SII-SWORD/CoKE huggingface dataset:
Single-stranded DNA-binding protein, BPT7 (SBB_BPT7)
Type: Domain

Single-stranded DNA-binding proteins (SSB, also known as helix-destabilising proteins and gp2.5) from Bacteriophage T7 is expressed in the late stage of lytic development, binding preferentially to single-stranded DNA and is implicated in DNA replication, formation of concatemers, recombination and repair of double-stranded breaks . It physically interacts with T7 DNA polymerase and T7 primase-helicase during replication to coordinate events at the replication fork . This entry represents the OB-fold domain which is well adapted for interactions with ssDNA.
Methylenetetrahydrofolate reductase (MTHFR)
Type: Family

This family represents a group of methylenetetrahydrofolate reductases from actinomycetes, including MSMEG_6596 (MTHFR1,

) and MSMEG_6649 (MTHFR2,

) from Mycolicibacterium smegmatis . Both MTHFR1 and MTHFR2 found in Mycobacterium smegmatis are involved in de novo methionine biosynthesis and required for antifolate resistance in mycobacteria . Both of these MTHFRs are monomeric and lack flavin coenzymes . They adopt a TIM barrel structure.
O-GlcNAcase BT_4395-like, post-catalytic domain (BT_4395-like_hel)
Type: Domain

This is a helical domain found after the catalytic domain of a goup of bacterial enzymes from the Glycoside hydrolase family 84, including O-GlcNAcase BT_4395 from Bacteroides thetaiotaomicron, which can hydrolyse the glycosidic link of O-GlcNAcylated proteins .
Cytosolic arginine sensor for mTORC1 subunit 1/2, ACT-like (CASTOR1_ACT-like)
Type: Domain

This domain is found in Cytosolic arginine sensor for mTORC1 subunit 1 from humans (CASTOR1) and in similar proteins predominantly from vertebrates. CASTOR1 functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway. This entry represents the third out of the four tandem ACT domains present in this protein. This domain adopts the typical β-α- β-β-α-β configuration of the ACT domain, although it lacks the last β-strand. It folds together with the first ACT domain to form an eight-stranded β-sheet flanked by four α-helices on one side, making up the dimerisation domain .
BVU_1015-like, N-terminal dimerisation-like domain (BVU_1015-like_N)
Type: Domain

This domain is found at the N-terminal end of a group of bacterial methyltransferases, including SAM-dependent methyltransferase from Phocaeicola vulgatus (BVU_1015,

). It has a winged-helix structure and is usually found associated with

.
Survival Motor Neuron, Gemin2-binding domain (SMN_G2-BD)
Type: Domain

Survival Motor Neuron (SMN) protein forms the oligomeric core of a multi-protein complex that functions in spliceosomal snRNP biogenesis. It has three highly conserved domains: a short N-terminal segment responsible for binding with high affinity to Gemin2 (a protein involved in snRNP assembly), therefore, called Gemin2-binding domain (G2-BD), a central Tudor domain (

) that recognises symmetric dimethylarginine (sDMA) modifications in proteins involved in RNA processing, and a C-terminal domain, referred to as the 'YG-box' domain

. This is the Gemin2-binding domain (G2-BD) of SMN proteins .
Protein arginine N-methyltransferase 3-like, C2H2 zinc finger domain (ANM3-like_C2H2_Zf)
Type: Domain

This is the N-terminal helical domain of protein arginine N-methyltransferase 3 (ANM3/PRMT3) which has a C2H2 zinc finger. ANM3 catalyses both the monomethylation and asymmetric dimethylation of the guanidino nitrogens of arginine residues in target proteins and may regulate retinoic acid synthesis and signalling by inhibiting ALDH1A1 retinal dehydrogenase activity . PRMT3 orthologue from fission yeast, is a ribosomal protein that methylates guanidino nitrogens of arginyl residues in ribosomal protein rps2 and may regulate ribosome biosynthesis . This zinc-finger is required for its optimal enzymatic activity and contributes to substrate specificity .
Fas-associated factor 1/2-like, UAS domain (FAF1_2-like_UAS)
Type: Domain

This entry represents the UAS domain from a group of eukaryotic proteins, including human Fas-associated factor 1 and 2 (FAF1/2). FAF1 is a ubiquitin-binding protein required for the progression of DNA replication forks by targeting DNA replication licensing factor CDT1 for degradation . FAF2 plays an important role in endoplasmic reticulum-associated degradation (ERAD) that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins . It is involved in stress granule disassembly . UAS domain in these proteins was shown as a motif interacting long-chain unsaturated fatty acids .
Transcriptional regulator Rv0078-like, C-terminal domain (Rv0078-like_C)
Type: Domain

This domain is found at the C-terminal end of bacterial transcriptional regulators of the TetR family, including

from Mycobacterium tuberculosis (Rv0078) and

from Myxococcus xanthus. This is the all-helical ligand-binding domain, which interacts with the respective effector molecule and transmits the signal to the DNA binding domain (

).
Translation initiation factor eIF4G-like, eIF4E-binding domain (eIF4G1-like_eIF4E-bd)
Type: Domain

This domain is found in proteins from insects and fish, including Translation initiation factor eIF4G (eIF4G1) from Drosophila melanogaster (

). This domain shows a canonical helix, a linker and an elbow loop. It contains a conserved sequence motif YXR/KXXLXXXR/K/Q that plays a role in the interaction with eIF4E .
Flavivridae NS3 helicase, C-terminal helical domain (NS3-hel_C_flaviviridae)
Type: Domain

This domain is found at the C-terminal end of NS3 helicase (Non-structural protein 3-helicase, NS3-Hel) found in Flavivirus such as Zika virus (ZIKV) and Dengue virus type 1 (DENV-1). This protein binds RNA and unwinds dsRNA in the 3' to 5' direction. It consists of three domains. This entry represent the final domain, which is mostly α-helical . A highly conserved arginine residue located in this domain was proven essential for the enzymatic activities of the protein .
Beta-galactosidase-like, galactose-binding domain (BgaA-like_CBM)
Type: Domain

This domain is found in Beta-galactosidase from Streptococcus pneumoniae (BgaA,

) and similar bacterial sequences. BgaA is specific for terminal galactose residues β-1-4 linked to glucose or N-acetylglucosamine. It is involved in pneumococcal growth, resistance to opsonophagocytic killing, and adherence. This entry represents two non-enzymatic carbohydrate-binding modules (CBMs) that mediate adherence to the host cell surface displayed lactose or N-acetyllactosamine. Each of these CBMs folds into a β-sandwich fold comprising opposing sheets of 4- and 5-antiparallel β-strands .
TetR transcriptional regulator TM_1030-like, C-terminal domain (TM_1030-like_C)
Type: Domain

This domain is found at the C-terminal end of the TetR family Transcriptional regulator TM_1030 from Thermotoga maritima (

) and similar sequences from bacteria. TM_1030 shows high similarity to members of the TetR family at the N-terminal DNA-binding domain (

). However, differences are much greater in the C-terminal regulatory domain, which shows an all-helical structure .
[Acyl-carrier-protein] S-malonyltransferase-like, inserted helical domain (FabD-like_helical_ins)
Type: Domain

This domain is found in the C-terminal region of [Acyl-carrier-protein] S-malonyltransferase from Bacillus velezensis (FabD,

) and similar bacterial proteins. FabD, a marine polyunsaturated fatty acid (PUFA) synthase involved in difficidin A biosynthesis, is organised into two domains: anacetyl-transferase (AT) domain (

) and an enoyl reductase (ER) domain that consists of a TIM-barrel domain (

) and an inserted α-helical substrate-binding domain (this entry) .
C883_1060-like, ketoreductase domain, N-terminal (C883_1060-like_KR_N)
Type: Domain

This is the N-terminal region of the ketoreductase (KR) domain of C883_1060 from Bacillus stratosphericus (

) and similar bacterial sequences. The KR domain reduces the alpha-keto acid giving rise to hydroxy acid residues.
Mucin-like domain, nairovirus (MLD_nairovirus)
Type: Domain

This is the mucin-like domain (MLD) located at the N-terminal of the glycoprotein precursor complex (GPC), encoded in the M segment of nairoviruses genome . It contains a furin cleavage site which separates MLD from GP38 (

).
BD-FAE-like domain (BD-FAE-like_dom)
Type: Domain

This entry represents a domain that covers most of the length of a novel bifunctional feruloyl and acetyl xylan esterase (BD-FAE, previously known as bifunctional carbohydrate esterase (CE)), which is active on complex natural xylans and was identified as the basis of a monophyletic clade gathering all homologues identified in PULs (polysaccharide utilisation loci) predicted to act on xylan. It adopts an α-β-hydrolase fold with the catalytic triad Ser-Asp-His . These proteins are new candidate for biomass processing due to its capacity to remove ferulic acid and acetic acid from natural corn and birchwood xylan substrates .

This domain is also found in Kynurenine formamidase from Mus musculus (KFase), which hydrolyses N-formyl-L-kynurenine to form L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation ; in Isoprenylcysteine alpha-carbonyl methylesterase ICME from Arabidopsis thaliana, which catalyses the demethylation of isoprenylcysteine methylesters ; Esterase LipQ from Mycobacterium tuberculosis, which shows lipase activity and is highly immunogenic, probably playing an important role in the virulence and pathogenesis of the bacterial infection by altering the balance of cytokines ; and other proteins widespread among all cellular organisms.
vWA-MoxR associated protein middle region 18 (VMAP-M18)
Type: Domain

This entry represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. VMAP-Ms may be involved in sensing of invasive entities. It is located C-terminal to

.
vWA-MoxR associated protein middle region 15 (VMAP-M15)
Type: Domain

This entry represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. VMAP-Ms may be involved in sensing of invasive entities. It is located C-terminal to
vWA-MoxR associated protein middle region 12 (VMAP-M12)
Type: Domain

This is a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. VMAP-Ms may be involved in sensing of invasive entities. It is located sometimes N-terminal to
vWA-MoxR associated protein middle region 20 (VMAP-M20)
Type: Domain

This entry represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. VMAP-Ms may be involved in sensing of invasive entities. This region is usually found N-terminal to

.
Formin C, N-terminal domain (ForC_N)
Type: Domain

This domain is found at the N-terminal of Formin-C from Dictyostelium discoideum (ForC) and similar proteins predominantly found in amoebas. ForC is involved in the regulation of local actin cytoskeleton reorganisation. It contains a N-terminal putative GTPase-binding domain (GBD, this entry), an FH3, and an FH2 domain (

). This domain adopts an ubiquitin-like fold with an unusually long loop between the first and second β-strands .
Cmr1-like, C-terminal domain (Cmr1-like_C)
Type: Domain

This entry represents the C-terminal RRM domain of CRISPR system Cmr subunit Cmr1-1 from P. furiosus . Cmr1 is part of the Cmr complex, an RNA-guided endonuclease that cleaves foreign RNA targets as part of the CRISPR prokaryotic defense system.
Dbr1, C-terminal domain (Dbr1_CTD)
Type: Domain

Dbr1 (Lariat debranching enzyme) is an eukaryotic intron debranching enzyme that hydrolyses the linkages produced by the spliceosome in RNA for them to be processed into essential cellular factors, such as snoRNA and miRNA. This protein is organized into an N-terminal metallophosphoesterase (MPE) domain (

) and a C-terminal domain which is represented in this entry. This domain consists of four α-helices and three connecting loops. It is located on the posterior of the protein, opposite the active site and is joined to the MPE domain by an extended linker region .
Peptidase M50B-like (Peptidase_M50B-like)
Type: Family

This entry represents a family of bacterial, fungal and plant peptidases in the same family as MEROPS M50B.
A-ATP synthase, subunit H, N-terminal, archaeal (A-ATP_synth_H_N_arc)
Type: Domain

This domain is found at the N-terminal of MJ0223 from Methanocaldococcus jannaschii (

), the subunit H of an archaeal A-ATP synthase. This entry represents the region that is involved in subunit H and E assembly. It folds into a continuous α-helix with a small kink in the centre of the molecule .
Suprabasin, GxHH repeat (SBSN_GxHH_rpt)
Type: Repeat

Suprabasin (SBSN) is involved in epidermal differentiation and may play a role in skin barrier formation. It has been proposed to be a component of the cornified envelope, an essential structure for skin protection . Its exact function is not yet clear; it has been associated with multiple diseases such as cancer and autoimmune disorders . It is a secreted molecule that may induce cellular signalling (AKT, WNT/beta-catenin, and/or p38MAPK signalling) and processes (migration, proliferation, neovascularization apoptosis- and immune-resistance). It contains a repeated sequence GxHH, with no other similar sequence in the human proteome, which suggests an evolutionarily unique and conserved role . It has also been described a FG (Phe-Gly) motif, which is common in scaffold proteins (keratin 1/2/10 and fillagrin-2 in addition to SBSN) . This entry represents the repeated sequence GxHH which may adopt a β-solenoid fold according to structure predictions.
HEPN, AbiJ-N-terminal domain 4 (AbiJ_NTD4)
Type: Domain

This entry represents a domain found in a group of prokaryotic proteins. In some proteins, it is found fused to AbiJ-like HEPN and heat repeats. It is predicted to adopt an α β structure .
O-antigen ligase-like membrane protein (O-antigen_lig)
Type: Family

This entry represents a functionally uncharacterised group of proteins predominantly found in firmicutes (Bacillota bacteria). AlphaFold predicts that this family adopts a fold structurally similar to O-antigen ligase WaaL and peptidoglycan glycosyltransferase RodA .
Rhabdovirus phosphoprotein, C-terminal domain (RABV_P-like_C)
Type: Domain

This entry represents the C-terminal domain of the P protein (phosphoprotein) from Rabies virus (RABV) and similar sequences from Rhabdoviridae. RABV P is known to counteract the functions of various cellular factors involved in antiviral responses, including STAT1, and interferon-induced promyelocytic leukaemia (PML) protein; the C-terminal domain of the RABV P protein includes STAT1 and PML binding sites. It plays multiple roles in transcription and translation, which include acting as a chaperone of nascent nucleoprotein (N), and as a cofactor of the viral polymerase (L) where P forms a two-subunit polymerase with a large catalytic subunit (L) and stabilises the polymerase on its template of N-RNA .
Shieldin complex subunit 2, first OB fold domain (SHLD2_OB1)
Type: Domain

This entry represents the first OB fold domain found in the middle of Shieldin complex subunit 2 (SHLD2, formerly known as FAM35A). SHLD2 is a component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) .
Serine/threonine-protein kinase MARK 1-4, catalytic domain (MARK1-4_cat)
Type: Domain

This entry represents the catalytic domain found in the animal Serine/Threonine Kinases (STKs) MAP/microtubule affinity-regulating kinases 1-4 (MARK1-4). STKs catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, and vertebrates. They are involved in embryogenesis, epithelial cell polarisation, cell signalling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport . Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2 .
DyP dimeric alpha+beta barrel domain (DyP_N)
Type: Domain

This entry represents the N-terminal dimeric α/β barrel domain from a group of the dye-decolorising peroxidase (DyP)-type peroxidase family of proteins. This is one of the six families of peroxidases .
RssB-like, receiver domain (RssB-like_REC)
Type: Domain

This entry represents the receiver domain (REC) found in the probable two-component response regulator RssB from Pseudomonas aeruginosa (

,

) and similar sequences mainly found in pseudomonadales. RssB contains a REC domain (this entry) and a PP2C-type protein phosphatase output domain (

). REC domains function as phosphorylation-mediated switches within response regulators, but some also transfer phosphoryl groups in multistep phosphorelays .

Escherichia RssB, which is not included in this group, is a ClpX adaptor protein which alters ClpX specificity by mediating a specific interaction between ClpX and the substrates such as RpoS, an RNA polymerase sigma factor .
Polyglycine hydrolase-like, tandem repeat (PGH-like_rpt)
Type: Repeat

Polyglycine hydrolase from Fusarium vanettenii is a serine-type endopeptidase that cleaves Gly-Gly bonds in the polyglycine linker of host plant class IV chitinases to disrupt their chitin-binding, and thereby plays a role in lowering the defence responses of the host to fungi. It is formed by two distinct domains that are connected by a linker. The N-terminal domain is comprised of five nearly identical structural repeats consisting of three antiparallel β-strands and an α-helix (this entry represents these structural repeats), while the C-terminal is represented by

.

In addition to fungal sequences, these structural repeats are also found in proteins from worms, rotifers and a wide variety of bacteria.
Double jelly roll-like domain (DJR-like_dom)
Type: Domain

This entry represents a domain found in a family of proteins mainly from arthropods containing a jelly-roll domain, which has similarity to domains otherwise found in a variety of large dsDNA virus capsid proteins.
Tetracyclin repressor-like 40, C-terminal domain (TetR_C_40)
Type: Domain

This domain is found at the C-terminal of bacterial transcriptional regulators, including RolR from Corynebacterium glutamicum (

), which is involved in aromatic catabolism. This signal-receiving domain shows an all-α-helical fold. It is found associated with

, responsible for DNA-binding .
Filamentation induced by cAMP protein Fic-like, C-terminal domain (Fic-like_C)
Type: Domain

This domain is found at the C-terminal of Filamentation induced by cAMP protein Fic (

) from Oleidesulfovibrio alaskensis and similar bacterial sequences. This domain adopts a winged helix structure (

). It is often found associated with

. This domain is also found in some archaeal sequences.
Medium-chain acyl-CoA synthetase, putative (MACS_put)
Type: Family

This entry represents a functionally uncharacterised group of medium-chain acyl-CoA synthetases (MACS) mainly found in proteobacteria. MACS catalyse the two-step activation of medium chain fatty acids (containing 4-12 carbons). The carboxylate substrate first reacts with ATP to form an acyl-adenylate intermediate, which then reacts with CoA to produce an acyl-CoA ester .
FAD-dependent protein, C-terminal domain-like (FAD-depend_C)
Type: Domain

This domain is found towards the C-terminal of a group of bacterial, archaeal and plant FAD-linked dehydrogenases, whose exact function is not yet clear. This domain is inserted in the FAD/NAD(P)-binding domain.
Acetophenone carboxylase-like, C-terminal domain (ACX-like_C)
Type: Domain

This domain is found at the C-terminal of acetophenone carboxylase subunits . According to ECOD this domain adopts a reverse ferredoxin fold. This domain is also found in a wide range of related enzymes subunits, such as 5-oxoprolinase, in which it is found in the central region.
Ant venom peptides (Pilosulin)
Type: Family

Members of this family are found in Myrmecia pilosula and represent a group of peptides that display cytotoxic, hypotensive, histamine-releasing and antimicrobial activities.

Pilosulins constitute the major allergens of the venom of Myrmecia pilosula (Myrmeciinae). Pilosulin 1 is a long linear peptide (57 amino acids) and displays haemolytic and cytolytic activities. Pilosulins 3, 4, and 5 are a group of homo- and heterodimeric peptides . Pilosulin 1 (

) is expressed in the venom sac of ants in the form of a propeptide (112 kDa) which undergoes extensive post-translational modification. It is proposed to give rise to a family of six homologous C-terminal peptide sub-sequences containing between 27 and 56 amino acid residues in the final venom. Furthermore, it is found to form random coils and have minimal secondary structure. However, in increasingly hydrophobic conditions, approximately one-third of the peptide forms an α-helix secondary structures. Studies on human erythrocytes and lymphocytes, show that Pilosulin 1 is highly lytic towards leukocytes and that the NH2-terminus (20 N-terminal residues) of Pilosulin 1 is critical for its cytotoxic activity and antimicrobial activities. Another family member Pilosulin 3

, is a heterodimer of Pilosulin 3a and Pilosulin 3b linked in antiparallel fashion through 2 disulfide bridges. This peptide is the most abundant peptide found in native venom .
Type II restriction enzyme SmaI (SmaI)
Type: Family

This entry includes the Type II site-specific deoxyribonuclease SmaI ([swissprot:P14229,

)) which recognizes and cleaves the sequence CCCGGGG on DNA, yielding a blunt end scission . It has been used for the diagnosis of neurogenic muscle weakness, ataxia and retinitis pigmentosa disease or Leigh's disease. Due to its specificity in recognizing the cleavage site, it is used in Leigh's disease to specifically eliminate the mutant mitochondrial DNA (mtDNA), which coexists with the wild-type mtDNA (heteroplasmy). Only the mutant mtDNA, but not the wild-type mtDNA, is selectively restricted by the enzyme. By delivering the SmaI gene fused to a mitochondrial targeting sequence, specific elimination of the mutant mtDNA was demonstrated, resulting in restoration of both the normal intracellular ATP level and normal mitochondrial membrane potential . The same strategy has also been demonstrated retinitis pigmentosa (NARP), where a mutant mitochondrial DNA carrying a T8993G transversion has been targeted by using SmaI enzymes .