SII-SWORD/CoKE huggingface dataset:
Trans-membrane regulatory protein ToxS (ToxS)
Type: Family

Gram-negative bacteria such as Vibrio cholera require the production of a number of virulence factors during infection. The ToxR and ToxS regulatory proteins control the expression of the master virulence regulator ToxT. ToxS serves as a mediator of ToxR function, perhaps by influencing its stability and/or capacity to dimerize .
Protein of unknown function DUF5366 (DUF5366)
Type: Family

This is a family of unknown function, found in Bacillales. Members of the family are predicted to have between 4 and 5 trans-membrane regions.
Beta/Mu-diguetoxin-1 (Beta/Mu-DGTX-Dc1)
Type: Family

This family members are 56-59 residue mu-diguetoxin-1 and beta-diguetoxin-1 toxins, which have been isolated from the weaving spider, Diguetia canities. These toxins were isolated as a result of their potent insect paralytic activities, and designated beta-DGTX-Dc1a, mu-DGTX-Dc1b and mu-DGTX-Dc1c (formerly DTX9.2, DTX11 and DTX12) . Diguetoxin-Dc1a (Dc1a) has been structurally characterised and shown to have disulfide bonds which form a classical inhibitor cysteine knot (ICK) motif in which the Cys13-Cys26 and Cys20-Cys40 disulfide bonds and the intervening sections of the polypeptide backbone form a 23-residue ring that is pierced by the Cys25-Cys54 disulfide bond. This ICK motif is commonly found in spider toxins, and this particular scaffold provides these peptides (so-called knottins) with an unusually high degree of chemical, thermal and biological stability. Dc1a contains an additional disulfide bond (Cys42-Cys52) that appears to serve as a molecular staple which limits the flexibility of a disordered serine-rich hairpin loop. The extended N terminus of Dc1a along with an unusually large loop between Cys26 and Cys40 enables the formation of an N-terminal three-stranded antiparallel β-sheet that is not found in any other knottin. The molecular surface of Dc1a contains a relatively uniform distribution of charged residues; moreover, there are no distinct clusters of hydrophobic residues that might mediate an interaction with lipid bilayers .
Protein of unknown function DUF5354 (DUF5354)
Type: Family

This family of unknown function is found mostly in nematodes.
Protein of unknown function DUF5363 (DUF5363)
Type: Family

Members of this entry are found in gammaproteobacteria. Their function is currently unknown.
Vacuole-related protein 17 (Vac17)
Type: Family

Vac17 serves as an adaptor protein recruiting vacuole vesicles to the actin cable tracks by its dual interaction with Vac8 and the Myo2 motor protein . It is directly phosphorylated by Cdk1. Vac17 plays an important role in vacuole inheritance and segregation in cell division .
Mating hormone A-factor 1/2 (Mfa1/2)
Type: Family

In budding yeasts, the mating hormone active factor is excreted into the culture medium by haploid cells of the A mating type and acts on cells of the opposite mating type (type alpha). It mediates the conjugation process between the two types by inhibiting the initiation of DNA synthesis in type alpha cells and synchronizing them with type A.

Mfa1 and Mfa2 are precursors of 36 and 38 amino acids, respectively. They have a single amino acid residue difference: Mfa1 contains a valine instead of the leucine in Mfa2 at position 6 of the mature a-factor .
26S Proteasome non-ATPase regulatory subunit 13 (PSMD13)
Type: Family

This entry represents non-ATPase regulatory subunit 13 of the 26S proteasome (gene name PSMD13 or Rpn9), a component of the 19S lid .
L1 transposable element, dsRBD-like domain (L1_dsRBD)
Type: Domain

This entry represents the double stranded RNA-binding-like domain of LINE-1 (L1) transposable elements .
L1 transposable element, trimerization domain (L1_trimer)
Type: Domain

This entry represents the trimerization domain found in protein ORF1 of the long interspersed nuclear element 1 (LINE-1 or L1) .
Protein of unknown function DUF5364 (DUF5364)
Type: Family

This family of unknown function is found in Saccharomycetales.
Acyl homoserine lactone synthase (AHL_synthase)
Type: Family

Members of this family are involved in quorum sensing processes. In Gram-negative bacteria, N-acylhomoserine lactones (AHLs) act as signals. As the bacterial density increases, AHLs accumulate, and once they reach a critical level (quorum), they interact with cognate receptor proteins, which then affect target gene expression. Some AHLs are synthesized by LuxM (AHL synthase) and homologues (VanM and opaM). LuxM enzyme uses S-adenosyl-methionine (SAM) as one of its two substrates and is capable of using either acyl-acyl-carrier-protein (acyl-ACP) or acyl-coenzyme A (acyl-CoA) as the other substrate . VanM, the LuxM homologue, produces two auto-inducers C6HSL and 3OC6HSL. Both autoinducers are detected by the VanN receptor. The autoinducers HAI-1, is synthesized by the cytoplasmic enzymes LuxM .
Herpesvirus glycoprotein H, C-terminal (Herpes_glycoH_C)
Type: Domain

Herpesvirus glycoprotein H (gH) is a virion associated envelope glycoprotein . Complex formation between gH and gL has been demonstrated in both virions and infected cells . This entry represents the C-terminal domain.
Small ribosomal subunit protein uS12m (Ribosomal_uS12m)
Type: Family

This entry represents the small ribosomal subunit protein uS12m found mainly in the mitochondria of some trypanosomatid species.

RPS12 is a ribosomal protein encoded by the kinetoplast mitochondrion of Kinetoplastida protists such as Trypanosoma. Homologous RPS12 proteins in bacterial ribosomes participate in stabilizing the second base pair of the codon-anticodon duplex in the A site and is likely to be critical for the fidelity of decoding process. A similar role can be anticipated for this protein in mitochondrial ribosomes. This has been shown where the product of edited RPS12 mRNA translation represented a component of the mitoribosome's small subunit .
Beta-defensin 136/42 (DEFB136/42)
Type: Family

Beta-defensins are small cationic peptides that have a triple-stranded β-sheet structure . They are characterised by the presence of multiple cysteine residues (forming three distinctive intramolecular disulfide bridges) and a highly similar tertiary structure known as the defensin motif . All beta-defensin genes encode a precursor peptide that consists of a hydrophobic, leucine-rich signal sequence, a pro-sequence, and a mature six-cysteine defensin motif at the carboxy terminus . They exhibit broad-spectrum antimicrobial properties and contribute to mucosal immune responses at epithelial sites . Several beta-defensin family members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans . In addition to the wide spectrum of antimicrobial activity, mammalian beta-defensins have been reported to have other roles in the immune system, such as the chemotactic ability for immature dendritic cells and memory T-cells via chemokine receptor-6 demonstrated by human beta-defensin-2 .

Defensin beta 136 exhibits antibacterial and antifungal activity . It has high lipopolysaccharide (LPS)-binding affinity, and may thereby be involved in immunoregulation through LPS neutralization .
Protein of unknown function DUF5368 (DUF5368)
Type: Family

This is a family of unknown function found in Proteobacteria and predicted to contain 2 trans-membrane regions.
Proteasome activator complex subunit 4 (PSME4)
Type: Family

This entry represents proteasome activator complex subunit 4 (gene name PSME4, PA2000 or BLM10), which is particularly associated with the spermatoproteasome. PSME4 binds acetylated histones which are degraded by the proteasome during spermatogenesis. Histones are bound via the bromodomain-like region. PSME4 also activates the proteasome, permitting entry of substrate into the internal chamber where degradation occurs . PSME4 is also required for the degradation of histones during the DNA damage response in somatic cells . The structure of the yeast BLM10/proteasome complex has been solved, and shows that BLM10 forms a dome structure over the proteasome entry pore, restricting access for potential substrates and inducing a disordered gate structure .
Galactose/N-acetyl-D-galactosamine lectin light subunit 1 (Gal_GalNac_light_su_1)
Type: Family

In Entamoeba histolytica, the Gal/GalNAc lectin contributes to its virulence by establishing adhesion to host cell . The Gal/GalNAc lectin is a heterodimeric molecule composed of a transmembrane heavy (170kDa) subunit and glycosylphosphatidylinositol-anchored light 31kDa and 35kDa subunits, which are non-covalently associated with an intermediate subunit of 150kDa . Inhibition of expression of 35kDa subunit of Gal/GalNAc lectin inhibits the cytotoxic and cytopathic activity of E. histolytica, but no decrease in adherence capacity to mammalian cells was evident. Interestingly, a carbohydrate-binding activity has been reported for the 35kDa light subunit of the lectin molecules of the closely related Entamoeba invadens .
Cystine knot toxin (Cys_Knot_tox)
Type: Family

This family is found in Araneaea (spiders) and family members are venomus peptides with 4 disulfide bonds. Cystine knot toxins (CKTs) are small, compact molecules cross-linked by three to five disulfide bonds and are often the key contributors to the activity and potency of the venom . While these disulfide-rich peptides can adopt a number of different structural motifs, three of the most observed structural scaffold motifs are the inhibitor cystine knot (ICK) and the disulfide-directed β-hairpin (DDH) and Kunitz motif. These venomus peptides mainly act on membrane proteins in electro-excitable cell membranes by modulating voltage-activated sodium (NaV), calcium (CaV), and potassium (KV) channels, acid-sensing ion channels (ASICs), transient receptor potential (TRP) channels, and mechanosensitive channels (MSCs) .
Satellite RNA 48kDa protein (SatRNA_48)
Type: Family

Satellite RNAs (satRNAs) are short RNA molecules, usually larger than 1,500 nt, that depend on cognate helper viruses for replication, encapsidation, movement, and transmission, but most share little or no sequence homology to the helper viruses. In contrast, satellite viruses are satRNAs that encode and are encapsidated in their own capsid proteins (CPs) . Members of this family are nonstructural proteins of 48kDa in size which have been shown to be involved in the replication of the sat-RNA. They are found in tomato black ring virus (TBRV) .
Transferrin-binding protein B, N-lobe handle (TbpB_N-lobe)
Type: Domain

Bacterial lipoproteins represent a large group of specialised membrane proteins that perform a variety of functions, including maintenance and stabilisation of the cell envelope, protein targeting and transit to the outer membrane, membrane biogenesis, and cell adherence . Pathogenic Gram-negative bacteria within the Neisseriaceae and Pasteurellaceae families rely on a specialised uptake system, characterised by an essential surface receptor complex that acquires iron from host transferrin (Tf) and transports the iron across the outer membrane. They have an iron uptake system composed of surface exposed lipoprotein, Tf-binding protein B (TbpB), and an integral outer-membrane protein, Tf-binding protein A (TbpA), that together function to extract iron from the host iron binding glycoprotein (Tf).

TbpB is a bilobed (N and C lobe) lipid-anchored protein, with each lobe consisting of an eight-stranded β barrel flanked by a 'handle' domain made up of four (N lobe) or eight (C lobe) β strands . TbpB extends from the outer membrane surface by virtue of an N-terminal peptide region that is anchored to the outer membrane by fatty acyl chains on the N-terminal cysteine, and is involved in the initial capture of iron-loaded Tf . The 4-residue conserved LSAC motif found at the amino terminus of TbpB represents a prototypical lipobox, with the cysteine residue serving as the first amino acid in the mature protein, which is subsequently modified by the addition of a diacyl glycerol. A second conserved motif of interest is located two amino acids downstream of the LSAC site. This region consists of four glycine residues in tandem. Deletion of the conserved polyglycine motif has significant negative effects on growth in certain conditions, while mutational analysis revealed that the LSAC motif constituting the lipobox of TbpB is necessary for lipidation and hence tethering of TbpB to the bacterial surface .

This entry represents a domain found on the N-terminal region of TbpB proteins, which comprises the N-lobe handle consisting of a four-stranded antiparallel β sheet held together by a short surface-exposed α helix. Tf-binding activity primarily resides in the TbpB N lobe .
Protein of unknown function DUF5370 (DUF5370)
Type: Family

This is a family of unknown function found in Bacillaceae.
Protein of unknown function DUF5372 (DUF5372)
Type: Family

This family of unknown function is mostly found in Bacteria.
Transferrin-binding protein B, C-lobe handle domain (TbpB_C-lobe)
Type: Domain

Bacterial lipoproteins represent a large group of specialised membrane proteins that perform a variety of functions, including maintenance and stabilisation of the cell envelope, protein targeting and transit to the outer membrane, membrane biogenesis, and cell adherence . Pathogenic Gram-negative bacteria within the Neisseriaceae and Pasteurellaceae families rely on a specialised uptake system, characterised by an essential surface receptor complex that acquires iron from host transferrin (Tf) and transports the iron across the outer membrane. They have an iron uptake system composed of surface-exposed lipoprotein, Tf-binding protein B (TbpB), and an integral outer-membrane protein, Tf-binding protein A (TbpA), that together function to extract iron from the host iron binding glycoprotein (Tf). TbpB is a bilobed (N and C lobe) lipid-anchored protein, with each lobe consisting of an eight-stranded β barrel flanked by a 'handle' domain made up of four (N lobe) or eight (C lobe) β strands . TbpB extends from the outer membrane surface by an N-terminal peptide region that is anchored to the outer membrane by fatty acyl chains on the N-terminal cysteine and is involved in the initial capture of iron-loaded Tf .
Protein of unknown function DUF5375 (DUF5375)
Type: Family

This is a family of unknown function found in Enterobacteriaceae.
Protein of unknown function DUF5377 (DUF5377)
Type: Family

This is a family of unknown function found in Pasteurellaceae.
Protein of unknown function DUF5378 (DUF5378)
Type: Family

This is a family of unknown function found in Mycoplasmataceae. Family members are predicted to contain 7 trans-membrane regions
Protein of unknown function DUF5373 (DUF5373)
Type: Family

This family of unknown function is found in Caenorhabditis. Members of this family are predicted to contain 4 trans-membrane regions.
Male Flower Specific protein 18 (MFS18)
Type: Family

In Maize, MFS18 mRNA accumulates in the glumes and in anther walls, paleas and lemmas of mature florets. It is particularly associated with the vascular bundle in the glumes and encodes a polypeptide of 12kDa, rich in glycine, proline and serine that has similarities with other plant structural proteins . There is no known function of this domain family in Maize or other Poaceae.
Facilitator of iron transport 2 (Fit2)
Type: Family

Budding yeast Fit proteins (facilitor of iron transport) found on cell wall are mannoproteins implicated in the siderophore-iron bound transport. The Fit1-3 cell wall mannoproteins are attached to the beta-glucan layer through a GPI (glycosylphosphatidylinoisitol) anchor .
Protein of unknown function DUF5381 (DUF5381)
Type: Family

This is a family of unknown function mostly found in Bacillales.
Protein of unknown function DUF5385 (DUF5385)
Type: Family

This is a family of unknown function found in Mycoplasmataceae. Family members are predicted to have one trans-membrane region.
Phage tail sheath protein-like, beta-sandwich domain (Beta_sandwich_Seath)
Type: Domain

This entry represents the N-terminal β-sandwich domain found in a variety of phage tail sheath proteins and Mu-like prophage FluMu tail sheath proteins from bacteria .
AlphaC, C-terminal (AlphaC_C)
Type: Domain

The alpha C protein (ACP) is found in Streptococcus and acts as an invasin which plays a role in the internalisation and translocation of the organism across human epithelial surfaces. Group B Streptococcus is the leading cause of diseases including bacterial pneumonia, sepsis and meningitis. The N-terminal domain of ACP is associated with virulence and forms a β sandwich and a three helix bundle . This entry is the C-terminal domain of APC. The C-terminal domain (45 amino acids) contains an LPXTG peptidoglycan-anchoring motif characteristic of cell-wall anchored surface proteins .
DUF3048, C-terminal domain (DUF3048_C)
Type: Domain

This entry represents the C-terminal domain of a group of proteins with unknown function. Proteins containing this domain include the YerB protein from Bacillus subtilis. YerB interacts with PcrA helicase. The interaction is not essential for cell viability or repair of UV-induced lesions .
Rotavirus VP4 helical domain (VP4_helical)
Type: Domain

This entry represents the C-terminal domain of VP4 . VP4 and VP7 are the two protein components of the outer protein layer of the virion of Rotavirus .
Rotavirus VP4, membrane interaction domain (Rota_VP4_MID)
Type: Domain

The spike protein VP4 is a key component of the membrane penetration apparatus of rotavirus. This entry represents the VP4 membrane interaction domain .
Clostridial binary toxin B/anthrax toxin PA, domain 3 (Binary_toxB_3)
Type: Domain

This entry represents the β-grasp domain in anthrax protective antigen.
Protein of unknown function DUF5386 (DUF5386)
Type: Family

This is a family of unknown function found in Chromadorea.
Protein of unknown function DUF5389 (DUF5389)
Type: Family

This is a family of unknown function found mostly in Pasteurellaceae. Family members are predicted to have 3 trans-membrane regions.
Protein of unknown function DUF5390 (DUF5390)
Type: Family

This is a family of unknown function found in Caenorhabditis.
Protein of unknown function DUF5397 (DUF5397)
Type: Family

This is a family of unknown function mostly found in Proteobacteria.
Protein of unknown function DUF5398 (DUF5398)
Type: Family

This is a family of unknown function mostly found in Chlamydiia.
Uncharacterized protein Ycf70-like (Ycf70-like)
Type: Family

This is a family of unknown function found in Poaceae.
Protein KleA/KleC-like (KleA/KleC-like)
Type: Family

This is a family of unknown function mostly found in Proteobacteria.
Protein of unknown function DUF5426 (DUF5426)
Type: Family

This is a family of unknown function found in Mycoplasma.
Protein of unknown function DUF5425 (DUF5425)
Type: Family

This is a family of unknown function found in Borreliella.
Gene product 63 (Gp63)
Type: Family

This is a family of unknown function found in Mycobacterium phages.
Phage gene product 45.2 (Gp45.2)
Type: Family

This is a family of unknown function found in Myoviridae.
Gp68-like predicted RNA polymerase component (Gp68)
Type: Domain

This is a family of unknown function found in Mycobacterium phages.

This is entry includes a protein that purifies with the non-virion RNA polymerase in group 1/PhiKZ-like phages . Structure predictions shows the protein contain a pair of β-strands and several short helical segments.
Phage gene product 52 (Gp52)
Type: Family

This is a family of unknown function found in Mycobacterium phages.
Protein E7, orthopoxvirus (E7R_orthopoxvir)
Type: Domain

This domain is found in protein E7 (also known as OPG069) from Vaccinia, Variola and Monkeypox viruses. Vaccinia virus (VV) is a large double-stranded DNA virus that replicates in the cytoplasm of infected cells. Many viruses express proteins that are modified by myristic acid. Myristic acid is a 14-carbon fatty acid that is cotranslationally transferred to the penultimate glycine residue found within the consensus sequence MGXXX(S/T/A/C/N) (where X is any amino acid) at the amino terminus of target proteins. E7R proteins in Vaccina virus have been shown to be myristylated. The expressed E7R protein has also been found to reside within mature infectious virions .
Protein of unknown function NinD (NinD)
Type: Family

This is a family of unknown function found in phages such as Enterobacteria phage P22 and Enterobacteria phage lambda.
Chemokine-like protein U83 (Putative_chemo_U83)
Type: Family

Human herpesvirus 6A (HHV-6A) and HHV-6B are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies . HHV6 A/B encode two putative chemokine receptors and a chemokine-like protein. The HHV6 U83 gene encodes a CC chemokine, which functions as a highly selective and efficacious agonist for the human CCR2 receptor, both in respect of signal transduction and the ability to induce chemotaxis. Homologues of the U83 gene products are found in Human cytomegalovirus encoded chemokines vCXC1 and vCXC2.

HHV-6 U83, also known as vCCL4, contains a region with the CC/CX3C chemokine motif and a glycosaminoglycan (GAG)-binding epitope, BBXB (B being a basic residue), found right before the third Cys residue, which very likely forms a disulfide bridge back to the first Cys of the protein . This gene is the only HHV-6A/B divergent gene that is specific for these viruses. The U83 chemokine gene is distinct between HHV-6A and HHV-6B strains, encoding up to 13 amino acid differences. The HHV-6A (U83A) and HHV-6B (U83B) chemokines have distinct specificities which determine chemoattraction or diversion of different leukocyte subsets for infection or immune evasion, thus an early component of cellular tropism as well as mediator of innate immunity. U83 also has a varied gene structure, with N-terminal length variation determining production of the encoded mature secreted chemokine, coupled with control by cell-directed splicing which truncates the chemokine gene early in replication to encode an antagonist. The 'long' active form of U83A has a unique broad specificity for receptors CCR1, CCR4, CCR5, CCR6 and CCR8 present on plasmacytoid and myeloid dendritic and monocyte/macrophage antigen presenting cells, as well as both TH1 and TH2 skin homing lymphocytes and NK cells; it is also amongst the highest affinity ligands for CCR5 and inhibits HIV-1 binding at this coreceptor. U83A can both block and divert human chemokine action while occupying the human chemokine receptors .
MoaF, C-terminal domain (MoaF_C)
Type: Domain

MoaF protein is essential for the production of the monoamine-inducible 30kDa protein in Klebsiella . It is necessary for reconstituting organoautotrophic growth in Ralstonia eutropha . It is conserved in Proteobacteria and some lower eukaryotes. The operon regulating the Moa genes is responsible for molybdenum cofactor biosynthesis. This entry corresponds to the C-terminal domain.
Meiotic recombination protein Rec104 (Rec104)
Type: Family

Rec104 is one of several meiosis specific genes required for generating meiotic DSBs (double strand breaks) . It is suggested that Rec102 and Rec104 directly promote DSB formation as part of a multiprotein complex with Spo11. Rec102 and Rec104 are mutually dependent for proper sub-cellular localization, and share a requirement for Spo11 and Ski8 for their recruitment to meiotic chromosomes. Moreover, Rec102 is required for Rec104 to accumulate to normal steady-state levels and to be properly phosphorylated. It is likely that Rec102 and Rec104 move freely in and out of the nucleus but are most stably sequestered there only when they can form a complex on chromosomes .
Protein of unknown function DUF5400 (DUF5400)
Type: Family

This is a family of unknown function found in Euryarchaeota. Members of this family are predicted to contain 4 trans-membrane regions.