SII-SWORD/CoKE huggingface dataset:
Poly(ADP-ribose) polymerase, regulatory domain superfamily (Poly(ADP-ribose)pol_reg_dom_sf)
Type: Homologous_superfamily

Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The regulatory domain of the polymerase is almost always associated with the C-terminal catalytic domain (see

).

This domain consists of a duplication of two helix-loop-helix structural repeats .
Barrier-to-autointegration factor, BAF superfamily (BAF_sf)
Type: Homologous_superfamily

Barrier-to-autointegration factor (BAF) is an essential protein that is highly conserved in metazoan evolution, and which may act as a DNA-bridging protein . BAF binds directly to double-stranded DNA, to transcription activators, and to inner nuclear membrane proteins, including lamin A filament proteins that anchor nuclear-pore complexes in place, and nuclear LEM-domain proteins that bind to laminins filaments and chromatin. New findings suggest that BAF has structural roles in nuclear assembly and chromatin organisation, represses gene expression and might interlink chromatin structure, nuclear architecture and gene regulation in metazoans .

BAF can be exploited by retroviruses to act as a host component of pre-integration complexes, which promote the integration of the retroviral DNA into the host chromosome by preventing autointegration of retroviral DNA . BAF might contribute to the assembly or activity of retroviral pre-integration complexes through direct binding to the retroviral proteins p55 Gag and matrix, as well as to DNA.
PtsI, HPr-binding domain superfamily (PtsI_HPr-bd_sf)
Type: Homologous_superfamily

This superfamily describes a domain that can be found in the N terminus of PtsI, a component of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). The PTS system is found throughout the bacterial kingdom, and is responsible for the coupled phosphorylation and translocation of numerous sugars across the cytoplasmic membrane . PtsI transfers the phosphoryl group from phosphoenolpyruvate (PEP) to the phosphoryl carrier protein (HPr) which in turn phosphorylates a group of membrane-associated proteins, known as enzyme II .

This region contains a SAM domain-like fold.
NinB superfamily (NinB_sf)
Type: Homologous_superfamily

The ninR region of Bacteriophage lambda contains two recombination genes, ninB and ninG (rap), that have roles when the RecF and RecBCD recombination pathways of Escherichia coli, respectively, operate on phage lambda . Genetic recombination in phage lambda relies on DNA end processing by Exo to expose 3'-tailed strands for annealing and exchange by beta protein. Phage lambda encodes an additional recombinase, NinB, which participates in the early stages of recombination by supplying a function equivalent to the E. coli RecFOR complex. These host enzymes assist loading of the RecA strand exchange protein onto ssDNA coated with ssDNA-binding protein. NinB has two structural domains with unusual folds, and exists as an intertwined dimer .
Chromosomal protein MC1 superfamily (MC1_sf)
Type: Homologous_superfamily

This superfamily represents the chromosomal protein MC1, which protects DNA against thermal denaturation and shapes DNA by binding to it . Its global fold consists of a pseudo barrel with an extension of the β-sheet (β4-β5) forming an arm (LP5) .
Anticodon-binding domain superfamily (Anticodon-bd_dom_sf)
Type: Homologous_superfamily

tRNA synthetases, or tRNA ligases are involved in protein synthesis. This domain is found in histidyl, glycyl, threonyl and prolyl tRNA synthetases . It is probably the anticodon binding domain .

Structurally, the anticodon-binding domain has three layers (α/β/α) containing a mixed β-sheet of five strands, where strand 4 is antiparallel to the rest.
Dioxygenase LigAB, LigA subunit superfamily (LigA_sf)
Type: Homologous_superfamily

LigAB is a protocatechuate 4,5-dioxygenase (

) that belongs to the extradiol class III enzyme family. The LigA subunit of this enzyme is multi-helical, containing a compact array of six short helices .
Hemimethylated DNA-binding domain superfamily (Hemimethylated_DNA-bd_sf)
Type: Homologous_superfamily

Heat shock protein HspQ, also known as YccV, is an Escherichia coli hemimethylated DNA binding protein which has been shown to regulate dnaA gene expression .

This entry represents a YccV-like hemimethylated DNA binding domain superfamily that is found in HspQ and also in longer eukaryotic proteins.
Hcp1-like superfamily (Hcp1-lik_sf)
Type: Homologous_superfamily

This entry consists of Hcp-like proteins. Hcp is part of the type VI secretion system of Gram-negative bacteria. Hcp is not only a secreted effector protein, but also might act as machine component .

Several bacterial pathogens mediate interactions with their hosts through protein secretion, often involving Hcp-like virulence loci, which are widely distributed among pathogenic bacteria. Homologues of Hcp are found in various bacteria of which most, but not all, are known pathogens. Many bacteria have two copies of hcp genes . In Pseudomonas syringae, Hcp1 is a virulence protein, while Hcp2 seems to be required for survival in competition with enterobacteria and yeasts, and its function is associated with the suppression of the growth of these competitors .

Hcp1 monomers form a hexameric ring with a large internal diameter. Assembly of this particle is likely to occur following secretion, and could have a role in building a channel for the transport of other macromolecules .
E3-binding domain superfamily (E3-bd_dom_sf)
Type: Homologous_superfamily

A small domain of the E2 subunit of 2-oxo-acid dehydrogenases that is responsible for the binding of the E3 subunit. Proteins containing this domain include the branched-chain alpha-keto acid dehydrogenase complex of bacteria, which catalyses the overall conversion of alpha-keto acids to acyl-CoA and carbon dioxide; and the E3 binding protein of eukaryotic pyruvate dehydrogenase .

The structure of the E3-binding domain has three helices with a close bundle fold and right-handed twist going up-and-down . This structure arrangement is also found at the C-terminal of Nucleoid-associated protein Lsr2 and Protein Ku, in which it is a DNA-binding domain .
Head-to-tail joining protein W superfamily (GpW_sf)
Type: Homologous_superfamily

GpW is a 68 residue protein known to be present in phage particles. Extracts of phage-infected cells lacking GpW contain DNA-filled heads, and active tails, but no infectious virions. GpW is required for the addition of GpFII to the head, which is, in turn, required for the attachment of tails. Since GpFII and tails are known to be attached at the connector, GpW is also likely to assemble at this site. The addition of GpW to filled heads increases the DNase resistance of the packaged DNA, suggesting that GpW either forms a plug at the connector to prevent ejection of the DNA, or binds directly to the DNA. The large number of positively charged residues in GpW (its calculated pI is 10.8) is consistent with a role in DNA interaction .

The structure of GpW has an α-β(2)-α fold with antiparallel hairpin.
CobW-like, C-terminal domain superfamily (CobW-likC_sf)
Type: Homologous_superfamily

CobW proteins are generally found proximal to the trimeric cobaltochelatase subunit CobN, which is essential for vitamin B12 (cobalamin) biosynthesis . They contain a P-loop nucleotide-binding loop in the N-terminal domain and a histidine-rich region in the C-terminal portion suggesting a role in metal binding, possibly as an intermediary between the cobalt transport and chelation systems. CobW might be involved in cobalt reduction leading to cobalt(I) corrinoids.

This entry represents the C-terminal domain found in CobW, as well as in P47K (

), a Pseudomonas chlororaphis protein needed for nitrile hydratase expression .
Clp, N-terminal domain superfamily (Clp_N_dom_sf)
Type: Homologous_superfamily

ClpA is an ATP-dependent chaperone and part of the ClpAP protease that participates in regulatory protein degradation and the dissolution and degradation of protein aggregates . ClpA recognises sequences in specific proteins, which it then unfolds in an ATP-dependent manner and transports into the degradation chamber of the associated ClpP protein . A small adaptor-like protein, ClpS, modulates the activity of ClpA and is an important regulatory factor for this protein . It protects ClpA from autodegradation and appears to redirect its activity away from soluble proteins and toward aggregated proteins.

Molecular chaperones recognise unfolded or misfolded proteins by binding to hydrophobic surface patches not normally exposed in the native proteins. Members of the Clp/Hsp100 family of chaperones are present in eubacteria and within organelles of all eukaryotes, promoting disaggregation and disassembly of protein complexes and participating in energy-dependent protein degradation. The ClpA, ClpB, and ClpC subfamilies of the Clp/Hsp100 ATPases contain a conserved N-terminal domain of ~150 amino acids, which in turn consists of two repeats of ~75 residues. Although the Clp repeat (R) domain, also known as the N domain, contains two approximate sequence repeats, it behaves as a single cooperatively folded unit. The Clp R domain is thought to provide a means for regulating the specificity of and to enlarge the substrate pool available to Clp/Hsp100 chaperone or protease complexes. These roles can be assisted through the binding of an adaptor protein. Adaptor proteins bind to the Clp R domain, modulate the target specificity of the Clp/Hsp100 complex to a particular substrate of interest, and may also regulate the activity of the complex . The Clp R domain structure consists of two four-helix bundles connected by a flexible loop . The ClpV R-domain exhibits weak sequence homology to the R-domains of ClpA, ClpB and ClpC. In ClpV, the R-domain interacts with the VipA/VipB complex .
YjbJ superfamily (YjbJ_sf)
Type: Homologous_superfamily

This entry represents a group of bacterial stress response proteins, including
CsbD. The expression of CsbD is mediated by sigma-B, an alternative sigma factor . These proteins contain a SAM domain-like fold.
Head decoration protein D superfamily (Head_decoration_D_sf)
Type: Homologous_superfamily

Bacteriophage lambda head decoration protein D stabilises the head shell after the rearrangement of GP7 subunits of the head shell lattice that accompanies expansion of the head. There are approximately 420 copies of protein D per mature phage.

Head decoration protein D structure has a β-clip fold, which consists of a double-stranded ribbon sharply bent in two places where the ribbon ends form incomplete barrel.
Methylated DNA-protein cysteine methyltransferase domain superfamily (MGMT_N_sf)
Type: Homologous_superfamily

Synonym(s): 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase

The repair of DNA containing O6-alkylated guanine is carried out by DNA-[protein]-cysteine S-methyltransferase (

). The major mutagenic and carcinogenic effect of methylating agents in DNA is the formation of O6-alkylguanine. The alkyl group at the O-6 position is transferred to a cysteine residue in the enzyme . This is a suicide reaction since the enzyme is irreversibly inactivated and the methylated protein accumulates as a dead-end product. Most, but not all of the methyltransferases are also able to repair O-4-methylthymine. DNA-[protein]-cysteine S-methyltransferases are widely distributed and are found in various prokaryotic and eukaryotic sources .

This superfamily represents the domain that contains an ribonuclease H-like motif associated with 6-O-methylguanine DNA methyltransferase activity (

).
Scaffold protein D superfamily (Scaffold_D_sf)
Type: Homologous_superfamily

The assembly of a macromolecular structure proceeds via a specific pathway of ordered events and occurs by changing of protein conformations as they join the assembly. The assembly process is aided by scaffolding proteins, which act as chaperones. In bacteriophages, scaffolding proteins B and D are responsible for procapsid formation. Copies of protein D (240) form the external scaffold, while 60 copies of protein B form the internal scaffold .

The structure of the scaffolding protein gpD is composed of six helices where one central helix is surrounded by 5 others.
Orn/Lys/Arg decarboxylase, C-terminal domain superfamily (Prn/Lys/Arg_de-COase_C_sf)
Type: Homologous_superfamily

Pyridoxal-dependent decarboxylases are bacterial proteins acting on ornithine, lysine, arginine and related substrates . One of the regions of sequence similarity contains a conserved lysine residue, which is the site of attachment of the pyridoxal-phosphate group. Ornithine decarboxylase is a dodecamer composed of six homodimers and catalyzes the decarboxylation of tryptophan. Arginine decarboxylase catalyzes the decarboxylation of arginine and lysine decarboxylase catalyzes the decarboxylation of lysine. Members of this superfamily are widely found in all three forms of life .
PRD domain superfamily (PRD_sf)
Type: Homologous_superfamily

Transcriptional antiterminators and activators containing phosphoenolpyruvate: sugar phosphotransferase system (PTS) regulation domains (PRDs) form a class of bacterial regulatory proteins whose activity is modulated by phosphorylation. These regulators stimulate the expression of genes and operons involved in carbohydrate metabolism.

PRD-containing proteins are involved in the regulation of catabolic operons in Gram-positive and Gram-negative bacteria and are often characterised by a short N-terminal effector domain that binds to either RNA (CAT-RBD for antiterminators,

) or DNA (for activators), and a duplicated PRD module which is phosphorylated on conserved histidines by the sugar phosphotransferase system (PTS) in response to the availability of carbon source. The phosphorylations are thought to modify the stability of the dimeric proteins and thereby the RNA- or DNA-binding activity of the effector domain .
UDP-N-acetylenolpyruvoylglucosamine reductase, C-terminal domain superfamily (MurB_C_sf)
Type: Homologous_superfamily

This entry represents a C-terminal conserved region of UDP-N-acetylenolpyruvoylglucosamine reductase

, which is also called UDP-N-acetylmuramate dehydrogenase. The C-terminal domain is involved in substrate binding . It is a part of the pathway for the biosynthesis of the UDP-N-acetylmuramoyl-pentapeptide, which is a precursor of bacterial peptidoglycan.
Cytochrome c oxidase subunit VIIc superfamily (COX7C/Cox8_sf)
Type: Homologous_superfamily

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.
Phosphohistidine domain superfamily (Phosphohistidine_dom_sf)
Type: Homologous_superfamily

A number of enzymes that catalyze the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) via a phospho-histidine intermediate have been shown to be structurally related . All these enzymes share the same catalytic mechanism: they bind PEP and transfer the phosphoryl group from it to a histidine residue. This domain is a "swivelling" β/β/α domain which is thought to be mobile in all proteins known to contain it .
Helix-loop-helix DNA-binding domain superfamily (HLH_DNA-bd_sf)
Type: Homologous_superfamily

This domain is found in a number of eukaryotic proteins, which probably are sequence specific DNA-binding proteins that act as transcription factors, share a conserved domain of 40 to 50 amino acid residues. It has been proposed that this domain is formed of two amphipathic helices joined by a variable length linker region that could form a loop. This 'helix-loop-helix' (HLH) domain mediates protein dimerisation and has been found in the proteins listed below . Most of these proteins have an extra basic region of about 15 amino acid residues that is adjacent to the HLH domain and specifically binds to DNA. They are referred as basic helix-loop-helix proteins (bHLH), and are classified in two groups: class A (ubiquitous) and class B (tissue-specific). Members of the bHLH family bind variations on the core sequence 'CANNTG', also referred to as
the E-box motif. The homo- or heterodimerisation mediated by the HLH domain is independent of, but necessary for DNA binding, as two basic regions are required for DNA binding activity. The HLH proteins lacking the basic domain (Emc, Id) function as negative regulators, since they form heterodimers, but fail to bind DNA. The hairy-related proteins (hairy, E(spl), deadpan) also repress transcription although they can bind DNA. The proteins of this subfamily act together with co-repressor proteins, like groucho, through their -terminal motif WRPW.
Cytochrome c oxidase subunit IV superfamily (Cyt_c_oxidase_su4_sf)
Type: Homologous_superfamily

This superfamily is composed of cytochrome c oxidase subunit 4 , subunits 5A and 5B , subunit 6 and subunit 7. Proteins in this entry also include the yeast COX IV subunit, Mtc3 (maintenance of telomere cappining 3) protein .

Cytochrome c oxidase (CcO) (

), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of prokaryotes. It catalyses the reduction of O2 and simultaneously pumps protons across the membrane. The number of subunits varies from three to five in bacteria and up to 13 in mammalian mitochondria. Subunits I, II, and III of mammalian CcO are encoded within the mitochondrial genome and the remaining 10 subunits are encoded within the nuclear genome. Found only in eukaryotes, subunit IV is the largest of the nuclear-encoded subunits. It binds ATP at the matrix side, leading to an allosteric inhibition of enzyme activity at high intramitochondrial ATP/ADP ratios. In mammals, subunit IV has a lung-specific isoform and a ubiquitously expressed isoform .
ABC transporter type 1, transmembrane domain superfamily (ABC1_TM_sf)
Type: Homologous_superfamily

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain .

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions . Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette . More than 50 subfamilies have been described based on a phylogenetic and functional classification ; (for further information see
Transporter Classification Database
).

This entry represents the transmembrane domain in cases where the TMD and ABC region are found in the same protein, and corresponds to ABC type 1 from
Transporter Classification Database
.
HPT domain superfamily (HPT_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain present at the N terminus in proteins which undergo autophosphorylation. The group includes histidine kinases such as CheA from Escherichia coli, the gliding motility regulatory protein from Myxococcus xanthus, and a number of bacterial chemotaxis proteins.

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .
Cytochrome b-c1 complex subunit 8 superfamily (Cyt_bc1_su8_sf)
Type: Homologous_superfamily

The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multi-enzyme complex , which recognises a mitochondrial targeting presequence. The bc1 complex contains 11 subunits: 3 respiratory subunits (cytochrome b, cytochrome c1 and Rieske protein), 2 core proteins and 6 low molecular weight proteins. This entry represents the 9.5kDa subunit of the complex, known as subunit 8 or protein QP-C . This subunit together with cytochrome B binds to ubiquinone.