SII-SWORD/CoKE huggingface dataset:
Aminomethyltransferase-like (GcvT/YgfZ/DmdA)
Type: Family

This entry represents aminomethyltransferases proteins including GcvT, YgfZ and DmdA.

Dimethlysulfonioproprionate (DMS) is catabolised in marine bacterioplankton through a pathway in which the initial step involves demethylation to methylmercaptopropionate (MMPA), which is then further catabolised to methane thiol and acetate. The enzyme responsible for the first step is dimethylsulfonioproprionate demethylase DmdA . The overall fold of DmdA is not similar to other enzymes that typically utilise the cofactor tetrahydrofolate (THF). Instead DmdA has a triple domain structure similar to that observed in GcvT .

The glycine cleavage multienzyme complex (GCV) catalyses the catabolism of glycine in eukaryotes. GcvT (aminomethyltransferase,

) is a folate-dependent enzyme that catalyses the release of ammonia and the transfer of the methylene carbon unit (C1 unit) to tetrahydrofolate (H4folate) from the aminomethyl intermediate attached to the lipoate cofactor of H-protein . GCV is found in bacteria and the mitochondria of eukaryotes. Mutations in the human GcvT gene are known to cause nonketotic hyperglycinemia .

YgfZ is a conserved bacterial protein that plays a crucial role in iron-sulphur cluster metabolism by facilitating the repair of damaged [Fe-S] clusters through folate-dependent mechanisms. While structurally homologous to glycine cleavage T-proteins (GcvT), YgfZ has evolved distinct functionality despite maintaining the characteristic folate-binding domain. Both proteins bind tetrahydrofolate derivatives, but where GcvT participates in glycine catabolism by transferring methylene groups to tetrahydrofolate, YgfZ instead uses its folate-binding capabilities to support cellular processes protecting iron-sulphur clusters from oxidative damage .
Tox-HDC domain (Tox-HDC_dom)
Type: Family

This entry represents a predicted α/β fold peptidase domain with a strongly conserved triad of a histidine, aspartate/asparagine and cysteine residues that are predicted to comprise the active site of the predicted peptidase. Proteins bearing this predicted toxin domain are particularly common in both intracellular and extracellular pathogens .
Tox-WTIP domain (Tox-WTIP_dom)
Type: Domain

This entry represents a predicted toxin domain with two membrane spanning α helices and RxxR, Wx[ST]IP motifs. The domain is present in bacterial polymorphic toxin systems. The toxin is usually exported by the type 2 or Photorhabdus virulence cassette (PVC)-type secretion system .
Tox-URI2 domain (Tox-URI2_dom)
Type: Domain

This entry represents a predicted URI nuclease fold present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2 or type 6 secretion system .
Tox-SHH domain (Tox-SHH_dom)
Type: Domain

This entry represents the HNH/Endonuclease VII fold present in bacterial polymorphic toxin systems with two conserved histidine residues. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 5, type 6 or type 7 secretion system .
Tox-SGS domain (Tox-SGS_dom)
Type: Domain

This entry represents an α+β fold domain with four conserved cysteine residues and a conserved [DE}xx[ND] motif. This domain is mainly present at the C terminus of RHS repeats containing proteins in insects and crustaceans. Although no bacterial homologues have been identified, the domain architecture suggests an origin from bacterial polymorphic toxin systems .
Tox-REase-9 domain (Tox-REase-9_dom)
Type: Domain

This entry represents a restriction endonuclease fold present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2 or type 7 secretion system .
Tox-REase-7 domain (Tox-REase-7_dom)
Type: Domain

This entry represents a restriction endonuclease fold present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 5, type 6, or type 7 secretion system .
Tox-REase-5 domain (Tox-REase-5_dom)
Type: Domain

This entry represents a restriction endonuclease fold present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 5, type 6, or PrsW-peptidase dependent secretion system. Versions of this domain are also found in caudoviruses .
Tox-REase-3 domain (Tox-REase-3_dom)
Type: Domain

This entry represents a restriction endonuclease fold present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 6, type 7 or PrsW-peptidase dependent secretion system .
Tox-REase-2 domain (Tox-REase-2_dom)
Type: Domain

This entry represents a restriction endonuclease fold present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 7 or PrsW-peptidase dependent secretion system .
Tox-PLDMTX domain (Tox-PLDMTX_dom)
Type: Domain

This entry represents a papain fold toxin domain found in bacterial polymorphic toxin systems .
Tox-PL domain (Tox-PL_dom)
Type: Domain

This entry represents a papain fold toxin domain found in bacterial polymorphic toxin systems. In these systems they might function either as a releasing peptidase or toxin .
Large ribosomal subunit protein bL21-like (bL21-like)
Type: Family

This entry represents large ribosomal subunit protein bL21 (previously known as L21) that is found in bacteria and eukaryotic organelles such as chloroplast and mitochondria. This entry also includes the S. pombe Aco2 protein, a fusion of mitochondrial ribosomal protein bL21m (Mrpl49) and aconitase that has essential function in mitochondrial translation in fission yeast. bL21 consists of a small β-barrel-like domain that is connected to an extended loop .

In Escherichia coli, bL21 is known to bind to the 23S rRNA in the presence of bL20. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:

Bacterial bL21 (old name L21).

Marchantia polymorpha chloroplast bL21 (old name L21).

Plant chloroplast bL21 (old name L21, nuclear-encoded).

Bacterial bL21 is a protein of about 100 amino-acid residues, the mature form of the spinach chloroplast L21 has 200 residues.
Tox-PL-2 domain (Tox-PL-2_dom)
Type: Domain

A papain fold toxin domain found in bacterial polymorphic toxin systems .
Tox-MPTase5 domain (Tox-MPTase5_dom)
Type: Domain

This entry represents a zincin-like metallopeptidase domain found in bacterial polymorphic toxin systems .
Tox-MPTase4 domain (Tox-MPTase4_dom)
Type: Domain

A zincin-like metallopeptidase domain found in bacterial polymorphic toxin systems .
Tox-MPTase3 domain (Tox-MPTase3_dom)
Type: Domain

This entry represents a zincin-like metallopeptidase domain found in bacterial polymorphic toxin systems .
Tox-MPTase2 domain (Tox-MPTase2_dom)
Type: Domain

This entry represents a zincin-like metallopeptidase domain found in bacterial polymorphic toxin systems .
Tox-HNH-HHH domain (Tox-HNH-HHH_dom)
Type: Domain

This entry represents the HNH/Endonuclease VII fold present in bacterial polymorphic toxin systems with characteristic conserved s[GD]xxR and HHH motifs. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 5, type 6, type 7 or Photorhabdus virulence cassette (PVC)-type secretion system .
Tox-GHH domain (Tox-GHH_dom)
Type: Domain

This entry represents the HNH/Endonuclease VII fold present in bacterial polymorphic toxin systems with a characteristic sG[HQ]H signature motif. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 6, type 7 or TcdB/TcaC-type secretion system .

In animals, an inactive version of the GHH domain can be found in the C-terminal of teneurin and Odd Oz proteins .
Tox-GHH2 domain (Tox-GHH2_domain)
Type: Domain

This entry represents the HNH/Endonuclease VII fold present in bacterial polymorphic toxin systems with a characteristic s[AGP]HH signature motif. In bacterial polymorphic toxin systems, the toxin is exported by the type 2 or type secretion system .
Tox-ART-HYE1 domain (Tox-ART-HYE1_dom)
Type: Domain

This entry represents a domain containing characteristic histidine, tyrosine and glutamate residues that comprise the active site . It is found in a predicted toxin of the ADP-ribosyltransferase superfamily present in bacterial polymorphic toxin systems .
Viral movement protein (Viral_movement)
Type: Family

This family includes a variety of movement proteins (MP)s. The MP is necessary for the initial cell-to-cell movement during the early stages of a viral infection. This movement is active, and it is known that the MP interacts with the plasmodesmata and possesses the ability to bind to RNA to achieve its role . It has been suggested in cauliflower mosaic virus that these proteins mediated viral movement by modifying plasmodesmata and forming tubules in the channel that can accommodate the virus particles . The family contains a conserved DXR motif that is probably functionally important.
Tox-ART-HYD1 domain (Tox-ART-HYD1_dom)
Type: Domain

This entry represents a domain that has characteristic histidine, tyrosine and aspartate residues that comprise the active site. It is found in a predicted toxin of the ADP-ribosyltransferase superfamily present in bacterial polymorphic toxin systems. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 6, or type 7 secretion system .
NTF2 fold domain (NTF2_fold_dom)
Type: Domain

This entry represents the NTF2 fold domain. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-NucA family . This domain is also fused to ankyrin repeats and an uncharacterised domain (

).
SAICAR synthetase/ADE2, N-terminal (SAICAR_synt/ADE2_N)
Type: Domain

Phosphoribosylaminoimidazole-succinocarboxamide synthase (

) (SAICAR synthetase) catalyses the seventh step in the
de novo
purine biosynthetic pathway; the ATP-dependent conversion of 5'-phosphoribosyl-5-aminoimidazole-4-carboxylic acid and aspartic acid to SAICAR .

This domain can be found in SAICAR synthetases as a monofunctional protein from the bacteria (purC), fungi (ADE1) and plants (Pur7). In animals, this domain can be found at the N-terminal of a multifunctional enzyme (ADE2) possessing both the SAICAR synthetase and the phosphoribosylaminoimidazole carboxylase (AIR carboxylase) activity.
Permuted single zf-CXXC unit (Perm-CXXC)
Type: Domain

This is a permuted version of a single unit of the zf-CXXC domain that is detected in the Demeter-like proteins and ROS1 (REPRESSOR OF SILENCING 1) from plants . Demeter and ROS1 proteins catalyse the release of 5-methylcytosine (5-meC) from DNA by a glycosylase/lyase mechanism . Structural comparisons show that the mono-CXXC is homologous to the structural-zinc binding domain of medium chain dehydrogenases . The classical zf-CXXC domain binds nonmethyl-CpG dinucleotides.
Demeter, RRM-fold domain (RRM_DME)
Type: Domain

This is a predicted RRM-fold domain present at the C terminus of Demeter-like glycoslyases . These proteins are involved in DNA demethylation in plants where they catalyse removal of the 5mC base and subsequently cleave the backbone through lyase activity. Orthologues of Demeter are present in plants and stramenopiles. The RRM fold domain is predicted to facilitate interaction of the catalytic domain with ssDNA or regulatory RNA .
CEP76, C2 domain (CEP76-C2)
Type: Domain

A C2 domain is usually involved in targeting proteins to cell membranes. This entry represents a C2 domain found in the CEP76 proteins . CEP76 is a centrosomal protein involved in regulation of centriole duplication .
Mannose-6-phosphate receptor (Man-6-P_rcpt)
Type: Family

This family includes both cation-dependent and cation independent mannose-6-phosphate receptors .
CC2D2A, N-terminal, C2 domain (CC2D2AN-C2)
Type: Domain

A C2 domain is usually involved in targeting proteins to cell membranes. Ciliary CC2D2A protein has two C2 domains and an inactive transglutaminase-like peptidase domain (CC2D2A-TGL) . This entry represents the first C2 domain.
Mif2, N-terminal (Mif2_N)
Type: Domain

Budding yeast Mif2 and fission yeast Cnp3 are homologous to human centromere constitutive-associated network (CCAN) subunit CENP-C. This entry represents the N-terminal of Mif2. Mif2 is required for mitotic spindle integrity during anaphase spindle elongation .
Cancer/testis antigen 47 (CT47)
Type: Family

CT47 is a family of proteins found in mammals. Proteins in this family are typically between 262 and 291 amino acids in length. There is a conserved HIL sequence motif. In humans, CT47 is expressed in the testis and in certain types of cancer, but not in non-malignant somatic tissue . The function of this family is not known.
CENP-C, middle DNMT3B-binding domain (CENP-C_mid)
Type: Domain

CENP-C is a component of the centromere assembly complex in eukaryotes. CENP-C recruits the DNA methyltransferases DNMT3B, in order to establish the necessary epigenetic DNA-methylation essential for maintenance of chromatin structure and genomic stability. This entry represents the middle DNMT3B binding region of CENP-C. Binding of CENP-C and DNMT3B to DNA occurs at both centromeric and peri-centromeric satellite repeats. CENP-C and DNMT3B regulate the histone code in these regions .
TerB-C domain (TerB-C)
Type: Domain

The ter gene products constitute chemical stress response and anti-viral defense systems of bacteria.

TerB-C occurs in the C terminus of TerB in TerB-N containing proteins. This domain displays multiple conserved acidic residues . The presence of conserved acidic residues in both TerB-N and TerB-C suggests that they, like the TerB domain, might also chelate metals. These two domains might also occur together in the same protein independently of TerB .
Lebercilin domain (Lebercilin_dom)
Type: Domain

This entry represents a domain found in lebercilin (LCA5) and lebercilin like proteins. LCA5 might be involved in minus end-directed microtubule transport . Defects in LCA5 are the cause of Leber congenital amaurosis type 5 (LCA5). LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. LCA represents the most common genetic cause of congenital visual impairment in infants and children .
Vacuolar protein sorting protein 26 related (Vps26-related)
Type: Family

VPS26 assembles into a multimeric complex with other vacuolar protein sorting proteins (VPSs) and plays a role in vesicular protein sorting .
Remodeling and spacing factor 1-like (Rsf1-like)
Type: Family

Remodelling and spacing factor 1 (Rsf-1, also known as HBXAP) and SNF2h ATPase form the RSF chromatin remodelling complex . Rsf-1 can induce chromosomal instability and is overexpressed in many types of cancer cells . Its overexpression induces DNA damage response through ATM-Chk2-p53-p21 pathway . It also interacts and collaborates with cyclin E1 in tumour development .

Rsf-1 is identical to the largest isoform of HBXAP (HBXAPalpha/Rsf-1), which interacts with hepatitis B virus X protein (HBx). HBXAP may function as a negative regulator for TNF-alpha-induced, NF-kappaB-mediated gene activation .
Pyrroline-5-carboxylate reductase, catalytic, N-terminal (P5C_Rdtase_cat_N)
Type: Domain

Pyrroline-5-carboxylate reductase consists of two domains, an N-terminal catalytic domain and a C-terminal dimerisation domain. This entry represents the N-terminal catalytic domain, which consists of an α/β/α sandwich with a canonical NADP-binding Rossmann fold . This type of NADP-binding domain is also found in F420-dependent NADP reductases .
Bromodomain adjacent to zinc finger domain protein 2A, PHD zinc finger (PHD_BAZ2A)
Type: Domain

Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A, also known as TIP5 or WALp3) is an epigenetic regulator. It forms the nucleolar remodeling complex (NoRC) with ATPase SNF2h, which mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing . BAZ2A contains a TAM (TIP5/ARBP/MBD) domain, a DDT domain, four AT-hooks, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain. The C-terminal bromodomain, which is found in many chromatin-associated proteins and has been shown to bind to acetylated histone tails. The bromodomain cooperates with an adjacent PHD finger to recruit HDAC1, DNMT1, DNMT3, and SNF2h to rDNA .

This entry represents the PHD zinc finger of BAZ2A.
WHIM2 domain (WHIM2_dom)
Type: Domain

This entry represents the WHIM2 domain found in diverse eukaryotic chromatin proteins, such as animal BAZ/WAL and BPTF proteins, plant RLT, and yeast Itc1. This domain contains the D-TOX E motif (also known as the Williams-Beuren syndrome DDT (WSD) motif) that is conserved from yeasts to animals .

WHIM2 domain is a conserved α helical motif that along with the WHIM1 and WHIM3 motifs, and the DDT domain comprise an α helical module found in diverse eukaryotic chromatin proteins . Based on the Ioc3 structure, this module is inferred to interact with nucleosomal linker DNA and the SLIDE domain of ISWI proteins . The resulting complex forms a protein ruler that measures out the spacing between two adjacent nucleosomes . The acidic residue from the GxD signature of WHIM2 is a major determinant of the interaction between the ISWI and WHIM motifs. The N-terminal portion of the WHIM2 motif also contacts the inter-nucleosomal linker DNA. The module shows a great domain architectural diversity and is often combined with other modified histone peptide recognizing and DNA binding domains, some of which discriminate methylated DNA .
WHIM1 domain (WHIM1_dom)
Type: Domain

WHIM1 is a conserved α helical motif that along with the WHIM2 and WHIM3 motifs, and the DDT domain comprise an α helical module found in diverse eukaryotic chromatin proteins .Based on the Ioc3 structure, this module is inferred to interact with nucleosomal linker DNA and the SLIDE domain of ISWI proteins . The resulting complex forms a protein ruler that measures out the spacing between two adjacent nucleosomes . The conserved basic residue in WHIM1 is involved in packing with the DDT motif. The module shows a great domain architectural diversity and is often combined with other modified histone peptide recognizing and DNA binding domains, some of which discriminate methylated DNA .
Zorya protein ZorC, EH signature domain (ZorC_EH_Signature_dom)
Type: Domain

This domain is found in Zorya protein ZorC, a component of antiviral defense system Zorya type I, which confers resistance to phage infection. The function of ZorC is not clear but it may be involved in the sensing and inactivation of phage DNA, and if phage inactivation fails, the ZorAB proton channel opens up, leading to membrane depolarization and cell death . This domain was described as EH_signature as it contains a strongly conserved glutamate at the N terminus and a histidine at the C terminus , first described in a SWI2/SNF2 four gene operon . Its strict-neighbourhood association with SWI2/SNF2 ATPase strongly suggests a function in conjunction with it . The other genes in the operon are a OmpA protein and a TM protein . This has a DNA related function along with the TerY-P triad .
PRTase ComF-like (PRTase_ComF-like)
Type: Family

This phosphoribosyltransferase (PRTase) family is related to the ComF PRTases . These genes are found in the smaller biosynthetic operon associated with the Ter stress response operon and are predicted to be involved in the biosynthesis of a ribo-nucleoside involved in stress response .
Get1 family (Get1)
Type: Family

In budding yeasts, Golgi to ER traffic protein 1 (Get1) is a component of the Golgi to ER traffic (GET) complex, which is composed of Get1, Get2 and Get3. The GET complex mediates posttranslational insertion of newly synthesised tail-anchored (TA) proteins to the endoplasmic reticulum (ER) membrane.The GET complex is composed of the homodimeric Get3 ATPase and its heterooligomeric receptor, Get1/2. Get1 stabilises an open dimer conformation of Get3 .

In metazoa, the homologue to Get1 is known as tail-anchored protein insertion receptor WRB, which is a receptor for ASNA1/TRC40 (Get3 in yeast) .
Bacterial toxin 44 (Ntox44)
Type: Domain

Prokaryotic polymorphic toxin systems are characterised by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. This entry represents a predicted RNase toxin found in bacterial polymorphic toxin systems. The toxin possesses an all-α-helical fold with conserved DxK, GNxxxG, and DxxxD motifs. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 6 or type 7 secretion system .
Bacterial toxin 34 (Ntox34)
Type: Domain

This entry represents a predicted RNase toxin domain found in bacterial polymorphic toxin systems. The toxin possesses an all-α helical fold and conserved lysine and cysteine residues, and GNxxD and WxCxH motifs. In bacterial polymorphic toxin systems, the toxin is exported by the type 2 or type 6 secretion system .

Proteins containing this domain include protein RhsA from E. coli . RhsA is part of the RHS elements, which are proteins of non-essential function believed to play an important role in the natural ecology of the cell.
Bacterial toxin 28 (Ntox28)
Type: Domain

Prokaryotic polymorphic toxin systems are characterised by a remarkable diversity of C-terminal toxin domains, generated by recombination with standalone toxin-coding cassettes. This entry represents a predicted RNase toxin domain found in bacterial polymorphic toxin systems. The toxin possesses an all α-helical fold and conserved aspartate and glutamate residues, and K[DE] and[DN]HxxE motifs. In bacterial polymorphic toxin systems, the toxin is exported by the type 2, type 5 or type 7 secretion system .
Novel toxin 15 (Ntox15)
Type: Domain

Prokaryotic polymorphic toxin systems are implicated in intra-specific conflicts. They are characterised by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. This entry represents a predicted RNase toxin found in bacterial polymorphic toxin systems. The toxin possesses a most all-α helical fold and a conserved HxxD motif. In bacterial polymorphic toxin systems, the toxin is usually exported by the type 2, type 6, type 7 or Photorhabdus virulence cassette (PVC)-type secretion systems . This is shown to be a type IV secretion system protein that behaves as DNase .
Immunity protein 71 (Imm71)
Type: Domain

This entry represents a predicted immunity protein with a mostly α-helical fold and conserved arginine and phenylalanine residues. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox48 family . This domain is often fused to the Imm72 immunity domain.
Immunity protein 64 (Imm64)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved DxEA motif and arginine residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-ColD family .