SII-SWORD/CoKE huggingface dataset:
Quinohemoprotein amine dehydrogenase, gamma subunit structural domain superfamily (QH-AmDH_gsu_sf)
Type: Homologous_superfamily

Quinohemoprotein amine dehydrogenases (QHNDH)

) are enzymes produced in the periplasmic space of certain Gram-negative bacteria, such as Paracoccus denitrificans and Pseudomonas putida, in response to primary amines, including n-butylamine and benzylamine. QHNDH catalyses the oxidative deamination of a wide range of aliphatic and aromatic amines through formation of a Schiff-base intermediate involving one of the quinone O atoms . Catalysis requires the presence of a novel redox cofactor, cysteine tryptophylquinone (CTQ). CTQ is derived from the post-translational modification of specific residues, which involves the oxidation of the indole ring of a tryptophan residue to form tryptophylquinone, followed by covalent cross-linking with a cysteine residue . There is one CTQ per subunit in QHNDH. In addition to CTQ, two haem c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor, cytochrome c-550 .

QHNDH is a heterotrimer of alpha, beta and gamma subunits. The alpha and beta subunits contain signal peptides necessary for the translocation of QHNDH to the periplasm. The alpha subunit is composed of four domains - domain 1 forming a dihaem cytochrome, and domains 2-4 forming antiparallel β-barrel structures; the beta subunit is a 7-bladed β-propeller that provides part of the active site; and the small, catalytic gamma subunit contains the novel cross-linked CTQ cofactor, in addition to additional thioester cross-links between Cys and Asp/Glu residues that encage CTQ. The gamma subunit assumes a globular secondary structure with two short α-helices having many turns and bends .

This entry represents the main structural domain of the QHNDH gamma subunit.
DUF1883-like superfamily (DUF1883-like_sf)
Type: Homologous_superfamily

This domain corresponds to a predicted ligand-binding domain of the PPC-like β-sandwich fold. It has been observed in conserved gene neighbourhoods with diverse nucleotide-activated effector and related conflict systems, which potentially recognises invasive molecules and initiates system responses or directly triggers directly-associated effector domains .
YoaG superfamily (YoaG_sf)
Type: Homologous_superfamily

This entry represents a group of uncharacterised bacterial proteins.
Thoeris protein ThsB, TIR-like domain superfamily (ThsB_TIR-like_sf)
Type: Homologous_superfamily

This is the TIR-like domain of ThsB proteins, which adopts a Rossmann-like fold . ThsB is responsible for recognizing phage infection .

Thoeris is a bacterial antiphage defense system, which consists of two genes, thsA and thsB, via NAD+ degradation . ThsA has robust NAD+ cleavage activity and a two-domain architecture containing an N-terminal NAD-binding domain (denoted as sirtuin-like or Macro) and C-terminal SLOG-like domain. In some instances, such as in B. amyloliquefaciens, ThsA has an N-terminal transmembrane domain . ThsB (also referred to as TIR1 and TIR2) is structurally similar to TIR domain proteins but without enzymatic activity.
YugN-like superfamily (YugN-like_sf)
Type: Homologous_superfamily

This entry contains proteins related to Bacillus subtilis YugN, they are functionally uncharacterised.
Hypothetical protein YojF superfamily (YojF_sf)
Type: Homologous_superfamily

This entry consists of bacterial uncharacterised proteins. The structure of one of the proteins has been solved and it adopts a β barrel-like structure.
Hypothetical protein YunC superfamily (YunC_sf)
Type: Homologous_superfamily

This protein is found in bacteria and archaea and has an N-terminal tetramerisation region that is composed of β sheets.
Ku, C-terminal domain superfamily (Ku_C_sf)
Type: Homologous_superfamily

The non-homologous end joining (NHEJ) pathway is one method by which double stranded breaks in chromosomal DNA are repaired. Ku is a component of a multi-protein complex that is involved in the NHEJ. Ku has affinity for DNA ends and recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Ku also binds RNA, mediating the assembly of DNA-PKcs which has a role in ribosomal RNA biogenesis . This domain is found at the C-terminal of Ku which binds to DNA-PKcs .
ORF7a superfamily, coronavirus (ORF7a_sf_CoV)
Type: Homologous_superfamily

This entry includes the structural accessory protein ORF7a, also called NS7a, X4 and U122, of Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoV) from betacoronavirus subgenera Sarbecovirus (lineage B), including SARS-CoV-2. ORF7a/NS7a from betacoronavirus in the subgenera Sarbecovirus (B lineage) are not related to NS7a proteins from other coronavirus lineages. The structure of the structural accessory protein ORF7a, shows similarities to the immunoglobulin-like fold with some features resembling those of the Dl domain of ICAM-1 and suggests a binding activity to integrin I domains . In SARS-CoV-infected cells, ORF7a is expressed and retained intracellularly within the Golgi network . ORF7a is thought to play an important role during the SARS-CoV replication cycle . Expression studies of ORF7a have shown that biological functions include induction of apoptosis through a caspase-dependent pathway, activation of the p38 mitogen-activated protein kinase signaling pathway, inhibition of host protein translation, and suppression of cell growth progression. These results collectively suggested that ORF7a protein may be involved in virus-host interactions . Studies in SARS-CoV-2 revealed that ORF7a plays a role as antagonist of host tetherin (BST2), disrupting its antiviral effect. ORF7a binds to BST2 and sequesters it to the perinuclear region, thereby preventing its antiviral function at cell membrane .
Cathepsin C, exclusion domain superfamily (CathepsinC_exc_dom_sf)
Type: Homologous_superfamily

Cathepsin C (dipeptidyl peptidase I) is the physiological activator of a group of serine proteases. This protein corresponds to the exclusion domain whose structure excludes the approach of a polypeptide apart from its termini and confers its exopeptidase specificity . It forms an enclosed β barrel structure composed from 8 anti-parallel β strands . Based on a structural comparison and interaction data, it is suggested that the exclusion domain originates from a metallo-protease inhibitor .
Glycolipid transfer protein superfamily (GLTP_sf)
Type: Homologous_superfamily

Glycolipid transfer protein (GLTP) is a cytosolic protein that catalyses the intermembrane transfer of glycolipids such as glycosphingolipids, glyceroglycolipids, and possibly glucosylceramides, but not of phospholipids. The GLTP protein consists of a single domain with a multi-helical structure consisting of two layers of orthogonally packed helices .
Scaffold protein Nfu/NifU, N-terminal domain superfamily (Nfu/NifU_N_sf)
Type: Homologous_superfamily

Iron-sulphur (FeS) clusters are important cofactors for numerous proteins involved in electron transfer, in redox and non-redox catalysis, in gene regulation, and as sensors of oxygen and iron. These functions depend on the various FeS cluster prosthetic groups, the most common being [2Fe-2S] and [4Fe-4S] . FeS cluster assembly is a complex process involving the mobilisation of Fe and S atoms from storage sources, their assembly into [Fe-S] form, their transport to specific cellular locations, and their transfer to recipient apoproteins. So far, three FeS assembly machineries have been identified, which are capable of synthesising all types of [Fe-S] clusters: ISC (iron-sulphur cluster), SUF (sulphur assimilation), and NIF (nitrogen fixation) systems.

In the NIF system, NifS and NifU are required for the formation of metalloclusters of nitrogenase in Azotobacter vinelandii, and other organisms, as well as in the maturation of other FeS proteins. Nitrogenase catalyses the fixation of nitrogen. It contains a complex cluster, the FeMo cofactor, which contains molybdenum, Fe and S. NifS is a cysteine desulphurase. NifU binds one Fe atom at its N-terminal, assembling an FeS cluster that is transferred to nitrogenase apoproteins . Nif proteins involved in the formation of FeS clusters can also be found in organisms that do not fix nitrogen .

This domain is found at the N terminus of NifU (from NIF system) and NifU related proteins, and in the human Nfu protein. Both of these proteins are thought to be involved in the assembly of iron-sulphur clusters, functioning as scaffolds .
Non-structural protein NSP9 superfamily, coronavirus (NSP9_sf_CoV)
Type: Homologous_superfamily

NSP9 is a single-stranded RNA-binding viral protein involved in RNA synthesis, essential for the coronavirus replication . The dimerisation of NSP9 is essential for binding and orienting RNA for subsequent use by the replicase machinery. NSP9 is composed of seven antiparallel β-strands and a single α-helix hat are arranged into a single compact domain and form a cone-shaped β-barrel flanked by the C-terminal α-helix (

) . The NSP9 dimer interface is formed by the N-finger motifs and the parallel association of the C-terminal α-helices GXXXG motifs. The N- and C-terminal regions are more conserved than the central core one, and the GXXXG motif is strictly conserved . NSP9 binds to discrete regions on the 7SL RNA component of the signal recognition particle (SRP) and interfere with protein trafficking to the cell membrane upon infection, which interferes with essential host functions, and suppresses host immune defenses .
Inhibitor of vertebrate lysozyme superfamily (Inhibitor_vert_lysozyme_sf)
Type: Homologous_superfamily

C-type lysozyme enzymes, such as hen egg white lysozyme (HEWL), provide anti-bacterial activity by cleaving peptidoglycan in Gram-positive bacterial cell walls. In humans, C-type lysozyme is found in all secretions, including tears and saliva. Certain Gram-positive bacteria can produce proteins with anti-lysozyme activity known as Inhibitor of Vertebrate Lysozyme (IVY), which act as virulence factors . IVY proteins have a 3-layer α(2)/β(5)/α(2) topology, and contain a protruding 5-residue loop that is essential for their inhibitory effect .
Nickel-containing superoxide dismutase superfamily (NiSOD_sf)
Type: Homologous_superfamily

This entry represents nickel-dependent superoxide dismutase (NiSOD) (

), a SOD enzyme that uses nickel, rather than iron, manganese, copper, or zinc. All SOD enzymes catalyse the dismutation of toxic superoxide radical anions to oxygen and hydrogen peroxide in order to protect cells from oxidative damage. The catalytic cycle of NiSOD consists of two half-reactions, each initiated by the successive approach of substrate to the metal centre. The first (reductive) phase involves Ni(III) reduction to Ni(II), and the second (oxidative) phase involves the metal reoxidation back to its resting state . NiSOD has a novel SOD fold and assembly, consisting of a hexameric assembly of 4-helix bundles of up-and-down topology, which contains a 9-residue nickel-hook structural motif that is critical for metal binding and catalysis . A gene for a required protease (NiSOD maturation protease;

) is adjacent to the NiSOD gene.
Aldehyde ferredoxin oxidoreductase, N-terminal domain superfamily (Ald_Fedxn_OxRdtase_N_sf)
Type: Homologous_superfamily

Enzymes of the aldehyde ferredoxin oxidoreductase (AOR) family contain a tungsten cofactor and an 4Fe4S cluster and catalyse the interconversion of aldehydes to carboxylates . This family includes AOR, formaldehyde ferredoxin oxidoreductase (FOR), glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), all isolated from hyperthermophilic archea ; carboxylic acid reductase found in clostridia ; and hydroxycarboxylate viologen oxidoreductase from Proteus vulgaris, the sole member of the AOR family containing molybdenum . GAPOR may be involved in glycolysis , but the functions of the other proteins are not yet clear. AOR has been proposed to be the primary enzyme responsible for oxidising the aldehydes that are produced by the 2-keto acid oxidoreductases .

This entry represents the N-terminal domain of these enzymes. This domain has been shown to interact with the tungsten cofactor .
CGI121/TPRKB superfamily (CGI121/TPRKB_sf)
Type: Homologous_superfamily

This entry represents the EKC/KEOPS complex subunit Cgi121 from fungi and its homologue, TPRKB from mammals. This entry also includes archaeal homologues .
N-acetylmuramoyl-L-alanine amidase/PGRP domain superfamily (Amidase/PGRP_sf)
Type: Homologous_superfamily

This entry represents a domain found in N-acetylmuramoyl-L-alanine amidases from bacteria and peptidoglycan recognition proteins (PGRP). PGRPs are ubiquitous proteins involved in innate immunity, conserved from insects to mammals. They have antibactericidal activity . PGRPs have at least one of these domains homologous to bacteriophage and bacterial type 2 amidases . Some PGRPs have been shown to be N-acetylmuramoyl-L-alanine amidases .
Telomere repeat-binding factor, dimerisation domain superfamily (Telomere_rpt-bd_fac_dimer_sf)
Type: Homologous_superfamily

Telomeres function to shield chromosome ends from degradation and end-to-end fusions, as well as preventing the activation of DNA damage checkpoints. Telomeric repeat binding factor (TRF) proteins TRF1 and TRF2 are major components of vertebrate telomeres required for regulation of telomere stability. TRF1 and TRF2 bind to telomeric DNA as homodimers. Dimerisation involves the TRF homology (TRFH) subdomain contained within the dimerisation domain. The TRFH subdomain is important not only for dimerisation, but for DNA binding, telomere localisation, and interactions with other telomeric proteins. The dimerisation domains of TRF1 and TRF2 show the same multi-helical structure, arranged in a solenoid conformation similar to TPR repeats, which can be divided into an α-α superhelix and a long α hairpin .

The two related human TRF proteins hTRF1 and hTRF2 form homodimers and bind directly to telomeric TTAGGG repeats via the myb DNA binding domain

at the carboxy terminus . TRF1 is implicated in telomere length regulation and TRF2 in telomere protection . Other telomere complex associated proteins are recruited through their interaction with either TRF1 or TRF2. The fission yeast protein Taz1p (telomere-associated in Schizosaccharomyces pombe (Fission yeast) has similarity to both hTRF1 and hTRF2 and may perform the dual functions of TRF1 and TRF2 at fission yeast telomeres .

This entry represents the dimerisation domain.
Chitin binding domain superfamily (Chitin-bd_dom_sf)
Type: Homologous_superfamily

This entry represents a chitin binding domain superfamily . It is found in (amongst others) the Peritrophin-A chitin binding proteins, particularly the peritrophic matrix proteins of insects and animal chitinases . Copies of the domain are also found in some baculoviruses. It is an extracellular domain that contains six conserved cysteines that probably form three disulphide bridges. Chitin binding has been demonstrated for a protein containing only two of these domains .
Peptide methionine sulphoxide reductase MsrA superfamily (Met_Sox_Rdtase_MsrA_sf)
Type: Homologous_superfamily

Peptide methionine sulphoxide reductase (Msr) reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulphoxide, Met(O), to methionine . It is present in most living organisms, and the cognate structural gene belongs to the so-called minimum gene set .

The domains MsrA and MsrB reduce different epimeric forms of methionine sulphoxide. This group represent MsrA, the crystal structure of which has been determined in a number of organisms. In Mycobacterium tuberculosis, the MsrA structure has been determined to 1.5 Angstrom resolution .

In contrast to the three catalytic cysteine residues found in previously characterised MsrA structures, M. tuberculosis MsrA represents a class containing only two functional cysteine residues. The overall structure shows no resemblance to the structures of MsrB (

) from other organisms; though the active sites show approximate mirror symmetry. In each case, conserved amino acid motifs mediate the stereo-specific recognition and reduction of the substrate.
Small ribosomal subunit protein bS20 superfamily (Ribosomal_bS20_sf)
Type: Homologous_superfamily

This superfamily consists of bacterial (and chloroplast) examples of the ribosomal small subunit protein bS20. Bacterial ribosomal protein bS20 forms part of the 30S ribosomal subunit, and interacts with 16S rRNA.

Structurally, the ribosomal protein bS20 has a spectrin repeat-like fold, which consists of three helices, a close bundle fold and left-handed twist going up-and-down.
Queuine tRNA-ribosyltransferase-like (TGT-like_sf)
Type: Homologous_superfamily

Queuine tRNA-ribosyltransferases, also known as tRNA-guanine transglycosylases (TGT)

, modify tRNAs for asparagine, aspartic acid, histidine and tyrosine with queuine at position 34 and with archaeosine at position 15 in archaeal tRNAs. In bacteria it catalyses the exchange of guanine-34 at the wobble position with 7-aminomethyl-7-deazaguanine (preQ1), and subsequently the addition of a cyclopentenediol moiety to 7-aminomethyl-7-deazaguanine-34 tRNA giving a hypermodified base queuine (Q) in the wobble position . In eukaryotes, TGT catalyses the irreversible exchange of guanine in the unmodified tRNA with free queuine. Eukaryotes cannot synthesize queuine
de novo
and must obtain it from the diet or gut flora .

The structure of TGT consists of an irregular (β/α)
8
barrel, represented by this entry, and a C-terminal zinc-containing subdomain .

This region is also found in DNA-guanine transglycosylase from Salmonella montevideo, which is involved in the insertion of 7-deazaguanine derivatives in DNA .
Photosystem II PsbZ superfamily (PSII_PsbZ_sf)
Type: Homologous_superfamily

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This superfamily represents PsbZ (Ycf9), which is a core low molecular weight transmembrane protein of photosystem II in thylakoid-containing chloroplasts of cyanobacteria and plants. It is thought to be located at the interface of PSII and LHCII (light-harvesting complex II) complexes, the latter containing the light-harvesting antenna. PsbZ appears to act as a structural factor, or linker, that stabilises the PSII-LHCII supercomplexes, which fail to form in PsbZ-deficient mutants. This may in part be due to the marked decrease in two LHCII antenna proteins, CP26 and CP29, found in PsbZ-deficient mutants, which result in structural changes, as well as functional modifications in PSII . PsbZ may also be involved in photo-protective processes under sub-optimal growth conditions.
Structurally, PsbZ has two antiparallel transmembrane helices.
STAS domain superfamily (STAS_dom_sf)
Type: Homologous_superfamily

The STAS (Sulphate Transporter and AntiSigma factor antagonist) domain is found in the bacterial anti-sigma factor antagonists (ASA) and the C-terminal region of SLC26 (SulP) anion transporters.

The activity of bacterial sigma transcription factors is controlled by a regulatory cascade involving an antisigma-factor, the antisigma-factor antagonist (ASA) and a phosphatase. The antisigma-factor binds to sigma and holds it in an inactive complex. The ASA can also interact with the anti-sigma-factor, allowing the release of the active sigma factor. As the antisigma-factor is a protein kinase, it can phosphorylate the antisigma antagonist on a conserved serine residue of the STAS domain. This phosphorylation inactivates the ASA that can be reactivated through dephosphorylation by a phosphatase . The STAS domain of the ASA SpoIIAA binds GTP and ATP and possesses a weak NTPase activity. Strong sequence conservation suggests that the STAS domain could possess general NTP-binding activity, and it has been proposed that the NTPs are likely to elicit specific conformational changes in the STAS domain through binding and/or hydrolysis . Resolution of the solution structure of the ASA SpoIIAA from Bacillus subtilis has shown that the STAS domain consists of a four-stranded β-sheet and four α-helices. The STAS domain forms a characteristic α-helical handle-like structure .

The STAS domain of E. coli YchM protein, a SLC26 (SulP) family member, has been shown to interact with acyl carrier protein (ACP), which is an activated thiol ester carrier of acyl intermediates during fatty acid biosynthesis (FAB) and other acylation reactions .

Malfunctions in members of the SLC26A family of anion transporters are involved in three human diseases: diastrophic dysplasia/achondrogenesis type 1B (DTDST), Pendred's syndrome (PDS) and congenital chloride diarrhea (CLD). These proteins contain 12 transmembrane helices followed by a cytoplasmic STAS domain at the C terminus. The importance of the STAS domain in these transporters is illustrated by the fact that a number of mutations in PDS and DTDST map to it .
SGNH hydrolase superfamily (SGNH_hydro_sf)
Type: Homologous_superfamily

SGNH hydrolase has a similar fold to flavoproteins, namely a three-layer α/β/α structure, where the β-sheets are composed of five parallel strands. Enzymes containing this domain act as esterases and lipases, but have little sequence homology to true lipases . Proteins containing this type of esterase domain have been found in a variety of hydrolases; those with structural information include an esterase from Streptomyces scabies ; the esterase domain of viral haemagglutinin-esterase surface glycoproteins (influenza C virus, coronaviruses and toroviruses) ; mammalian acetylhydrolases ; fungal rhamnogalacturonan acetylesterase ; and the multifunctional enzyme thioesterase I (TAP) from Escherichia coli . SGNH hydrolase-type esterase domains contain unique hydrogen bond network that stabilises their catalytic centres; they usually contain the catalytic triad Ser/Acid/His .
Transposase IS200-like superfamily (Transposase_17_sf)
Type: Homologous_superfamily

Transposases are needed for efficient transposition of the insertion sequence or transposon DNA. This entry represents a domain superfamily found in transposases for IS200 from Escherichia coli . The structure of this domain has a ferredoxin-like fold, which consists of an α-β sandwich with antiparallel β-sheet.
Translation repressor RegA superfamily (Transl_repress_RegA_sf)
Type: Homologous_superfamily

The translational regulator protein RegA, found in Bacteriophage T4 and related phages, binds to a region of messenger RNA (mRNA) that includes the initiator codon. RegA is unusual in that it represses the translation of about 35 early T4 mRNAs but does not affect nearly 200 other mRNAs . The structure of RegA has a ferredoxin-like fold, which consists of an α+β sandwich with antiparallel β-sheet.
FF domain superfamily (FF_domain_sf)
Type: Homologous_superfamily

This entry represents the FF domain superfamily.

The FF domain may be involved in protein-protein interaction . It often occurs as multiple copies and often accompanies WW domains

. PRP40 from yeast encodes a novel, essential splicing component that associates with the yeast U1 small nuclear ribonucleoprotein particle .

The structure of the FF domain is composed of three α helices arranged in an orthogonal bundle with a 3(10) helix in the loop between the second and third α helices .