SII-SWORD/CoKE huggingface dataset:
Vanillate O-demethylase oxygenase-like, C-terminal catalytic domain (VanA_C_cat)
Type: Domain

The oxidative degradation of aromatic compounds implies several steps, the initial one consists in the addition of hydroxyl groups to the aromatic ring by Rieske-type non-heme iron aromatic ring-hydroxylating oxygenases (RHOs) that utilise non-heme Fe+2 to catalyse this step. RHOs are composed of two or three proteins which comprise an electron transport chain (ETC) and an oxygenase. The ETC transfers reducing equivalents from the electron donor to the oxygenase component, and then the latter transfers electrons to the oxygen molecules . The oxygenase components are oligomers, either (alpha)n or (alpha)n(beta)n. The alpha subunits constitute the catalytic component, which includes an N-terminal Rieske-like 2Fe-2S cluster binding domain and a C-terminal domain that binds the non-heme Fe 2, coordinated by conserved His and Asp residues. The beta subunit has a structural role. Some examples include carbazole 1,9a-dioxygenase, phthalate dioxygenase as well as oxidative demethylation enzymes like vanillate O-demethylase and its close relative Dicamba O-demethylase (also known as dicamba monooxygenase or DMO) , Comamonas testosteroni T-2 p-toluenesulfonate dioxygenase and methylxanthine N-demethylases NdmA, NdmB, and NdmC, which catalyse the N-1-, N-3-, and N-7-specific demethylation of caffeine, respectively, in Pseudomonas putida .

This entry represents the C-terminal catalytic domain of a group of Rieske [2Fe-2S]-domain-containing non-haem iron oxygenases, including vanillate O-demethylase oxygenase subunit, dicamba O-demethylase, methylxanthine N-demethylases NmdA, NmdB and NmdC, Toluene-4-sulfonate monooxygenase and Chloroacetanilide N-alkylformylase. Proteins containing this domain also include plant chlorophyllide a oxygenases that catalyse a two-step oxygenase reaction involved in the synthesis of chlorophyll b .
Domain of unknown function DUF5679 (DUF5679)
Type: Domain

This domain can be found in bacteria, archaea, eukaryotes and viruses. These domains contain four conserved cysteines suggesting that this domain is zinc binding.
E3 ubiquitin-protein ligase UBR-like, C-terminal (E3_ligase_UBR-like_C)
Type: Domain

UBR box family is a unique class of E3 ligases that recognise N-degrons or structurally related determinants for ubiquitin-dependent proteolysis. They belong to the N-end rule pathway which relates the identity of the N-terminal residue of a protein with its half-life, recognising destabilising ones. Some of the functions of this pathway include the control of peptide import, the fidelity of chromosome segregation, the regulation of apoptosis, as well as regulation of meiosis in yeasts and metazoans, leaf senescence in plants, and cardiovascular development in mammals . These proteins contain an N-terminal UBR box (a substrate-binding domain), which is highly conserved among UBR family members, a cysteine- and histidine-rich RING (RING-H2) domain, which is present in a larger class of E3 ubiquitin ligases and some additional domains that vary among UBR family members, like these described in UBR1 : ClpS, a region of sequence similarity to prokaryotic ClpS which acts as an accessory subunit that contributes to recognition of degrons by the ATP-dependent protease ClpAP, a BRR (basic residue-rich region), a conserved motif that contributes to the binding of yeast UBR1 to the E2 enzyme RAD6, and conserved regions .

This entry represents the C-terminal domain which includes a conserved region found in E3 ubiquitin-protein ligase UBR1, 2, 3 from animals, UBR1/11 from fission yeast, and also in PRT6 from Arabidopsis thaliana .
Bacterial Ig-like domain 12 (Big_12)
Type: Domain

This is a presumed domain found as tandem repeats of high sequence identity in bacterial cell surface proteins. This domain can also be found in eukaryotic proteins.
EccD-like transmembrane domain (EccD_transm)
Type: Domain

This domain is found in EccD members from the Type VII secretion system such as EccD2, EccD4 and EccD5, which includes 11 predicted transmembrane α-helices.

ESX-1 to ESX-5 gene clusters encode proteins that are either secreted or building blocks of the actinobacterial Type 7 secretion system (T7SS) . In Mycobacterium tuberculosis ESX-1 is responsible for secretion of important virulence factors such as EsxA and EsxB as well as other virulence-associated proteins, ESX-3 is involved in metal acquisition being critical for mycobacterial survival. ESX-5 is also important for the secretion of members of the PE/PPE family of proteins that play a role in virulence and cell wall integrity. The function of ESX-2 and ESX-4 is still unknown although ESX-4 seems to be the ancestral system from which ESX systems have evolved. All ESX gene clusters contain three or four ESX conserved components (Ecc), named EccB, EccC, and EccD, with EccE being present in all ESX systems, except of ESX-4. EccC is a member of the FtsK/SpoIIIE-like ATPase family and provides the energy to transport proteins across the mycobacterial membrane; EccB and EccE have N-terminal transmembrane elements and large C-terminal regions predicted to be localised in the periplasm, but their function, molecular function or interacting partners remain unknown. EccD contains an N-terminal cytoplasmic domain followed by 11 predicted transmembrane helices, which is thought to form a cytoplasmic membrane channel through which the proteins are secreted .
Protein of unknown function DUF5837 (DUF5837)
Type: Family

This entry represents a family of unknown function associated with the tenuecyclamide A biosynthetic gene cluster.
Prophage endopeptidase tail, N-terminal (Prophage_tail_N)
Type: Domain

This entry represents the N-terminal domain of prophage tail proteins that are probably acting as endopeptidases. This domain has a RIFT related fold. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Hydroxylase/desaturase AsaB-like (AsaB-like)
Type: Family

This entry includes a group of oxidoreductases, including AsaB from Aspergillus flavus , Oxidoreductase R1/R2 from Phoma sp., DES from Gibberella fujikuroi, and Chry3 from Gibberella zeae. AsaB is involved in secondary metabolite biosynthesis. It converts aspergillic acid to hydroxyaspergillic acid . R1/R2 is part of the gene cluster that mediates the biosynthesis of squalestatin S1 . Chry3 is part of the gene cluster that mediates the biosynthesis of the yellow pigment chrysogine . DES is part of the gene cluster that mediates the biosynthesis of gibberellins (GAs), diterpenoids that may provide a selective advantage during infection of the preferred host plant, rice .

Proteins in this entry are related to RbtB and RbtG from Penicillium dangeardii. RbtB and RbtG are alpha-ketoglutarate-dependent dioxygenases involved in rubratoxin biosynthesis .
Rv0078B-like antitoxin (Rv0078B)
Type: Family

This entry represents a putative antitoxin protein according to TASmania database . Toxin-antitoxin systems (TAS) are found nearly in all phyla and have important roles like plasmid maintenance, phage defense, persistence and virulence.
Long Rib domain (RibLong)
Type: Domain

This entry represents the Long Rib domain that is closely related to the Rib domain [

], but has a conserved insertion. These domains are found in bacterial cell surface proteins.
Internalin I, Ig-like domain (InlI_Ig-like)
Type: Domain

Internalins (Inl) are virulence factors exposed in the surface of many Gram-positive bacteria and are involved in several processes such as recognition of cellular receptors and pathogen entry to escape from autophagy. These surface proteins were found as markers for Listeria monocytogenes species and essential for infection. Internalins are modular proteins composed by the characteristic N-terminal LRR repeats followed by domains that may vary among the members internalins family, explaining the distinct roles they play during infection. LRR repeats are followed by a conserved immunoglobulin-like domain , a variable region that corresponds to MucBP (mucin binding protein) domains, and a C-terminal LPXTG motif, also characteristic of these proteins and is expected to anchor the protein to the peptidoglycan as seen in internalins structures such as InlA, InlI, InlJ or InlK .

The solved structure of InlK, revealed the classical LRR domain at its N-terminal, followed by three domains generating a structure that resembles a "bent arm", with a potential partner recognition domain localised at the "elbow" region. Domains D1 and D2 are potentially involved in binding to protein partners while D3 and D4 most probably serve as pedestals. Elbow and pedestal domains might act as platforms for binding partner molecules . InlK recruits the Major vault protein (MVP) in an interaction that allows L. monocytogenes to escape from autophagy .

This entry corresponds to a conserved Ig-like fold domain, also known as the inter-repeat region that follows the LRRs , and corresponds to the elbow domain described in the InlK structure . This domain and the LRRs are required and sufficient for attachment to host cells.
SnTox1, chitin binding-like domain (SnTox1_CBL)
Type: Domain

The host selective cysteine rich necrotrophic effector Tox1(SnTox1) found in Parastagonospora nodorum is a necrotrophic effector that contains 6 cysteine residues, a common feature for some fungal avirulence effectors such as the Avr and ECP effectors from Cladosporium fulvum. The high content of cysteine residues and high stability suggest that SnTox1 may function in the plant apoplastic space which is abundant in plant defense components. Protein sequence analysis indicate that SnTox1 contains a C-terminal chitin binding (CB) like motif. Three-dimensional (3D) structure-based sequence alignment suggested that the putative CB motif in SnTox1 was more similar to those of plant-specific ChtBDs than to Avr4 proteins, which are related to invertebrate ChtBDs. Furthermore, SnTox1 contained all secondary-structure-related residues including the strictly conserved b-strand-forming 'CCS' motif found only in plant-specific ChtBD1 proteins . It interacts with the host Snn1 protein conferring susceptibility. Binding of SnTox1 to chitin in the fungal cell wall protects the pathogen from chitinase activity.

This entry represents the putative chiting binding-like domain found in SnTox1 from Parastagonospora nodorum.
Uncharacterised lipoprotein (Lipoprotein_23)
Type: Family

This entry includes members predominantly found in Actinobacteria. Some members are annotated as lipoproteins.
Cns1/TTC4, wheel domain (Csn1/TTC4_wheel)
Type: Domain

Co-chaperones are helper interacting proteins that modulate the chaperone cycle, being involved in substrate specificity and stimulation of chaperone activity of HSP90/70 and include other heat shock proteins, TPR containing proteins, cyclophilins and others. The TPR containing proteins possess an N-terminal TPR domain, which are more closely related to each other than to TPR domains from other proteins with different functionality , which is involved in HSP90/70 direct interaction. The first N-terminal residues prior to the TRP domain and the C-terminal domain are involved and important for domain interplay and stabilisation of its interactions . The Hsp90 chaperone machinery in eukaryotes comprises a number of distinct accessory factors, among them TTC4 from human and its homologues Cns1 from yeast and Dpit47 from Drosophila, structurally and functionally conserved from yeast to human. Cns1 is one of the few essential co-chaperones in yeast, important for maintaining translation elongation, specifically chaperoning the elongation factor eEF2. Cns1 interacts with Hgh1 and forms a quaternary complex together with eEF2 and Hsp90 mediating the proper folding and solubility of eEF2. Recently, the C-terminal structure has been solved and is called the "wheel" domain according to its 2D projection. It shows an overall fold consisting of a twisted five-stranded β sheet surrounded by several α helices .

This entry represents the wheel domain found at the C terminus of yeast Cns1, human TTC4 and Drosophila Dpit47 proteins.
Bacterial repeat domain (Bacterial_rp_domain)
Type: Domain

This domain is found in bacterial cell surface proteins, often found in tandem array although single copies are found in some proteins. This domain is closely related to (

).
Oxytoxin-type inhibitor cystine knot (ICK) domain (OXYTX_ICK)
Type: Domain

This entry represents the oxytoxin-type ICK domain.

Spiders are widely acknowledged to produce potent and selective toxins. In addition to the conventional neurotoxins and cytotoxins, venom of lynx spiders (genus Oxyopes) was found to contain two-domain modular toxins named spiderines: OspTx1a, 1b, 2a and 2b . Spiderines consist of two distinct modules separated by a short linker. The N-terminal part (~40 residues) contains no cysteine residues, is highly cationic, forms amphipathic α-helical structures in a membrane-mimicking environment, and shows potent cytolytic effects on cells of various origins. The short linker resembles closely the processing quadruplet motif (PQM), which is known to indicate the processing cleavage site in precursors of spider toxins and separate the prosequence from the mature chain. The C-terminal part (~60 residues) is a disulfide rich domain reticulated by five S-S bridges that is homologous to one-domain oxytoxins (OxyTx1 and OxyTx2) from Oxypes species. Oxytoxins are disulphide-rich polypeptides that contain five disulfide bridges and block L-, N- and P/Q-type voltage-sensitive calcium ion channels (VSCCs) . The core of the oxytoxin-like domain is the inhibitor cystine knot (ICK) or knottin motif. The domain is stabilised by five disulfides and 13 hydrogen bonds. Two antiparallel β-strands form a short β-sheet, and there are two β-turns in the N-terminal part of of the domain. C1-C5, C2-C6, and C4-C9 disulfides contribute to the ICK motif, whereas C7-C8 stabilises the extended loop of the β-hairpin and C3-C10 staples the lengthy C-terminal of the domain to its core .
LCN-type cysteine-stabilized alpha/beta (CS-alpha/beta) domain (LCN-type_CS_alpha_beta_dom)
Type: Domain

This entry represents the LCN-type CS-α/β domain consisting of one or two short segments of α-helix and a triple-stranded β-sheet which are held together by two disulfide bridges and connected by variable regions forming loops . Neurotoxins of the birtoxin family are also included in this group, although they possess three disulfide bridges instead of the usual four disulfide bridges of other members of the group and they are uniquely shorter than other LCNs .

Scorpion venoms comprise complex mixtures of neurotoxins (low molecular weight proteins), cardiotoxins, hemolytic toxins, antimicrobial peptides, enzymes (such as hyaluronidase, acetylcholinesterase, phospholipase and metalloproteinases), lipides, nucleotides, mucopolysaccharides and biogenic amines. Neurotoxins can be classified as either short- or long-chain toxins, which share a common structural motif, named cysteine-stabilized α-helix/β-sheet (CS-α/β). Short-chain neurotoxins (SCNs) usually contain 30-40 residues and three or four disulphide bridges. Most of the short chain toxins block voltage-dependent or Ca+2-activated K+ channels. Most long-chain neurotoxins (LCNs) are composed of 60-70 residues and are cross-linked by four disulphide bridges. The long chain or voltage-gated sodium channels scorpion neurotoxins (NaScTxs) can be classified either as alpha-toxins, which slow down Na+ channel inactivation, or beta-toxins, which affect the channel activation process. Both types make the inactivation of the sodium channel incomplete .
Gid-type RING finger domain (ZF_RING_GID)
Type: Domain

The two major antagonistic pathways of carbon metabolism in cells, glycolysis and gluconeogenesis, are tightly regulated. In yeast, the switch from gluconeogenesis to glycolysis is brought about by proteasomal degradation of the gluconeogenic enzyme fructose-1,6-bisphosphate. The ubiquitin ligase responsible for polyubiquitylation of fructose-1,6-bisphosphate is the Gid (glucose induced degradation deficient) complex. This complex consists of seven subunits of which two, Gid2/Rmd5 and Gid9/Fyv10, contain a degenerated RING finger domain providing E3 ligase activity. The two subunits form the heterodimeric E3 ligase unit of the Gid complex . The orthologous complex found in mammalian cells is called CTLH, which has been linked to several different functions like regulation of cell morphology, proteasome-dependent degradation of non-ubiquitinated alpha-catenin, or modulation of endosome/lysosome-dependent degradation of ubiquitinated proteins via interaction with HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) .

This entry represents the degenerated Gid-type RING finger which comprises an incomplete serie of Zn ion-coordinating residues compared with the canonical RING finger, which encompasses eight Cys/His residues coordinating two Zn cations. A complete cysteine and histidine pattern is not necessarily critical for the E3 function .
Zinc finger ZBR-type domain (ZF_ZBR)
Type: Domain

The anaphase-promoting complex or cyclosome (APC/C) is a multisubunit E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell-cycle regulatory proteins. Emi1/Fbx5 (early mitotic inhibitor 1; gene symbol, FBX05) and Emi2/Erp1/Fbx43 (endogenous meiotic inhibitor 2 or Emi1-related protein 1; gene symbol, FBX043) constitute the Emi/Erp protein family of APC/C inhibitors against the APC/C function, which controls cell division progress. Emi1 and Emi2 share the F-box and DB motifs, the zinc-binding region (ZBR) with the in-between-RING (IBR) topology and the C6HC-type zinc-binding motif, and the C-terminal region with a conserved 14-residue sequence ending in the RL residues, termed the RL tail .

This entry represents the ZBR-type zinc finger which is arranged in a central, twisted, four-stranded β-sheet and coordinates two zinc ions on opposite ends of the sheet. One zinc is chelated by the β1-β2 and β3-β4 loops and the other by the β2-β3 loop and a loop following β4. The ZBR finger displays an In-Between-RING (IBR) domain topology .
Archaeal CBS protein, (ACP)-type metal binding domain (ACP_MB)
Type: Domain

This domain can be found in a group of archaeal proteins that function as electron transfer proteins. They consist of a small (~35 amino acids) C- terminal metal-binding (MB) domain containing four cysteine residues arranged in a Cys-X(2)-Cys-X(14-19)-Cys-X(1-4)-Cys motif. The archaeal CBS proteins (ACP)-type MB domain can bind several metals, with iron and zinc being the most abundant metals .

The ACP-type MB domain consists of three short β-strands forming a compact anti-parallel β-sheet that packs against the CBS domains .
Picornavirales 3C/3C-like protease domain (PCV_3C_PRO)
Type: Domain

Viruses in the order Picornavirales infect different vertebrate, invertebrate, and plant hosts and are responsible for a variety of human, animal, and plant diseases. These viruses have a single-stranded, positive sense RNA genome that generally translates a large precursor polyprotein which is proteolytically cleaved after translation to generate mature functional viral proteins. This process is usually mediated by (more than one) proteases, and a 3C (for the family Picornaviridae) or 3C-like (3CL) protease (for other families) plays a central role in the cleavage of the viral precursor polyprotein. In addition to this key role, 3C/3C-like protease is able to cleave a number of host proteins to remodel the cellular environment for virus reproduction . The Picornavirales 3C/3C-like protease domain forms the MEROPS peptidase family C3 (picornain family) of clan PA.

The 3C/3CL protease domain adopts a chymotrypsin-like fold with a cysteine nucleophile in place of a commonly found serine which suggests that the cysteine and serine perform an analogous catalytic function. The catalytic triad is made of a histidine, an aspartate/glutamate and the conserved cysteine in this sequential order. The 3C/3CL protease domain folds into two antiparallel β barrels that are linked by a loop with a short α-helix in its middle, and flanked by two other α-helices at the N- and C-terminal. The two barrels are topologically equivalent and are formed by six antiparallel β strands with the first four organised into a Greek key motif. The active-site residues are located in the cleft between the two barrels with the nucleophilic Cys from the C-terminal barrel and the general acid base His-Glu/Asp from the N-terminal barrel .
Core-binding (CB) domain (CB)
Type: Domain

Tyrosine-type site-specific recombinases mediate a wide range of important genetic rearrangement reactions. They catalyse functionally diverse processes, including integration and excision of phages from their host chromosomes, conjugative transposition, partitioning of phage, bacterial and plasmid genomes during cell division, antigenic phase variation, dissemination of antibiotic- and antiseptic-resistance gene cassettes, and relaxation of DNA supercoils. Tyrosine recombinases have two or three domains, depending upon whether the system includes regulated integration and excision reactions. The C-terminal catalytic domain contains six active site amino acids, RK(H/K)R(H/W)Y, required for catalysis. The core-binding (CB) domain, which interacts primarily with the major groove on the attachment site and facilitates binding to the core DNA sequence, is widely conserved among viral, eubacterial and archaeal recombinases. It is also involved in protein-protein interactions. Some recombinases, like lambda Int and IntDOT, have an additional amino-terminal domain that recognises sites, called arm-type sites, that flank the crossover region and gives directionality to the recombination reaction .

This entry represents the CB domain, which contains four major α-helices, arranged in an orthogonally crossed conformation .
Zinc finger C4H2-type (ZF_C4H2)
Type: Domain

This domain can be found in a conserved family (known as ZC4H2 family) in metazoans. The gene that encodes the human ZC4H2 is located on the X chromosome and has been found to be expressed in various human tissues, particularly fetal brain. ZC4H2 plays an important role during embryonic development of the central and peripheral nervous systems. Alterations of ZC4H2 orthologues in mouse brain and zebrafish affect central nervous system (CNS) embryogenesis, particularly the development and specification of dendritic spines. In humans, defects in ZC4H2 have been found in males affected by severe intellectual disability in variable association with spasticity, hypereflexia and/or pyramidal signs, seizures or CNS abnormalities, muscle weakness, and joint contractures (arthrogryposis multiplex congenital; AMC). The ZC4H2 gene encodes a zinc-finger protein with a C-terminal domain, which includes a putative C4H2 zinc-finger characterised by four cysteine residues and two histidine residues, and a coiled-coil domain .

This entry represents the C4H2-type zinc finger domain.