SII-SWORD/CoKE huggingface dataset:
PADR1, C-terminal domain superfamily (PADR1_C_dom_sf)
Type: Homologous_superfamily

This entry represents the C-terminal of PADR1 domain which covers the zinc ribbon fold and the C-terminal tail .

Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme involved in multiple cellular processes including DNA repair, cell cycle control, apoptotic signalling, and transcriptional regulation. Stimulated by binding to nicked DNA, PARP-1 catalyses poly(ADP-ribosyl)ation of the acceptor proteins using NAD as a substrate. PARP-1 has a modular architecture composed of multiple, independently folded domains that can be generally described in three major segments representing the biochemical activities and functional roles of the enzyme: the DNA-binding domain (DBD), the automodification domain which contains a BRCT fold, and the catalytic domain, which consists of the helical (HD) and the ART subdomains. The catalytic domain of PARP-1 is located at the C-terminal end of the protein. The DNA-binding domain is located at the N terminus of PARP-1 and contains two zinc fingers that bind to various DNA structures, a nuclear localization signal, and a caspase-3 cleavage site. The two N-terminal zinc fingers of PARP-1 bind to DNA structures to trigger activation of the C-terminal catalytic domain of PARP-1. The DBD of human PARP-1 contains yet a third zinc-binding domain, referred to as PADR1, located between the N-terminal PARP-type zinc fingers and the central BRCT domain and it is required to mediate interdomain contacts essential for the efficient assembly of PARP-1 domains .

The fold of the PADR1 zinc-binding domain consists of an N-terminal helical region, a central zinc ribbon fold, and a C-terminal tail. Three α-helices form a subdomain at the N terminus, with the first helix extending away from the subdomain. The zinc-binding region forms a separate subdomain, making primarily water-mediated contacts with the N-terminal helical subdomain. The zinc-binding subdomain resembles a zinc ribbon fold with four Cys ligands. The spacing between the four Cys residues is strongly conserved among all organisms, following the pattern C-x(2)-C-x(11,12)-C-x(9)-C where C is cysteine and x(n) is the number of amino acids between the Cys
residues. The zinc-binding subdomain contains a three-stranded antiparallel β-sheet, with the first pair of zinc ligands located in the loop running over the top of the sheet. The other pair of zinc ligands is centrally located within β-strands, a result of a long (nine-amino acid) insertion between the third and fourth cysteines. An α-helix on the C-terminal tail of the PADR1 zinc-binding domain contributes to the fold of the N-terminal helical region, and the remainder of the C terminus extends away from the N-terminal subdomain .
Yeast killer toxin superfamily (Yeast_kill_tox_sf)
Type: Homologous_superfamily

Proteins in this superfamily, which are produced by Williopsis fungi, adopt a secondary structure consisting of eight strands in two β sheets, in a Greek-key topology . They are toxic, killing sensitive strains of yeast.
Circovirus capsid superfamily (Circovirus_capsid_sf)
Type: Homologous_superfamily

Circoviruses are small circular single stranded viruses. This superfamily represents the capsid protein from viruses such as Porcine circovirus and Beak and feather disease virus (

). These proteins are about 220 amino acids long and of unknown function.
Putative carbohydrate metabolism domain superfamily (Put_CMD_sf)
Type: Homologous_superfamily

This domain has been suggested to participate in carbohydrate metabolism . Structural evidence indicates that it might be a carbohydrate binding domain, with or without enzymatic activity. In particular, it has been hypothesised that it might act as a glycoside hydrolase .
PINIT domain superfamily (PINIT_sf)
Type: Homologous_superfamily

This entry represents the PINIT domain found in the Siz/PIAS RING family of SUMO E3 ligases . These proteins present a tripartite architecture with an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain desginated SP-CTD. Structural and biochemical studies have shown that both SP-RING and SP-CTD are required for activation of the E2-SUMO thioester while the PINIT domain is required for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a non-consensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1 .
Large ribosomal subunit protein eL27 superfamily (Ribosomal_eL27_sf)
Type: Homologous_superfamily

This entry represents the large ribosomal subunit protein eL27 (also known as L27) found in fungi, plants, algae and vertebrates .

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 .
Peptidase G1 superfamily (Peptidase_G1_sf)
Type: Homologous_superfamily

The peptidases in superfamily G1 form a subset of what were formerly termed 'pepstatin-insensitive carboxyl proteinases'. After its discovery in about 1970, the pentapeptide pepstatin soon came to be thought of as a very general inhibitor of the endopeptidases that are active at acidic pH. But more recently several acid-acting endopeptidases from bacteria and fungi had been found to be resistant to pepstatin. The unusual active sites of the 'pepstatin-insensitive carboxyl peptidases' proved difficult to characterise, but it has now been established that the enzymes from bacteria are acid-acting serine peptidases in superfamily S53 (clan SB), whereas the fungal enzymes are in superfamily G1 (formerly A4) . The importance of glutamate ('E') and glutamine ('Q') residues in the active sites of the superfamily G1 enzymes led to the superfamily name, Eqolisin .

This group of glutamate/glutamine peptidases belong to MEROPS peptidase superfamily G1 (eqolisin superfamily, clan GA). An example of this group is scytalidoglutamic peptidase. The proteins are thermostable, pepstatin insensitive and are active at low pH ranges . The enzyme has a unique heterodimeric structure, with a 39-residue light chain and a 173-residue heavy chain bound to each other non-covalently . The tertiary structure of the active site of scytalidoglutamic peptidase (MEROPS G01.001) with a bound tripeptide product has been interpreted as showing that Glu136 is the primary catalytic residue. The most likely mechanism is suggested to be nucleophilic attack by a water molecule activated by the Glu136 side chain on the si-face of the scissile peptide bond carbon atom to form the tetrahedral intermediate. Electrophilic assistance, and oxyanion stabilisation, are provided by the side-chain amide of Gln53.

Both scytalidoglutamic peptidase (MEROPS G01.001) and aspergilloglutamic peptidase (MEROPS G01.002) cleave the Tyr26 Thr27 bond in the B chain of oxidized insulin ; a bond not cleaved by other acid-acting endopeptidases. Scytalidoglutamic peptidase is most active on casein at pH 2 and is inhibited by 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP), a compound that also inhibits pepsin.
Large ribosomal subunit protein bL19 superfamily (Ribosomal_bL19_sf)
Type: Homologous_superfamily

This family represents the large ribosomal subunit protein bL19 found in bacteria and eukaryotes (which includes bL19c from plants (chloroplast), mitochondrial bL19m from animals, also referred to as MRLP19) . In Escherichia coli, bL19 is known to be located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site.
Sporulation-specific cell division protein SsgB superfamily (SsgB_sf)
Type: Homologous_superfamily

SsgB is a conserved activator of developmental cell division in morphologically complex actinomycetes . It controls cell division and spore maturation in streptomycetes. Together with SsgA, SsgB activates sporulation-specific cell division by controlling the localisation of FtsZ .

SsgB shows structural similarity to whirly ssDNA/guide RNA-binding proteins found in mitochondria or in plants, but the interaction of this protein with nucleic acids is unlikely. On the other hand, a conserved surface for protein-protein interaction has been identified and suggest that SsgB might be a binding partner .
Alternative oxidase superfamily (AOX_sf)
Type: Homologous_superfamily

The alternative oxidase (AOX) is an enzyme that forms part of the electron transport chain in mitochondria of different organisms . Proteins homologous to the mitochondrial oxidase have also been identified in bacterial genomes . The oxidase provides an alternative route for electrons passing through the electron transport chain to reduce oxygen. However, as several proton-pumping steps are bypassed in this alternative pathway, activation of the oxidase reduces ATP generation. This enzyme was first identified as a distinct oxidase pathway from cytochrome c oxidase as the alternative oxidase is resistant to inhibition by the poison cyanide .

The alternative oxidase (also known as ubiquinol oxidase) is used as a second terminal oxidase in the mitochondria, electrons are transferred directly from reduced ubiquinol to oxygen forming water . This is not coupled to ATP synthesis and is not inhibited by cyanide, this pathway is a single step process . In Oryza sativa (rice) the transcript levels of the alternative oxidase are increased by low temperature . It has been predicted to contain a coupled diiron centre on the basis of a conserved sequence motif consisting of the proposed iron ligands, four Glu and two His residues . The EPR study of Arabidopsis thaliana (mouse-ear cress) alternative oxidase AOX1a shows that the enzyme contains a hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron centre . A catalytic cycle has been proposed that involves a di-iron centre and at least one transient protein-derived radical, most probably an invariant Tyr residue .

The structure of alternative oxidase from Trypanosoma brucei has been solved. The enzyme is a homodimer with the nonhaem di-iron carboxylate active site buried within a four-helix bundle. In the inhibitor-free state, the di-iron carboxylate is ligated by four glutamate residues, but on binding of an inhibitor, a histidine is also induced to act as a ligand. A highly conserved tyrosine is close to the active site and required for activity . This entry represents proteins with a structure similar to that of alternative oxidase.
OspE-like superfamily (OspE-like_sf)
Type: Homologous_superfamily

This entry represents outer surface proteins (Osp) from the Borrelia spp. spirochete . The superfamily includes OspE, OspF, and OspEF-related proteins (Erp) . These proteins are coded for on different circular plasmids in the Borrelia genome.

Borrelia burgdorferi spirochetes, that cause Lyme borreliosis, survive for a long time in human serum due to their ability to succesfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is required for this since it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis .
Large ribosomal subunit protein eL33 superfamily (Ribosomal_eL33_sf)
Type: Homologous_superfamily

This entry represents the large ribosomal subunit protein eL33 (also known as L35A in vertebrates) which is required for the proliferation and viability of hematopoietic cells and plays a role in the 60S ribosomal subunit formation. Its structure adopts a six-stranded antiparallel β-barrel analogous to the "tRNA binding motif" fold .
F1F0 ATP synthase subunit C superfamily (ATP_synth_F0_csu_sf)
Type: Homologous_superfamily

This entry represents subunit C (also called subunit 9, or proteolipid) found in the F0 complex of F-ATPases. Ten C subunits form an oligomeric ring that makes up the F0 rotor. The flux of protons through the ATPase channel drives the rotation of the C subunit ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the C subunit ring of F0. The sequential protonation and deprotonation of Asp61 of subunit C is coupled to the stepwise movement of the rotor .

F1F0 ATP synthase subunit C is a mainly all-alpha protein with the helices arranged in an up-down bundle. The protein fold is a hairpin of two antiparallel helical segments connected by a short structured loop .
Bacteriophage PRD1, P5 C-terminal domain superfamily (PRD1_P5_C_sf)
Type: Homologous_superfamily

The spike structure of bacteriophage PRD1 is comprised of proteins P2, P5, and P31. P5 is an elongated multidomain trimer. The C-terminal fragment of P5 appears to contain the residues responsible for the trimerization of the protein, whereas the smaller N-terminal part mediates the interaction with protein P31 .
H/ACA RNP complex subunit Gar1/Naf1, Cbf5-binding domain (Gar1/Naf1_Cbf5-bd_sf)
Type: Homologous_superfamily

H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. The function of these H/ACA RNPs is essential for biogenesis of the ribosome, splicing of precursor mRNAs (pre-mRNAs), maintenance of telomeres and probably for additional cellular processes . All H/ACA RNPs contain a specific RNA component (snoRNA or scaRNA) and at least four proteins common to all such particles: Cbf5, Gar1, Nhp2 and Nop10. These proteins are highly conserved from yeast to mammals and homologues are also present in archaea . The H/ACA protein complex contains a stable core composed of Cbf5 and Nop10, to which Gar1 and Nhp2 subsequently bind .

Naf1 is an RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex, disappearing during maturation of the complex and being replaced by Gar1 to yield mature H/ACA snoRNPs complex. The core domain of Naf1 is homologous to the core domain of Gar1, suggesting that they share a common Cbf5 binding surface .
Voltage-dependent anion channel superfamily (Voltage-dep_anion_channel_sf)
Type: Homologous_superfamily

Each of these transporters has ten α helical transmembrane segments . The structure of a bacterial homologue of SLAC1 shows it to have a trimeric arrangement. The pore is composed of five helices with a conserved Phe residue involved in gating. One homologue, Mae1 from the yeast Schizosaccharomyces pombe, functions as a malate uptake transporter; another, Ssu1from Saccharomyces cerevisiae and other fungi including Aspergillus fumigatus, is characterised as a sulfite efflux pump; and TehA from Escherichia coli is identified as a tellurite resistance protein by virtue of its association in the tehA/tehB operon. In plants, homologues are found in the stomatal guard cells functioning as an anion-transporting pore . Many homologues are incorrectly annotated as tellurite resistance or dicarboxylate transporter (TDT) proteins.
Bacteriophage SPP1, head-tail adaptor superfamily (SSP1_head-tail_sf)
Type: Homologous_superfamily

This entry describes the head-tail adaptor protein of bacteriophage SPP1
and related proteins in other bacteriophage and prophage regions of bacterial genomes. Homologues are also found in Gene Transfer Agents (GTA) , including ORFg7 (RCAP_rcc01689) of the GTA of Rhodobacter capsulatus (Rhodopseudomonas capsulata) . This entry also includes gp7.

In bacteriophage SPP1, the gp16 protein functions as a stopper, locking the viral DNA into the capsid. When the tail attachment binds to the entry receptor, gp16 opens by a diaphragm-like motion, allowing the genome to exit the capsid through the tail tube to the host cell. During virion assembly, gp16 functions as a docking platform to which the preassembled tail binds .

The gp7 protein functions as a stopper within the head-tail connector, locking the viral DNA inside the capsid . Upon attachment of the tail to the host cell entry receptor, gp7 appears to open via a diaphragm-like motion, allowing the genome to exit the capsid through the tail tube and enter the host cell. During viral assembly, gp7 also acts as a docking platform for the preassembled tail, which is tapered by the head-tail joining protein gp17.

The SPP1 head-to-tail connector is composed of cyclical dodecamers of the portal protein gp6 and of the 2 head completion proteins gp15 and gp16 .
XkdH-like superfamily (XkdH-like_sf)
Type: Homologous_superfamily

This superfamily represents the phage-like element PBSX protein XkdH from Bacillus subtilis and related proteins. Its function is still not clear.
Lipid-binding superfamily (Lipid-bd_sf)
Type: Homologous_superfamily

This entry represents a small superfamily of uncharacterised proteins found in Bacteroidetes that may be involved in lipid binding.
TbpB, N-lobe handle domain superfamily (TbpB_N-lobe_sf)
Type: Homologous_superfamily

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 .
HslJ-like superfamily (HslJ-like_sf)
Type: Homologous_superfamily

This entry represents a domain found in proteins of unknown function , some of which are described as heat shock protein (HslJ). In Helicobacter pylori (Campylobacter pylori) the protein is secreted e.g. (

) and implicated in motility. In Leishmania spp. it is described as an essential protein, over-expression of which, in Leishmania amazonensis increases virulence (

). In E. coli, hslJ is not induced by heat shock. It encodes a putative outer-membrane protein that is CysB-regulated and is involved in displaying novobiocin resistance .

A pair of cysteine residues show correlated conservation, suggesting that they form a disulphide bond.
Human cytomegalovirus, UL16 ectodomain (HCMV_UL16_sf)
Type: Homologous_superfamily

Protein UL16 from human cytomegalovirus (HCMV) is an immunoevasin which subverts NKG2D-mediated immune responses by retaining a select group of diverse NKG2D ligands inside the cell. UL16 is a heavily glycosylated 50kDa type I trans-membrane glycoprotein. The ectodomain folds into a modified version of the a variable (V-type) immunoglobulin Ig-like domain. The N-terminal 'plug' region (amino acids 27-50) is covalently linked to the Ig-like core with a disulfide bond. UL16 protein utilizes a three-stranded β-sheet to engage the α-helical surface of the MHC class I-like MICB platform domain. Residues at the centre of this β-sheet mimic a central binding motif employed by the structurally unrelated C-type lectin-like NKG2D to facilitate engagement of diverse NKG2D ligands .
Chromophore lyase CpcT/CpeT superfamily (CpcT/CpeT_sf)
Type: Homologous_superfamily

This entry represents the CpcT/CpeT biliprotein lyase, which has been shown to covalently attach chromophores to cystiene residue(s) of phycobiliproteins . These proteins contain a conserved motif PYR in the amino terminal half of the protein that may be functionally important. In the chromatically adapting cyanobacterium Fremyella diplosiphon, the proteins have been shown to be induced by green light, as part of the cpeCDESTR operon .

Structurally, CpcT forms a dimer and adopts a calyx-shaped β-barrel fold. Each CpcT subunit adopts a conical, goblet-shaped β-barrel with 10 anti-parallel β-strands; this fold is characteristic for the FABP subfamily of the calycin superfamily.
Carbohydrate-selective porin OprB superfamily (OprB_sf)
Type: Homologous_superfamily

The carbohydrate-selective porin OprB superfamily includes the Pseudomonas aeruginosa porin B, a substrate-selective channel for a variety of different sugars. This protein may facilitate diffusion of a variety of diverse compounds, but is probably restricted to carbohydrates, and does facilitate glucose fusion across the outer membrane. Its structure shows that OprB forms a monomeric 16-stranded β-barrel .

This entry also includes the porin AaxA from Chlamydophila pneumoniae. It facilitates L-arginine uptake, as part of the AaxABC system . The arginine uptake by the bacterium in the macrophage may be a virulence factor against the host innate immune response.