SII-SWORD/CoKE huggingface dataset:
Bypass-of-forespore C, N-terminal (BOFC_N)
Type: Domain

Bypass of forespore C (BofC) is a monomer made up of two domains, an N-terminal and a C-terminal domain. The N-terminal domain of BofC is composed of a four-stranded β-sheet covered by an α-helix. The β-sheet has a beta2-beta1-beta4-beta3 topology, where strands beta1 and beta2 and strands beta3 and beta4 are connected by β-turns, whereas strands beta2 and beta3 are joined by an α-helix that runs across one face of the β-sheet. This domain is similar to the third immunoglobulin G-binding domain of protein G from Streptococcus, the latter belonging to a large and diverse group of cell surface-associated proteins that bind to immunoglobulins. It has been hypothesised that this domain may be a mediator of protein-protein interactions involved in proteolytic events at the cell surface .
Outer capsid protein VP9/VP10/VP11 (VP9/VP10/VP11)
Type: Family

The entry represents proteins with various designations in the seadornavirus group: VP9 in Banna virus, VP10 in Liao ning virus, and VP11 in Kadipiro virus. VP9 is a spike-forming protein that mediates virion attachment to the host cell receptors and plays a major role in cell penetration .
Domain of unknown function DUF1883 (DUF1883)
Type: Domain

This domain corresponds to a predicted ligand-binding domain of the PPC-like β-sandwich fold. It has been observed in conserved gene neighbourhoods with diverse nucleotide-activated effector and related conflict systems, which potentially recognises invasive molecules and initiates system responses or directly triggers directly-associated effector domains .
Protein of unknown function DUF1867 (DUF1867)
Type: Family

This entry represents a group of hypothetical proteins found in various bacteria and archaea. The structure of MTH1675 from Methanobacterium thermoautotrophicum has a three-layer α/β/α structure, similar to that found in the C-terminal domain of pyruvate kinase.
Acetylaranotin biosynthesis cluster protein L (AtaL)
Type: Family

This entry includes acetylaranotin biosynthesis cluster protein L (AtaL) from Aspergillus terreus, which is a non-ribosomal peptide synthetase. It is required for the biosynthesis of the toxin acetylaranotin, which is a disulfide bridged cyclic dipeptide . There are a number of steps in the biosyntheis of this epipolythiodioxopiperazine toxin from two phenylananines, but the specific function of AtaL has yet to be determined . Homologues are also known from bacteria.
Vasopressin V1 receptor, C-terminal (V1R_C)
Type: Domain

This is the conserved C-terminal domain of Vasopressin V1a/b receptors (V1R), which is involved in receptor trafficking and facilitates the interaction between the intracellular loops of the receptor, the G proteins and coupling to phospholipase C . This domain is unstructured and may reflect a conformational plasticity that may be necessary for proper function of V1R .
Domain of unknown function DUF1858 (DUF1858)
Type: Domain

This protein has no known function. It is found in various hypothetical bacterial proteins.
DP-EP family (DP-EP)
Type: Family

The DP-EP family of proteins, formerly known as DUF1888 have been shown to catalyse a cleavage of an internal peptide bond .
Protein of unknown function DUF1889 (DUF1889)
Type: Family

This family consist of hypothetical bacterial proteins.
Protein of unknown function DUF1892 (DUF1892)
Type: Family

Proteins in this entry, which are synthesised by Saccharomycetes, adopt a structure consisting of a four-stranded β-sheet, with strand order beta2-beta1-beta4-beta3, and two α-helices, with an overall topology of β-β-α-β-β-α. They have no known function .
Protein of unknown function DUF1896 (DUF1896)
Type: Family

This domain is found in a set of hypothetical bacterial proteins.
Polyketide synthase NorB/C/GfsB-E-like, docking domain (NorB/c/GfsB-D-like_docking)
Type: Domain

This entry represents the N-terminal docking domain found in modular polyketide synthases, such as Spectinabilin polyketide synthase system protein NorB/C and polyketide synthase GfsB-D and related sequences from actinomycetes, which assumes an α-helical structure, wherein two α-helices are connected by a short loop. Two such N-terminal domains dimerise to form amphipathic parallel α-helical coiled coils: dimerisation is essential for protein function .
Quinohemoprotein amine dehydrogenase, gamma subunit, structural domain (QH-AmDH_gsu_dom)
Type: Domain

Quinohemoprotein amine dehydrogenases (QHNDH)

) are enzymes produced in the periplasmic space of certain Gram-negative bacteria, such as Paracoccus denitrificans and Pseudomonas putida, in response to primary amines, including n-butylamine and benzylamine. QHNDH catalyses the oxidative deamination of a wide range of aliphatic and aromatic amines through formation of a Schiff-base intermediate involving one of the quinone O atoms . Catalysis requires the presence of a novel redox cofactor, cysteine tryptophylquinone (CTQ). CTQ is derived from the post-translational modification of specific residues, which involves the oxidation of the indole ring of a tryptophan residue to form tryptophylquinone, followed by covalent cross-linking with a cysteine residue . There is one CTQ per subunit in QHNDH. In addition to CTQ, two haem c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor, cytochrome c-550 .

QHNDH is a heterotrimer of alpha, beta and gamma subunits. The alpha and beta subunits contain signal peptides necessary for the translocation of QHNDH to the periplasm. The alpha subunit is composed of four domains - domain 1 forming a dihaem cytochrome, and domains 2-4 forming antiparallel β-barrel structures; the beta subunit is a 7-bladed β-propeller that provides part of the active site; and the small, catalytic gamma subunit contains the novel cross-linked CTQ cofactor, in addition to additional thioester cross-links between Cys and Asp/Glu residues that encage CTQ. The gamma subunit assumes a globular secondary structure with two short α-helices having many turns and bends .

This entry represents the main structural domain of the QHNDH gamma subunit.
Bacteriophage T4, Gp59, helicase assembly protein, N-terminal (Phage_T4_Gp59_N)
Type: Domain

The Bacteriophage T4 gene 59 helicase assembly protein (Gp59) is required for recombination-dependent DNA replication and repair, which is the predominant mode of DNA replication in the late stage of T4 infection. Gp59 accelerates the loading of the T4 gene 41 helicase during DNA synthesis by the T4 replication system in vitro. This protein binds to both T4 gene 41 helicase and T4 gene 32 single-stranded DNA binding protein, and to single and double-stranded DNA .

The structure of Gp59 helicase assembly protein reveals a novel α-helical bundle fold with two domains of similar size. Surface residues are predominantly basic (pI 9.37) with clusters of acidic residues but exposed hydrophobic residues suggest sites for potential contact with DNA and with other protein molecules . The N-terminal domain shares structural homology with the high mobility group (HMG) proteins from eukaryotic organisms and it has been suggested that it plays a role in duplex DNA binding ahead of the fork. The C-terminal domain interacts with the helicase (T4 gp41) and with SSB (single-stranded binding protein T4 gp32) .
Bacteriophage T4, Gp59, helicase assembly protein, C-terminal (Phage_T4_Gp59_C)
Type: Domain

The Bacteriophage T4 gene 59 helicase assembly protein (Gp59) is required for recombination-dependent DNA replication and repair, which is the predominant mode of DNA replication in the late stage of T4 infection. Gp59 accelerates the loading of the T4 gene 41 helicase during DNA synthesis by the T4 replication system in vitro. This protein binds to both T4 gene 41 helicase and T4 gene 32 single-stranded DNA binding protein, and to single and double-stranded DNA .

The C-terminal domain of the T4 gene 59 helicase assembly protein consists of seven α-helices with short intervening loops and turns; the surface of the domain contains large regions of exposed hydrophobic residues and clusters of acidic and basic residues. The hydrophobic region on the 'bottom' surface of the domain near the C-terminal helix binds the leading strand DNA, whilst the hydrophobic region on the, top, surface of the domain lies between the two arms of the fork DNA, allowing for T4 gene 41 helicase binding and assembly into a hexameric complex around the lagging strand .
Necrosis inducing protein-1 (NIP1)
Type: Family

Necrosis inducing protein-1 (NIP1) is a small phytotoxic protein secreted by the barley pathogen Rhynchosporium secalisconsists. It is a fungal avirulence protein on host plants of the Rrs1 resistance genotype . NIP1 consists of two parts containing β-sheets of two and three anti-parallel strands, respectively. Five intramolecular disulphide bonds stabilise these parts and their position with respect to each other, providing a high level of stability .
Zinc finger, DNA-directed DNA polymerase, family B, alpha (Znf_DNA-dir_DNA_pol_B_alpha)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

The DNA Polymerase alpha zinc finger domain adopts an α-helix-like structure, followed by three turns, all of which involve proline. The resulting motif is a helix-turn-helix motif, in contrast to other zinc finger domains, which show anti-parallel sheet and helix conformation. Zinc binding occurs due to the presence of four cysteine residues positioned to bind the metal centre in a tetrahedral coordination geometry. The function of this domain is uncertain: it has been proposed that the zinc finger motif may be an essential part of the DNA binding domain. It is involved in providing a structural platform for interactions with both oligonucleotide/oligosaccharide (OB) and phosphoesterase domains of the B subunit .
Cytochrome b-c1 complex subunit 10 (UQCR)
Type: Family

The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is an essential component of the mitochondrial cellular respiratory chain. This family represents the 6.4kDa protein, which may be closely linked to the iron-sulphur protein in the complex and function as an iron-sulphur protein-binding factor .
Antitoxin epsilon/PezA domain (Epsilon_PezA_dom)
Type: Domain

The epsilon antitoxin, produced by various prokaryotes, forms part of a post-segregational killing system, which is involved in the initiation of programmed cell death of plasmid-free cells. The protein is folded into a three-helix bundle directly interacting with the zeta toxin, inactivating it .

PezA is the cognate antitoxin to the S. pneumoniae PezT toxin. PezA shares sequence similarity in the C-terminal region with the epsilon antitoxin. The PezA protein functions as a transcriptional repressor of the pezAT operon together with PezT, by binding a palindrome sequence that overlaps the promoter. This differs from the epsilon-zeta system in which epsilon functions solely as the antitoxin and transcriptional regulation is carried out by another protein designated omega .
Surfactant protein C, N-terminal propeptide (Surfactant_protein_propep)
Type: Domain

The N-terminal propeptide of surfactant protein C adopts an α-helical structure, with turn and extended regions. Its main function is the stabilisation of metastable surfactant protein C (SP-C), since the latter can irreversibly transform from its native α-helical structure to β-sheet aggregates and form amyloid-like fibrils. The correct intracellular trafficking of proSP-C has also been reported to depend on the propeptide .
Card1, endonuclease domain (Card1_endonucl_dom)
Type: Domain

This entry represents the endonuclease domain found in a set of proteins mainly found in bacteria, including Card1 (cyclic-oligoadenylate-activated single-stranded ribonuclease and single-stranded deoxyribonuclease 1) from Treponema succinifaciens (

), a protein that is part of type III CRISPR-Cas immune response system. This protein consists of a CARF (CRISPR-associated Rossman fold) domain at the N terminus, an helical hinge domain and a C-terminal endonuclease domain . This group of proteins was previously known as DUF1887.
Integrase, lambda-type, N-terminal DNA-binding (Integrase_lambda-typ_DNA-bd_N)
Type: Domain

The amino terminal domain of bacteriophage lambda integrase folds into a three-stranded, antiparallel β-sheet that packs against a C-terminal α-helix, adopting a fold that is structurally related to the three-stranded β-sheet family of DNA-binding domains (which includes the GCC-box DNA-binding domain and the N-terminal domain of Tn916 integrase). This domain is responsible for high-affinity binding to each of the five DNA arm-type sites and is also a context-sensitive modulator of DNA cleavage .
Alkylated DNA repair protein AlkB, homologue 8, N-terminal (AlkB_hom8_N)
Type: Domain

This domain is found at the extreme N terminus of eukaryotic alkylated DNA repair protein homologues.
Far upstream element-binding protein, C-terminal (FUBP_C)
Type: Domain

This entry represents the transactivation domain found in the C-terminal of Far upstream element-binding protein 1/2 (FUBP1/2) . FUBP1 regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter . FUBP2, also known as KSRP (K homology-type splicing regulatory protein), is a single-strand-RNA binding protein that integrate different levels of gene expression and is required for proper immune response, lipid metabolism, cell fate decisions, and tissue regeneration . This domain contains the tyrosine residues required for transactivation and adopts an α-helical configuration .
Lung surfactant protein D coiled-coil trimerisation (Surfac_D-trimer)
Type: Domain

This domain is found in the SFTPD family, which includes lung surfactant protein D (SFTPD), conglutinin, collectin-43 and collectin-46. It forms a triple-helical parallel coiled coil, and mediates trimerisation of the protein .
EBP50, C-terminal (EBP50_C)
Type: Domain

This entry represents the C-terminal domain of EBP50 and similar proteins from vertebrates. This region comprises a mostly disordered region and the EBD. Association of Ezrin allows interaction of EBP50 with FERM (four-point one ERM) domains, resulting in the activation of Ezrin-radixin-moesin (ERM), with subsequent cytoskeletal modulation and cellular growth control .

This entry includes NHERF-1 and NHERF-2. These proteins, which consist of two PDZ domains and a carboxy-terminal ezrin binding domain (EBD) , function as a scaffolding protein for the glutamate transporter GLAST. NHERF1 interacts with GLAST during ER export, while NHERF2 interacts with GLAST in the secretory pathway from the ER-Golgi intermediate compartment to the plasma membrane .
Exotoxin A catalytic domain (Exotox-A_cataly_dom)
Type: Domain

Prokaryotic exotoxin A catalyses the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, with subsequent inhibition of protein synthesis .
Anti-Sigma Factor A (AsiA)
Type: Family

Anti-sigma factor A is a transcriptional inhibitor that inhibits sigma 70-directed transcription by weakening its interaction with the core of the host's RNA polymerase. It is an all-helical protein, composed of six helical segments and intervening loops and turns, as well as a helix-turn-helix DNA binding motif, although neither free anti-sigma factor nor anti-sigma factor bound to sigma-70 has been shown to interact directly with DNA. In solution, the protein forms a symmetric dimer of small (10.59kDa) protomers, which are composed of helix and coil regions and are devoid of β-strand/sheet secondary structural elements .
Transcriptional regulator HTH-type, FeoC (Tscrpt_reg_HTH_FeoC)
Type: Domain

This entry contains several transcriptional regulators, including FeoC, which contain a HTH motif. FeoC acts as a [Fe-S] dependent transcriptional repressor .
Protein-tyrosine phosphatase, YopH, N-terminal (ProtTyrPase_YopH_N)
Type: Domain

This entry represents the N-terminal domain of YopH protein tyrosine phosphatase (PTP). This domain has a compact structure composed of four α-helices and two β-hairpins. Helices alpha-1 and alpha-3 are parallel to each other and antiparallel to helices alpha-2 and alpha-4. This domain targets YopH for secretion from the bacterium and translocation into eukaryotic cells, and has phosphotyrosyl peptide-binding activity, allowing for recognition of p130Cas and paxillin . YopH from Yersinia sp. is essential for pathogenesis, as it allows the bacteria to resist phagocytosis by host macrophages through its ability to dephosphorylate host proteins, thereby interfering with the host signalling process. Yersinia has one of the most active PTP enzymes known. YopH contains a loop of ten amino acids (the WPD loop) that covers the entrance of the active site of the enzyme during substrate binding .
Beta-2-glycoprotein-1 fifth domain (Sushi_2)
Type: Domain

The fifth domain of beta-2-glycoprotein-1 (b2GP-1) is composed of four well-defined anti-parallel β-strands and two short α-helices, as well as a long highly flexible loop. It plays an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies .
Type-2 restriction enzyme NgoMIV (NgoMIV)
Type: Family

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

This entry represents NgoMIV-type prokaryotic DNA restriction enzymes exhibiting an α/β structure, with a central region comprising a mixed six-stranded β-sheet with α-helices on each side. A long 'arm' protrudes out of the core of the domain between strands beta2 and beta3 and is mainly involved in the tetramerisation interface of the protein. These restriction enzymes recognise the double-stranded sequence GCCGGC and cleave after G-1 .
Pas factor saposin domain (Pas_Saposin)
Type: Domain

Members of this entry adopt a compact structure comprising five α helices. Charged and polar residues are exposed mostly on the surface, while most of the hydrophobic residues are buried inside the hydrophobic core of the helical bundle. The precise function of this domain is unknown, but it is has been shown to induce secretion of periplasmic proteins, especially collagenase .
Protein-glutamine gamma-glutamyltransferase (Transglut_prok)
Type: Family

Protein-glutamine gamma-glutamyltransferase (also known as microbial transglutaminase, MTG) catalyses an acyl transfer reaction by means of a Cys-Asp diad mechanism, in which the gamma-carboxyamide groups of peptide-bound glutamine residues act as the acyl donors. The MTG molecule forms a single, compact domain belonging to the α+β folding class, containing 11 α-helices and 8 β-strands. The α-helices and the β-strands are concentrated mainly at the amino and carboxyl ends of the polypeptide, respectively. These secondary structures are arranged so that a β-sheet is surrounded by α-helices, which are clustered into three regions .
P3, N-terminal domain (P3_N)
Type: Domain

This entry represents the N-terminal in P3 major capside protein from Bacteriophage PRD1.

P3 adopts a double-barrel structure comprising two eight-stranded viral β-barrels or jelly rolls, each of which contains a 12-residue α-helix. This protein then trimerises through a 'trimerisation loop' sequence, and is incorporated within the viral capsid .