SII-SWORD/CoKE huggingface dataset:
Filoviruses VP35 interferon inhibitory domain, helical subdomain (VP35_IID_hlx)
Type: Homologous_superfamily

This superfamily represents the N-terminal α-helical subdomain of VP35 IID.

The C-terminal interferon inhibitory (IID) domain of VP35, also known as RNA-binding domain (RBD) IID is made of a stretch of about 120 residues that folds
independently. The VP35 IID structure is organised into 2 subdomains: an N-
terminal α-helical subdomain and a C-terminal β-sheet subdomain. The α-helical subdomain consists of a four helix bundle, while the β-sheet subdomain is formed by four antiparallel β-strands as well as an α-helix and a type II polyproline helix. The VP35 IID structure contains 2 basic patches that are highly conserved among members of the Filoviridae family. The first basic patch is located in the helical subdomain and its functional significance remains unknown. The second one, the so-called central basic patch, is located in the β-sheet subdomain and contains residues that are required for dsRNA binding and IFN inhibition .

The Filoviridae family of viruses, which includes marburgvirus (MARV) and
ebolavirus (EBOV), can cause intermittent outbreaks that often result in high
fatality rates. The family consists of five species of EBOV, Zaire, Reston,
Sudan, Tai Forest, and Bundibugyo; one species of MARV; and a proposed genus
Cuevavirus possessing a single species Lloviu cuevavirus. MARV and EBOV share
a common genome organisation but show important differences in replication
complex formation, cell entry, host tropism, transcriptional regulation, and
immune evasion .

Filoviruses counteract innate immunity through the multifunctional viral
protein (VP) 35 proteins, which perform critical roles in viral RNA synthesis,
virus assembly, and virus structure. VP35 contains an N-terminal coiled-coil
domain required for its oligomerisation and a C-terminal interferon (IFN)
inhibitory domain (IID). Mutations within the VP35 IID result in loss of host
immune suppression. The N terminus provides a critical oligomerisation
function, which facilitates efficient IFN inhibition through elements located
at the C terminus of VP35. The VP35 IID can also bind dsRNA and VP35-mediated
IFN antagonism correlates with dsRNA-binding activity .
Filoviruses VP35 interferon inhibitory domain, beta-sheet subdomain (VP35_IID_b-sht)
Type: Homologous_superfamily

This superfamily represents the C-terminal β-sheet subdomain of VP35 IID. The β-sheet subdomain (residues 294-340) is composed of a 4-stranded mixed β-sheet and a short helical segment .

The C-terminal interferon inhibitory (IID) domain of VP35, also known as RNA-binding domain (RBD) IID is made of a stretch of about 120 residues that folds
independently. The VP35 IID structure is organised into 2 subdomains: an N-
terminal α-helical subdomain and a C-terminal β-sheet subdomain. The α-helical subdomain consists of a four helix bundle, while the β-sheet subdomain is formed by four antiparallel β-strands as well as an α-helix and a type II polyproline helix. The VP35 IID structure contains 2 basic patches that are highly conserved among members of the Filoviridae family. The first basic patch is located in the helical subdomain and its functional significance remains unknown. The second one, the so-called central basic patch, is located in the β-sheet subdomain and contains residues that are required for dsRNA binding and IFN inhibition .

The Filoviridae family of viruses, which includes marburgvirus (MARV) and
ebolavirus (EBOV), can cause intermittent outbreaks that often result in high
fatality rates. The family consists of five species of EBOV, Zaire, Reston,
Sudan, Tai Forest, and Bundibugyo; one species of MARV; and a proposed genus
Cuevavirus possessing a single species Lloviu cuevavirus. MARV and EBOV share
a common genome organisation but show important differences in replication
complex formation, cell entry, host tropism, transcriptional regulation, and
immune evasion .

Filoviruses counteract innate immunity through the multifunctional viral
protein (VP) 35 proteins, which perform critical roles in viral RNA synthesis,
virus assembly, and virus structure. VP35 contains an N-terminal coiled-coil
domain required for its oligomerisation and a C-terminal interferon (IFN)
inhibitory domain (IID). Mutations within the VP35 IID result in loss of host
immune suppression. The N terminus provides a critical oligomerisation
function, which facilitates efficient IFN inhibition through elements located
at the C terminus of VP35. The VP35 IID can also bind dsRNA and VP35-mediated
IFN antagonism correlates with dsRNA-binding activity .
Pneumovirus matrix, N-terminal (Pneu_matrix_N)
Type: Homologous_superfamily

The matrix proteins of Pneumovirus are transcriptional processivity and antitermination factor, and play a crucial role in viral assembly.

This superfamily represents the N-terminal domain found in Pneumovirus matrix protein. Structurally, it consists of 8 β strands and 3 α helices. Within Pneumovirus matrix protein, this domain is believed to mediate species-specific interactions.
Agglutinin-like protein, N-terminal, N2 subdomain (Agglutinin-like_N_N2)
Type: Homologous_superfamily

Candida albicans is the most prevalent fungal pathogen in humans and a major source of life-threatening nosocomial infections . It codes for several cell surface Als (agglutinin-like sequence) glycoproteins (Als1-Als7 and Als9) which are key virulence factors and have been associated with binding of host-cell surface proteins and small peptides of random sequence, the formation of biofilms and amyloid fibres. The N-terminal domain of Als proteins (NT-Als) is involved in adhesive function and comprises two tandem DEv-IgG type immunoglobulin domains, N1 and N2, arranged in a fold similar to that of the MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) domain . It also possesses a peptide-binding cavity (PBC) that can bind peptides with broad specificity.

This superfamily represents the N2 subdomain found in the N-terminal of Als proteins.
Long-chain fatty acyl-CoA thioesterase, Rv0098-like superfamily (FcoT_ThioEstase_Rv0098-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain with a hot-dog fold. The structure of Rv0098 from M. tuberculosis suggested a thioesterase function. Assays showed that this protein was a thioesterase with a preference for long chain fatty acyl groups . The maximal Kcat was observed for palmitoyl-CoA, although longer and shorter molecules were also cleaved. In solution this protein forms a homo-hexameric complex.

The M. tuberculosis FcoT protomer has an alpha/beta "hot dog" fold, in which an antiparallel β sheet (B1-B6), referred to in the literature as the "bun," wraps around a six-turn α helix (H3) typically called the "sausage." Three short α helices (H1, H2, and H4) cover the open side of the "bun" . This "hot dog" topology is common for dehydratases and thioesterases .
Carboxysome shell carbonic anhydrase, N-terminal domain superfamily (CsoSCA_N_sf)
Type: Homologous_superfamily

Carboxysome Shell Carbonic Anhydrase (Csos3) is a bacterial carbonic anhydrase localised in the carboxysome, where it converts bicarbonate ions to carbon dioxide for use in carbon fixation. The superfamily represents one of the three domains of Csos3, the N-terminal domain, composed primarily of four α-helices .
Carboxysome shell carbonic anhydrase, C-terminal domain superfamily (CsoSCA_C_sf)
Type: Homologous_superfamily

Carboxysome Shell Carbonic Anhydrase (Csos3) is a bacterial carbonic anhydrase localised in the carboxysome, where it converts bicarbonate ions to carbon dioxide for use in carbon fixation. This superfamily represents one of the three domains of Csos3, the C-terminal domain, which has a weak structural similarity to the central catalytic domain .
Calcium binding protein CcbP, beta-barrel domain (CcbP_b-brl)
Type: Homologous_superfamily

This superfamily represents a domain of 5 anti-parallel β strands arranged into a β-barrel from the calcium-binding protein CcbP. The 2nd and 3rd strands are linked by a short 3(10)-helix. The 4th and 5th strands are also linked by a short 3(10)-helix.

CcbP is a Ca(2+) binding protein found in bacteria which is thought to bind Ca(2+) by protein surface charge. When bound to Ca(2+), the protein becomes more compact and the level of free calcium decreases. Within the bacteria, Ca(2+) has a role in the early stages of heterocyst differentiation. The free Ca(2+) concentration which is regulated by CcbP is critical for the differentiation process . Calcium signalling is widespread in bacterial species, and prokaryotic cells like eukaryotes are equipped with all the elements to maintain Ca2+ homeostasis .
Uracil DNA glycosylase inhibitor superfamily (SAUGI_sf)
Type: Homologous_superfamily

Uracil-DNA glycosylase inhibitors are DNA mimic proteins that prevent the DNA binding sites of UDGs (Uracil DNA glycosylase) from interacting with their DNA substrate . This superfamily represents the Staphylococcus aureus' uracil-DNA glycosylase inhibitor (SAUGI) which acts as a uracil-DNA glycosylase inhibitor that breaks the uracil-removing activity of S. aureus uracil-DNA glycosylase (SAUDG). This way, SAUGI prevents SAUDG from binding to its DNA substrate and performing DNA repair .
Stc1 domain superfamily (Stc1_sf)
Type: Homologous_superfamily

The Stc1 domain contains 8 conserved cysteines that may bind to zinc. In S. pombe, proteins containing the domain act as protein linkers, which link the chromatin modifying CLRC complex to RNAi by tethering it to the RITS complex. This domain has a slightly different arrangement of its CxxC pairs from the LIM domain, hence it is not part of that family . The tandem zinc-finger structure is involved in binding Ago1, whereas the non-conserved C-terminal region mediates association with CLRC .

This superfamily represents the Stc1 domain.
Spidroin, repetitive domain (Spidroin_repeat)
Type: Homologous_superfamily

Spidroins are large silk proteins which display relatively conserved terminal domains and a characteristic core repetitive region that amounts to around 90 % of the full length sequence and is believed to dominate the mechanical properties of spider silk. Spidroins are secreted into silk glands and then stably stored where their concentration increases up to 50 % (w/w) allowing them to self-assemble into silk fibres. Spider silks are renowned for their excellent mechanical properties and biomimetic and industrial potentials. The orb-web spiders employ up to seven types of abdominal glands to produce silks for various purposes, ranging from prey capture to offspring protection in egg cases. Egg-case silk fibroins are synthesised only in female tubuliform (cylindrical) silk glands for the construction of protective egg cases, where eggs undergo development. Two spidroins, tubliform spidroin (TuSp1), the major component of egg-case silk, and the recently characterised aciniform spidroin (AcSp1) participate in the egg case formation: AcSp1 forms the inner egg case, while TuSp1 forms the outer egg case. Studies on both proteins have revealed poor sequence similarity between their respective repetitive (RP) domains but a remarkable structural identity. The latter suggests that these two spidroins may share some common characters in fibre formation mechanism and silk fibre properties .

This superfamily represents a structural domain which is found in repeats of up to 20 in many individuals (although this is not necessarily the case). RP1 makes up structural domains in the N terminus while RP2 makes up structural domains in the C terminus .
Staphylcoagulase, N-terminal, subdomain 2 (Staphylcoagulase_N_2)
Type: Homologous_superfamily

Staphylococcus aureus secretes a cofactor called staphylocoagulase. Staphylocoagulase is an extracellular protein that forms a complex with human prothrombin, and activates it without the usual proteolytic cleavages . The resulting complex directly initiates blood clotting.

This superfamily represents the subdomain 2 found in the N-terminal domain of staphylocoagulase. Structurally it consists of a three-helix bundle.
Staphylcoagulase, N-terminal, subdomain 1 (Staphylcoagulase_N_1)
Type: Homologous_superfamily

Staphylococcus aureus secretes a cofactor called staphylocoagulase. Staphylocoagulase is an extracellular protein that forms a complex with human prothrombin, and activates it without the usual proteolytic cleavages . The resulting complex directly initiates blood clotting.

This superfamily represents the subdomain 1 found in the N-terminal domain of staphylocoagulase. Structurally it consists of a three-helix bundle.
Baseplate protein Gp16, domain D4 (Gp16_domD4)
Type: Homologous_superfamily

ORF16 (or gp16) is a tail-phage P2-like protein that forms part of the base-plate at the tip of the phage tail. The whole base-plate complex is involved in host recognition and attachment, and consists of several proteins derived from consecutive open-reading-frames. This central domain is expressed from ORF16 in the lactococcal P2-phage and forms a trimer. ORF16 is a four domain protein that adopts a fold comparable to that of gp27 of myophage T4 .

This superfamily represents the domain 4 of the ORF16 protein . Structurally, it consists of 3 α helices and 3 β sheets.
Baseplate protein Gp16, domain 1 and 2 (Gp16_dom1_2)
Type: Homologous_superfamily

ORF16 (or gp16) is a tail-phage P2-like protein that forms part of the base-plate at the tip of the phage tail. The whole base-plate complex is involved in host recognition and attachment, and consists of several proteins derived from consecutive open-reading-frames. This central domain is expressed from ORF16 in the lactococcal P2-phage and forms a trimer. ORF16 is a four domain protein that adopts a fold comparable to that of gp27 of myophage T4 .

This superfamily represents the domains 1 and 2 of the ORF16 protein .
Cell-cell fusogen EFF/AFF, domain 3 (Fusogen_EFF/AFF_dom3)
Type: Homologous_superfamily

Cell fusion is fundamental for reproduction and organ formation. Fusion between most Caenorhabditis elegans epithelial cells is mediated by the EFF1 fusogen. AFF was first identified in EFF1 mutants. Cell fusion in all epidermal and vulval epithelia was blocked in EFF1 mutants. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeded normally . AFF1 was established as necessary for this and for the fusion of heterologous cells in C. elegans .

The transmembrane forms of FF proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of FF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity . C. elegans AFF1 and EFF1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle .

Cell-cell fusogen EFF/AFF is a three domain protein involved in cell fusion, a process that is essential for development. These proteins can be found either as a monomer or trimer. Crystal structures of the trimer show unambiguous structural homology to class II viral fusion proteins in their characteristic post-fusion hairpin conformation. The trimer subunits feature the three class II β sandwich domains, termed I, II, and III, organised in the same way as in the viral proteins .

This superfamily represents the domain 3 of the cell-cell fusogen EFF/AFF protein.
Chaperone protein gp12 superfamily (Gp12_sf)
Type: Homologous_superfamily

This entry represents a group of proteins from tailed bacteriophages and prophages from firmicutes, including Chaperone protein gp12 from Lactococcus phage p2 (also known as ORF12), which is thought to be a chaperone for the tape measure protein that might help to maintain the tape measure protein in solution during tail assembly. This late-expressed protein shows an all-α structure with five α-helices oriented to form a hydrophobic cleft on the inner surface of the protein. It adopts a trimeric assembly, forming long spirals .

ORF12 forms a trimer in phage p2, and it is suggested that this trimer acts as a chaperone for TMP hydrophobic repeats .
Sialyltransferase, N-terminal GT-B Rossman nucleotide-binding domain (Sialyltransferase_N)
Type: Homologous_superfamily

Sialyltransferases are enzymes that catalyse the transfer of sialic acid from its activated sugar nucleotide form, cytidine 5'-monophosphate sialic acid (CMP-sialic acid or CMP-Sia), to the terminal positions of glycans on glycoproteins and glycolipids.
The second and third domains in certain sialyltransferases resemble the Rossmann nucleotide-binding domain. Together, these two domains form a structure found in the glycosyltransferase B (GT-B) superfamily, and hence they are named N-terminal GT-B and C-terminal GT-B domains . A deep nucleotide-binding cleft is formed between the two domains that can accommodate substrate molecules of varied sizes and diverse structures and exhibits a large conformational change of the enzyme upon binding to CMP .

This superfamily represents the N-terminal GT-B glycosyltransferase B domain.
EV matrix protein, N-terminal (EV_matrix_protein_N)
Type: Homologous_superfamily

Ebola virus sp. are non-segmented, negative-strand RNA viruses that causes severe haemorrhagic fever in humans with high rates of mortality. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins associate with cellular membranes, interact with the cytoplasmic tails of glycoproteins, and bind to the ribonucleoprotein complex. The VP40 monomer consists of two domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N-and C-terminal domains fold into β sandwich structures of similar topology . Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to13, which are required for efficient budding . L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 .

This entry describes the VP40 N-terminal domain. It is the region of the protein where the two VP40 monomers bind.
Hemolytic toxin, N-terminal domain superfamily (Hemolysin_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in bacterial virulence factor - hemolysin - which forms pores in erythrocytes and causes them to lyse. Structurally, it consists of 3 α helices and 4 β strands, where 4 strands make up a β sheet, and pack up against the 3 short α helices. Within hemolytic toxin, e.g. cytolysin, this N-terminal domain makes up the 'pro-domain' and is cleaved from the pro-toxin to activate the toxins hemolytic function.
Apolipoprotein C-I domain superfamily (ApoC-1_sf)
Type: Homologous_superfamily

Exchangeable apolipoproteins are water-soluble protein components of lipoproteins that solubilise lipids and regulate their metabolism by binding to cell receptors or activating specific enzymes. Apolipoprotein C-I (ApoC-1) is the smallest exchangeable apolipoprotein and transfers among HDL (high density lipoprotein), VLDL (very low-density lipoprotein) and chlylomicrons. ApoC-1 activates lecithin:choline acetyltransferase (LCAT), inhibits cholesteryl ester transfer protein, can inhibit hepatic lipase and phospholipase 2 and can stimulate cell growth. ApoC-1 delays the clearance of beta-VLDL by inhibiting its uptake via the LDL receptor-related pathway . ApoC-1 has been implicated in hypertriglyceridemia , and Alzheimer s disease .

ApoC-1 is believed to comprise of two dynamic helices that are stabilised by interhelical interactions and are connected by a short linker region. The minimal folding unit in the lipid-free state of this and other exchangeable apolipoproteins comprises the helix-turn-helix motif formed of four 11-mer sequence repeats.
Baculovirus occlusion-derived virus envelope, E66, core domain (Baculo_ODV-E66_core)
Type: Homologous_superfamily

Baculovirus occlusion-derived virus (ODV) derives its envelope from an intranuclear membrane source. N-terminal amino acid sequences of the Autographa californica MNPV nuclear polyhedrosis virus (AcMNPV) envelope protein ODV-E66 is highly hydrophobic. This defined hydrophobic domain was shown to direct the protein, E66, to induce membrane microvesicles within a baculovirus-infected cell nucleus and the viral envelope. In addition, it was suggested that movement of this protein into the nuclear envelope may initiate through cytoplasmic membranes, such as endoplasmic reticulum, and that transport into the nucleus may be mediated through the outer and inner nuclear membrane .

This superfamily represents the core domain found in ODV-E66. Structurally, this domain consists of 12 β strands and 3 α helices.
Gp27, baseplate hub, domain 3 (Gp27_dom3)
Type: Homologous_superfamily

This superfamily represents the domain 3 of the baseplate hub of Gp27. Structurally, this domain consists of 7 anti-parallel β sheets and 1 α helix. Within the baseplate hub of Gp27, this domain forms a torus with domain 1, which has a similar β barrel, comprised of 8 strands. The surface of the barrel is almost entirely hydrophobic, so provides a surface for assembly of the larger baseplate complex .
Gp27, baseplate hub, domain 4 (Gp27_dom4)
Type: Homologous_superfamily

This superfamily represents the domain 4 of the baseplate hub of Gp27. Structurally, this domain consists of 3 β sheets and 2 α helices.
Gp27, baseplate hub, domain 2 (Gp27_dom2)
Type: Homologous_superfamily

This superfamily represents the domain 2 of the baseplate hub of Gp27. Structurally, this domain consists of 2 anti-parallel β sheets and 2 α helices.
EME1, nuclease domain, subdomain 1 (EME1_nucdom_sub1)
Type: Homologous_superfamily

The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix.

The nuclease domain is found in several DNA repair nucleases, including Rad1, XPF and crossover junction endonucleases EME1 (an essential component of a Holliday junction resolvase) and Mus81 . The XPF/Rad1/Mus81-dependent nuclease family specifically cleaves branched structures generated during DNA repair, replication, and recombination, and is essential for maintaining genome stability. The nuclease domain architecture exhibits remarkable similarity to those of restriction endonucleases.

This superfamily consists of the first part of the nuclease domain found in EME1.
EME1, nuclease domain, subdomain 2 (Eme1_nucdom_sub2)
Type: Homologous_superfamily

The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix.

The nuclease domain is found in several DNA repair nucleases, including Rad1, XPF and crossover junction endonucleases EME1 (an essential component of a Holliday junction resolvase) and Mus81 . The XPF/Rad1/Mus81-dependent nuclease family specifically cleaves branched structures generated during DNA repair, replication, and recombination, and is essential for maintaining genome stability. The nuclease domain architecture exhibits remarkable similarity to those of restriction endonucleases.

This superfamily consists of the second subdomain of the nuclease domain found in EME1.