SII-SWORD/CoKE huggingface dataset:
Tail spike TSP1/Gp66, N-terminal domain (Tail_spike_N)
Type: Domain

Bacteriophages recognize and bind to their hosts with the help of receptor-binding proteins (RBPs) that emanate from the phage particle in the form of fibres or tailspikes. RBPs of podovirus G7C tailspikes gp63.1 and gp66 are essential for infection of its natural host bacterium E. coli 4s. Gp63.1 and gp66 form a stable complex, in which the N-terminal part of gp66 serves as an attachment site for gp63.1 and anchors the gp63.1-gp66 complex to the G7C tail. The two N-terminal domains show 70% sequence identity to the N-terminal region of the CBA120 phage tailspike 1 (orf210, TSP1) . The N-terminal domain of TSP1 is the virion head binding domain that interfaces with the phage baseplate. The N-terminal domain can be further divided into two subdomains, each beginning with a α-helix followed by an anti-parallel β-sandwich. Subdomain two folds similarly to the chitin binding domain of Chitinase from Bacillus circulans .
ThcOx, helix turn helix domain (ThcOx_HTH)
Type: Domain

This is a winged helix turn helix domain which is found in cyanobactin oxidase ThcOx N-terminal region. The oxidase converts thiazolines to thiazoles .
Domain of unknown function DUF5591 (DUF5591)
Type: Domain

This is a domain of unknown function found in archaeal tRNA-guanine transglycosylase (

) and in archaeosine synthase (

) proteins.
CASTOR1, N-terminal (CASTOR1_N)
Type: Domain

CASTOR1 (Cytosolic arginine sensor for mTORC1 subunit 1) has been identified as the cytosolic arginine sensor for the mTORC1 pathway. In the absence of arginine, CASTOR1 binds to GATOR2 and inhibits mTORC1 signaling; whereas in the presence of arginine, CASTOR1 interacts with arginine and no longer associates with GATOR2. The arginine sits in a pocket between the N-terminal domain (NTD) and the C-terminal domain (CTD) of CASTOR1. The CASTOR1-NTD on the opposite side of the arginine-binding site was identified to mediate direct physical interaction with its downstream effector GATOR2, via GATOR2 subunit Mios .
Protein of unknown function DUF5538 (DUF5538)
Type: Family

This family of proteins with unknown function can be found in mammals.
6S proteasome subunit Rpn6, C-terminal helix domain (Rpn6_C_helix)
Type: Domain

This is the C-terminal helix domain found in Rpn6, a component of the 26S proteasome. The C-terminal helices are essential for lid assembly .
Rubisco accumulation factor 1, helix turn helix domain (Raf1_HTH)
Type: Domain

This is helix turn helix domain found in α helical region of Rubisco accumulation factor1 (Raf1). Raf1 from Arabidopsis thaliana consists of an N-terminal alpha-domain, a flexible linker segment and a C-terminal β-sheet domain that mediates dimerization. The α-domains mediate the majority of functionally important contacts with RbcL (Rubisco large subunits) by bracketing each RbcL dimer at the top and bottom. The alpha-domain alone is essentially inactive .
KfrB domain (KfrB)
Type: Domain

The KrfB domain is found at the C-terminal end of TraB from Escherichia coli and similar sequences mainly found in proteobacteria. This domain, found in polyvalent proteins of conjugative element or often in the neighbourhood of one, is related to Type IV Secretion Systems (T4SS) and plays a key role in discrimination of self from non-self . It adopts the fold of an oligonucleotide/oligosaccharide binding domain (OB-domain) and consists of a five-stranded Greek-key β-barrel in an open distorted conformation that is capped by a short α-helix .
Actinobacteria/chloroflexi VLRF1 release factor (VLRF1)
Type: Domain

Archaeo-eukaryotic release factor domain belonging to the VLRF1 clade, observed primarily in the actinbacteria and chloroflexi bacterial lineages. Contains a conserved glutamine residue in the release factor catalytic loop, suggesting it functions as an active peptidyl-tRNA hydrolase at the ribosome .
Glycogen debranching enzyme, C-terminal domain (GlgX_C)
Type: Domain

This is the C-terminal domain of the glycogen debranching enzyme GlgX. GlgX hydrolyzes alpha-1,6-glycosidic linkages of phosphorylase-limit dextrin containing only three or four glucose subunits produced by glycogen phosphorylase. Sequence analysis suggests that GlgX is a debranching enzyme belonging to the glycoside hydrolase GH-13 family in the CAZy database .
Immune Mapped Protein 1-like, C-terminal domain (IMP1-like_C)
Type: Domain

This entry represents the C-terminal domain of the Immune Mapped Protein 1-like (IMP1-like), conserved across the members of Apicomplexa. .
RXLR phytopathogen effector protein, WY-domain (RXLR_WY)
Type: Domain

Filamentous plant pathogens cause devastating diseases of crops. Phytophthora infestans, the Irish potato famine pathogen, facilitates disease on its hosts by delivering effector proteins that modulate host cell processes to the benefit of the parasite, a strategy used by many biotrophic plant pathogens. The Phytophthora infestans RXLR-type effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and perturbs host-selective autophagy. The N-terminal region of PexRD54 contains 5 tandem WY domains. 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. Deletion analysis show that the WY domains of PexRD54 are dispensable for ATG8CL binding suggesting an alternative function for these domains .
Cas12a, REC1 domain (Cas12a_REC1)
Type: Domain

Cpf1, also known as CRISPR-associated endonuclease Cas12a, is an RNA-guided endonuclease of a type V CRISPR-Cas system. Cpf1 adopts a bilobed architecture consisting of an α-helical recognition (REC) lobe and a nuclease (NUC) lobe, with the small CRISPR RNAs (crRNAs)-target DNA heteroduplex bound to the positively charged, central channel between the two lobes. The REC lobe consists of the REC1 and REC2 domains where REC1 comprises 13 α helices, and REC2 comprises ten α helices and two β strands that form a small antiparallel sheet . This entry represents REC1 domain.
MAE_28990/MAE_18760-like HEPN (HEPN_MAE_28990)
Type: Domain

HEPN-like nuclease. MAE_28990 In operon with a ParB nuclease and DNA methylase genes. MAE_18760-like HEPN found fused to HEPN/RES-NTD1, HEPN/Toprim-NTD1, Schlafen and a novel β rich domain. In operon with ParA/Soj ATPase of SIMIBI-type GTPase fold .
Large polyvalent protein-associated domain 11 (LPD11)
Type: Domain

This is an α-helical domain with conserved hydrophobic residues . It is found in polyvalent proteins of conjugative elements .
Kindlin-2, N-terminal (Kindlin_2_N)
Type: Domain

This is the N-terminal domain (K2-N) of Kindlin-2 protein from humans. Kindlin-2 is a regulator for heterodimeric integrin adhesion receptors that promotes integrin activation. Activation depends on binding of the N-terminal domain to the integrin beta cytoplasmic tail (CT), which disrupts the receptors association with alpha-CT and triggers the conformational transitions in the receptor. K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate (PIP2). K2-N is also very similar to the homologous kindlin-1 F0 .
Protein of unknown function DUF5555 (DUF5555)
Type: Family

This is a family of unknown function found in mammals.
Zap1, zinc finger 2 (Zap1_Znf2)
Type: Domain

This domain can be found in Zap1 present in Saccharomyces cerevisiae. Zap1 regulates S. cerevisiae which mediates the transcription of genes encoding uptake vacuolar transporters. This domain corresponds to zinc finger 2 (Znf2) which has been shown to be a constitutive transcriptional activator. The two zinc fingers interactions stabilizes Zn(II)-binding .
CDH1/2, SANT-Helical linker 1 (CDH1_2_SANT_HL1)
Type: Domain

CDH1 is an ATP-dependent chromatin-remodelling factor and plays an important role in regulating nucleosome assembly and mobilization. CHD1 consists of double chromodomain, SNF2-related ATPase domain, and a C-terminal DNA-binding domain. The DNA-binding domain contains SANT (Swi3, Ada2, N-CoR, TFIIIB) and SLIDE (SANT-like ISWI) domains in its C-terminal region . SANT domains are structurally related to Myb-like domains are common motifs found in chromatin interacting proteins. Deletion of individual SANT or SLIDE domains in CDH1 does not significantly affect nucleosome binding, but combined deletion of both domains severely compromise binding, suggesting that the SANT-SLIDE motif recognizes DNA/nucleosomes as a single cooperative unit. SANT sequences of Chd1 proteins are the most distantly relation group of sequences relation to other SANT/Myb sequences, and are more diverse than other SANT proteins . The SANT and SLIDE regions are well conserved in both Chd1 and ISWI (imitation switch) remodelling enzymes . This domain comprises the SANT region and the helical linker region 1 (HL1).
Carbohydrate esterase 2, N-terminal (CE2_N)
Type: Domain

This is the N-terminal β-sheet domain with jelly roll topology found in CE2 acetyl-esterase from the bacterium Clostridium thermocellum. This enzyme displays dual activities, it catalyses the deacetylation of plant polysaccharides and also potentiates the activity of its appended cellulase catalytic module through its noncatalytic cellulose binding function. This N-terminal jelly-roll domain appears to extend the substrate/cellulose binding cleft of the catalytic domain in C. thermocellum .
Non-structural protein 2, gammacoronavirus (NSP2_gammaCoV)
Type: Domain

Avian infectious bronchitis virus (IBV) is a gammacoronavirus that belongs to Group III of coronaviruses. As all coronaviruses, they have a large genome containing the replicase gene consisting of two large ORFs, ORF1a and 1b that encode two replicase polyproteins ppa1a/1ab, which are then autoproteolytically processed into 15 or 16 matured nonstructural proteins to achieve viral genomic replication, assembly and maturation. This group contains avian viruses and differs from the other groups in that they do not encode the essential pathogenic factor nonstructural protein 1 (NSP1) and instead start with NSP2. IBV NSP2 is one of the first replicase proteins to be translated and processed in the viral life cycle . NSP2 is a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity .
CRISPR-associated endonuclease Cas9, beta-hairpin domain (Cas9_b_hairpin)
Type: Domain

This is β-hairpin domain found in Cas9 proteins from Actinobacteria. The β-hairpin domain is not conserved in all type II-C Cas9 proteins. The β-hairpin in Cas 9 from Streptococcus pyogenes blocks the HNH domain active site .
ZMIZ1, N-terminal domain (ZMIZ1_N)
Type: Domain

This is the N-terminal domain found in ZMIZ1 proteins. Functional analysis indicates that the N-terminal Domain of ZMIZ1 is important for driving Myc transcription and proliferation .

ZMIZ1 is a transcriptional regulator that functions as a direct cofactor of Notch1, modulating Notch target gene expression through interaction with the RAM1 domain via its N-terminal tetratricopeptide repeat (TPR) domain (

) . It has been shown that ZMIZ1 and Notch1 cooperatively recruit one another to chromatin through direct TPR-mediated interaction, leading to a modest increase in activating histone marks and a corresponding reduction in repressive marks . In addition to its role in Notch signalling, ZMIZ1 enhances ligand-dependent transcriptional activity of the androgen receptor (AR) and promotes AR sumoylation , . It also acts as a coactivator in the TGF-beta signalling pathway by potentiating the transcriptional activity of the SMAD3/SMAD4 complex .
Rpn9, C-terminal helix (Rpn9_C)
Type: Domain

The 26S proteasome is the major ATP-dependent protease in eukaryotes which plays a key role in intracellular protein degradation .

The lid of the 26S proteasome contains six PCI-domain-containing proteins (Rpn3/5/6/7/9/12), two MPN-domain-containing proteins (Rpn8/11), and one peptide, Sem1 . The only catalytically active member of the lid is Rpn11, which serves as the essential deubiquitinase of the proteasome . The C terminus of each subunit in the lid is predicted to form one or more helices. These C-terminal helices are highly conserved and have been predicted to form a helical bundle structure .

In yeast, Rpn9 was found to be necessary for the integrity and efficiency of the 26S proteasome .

This entry represents a helix domain C-terminal to the PCI domain found in Rpn9, a subunit of the 26S proteasome. C-terminal truncations of Rpn5 or Rpn9 have been shown not to cause any major lid assembly defects but to prevent the association of Rpn12 .
ComR, tetratricopeptide (ComR_TPR)
Type: Domain

In Gram-positive bacteria, cell-to-cell communication mainly relies on extracellular signaling peptides. ComR is a member of the RNPP family, which positively controls competence for natural DNA transformation in streptococci. It is directly activated by the binding of its associated pheromone XIP . The crystal structure analysis of ComR shows that it contains an N-terminal helix-turn-helix (HTH), DNA binding domain (DBD) and a C-terminal tetratricopeptide repeat (TPR) domain. The TPR domain is composed of 11 α-helices forming 5 TPR motifs followed by an additional C-terminal α-helix 16 called CAP. The pheromone XIP binding site is found in the TPR region. Biochemical and mutational analysis indicate that, if the interacting XIP is accepted it can then trigger the conformational change of the TPR domain to open the DBD-TPR interface to allow dimer formation that is required to bind DNA .
Methyltransferase MycE, N-terminal (MycE_N)
Type: Domain

This is the N-terminal domain found in MycE from the mycinamicin biosynthetic pathway. MycE is a tetramer of a two-domain polypeptide, comprising a C-terminal catalytic MT domain and an N-terminal auxiliary domain, which is important for quaternary assembly and for substrate binding .
Ski2, N-terminal domain (Ski2_N)
Type: Domain

This domain is the N-terminal extended region found in the Ski2 protein. Ski2 is the helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways, required for the cytoplasmic functions of the exosome, including RNA turnover, surveillance, and interference .
Ski2, Ski3, and Ski8 assemble in a tetramer with 1:1:2 stoichiometry.
Peptidoglycan GlcNAc deacetylase, N-terminal (PgdA_N)
Type: Domain

This is the N-terminal and middle domain found in Streptococcus pneumoniae peptidoglycan GlcNAc deacetylase (SpPgdA). PgdA protects the Gram-positive bacterial cell wall from host lysozymes by deacetylating peptidoglycan GlcNAc residues. It is a member of the family 4 carbohydrate esterases (CE-4) .
Tyramine--L-glutamate ligase, pre ATP-grasp domain (MfnD_preATP-grasp)
Type: Domain

This domain is found N-terminal to the ATP grasp domain (

) in tyramine--L-glutamate ligase .
Tetracyclin repressor-like, C-terminal domain 18 (TetR_C_18)
Type: Domain

TetR family regulators are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity . The TetR proteins identified in overm ultiple genera of bacteria and archaea share a common helix-turn-helix (HTH) structure in their DNA-binding domain. However, TetR proteins can work in different ways: they can bind a target operator directly to exert their effect (e.g. TetR binds Tet(A) gene to repress it in the absence of tetracycline), or they can be involved in complex regulatory cascades in which the TetR protein can either be modulated by another regulator or TetR can trigger the cellular response . TetR regulates the expression of the membrane-associated tetracycline resistance protein, TetA, which exports the tetracycline antibiotic out of the cell before it can attach to the ribosomes and inhibit protein synthesis . TetR blocks transcription from the genes encoding both TetA and TetR in the absence of antibiotic. The C-terminal domain is multi-helical and is interlocked in the homodimer with the helix-turn-helix (HTH) DNA-binding domain .

This entry represents the C-terminal domain present in TetR transcriptional regulations mostly found in proteobacteria.
EMP3/KAHRP, N-terminal (EMP3/KAHRP_N)
Type: Domain

This entry represents a domain found at the N terminus of the erythrocyte cytoskeleton-associated protein (EMP3) and the knob-associated histidine-rich protein (KAHRP). KAHRP found in protozoan parasites such as Plasmodium falciparum, is involved in both rigidifying the host cell and the formation of cytoadherent knob structures .
SpuA, C-terminal (SpuA_C)
Type: Domain

This is the C-terminal β sandwich domain found in Streptococcus pneumoniae SpuA proteins. SpuA is a large multimodular cell wall-attached enzyme involved in the degradation of glycogen .
Protein of unknown function DUF5522 (DUF5522)
Type: Family

This is a family of unknown function from Bacteria and Eukaryotes. Proteins in this entry contain 4 highly conserved cysteines.
Protein of unknown function DUF5630 (DUF5630)
Type: Family

This family of unknown function consists of proteins mostly found in Legionella.
Large polyvalent protein associated domain 28 (LPD28)
Type: Domain

This is a β strand rich domain that lacks strongly conserved polar residues . It is fast diverging and is found in polyvalent proteins of conjugative elements .
Calcium-regulated actin-bundling protein, C-terminal (F_actin_bund_C)
Type: Domain

This is the C-terminal domain found in 34kDa F actin bundling protein ABP34, a calcium regulated actin binding protein that cross links actin filaments into bundles. Residues 216-244 in the C-terminal domain are part of the strongest actin-binding sites (residue 193 residue 254) and have conserved sequences with the actin-binding regions of alpha-actinin and ABP120 .
SMODS and SLOG-associating 2TM effector domain (SLATT_4)
Type: Domain

The SLATT domain contains two transmembrane helices. SLATT domains are generally predicted to function as pore-forming effectors in a class of conflict systems which are reliant on the production of second messenger nucleotide or nucleotide derivatives. SLATT domains are predicted to initiate cell suicide responses upon their activation. This SLATT family is often coupled to the SMODS nucleotide synthetase and is sometimes further embedded in other conflict systems like CRISPR/Cas or R-M systems .
RNA helicase UPF1, 1B domain (UPF1_1B_dom)
Type: Domain

UPF1 (or regulator of nonsense transcripts 1 homologue) is an essential RNA helicase that detects mRNAs containing premature stop codons and triggers their degradation. Together with UPF2 and UPF3, forms a surveillance complex, in which UPF2 acts as a bridge between UPF1 and UPF3. UPF2 and UPF3 are nonenzymatic components of the complex that stimulate the activity of UPF1 . UPF1 has a N-terminal cysteine/histidine-rich zinc-binding domain (CH/ZBD), a regulatory 1B domain, followed by a helicase core that belongs to superfamily 1 (SF1).

This is 1B domain of UPF1 which has a regulatory role. It suffers conformational changes from an inhibitory state to a transition-state complex that modulate RNA binding .
Small RNA 2'-O-methyltransferase Hen1, La-motif C-terminal domain (Hen1_Lam_C)
Type: Domain

RNA silencing is a conserved regulatory mechanism in fungi, plants and animals that regulates gene expression and defence against viruses and transgenes. A conserved S-adenosyl-l-methionine-dependent RNA methyltransferase, HUA ENHANCER 1 (HEN1), and its homologues are responsible for 2'-O-methylation on the 3' terminal nucleotide of microRNAs and small interfering RNAs (siRNAs). The 2'-O-methylation protects miRNAs and siRNAs from 3'-end uridylation and 3'-to-5' exonuclease-mediated degradation. This domain lies on the C-terminal region of the La-motif domain found in HEN1 .
Activity-regulated cytoskeleton-associated protein, C-terminal domain (Arc_C)
Type: Domain

This entry represents the C-terminal capsid-like domain of the Activity-regulated cytoskeleton-associated protein (Arc). The Arc protein modulates the trafficking of AMPA-type glutamate receptors . The tertiary structure of this two-lobe capsid domain is similar to the capsid domain of HIV gag protein. The domain is thought to have evolved from the capsid domain of Ty3/Gypsy retrotransposon .
Nas2, N-terminal (Nas2_N)
Type: Domain

This entry represents the N-terminal domain of Nas2, which is a proteosome assembly chaperone. Nas2 bivalently binds the proteasome Rpt5 subunit. The Nas2 N-terminal helical domain masks the Rpt1-interacting surface of Rpt5 .
STY4199-like HEPN domain (STY4199_HEPN_dom)
Type: Domain

STY4199-like HEPN nuclease domain .
Leukemia inhibitory factor receptor, D2 domain (LIFR_D2)
Type: Domain

This is the D2 domain in cytokine-binding module 1 (CBM1) found in Leukemia inhibitory factor receptor (LIFR) and OSM receptors (OSMR). LIFR has an extracellular region with a modular structure containing two cytokine-binding modules (CBM) separated by an Ig-like domain and followed by three membrane-proximal fibronectin type-III (FNIII) domains. The D2 domain in CBM1 shows structural similarity to the corresponding CBM domains of both gp130 and IL-6Ralpha because it contains conserved structural features like the WSXWS motif . The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation .
Tsi6 (Tsi6)
Type: Domain

Tsi6 inhibits the NADase activity of Tse6, an integral membrane toxin from Pseudomonas aeruginosa. The Tsi6 immunity protein adopts an all-α-helical fold that binds to a surface of Tse6 .
Rolling Circle replication initiation protein, N-terminal (Rol_Rep_N)
Type: Domain

This is the N-terminal domain of the Rolling Circle Replication Initiator Protein (Rep) from Geobacillus stearothermophilus. This protein acts on plasmids from family pT181 to initiate replication, recruit a helicase to the site of initiation and terminate replication after DNA synthesis. These proteins possess a unique active site and a catalytically essential metal ion is bound in a distinct manner from other rolling circle Reps .
Secreted Novel AID/APOBEC-like Deaminase 3 (SNAD3)
Type: Family

This is a family of AID/APOBEC like deaminases found in vertebrates that were derived from secreted versions of the family .
Testis-specific protein LINC02914-like (LINC02914-like)
Type: Family

LINC02914 may play a role in the flagellum biology.
Swi6, N-terminal (Swi6_N)
Type: Domain

This is a putative DNA binding domain found in Swi6, which is part of a complex involved in cell-cycle-dependent transcription . This domain comprises four α helices and five β strands arranged in a mixed α/β fold .
Large polyvalent protein-associated domain 14 (LPD14)
Type: Domain

This is an α-helical domain with a conserved glutamate residue that is mainly found in polyvalent proteins of prophages .
Large polyvalent protein-associated domain 3 (LPD3)
Type: Domain

This domain is predicted to adopt an α and β fold . The secondary structure arrangement suggests it to be a member of the BECR fold . The domain is found in polyvalent proteins of both conjugative elements and phages/prophages.
FKBP26, C-terminal (FKBP26_C)
Type: Domain

This is the C-terminal domain (CTD) of Methanocaldococcus jannaschii peptidyl-prolyl cis/trans isomerase FKBP26. FKBP26 mediates protein folding. CTD has an α/β-sandwich structure composed of three α-helices and a three-stranded, mixed-orientation β-sheet. The CTD domain is responsible for dimerization of FKBP26 by through inter-subunit antiparallel pairing of the third β-strands of the two CTDs. The CTD dimer forms a continuous, six-stranded mixed β-sheet .
LA2681-like HEPN domain (HEPN_LA2681)
Type: Domain

LA2681-like HEPN nuclease .
Arcadin 1 (Arcadin_1)
Type: Domain

Arcadin-1 is encoded by arcade gene cluster which also encodes cernactin. Crenactin is a filament-forming protein from the crenarchaeon Pyrobaculum calidifontis which shows exceptional similarity to eukaryotic F-actin. Arcadin-1 on the other hand does not seem to be related to any known eukaryotic actin binding proteins nor does it affect crenactin polymerisation .