SII-SWORD/CoKE huggingface dataset:
TERF2-interacting telomeric protein 1, Myb domain (TERF2IP_Myb)
Type: Domain

TERF2-interacting telomeric protein 1 (TERF2IP) is the homologous of Rap1 from yeast (not included in this entry). These proteins are involved in the regulation of telomere length, clustering and has a specific role in telomere position effect (TPE) . TERF2IP is required for repression of homology-directed repair (HDR) .

This domain adopts a canonical three-helix bundle tertiary structure, with the second and third helices forming a helix-turn-helix variant motif. The function is unclear but it may either interact with DNA via an adaptor protein or it may be only involved in protein-protein interactions .
Threonyl-tRNA synthetase, editing domain, archaea (Threonyl-tRNA_syn_edit_dom_arc)
Type: Domain

Archaea-specific editing domain of threonyl-tRNA synthetase, with marked structural similarity to D-amino acids deacylases found in eubacteria and eukaryotes. This domain can bind D-amino acids, and ensures high fidelity during translation. It is especially responsible for removing incorrectly attached serine from tRNA-Thr. The domain forms a fold that can be defined as two layers of β-sheets (a three-stranded sheet and a five-stranded sheet), with two α-helices located adjacent to the five-stranded sheet .
Phenylalanine zipper (Phe_ZIP)
Type: Domain

The phenylalanine zipper consists of aromatic side chains from ten phenylalanine residues that are stacked within a hydrophobic core. This zipper mediates dimerisation of various proteins, such as APS, SH2-B and Lnk .
Transforming growth factor beta receptor 2 ectodomain (Transforming_GF_b_rcpt_2_ecto)
Type: Domain

The Transforming growth factor beta receptor 2 ectodomain is a compact fold consisting of nine β-strands and a single helix stabilised by a network of six intra strand disulphide bonds. The folding topology includes a central five-stranded antiparallel β-sheet, eight-residues long at its centre, covered by a second layer consisting of two segments of two-stranded antiparallel β-sheets (beta1-beta4, beta3-beta9) .
PhoQ Sensor domain (PhoQ_Sensor)
Type: Domain

The PhoQ Sensor is required for the virulence of various Gram-negative bacteria by allowing interaction of PhoPQ with the intracellular membrane, resulting in remodelling of the bacterial cell surface and subsequent bacterial resistance to host antimicrobial peptides. The domain contains a major flat acidic surface, which binds to at least 3 calcium ions, neutralising the domain's negative charge and allowing interaction with the negatively charged membrane . This domain recognises divalent metal cations and antimicrobial cationic peptides (Matilla et. el., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
F-actin binding (F-actin-binding)
Type: Domain

The F-actin binding domain forms a compact bundle of four antiparallel α-helices, which are arranged in a left-handed topology. Binding of F-actin to the F-actin binding domain may result in cytoplasmic retention and subcellular distribution of the protein, as well as possible inhibition of protein function . Proteins containing this domain include tyrosine-protein kinases Abl1, which is a non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis . Abl1 is linked to different forms of leukemia in humans.
Splicing factor 3B subunit 1 (SF3b_su1)
Type: Domain

This group of proteins consists of several eukaryotic splicing factor 3B subunit 1 proteins, which associate with p14 through a C terminus β-strand that interacts with beta-3 of the p14 RNA recognition motif (RRM) β-sheet, which is in turn connected to an α-helix by a loop that makes extensive contacts with both the shorter C-terminal helix and RRM of p14. This subunit is required for 'A' splicing complex assembly (formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA) and 'E' splicing complex assembly .
Protein of unknown function DUF1904 (DUF1904)
Type: Family

This entry represents a family of hypothetical bacterial proteins.
Protein of unknown function DUF1905 (DUF1905)
Type: Family

This family consist of hypothetical bacterial proteins.
Ragulator complex protein LAMTOR3 (LAMTOR3)
Type: Family

Ragulator complex protein LAMTOR3 (for lysosomal adaptor and MAPK and MTOR activator 3) is a regulator of the TOR pathway, which is a signalling cascade that promotes cell growth in response to growth factors, energy levels, and amino acids .
Rv2525c-like, glycoside hydrolase-like domain (Rv2525c-like_Glyco_Hydro-like)
Type: Domain

This domain is found in uncharacterised bacterial proteins, including the putative peptidoglycan hydrolase Rv2525c from Mycobacterium tuberculosis . Rv2525c may function as a peptidoglycan hydrolase with glycosidase activity as this domain has a typical TIM barrel-like fold characteristic of glycoside hydrolases . However, it displays esterase activity toward p-nitrophenyl esters of various acyl chain length in vitro . This domain is also found in BacA

from E. faecalis, which has a significant degree of homology to YbfG. BacA together with BacL1 are cell wall lytic enzymes .
Ester hydrolase C11orf54, Domain of unknown function DUF1907 (C11orf54_DUF1907)
Type: Domain

This entry represents a domain found in Ester hydrolase C11orf54 (also known as PTD012) and similar proteins predominantly found in animals and fungi. The structure of this domain displays an α-β-β-α four layer topology, with an HxHxxxxxxxxxH motif that coordinates a zinc ion, and an acetate anion at a site that likely supports the enzymatic activity of an ester hydrolase .
Microtubule-associated serine/threonine-protein kinase, pre-PK domain (MAST_pre-PK_dom)
Type: Domain

This domain is found at the N-terminal of microtubule-associated serine/threonine-protein kinases, which is followed by the kinase domain.
PoNi, N-terminal (PoNi_N)
Type: Domain

This entry represents the N-terminal domain of the PoNe immunity proteins (PoNi), which antagonise the DNAse toxin PoNe (Polymorphic Nuclease effector) . PoNi proteins may directly interact with PoNe.
PoNi, C-terminal (PoNi_C)
Type: Domain

This entry represents the C-terminal domain of the PoNe immunity proteins (PoNi) which antagonise the DNAse toxin PoNe (Polymorphic Nuclease effector) . PoNi proteins may directly interact with PoNe .
Protein of unknown function DUF1912 (DUF1912)
Type: Family

This protein has no known function. It is found in various Streptococcal proteins.
Receptor-binding protein of phage tail base-plate Siphoviridae, head (Caudo_bapla_RBP)
Type: Domain

This domain (caudo_bapla_RBP) can be found in a family of proteins expressed from ORF18 of the Lactococcus P2-like phage. This is one of three protein species, shoulders, neck, and head, that form the phage tail base-plate. In the overall structure this head domain exists as six trimers, and is necessary for specific recognition of the receptors at the host cell surface. Siphoviridae are the P2-like Caudovirales of Lactococcus .
Monodechloroaminopyrrolnitrin synthase PrnB (PrnB)
Type: Family

This protein family includes Monodechloroaminopyrrolnitrin synthase PrnB from Pseudomonas fluorescens and similar bacterial proteins. PrnB is involved in the biosynthesis of the antifungal compound pyrrolnitrin. It is organised into two domains: a small N-terminal capping domain that consists of 7 α-helices and the core helical domain, which is related to myoglobin. PrnB shows structural homology to the heme b-dependent two-domain indoleamine 2,3-dioxygenase enzyme (IDO) and to the tryptophan 2,3-dioxygenase (TDO) family .
Retinoblastoma-associated protein, C-terminal (RB_C)
Type: Domain

The RB C-terminal domain is required for high-affinity binding to E2F-DP complexes and for maximal repression of E2F-responsive promoters, thereby acting as a growth suppressor by blocking the G1-S transition of the cell cycle. This domain has a strand-loop-helix structure, which directly interacts with both E2F1 and DP1, followed by a tail segment that lacks regular secondary structure .
Capsid protein VP4, Picornavirus (Capsid_VP4_Picornavir)
Type: Domain

This entry represents the VP4 coat protein found in Picornaviruses, small RNA-containing mammalian viruses such as Foot-and-mouth disease virus (FMDV) , Mengo encephalomyocarditis virus and Theiler's murine encephalomyelitis virus (strain DA) (TMEV) .
Thoeris protein ThsB, TIR-like domain (ThsB__TIR-like_domain)
Type: Domain

This is the TIR-like domain of ThsB proteins, which adopts a Rossmann-like fold . ThsB is responsible for recognizing phage infection .

Thoeris is a bacterial antiphage defense system, which consists of two genes, thsA and thsB, via NAD+ degradation . ThsA has robust NAD+ cleavage activity and a two-domain architecture containing an N-terminal NAD-binding domain (denoted as sirtuin-like or Macro) and C-terminal SLOG-like domain. In some instances, such as in B. amyloliquefaciens, ThsA has an N-terminal transmembrane domain . ThsB (also referred to as TIR1 and TIR2) is structurally similar to TIR domain proteins but without enzymatic activity.
HBS1-like protein, N-terminal (HBS1-like_N)
Type: Domain

This domain is found at the N terminus of HBS1 proteins. It interacts with the ribosomal protein rpS3 at the mRNA entry site .
Basophilic leukemia-expressed protein Bles03-like (Bles03)
Type: Family

This family includes Basophilic leukemia-expressed protein Bles03 (also known as UPF0696 protein C11orf68,

) and various uncharacterised proteins of unknown function from eukaryotes, bacteria and archaea. Bles03 shows a two-layer sandwich architecture with a a nine-stranded β-sheet, three α-helices on each side and one solvent-exposed amino-terminal α-helix . This protein has been suggested to have phosphothreonine lyase activity and to play a role in the biosynthesis of dehydro amino acids .
Domain of unknown function DUF1918 (DUF1918)
Type: Domain

This domain is found in various hypothetical bacterial proteins, and has no known function. It adopts SH3-like β-barrel with an additional C-terminal α-helix that packs on one side of the barrel .
E3 ubiquitin-protein ligase NRDP1 (NRDP1)
Type: Domain

NRDP1 acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins .
Protein of unknown function DUF1919 (DUF1919)
Type: Family

This protein has no known function. It is found in various hypothetical and putative bacterial proteins.
Glutarate 2-hydroxylase GlaH (GlaH)
Type: Family

GlaH (also known as CsiD) acts as an alpha-ketoglutarate-dependent dioxygenase catalyzing hydroxylation of glutarate (GA) to L-2-hydroxyglutarate (L2HG) in the stationary phase of E.coli. It functions in a L-lysine degradation pathway that proceeds via cadaverine, glutarate and L-2-hydroxyglutarate. Other dicarboxylic acids (oxalate, malonate, succinate, adipate, and pimelate) are not substrates for this enzyme .
Neutrophil cytosol factor 1, C-terminal (NCF1_C)
Type: Domain

NCF1 (also known as NADPH oxidase subunit p47Phox) is one of the cytosolic regulatory components of NADPH oxidase and consists of a PX domain at the N-terminal, two tandem SH3 domains, a polybasic or autoinhibitory region (PBR/AIR, an arginine/lysine rich region) and a proline-rich region at the C-terminal. In the resting state, the SH3 domains of NCF1 are masked by an intramolecular interaction with the PBR/AIR, which maintains the enzyme in an inactive form . This entry represents the C-terminal domain which contains conserved PxxP motifs that allow binding to SH3 domains, with subsequent activation of the NADPH oxidase, and generation of superoxide, which plays a crucial role in host defence against microbial infection .
Bcl-x interacting, BH3 domain (Bcl-x_interacting_BH3_dom)
Type: Domain

This domain is a long α helix, required for interaction with Bcl-x. It is found in BAM, Bim and Bcl2-like protein 11 . This domain is also known as the BH3 domain between residues 146 and 161.
Osmosensory transporter coiled coil (Osmo_CC)
Type: Domain

The osmosensory transporter coiled coil is a C-terminal domain found in various bacterial osmoprotective transporters, such as ProP, Proline/betaine transporter, Proline permease 2 and the citrate proton symporters. It adopts an antiparallel coiled-coil structure, and is essential for osmosensory and osmoprotectant transporter function .
BPS (Between PH and SH2) domain (BPS-dom)
Type: Domain

The BPS (Between PH and SH2) domain, comprised of 2 β strands and a C-terminal helix, is an approximately 45 residue region found in the adaptor proteins Grb7/10/14 that mediates inhibition of the tyrosine kinase domain of the insulin receptor by binding of the N-terminal portion of the BPS domain to the substrate peptide groove of the kinase, acting as a pseudosubstrate inhibitor .
Bacteriophage PRD1, P5, spike N-terminal (Phage_PRD1_P5_spike_N)
Type: Domain

The spike structure of bacteriophage PRD1 is comprised of proteins P2, P5, and P31. P5 is an elongated multidomain trimer. The C-terminal fragment of P5 appears to contain the residues responsible for the trimerization of the protein, whereas the smaller N-terminal part mediates the interaction with protein P31 .

This domain is found at the N terminus of bacteriophage PRD1 spike protein P5.
Bacteriophage PRD1, spike protein P5, C-terminal (Phage_PRD1_P5_C)
Type: Domain

This domain is found at the C terminus of bacteriophage PRD1 spike protein P5.

The spike structure of bacteriophage PRD1 is comprised of proteins P2, P5, and P31. P5 is an elongated multidomain trimer. The C-terminal fragment of P5 appears to contain the residues responsible for the trimerization of the protein, whereas the smaller N-terminal part mediates the interaction with protein P31 .
Mannosyltransferase/phosphorylase 1-like, Leishmania (MPT-1-like_LmxM)
Type: Family

This entry represents a group of proteins predominantly found in bacteria and in the eukaryote Leishmania, including a dual-activity mannosyltransferase/phosphorylases MTP-1 from Leishmania mexicana (

). MTPs catalyse both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. These proteins are structurally related to bacterial mannan phosphorylases .
Lactococcin-A immunity protein-like (LciA_Immunity-like)
Type: Family

Gram-positive lactobacilli produce bacteriocins to kill closely-related competitor species . To protect themselves from the bactericidal activity of this molecule they co-express an immunity protein. This entry represents Lactococcin-A immunity protein from Lactococcus lactis and similar proteins predominantly found in the bacterial class Bacilli.
Synaptojanin-1/2, RNA recognition motif (SYNJ1/2_RRM)
Type: Domain

This domain represents the RNA recognition motif found in Synaptojanin proteins.

Synaptojanins are phosphoinositide phosphatases known to play an important role in vesicle recycling by promoting the uncoating of clathrin following synaptic vesicle uptake . Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p , a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2 . Synaptojanin-2 is a ubiquitously expressed central regulatory enzyme in the phosphoinositide-signaling cascade . As a novel Rac1 effector regulating an early step of clathrin-mediated endocytosis, synaptojanin-2 acts as a polyphosphoinositide phosphatase, directly and specifically interacting with Rac1 in a GTP-dependent manner. Synaptojanin-2 shows high sequence homology to the N-terminal Sac1p homology domain , the central inositol 5-phosphatase domain, and the putative RNA recognition motif (RRM) of synaptojanin-1, but differs in the proline-rich region.
Domain of unknown function DUF1899 (DUF1899)
Type: Domain

Coronins are evoluntionarily conserved proteins, mainly involved in actin cytoskeleton organisation.
Typically Coronins contain a DUF1899 domain, a series of WD40 repeats, a DUF1900 domain (

) and a C-terminal coiled-coil domain .
Trimerisation motif (Trimer_CC)
Type: Domain

This domain is predominantly found in the structural protein coronin, and is duplicated in some sequences. It appears to have the function of stabilising the topology of short coiled-coils in proteins .

Coronins are evoluntionarily conserved proteins, mainly involved in actin cytoskeleton organisation .
Bypass of forespore C, C-terminal (BofC_C)
Type: Domain

BofC (bypass of forespore C) protein acts negatively on inter-compartmental signalling of pro-sigma(K) processing in the sigma(K)-checkpoint of Bacillus subtilis. This is achieved through its interaction with SpoIV inhibiting autoproteolysis of the latter which leads to a delay in proteolytic cleavage of pro-sigma(K) . BofC is a monomer made up of two domains, an N-terminal and a C-terminal domain.
Protein YoaG (YoaG)
Type: Family

This entry represents a group of uncharacterised bacterial proteins.
Protein of unknown function DUF1871 (DUF1871)
Type: Family

This set of hypothetical proteins is produced by prokaryotes pertaining to the Bacillus genus.
STIV B116-like (STIV_B116-like)
Type: Family

The sulfolobus turreted icosahedral virus (STIV) infects Sulfolobus species found in the hot springs of Yellowstone National Park. It has 37 ORFs including B116, whose function is unknown. The structure of B116 reveals a fold consisting of a five-stranded β-sheet flanked on one side by three α helices. Two subunits come together to form a homodimer with a 10-stranded mixed β-sheet, where the topology of the central strands resembles an unclosed β-barrel .
Nuclear receptor-binding factor 2, C-terminal (NRBF2_C)
Type: Domain

Nuclear receptor-binding factor 2 (NRBF2) plays an essential role in autophagy, the cellular pathway that degrades long-lived proteins and other cytoplasmic contents through lysosomes. NRBF2 binds Atg14L - a Beclin-binding protein - directly via the MIT domain and enhances Atg14L-linked Vps34 kinase (a class III phosphatidylinositol-3 kinase) activity and autophagy induction .

This entry represents the C-terminal domain of NRBF2.
Rv2632c-like (Rv2632c-like)
Type: Family

This entry includes a set of Actinobacterial proteins, including Rv2632c from Mycobacterium tuberculosis that is strongly implicated in the onset of non-replicating persistence, and thereby latent tuberculosis. Rv2632c contains a dsRBD-like (2 layers α/β) fold (PDBe:2fgg). It shares remarkable similarity with bacterial hibernation factors, despite very low sequence similarity. Based on this structure it was predicted that Rv1738, highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome .
Protein of unknown function DUF1878 (DUF1878)
Type: Family

This family consist of hypothetical bacterial proteins.
Calcium-dependent cell adhesion molecule, N-terminal (Ca_cell_adhesion_N_dom)
Type: Domain

This entry represents the N-terminal domain of the calcium-dependent cell adhesion molecule 1 (CAD-1) from Dictyostelium. CAD-1 mediates calcium-dependent cell-cell adhesion during the early stage of development . This domain is also found in Spherulin-3A protein from Physarum polycephalum .
Aca2/YdiL-like (Aca2_YdiL-like)
Type: Family

This family includes Aca2 repressor from Pectobacterium phage ZF40, the uncharacterised protein YdiL from Escherichia coli and similar sequences found in tailed bacteriophages, proteobacteria and actinomycetes. Aca2 regulates the transcription and translation of phage anti-CRISPR acrIF8 gene through DNA binding to 2 inverted repeats in the promoter region and translationally by binding conserved RNA stem-loops on mRNAs thereby blocking ribosome access . This protein contains six α-helices and two parallel β-strands . The function of YdiL, which is predicted to adopt a very similar structure, is still unknown.
Domain of unknown function DUF1882 (DUF1882)
Type: Domain

This domain is found in a set of hypothetical bacterial proteins.
Protein of unknown function DUF1885 (DUF1885)
Type: Family

This family consists of hypothetical proteins produced by Bacilli.
USP8 dimerisation domain (USP8_dimer)
Type: Domain

This domain is found in the amino terminal region of Ubiquitin carboxyl-terminal hydrolase 8 (USP8). It forms a five helical bundle that dimerises . It is also found in other proteins, including AMSH-like protease and STAM-binding protein.
Sporulation inhibitor A (Sda)
Type: Family

Members of this protein group contain two antiparallel α helices that are linked by a highly structured inter-helix loop to form a helical hairpin; the structure is stabilised by numerous hydrophobic and electrostatic interactions. These sporulation inhibitors are antikinases that bind to the histidine kinase KinA phosphotransfer domain and act as a molecular barricade that inhibit productive interaction between the ATP binding site and the phosphorylatable KinA His residue. This results in the inhibition of sporulation (by preventing phosphorylation of spo0A) .
Surface composition regulator (GlgS)
Type: Family

GlgS (surface composition regulator) is a major determinant of cell surface composition. It negatively regulates motility, adhesion and synthesis of biofilm exopolysaccharides in Escherichia coli . The structure of the polypeptide chain comprises a bundle of two parallel amphipathic helices, α1 and α3, and a short hydrophobic helix α2 sandwiched between them .
Domain of unknown function DUF1902 (DUF1902)
Type: Domain

These prokaryotic proteins adopt a fold consisting of one α-helix and four β-strands, as described for TTHA1013 from Thermus thermophilus HB8. Their function has not, as yet, been elucidated .
Protein of unknown function DUF1893, TM1506-like (DUF1893_TM1506-like)
Type: Family

This group of functionally uncharacterised bacterial proteins includes TM1506 from Thermotoga maritima (

), which has a cytidine deaminase-like fold. It binds an unknown ligand in the crystal structure. The protein is ADP-ribosylated at a conserved aspartate .
Protein of unknown function DUF1877 (DUF1877)
Type: Family

This entry represents Protein YfbM from Escherichia coli (strain K12) and similar proteins mainly found in bacteria. The structure of YfbM has been solved, showing α/β/α layers with an antiparallel β-sheet. Although this protein is been suggested to be a binding site for peptide nucleic acids (PNAs, species-selective antibacterials, ), its function is yet to be characterised.
2H-phosphodiesterase-like, Domain of unknown function DUF1868 (2H-PEstase_DUF1868)
Type: Domain

This presumed domain is found in a group of 2H-phosphodiesterases predominantly from bacteria. Its presence in a large eukaryotic DNA virus represents a potential case of horizontal transfer from a bacterial source into a virus. Several proteins of bacterial origin have been noticed in the insect viruses and these appear to have been acquired from endo-symbiotic or parasitic bacteria that share the same host cells with the viruses. Presence of 2H proteins in the proteomes of large DNA viruses (e.g. T4 57B protein and the Fowl-pox virus FPV025) may point to some role for these proteins in regulating the viral tRNA metabolism .
DJBP, EF-hand domain (EF_hand_DJBP)
Type: Domain

This domain is found in DJ binding protein DJBP.

This domain is found in DJ binding protein DJBP. DJBP or EF-hand calcium-binding domain-containing protein 6 is a DJ-1-binding protein that negatively regulates the androgen receptor by recruiting the histone deacetylase complex. Protein DJ-1 antagonises this inhibition by abrogation of this complex .