SII-SWORD/CoKE huggingface dataset:
Regulator of RNA polymerase sigma(70) subunit, Rsd/AlgQ superfamily (Rsd/AlgQ_sf)
Type: Homologous_superfamily

This superfamily includes bacterial transcriptional regulators (Rsd) that are thought to act through an interaction with the conserved region 4 of the sigma(70) subunit of RNA polymerase . The Pseudomonas aeruginosa homologue, AlgQ, positively regulates virulence gene expression and is associated with the mucoid phenotype observed in P. aeruginosa isolates from cystic fibrosis patients. Rsd structure consists of four α helices packed in an up-and-down bundle .
DUF1104 superfamily (DUF1104_sf)
Type: Homologous_superfamily

This superfamily consists of several hypothetical proteins of unknown function which appear to be found mainly in Helicobacter pylori. The structure of HP0721 protein consists of a bundle of four α-helices connected by loops and stabilised by hydrophobic interactions. It has been suggested that this protein might represent a novel H. pylori .
Herpesvirus glycoprotein L, N-terminal domain superfamily (Herpes_gL_N_sf)
Type: Homologous_superfamily

Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen .

Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH .

This entry represents Herpesvirus glycoprotein L (gL), which is a virion associated envelope glycoprotein . Heterodimer formation between gH and gL has been demonstrated in both virions and infected cells . Heterodimer formation between gL and gH is important for the proper folding of gH and its insertion into the membrane because the anti-gH conformation-dependent monoclonal antibodies (mAbs) 53S and LP11 bind gH only when gL is present .
DUF5063 superfamily (DUF5063_sf)
Type: Homologous_superfamily

The function of DUF5063 is not clear.
Herpesvirus glycoprotein L, rhadinovirus-type superfamily (Herpes_gL_rhadinovirus_sf)
Type: Homologous_superfamily

Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen .

Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH .

This superfamily represents a subgroup of gL found in rhadinoviruses.
T6SS superfamily (T6SS_sf)
Type: Homologous_superfamily

Tai4 is a new form of autoimmunity protein for a type VI secretion system, T6SS. T6SS has roles in interspecies interactions, as well as higher order host-infection, by injecting effector proteins into the periplasmic compartment of the recipient cells of closely related species. Pseudomonas aeruginosa produces at least three effector proteins to other cells and thus has three specific cognate immunity proteins to protect itself. Tae4, or type VI amidase effector 4, in Enterobacter cloacae has a cognate Tai4 or type VI amidase immunity 4 protein .
FLiS export co-chaperone, HP1076 superfamily (FliS_cochap_sf)
Type: Homologous_superfamily

HP1076 is a co-chaperone for FliS, one of the type III secretion system flagellar chaperones. The HP1076 and FliS complex together prevents premature polymerisation of flagellins and is critical for flagellar assembly and bacterial colonisation. The HP1076 shows co-chaperone activity that promotes protein folding of FliS with mutations in the flagellin binding pocket and enhances the chaperone activity of FliS .
DUF5062 superfamily (DUF5062_sf)
Type: Homologous_superfamily

The function of DUF5062 is not known.
Pf1176-like superfamily (Pf1176-like_sf)
Type: Homologous_superfamily

This domain is found in a family of proteins with unknown function and appears to be restricted to the Thermococcaceae.
KdpD, transmembrane domain superfamily (KdpD_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in sensor protein KdpD. It is likely to be a transmembrane domain involved in ligand sensing.

KdpD is part of the two-component regulatory system KdpD/KdpE involved in the regulation of the kdp operon, a three-component K+ transport system. KdpD may function as a membrane-associated protein kinase that phosphorylates KdpE in response to environmental signals .
CAS, serine rich four helix bundle domain superfamily (Serine_rich_sf)
Type: Homologous_superfamily

This superfamily represents a serine rich protein that is found in the docking protein p130(cas) (Crk-associated substrate). The protein folds into a four helix bundle which is associated with protein-protein interactions .
KinB, N-terminal domain superfamily (KinB_N_sf)
Type: Homologous_superfamily

This entry reprsents the N-terminal sensor domain of histidine kinase from Pseudomonas species. The domain is the extracellular sensing domain with four helical bundle . It recognises inorganic phosphate .
TmcA, C-terminal domain superfamily (TmcA_C_sf)
Type: Homologous_superfamily

This superfamily represents the helical tail domain found at the C terminus of tRNA(Met) cytidine acyltransferase (TmcA), which may be involved in tRNA-binding .
Pex19, C-terminal domain superfamily (Pex19_C_sf)
Type: Homologous_superfamily

Peroxisome(s) form an intracellular compartment, bounded by a typical lipid bilayer membrane. Peroxisome functions are often specialised by organism and cell type; two widely distributed and well-conserved functions are H2O2-based respiration and fatty acid beta-oxidation. Other functions include ether lipid (plasmalogen) synthesis and cholesterol synthesis in
animals, the glyoxylate cycle in germinating seeds ("glyoxysomes"), photorespiration in leaves, glycolysis in trypanosomes ("glycosomes"), and methanol and/or amine oxidation and assimilation in some yeasts.

PEX genes encode the machinery ("peroxins") required to assemble the peroxisome. Membrane assembly and maintenance requires three of these (peroxins 3, 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Matrix protein import follows a branched pathway of soluble recycling receptors, with one branch for each class of peroxisome targeting sequence (two are well characterised), and a common trunk for all. At least one of these receptors, Pex5p, enters and exits peroxisomes as it functions. Proliferation of the organelle is regulated by Pex11p. Peroxisome biogenesis is remarkably conserved among eukaryotes. A group of fatal, inherited neuropathologies are recognised as peroxisome biogenesis diseases. Pex19 is involved in membrane assembly and maintenance and functions as a receptor and chaperone of peroxisomal membrane proteins (PMPs) .

This superfamily represents the C-terminal domain of Pex19, which is assembled in a three-helical bundle and represents the mPTS (PMP-targeting signal) binding site .
Putative aromatic acid exporter, C-terminal domain superfamily (ArAE_1_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal of a presumed intracellular domain found in a set of bacterial presumed transporter proteins. The region is about 160 amino acids in length.
Rpb4/RPC9 superfamily (Rpb4/RPC9_sf)
Type: Homologous_superfamily

A major role in the regulation of eukaryotic protein-coding genes is played by the gene-specific transcriptional regulators, which recruit the RNA polymerase II holoenzyme to the specific promoter. The Rpb4 and Rpb7 subunits of yeast RNA polymerase II form a heterodimeric complex essential for promoter-directed transcription initiation. The Rpb4-Rpb7 complex is not required for stable recruitment of polymerase to active preinitiation complexes, suggesting that Rpb4-Rpb7 mediates an essential step subsequent to promoter binding .

This superfamily includes DNA-directed RNA polymerase II subunit Rpb4 and DNA-directed RNA polymerase III subunit RPC9.
Interleukin-7 superfamily (IL7_sf)
Type: Homologous_superfamily

This entry represents interleukin-7 (IL7), it is a hematopoietic growth factor produced by bone marrow stromal cells. It promotes growth of B- and T-cell precursors and functions with IL2 in the activation of mature T-cells . IL-7 and IL-7Ralpha bind the gamma-c receptor forming a complex required for the development and homeostasis of T and B cells . Interleukin-7 and Interleukin-9 belong to the same larger family.
Interferon lambda superfamily (IFN-lambda_sf)
Type: Homologous_superfamily

Interferon (IFN)-lambda proteins belong to the new type III IFN group. In contrast to type I or type II IFNs, the response to type III IFN is cell-type specific. Only epithelial-like cells and some immune cells respond to IFN-lambda . In human,four distinct proteins called IFN-lambda1 (interleukin-29, IL-29), IFN-lambda2 (IL-28A), IFN_lambda3 (IL-28B) and IFNL4 have been identified . IFN-lambda proteins activate IFN-stimulated gene factor 3 (ISGF3), and are capable of inducing antiviral protection and MHC class I antigen expression .
Interleukin-34 superfamily (IL-34_sf)
Type: Homologous_superfamily

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

This entry represents interleukin-34 (IL-34), it was identified via functional screening of a library of secreted proteins . This cytokine promotes the differentiation and viability of monocytes and macrophages through the colony-stimulating factor-1 receptor (CSF1R) .
Thymic stromal lymphopoietin superfamily (TSLP_sf)
Type: Homologous_superfamily

Thymic stromal lymphopoietin (TSLP) is a cytokine that functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of CD11c(+) dendritic cells . TSLP has proliferative effects on the myeloid cell line and may initiate asthma or atopic dermatitis responses by directly activating mast cells .
TspO/MBR-related superfamily (TspO/MBR-related_sf)
Type: Homologous_superfamily

Members of this group are involved in transmembrane signalling. In both prokaryotes and mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway . They are associated with the major outer membrane porins (in prokaryotes) and with the voltage-dependent anion channel (in mitochondria) .

Rhodobacter sphaeroides TspO (previously CrtK) is involved in signal transduction, functioning as a negative regulator of the expression of some photosynthesis genes (PpsR/AppA repressor/antirepressor regulon). This down-regulation is believed to be in response to oxygen levels. TspO works through (or modulates) the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins . It has been suggested that the TspO regulatory pathway works by regulating the efflux of certain tetrapyrrole intermediates of the haem/bacteriochlorophyll biosynthetic pathways in response to the availability of molecular oxygen, thereby causing the accumulation of a biosynthetic intermediate that serves as a corepressor for the regulated genes . A homologue of the TspO protein in Rhizobium meliloti (Sinorhizobium meliloti) is involved in regulating expression of the ndi locus in response to stress conditions . There is evidence that the S. meliloti TspO acts through, or in addition to, the FixL regulatory system.

In animals, translocator protein (TSPO), previously known as peripheral-type benzodiazepine receptor (PBR, MBR) is a mitochondrial protein (located in the outer mitochondrial membrane) where it forms a complex with several proteins of the mitochondrial permeability transition pore (MPTP). TSPO is involved in multiple processes, including regulation of cell death, cholesterol transport and steroid biosynthesis, mitochondrial respiration and oxidation and mitochondrial protein import .

These observations suggest that fundamental aspects of this receptor and the downstream signal transduction pathway are conserved in bacteria and higher eukaryotic mitochondria. The alpha-3 subdivision of the purple bacteria is considered to be a likely source of the endosymbiont that ultimately gave rise to the mitochondrion. Therefore, it is possible that the mammalian PBR remains both evolutionarily and functionally related to the TspO of R. sphaeroides.
DisA, linker domain superfamily (DisA_sf)
Type: Homologous_superfamily

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. the first, N-terminal region, from 1-145 is globular and is represented by

; the next 146-289 residues is this domain that consists of an elongated bundle of three α-helices (α6, α10, and α11), one side of which carries an additional three helices (α7-9), thus forming a spine like-linker between domains 1 and 3. The C-terminal residues of domain 3 (

), represent the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis .
PPE superfamily (PPE_sf)
Type: Homologous_superfamily

This entry represents the PPE superfamily.

This entry also includes ESX-1 secreted protein B (EspB), which is the only member of the PE/PPE family described to date to form higher-order oligomers. It contains PE and PPE domains and a C-terminal domain, which is processed by MycP1 protease during secretion. Once secreted across the inner mycobacterial membrane, EspB oligomerizes into a cylinder-like heptamer through its N-terminal domain that forms channel-like structures, enabling other ESX-1 secreted substrates to pass through and beyond the inner mycobacterial envelope .

The human pathogen Mycobacterium tuberculosis harbours a large number of genes that encode proteins whose N-terminals contain the characteristic motifs Pro-Glu (PE) or Pro-Pro-Glu (PPE). These proteins are exported to the bacterial surface via type VII secretion systems known as ESX . A subgroup of the PE proteins contains polymorphic GC-rich sequences (PGRS), while a subgroup of the PPE proteins contains major polymorphic tandem repeats (MPTR). The function of most of these proteins remains unknown . However, the PE_PGRS proteins from Mycobacterium marinum are secreted by components of the ESX-5 system that belongs to the recently defined type VII secretion systems . It has also been reported that the PE_PGRS family of proteins contains multiple calcium-binding and glycine-rich sequence motifs GGXGXD/NXUX. This sequence repeat constitutes a calcium-binding parallel β-roll or parallel β-helix structure and is found in RTX toxins secreted by many Gram-negative bacteria .

PPE51 member has been described as a small molecule-selective channel required for the uptake of nutrients across the outer mycomembrane . This protein transports glycerol and glucose as well as maltose and lactose disaccharides. It is involved in sensitivity to M.tuberculosis growth inhibitory agrichemical 3,3-bis-di(methylsulfonyl)propionamide (3bMP1) and sensitivity to bactericidal thio-disaccharide T-6 compound .
Type I restriction enzyme EcoKI-like, methylase subunit, N-terminal domain superfamily (T1MK-like_N_sf)
Type: Homologous_superfamily

This superfamily represents a domain found at the N terminus of the methylase subunit of Type I DNA methyltransferases. This domain is found in bacteria and archaea, and is typically between 123 and 138 amino acids in length. Mutations in this region of EcoKI methyltransferase

abolish the normally strong preference of this system for methylating hemimethylated substrate . The structure of this domain has been shown to be all α-helical.
NleF superfamily (NleF_sf)
Type: Homologous_superfamily

NleF (Non-LEE-encoded type III effector F) is an effector protein that alters host cell physiology and promotes bacterial survival in host tissues. It binds to and inhibits caspase-9, caspase-8 and caspase-4, and therefore preventing caspase-induced apoptosis in the host cell .
ACP, C-terminal domain superfamily (ACP_C_sf)
Type: Homologous_superfamily

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 .
NET domain superfamily (NET_sf)
Type: Homologous_superfamily

The bromodomain and extraterminal (BET) proteins are a class of transcriptional regulators whose members can be found in animals, plants and fungi. BET proteins are involved in diverse cellular phenomena such as meiosis, cell-cycle control, and homeosis and have been suggested to modulate chromatin structure and affect transcription via a sequence-independent mechanism. BET proteins are defined as having one (plants) or two (animals/yeast) bromodomains and an Extra Terminal (ET) domain. The ET domain consists of three separate regions, only one of which, the N-terminal ET (NET) domain is conserved in all BET proteins. The function of the NET domain is assumed to be protein binding .

The structure of the NET domain comprises three α-helices and a characteristic loop region of an irregular but well-defined structure. The NET structure has an acidic patch that forms a continuous ridge with a hydrophobic cleft. which may interact with other proteins and/or DNA .
Poxvirus poly(A) polymerase, catalytic subunit, N-terminal domain superfamily (Poxvirus_polyA_pol_cat_N_sf)
Type: Homologous_superfamily

Poly(A) polymerase (

) catalyses template-independent extension of the 3'-end of a DNA or RNA strand by one nucleotide at a time. The Poxvirus enzyme creates the 3'(poly)A tail of mRNAs, and is a heterodimer of a catalytic and a regulatory subunit.

This superfamily represents a domain found at the N terminus of the pox virus Poly(A) polymerase protein catalytic subunit.
PriC superfamily (PriC_sf)
Type: Homologous_superfamily

This superfamily contains the bacterial primosomal replication restart protein priC. PriC forms a compact bundle of α-helices that brings together residues involved in single-stranded DNA (ssDNA) and the ssDNA-binding protein (SSB) binding at adjacent sites on the protein surface

.

Replication restart protein PriC is involved in the reactivation of stalled replication forks by facilitating the reloading of the DnaB replicative helicase at sites other than the origin of replication . It recognises abandoned replication forks and remodels DNA single-stranded binding protein (SSB) bound to single-stranded DNA (ssDNA), thereby exposing a loading site for DnaB . PriC functions in multiple restart pathways: it is part of the minor PriC-Rep pathway, which exhibits distinct substrate specificity from the PriA-dependent pathway, and also contributes to the major replication restart pathway alongside PriA, PriB, DnaB, DnaT, and the DnaG primase. Notably, priB and priC have redundant roles in the cell. PriC has been shown to bind 7-9 nucleotides of ssDNA .
MatP, N-terminal domain superfamily (MatP_N_sf)
Type: Homologous_superfamily

MatP organises the macrodomain Ter of the chromosome of bacteria such as E coli. In these bacteria, insulated macrodomains influence the segregation of sister chromatids and the mobility of chromosomal DNA. Organisation of the Terminus region (Ter) into a macrodomain relies on the presence of a 13 bp motif called matS repeated 23 times in the 800-kb-long domain. MatS sites are the main targets in the E. coli chromosome of YcbG or MatP (macrodomain Ter protein). MatP accumulates in the cell as a discrete focus that co-localises with the Ter macrodomain. The effects of MatP inactivation reveal its role as the main organiser of the Ter macrodomain: in the absence of MatP, DNA is less compacted, the mobility of markers is increased, and segregation of the Ter macrodomain occurs early in the cell cycle. A specific organisational system is required in the Terminus region for bacterial chromosome management during the cell cycle .

This entry represents the N-terminal domain of MatP.
MRP-L47 superfamily, mitochondrial (MRP-L47_sf)
Type: Homologous_superfamily

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .

This entry represents the eukaryotic mitochondrial ribosomal protein uL29 (also known as MRP-L47). Mitochondrial ribosomal proteins (MRPs) are the counterparts of the cytoplasmic ribosomal proteins, in that they fulfil similar functions in protein biosynthesis. However, they are distinct in number, features and primary structure .