SII-SWORD/CoKE huggingface dataset:
PhoD-like superfamily (PhoD-like_sf)
Type: Homologous_superfamily

Alkaline phosphatase D (PhoD) catalyses the reaction: phosphate monoester + H(2)O = an alcohol + phosphate. PhoD is similar to Ca(2+)-dependent phospholipase D , which catalyses the hydrolysis of the ester bond between the phosphatidic acid and alcohol moieties of phospholipids .
Csm1/Pcs1, C-terminal domain superfamily (Csm1/Pcs1_C_sf)
Type: Homologous_superfamily

Saccharomyces cerevisiae Csm1 is part of the monopolin complex. Csm1 forms a complex with Mde4 and promotes monoorientation during meiosis . It plays a mitotic role in DNA replication and is required for condensin recruitment to the replication fork barrier site and rDNA repeat segregation . This entry also contains the Schizosaccharomyces pombe homologue to Csm1, Pcs1. Pcs1 forms a complex with Mde4 and acts in the central kinetochore domain to clamp microtubule binding sites together. The two complexes (Csm1/Lrs4 and Pcs1/Mde4) contribute to the prevention of merotelic attachment .
HDA1 complex subunit 2/3 superfamily (HDA1_su2/3_sf)
Type: Homologous_superfamily

Hda2/3 associate with Hda1 to generate the activity of the Hda1 histone deacetylase complex. Hda1 interacts with itself and with the Hda2-Hda3 subcomplex to form a probable tetramer and these interactions are necessary for catalytic activity. The Hda1 histone deacetylase complex is responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Hda2 and Hda3 have a conserved coiled-coil domain towards their C terminus .
FliK-like, C-terminal domain superfamily (FliK-like_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of the flagellar hook-length control protein FliK. This entry also includes the chemotaxis protein MotD which is required for the rotation of the flagellar motor.

FliK controls the length of the flagellar hook. It detects when the flagellar hook substructure has reached its optimal length. Then, it terminates hook export and assembly and transmits a signal to begin filament export, the final stage in flagellar biosynthesis. The exact mechanism of how FliK achieves this is not known . FliK is a two-domain protein with the central portion of the sequence acting as a hinge or connector between the two .
Rifampin ADP-ribosyltransferase superfamily (Arr_sf)
Type: Homologous_superfamily

Arr enzymes catalyze ADP-ribosylation of rifamycins, thus rendering rifamycin antibiotics ineffective. The opportunistic pathogen Mycobacterium smegmatis possesses a chromosomally encoded rifampin ADP-ribosyltransferase (Arr-ms). An homologue of Arr, Arr-2, is present in several transposons and integrons found in Gram-negative pathogenic bacteria. The structure of Arr-ms reveals similarity to protein ADP-ribosyltransferases, despite a lack of amino acid sequence similarity .
YkfF-like domain superfamily (YkfF-like_sf)
Type: Homologous_superfamily

This superfamily represents a putative double-stranded RNA binding domain found in uncharacterised proteins, such as YkfF from Escherichia coli (

).
Peroxin 22, C-terminal domain superfamiliy (Peroxin-22_C_sf)
Type: Homologous_superfamily

Peroxin-22 is an integral peroxisomal membrane protein. The N terminus of peroxin-22 is located in the matrix, while the C terminus is located in the cytosol. Peroxin-22 interacts with the ubiquitin-conjugating enzyme Pex4p, anchoring it at the peroxisomal membrane . This association is required for ubiquitination of peroxisomal import receptor Pex5p mediated by Pex4p .

This superfamily represents the C-terminal soluble domain, which corresponds to the region required for Pex4p binding .
Glycerate kinase, N-terminal domain superfamily (GK_N_sf)
Type: Homologous_superfamily

Two groups of glycerate kinases are known, which share no significant sequence similarity. One of the groups includes glycerate kinases from eukaryotes and archaea, in addition to several bacterial species . TM1585 from Thermotoga maritima, a putative glycerate kinase, belongs to this group.

The TM1585 monomer is comprised of two dissimilar α-β domains: an N-terminal, Rossmann-like domain (residues 23-249) and a C-terminal domain that adopts a new fold. The N-terminal domain has a central, six-stranded, parallel β-sheet and an all-helical subdomain. The active site is likely to be in the cleft between the N- and C-terminal domains .
Pichia pastoris 6-phosphofructokinase, gamma subunit superfamily (PpPFK_gamma_sf)
Type: Homologous_superfamily

Pichia pastoris 6-phosphofructokinase (PpPfk) is the most complex and probably largest (1 MDa) eukaryotic Pfk . It forms a dodecamer of four α-β-γ trimers . The gamma subunit is unique, in contrast to other eukaryotic ATP-dependent 6-phosphofructokinases, and participates in oligomerization of the alpha and beta chains . It is not essential for enzymatic activity, but it modulates the allosteric behavior of the enzyme .
Phosphotransferase RcsD, RcsD-ABL domain superfamily (RcsD_ABL_sf)
Type: Homologous_superfamily

This domain is part of the RcsD phosphotransferase. RcsD is a phosphotransfer intermediate between the sensor kinase RcsC and the response regulator RcsB. This domain recognises and interacts with the DNA-binding domain of RcsB .
Rhabdovirus matrix protein superfamily (Rhabdovirus_M_sf)
Type: Homologous_superfamily

Matrix (M) protein is an important structural component of rhabdovirus virions, and also plays a number of roles during the replication cycle of the virus . It is involved in condensing and targeting the ribonucleoprotein (RNP) coil to the plasma membrane. M interacts specifically with the transmembrane spike protein (G) and it is important for the incorporation of G protein into budding virions .
CTXphi pIII, N1 domain superfamily (CTXphi_pIII_N1_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain, N1, of the pIII protein of the CTXphi bacteriophage of Vibrio cholerae. CTXphi is a ssDNA Inovirus. pIII is a minor coat protein. This domain interacts directly with the C terminus of TolA, a periplasmic protein of Vibrio cholerae itself as part of the infection mechanism .

Structurally, this domain consists of 5 β strands. The third strand has small breaks within the strand, referred to as beta3a-c.
MraZ superfamily (MraZ_sf)
Type: Homologous_superfamily

The gene encoding MraZ is often found with other genes of the dcw (division cell wall) gene cluster, including mraW, ftsI, murE, murF, ftsW, murG, etc. In E. coli, MraZ is a DNA-binding transcription factor . It acts as a repressor of Pmra, which is a promoter for mraZ and mraW. It also regulates the expression of genes outside the dcw cluster. Overproduction of Escherichia coli MraZ inhibits cell division .
YdcP-like superfamily (YdcP-like_sf)
Type: Homologous_superfamily

This entry consists of several hypothetical bacterial proteins of unknown function.
Lactococcus phage SSB superfamily (Lacto_phage_SSB_sf)
Type: Homologous_superfamily

This single-stranded DNA binding protein (SSB) is found in Lactococcus phage. It can stimulate RecA-mediated homologous recombination. Its structure is a variation of the typical oligonucleotide/oligosaccharide binding-fold of single-stranded DNA binding proteins .
Cyclodipeptide synthase superfamily (CDPS_sf)
Type: Homologous_superfamily

Cyclodipeptide synthase (CDPS) is a tRNA-dependent peptide bond-forming enzyme that uses aminoacyl-tRNAs (aa-tRNAs) as substrates to synthesise the two peptide bonds of various cyclodipeptides, which are the precursors of many natural products with biological activities . This entry includes the cyclodityrosine synthase from Mycobacterium tuberculosis (an essential gene), the cyclo(L-Phe-L-Leu) synthase from Streptomyces noursei and cyclodileucine synthase YvmC from Bacillus licheniformis. Many cyclodipeptide synthases are found next to a cytochrome P450 that further modifies the product .
Stimulator of interferon genes protein, C-terminal domain superfamily (STING_C_sf)
Type: Homologous_superfamily

STING (stimulator of interferon genes, also known as MITA, ERIS, MPYS and TMEM173) is a master regulator that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) and leading to the activation of IFN regulatory factor 3 (IRF3) through TANK-binding kinase 1 (TBK1) stimulation . STING is also a signaling adaptor in the IFN response to cytosolic DNA. This detection of foreign materials is the first step to a successful immune responses. STING is localized in the ER and comprised of an predicted N-terminal transmembrane region and a C-terminal c-di-GMP binding domain . Members of this entry also play a direct role in autophagy .

This entry represents the C-terminal domain.
YedD-like superfamily (YedD-like_sf)
Type: Homologous_superfamily

This superfamily of proteins includes the uncharacterised lipoprotein YedD.
Rhodococcus equi virulence-associated superfamily (R_equi_Vir_sf)
Type: Homologous_superfamily

This superfamily consists of several virulence-associated proteins, mainly from Corynebacterium equii (Rhodococcus equi, Rhodococcus hoagii). R. equi is an important pulmonary pathogen of foals and is increasingly isolated from pneumonic infections and other infections in Homo sapiens immunodeficiency virus-infected patients. Both virulent and avirulent strains of R. equi differ in the possession of a virulence-associated plasmid . The type of virulence plasmid carried is host specific; the pVapA is the plasmid type carried by R. equi isolates infecting equine. These virulence plasmids have four common regions known as the conjugation, replication, unknown function and the virulence or pathogenicity island (PAI) regions, where the members of the vap (virulence associated protein) family reside . The virulence protein VapA has been shown to inhibit the maturation of R. equi-containing phagosomes and promote intracellular bacterial survival .
Rof-like superfamily (Rof-like_sf)
Type: Homologous_superfamily

This superfamily consists of several bacterial modulator of Rho-dependent transcription termination (ROF) proteins. ROF binds transcription termination factor Rho and inhibits Rho-dependent termination
in vivo
.

ROF (also known as YaeO) contains an N-terminal helix and a seven-stranded β sandwich .
YebG-like superfamily (YebG-like_sf)
Type: Homologous_superfamily

This superfamily consists of several bacterial YebG proteins. The exact function of this protein is unknown but it is thought to be involved in the SOS response. The induction of the yebG gene occurs as cell enter into the stationary growth phase and is dependent on is dependent on cyclic AMP and H-NS .
XkdM-like superfamily (XkdM-like_sf)
Type: Homologous_superfamily

This is a superfamily of phage tail tube proteins including protein XkdM from phage-like element PBSX protein (

) whose structure adopts a β barrel flanked with α helical regions .
Type II heat-labile enterotoxin, B subunit superfamily (LT-IIB_sf)
Type: Homologous_superfamily

This entry represents the B subunits from the type II heat-labile enterotoxin. It forms a pentameric ring, which interacts with one A subunit. Thus, the structural arrangement of type I and type II heat-labile enterotoxins are very similar .

The structure of the B subunit is a β barrel with an OB fold.
Ribosomal protein L24e/L24 superfamily (L24e/L24_sf)
Type: Homologous_superfamily

Ribosomal protein eL24/L24 is a ribosomal protein found in eukaryotes (L24) and in archaea (eL24, distinct from archaeal L24). eL24/L24 is located on the surface of the large subunit, adjacent to proteins L14 and L3, and near the translation factor binding site. eL24/L24 appears to play a role in the kinetics of peptide synthesis, and may be involved in interactions between the large and small subunits, either directly or through other factors. In mouse, a deletion mutation in L24 has been identified as the cause for the belly spot and tail (Bst) mutation that results in disrupted pigmentation, somitogenesis and retinal cell fate determination . L24 may be an important protein in eukaryotic reproduction: in shrimp, L24 expression is elevated in the ovary, suggesting a role in oogenesis , and in Arabidopsis, L24 has been proposed to have a specific function in gynoecium development .

The crystal structure of the eL24 protein from Halobacterium marismortui (Haloarcula marismortui) has been determined . The protein is composed of a single structural domain which forms an α/β zinc-binding fold.
Herpesvirus Glycoprotein B, PH-like domain 2 superfamily (Glycoprot_B_PH2_sf)
Type: Homologous_superfamily

This entry represents the second PH-like fold domain found in Herpesvirus glycoprotein B.

Glycoprotein B is an envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells .
Zinc finger FYVE 21, C-terminal domain superfamily (ZFYVE21_C_sf)
Type: Homologous_superfamily

Zinc finger FYVE domain-containing protein 21 (ZF21) regulates focal adhesions and cell migration binds by binding multiple factors that promote disassembly of focal adhesions (FAs) such as FAK, beta-tubulin, m-calpain, and SHP-2 .

This is the C-terminal domain of ZF21. It has a PH-like fold and is required for the regulation of focal adhesions and in cell migration .
Proteasomal ubiquitin receptor Rpn13/ADRM1, Pru domain superfamily (Rpn13/ADRM1_Pru_sf)
Type: Homologous_superfamily

This superfamily includes Rpn13 from budding yeasts and its homologue, ADRM1 from animals.

Rpn13 is a subunit and an ubiquitin receptor of the 19S regulatory particle of the 26S proteasome lid. The 26S proteasome is a huge macromolecular protein-degradation machine consisting of a proteolytically active 20S core, in the form of four disc-like proteins, and one or two 19S regulatory particles. The regulatory particle(s) sit on the top and or bottom of the core, de-ubiquitinate the substrate peptides, unfold them and guide them into the narrow channel through the centre of the core. Rpn13 and its homologues dock onto the regulatory particle through the N-terminal region which binds Rpn2. The C-terminal part of the domain binds de-ubiquitinating enzyme Uch37/UCHL5 and enhances its isopeptidase activity. Rpn13 binds ubiquitin via a conserved amino-terminal region called the pleckstrin-like receptor for ubiquitin, termed Pru, domain . The domain forms two contiguous anti-parallel β-sheets with a configuration similar to the pleckstrin-homology domain (PHD) fold . Rpn13's ability to bind ubiquitin and the proteasome subunit Rpn2/S1 simultaneously supports evidence of its role as a ubiquitin receptor. Finally, when complexed to di-ubiquitin, via the Pru, and Uch37 via the C-terminal part, it frees up the distal ubiquitin for de-ubiquitination by the Uch37 .

This superfamily represents the Pru (pleckstrin-like receptor for the Ub) domain.
Alphacoronavirus nsp1 domain superfamily (A-CoV_nsp1_sf)
Type: Homologous_superfamily

This entry represents the N-terminal region of the alphacoronovirus polyprotein, which contains non-structural protein 1 (Nsp1). Nsp1 from alphacoronavirus transmissible gastroenteritis virus (TGEV) folds into a six-stranded β-barrel fold with a long α helix on the rim of the barrel. This fold is shared with betacoronavirus SARS-CoV nsp1 .
CCR4-NOT complex subunit 2/3/5, C-terminal domain superfamily (CCR4-NOT_su2/3/5_C_sf)
Type: Homologous_superfamily

The Ccr4-Not complex controls mRNA metabolism at multiple levels in eukaryotic cells . This complex is a major cytoplasmic deadenylase consisting of a combination of at least nine subunits, four of which have deadenylase activity . The conserved core of the CCR4-NOT complex consists of two major modules: a catalytic module comprising two deadenylases (CAF1 or its paralogue POP2, and CCR4a or its paralogue CCR4b) and the NOT module, which minimally consists of NOT1, NOT2 and NOT3 .

This entry represents the C-terminal domain of NOT2, NOT3 and NOT5 (subunits 2, 3 and 5 of the complex). The C-terminal regions of NOT2 and NOT3 contain a conserved SH3-like NOT-box domain which mediates NOT-module assembly .
Capsule assembly protein Wzi superfamily (Wzi_sf)
Type: Homologous_superfamily

Many bacteria are covered in a layer of surface-associated polysaccharide called the capsule. These capsules can be divided into four groups depending upon the organisation of genes responsible for capsule assembly, the assembly pathway and regulation . This superfamily plays a role in group 1 capsule biosynthesis. It is likely to be involved in the later stages of capsule assembly.
NPCBM domain superfamily (NPCBM_sf)
Type: Homologous_superfamily

The novel putative carbohydrate binding module (NPCBM) domain, also known as NEW2, is found at the N terminus of glycosyl hydrolase family 98 (GH98) and at the C terminus of several proteins .

NPCBM plays a role in the recognition of host glycans by pathogenic bacteria, in the context of either pathogenesis or colonisation, and in the recognition of environmental glycans, perhaps in the classical CBM role of plant cell wall degradation .

GH98 from C. perfringens specifically hydrolyses fucose-containing trisaccharides from the glycotopes of blood groups A and B and is implicated in the infectivity and virulence of this pathogen .
RbpA superfamily (RbpA_sf)
Type: Homologous_superfamily

RbpA binds to RNA polymerase (RNAP), stimulating transcription from principal, but not alternative sigma factor promoters . RbpA stimulates transcription from several principal sigma factor HrdB (SigA)-dependent promoters but not from a SigR-dependent promoter. Stimulation occurs in the presence of the transcription inititation inhibitor rifampicin .
AlgX, C-terminal domain superfamily (AlgX_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of the alginate biosynthesis protein AlgX. This domain is a bacterial carbohydrate-binding module (CBM) frequently found at the C terminus of enzymes. The combination is not unusual as the CBMs function to bring the relevant polysaccharide into close proximity to the active site . Structurally, this domain consists of 8 β sheets, arranged into a jelly-roll β sandwich.
Benzylsuccinate synthase gamma subunit superfamily (BssC_sf)
Type: Homologous_superfamily

BssC short protein (57 amino acids) has been described as the gamma-subunit of benzylsuccinate synthase from Thauera aromatica strain K172 . It catalyzes the addition of fumarate to the methyl group of toluene, leading to the formation of benzylsuccinate. TutF has been identified and described as highly similar to BssC in T. aromatica strain T1 .
Csa superfamily (Csa_sf)
Type: Homologous_superfamily

This superfamily contains several uncharacterised proteins mostly staphylococcal. These proteins have been called conserved staphylococcal antigens (Csa) .
VioE superfamily (VioE_sf)
Type: Homologous_superfamily

Violacein is a purple-coloured pigment produced by bacteria such as Chromobacterium violaceum. Violacein exhibits significant biological activities, such as strong inhibition of several tumor cell lines, as well as antibacterial and trypanocidal activities.

Violacein is synthesised from two molecules of tryptophan by the enzymes VioA-E.
VioE is important for formation of the intermediate prodeoxyviolacein in this biosynthetic pathway .

This entry represents the enzyme VioE.
PliI superfamily (PliI_sf)
Type: Homologous_superfamily

This entry includes the PliI protein from Aeromonas hydrophila (PliI-Ah). PliI is a dimeric periplasmic protein that enables bacteria to resist permeabilisation of the outer membrane by the bactericidal action of lysozyme. PliI achieves its inhibitory action via an insertion of a loop containing the conserved SGxY motif into the active centre of I-type lysozymes .
CopK superfamily (CopK_sf)
Type: Homologous_superfamily

Copper resistance protein K (CopK) is a periplasmic dimeric protein which is strongly up-regulated in the presence of copper, leading to a high periplasmic accumulation . CopK has two different binding sites for Cu(I), each with a different affinity for the metal. Binding of the first Cu(I) ion (CuI) induces a conformational change of CopK which involves dissociation of the dimeric apo-protein. Binding of a second Cu(I) (CuII) further increases the plasticity of the protein. The binding of CuI greatly enhances the specific affinity for CuII and, in turn, CuII binding increases the specific affinity for CuI, although to a lesser extent. This type of cooperative behaviour is unprecedented in copper binding proteins . CopK has features that are common with functionally related proteins such as a structure consisting of an all-β fold and a methionine-rich Cu(I) binding site .
TTC5, OB fold domain superfamily (TTC5_OB_sf)
Type: Homologous_superfamily

This OB fold domain is located at the C terminus of tetratricopeptide repeat protein 5 (TTC5) and is required for effective p53 response . TTC5 can activate the p53 pathway and inhibit AP-1 transcriptional activity .
Atu4866-like superfamily (Atu4866-like_sf)
Type: Homologous_superfamily

The function of the proteins in this entry is not known, though Atu4866 from Agrobacterium tumefaciens has been structurally characterised. Atu4866 adopts a streptavidin-like fold and has a β-barrel/sandwich which is formed by eight antiparallel β-strands . Atu4866 has a potential ligand-binding site where it has a stretch of conserved residues on the surface.
Cren7 superfamily (Cren7_sf)
Type: Homologous_superfamily

Cren7 is a chromatin protein found in Crenarchaeota and has a higher affinity for double-stranded DNA than for single-stranded DNA. The protein contains negative DNA supercoils and is associated with genomic DNA in vivo. Cren7 interacts with duplex DNA through a β-sheet and a long flexible loop. It is binding to double-stranded DNA without sequence specificity . There is approximately 1 Cren7 molecule for 12 bp of DNA. The function of Cren7 has not been completely determined but it is thought that the protein may have a role similar to that of archaeal proteins in Euryarchaea .
PHR domain superfamily (PHR_sf)
Type: Homologous_superfamily

This domain is called PHR as it was originally found in the E3 ubiquitin-protein ligase proteins PAM (

), highwire (

) and RPM-1 (

) .

PHR proteins are conserved, large multi-domain E3 ubiquitin ligases with modular architecture. PHR proteins presynaptically control synaptic growth and axon guidance and postsynaptically regulate endocytosis of glutamate receptors. Dysfunction of neuronal ubiquitin-mediated proteasomal degradation is implicated in various neurodegenerative diseases. PHR proteins are characterised by the presence of two PHR domains near the N terminus, which are essential for proper localisation and function. The domain has a β-sandwich fold composed of 11 anti-parallel β-strands .

The C-terminal region of the protein BTBD1 includes the PHR domain and is known to interact with Topoisomerase I, an enzyme which relaxes DNA supercoils .
Exonuclease I, SH3-like domain superfamily (EXOI_SH3_sf)
Type: Homologous_superfamily

In bacteria, exonuclease I (ExoI) is a monomeric processive 3'-5' exonuclease that degrades single-stranded DNA. The enzyme has been implicated as primarily being involved in repairing frameshift mutations. ExoI consists of three domains: an N-terminal nuclease domain with homology to the proofreading domain of E. coli DNA polymerase I and other DnaQ superfamily enzymes, a central domain with a portion that resembles an SH3 domain fold and a C- terminal α-helical domain. While a typical SH3-like domain consists of five or six antiparallel β-strands that form a compact β-sandwich, the β-sandwich of the SH3-like domain in ExoI is surrounded by α-helices, resulting in a substantially elaborated fold .

This entry represents the ExoI SH3-like domain.