SII-SWORD/CoKE huggingface dataset:
Transcription regulators MarR/SlyA-like (MarR/SlyA-like)
Type: Family

Transcription regulators of the MarR/SlyA family, involved in the development of antibiotic resistance, contain the MarR-type HTH domain, which is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 135 amino acids. The MarR family of transcription regulators is named after Escherichia coli MarR, a repressor of genes which activate the multiple antibiotic resistance and oxidative stress regulons, and after slyA from Salmonella typhimurium and E. coli, a transcription regulator that is required for virulence and survival in the macrophage environment. Regulators with the MarR-type HTH domain are present in bacteria and archaea and control a variety of biological functions, including resistance to multiple antibiotics, household disinfectants, organic solvents, oxidative stress agents and regulation of the virulence factor synthesis in pathogens of humans and plants. Many of the MarR-like regulators respond to aromatic compounds .

The crystal structures of MarR and SlyA have been determined and show a winged HTH DNA-binding core flanked by helices involved in dimerisation. The DNA-binding domains are ascribed to the superfamily of winged helix proteins, containing a three (four)-helix (H) bundle and a three-stranded antiparallel β-sheet (B) in the topology: H1-(H1')-H2-B1-H3-H4-B2-B3-H5-H6. Helices 3 and 4 comprise the helix-turn-helix motif and the β-sheet is called the wing. Helix 4 is termed the recognition helix, like in other HTHs where it binds the DNA major groove. The helices 1, 5 and 6 are involved in dimerisation, as most MarR-like transcription regulators form dimers .

This is a group of HTH-type transcriptional regulators including SlyA, Hpr and MarR.
Solute-binding protein family 5 (SBP_5)
Type: Family

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight families or clusters, which generally correlate with the nature of the solute bound.
RNA polymerase sigma-70-like (RNA_pol_sigma-70-like)
Type: Family

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .
TonB-dependent receptor-like (TonB-dep_rcpt-like)
Type: Family

This entry represents TonB proteins in bacteria and similar membrane proteins. This entry also includes the vitamin B12 transporter BtuB from Escherichia coli, which translocates vitamin B12 (cyanocobalamin) across the outer membrane to the periplasmic space. A conserved sequence of seven residues, the Ton box, faces the periplasm and interacts with the inner membrane TonB protein to energize this active transport cycle .

TonB proteins are bacterial membrane proteins that play a crucial role in energy-dependent active transport systems. They have an N-terminal plug domain which acts as the channel gate, blocking the pore until the channel is bound by a ligand when it undergoes conformational changes and opens the channel and a C-terminal β-barrel domain. In Escherichia coli, the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space . These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of TonB, these receptors bind their substrates but do not carry out active transport. TonB-dependent regulatory systems consist of six components: a specialised outer membrane-localised TonB-dependent receptor (TonB-dependent transducer) that interacts with its energising TonB-ExbBD protein complex, a cytoplasmic membrane-localised anti-sigma factor and an extracytoplasmic function (ECF)-subfamily sigma factor . The TonB complex senses signals from outside the bacterial cell and transmits them via two membranes into the cytoplasm, leading to transcriptional activation of target genes. Energy for active transport is again obtained through physical interaction with TonB . The proteins that are currently known or presumed to interact with TonB include BtuB, CirA, FatA, FcuT, FecA , FhuA , FhuE, FepA which is important for iron uptake and allows the bacterium to extract iron from the environment , FptA, HemR, IrgA, IutA, PfeA, PupA and Tbp1. The TonB protein also interacts with some colicins.
NADH-ubiquinone oxidoreductase chain 4L/Mnh complex subunit C1-like (NUOK/Mnh_C1-like)
Type: Family

This entry includes NADH:ubiquinone oxidoreductase, chain 4L and bacterial Mnh complex subunit C. They share significant protein sequence similarity .

ADH:ubiquinone oxidoreductase (complex I) (

) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) . In eukaryotes, NADH:ubiquinone oxidoreductase, chain 4L is usually found in either mitochondria or chloroplasts as part of the respiratory-chain NADH dehydrogenase (also known as complex I or
NADH-ubiquinone oxidoreductase), an oligomeric enzymatic complex . However, it is also found in bacteria and archaea where it is annotated as NuoK subunit.

Mnh subunit C1 is a cation antiporter, involved in K(+) and Na(+) excretion .
Serine hydroxymethyltransferase-like domain (SHMT-like_dom)
Type: Domain

Proteins containing this domain include serine hydroxymethyltransferase, alpha-methylserine aldolase and fluorothreonine transaldolase.

Serine hydroxymethyltransferase (SHMT) is a pyridoxal phosphate-dependent enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and methylenetetrahydrofolate . This reaction generates single carbon units for purine, thymidine, and methionine biosynthesis. It belongs to the aspartate aminotransferase superfamily (fold type I) . The pyridoxal-P group is attached to a lysine residue around which the sequence is highly conserved in all forms of the enzyme . SHMT catalyses the transfer of a hydroxymethyl group from N5, N10- methylene tetrahydrofolate to glycine, resulting in the formation of serine and tetrahydrofolate. Both eukaryotic and prokaryotic SHMT enzymes form tight obligate homodimers and the mammalian enzyme forms a homotetramer .

Fluorothreonine transaldolase catalyzes the final step in 4-fluorothreonine biosynthesis. It mediates a L-threonine/fluoroaceldehyde to 4-fluoro-L-threonine/acetaldehyde crossover reaction. It shares protein sequence similarity with SHMT .

Alpha-methylserine aldolase catalyses the reversible interconversion of alpha-methyl-L-serine to L-alanine and formaldehyde . This enzyme also catalysed alanine racemization.
Thymidylate kinase-like domain (Thymidylate_kin-like_dom)
Type: Domain

This entry represents a domain found in thymidylate kinase and mitochondrial UMP-CMP kinase.

Thymidylate kinase (

; dTMP kinase) catalyses the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium:

ATP + thymidine 5'-phosphate = ADP + thymidine 5'-diphosphate

Thymidylate kinase is an ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. The function of dTMP kinase in eukaryotes comes from the study of a cell cycle mutant, cdc8, in Saccharomyces cerevisiae. Structural and functional analyses suggest that the cDNA codes for authentic human dTMP kinase. The mRNA levels and enzyme activities corresponded to cell cycle progression and cell growth stages .

From a phylogenetic analysis, human mitochondrial UMP-CMP kinase has been shown to be closer to thymidylate kinase than to cytosolic UMP-CMP kinase. It phosphorylates dUMP, dCMP, CMP, and UMP with ATP as phosphate donor .
Vta1/callose synthase, N-terminal (Vta1/CALS_N)
Type: Domain

This domain can be found in the N terminus of the Vta1 protein, which is a class E vacuolar protein sorting (VPS) protein required for the formation of the multivesicular body (MVB) . Proteins containing this domain also include Vta1 homologues, such as SBP1 from humans and LIP5 from Arabidopsis thaliana . This domain can also be found in plant callose synthase, which is involved in callose synthesis at the forming cell plate during cytokinesis .
SRP9 domain (SRP9_dom)
Type: Domain

This domain can be found in human SRP9 protein and its homologues, such as the Srp21 protein from budding yeasts . These proteins are part of the signal recognition particle (SRP) .

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .
Mff-like domain (Mff-like_dom)
Type: Domain

This entry represents a domain found in mitochondrial fission factor (Mff) and at the C terminus of FATE1. This domain has a predicted transmembrane segment preceded by a coiled-coil region. Despite their similarity in the C terminus, FATE1 lacks a Mff-similar N-terminal domain that is essential for interaction of Mff with the dynamin-related GTPase Drp1, which mediates mitochondrial fission. Instead, FATE1 is involved in the regulation of ER-mitochondria distance and Ca(2+) uptake by mitochondria .
Rift valley fever virus non structural protein-like (NSs-like)
Type: Family

This family contains several Phlebovirus non structural proteins which act as a major determinant of virulence by antagonising interferon-beta gene expression . It also includes the hypotetical protein FPV063 from Fowlpox virus .
Diguanylate cyclase DosC, globin sensor domain (DosC_GS)
Type: Domain

Proteins containing this domain have a C-terminal diguanylate cyclase (DGC/GGDEF) domain coupled to the globin sensor domain. DGC/GGDEF likely functions as a c-di-GMP cyclase in the synthesis of the second messenger cyclic-di-GMP (c-di-GMP). Members include Escherichia coli DosC (also known as YddV), the gene for which is found in a two-gene operon, dosCP. In DosC, the sensory globin domain is coupled to a GGDEF-class diguanylate cyclase, while in DosP, a heme-containing PAS domain is coupled to an EAL-class c-di-GMP phosphodiesterase . DosP and DosC associate in a di-GMP-responsive Escherichia coli RNA processing complex along with polynucleotide phosphorylase (PNPase), enolase, RNase E, and RNA .
Asteroid domain (Asteroid_dom)
Type: Domain

This entry represents a domain found in Asteroid, which plays a possible role in EGF receptor signalling .
Aldolase FrzH/putative lumazine-binding (FrzH/put_lumazine-bd)
Type: Family

This protein family includes Aldolase FrzH from the fungi Cladobotryum sp., bacterial lumazine-binding proteins and similar sequences from cellular organisms. FrzH is involved in the biosynthesis of the alkaloid (-)-FR901483, a potent immunosuppressant that shows efficacy in animal models and a probable inhibitor of purine nucleotide biosynthesis . Members of this entry show a six-stranded β-sheet with three α-helices on one side (

) and belong to the NTF2-like superfamily of various enzymes. Some proteins in this family are putative dehydrogenases.
At2g23090-like, zinc-binding domain (At2g23090-like_Znf)
Type: Domain

This entry represent the zinc-binding domain found in a group of uncharacterised proteins, including At2g23090 from Arabidopsis.
SH3b1 domain (SH3b1_dom)
Type: Domain

This domain appears to be an SH3 domain of the SH3b1-type, and is just C-terminal to an N-terminal domain that is probably the stabilising domain for the structure from

(PDB:3m1u), which is a four-domain protein.
Domain of unknown function DUF3850 (DUF3850)
Type: Domain

The search results from NCBI sequence alignment indicates a conserved domain belonging to ASCH superfamily . Dali searching results show that the protein is a structurally similar to the PUA domain, suggesting it may be involved in RNA recognition. It has been reported that the deletion of PUA genes results in impaired growth (RluD) and competitive disadvantage (TruB) in Escherichia coli. Suggestions have been put forward that, apart from their usual catalytic role, certain PUS (pseudouridine synthase) enzymes (e.g. TruB) may also act as chaperones for RNA folding. The interface interaction indicates that the biomolecule of protein NP_809782.1 should be a dimer.
Mrr-like domain (Mrr-like_dom)
Type: Domain

This entry represents the Mrr-like domain that contains the (D/E)-(D/E)XK active site which can be found in type II restriction enzymes .
Transcriptional regulator DauR-like, HTH domain (DauR-like_HTH)
Type: Domain

This domain is a helix-turn-helix domain that is likely to act as a DNA-binding domain. This domain can be found in DauR, a transcriptional regulator that represses the dauBAR operon in Pseudomonas aeruginosa .
Transcriptional regulator DauR-like (DauR-like)
Type: Family

DauR is a transcriptional regulator that represses the dauBAR operon in Pseudomonas aeruginosa .
Urease accessory protein UreH-like, transmembrane domain (UreH-like_TM_dom)
Type: Domain

Urease is a nickel containing metalloenzyme that hydrolyses urea into ammonia . This entry represents a transmembrane domain found in UreH, an urease accessory protein . In Helicobacter pylori, UreH is part of the UreG/UreF/UreH complex that may be responsible for delivery of nickel ions into the urease active site .

This entry also includes Chloroplast protein FOR GROWTH AND FERTILITY 1/2 from Arabidopsis, transmembrane proteins essential for supporting female gametogenesis and embryogenesis, probably by securing local energy supply .
Right handed beta helix domain (Beta_helix)
Type: Domain

This region contains a parallel β-helix region that shares some similarity with Pectate lyases.
Type VI secretion system TssO (TssO)
Type: Family

TssO proteins have one predicted TM region near their N-termini. In Flavobacterium johnsoniae, three specific components (TssN, TssO and TssP) are absent in the other sub-types of T6SS .

The type VI secretion system (T6SS), also known as CIS contractile injection system , is a supra-molecular bacterial complex that resembles phage tails. It is a toxin delivery systems which fires toxins into target cells upon contraction of its TssBC sheath . Thirteen essential core proteins are conserved in all T6SSs: the membrane associated complex TssJ-TssL-TssM, the baseplate proteins TssE, TssF, TssG, and TssK, the bacteriophage-related puncturing complex composed of the tube (Hcp), the tip/puncturing device VgrG, and the contractile sheath structure (TssB and TssC). Finally, the starfish-shaped dodecameric protein, TssA, limits contractile sheath polymerization at its distal part when TagA captures TssA .
Family of unknown function DUF5419 (DUF5419)
Type: Family

The function of DUF5419 is not known. It can be found in gene 87 protein from Mycobacterium phage D29.
Protein of unknown function DUF5403 (DUF5403)
Type: Family

The function of DUF5403 is not known.
Mitochondrial outer membrane protein OM14, C-terminal (OM14_C)
Type: Domain

This entry includes Mitochondrial outer membrane protein OM14 from yeast and similar fungal sequences. OM14 is a mitochondrial membrane receptor for cytosolic ribosomes. It interacts with the nascent chain-associated complex (NAC) bound to ribosomes, contributing to co-translational mitochondrial import . This entry represents two transmembrane helices found at the C-terminal of OM14.
Mitochondrial outer membrane protein OM14 (OM14)
Type: Family

OM14 is a mitochondrial outer membrane receptor for cytosolic ribosomes .
EPIDERMAL PATTERNING FACTOR-like protein (EPFL)
Type: Family

EPIDERMAL PATTERNING FACTOR (EPF) is a family of plant epidermal cell growth factors. It is a signalling peptide that determines the spacing and separation of the development of stomatal cells in the upper epidermis of plant leaf cells .
WDR59, modified RING finger, H2 subclass, C3H3C2-type (WDR59_mRING-H2-C3H3C2)
Type: Domain

WDR59 is a component of GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea2/WDR24, and Mio/Sea4. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. WDR59 contains an N-terminal WD40 domain followed by a RWD domain, and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type. Sea3 is the yeast counterpart of WDR59. It is not included in this entry .
Ly6/PLAUR domain-containing protein 6-like (LYPD6-like)
Type: Family

This entry includes Ly6/PLAUR domain-containing protein 6 and Ly6/PLAUR domain-containing protein 6B (LYPD6/6B). They are prototoxins that belong to a larger family known as Ly-6/urokinase plasminogen activator receptor (Ly6/uPAR). They have 8-10 conserved cysteine residues that allow for the formation of disulfide bonds, constraining the protein to the 3-fingered motif secondary structure .

Ly6/PLAUR domain-containing protein 6 (LYPD6) is a higher eukaryotic protein expressed in neurons. It modulates nicotinic acetylcholine receptors by selectively increasing Ca2+-influx through this ion channel . LYPD6 carries an LU protein domain - about 80 amino acids long characterised by a conserved pattern of 10 cysteine residues . It is a positive feedback regulator of Wnt/beta-catenin signalling, e.g. for patterning of the mesoderm and neuroectoderm in zebrafish gastrulation, where Lypd6 is GPI-anchored to the plasma-membrane and interacts with the Wnt receptor Frizzled8 and the co-receptor Lrp6 .

LYPD6B has been shown to modulate heteromeric alpha3beta4-containing nicotinic acetylcholine receptors .
FimA-like (FimA-like)
Type: Family

FimA is a family of fimbrial component A proteins that form part of the pili from Gram-negative bacteria. There are usually up to 1000 copies of this subunit in one pilus that form a helically wound rod onto which the tip fibrillum (FimF, FimG, FimH) is attached. Pilus subunits are translocated from the cytoplasm to the periplasm via the general secretory pathway SecYEG .

This entry includes FimA and other fimbrial proteins.
RepB-like DNA primase domain (RepB-like_DNA_primase_dom)
Type: Domain

This domain can be found in the phage RepB primase and the C terminus of the E. coli MobA protein.
STAGA complex 65 subunit gamma/SAGA complex subunit Spt7 (SUPT7L/Spt7)
Type: Family

This protein family includes mammal STAGA complex 65 subunit gamma (SUPT7L) and fly SAGA complex subunit Spt7. These proteins different SAGA complexes from different animal organisms.

SUPT7L is a component of the structural core of the STAGA transcription coactivator-histone acetyltransferase (HAT) complex (mammal SAGA), which is composed of at least SUPT3H, SUPT7L, GCN5L2, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12 and TAF9. This complex, the TAF8-TAF10 histone fold (HF)-containing protein complex and the SMAT complex are important regulators of the composition of different TFIID and/or STAGA/TFTC complexes in the nucleus and consequently may play a role in gene regulation .

Spt7 is a component of the transcription regulatory complex dSAGA (Drosophila SAGA), which predominantly acetylates histone H3 .