstream of the Middle Component and ABC ATPase components on the genome. Due to the typically large size of these CTDs relative to the actual effector and MC domains, the CTDs are predicted to serves as the platform on which the remaining two components assemble. Therewith, conformational changes transmitted by the ABC ATPase-mediated detection of invasive elements like DNA viruses would result in an unfurling and activation of the CTD-associated effector .
ABC-three component systems, C-terminal domain 8 (ABC-3C_CTD8)
Type: Domain

C-terminal domains (CTDs) of ABC-3C systems, contain distinct patterns of charged and polar residues and are not yet unifiable with known domains. These domains are found at the C terminus of the effector component of the systems, which are upstream of the Middle Component and ABC ATPase components on the genome. Due to the typically large size of these CTDs relative to the actual effector and MC domains, the CTDs are predicted to serve as the platform on which the remaining two components assemble. Therewith, conformational changes transmitted by the ABC ATPase-mediated detection of invasive elements like DNA viruses would result in an unfurling and activation of the CTD-associated effector .
ABC-three component systems, C-terminal domain 7 (ABC-3C_CTD7)
Type: Domain

C-terminal domains (CTDs) of ABC-3C systems, contain distinct patterns of charged and polar residues and are not yet unifiable with known domains. These domains are found at the C terminus of the effector component of the systems, which are upstream of the Middle Component and ABC ATPase components on the genome. Due to the typically large size of these CTDs relative to the actual effector and MC domains, the CTDs are predicted to serve as the platform on which the remaining two components assemble. Therewith, conformational changes transmitted by the ABC ATPase-mediated detection of invasive elements like DNA viruses would result in an unfurling and activation of the CTD-associated effector .
ABC-three component systems, C-terminal domain 6 (ABC-3C_CTD6)
Type: Domain

C-terminal domains (CTDs) of ABC-3C systems, contain distinct patterns of charged and polar residues and are not yet unifiable with known domains. These domains are found at the C terminus of the effector component of the systems, which are upstream of the Middle Component and ABC ATPase components on the genome. Due to the typically large size of these CTDs relative to the actual effector and MC domains, the CTDs are predicted to serve as the platform on which the remaining two components assemble. Therewith, conformational changes transmitted by the ABC ATPase-mediated detection of invasive elements like DNA viruses would result in an unfurling and activation of the CTD-associated effector .