SII-SWORD/CoKE huggingface dataset:
Surface-adhesin protein E (Adhesin_E)
Type: Homologous_superfamily

This superfamily represents the surface-adhesion protein E. Adhesin E plays a role in pathogenesis . It binds to host proteins including plasminogen, vitronectin and laminin .
Dot/Icm secretion system IcmQ, C-terminal (Dot_Icm_IcmQ_C)
Type: Homologous_superfamily

The obligate intracellular pathogen Legionella pneumophila requires a T4bSS, known as the Dot/Icm secretion system or translocase, for growth in alveolar macrophages. It is encoded by roughly 26 dot/icm genes and its main job is to export protein effectors into the cytoplasm of host cells during infection. Many of the constituant proteins share sequence homology to genes in other bacterial conjugation systems; however, others, such as IcmR and IcmQ do not and therefore are thought to have a unique role in this secretion system. IcmQ has been shown to associate with IcmR, bind to membranes and have a critical role in the T4bSS .

This superfamily represents the C-terminal domain of IcmQ (Qc). Qc presents a novel NAD binding fold and it is believed that this causes it to act as a sensor which allows IcmR-IcmQ to interact with a critical component of the T4bSS when intracellular NAD levels are sufficient for binding .
Low molecular weight S layer protein, N-terminal, subdomain (Low_molc_weight_S-layer_N_sub)
Type: Homologous_superfamily

Clostridial species have a layer of surface proteins surrounding their membrane. This layer is comprised of a high molecular weight protein and a low molecular weight protein.

This superfamily represents a subdomain of the N-terminal domain of the Low molecular weight S layer protein (LMW SLP). Structurally, it consists of 2 α helices and 5 β strands and adopts a 2-layer sandwich architecture. Within this domain, one of the β strands is composed of C-terminal residues, while the rest of the protein is contributed to by a contiguous polypeptide chain at the N terminus .
Restriction endonuclease, type II, AvaI/BsoBI, helical domain (Restr_endonucII_AvaI/BsoBI_hel)
Type: Homologous_superfamily

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 superfamily represents the helical domain of AvaI and BsoBI restriction endonucleases, both of which recognise the double-stranded sequence CYCGRG (where Y = T/C, and R = A/G) and cleave after C-1 . Structurally, this domain consists of two long α helices joined by some shorter ones. One of the longer helices curves inwards towards DNA, while the other is kinked outwards. BsobI is made up of this helical domain, and another more compact globular domain (consisting of smaller helices and some b-strand elements). Within the endonuclease, this domain plays a role in DNA binding, so that the globular (catalytic domain) has a higher concentration of localised substrate .
Nab2/ZC3H14, N-terminal domain superfamily (Nab2/ZC3H14_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of the nuclear abundant poly(A) RNA-bind protein 2 (Nab2), a yeast heterogeneous nuclear ribonucleoprotein that modulates poly(A) tail length and mRNA. This domain can also be found in Its animal homologue, ZC3H14, which has been shown to control poly(A) tail length in neuronal cells . The N-terminal domain mediates interactions with the C-terminal globular domain, Myosin-like protein 1 and the mRNA export factor, Gfd1. An essential hydrophobic Phe73 patch on the N-terminal domain is thought to be an important component of the interface between Nab2 and Mlp1 .
Poxvirus mRNA capping enzyme, small subunit superfamily (Poxvirus_mRNA-cap_ssu_sf)
Type: Homologous_superfamily

This superfamily represents the small subunit of the poxvirus mRNA capping enzyme. Its structure suggests that it started as an RNA cap 2-prime O-methyltransferase, subsequently evolving to a catalytically inactive form that has been retained in order to help stabilise the large subunit, D1, and to enhance its methyltransferase activity through an allosteric mechanism .
Phosphoprotein P, oligomerisation domain 1 (PProtein_oligomer_dom1)
Type: Homologous_superfamily

Phosphoprotein P, an indispensable subunit of the viral polymerase complex, is a modular protein organised into two moieties that are both functionally and structurally distinct: a well-conserved C-terminal moiety that contains all the regions required for transcription, and a poorly conserved, intrinsically unstructured N-terminal moiety that provides several additional functions required for replication. The N-terminal moiety is responsible for binding to newly synthesised free N(0) (nucleoprotein that has not yet bound RNA), in order to prevent the binding of N(0) to cellular RNA. The C-terminal moiety consists of an oligomerisation domain, an N-RNA (nucleoprotein-RNA)-binding domain and an L polymerase-binding domain . The oligomerisation domain reveals a homotetrameric coiled coil structure with many details that are different from classic coiled coils with canonical hydrophobic heptad repeats .

This superfamily represents domain 1 of the phosphoprotein P oligomerisation domain from Sendai virus as well as from close family members.
Cysteine protease, VirA/EspG, N-terminal (Cys_protease_VirA/EspG_N)
Type: Homologous_superfamily

EspG and VirA are delivered into infected host epithelial cells by a type III secretory system . These proteins function through the disruption of the host cell microtubule network . VirA acts as a cysteine protease (

) on alpha-tubulin, a major component of microtubules, in order to destabilise surrounding microtubules and invade the cytoplasm of their target host cells . VirA also promotes the formation of membrane ruffles through the activation of host rac1, which is associated with the destruction of microtubule networks . In this way, VirA creates a tunnel inside the host cell cytoplasm by breaking down the microtubule infrastructure, which facilitates the bacterium's movement through the cytoplasm and also helps other bacteria move faster during the invasion of the eukaryotic cell.

This superfamily family represents the N-terminal domain of VirA/EspG. Structurally, this domain consists of 4 β strands and 2 α helices.
Thiamine-binding lipoprotein, domain I (CypI_dom_I)
Type: Homologous_superfamily

Thiamine-binding lipoprotein (Cypl) and related proteins are specific to Mycoplasma species. Cypl, also known as p37, whose gene is part of an operon encoding two additional proteins, which are highly similar to components of the periplasmic binding-protein-dependent transport systems of Gram-negative bacteria. It has been suggested that p37 is part of a homologous, high-affinity transport system in Mycoplasma hyorhinis, a Gram-positive bacterium . Its structure indicates that it is a thiamine pyrophosphate-binding protein . The monomer is a mixed α/β fold split into two globular domains (domains I and II) connected by two linker regions and the C-terminal helix.

This entry represents domain I, which consists of a six-stranded β-sheet flanked by seven helices.
Extracytoplasmic thiamine-binding lipoprotein, domain II (CypI_dom_II)
Type: Homologous_superfamily

Thiamine-binding lipoprotein (Cypl) and related proteins are specific to Mycoplasma species. Cypl, also known as p37, whose gene is part of an operon encoding two additional proteins, which are highly similar to components of the periplasmic binding-protein-dependent transport systems of Gram-negative bacteria. It has been suggested that p37 is part of a homologous, high-affinity transport system in Mycoplasma hyorhinis, a Gram-positive bacterium . Its structure indicates that it is a thiamine pyrophosphate-binding protein . The monomer is a mixed α/β fold split into two globular domains (domains I and II) connected by two linker regions and the C-terminal helix.

This entry represents domain II, which consists of five β strands and five α helices.
Antiactivator protein ExsD, domain 1 (ExsD_dom1)
Type: Homologous_superfamily

The antiactivator protein ExsD represses the transcriptional activator ExsA. ExsA activates expression of type III secretion system genes. ExsD inhibits the DNA-binding and self-association properties of ExsA . Repression of ExsA by ExsD is relieved by the secretion chaperone ExsC .

This superfamily represents the domain 1 of ExsD, located at the N terminus of the protein, which is exclusively helical.
Antiactivator protein ExsD, domain 2 (ExsD_dom2)
Type: Homologous_superfamily

The antiactivator protein ExsD represses the transcriptional activator ExsA. ExsA activates expression of type III secretion system genes. ExsD inhibits the DNA-binding and self-association properties of ExsA . Repression of ExsA by ExsD is relieved by the secretion chaperone ExsC .

This superfamily represents the domain 2 of ExsD, which is consists of five helices and two β sheets.
Putative mobile pathogenicity island, N-terminal domain (SAPI_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in a group of putative Staphylococcus pathogenicity island proteins. SAPIs (S. aureus pathogenicity islands) are responsible for many superantigen-related diseases in humans as they carry two or more superantigens . This domain consists of 5 β strands and 1 α helix.
Tenuivirus NS3 (Tenui_NS3)
Type: Homologous_superfamily

Plant viruses encode specific proteins known as movement proteins (MPs) to control their spread through plasmodesmata (PD) in walls between cells as well as from leaf to leaf via vascular-dependent transport. During this movement process, the virally encoded MPs interact with viral genomes for transport from the viral replication sites to the PDs in the walls of infected cells along the cytoskeleton and/or endoplasmic reticulum (ER) network. The virus is then thought to move through the PDs in the form of MP-associated ribonucleoprotein complexes or as virions . The NS3 protein appears to function as an RNA silencing suppressor .

This superfamily includes ssRNA negative-strand crop plant tenuivirus NS3.
Rubella capsid domain superfamily (Rubella_Capsid_sf)
Type: Homologous_superfamily

Rubella virus is an enveloped positive-strand RNA virus of the family Togaviridae. Virions are composed of three structural proteins: a capsid and two membrane-spanning glycoproteins, E2 and E1. During virus assembly, the capsid interacts with genomic RNA to form nucleocapsids. It has been discovered that capsid phosphorylation serves to negatively regulate binding of viral genomic RNA. This may delay the initiation of nucleocapsid assembly until sufficient amounts of virus glycoproteins accumulate at the budding site and/or prevent non-specific binding to cellular RNA when levels of genomic RNA are low. It follows that at a late stage in replication, the capsid may undergo dephosphorylation before nucleocapsid assembly occurs .

This superfamily represents a domain found in the rubella capsid protein. Structurally, it consists of 5 β strands and a two-turn α helix. The 5 β strands are arranged anti-parallel and within the capsid protein are labelled ABCDE. The two-turn α helix is positioned between strands B and C. Within rubella virus, capsid protein forms a two-fold symmetric dimer.
Fimbrillin-like, C-terminal (Mfa-like_2_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain found in fimbrillin proteins. Proteins in this family are typically between 348 and 360 amino acids in length. Analysis of structural comparisons shows this family to be part of the FimbA (CL0450) superfamily of adhesin components or fimbrillins.
Her-1, C-terminal (Her-1_C)
Type: Homologous_superfamily

Her-1 adopts an all-helical structure with two subdomains: residues 19-80 comprise a left-handed three-helix bundle with an overhand connection between the second and third helices, whilst residues 81-164 comprise a left-handed anti-parallel four-helix bundle in which the first helix consists of four consecutive turns of 3-10-helix. Fourteen Cys residues are conserved in all known HER-1 sequences and form seven disulphide bonds. The protein dictates male development in Caenorhabditis elegans, probably by playing a direct role in cell signalling during C. elegans sex determination. It also inhibits the function of tra-2a .

This superfamily represents the second subdomain located in the C-terminal region of Her-1.
Cystovirus, RNA-directed RNA polymerase, N-terminal (Cystovir_RNA-dir_pol_N)
Type: Homologous_superfamily

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This superfamily represents the N-terminal region of RNA-directed RNA polymerase (also known as protein P2) from various Cystoviruses, such as Bacteriophage phi-6 and Bacteriophage phi-13 . The RdRp protein of Cystoviruses is capable of primer-independent initiation, as are many RNA polymerases.
JBP1, DNA-binding domain superfamily (DB_JBP1_sf)
Type: Homologous_superfamily

The J-binding protein 1 (JBP1) is essential for biosynthesis and maintenance of DNA base-J (beta-d-glucosyl-hydroxymethyluracil). Base-J and JBP1 are confined to some pathogenic protozoa and are absent from higher eukaryotes, prokaryotes and viruses. JBP1 recognizes J-containing DNA (J-DNA) through the DNA-Binding JBP1 domain (DB-JBP1), which binds to J-DNA with approximately the same affinity and specificity as full-length JBP1. Structure analysis of DB-JBP1 revealed a helix-turn-helix variant fold, a 'helical bouquet' with a 'ribbon' helix encompassing the amino acids responsible for DNA binding. Mutation of a single residue (Asp525) in the ribbon helix abrogates specificity toward J-DNA .
TBP-interacting protein, C-terminal (TIP_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal of the TBP-interacting proteins (TIPs), which includes several newly discovered transcription factors that could interact with TBP (TATA-box binding protein). This interaction would in turn prevent interaction between TBP and TATA-DNA, required for basal transcription in eukaryotic and archaeal cells. The C-terminal domain comprises three α-helices, six β-strands, and two 3(10)-helices; however, the specific function of this domain is yet to be elucidated .
LntA, helical domain (LntA_helix)
Type: Homologous_superfamily

LntA is a virulence factor from the bacterium Listeria monocytogenes that stimulates interferon responses during infection by inhibiting BAHD1, a nuclear protein involved in gene silencing by promoting heterochromatin formation. The secreted form of LntA can be subdivided into two domains; the trunk of the protein is formed by a bundle of helices, H1 to H3, while H4 and H5 protrude from one side of the protein. The positioning of the elbow relative to the trunk creates an elongated groove on LntA's surface, lined by charged patches. The K180/K181 dilysine motif on the surface of helix H5 is essential for BAHD1 recognition .
T26-6p, C-terminal domain superfamily (T26-6p_C_sf)
Type: Homologous_superfamily

The T26-6p protein, a large protein encoded by a plasmid from the hyperthermophilic archaea Thermococcus, consists of three domains - two β-sandwich domains and a bundle of five α-helices. The C-terminal domain is a five-helical bundle that contains five antiparallel helices . The function of these domains is unknown.
D212, catalytic domain superfamily (D212_cat_dom_sf)
Type: Homologous_superfamily

This superfamily includes proteins found in viruses and archaea, represented by Sulfolobus spindle-shaped virus ORF D212. D212 is a type II restriction endonuclease that contains the PD-(D/E)XK catalytic motif and hence it belongs to this diverse PD-(D/E)XK nuclease superfamily. This fold and its associated catalytic residues are also found in nucleases, where they play roles in DNA replication, repair, recombination, and other processes requiring nuclease activity. While the function of D212 in the phage replication cycle remains unknown, it is speculated to be a Holliday junction cleavage .
Outer capsid protein VP9, N-terminal (VP9_N)
Type: Homologous_superfamily

VP9 is a spike-forming protein that mediates virion attachment to the host cell receptors and plays a major role in cell penetration . This superfamily represents the N-terminal domain of the VP9 protein. Structurally, this domain has a left-handed superhelix made up of three α helices. These helices interact with sister helices on other VP9 monomers to form a VP9 trimer. This VP9 trimer is then expressed on the surface of the virus particle, and implicated in receptor binding interactions.
Restriction endonuclease, type II SfiI, domain 2 (Restrct_endonuc_II_SfiI_dom2)
Type: Homologous_superfamily

SfiI is a restriction enzyme that can cleave two DNA sites simultaneously to leave 3-base 3' overhangs. It acts as a homo-tetramer and recognises a specific eight base-paid palindromic DNA sequence. After binding two copies of its recognition sequence, SfiI becomes activated leading to cleavage of all four DNA strands. The structure of SfiI consists of a central twisted β-sheet surrounded by α-helices.

This superfamily represents the domain 2 of Sfil. Structurally, it consists of 5 β-strands, 1 α-helix, and a long loop. The strands within this β-substructure are responsible for recognition of the major groove of DNA.
Restriction endonuclease, type II SfiI, domain 1 (Restrct_endonuc_II_SfiI_dom1)
Type: Homologous_superfamily

SfiI is a restriction enzyme that can cleave two DNA sites simultaneously to leave 3-base 3' overhangs. It acts as a homo-tetramer and recognises a specific eight base-paid palindromic DNA sequence. After binding two copies of its recognition sequence, SfiI becomes activated leading to cleavage of all four DNA strands. The structure of SfiI consists of a central twisted β-sheet surrounded by α-helices.

This superfamily represents the domain 1 of the Sfil.
Rac1-binding domain, C-terminal (Rac1-bd_C)
Type: Homologous_superfamily

The Rac1-binding domain is the C-terminal portion of YpkA from Yersinia. It is an all-helical molecule consisting of two distinct subdomains connected by a linker. The N-terminal end of this domain (residues 434-615) consists of six helices organised into two three-helix bundles packed against each other. This region is involved with binding to GTPases. The C-terminal end (residues 705-732) is a novel and elongated fold consisting of four helices clustered into two pairs, and this fold carries the helix implicated in actin activation. The Rac1-binding domain mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases, thereby inhibiting nucleotide exchange in Rac1 and causing cytoskeletal disruption in the host .

This superfamily represents the C-terminal subdomain of the Rac1-binding domain. This domain is made up of one long, kinked helix and three smaller helices. The long helix has 2 points of contact which allow the domain to bind Rac1 at regions called Switch I and Switch II on the Rac1 protein.
Rac1-binding domain, N-terminal (Rac1-db_N)
Type: Homologous_superfamily

The Rac1-binding domain is the C-terminal portion of YpkA from Yersinia. It is an all-helical molecule consisting of two distinct subdomains connected by a linker. The N-terminal end of this domain (residues 434-615) consists of six helices organised into two three-helix bundles packed against each other. This region is involved with binding to GTPases. The C-terminal end (residues 705-732) is a novel and elongated fold consisting of four helices clustered into two pairs, and this fold carries the helix implicated in actin activation. The Rac1-binding domain mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases, thereby inhibiting nucleotide exchange in Rac1 and causing cytoskeletal disruption in the host .

This superfamily represents the N-terminal GTPase binding subdomain of the Rac1-binding domain.
Restriction endonuclease, type II, BglI superfamily (Restrct_endonuc_II_BglI_sf)
Type: Homologous_superfamily

This superfamily represents the homodimeric type II restriction endonuclease BglI. It recognises the interrupted DNA sequence GCCNNNNNGGC and cleaves between the fourth and fifth unspecified base pair to produce 3' overhanging ends .
Phage bIL170 RBP, head domain (Phage_bIL170_RBP_head)
Type: Homologous_superfamily

This superfamily represents the RBP (receptor-binding protein) head domain from phage bIL170. The structure of the head monomer is remarkably close to those of other lactococcal phages, p2 and TP901-1, despite any sequence identity with them. The head domain of the bIL170 RBP binds saccharides efficiently .
DNA terminal protein Gp3, C-terminal (DNA_terminal_Gp3_C)
Type: Homologous_superfamily

The DNA terminal protein Gp3, found in a number of Bacillus phages, is linked to the 5' ends of both strands of the genome through a phosphodiester bond between the β-hydroxyl group of a serine residue and the 5'-phosphate of the terminal deoxyadenylate. This protein is essential for DNA replication and is involved in the priming of DNA elongation .

This superfamily entry represents the C-terminal priming domain of the DNA terminal protein GP3 sequences from Phi-29 like bacteriophages. In the transition from the initiation to the elongation phases, the priming domain of terminal protein moves out of the active site as polymerase elongates the primer strand. The terminal protein dissociates from the polymerase after the incorporation of approximately six nucleotides .

This domain is a four-helix bundle with a left turning up-down-up-down topology. Serine-232, which provides the priming hydroxyl group for DNA synthesis, lies in a loop at the end of the domain closest to the active site of the DNA polymerase .